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Occlusive Vascular Diseases in Oral Contraceptive Users

Epidemiology, Pathology and Mechanisms

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Abstract

Despite being an unprecedented departure from normal physiology, the combined oral contraceptive is not only highly effective, but it also has a remarkably good safety record. Concerns over safety persist, though, particularly with regard to venous thromboembolism (VTE), stroke and myocardial infarction (MI). Epidemiological studies consistently show an increase in risk of VTE, but the results are more contentious with regard to arterial diseases. Despite 40 years of research, the mechanisms behind these adverse effects are not understood. In this review, we integrate information from published studies of the epidemiology and pathology of the occlusive vascular diseases and their risk factors to identify likely explanations for pathogenesis in oral contraceptive users. Oral contraceptives induce both prothrombotic and fibrinolytic changes in haemostatic factors and an imbalance in haemostasis is likely to be important in oral contraceptive-induced VTE. The complexity of the changes involved and the difficulty of ascribing clinical significance has meant that uncertainty persists. A seriously under-researched area concerns vascular changes in oral contraceptive users. Histologically, endothelial and intimai proliferation have been identified in women exposed to high plasma estrogen concentrations and these lesions are associated with thrombotic occlusion. Other structural changes may result in increased vascular permeability, loss of vascular tone and venous stasis. With regard to arterial disease risk, epidemiological information relating to dose effects and joint effects with other risk factors, and studies of pathology and changes in risk factors, suggests that oral contraceptive use per se does not cause arterial disease. It can, nevertheless, synergise very powerfully with subclinical endothelial damage to promote arterial occlusion. Accordingly, the prothrombotic effects of the oral contraceptive estrogen intervene in a cycle of endothelial damage and repair which would otherwise remain clinically silent or would ultimately progress — in, for example, the presence of cigarette smoking or hypertension — to atherosclerosis. Future work in this area should focus on modification of the effects of established risk factors by oral contraceptive use rather than modification of the supposed risk of oral contraceptive use by established risk factors. Attempts to understand vascular occlusion in oral contraceptive users in terms of the general features of VTE or with reference to atherosclerosis may be limiting, and future work needs to acknowledge that such occlusions may have unique features. Unequivocal identification of the mechanisms involved would contribute considerably to the alleviation of fears over vascular disease and to the development of even safer formulations.

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References

  1. WHO Scientific Group on Cardiovascular Disease and Steroid Contraception. Cardiovascular disease and steroid hormone contraception. WHO Technical Report Series 1998; 877: 1–89

    Google Scholar 

  2. Dickson R, Eisenfeld A. 17-alpha ethinyl estradiol is more potent than estradiol in receptor interactions with isolated hepatic parenchymal cells. Endocrinology 1981; 108: 1511–8

    Article  PubMed  CAS  Google Scholar 

  3. Ory HW. Association between oral contraceptives and myocardial infarction: a review. JAMA 1977; 237: 2619–22

    Article  PubMed  CAS  Google Scholar 

  4. Stolley PD, Shapiro S, Slone D, et al. Cardiovascular effects of oral contraceptives. South Med J 1978; 71: 821–4

    Article  PubMed  CAS  Google Scholar 

  5. Vessey MP, Mann JI. Female sex hormones and thrombosis: epidemiological aspects. Br Med Bull 1978; 34: 157–62

    PubMed  CAS  Google Scholar 

  6. Vessey M. Female hormones and vascular disease: an epidemiological overview. Br JFamily Planning 1980; 6 Suppl.: 1–12

    Google Scholar 

  7. Stadel B. Oral contraceptives and cardiovascular disease 1. N Engl J Med 1981; 305: 612–8

    Article  PubMed  CAS  Google Scholar 

  8. Stadel B. Oral contraceptives and cardiovascular disease 2. N EnglJ Med 1981; 305: 672–7

    Article  CAS  Google Scholar 

  9. Dalen JE, Hickler RB. Oral contraceptives and cardiovascular disease. Am Heart J 1981; 101: 626–39

    Article  PubMed  CAS  Google Scholar 

  10. Sartwell PE, Stolley PD. Oral contraceptives and vascular disease. Epidemiol Rev 1982; 4: 95–109

    PubMed  CAS  Google Scholar 

  11. Realini J, Goldzieher J. Oral contraceptives and cardiovascular disease: a critique of the epidemiological studies. Am J Obstet Gynecol 1985; 152: 729–98

    PubMed  CAS  Google Scholar 

  12. Meade TW. Risks and mechanisms of cardiovascular events in users of oral contraceptives. Am J Obstet Gynecol 1988; 158: 1646–52

    PubMed  CAS  Google Scholar 

  13. Thorogood M. Oral contraceptives and cardiovascular disease: an epidemiologic overview. Pharmacoepidemiol Drug Saf 1993; 2: 3–16

    Article  Google Scholar 

  14. Petitti D, Sidney S, Quesenberry C. Oral contraceptive use and myocardial infarction. Contraception 1998; 57: 143–55

    Article  PubMed  CAS  Google Scholar 

  15. Farmer RDT, Preston TD. The risk of venous thromboembolism associated with low oestrogen oral contraceptives. J Obstet Gynaecol 1995; 15: 195–200

    Article  Google Scholar 

  16. World Health Organization (WHO). WHO Collaborative Study of Cardiovascular Disease and Steroid Contraception. A multinational case-control study of cardiovascular disease and steroid hormone contraceptives: description and validation of methods. J Clin Epidemiol 1995; 48: 1513–47

    Article  Google Scholar 

  17. Fuertes de la Halba A, Cuevas JOC, Pelegrina I, et al. Deaths among users of oral and non-oral contraceptives. Obstet Gynecol 1970; 36: 597–602

    Google Scholar 

  18. Fuertes de la Halba A, Bangdiwala IS, Pelegrin I. Success of randomisation in a controlled contraceptive experiment. J Reprod Med 1973; 11: 142–8

    Google Scholar 

  19. Hannaford P. The collection and interpretation of epidemiological data about the cardiovascular risks associated with the use of steroid contraceptives. Contraception 1998;57: 137–42

    Article  PubMed  CAS  Google Scholar 

  20. Royal College of General Practitioners’ Oral Contraception Study. Oral contraceptives and health. London: Pitman, 1974

    Google Scholar 

  21. Croft P, Hannaford P. Risk factors for acute myocardial infarction in women: evidence from the Royal College of General Practitioners’ oral contraception study. BMJ 1989; 298: 165–8

    Article  PubMed  CAS  Google Scholar 

  22. Vessey M, Doll R, Peto R, et al. A long-term follow-up study of women using different methods of contraception: an interim report. J Biosoc Sci 1976; 8: 373–427

    Article  PubMed  CAS  Google Scholar 

  23. Stampfer M, Willett W, Colditz G, et al. A prospective study of past use of oral contraceptive agents and risk of cardiovascular disease. N Engl J Med 1988; 319: 1313–7

    Article  PubMed  CAS  Google Scholar 

  24. Ramcharan S, Pelligrin FA, Ray R, et al. The Walnut Creek Contraceptive Drug Study: Center for Population Research. Washington (DC): National Institutes of Health, 1981: monograph number 81-564

    Google Scholar 

  25. Poulose KP, Reba RC, Gilday DL, et al. Diagnosis of pulmonary embolism: a correlative study of the clinical, scan and angiographic findings. BMJ 1970; 3: 67–71

    Article  PubMed  CAS  Google Scholar 

  26. Wells PS, Hirsh J, Anderson DR, et al. Accuracy of clinical assessment of deep-vein thrombosis. Lancet 1995; 345: 1326–30

    Article  PubMed  CAS  Google Scholar 

  27. Porter JB, Hunter JR, Jick H, et al. Oral contraceptives and non-fatal vascular disease. Obstet Gynecol 1985; 66: 1–4

    PubMed  CAS  Google Scholar 

  28. Jick H, Jick SS, Gurewich V, et al. Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet 1995; 346: 1589–93

    Article  PubMed  CAS  Google Scholar 

  29. Lidegaard Ø. Thrombotic diseases in young women and the influence from oral contraceptives. Am J Obstet Gynecol 1998; 179: S62–7

    Article  PubMed  CAS  Google Scholar 

  30. UK Office for National Statistics. 1997 mortality statistics: cause. England and Wales. Series DH2, no. 24. London: The Stationery Office, 1997

    Google Scholar 

  31. Lidegaard Ø, Edström B, Kreiner S. Oral contraceptives and venous thromboembolism: a case-control study. Contraception 1998; 57: 291–301

    Article  PubMed  CAS  Google Scholar 

  32. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Venous thromboembolic disease and combined oral contraceptives: results of international multicentre case-control study. Lancet 1995; 346: 1575–82

    Google Scholar 

  33. Vessey M, Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease: a further report. BMJ 1969; 2: 651–7

    Article  PubMed  CAS  Google Scholar 

  34. Farmer RDT, Lawrenson RA, Todd J-C, et al. Oral contraceptives and venous thromboembolic disease: analyses of the UK General Practice Research Database and the UK MediPlus Database. Hum Reprod Update 1999; 5: 688–706

    Article  PubMed  CAS  Google Scholar 

  35. Vandenbroucke JP, Koster T, Briet E, et al. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994; 344: 1453–7

    Article  PubMed  CAS  Google Scholar 

  36. Bloemenkamp KWM, Rosendaal FR, Büller HR, et al. Risk of venous thrombosis with use of current low-dose oral contraceptives is not explained by diagnostic suspicion and referral bias. Arch Intern Med 1999; 159: 65–70

    Article  PubMed  CAS  Google Scholar 

  37. Jordan W. Pulmonary embolism. Lancet 1961; II: 1146–7

    Article  Google Scholar 

  38. Royal College of General Practitioners’ Oral Contraception Study. Oral contraceptives and thromboembolic disease. J R Coll Gen Pract 1967; 13: 267–79

    Google Scholar 

  39. Greene GR, Sartwell PE. Oral contraceptive use in patients with thromboembolism following surgery, trauma or infection. Am J Public Health 1972; 62: 680–5

    Article  PubMed  CAS  Google Scholar 

  40. Vessey MP, Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease. BMJ 1968; 2: 199–205

    Article  PubMed  CAS  Google Scholar 

  41. Vessey MP, Doll R, Fairbairn AS, et al. Postoperative thromboembolism and the use of oral contraceptives. BMJ 1970; 3: 123–6

    Article  PubMed  CAS  Google Scholar 

  42. Sartwell PE, Masi AT, Arthes FG, et al. Thromboembolism and oral contraceptives: an epidemiologic case control study. Am J Epidemiol 1969; 90: 365–80

    PubMed  CAS  Google Scholar 

  43. Sartwell PE. Oral contraceptives and thromboembolism: a further report. Am J Epidemiol 1971; 94: 192–201

    PubMed  CAS  Google Scholar 

  44. Böttiger LE, Westerholm B. Oral contraceptives and thromboembolic disease: Swedish experience. Acta Med Scand 1971; 190(5): 455–63

    PubMed  Google Scholar 

  45. Inman W, Vessey M. Investigation of deaths from pulmonary, coronary, and cerebral thrombosis and embolism in women of child-bearing age. BMJ 1968; 2: 193–9

    Article  PubMed  CAS  Google Scholar 

  46. Petitti DB, Wingerd J, Pellegrin F, et al. Oral contraceptives, smoking and other factors in relation to risk of venous thromboembolic disease. Am J Epidemiol 1978; 108: 480–5

    PubMed  CAS  Google Scholar 

  47. Boston Collaborative Drug Surveillance Program. Oral contraceptives and venous thromboembolic disease, surgically confirmed gallbladder disease and breast tumours. Lancet 1973; I: 1399–404

    Google Scholar 

  48. Maguire MG, Tonascia J, Sartwell PE, et al. Increased risk of thrombosis due to oral contraceptives: a further report. Am J Epidemiol 1979; 110: 188–95

    PubMed  CAS  Google Scholar 

  49. Stolley PD, Tonascia JA, Tockman MS, et al. Thrombosis with low estrogen oral contraceptives. Am J Epidemiol 1975; 102: 197–208

    PubMed  CAS  Google Scholar 

  50. Helmrich SP, Rosenberg L, Kaufman DW, et al. Venous thromboembolism in relation to oral contraceptive use. Obstet Gynecol 1987; 69: 91–5

    PubMed  CAS  Google Scholar 

  51. Thorogood M, Mann J, Murphy M, et al. Risk factors for fatal venous thromboembolism in young women: a case control study. Int J Epidemiol 1992; 21

  52. Spitzer WO, Lewis MA, Heinemann LAJ, et al. Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study. BMJ 1996; 312:83–8

    Article  PubMed  CAS  Google Scholar 

  53. Lewis MA, Heinemann LAJ, MacRea KD, et al. The increased risk of venous thromboembolism and the use of third generation progestagens: role of bias in observational research. Contraception 1996; 54: 5–13

    Article  PubMed  CAS  Google Scholar 

  54. Fuertes-de la Halba A, Curet JO, Pelegrina I, et al. Thrombophlebitis among oral and non-oral contraceptive users. Obstet Gynecol 1971; 38: 259–63

    Google Scholar 

  55. Kay CR. Oral contraceptives and venous thrombosis [letter]. Lancet 1975; I: 1381

    Article  Google Scholar 

  56. Royal College of General Practitioners’ Oral Contraception Study. Oral contraceptives, venous thrombosis and varicose veins. J R Coll Gen Pract 1978; 28: 393–9

    Google Scholar 

  57. Royal College of General Practitioners’ Oral Contraception Study. Mortality among oral contraceptive users. Lancet 1977; II: 727–31

    Google Scholar 

  58. Royal College of General Practitioners’ Oral Contraception Study. Further analyses of mortality in oral contraceptive users. Lancet 1981; I: 541–6

    Google Scholar 

  59. Vessey MP. Steroid contraception, venous thromboembolism and stroke: data from countries other than the United States. In: Sciarra JJ, Zatuchni GI, Speidel JJ, editors. Risks, benefits and controversies in fertility control. Hagerstown: Harper & Row, 1978: 113

    Google Scholar 

  60. Vessey M, McPherson K, Yeates D. Mortality in oral contraceptive users. Lancet 1981; I: 549–50

    Article  Google Scholar 

  61. Vessey MP, McPherson K, Johnson B. Mortality among women participating in the Oxford/Family Planning Association Contraceptive Study. Lancet 1977; II: 731–3

    Article  Google Scholar 

  62. Vessey M, Villard-Mackintosh L, Yeates D. Mortality among oral contraceptive users: 20 year follow up of women in a cohort study. BMJ 1989; 299: 1487–91

    Article  PubMed  CAS  Google Scholar 

  63. Porter JB, Hunter JR, Danielson DA, et al. Oral contraceptives and nonfatal vascular disease: recent experience. Obstet Gynecol 1982; 59: 299–302

    PubMed  CAS  Google Scholar 

  64. Ludwig H. Anovulatory agents and venous diseases. Ergeb Angiol Plebol 1970; 4: 81–102

    Google Scholar 

  65. Grounds M. Anovulants: thrombosis and other associated changes. Med J Aust 1974; 2: 440–6

    PubMed  CAS  Google Scholar 

  66. Sagar S, Stamatakis JD, Thomas DP, et al. Oral contraceptives, antithrombin-III activity and postoperative deep-vein thrombosis. Lancet 1976; I: 509–11

    Article  Google Scholar 

  67. Hoover R, Bain C, Cole P, et al. Oral contraceptive use: association with frequency of hospitalisation and chronic disease risk indicators. Am J Public Health 1978; 68: 335–41

    Article  PubMed  CAS  Google Scholar 

  68. Diddle AW, Gardner WH, Williamson PJ, et al. Oral contraceptive steroids and thrombophlebitis. J Tenn Med Assoc 1978; 71: 22–6

    PubMed  CAS  Google Scholar 

  69. Lawson DH, Davidson JF, Jick H. Oral contraceptive use and venous thromboembolism: absence of an effect of smoking. BMJ 1977; 2: 729–30

    Article  PubMed  CAS  Google Scholar 

  70. Rosendaal FR, Koster T, Vandenbroucke JP, et al. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 1995; 85: 1504–8

    PubMed  CAS  Google Scholar 

  71. Martinelli I, Taioli E, Bucciarelli P, et al. Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis. Arterioscler Thromb Vasc Biol 1999; 19:700–3

    Article  PubMed  CAS  Google Scholar 

  72. Bloemenkamp KWM, Rosendaal FR, Heimerhorst FM, et al. Enhancement by factor V Leiden mutation of risk of deepvein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 1995; 346: 1593–6

    Article  PubMed  CAS  Google Scholar 

  73. Poulter NR, Farley TMM, Chang CL, et al. Safety of combined oral contraceptive pills [letter]. Lancet 1996; 347: 547

    Google Scholar 

  74. Suissa S, Biais L, Spitzer WO, et al. First-time use of newer oral contraceptives and the risk of venous thromboembolism. Contraception 1997; 56: 141–6

    Article  PubMed  CAS  Google Scholar 

  75. Herings RMC, Urquhart J, Leufkens HGM. Venous theomboembolism among new users of different oral contraceptives. Lancet 1999; 354: 127–8

    Article  PubMed  CAS  Google Scholar 

  76. Inman W, Vessey M, Westerholm B, et al. Thromboembolic disease and the steroidal content of oral contraceptives: a report to the Committee on Safety of Drugs. BMJ 1970; 2: 203–9

    Article  PubMed  CAS  Google Scholar 

  77. Meade T, Greenberg G, Thompson S. Progestagens and cardiovascular reactions associated with oral contraceptives, and a comparison of the safety of 50 and 30μg oestrogen preparations. BMJ 1980; 280: 1157–61

    Article  PubMed  CAS  Google Scholar 

  78. Mann J, Inman W. Oral contraceptives and death from myocardial infarction. BMJ 1975; 2: 245–8

    Article  PubMed  CAS  Google Scholar 

  79. Gerstman BB, Piper JM, Frieman JP, et al. Oral contraceptive oestrogen and progestin potencies and the incidence of deep venous thrombosis. Int J Epidemiol 1990; 19: 931–6

    Article  PubMed  CAS  Google Scholar 

  80. Gerstman BB, Piper JM, Tomita DK, et al. Oral contraceptive estrogen dose and risk of deep venous thromboembolic disease. Am J Epidemiol 1991; 133: 32–7

    PubMed  CAS  Google Scholar 

  81. Lewis MA, MacRae KD, Kühl-Habich D, et al. The differential risk of oral contraceptives: the impact of full exposure history. Hum Reprod 1999; 14: 1493–9

    Article  PubMed  CAS  Google Scholar 

  82. Vessey M, Mant-Villard D, Smith A, et al. Oral contraceptives and venous thromboembolism: findings in a large prospective study. BMJ 1986; 292(6519): 526

    Article  PubMed  CAS  Google Scholar 

  83. Gerstman BB. Oral contraceptive oestrogen dose and risk of deep venous thromboembolic disease [letter]. Am J Epidemiol 1991; 134: 1009–10

    Google Scholar 

  84. Andersen BS, Steffensen FH, Sørensen HT, et al. The cumulative incidence of venous thromboembolism during pregnancy and puerperium. Acta Obstet Gynecol Scand 1998; 77: 170–3

    Article  PubMed  CAS  Google Scholar 

  85. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. Lancet 1995; 346: 1582–8

    Google Scholar 

  86. Farmer RTD, Lawrenson RA, Thompson CR, et al. Population-based study of risk of venous thromboembolism associated with various oral contraceptives. Lancet 1997; 349: 83–8

    Article  PubMed  CAS  Google Scholar 

  87. Lidegaard Ø, Milsom I. Oral contraceptives and thrombotic diseases: impact of new epidemiological studies. Contraception 1996; 53: 135–9

    Article  PubMed  CAS  Google Scholar 

  88. Mant D, Villard-Mackintosh L, Vessey MP, et al. Myocardial infarction and angina pectoris in young women. J Epidemiol Community Health 1987; 41: 215–9

    Article  PubMed  CAS  Google Scholar 

  89. Oliver MF. Ischaemic heart disease in young women. BMJ 1974; 4: 253–9

    Article  PubMed  CAS  Google Scholar 

  90. Mann J, Vessey M, Thorogood M, et al. Myocardial infarction in young women with special reference to oral contraceptive practice. BMJ 1975; 2: 241–5

    Article  PubMed  CAS  Google Scholar 

  91. Adam SA, Thorogood M, Mann JI. Oral contraception and myocardial infarction revisited: the effects of new preparations and prescribing patterns. Br J Obstet Gynaecol 1981; 88: 838–45

    Article  PubMed  CAS  Google Scholar 

  92. Thorogood M, Mann J, Murphy M, et al. Is oral contraceptive use still associated with increased risk of myocardial infarction? Report of a case-control study. Br J Obstet Gynaecol 1991; 98: 1245–53

    Article  PubMed  CAS  Google Scholar 

  93. Jick H, Dinan B, Rothman K. Oral contraceptives and nonfatal myocardial infarction. JAMA 1978; 239: 1403–6

    Article  PubMed  CAS  Google Scholar 

  94. Petitti D, Wingerd J, Pellegrin F, et al. Risk of vascular disease in women: smoking, oral contraceptives, noncontraceptive estrogens and other factors. JAMA 1979; 242: 1150–4

    Article  PubMed  CAS  Google Scholar 

  95. Shapiro S, Slone D, Rosenberg L, et al. Oral contraceptive use in relation to myocardial infarction. Lancet 1979; I: 743–7

    Article  Google Scholar 

  96. Krueger DE, Ellenberg SS, Bloom S, et al. Fatal myocardial infarction and the role of oral contraceptives. Am J Epidemiol 1980; 111:655–74

    PubMed  CAS  Google Scholar 

  97. Rosenberg L, Hennekens C, Rosner B, et al. Oral contraceptive use in relation to non-fatal myocadial infarction. Am J Epidemiol 1980; 111: 59–66

    PubMed  CAS  Google Scholar 

  98. La Vecchia C, Franceschi S, Decarli A, et al. Risk factors for myocardial infarction in young women. Am J Epidemiol 1987; 125: 832–43

    PubMed  Google Scholar 

  99. Sidney S, Petitti DB, Quesenberry Jr CP, et al. Myocardial infarction in users of low-dose oral contraceptives. Obstet Gynecol 1996; 88: 939–44

    Article  PubMed  CAS  Google Scholar 

  100. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case-control study. Lancet 1997; 349(9060): 1202–9

    Article  Google Scholar 

  101. Rosenberg L, Kaufman D, Helmrich S, et al. Myocardial infarction and cigarette smoking in women younger than 50 years of age. JAMA 1985; 253: 2965–9

    Article  PubMed  CAS  Google Scholar 

  102. Dunn NR, Faragher B, Thorogood M, et al. Risk of myocardial infarction in young female smokers. Heart 1999; 82: 581–3

    PubMed  CAS  Google Scholar 

  103. Boyce J, Fawcett JW, Noall EWP. Coronary thrombosis and Conovid [letter]. Lancet 1963; I: 111

    Article  Google Scholar 

  104. Hartveit F. Complications of oral contraceptives. BMJ 1965; 1: 60–1

    Article  PubMed  CAS  Google Scholar 

  105. Naysmith JH. Oral contraceptives and coronary thrombosis [letter]. BMJ 1965; 1: 250

    Article  PubMed  CAS  Google Scholar 

  106. Osborn GR. Oral contraception and thrombosis [letter]. BMJ 1965; 1: 1128

    Article  PubMed  CAS  Google Scholar 

  107. Scharf J, Nahir AM, Peled B, et al. Oral contraceptives and myocardial infarction. Lancet 1968; II: 411–2

    Article  Google Scholar 

  108. Oliver M. Oral contraceptives and myocardial infarction. BMJ 1970; 2: 210–3

    Article  PubMed  CAS  Google Scholar 

  109. Arthes FG, Masi AT. Myocardial infarction in younger women: associated clinical features and relationship to use of oral contraceptive drugs. Chest 1976; 70: 574–83

    Article  PubMed  CAS  Google Scholar 

  110. Mann JI, Thorogood M, Waters WE, et al. Oral contraceptives and myocardial infarction in young women: a further report. BMJ 1975; 3: 631–2

    Article  PubMed  CAS  Google Scholar 

  111. Rosenberg L, Armstrong B, Jick H. Myocardial infarction and estrogen therapy in premenopausal women. N Engl J Med 1976; 294: 1290–1

    Article  PubMed  CAS  Google Scholar 

  112. Mann J, Inman W, Thorogood M. Oral contraceptive use in older women and fatal myocardial infarction. BMJ 1976; 2: 445–7

    Article  PubMed  CAS  Google Scholar 

  113. Jick H, Dinan B, Herman R, et al. Myocardial infarction and other vascular diseases in young women. JAMA 1978; 240: 2548–52

    Article  PubMed  CAS  Google Scholar 

  114. Slone D, Shapiro S, Kaufman D, et al. Risk of myocardial infarction in relation to current and discontinued use of oral contraceptives. N Engl J Med 1981; 305: 420–4

    Article  PubMed  CAS  Google Scholar 

  115. Talbott E, Kuller LH, Detre K, et al. Reproductive history of women dying of sudden cardiac death. Int J Epidemiol 1989; 18: 589–94

    Article  PubMed  CAS  Google Scholar 

  116. Ananjevic-Pandey J, Vlajinac H. Myocardial infarction in young women with reference to oral contraceptive use. Int J Epidemiol 1989; 18: 585–8

    Article  Google Scholar 

  117. Rosenberg L, Palmer J, Lesko S, et al. Oral contraceptive use and the risk of myocardial infarction. Am J Epidemiol 1990; 131: 1009–16

    PubMed  CAS  Google Scholar 

  118. D’Avanzano B, La Vecchia C, Negri E, et al. Oral contraceptive use and risk of myocardial infarction: an Italian case-control study. J Epidemiol Community Health 1994; 48: 324–5

    Article  Google Scholar 

  119. Lewis MA, Spitzer WO, Heinemann LAJ, et al. Third generation oral contraceptives and risk of myocardial infarction: an international case-control study. BMJ 1996; 312: 88–90

    Article  PubMed  CAS  Google Scholar 

  120. Sidney S, Siscovick DS, Petitti DB, et al. Myocardial infarction and use of low-dose oral contraceptives. Circulation 1998; 98: 1058–63

    Article  PubMed  CAS  Google Scholar 

  121. Dunn N, Thorogood M, Faragher B, et al. Oral contraceptives and myocardial infarction: results of the MICA case-control study. BMJ 1999; 318: 1579–84

    Article  PubMed  CAS  Google Scholar 

  122. Lewis MA, Heinemann LAJ, Spitzer WO, et al. The use of oral contraceptives and the occurence of acute myocardial infarction in young women. Contraception 1997; 56: 129–40

    Article  PubMed  CAS  Google Scholar 

  123. Lewis MA, Spitzer WO, Heinemann LAJ, et al. Lowered risk of dying of heart attack with third generation pill may offset risk of dying of thromboembolism. BMJ 1997; 315: 679–80

    Article  CAS  Google Scholar 

  124. Royal College of General Practitioners’ Oral Contraception Study. Incidence of arterial disease among oral contraceptive users. J R Coll Gen Pract 1983; 33: 75–82

    Google Scholar 

  125. Porter JB, Jick H, Walker AM. Mortality among oral contraceptive users. Obstet Gynecol 1987; 70: 29–32

    PubMed  CAS  Google Scholar 

  126. Radford D, Oliver M. Oral contraceptives and myocardial infarction. BMJ 1973; 3: 428–30

    Article  PubMed  CAS  Google Scholar 

  127. Mann JI, Doll R, Thorogood M, et al. Risk factors for myocardial infarction in young women. Br J Prev Soc Med 1976; 30: 95–100

    Google Scholar 

  128. Jain AK. Cigarette smoking, use of oral contraceptives and myocardial infarction. Am J Obstet Gynecol 1976; 126: 301–7

    PubMed  CAS  Google Scholar 

  129. Sturtevant FM. Smoking oral contraceptives and thromboembolic disease. Int J Fertil 1982; 27 Suppl. 1:2–13

    PubMed  CAS  Google Scholar 

  130. Thorogood M, Vessey MP Trends in use of oral contraceptives in Britain. Br J Family Planning 1990; 16: 41–53

    Google Scholar 

  131. Thorogood M, Vessey MP. Oral contraceptive prescribing in the presence of risk factors. Br J Family Planning 1991; 17: 2–3

    Google Scholar 

  132. Stampfer MJ, Willett WC, Colditz GA, et al. Past use of oral contraceptives and cardiovascular disease: a meta-analysis in the context of the Nurses’ Health Study. Am J Obstet Gynecol 1990; 163: 285–91

    PubMed  CAS  Google Scholar 

  133. Colditz GA. Oral contraceptive use and mortality during 12 years of follow-up: the Nurses’ Health Study. Ann Intern Med 1994; 120(10): 821–6

    PubMed  CAS  Google Scholar 

  134. Kay CR. James Mackenzie lecture 1979: the happiness pill? J Royal Coll Gen Pract 1980; 30: 8–19

    CAS  Google Scholar 

  135. Kay C. Progestagens and arterial disease: evidence from the Royal College of General Practioners’ Study. Am J Obstet Gynecol 1982; 142 (Pt 2): 758–61

    Google Scholar 

  136. Wingrave SJ. Progestogen effects and their relationship to lipoprotein changes. Acta Obstet Gynecol Scand 1982; 105 Suppl.: 33–6

    Article  CAS  Google Scholar 

  137. Croft P, Hannaford P. Risk factors for acute myocardial infarction in women [letter]. BMJ 1989; 298: 674

    Article  PubMed  CAS  Google Scholar 

  138. Lidegaard Ø. Decline in cerebral thromboembolism among young women after introduction of low-dose oral contraceptives: an incidence study for the period 1980–1993. Contraception 1995; 52: 85–92

    Article  PubMed  CAS  Google Scholar 

  139. Robins M, Baum H. Stroke incidence. Stroke 1981; 12 Suppl. 1:45–57

    Google Scholar 

  140. Bonita R, Anderson CS, Broad JB, et al. Stroke incidence and case fatality in Australasia. Stroke 1994; 25: 552–7

    Article  PubMed  CAS  Google Scholar 

  141. Lidegaard Ø. Oral contraceptives and stroke: issues and recommendations. CNS Drugs 1997; 1: 1–5

    Article  Google Scholar 

  142. Bevan H, Sharma K, Bradley W Stroke in young adults. Stroke 1990; 21: 382–6

    Article  PubMed  CAS  Google Scholar 

  143. Hannaford PC, Croft PR, Kay CR. Oral contraception and stroke: evidence from the Royal College of General Practitioners’ Oral Contraception Study. Stroke 1994; 25: 935–42

    Article  PubMed  CAS  Google Scholar 

  144. Lidegaard Ø. Oral contraceptives, pregnancy and the risk of cerebral thromboembolism: the influence of diabetes, hypertension, migraine and previous thrombotic disease. Br J Obstet Gynaecol 1995; 102: 153–9

    Article  PubMed  CAS  Google Scholar 

  145. Heyman A, Arons M, Quinn M, et al. The role of oral contraceptive agents in cerebral arterial occlusion. Neurology 1969; 19: 519–24

    Article  PubMed  CAS  Google Scholar 

  146. Hindfelt B, Nilsson O. Brain infarction in young adults. Acta Neurol Scand 1977; 55: 145–57

    Article  PubMed  CAS  Google Scholar 

  147. Grindal AB, Cohen RJ, Saul RF, et al. Cerebral infarction in young adults. Stroke 1978; 9: 39–42

    Article  PubMed  CAS  Google Scholar 

  148. Hillbom M, Kaste M. Ethanol intoxication: a risk factor for ischaemic brain infarction. Stroke 1983; 14: 694–9

    Article  PubMed  CAS  Google Scholar 

  149. Lacy JR, Filley CM, Earnest MP, et al. Brain infarction and hemorrhage in young and middle-aged adults. West J Med 1984; 141: 329–34

    PubMed  CAS  Google Scholar 

  150. Klein GM, Seland TP. Occlusive cerebro-vascular disease in young adults. Can J Neurol Sci 1984; 11: 302–4

    PubMed  CAS  Google Scholar 

  151. Spaccavento LJ, Solomon GD. Migraine as an etiology of stroke in young adults. Headache 1984; 24: 19–22

    Article  PubMed  CAS  Google Scholar 

  152. Hilton-Jones D, Warlow CP The causes of stroke in the young. J Neurol 1985; 232: 137–43

    Article  PubMed  CAS  Google Scholar 

  153. Larsen BH, Sørensen PS, Marquardsen J. Transient ischaemic attacks in young patients: a thromboembolic or migrainous manifestation? A 10 year follow-up study of 46 patients. J Neurol Neurosurg Psychiatry 1990; 53: 1029–33

    Article  PubMed  CAS  Google Scholar 

  154. Matias-Guiu J, Alvarez J, Insa R, et al. Ischaemic stroke in young adults: II. Analysis of risk factors in the etiological subgroups. ActaNeurol Scand 1990; 81: 314–7

    CAS  Google Scholar 

  155. Berlit P, Endemann B, Veter P. Cerebral ischemia in young adults [in German]. Fortschr Neurol Psychiatr 1991; 59(8): 322–7

    Article  PubMed  CAS  Google Scholar 

  156. Lanzino G, Andreoli A, Di Pasquale G, et al. Etiopathologenesis and prognosis of cerebral ischaemia in young adults. Acta Neurol Scand 1991; 84: 321–5

    Article  PubMed  CAS  Google Scholar 

  157. Lisovoski F, Rouseaux P. Cerebral infarction in young people: a study of 148 patients with early cerebral angiography. J Neurol Neurosurg Psychiatry 1991; 54: 576–9

    Article  PubMed  CAS  Google Scholar 

  158. Carolei A, Marini C, Ferranti E, et al. A prospective study of cerebral ischaemia in the young: analysis of pathogenic determinants. Stroke 1993; 24: 362–7

    Article  PubMed  CAS  Google Scholar 

  159. Zuber M, Toulon P, Marnet L, et al. Factor V Leiden mutation in cerebral venous thrombosis. Stroke 1996; 27: 1721–3

    Article  PubMed  CAS  Google Scholar 

  160. Wilder-Smith E, Kothbauer-Margreiter I, Lammle B, et al. Durai puncture and activated protein C resistance: risk factors for cerebral venous sinus thrombosis. J Neurol Neurosurg Psychiatry 1997; 63: 351–6

    Article  PubMed  CAS  Google Scholar 

  161. Margaglione M, D’Andrea G, Giuliani N, et al. Inherited prothrombotic conditions and premature ischccmic stroke: sex difference in the association with factor V Leiden. Arterioscler Thromb Vasc Biol 1999; 19: 1751–6

    Article  PubMed  CAS  Google Scholar 

  162. Lorentz IT. Parietal lesion and Enovid [letter]. BMJ 1962; 2: 1191

    Article  Google Scholar 

  163. Mettinger KL, Söderström CE, Allander E. Epidemiology of acute cerebrovascular disease before the age of 55 in Stockholm county 1973–77: 1. Incidence and mortality rates. Stroke 1984; 15: 795–801

    Article  PubMed  CAS  Google Scholar 

  164. Arbuckle DD, Harris RI, Goldacre MJ. Stroke in people under 55 years of age. Public Health 1982; 96: 96–100

    Article  PubMed  CAS  Google Scholar 

  165. Lidegaard Ø, Søe M, Andersen MVN. Cerebral thromboembolism among young women and men in Denmark 1977–1982. Stroke 1986; 17: 670–5

    Article  PubMed  CAS  Google Scholar 

  166. Bickerstaff ER. Neurological complications of oral contraceptives. Oxford: Clarendon Press, 1975

    Google Scholar 

  167. Lidegaard Ø. Oral contraception and risk of cerebral thrombolic attacks: results of a case-control study. BMJ 1993; 306: 956–63

    Article  PubMed  CAS  Google Scholar 

  168. Lidegaard Ø. Oral contraceptives and cerebral thromboembolism: an epidemiological approach. Copenhagen: The University of Copenhagen, 1996

    Google Scholar 

  169. Firnhaber W, Fügemann W. Oral contraceptives as a cause of cerebral circulatory disturbances [in German]? Z Neurol 1974; 206(3): 177–91

    Article  PubMed  CAS  Google Scholar 

  170. Collaborative Group for the Study of Stroke in Young Women. Oral contraceptives and stroke in young women: associated risk factors. JAMA 1975; 231: 718–22

    Article  Google Scholar 

  171. Collaborative Group for the Study of Stroke in Young Women. Oral contraception and increased risk of cerebral ischaemia or thrombosis. N Engl J Med 1973; 288: 871–8

    Article  Google Scholar 

  172. Jick H, Porter J, Rothman KJ. Oral contraceptives and non-fatal stroke in healthy young women. Ann Intern Med 1978; 88: 58–60

    Google Scholar 

  173. Mettinger KI, Söderström CE, Neiman J. Stroke before 55 years of age at Karolinska Hospital 1973–77: a study of 388 well-defined cases. Acta Neurol Scand 1984; 70: 415–22

    Article  PubMed  CAS  Google Scholar 

  174. Oleckno WA. The risk of stroke in young adults: an analysis of the contribution of cigarette smoking and alcohol consumption. Public Health 1988; 102: 45–55

    Article  PubMed  CAS  Google Scholar 

  175. Chang KK, Chow LP, Rider RV. Oral contraceptives and stroke: a preliminary report on an epidemiological study in Taiwan, China. Int J Gynecol Obstet 1986; 24: 421–30

    Article  CAS  Google Scholar 

  176. Thorogood M, Mann J, Murphy M, et al. Fatal stroke and use of oral contraceptives: findings from a case-control study. Am J Epidemiol 1992; 136: 35–45

    PubMed  CAS  Google Scholar 

  177. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study. Lancet 1996; 348: 498–505

    Article  Google Scholar 

  178. Tzourio C, Tehindrazanarivelo A, Iglesias S, et al. Case-control study of migraine and risk of ischemic stroke in young women. BMJ 1995; 310: 830–3

    Article  PubMed  CAS  Google Scholar 

  179. Petitti DB, Sidney S, Bernstein A, et al. Stroke in users of low-dose oral contraceptives. N Engl J Med 1996; 335: 8–15

    Article  PubMed  CAS  Google Scholar 

  180. Schwartz SM, Siscovick DS, Longstreth Jr WT, et al. Use of low dose oral contraceptives and stroke in young women. Ann Intern Med 1997; 127: 596–603

    PubMed  CAS  Google Scholar 

  181. Schwartz SM, Petitti DB, Siscovick DS, et al. Stroke and use of low-dose oral contraceptives in young women: a pooled analysis of two US studies. Stroke 1998; 29: 2277–84

    Article  PubMed  CAS  Google Scholar 

  182. Heinemann LAJ, Lewis MA, Thorogood M, et al. Case-control study of oral contraceptives and risk of thromboembolic stroke: results from an international study of oral contraceptives and health in young women. BMJ 1997; 315: 1502–4

    Article  PubMed  CAS  Google Scholar 

  183. Lidegaard Ø, Kreiner S. Cerebral thrombosis and oral contraceptives: a case control study. Contraception 1998; 57: 303–14

    Article  PubMed  CAS  Google Scholar 

  184. Martinelli I, Sacchi E, Landi G, et al. High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives. N Engl J Med 1998; 338: 1793–7

    Article  PubMed  CAS  Google Scholar 

  185. de Bruijn SF, Stam J, Koopman MM, et al. Case-control study of risk of cerebral sinus thrombosis in oral contraceptive users and in carriers of hereditary prothrombotic conditions: the Cerebral Venous Sinus Thrombosis Study Group. BMJ 1998; 316: 589–92

    Article  PubMed  Google Scholar 

  186. Petitti DB, Wingerd J. Use of oral contraceptives, cigarette smoking and risk of subarachnoid haemorrhage. Lancet 1978; II: 234–6

    Article  Google Scholar 

  187. Inman WHW. Oral contraceptives and fatal subarachnoidal haemorrhage. BMJ 1979; 2: 1468–70

    Article  PubMed  CAS  Google Scholar 

  188. Thorogood M, Adam SA, Mann JI. Fatal subarachnoid haemorrhage in young women: role of oral contraceptives. BMJ 1981; 283(6294): 762

    Article  PubMed  CAS  Google Scholar 

  189. Longstreth WT, Nelson LM, Koepsell TD, et al. Subarachnoid haemorrhage and hormonal factors in women: a population based case control study. Ann Intern Med 1994; 121: 168–73

    PubMed  CAS  Google Scholar 

  190. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Haemorrhagic stroke, overall stroke risk, and combined oral contraceptives: results of an international, multicentre, case-control study. Lancet 1996; 348: 505–10

    Article  Google Scholar 

  191. Beral V, Hermon C, Kay C, et al. Mortality associated with oral contraceptive use: 25 year follow up of cohort of 46000 women from Royal College of General Practitioners’ oral contraception study. BMJ 1999; 318: 96–100

    Article  PubMed  CAS  Google Scholar 

  192. Vessey MP, Lawless M, Yeates D. Oral contraceptives and stroke: findings from a large prospective study. BMJ 1984; 289: 530–1

    Article  PubMed  CAS  Google Scholar 

  193. Royal College of General Practitioners’ Oral Contraception Study. Effect on hypertension and benign breast disease of progestogen component in combined oral contraceptives. Lancet 1977; I: 624

    Google Scholar 

  194. Gillum LA, Mamidipudi SK, Johnston SC. ischemic stroke risk with oral contraceptives: a meta-analysis. JAMA 2000; 284: 72–8

    Article  PubMed  CAS  Google Scholar 

  195. Farley T, Colins J, Schlesselman J. Hormonal contraception and risk of cardiovascular disease: an international perspective. Contraception 1998; 57: 211–30

    Article  PubMed  CAS  Google Scholar 

  196. Basdevant A, de Lignieres B, Mauvais-Jarvis P. Effects of oral contraceptives on the vascular wall [in French]. Nouv Presse Méd 1980; 9(8): 519–22

    PubMed  CAS  Google Scholar 

  197. Petty RG, Pearson JD. Endothelium: the axis of vascular health and disease. J R Coll Physicians Lond 1989; 23: 92–102

    PubMed  CAS  Google Scholar 

  198. Lüscher TF, Noll G. The pathogenesis of cardiovascular disease: role of the endothelium as a target and mediator. Atherosclerosis 1995; 118 Suppl. 1: S81–90

    Article  PubMed  Google Scholar 

  199. Mano T, Masuyama T, Yamamoto K, et al. Endothelial dysfunction in the early stages of atherosclerosis precedes appearance of intimai lesions assessable with intravascular ultrasound. Am Heart J 1996; 131: 231–8

    Article  PubMed  CAS  Google Scholar 

  200. Jaffe EA, editor. Biology of endothelial cells. Boston (NY): Martinus Nijhoff, 1984

    Book  Google Scholar 

  201. Palmer RMJ, Ashton DS, Moncada S. Vascular endothelial cells synthesise nitric oxide from L-arginine. Nature 1988; 333: 664–6

    Article  PubMed  CAS  Google Scholar 

  202. Vanhoutte PM. The endothelium: modulator of vascular smooth muscle tone. N Engl J Med 1988; 319: 512–3

    Article  PubMed  CAS  Google Scholar 

  203. Madri JA, Pratt BM, Yannariello-Brown J. Matrix-driven cell size change modulates aortic endothelial cell proliferation and sheet migration. Am J Physiol 1988; 1988: 18–27

    Google Scholar 

  204. Campbell JH, Campbell GR. Endothelial cell influences on vascular smooth muscle phenotype. Annu Rev Physiol 1986; 48: 295–306

    Article  PubMed  CAS  Google Scholar 

  205. Simeonescu M, Simeonescu N. Endothelial transport of macromolecules: transcytosis and endocytosis. A look from cell biology. Cell Biol Rev 1991; 25: 1–78

    Google Scholar 

  206. Ghinea N, Milgrom E. Transport of protein hormones through the vascular endothelium. J Endocrinol 1995; 145: 1–9

    Article  PubMed  CAS  Google Scholar 

  207. Michel CC. Capillary permeability and how it may change. J Physiol 1988; 404: 1–29

    PubMed  CAS  Google Scholar 

  208. Fielding PE, Vlodavsky L, Gospodarowicz D, et al. Effect of contact inhibition on the regulation of cholesterol metabolism in cultured vascular endothelial cells. J Biol Chem 1979; 254: 749–55

    PubMed  CAS  Google Scholar 

  209. Vita JA, Treasure CB, Nabel EG, et al. The coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation 1989; 81: 491–7

    Article  Google Scholar 

  210. Glasser S, Selwyn AP, Ganz P. Atherosclerosis: risk factors and the endothelium. Am Heart J 1996; 131: 379–84

    Article  PubMed  CAS  Google Scholar 

  211. Carter CJ. The natural history and epidemiology of venous thrombosis. Prog Cardiovasc Dis 1994; 36: 423–38

    Article  PubMed  CAS  Google Scholar 

  212. Stamatakis JD, Kakkar VV, Lawrence D, et al. The origin of thrombi in the deep veins of the lower limb: a venographic study. Br J Surg 1978; 65: 449–51

    Article  PubMed  CAS  Google Scholar 

  213. Kakkar VV, Flanc C, Howe CT, et al. Natural history of postoperative deep-vein thrombosi. Lancet 1969; II: 230–3

    Article  Google Scholar 

  214. Having O. Deep vein thrombosis and pulmonary embolism: an autopsy study with multiple regression analysis of possible risk factors. Acta Surg Scand 1977; 478 Suppl.: 1–120

    Google Scholar 

  215. Lohr JM, Kerr TM, Lutter KS, et al. Lower extremity calf thrombosis: to treat or not to treat. J Vasc Surg 1991; 14: 618–23

    Article  PubMed  CAS  Google Scholar 

  216. Thomas DP. Pathogenesis of venous thrombosis. In: Bloom AL, Forbes CD, Thomas DP, et al., editors. Haemostasis and thrombosis. Edinburgh: Chuchill Livingstone, 1994: 2: 1335–47

    Google Scholar 

  217. Sevitt S. The structure and growth of valve-pocket thrombi in femoral veins. J Clin Pathol 1974; 27: 517–28

    Article  PubMed  CAS  Google Scholar 

  218. Hewson W. An experimental enquiry into the properties of the blood. London: Cadell, 1771

    Google Scholar 

  219. Wessler S. Thrombosis in the presence of vascular stasis. Am J Med 1962; 3: 648–66

    Article  Google Scholar 

  220. Gitel SN, Stephenson RC, Wessler S. In vitro and in vivo correlation of clotting protease activity: effect of heparin. Proc Natl Acad Sci U S A 1977; 74: 3028–32

    Article  PubMed  CAS  Google Scholar 

  221. Pandolfi M, Nilsson I-M, Robertson B, et al. Fibrinolytic activity in human veins. Lancet 1967; II: 127–8

    Article  Google Scholar 

  222. Juhan-Vague I, Valadier J, Allessi MC, et al. Deficient t-PA release and elevated PA inhibitor levels in patients with spontaneous or recurrent DVT. Thromb Haemost 1987; 57: 67–72

    PubMed  CAS  Google Scholar 

  223. Thomas DP, Merton RE, Wood RD, et al. The relationship between vessel wall injury and venous thrombosis: an experimental study. Br JHaematol 1985; 59: 449–57

    Article  CAS  Google Scholar 

  224. Sevitt S. Pathology and pathogenesis of deep vein thrombi. In: Bergan JJ, Yao JST, editors. Venous problems. Chicago (IL): Year Book, 1978:257

    Google Scholar 

  225. Kakkar VV, Day TK. The vessel wall and venous thrombosis. In: Woolf N, editor. Biology and pathology of the vessel wall. Eastbourne: Praeger, 1983: 229

    Google Scholar 

  226. Stewart GJ, Ritchie WGM, Lynch PR. Venous endothelial damage produced by massive sticking and emigration of leucocytes. Am J Pathol 1974; 74: 507–32

    PubMed  CAS  Google Scholar 

  227. Stewart GJ, Stern HS, Lynch PR, et al. Responses of canine jugular veins and carotid arteries to hysterectomy: increased permeability and leucocyte adhesions and invasion. Thromb Res 1980; 20: 473–89

    Article  PubMed  CAS  Google Scholar 

  228. Schaub RG, Simmons CA, Koets MH, et al. Early events in the formation of venous thrombus following local trauma and stasis. Lab Invest 1984; 51: 218–24

    PubMed  CAS  Google Scholar 

  229. Kawasaki T, Kambayashi J-I, Sakon M. Hyperlipidemia: a novel etiologic factor in deep vein thrombosis. Thromb Res 1995; 79: 147–51

    Article  PubMed  CAS  Google Scholar 

  230. Silkworth JB, McLean B, Stehbens WE. The effect of hyperchoelsterolaemia on aortic endothelium studied en face. Atherosclerosis 1975; 22: 335–48

    Article  PubMed  CAS  Google Scholar 

  231. Arcaro G, Zenere BM, Travia D, et al. Non-invasive detection of early endothelial dysfunction in hypercholesterolaemic subjects. Atherosclerosis 1995; 114: 247–54

    Article  PubMed  CAS  Google Scholar 

  232. Proudfit WL, Shirey EK, Sones Jr FM. Selective coronary cinearteriography: correlation with clinical findings in 1000 patients. Circulation 1966; 33: 901–10

    Article  PubMed  CAS  Google Scholar 

  233. Proudfit WL, Shirey EK, Sones Jr FM. Distribution of arterial lesions demonstrated by selective cinecoronary arteriography. Circulation 1967; 36: 54–62

    Article  PubMed  CAS  Google Scholar 

  234. Blumengart HL, Gilligan R, Schlesinger MJ. Experimental studies on the effects of temporary occlusion of coronary arteries. II. The production of myocardial infarction. Am Heart J 1941; 22: 374–89

    Article  Google Scholar 

  235. Miller RD, Burchell HB, Edwards JE. Myocardial infarction with and without acute coronary occlusion: a pathologic study. Arch Intern Med 1951; 88: 597–604

    Article  CAS  Google Scholar 

  236. Dintenfass L. Effect of velocity gradient on the clotting time of blood and on the consistency of clots formed in vitro. Circ Res 1966; 18: 349–56

    Article  PubMed  CAS  Google Scholar 

  237. DeWood MA, Spores J, Notske R, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med 1980; 303: 897–902

    Article  PubMed  CAS  Google Scholar 

  238. Feldman RL. Coronary thrombosis, coronary spasm, and coronary atherosclerosis and speculation on the link between unstable angina and acute myocardial infarction. Am J Cardiol 1987; 59: 1187–90

    Article  PubMed  CAS  Google Scholar 

  239. Ross R. The pathogenesis of atherosclerosis: an update. N Engl J Med 1986; 314: 488–500

    Article  PubMed  CAS  Google Scholar 

  240. Schwarz CJ, Valente AJ, Sprague EA, et al. The pathogenesis of atherosclerosis: an overview. Clin Cardiol 1991; 14:I1–16

    Article  Google Scholar 

  241. Fuster V, Badimon L, Badimon JJ, et al. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992; 326: 242–50

    Article  PubMed  CAS  Google Scholar 

  242. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362: 801–9

    Article  PubMed  CAS  Google Scholar 

  243. Davies MJ. A macro and micro view of coronary vascular insult in ischaemic heart disease. Circulation 1990; 82 Suppl. II: 38–46

    Google Scholar 

  244. Roberts WC, Buja LM. The frequency and significance of coronary arterial thrombi and other observations in fatal acute myocardial infarction: a study of 107 necropsy patients. Am J Med 1972; 52: 425–43

    Article  PubMed  CAS  Google Scholar 

  245. Little WC, Constantinescu M, Applegate RJ, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease. Circulation 1988; 78: 1157–66

    Article  PubMed  CAS  Google Scholar 

  246. Fishbein MC, Siegel RJ. How big are coronary atherosclerotic plaques that rupture? Circulation 1996; 94: 2662–6

    Article  PubMed  CAS  Google Scholar 

  247. Glagov S, Weisenberd E, Zarins C, et al. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987; 316: 1371–5

    Article  PubMed  CAS  Google Scholar 

  248. Raizner AE, Chahine RA. Myocardial infarction with normal coronary arteries. In: Hurst JW, editor. Update I: the heart. New York (NY): McGraw-Hill, 1979: 147–66

    Google Scholar 

  249. Mintz GS, Painter JA, Pichard AD, et al. Atherosclerosis in angiographically ‘normal’ coronary artery reference segments: an intravascular ultrasound study with clinical correlates. J Am Coll Cardiol 1995; 25: 1479–85

    Article  PubMed  CAS  Google Scholar 

  250. Hale G, Dexter D, Jeferson K, et al. Value of coronary arteriography in the investigation of ischaemic heart disease. Br Heart J 1966; 28: 40–54

    Article  PubMed  CAS  Google Scholar 

  251. Ross RS, Friesinger GC. Coronary arteriography. Am Heart J 1966; 72: 437–41

    Article  PubMed  CAS  Google Scholar 

  252. Eliot RS, Bratt G. The paradox of myocardial ischaemia and necrosis in young women and normal coronary arteriograms: relation to abnormal hemoglobin-oxygen dissociation. Am J Cardiol 1969; 23: 633–8

    Article  PubMed  CAS  Google Scholar 

  253. Sidd JJ, Kemp HG, Gorlin R. Acute myocardial infarction in a nineteen-year-old student in the absence of coronary obstructive disease. N Engl J Med 1970; 282: 1306–7

    Article  PubMed  CAS  Google Scholar 

  254. Nizet PM, Robertson L. Normal coronary arteriogram following myocardial infarction in a 17 year old boy. Am J Cardiol 1971; 28: 715–7

    Article  PubMed  CAS  Google Scholar 

  255. Dear HD, Russell RO, Jones WB, et al. Myocardial infarction in the absence of coronary occlusion. Am J Cardiol 1971; 28: 718–21

    Article  PubMed  CAS  Google Scholar 

  256. Glancy DL, Marcus ML, Epstein SE. Myocardial infarction in young women with normal coronary arteriograms. Circulation 1971; 41: 495–502

    Article  Google Scholar 

  257. Brushke AVG, Bryneel KKJ, Bloch A, et al. Acute myocardial infarction without obstructive coronary artery disease demonstrated by selective cine arteriography. Br Heart J 1971; 33: 585–94

    Article  Google Scholar 

  258. Kimbris D, Segal BL, Munir M, et al. Myocardial infarction in patients with normal patent coronary arteries as visulaised by cinearteriography. Am J Cardiol 1972; 29: 724–8

    Article  Google Scholar 

  259. Potts KH, Stein PD, Houk PC. Transmural myocardial infarction with arteriographically normal appearing coronary arteries. Chest 1972; 62: 549–52

    Article  PubMed  CAS  Google Scholar 

  260. Likoff W. Myocardial infarction in subjects with normal coronary arteriograms. Am J Cardiol 1971; 28: 742–3

    Article  PubMed  CAS  Google Scholar 

  261. Lange RL, Reid MS, Tresch DD, et al. Nonatheromatous ischemic heart disease following withdrawal from chronic nitroglycerin exposure. Circulation 1972; 46: 666–78

    Article  PubMed  CAS  Google Scholar 

  262. Salky N, Dugdale M. Platelet abnormalities in ischaemic heart disease. Am J Cardiol 1973; 32: 612–7

    Article  PubMed  CAS  Google Scholar 

  263. Schatz IJ, Mizukami H, Gallagher J, et al. Myocardial infarction in a 14 year old boy with normal coronary arteriograms: studies of blood oxygen release rates. Chest 1973; 63: 963–8

    Article  PubMed  CAS  Google Scholar 

  264. De Pasquale NP, Bruno MS. Normal arteriography in a patient with clinical evidence of myocardial infarction. Chest 1973; 63: 618–9

    Article  Google Scholar 

  265. Eliot RS, Baroldi G, Leone A. Necropsy studies in myocardial infarction with minimal or no coronary luminal reduction due to atherosclerosis. Circulation 1974; 49: 1127–31

    Article  PubMed  CAS  Google Scholar 

  266. Brest AN, Wiener L, Kasparian H, et al. Myocardial infarction without obstructive coronary artery disease. Am Heart J 1974; 88: 219–24

    Article  PubMed  CAS  Google Scholar 

  267. Greenberg H, Dwyer EM. Myocardial infarction and ventricular aneurysm in a patient with normal coronary arteries. Chest 1974; 66: 306–8

    Article  PubMed  CAS  Google Scholar 

  268. Smith DC, Vieweg VR. Acute transmural myocardial infarction: its occurence in a young man without demonstrable coronary artery disease. JAMA 1974; 229: 811–3

    Article  PubMed  CAS  Google Scholar 

  269. Sasse L, Wagner R, Murray FE. Transmural myocardial infarction during pregnancy. Am J Cardiol 1975; 35: 448–52

    Article  PubMed  CAS  Google Scholar 

  270. Rosenblatt A, Selzer A. The nature and clinical features of myocardial infarction with normal coronary arteriogram. Circulation 1977; 55: 578–80

    Article  PubMed  CAS  Google Scholar 

  271. Oliva PB, Breckenridge JC. Acute myocardial infarction with normal and near normal coronary arteries. Am J Cardiol 1977; 40: 1000–7

    Article  PubMed  CAS  Google Scholar 

  272. Erlebacher JA. Transmural myocardial infarction with ‘normal’ coronary arteries. Am Heart J 1979; 98: 421–30

    Article  PubMed  CAS  Google Scholar 

  273. Ciraulo DA, Bresnaham GF, Frankel PF, et al. Transmural myocardial infarction with normal coronary angiograms and with single vessel coronary obstruction. Chest 1983; 2: 196–202

    Article  Google Scholar 

  274. Campeau L, Lesperance J, Bourassa MG, et al. Myocardial infarction without obstructive disease at coronary arteriography. Can Med Assoc J 1968; 99: 837–43

    PubMed  CAS  Google Scholar 

  275. Welch CC, Proudfit WL, Sones Jr FM, et al. Cinecoronary arteriography in young men. Circulation 1970; 42: 647–52

    Article  PubMed  CAS  Google Scholar 

  276. Betriu A, Pare JC, Sanz GI, et al. Myocardial infarction with normal coronary arteries; a prospective clinical-angiographic study. Am J Cardiol 1981; 48: 28–32

    Article  PubMed  CAS  Google Scholar 

  277. Legrand V, Deliege M, Henrard L, et al. Patients with myocardial infarction and normal coronary arteriogram. Chest 1983; 2: 196–202

    Google Scholar 

  278. Khan AH, Haywood LJ. Myocardial infarction in nine patients with radiologically patent coronary arteries. N Engl J Med 1974; 291: 427–31

    Article  PubMed  CAS  Google Scholar 

  279. Waters DD, Halphen C, Theroux P, et al. Coronary artery disease in young women: clinical and angiographic features and correlation with risk factors. Am J Cardiol 1978; 42: 41–7

    Article  PubMed  CAS  Google Scholar 

  280. Bemiller CR, Pepine CJ, Rogers AK. Long-term observations in patients with angina and normal coronary arteriograms. Circulation 1973; 47: 36–43

    Article  PubMed  CAS  Google Scholar 

  281. Regan T, Wu CF, Weisse AB, et al. Acute myocardial infarction in toxic cardiomyopathy without coronary obstruction. Circulation 1975; 51: 453–61

    Article  PubMed  CAS  Google Scholar 

  282. Raymond R, Lynch J, Underwood D, et al. Myocardial infarction and normal coronary arteriography: a 10 year clinical and risk analysis of74 patients. J Am Coll Cardiol 1988; 11:471–7

    Article  PubMed  CAS  Google Scholar 

  283. Arnett EN, Roberts WC. Acute myocardial infarction and angiographically normal coronary arteries: an unproven combination. Circulation 1976; 53: 395–400

    Article  PubMed  CAS  Google Scholar 

  284. Lindsay J, Pichard AD. Acute myocardial infarction with normal coronary arteries. Am J Cardiol 1984; 54: 902–4

    Article  PubMed  Google Scholar 

  285. Ciraulo DA. Recurrent myocardial infarction and angina in a woman with normal coronary angiograms. Am J Cardiol 1975; 35: 923–6

    Article  PubMed  CAS  Google Scholar 

  286. Vincent GM, Anderson JL, Marshall HW. Coronary spasm producing coronary thrombosis and myocardial infarction. N Engl J Med 1983; 309: 220–3

    Article  PubMed  CAS  Google Scholar 

  287. Gonzalez M, Hernandez E, Aranda JM, et al. Acute myocardial infarction due to intracoronary occlusion after elective cardioversion for atrial fibrillation in a patient with angiographic nearly normal arteries. Am Heart J 1981; 102: 932–4

    Article  PubMed  CAS  Google Scholar 

  288. Morris DC, Hurst JW, Logue RB. Myocardial infarction in young women. Am J Cardiol 1976; 38: 299–304

    Article  PubMed  CAS  Google Scholar 

  289. Isner JM, Estes NAM, Thompson PD, et al. Acute cardiac events temporally related to cocaine abuse. N Engl J Med 1986; 315: 1438–43

    Article  PubMed  CAS  Google Scholar 

  290. O’Neil D, McArthur JD, Kennedy JA, et al. Myocardial infarction and the normal arteriogram: possible role of viral myocarditis. Postgrad Med J 1985; 61: 485–8

    Article  Google Scholar 

  291. Henderson RR, Hansing CE, Razavi M, et al. Resolution of an obstructive coronary lesion as demonstrated by selective angiography in a patient with transmural myocardial infarction. Am J Cardiol 1973; 31: 785–8

    Article  PubMed  CAS  Google Scholar 

  292. Willerson JT, Yao SK, McNatt J, et al. Frequency and severity of cyclic flow alterations and platelet aggregation predict the severity of neointimal proliferation following experimental coronary stenosis and endothelial injury. Proc Natl Acad Sci U S A 1991; 15: 1667–87

    Google Scholar 

  293. Casscells W Migration of smooth muscle cells and endothelial cells: critical events inrestenosis. Circulation 1992; 86: 723–9

    Article  PubMed  CAS  Google Scholar 

  294. Casscells W, Ferguson JJ, Willerson JT, et al. Thrombus and unstable angina. Lancet 1993; 342: 1151–5

    Article  Google Scholar 

  295. Ludmer PL, Selwyn AP, Shook TL, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 1986; 315: 1046–51

    Article  PubMed  CAS  Google Scholar 

  296. Cheng TO, Bashour T, Singh BK, et al. Myocardial infarction in the absence of coronary arteriosclerosis. Am J Cardiol 1972; 30: 680–2

    Article  PubMed  CAS  Google Scholar 

  297. Johnson AD, Detwiler JH. Coronary spasm, variant angina, and recurrent myocardial infarctions. Circulation 1977; 55: 947–50

    Article  PubMed  CAS  Google Scholar 

  298. Heupler FA. Syndrome of symptomatic coronary arterial spasm with nearly normal coronary arteriograms. Am J Cardiol 1979; 45: 873–81

    Article  Google Scholar 

  299. Gersh BJ, Bassendine MF, Forman R, et al. Coronary artery spasm and myocardial infarction in the absence of angiographically demonstrable obstructive coronary disease. Mayo Clin Proc 1981; 56: 700–8

    PubMed  CAS  Google Scholar 

  300. Bott-Silverman C, Heupler FA. Natural history of pure coronary artery spasm in patients treated medically. J Am Coll Cardiol 1983; 2: 200–5

    Article  PubMed  CAS  Google Scholar 

  301. Conti CR. Myocardial infarction: thoughts about pathogenesis and the role of coronary artery spasm. Am Heart J 1985; 110: 187–93

    Article  PubMed  CAS  Google Scholar 

  302. Madias JE. The long-term outcome of patients who suffered an acute myocardial infarction in the midst of recurrent attacks of variant angina. Clin Cardiol 1986; 9: 277–84

    Article  PubMed  CAS  Google Scholar 

  303. Maseri A, L’Abbate A, Baroldi G, et al. Coronary vasospasm as a possible cause of myocardial infarction. N Engl J Med 1978; 299: 1271–7

    Article  PubMed  CAS  Google Scholar 

  304. Haerem JW. Platelet aggregates in intramyocardial vessels of patients dying suddenly and unexpectedly of coronary artery disease. Atherosclerosis 1974; 15: 199–213

    Article  Google Scholar 

  305. Folts JD, Crowell EB, Rowe GG. Platelet aggregation in partially obstructed vessels and its elimination with aspirin. Circulation 1976; 54: 365–70

    Article  PubMed  CAS  Google Scholar 

  306. Fleischman AI, Bierenbaum ML, Justico D, et al. In vivo platelet function in acute myocardial infarction, acute cerebrovascular accidents and following surgery. Thromb Res 1975; 6: 205–7

    Article  PubMed  CAS  Google Scholar 

  307. Nobuyoshi M, Tanaka M, Nosaka H, et al. Progression of coronary atherosclerosis: is coronary spasm related to progression? J Am Coll Cardiol 1991; 18: 904–10

    Article  PubMed  CAS  Google Scholar 

  308. O’Reilly RJ, Spellberg RD. Rapid resolution of coronary arterial emboli: myocardial infarction and subsequent normal coronary arteriograms. Ann Intern Med 1974; 81: 348–50

    PubMed  Google Scholar 

  309. Lindley RI, Warlow CR Acute ischaemic stroke and transient ischaemic attacks. In: Bloom AL, Forbes CD, Thomas DP, et al., editors. Haemostasis and thrombosis. Edinburgh: Churchill Livingstone, 1994: 1255–73

    Google Scholar 

  310. Wolf PA, Cobb JL, D’Agostino RB. Epidemiology of stroke. In: Barnett HJM, Mohr JP, Stein BM, et al., editors. Stroke: pathophysiology, diagnosis and management. New York (NY): Churchill Livingstone, 1992

    Google Scholar 

  311. Yano K, Reed DM, MacLean CJ. Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program. Stroke 1989; 20: 1460–5

    Article  PubMed  CAS  Google Scholar 

  312. Dear HD, Jones WB. Myocardial infarction associated with the use of oral contraceptives. Ann Intern Med 1971; 74: 236–9

    PubMed  CAS  Google Scholar 

  313. Waxier EB, Kimbris D, van den Broek H, et al. Myocardial infarction and oral contraceptive agents. Am J Cardiol 1971; 28: 96–101

    Article  Google Scholar 

  314. Maleki M, Lange RL. Coronary thrombosis in young women on oral contraceptives: report of two cases and review of the literature. Am Heart J 1973; 85: 749–54

    Article  PubMed  CAS  Google Scholar 

  315. Jugdutt BI, Stevens GF, Zacks DJ, et al. Myocardial infarction, oral contraception, cigarette smoking, and coronary artery spasm in young women. Am Heart J 1983; 106: 757–61

    Article  PubMed  CAS  Google Scholar 

  316. Landau E, Lessing JB, Weintraub M, et al. Acute myocardial infarction in a young woman taking oral contraceptive: a case report. J Reprod Med 1986; 31: 1008–10

    PubMed  CAS  Google Scholar 

  317. Engel H-J, Hundeshagen H, Lichtlen P. Transmural myocardial infraction in young women taking oral contraceptives: evidence of reduced regional coronary flow in spite of normal coronary arteries. Br Heart J 1977; 39: 477–84

    Article  PubMed  CAS  Google Scholar 

  318. Engel H-J, Engel E, Lichtlen PR. Coronary atherosclerosis and myocardial infarction in young women: role of oral contraceptives. Eur Heart J 1983; 4: 1–8

    PubMed  CAS  Google Scholar 

  319. Engel H-J, Engel E, Lichtlen P. Coronary arteriosclerosis and myocardial infarction in young women: the role of oral contraceptive (in German). Munch Med Wschr 1985; 127: 415–7

    Google Scholar 

  320. Engel H-J. Angiographic findings after myocardial infarctions of young women: role of oral contraceptives. Adv Contracept 1991; 7 Suppl. 3:235–43

    Google Scholar 

  321. Myhre E. Oral contraceptives and myocardial infarction [letter]. BMJ 1973; 4: 737

    Article  Google Scholar 

  322. Stout C. Coronary thrombosis without coronary atherosclerosis. Am J Cardiol 1969; 24: 564–9

    Article  PubMed  CAS  Google Scholar 

  323. Weiss S. Myocardial infarction and oral contraceptives. N Engl J Med 1972; 286: 436–7

    PubMed  CAS  Google Scholar 

  324. Altshuler JH, McLaughlin RA, Neuberger KT. Neurological catastrophe related to oral contraceptives. Arch Neurol 1968; 19: 264–73

    Article  PubMed  CAS  Google Scholar 

  325. Buchanan DS, Brazinsky JH. Durai sinus and cerebral venous thrombosis: incidence in young women receiving oral contraceptives. Arch Neurol 1970; 22: 440–4

    Article  PubMed  CAS  Google Scholar 

  326. Hartman JD, Young I, Bank AA. Fibromuscular hyperplasia of internal carotid arteries. Arch Neurol 1971; 25: 295–301

    Article  PubMed  CAS  Google Scholar 

  327. Poltera AA. The pathology of intracranial venous thrombosis in oral contraception. J Pathol 1972; 106: 209–19

    Article  PubMed  CAS  Google Scholar 

  328. Reed DL, Coon WW. Thromboembolism in patients receiving progestational drugs. N Engl J Med 1963; 269: 622–4

    Article  PubMed  CAS  Google Scholar 

  329. Lowry JB, Orr KG, Wade WG. Infarction of the small intestine associated with oral contraceptives. J Ir Med Assoc 1969; 62(385): 260–2

    PubMed  CAS  Google Scholar 

  330. Hurwitz RL, Martin AJ, Grossman BE, et al. Oral contraceptives and gastrointestinal disorders. Ann Surg 1970; 172: 892–6

    Article  PubMed  CAS  Google Scholar 

  331. Rose MB. Superior mesenteric vein thrombosis and oral contraceptives. Postgrad Med J 1972; 48: 430–3

    Article  PubMed  CAS  Google Scholar 

  332. Hoyle M, Kennedy A, Prior L, et al. Small bowel ischaemia and infarction in young women taking oral contraceptives and progestational agents. Br J Surg 1977; 64: 533–7

    Article  PubMed  CAS  Google Scholar 

  333. Kennedy HA, Prior AL, Thomas GE. Small bowel ischaemia and infarction in young women taking oral contraceptives and progestational agents. Br J Surg 1977; 64: 533–7

    Article  PubMed  Google Scholar 

  334. Lescher TJ, Bombeck CT. Mesenteric vascular occlusion associated with oral contraceptive use. Arch Surg 1977; 112: 1231–2

    Article  PubMed  CAS  Google Scholar 

  335. Civetta MJM, Kolodny MM. Mesenteric venous thrombosis associated with oral contraceptives. Gastroenterology 1980; 58: 713–7

    Google Scholar 

  336. Welin G, Persson T. Oral contraceptive and thrombosis of coeliac artery [letter]. Lancet 1968; II: 1348

    Article  Google Scholar 

  337. Keown D. Review of arterial thrombosis in association with oral contraceptives. Br J Surg 1969; 56: 486–8

    Article  PubMed  CAS  Google Scholar 

  338. Koh KS, Danzinger RG. Massive intestinal infarction in young women: complication of use of oral contraceptives. Can Med Assoc J 1977; 116:513–5

    PubMed  CAS  Google Scholar 

  339. Lamy AL, Roy PH, Morisette J-J, et al. Intimai hyperplasia and thrombosis of the visceral arteries in a young woman: possible relation with oral contraceptives and smoking. Surgery 1988; 103: 706–9

    PubMed  CAS  Google Scholar 

  340. Irey NS, Manion WC, Taylor HB. Vascular lesions in women taking oral contraceptives. Arch Pathol 1970; 89(1): 1–8

    PubMed  CAS  Google Scholar 

  341. Irey NS, Norris HJ. Intimai vascular lesions associated with female reproductive steroids. Arch Pathol 1973; 96: 227–34

    PubMed  CAS  Google Scholar 

  342. Manolo-Estrella P, Barker AE. Histopathologic findings in human aortic media associated with pregnancy: a study of 16 cases. Arch Pathol 1967; 83: 336–41

    Google Scholar 

  343. Irey NS, McAllister HA, Henry JM. Oral contraceptives and stroke in young women: a clinicopathologic correlation. Neurology 1978; 28: 1216–9

    Article  PubMed  CAS  Google Scholar 

  344. MacKinnon HH, Fekete JK. Congenital afibrinogenemia: vascular changes and multiple thromboses induced by fibrinogen infusions and contraceptive medication. Can Med Assoc J 1971; 104:597–9

    PubMed  CAS  Google Scholar 

  345. Dindar F, Platts ME. Intracranial venous thrombosis complicating oral contraception. Can Med Assoc J 1974; 111: 545–8

    PubMed  CAS  Google Scholar 

  346. Barillon A, Allard J, Vorhauer W, et al. Coronary thrombosis after oral contraception [in French]. Nouv Presse Med 1977; 6: 2758–60

    Google Scholar 

  347. Taylor ES. Editorial comment. ObstetGynecol Surv 1974; 29:182

    Google Scholar 

  348. Blaustein A, Shenker L, Post RC. The effects of oral contraceptives on the endometrium. Int J Fertil 1968; 13: 466–75

    PubMed  CAS  Google Scholar 

  349. Grant ECG. Venous effects of oral contraceptives. BMJ 1969; 4: 73–7

    Article  PubMed  CAS  Google Scholar 

  350. Osterholzer HO, Grillo D, Kruger PS, et al. The effect of oral contraceptive steroids on branches of the uterine artery. Obstet Gynecol 1977; 49: 227–32

    PubMed  CAS  Google Scholar 

  351. Schenker JG, Ivry M, Oliver M. The effect of oral contraceptives on microcirculation. Obstet Gynecol 1972; 93: 909–16

    Google Scholar 

  352. Lipschutz A. Steroid hormones and tumours. Baltimore (MD): Williams and Wilkins, 1950

    Google Scholar 

  353. Bruzzone S. Oestrogen-induced fibroids of the thoracic serosa. Br J Cancer 1948; 2: 267–72

    Article  PubMed  CAS  Google Scholar 

  354. Danforth DN, Mnalo-Estrella P, Buckingham JC. The effect of pregnancy and of Enovid on the rabbit vasculature. Am J Obstet Gynecol 1964; 88: 952–62

    PubMed  CAS  Google Scholar 

  355. Cutts JH. Vascular lesions resembling polyarteritis nodosa in rats undergoing prolonged stimulation with oestrogen. Br J Exp Pathol 1966; 47: 401–4

    PubMed  CAS  Google Scholar 

  356. Albert EN. The effect of pregnancy on the elastic membranes of mesometrial arteries in the guinea pig. Am J Anat 1967; 120:611–25

    Article  PubMed  CAS  Google Scholar 

  357. Albert E, Bhussry BR. The effect of multiple pregnancies and age on the elastic tissue of uterine arteries in the guinea pig. Am J Anat 1967; 121: 259–69

    Article  PubMed  CAS  Google Scholar 

  358. Friederici HHR. The early response of uterine capillaries to estrogen stimulation. Lab Invest 1967; 17: 322–33

    PubMed  CAS  Google Scholar 

  359. Wexler BC. Vascular degenerative changes in the uterine arteries and veins of multiparous rats. Am J Obstet Gynecol 1970; 107: 6–16

    PubMed  CAS  Google Scholar 

  360. Gammal EB. Intimai thickening in the arteries of rats treated with synthetic sex hormones. Br J Exp Pathol 1976; 57: 248–54

    PubMed  CAS  Google Scholar 

  361. Widmann J, Fahimi HD. Proliferation of endothelial cells in oestrogen-stimulated rat liver. Lab Invest 1976; 34: 141–9

    PubMed  CAS  Google Scholar 

  362. Gammal EB, Monture MC. Uptake of Evans blue-bound albumin in the aorta of estrogen-treated rats. Br J Exp Pathol 1979; 60: 58–64

    PubMed  CAS  Google Scholar 

  363. Adams MR, Clarkson TB, Koritnik DR, et al. Contraceptive steroids and coronary artery atherosclerosis in cynomolgus macaques. Fertil Steril 1987; 47: 1010–8

    PubMed  CAS  Google Scholar 

  364. Shively CA, Kaplan JR, Clarkson TB. Carotid artery atherosclerosis in cholesterol-fed female cynomolgus: effects of oral contraceptive treatment, social factors, and regional adiposity. Arteriosclerosis 1990; 10: 358–66

    Article  PubMed  CAS  Google Scholar 

  365. Kaplan JR, Adams MR, Anthony MS, et al. Dominant social status and contraceptive hormone treatment inhibit atherogenesis in premenopausal monkeys. Arterioscler Thromb Vasc Biol 1995; 15: 2094–100

    Article  PubMed  CAS  Google Scholar 

  366. Adams MR, Anthony MS, Manning JM, et al. Low-dose contraceptive estrogen-progestin and coronary artery atherosclerosis of monkeys. Obstet Gynecol 2000; 96: 250–5

    Article  PubMed  CAS  Google Scholar 

  367. Hopkins PN, Williams RR. A survey of 246 suggested coronary risk factors. Atherosclerosis 1981; 40: 1–52

    Article  PubMed  CAS  Google Scholar 

  368. Wilson PWF, Garrison RJ, Castelli WP. Postmenopausal oestrogen use, cigarette smoking, and cardiovascular morbidity in women over 50. N Engl J Med 1985; 313: 1038–43

    Article  PubMed  CAS  Google Scholar 

  369. Reaven G. Banting lecture 1988: role of insulin resistance in human disease. Diabetes 1988; 37: 1595–607

    Article  PubMed  CAS  Google Scholar 

  370. Edwards KL, Austin MA, Newman B, et al. Multivariate analysis of the insulin resistance syndrome in women. Arterioscler Thromb 1994; 14: 1940–5

    Article  PubMed  CAS  Google Scholar 

  371. Leyva F, Godsland IF, Walton C, et al. Factors of the metabolic syndrome: baseline interrelationships in the first follow-up cohort of the HDDRISC Study (HDDRISC-1). Arterioscler Throm Vasc Biol 1998; 18: 208–14

    Article  CAS  Google Scholar 

  372. Pyorälä M, Miettinen H, Halonen P, et al. Insulin resistance syndrome predicts the risk of coronary heart disease and stroke in healthy middle-aged men: the 22-year follow-up of the Helsinki Policemen Study. Arterioscler Thromb Vasc Biol 2000; 20: 538–44

    Article  PubMed  Google Scholar 

  373. Manalo-Estrella P, Danforth DN, Buckingham JC. Regression rate of vascular effects induced by pregnancy and by norethynodrel-mestranol. Fertil Steril 1965; 16: 81–4

    PubMed  CAS  Google Scholar 

  374. Almén T, Härtel M, Nylander G, et al. The effect of estrogen on the vascular endothelium and its possible relation to thrombosis. Surg Gynecol Obstet 1975; 140: 938–40

    PubMed  Google Scholar 

  375. Goodrich SM, Wood JE. Peripheral venous distensibility and velocity of venous blood flow during pregnancy or during oral contraceptive therapy. Am J Obstet Gynecol 1964; 90: 740–4

    PubMed  CAS  Google Scholar 

  376. Fawer R, Dettling A, Weihs D, et al. Effect of the menstrual cycle, oral contraception and pregnancy on forearm blood flow, venous distensibility and clotting factors. Eur J Clin Pharmacol 1978; 13: 251–7

    Article  PubMed  CAS  Google Scholar 

  377. Tollan A, Kvenild K, Strand H, et al. Increased capillary permeability for plasma proteins in oral contraceptive users. Contraception 1992; 45: 473–81

    Article  PubMed  CAS  Google Scholar 

  378. Srivastava M, Oakley N, Tompkins C, et al. Insulin metabolism, insulin sensitivity and hormonal responses to insulin infusion in patients taking oral contraceptive steroids. Eur J Clin Invest 1975; 5: 425–33

    PubMed  CAS  Google Scholar 

  379. Wingrove C, Garr E, Godsland IF, et al. 17 beta oestradiol enhances release of matrix metalloproteinase-2 from human vascular smooth muscle cells. Biochim Biophys Acta 1998; 1406: 169–74

    Article  PubMed  CAS  Google Scholar 

  380. Bagdade JD, Subbaiah PV Atherosclerosis and oral contraceptive use: serum from contraceptive users stimulates growth of arterial smooth muscle cells. Arteriosclerosis 1982; 2: 170–6

    Article  PubMed  CAS  Google Scholar 

  381. Bagdade JD, Subbaiah PV, Hintz RL, et al. The measurement of arterial smooth muscle cell mitogens in the blood of oral contraceptive users. Atherosclerosis 1985; 56: 149–55

    Article  PubMed  CAS  Google Scholar 

  382. Godsland IF. The influence of female sex steroids on glucose metabolism and insulin action. J Intern Med Suppl 1996; 738: 1–60

    PubMed  CAS  Google Scholar 

  383. Robertson OH, Wexler BC, Miller BF. Degenerative changes in the cardiovascular system of the spawning Pacific salmon (Oncorhynchus tshawytscha). Circ Res 1967; 9: 826–34

    Article  Google Scholar 

  384. Griffin JH, Kojima K, Banka CL, et al. High-density lipoprotein enhancement of anticoagulant activities of plasma protein S and activated protein C. J Clin Invest 1999; 103: 219–27

    Article  PubMed  CAS  Google Scholar 

  385. Epand RM, Stafford A, Leon B, et al. HDL and apolipoprotein A-I protect erythrocytes against generation of procoagulant activity. Arterioscler Thromb 1994; 14: 1775–83

    Article  PubMed  CAS  Google Scholar 

  386. Yui Y, Aoyama T, Morishita H, et al. Serum prostacyclin stabilizing factor is identical to apolipoprotein A-1 (Apo A-I). J Clin Invest 1988; 82: 803–7

    Article  PubMed  CAS  Google Scholar 

  387. Desai K, Mistry P, Bagget C, et al. Inhibition of platelet aggregation by abnormal high density lipoprotein particles in plasma from patients with hepatic cirrhosis. Lancet 1989; I: 693–5

    Article  Google Scholar 

  388. Cockerill GW, Rye K-A, Gamble JR, et al. High-density lipo-proteins inhibit cytokine-induced expression of endothelial cell adhesion molecules. Arterioscler Thromb Vasc Biol 1995; 15: 1987–94

    Article  PubMed  CAS  Google Scholar 

  389. Navab M, Imes S, Hough G, et al. Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein. J Clin Invest 1991; 88(6): 2039–46

    Article  PubMed  CAS  Google Scholar 

  390. Mackness MI, Durrington PN. HDL, its enzymes and its potential to influence lipid peroxidation. Atherosclerosis 1995; 115: 243–53

    Article  PubMed  CAS  Google Scholar 

  391. Matsuda Y, Hirata K, Inoue N, et al. High density lipoprotein reverses inhibitory effect of oxidized low density lipoprotein on endothelium-dependent arterial relaxation. Circ Res 1993; 72: 1103–9

    Article  PubMed  CAS  Google Scholar 

  392. Zeiher AM, Schachinger V, Hohnloser SH, et al. Coronary atherosclerotic wall thickening and vascular reactivity in humans. Circulation 1994; 89: 2525–32

    Article  PubMed  CAS  Google Scholar 

  393. Pincus G. Control of fertility. New York (NY): Academic Press, 1965

    Google Scholar 

  394. Aurell M, Cramer K, Rybo G. Serum lipids and lipoproteins during long-term administration of an oral contraceptive. Lancet 1966; I: 291–3

    Article  Google Scholar 

  395. Wynn V, Doar J, Mills G. Some effects of oral contraceptives on serum-lipid and lipoprotein levels. Lancet 1966; II: 720–3

    Article  Google Scholar 

  396. Wynn V, Doar J, Mills G, et al. Fasting serum triglyceride, cholesterol, and lipoprotein levels during oral-contraceptive therapy. Lancet 1969; II: 756–60

    Article  CAS  Google Scholar 

  397. Bickerstaff ER, Macdonald G, Holmes J. Cerebral arterial insufficiency and oral contraceptives. BMJ 1967; 1: 726–9

    Article  PubMed  CAS  Google Scholar 

  398. de Graaf J, Swinkels D, Demacker P, et al. Differences in low density lipoprotein subfraction profile between oral contraceptive users and controls. J Clin Endocrinol Metab 1993; 76: 197–202

    Article  PubMed  Google Scholar 

  399. Stokes T, Wynn V. Serum-lipids in women on oral contraceptives. Lancet 1971; II: 677–80

    Article  Google Scholar 

  400. Wallace RB, Hoover J, Sandier D, et al. Altered plasma lipids associated with oral contraceptive or oestrogen consumption: the Lipid Research Clinic Program. Lancet 1977; I: 11–4

    Article  Google Scholar 

  401. Wallace RB, Hoover J, Barrett-Connor E, et al. Altered plasma lipoprotein levels associated with oral contraceptive and oestrogen use. Lancet 1979; I: 111–5

    Article  Google Scholar 

  402. Wahl PW, Waiden R, Knopp R, et al. Effect of estrogen/progestin potency on lipid/lipoprotein cholesterol. N Engl J Med 1983; 308: 862–7

    Article  PubMed  CAS  Google Scholar 

  403. Wahl PW, Waiden CE, Knopp RH, et al. Lipid and lipoprotein triglyceride and cholesterol interrelationships: effects of sex, hormone use and hyperlipidaemia. Metabolism 1984; 33: 502–8

    Article  PubMed  CAS  Google Scholar 

  404. Tall AR. Plasma high density lipoproteins: metabolism and relationship to atherogenesis. J Clin Invest 1990; 86: 379–84

    Article  PubMed  CAS  Google Scholar 

  405. Bradley D, Wingerd J, Petitti D, et al. Serum high-density-lipo-protein cholesterol in women using oral contraceptives, estrogens and progestins. N Engl J Med 1978; 299: 17–20

    Article  PubMed  CAS  Google Scholar 

  406. Fotherby K. Oral contraceptives, lipids and cardiovascular disease. Contraception 1985; 31: 376–94

    Article  Google Scholar 

  407. Burkman RT. Lipid and lipoprotein changes in relation to oral contraception and hormonal replacement therapy. Fertil Steril 1988; 49: 39S–50

    PubMed  CAS  Google Scholar 

  408. Crook D, Godsland I, Wynn V. Oral contraceptives and coronary heart disease: modulation of glucose tolerance and plasma lipid risk factors by progestins. Am J Obstet Gynecol 1988; 158: 1612–20

    PubMed  CAS  Google Scholar 

  409. Speroff L, DeCherney A, Burkman RT, et al. Evaluation of a new generation of oral contraceptives. Obstet Gynecol 1993; 81: 1034–47

    PubMed  CAS  Google Scholar 

  410. Newton JR. Classification and comparison of oral contraceptives containing new generation progestogens. Hum Reprod Update 1995; 1: 231–63

    Article  PubMed  CAS  Google Scholar 

  411. Godsland I, Crook D, Simpson R, et al. The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism. N Engl J Med 1990; 323: 1375–81

    Article  PubMed  CAS  Google Scholar 

  412. Lipson A, Stoy D, LaRosa J, et al. Progestins and oral contraceptive-induced lipoprotein changes: a prospective study. Contraception 1986; 34: 121–33

    Article  PubMed  CAS  Google Scholar 

  413. Burkman RT, Zacur HA, Kimball AW, et al. Oral contraceptives and lipids and lipoproteins: Pt 1. Variations in mean levels by oral contraceptive type. Contraception 1989; 40: 553–61

    Article  PubMed  CAS  Google Scholar 

  414. Lobo RA, Skinner JB, Lippman JS, et al. Plasma lipids and desogestrel and ethinyl estradiol: a meta-analysis. Fertil Steril 1996; 65: 1100–9

    PubMed  CAS  Google Scholar 

  415. Godsland I, Crook D, Worthington M, et al. Effects of a low-estrogen, desogestrel-containing oral contraceptive on lipid and carbohydrate metabolism. Contraception 1993; 48: 217–27

    Article  PubMed  CAS  Google Scholar 

  416. Crook D, Godsland I, Worthington M, et al. A comparative metabolic study of two low-dose oral contraceptives containing gestodene and desogestrel progestins. Am J Obstet Gynecol 1993; 169: 1183–9

    PubMed  CAS  Google Scholar 

  417. Wiegratz I, Jung-Hoffman C, Gross W, et al. Effect of two oral contraceptives containing ethinyl estradiol and gestodene or norgestimate on different lipid and lipoprotein parameters. Contraception 1998; 58: 83–91

    Article  PubMed  CAS  Google Scholar 

  418. Hokanson JE, Austin MA. Plasma triglyceride as a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996; 3: 213–20

    Article  PubMed  CAS  Google Scholar 

  419. Manninen V, Elo MO, Frick MH, et al. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. JAMA 1988; 260: 641–51

    Article  PubMed  CAS  Google Scholar 

  420. Ericsson CG, Hamsten A, Nilsson J, et al. Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients. Lancet 1996; 347: 849–53

    Article  PubMed  CAS  Google Scholar 

  421. Walsh BW, Sacks FM. Effects of low dose oral contraceptives on very low density lipoprotein metabolism. J Clin Invest 1993; 91: 2126–32

    Article  PubMed  CAS  Google Scholar 

  422. Berr F, Eckel RH, Kern F Contraceptive steroids increase hepatic uptake of chylomicron remnants in healthy young women. J Lipid Res 1986; 27: 645–51

    PubMed  CAS  Google Scholar 

  423. Miller GJ. Hyperlipidemia and hypercoagulability. Prog Lipid Res 1993; 32: 61–69

    Article  PubMed  CAS  Google Scholar 

  424. Mussoni L, Maderna P, Camera M, et al. Atherogenic lipoproteins and release of plasminogen activator inhibitor-1 (PSAI-1) by endothelial cells. Fibrinolysis 1990; 4 Suppl. 2: 79–81

    Article  CAS  Google Scholar 

  425. Crook D. HRT and hypertriglyceridaemias. In: Whitehead MI, editor. The prescriber’s guide to hormone replacement therapy. London: Parthenon Publishing, 1998: 183–92

    Google Scholar 

  426. Miller-Bass K, Newschaffer CJ, Klag MJ, et al. Plasma lipoprotein levels as predictors of cardiovascular death in women. Arch Intern Med 1993; 153: 2209–16

    Article  Google Scholar 

  427. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol: Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999; 34: 410–8

    Article  Google Scholar 

  428. Tangirala RK, Tsukamoto K, Chun SH, et al. Regression of atherosclerosis induced by liver-directed gene transfer of apolipoprotein A-I in mice. Circulation 1999; 100: 1816–22

    Article  PubMed  CAS  Google Scholar 

  429. Reaven GM, Laws A. Insulin resistance, compensatory hyper-insulinaemia, and coronary heart disease. Diabetologia 1994; 37(9): 948–52

    Article  PubMed  CAS  Google Scholar 

  430. Barrett-Connor EL, Cohn BA, Wingard DL, et al. Why is diabetes mellitus a stronger risk factor for fatal ischaemic heart disease in women than in men? The Rancho Bernardo Study. JAMA 1991; 265: 627–31

    Article  PubMed  CAS  Google Scholar 

  431. Wynn V, Doar J. Some effects of oral contraceptives on carbohydrate metabolism. Lancet 1966; II: 715–9

    Article  Google Scholar 

  432. Houssay BA, Foglia VG, Rodriguez RR. Production and prevention of some types of experimental diabetes by oestrogens or corticosteroids. Acta Endocrinol 1954; 17: 146–64

    PubMed  CAS  Google Scholar 

  433. Godsland IF. Interactions of oral contraceptive use with the effects of age, exercise habit and other cardiovascular risk modifiers on metabolic risk markers. Contraception 1996; 53: 9–16

    Article  PubMed  CAS  Google Scholar 

  434. Bergman R, Finegood D, Ader M. Assessment of insulin sensitivity in vivo. Endocr Rev 1985; 6: 45–86

    Article  PubMed  CAS  Google Scholar 

  435. Horwitz D, Starr J, Mako M, et al. Proinsulin, insulin and C-peptide concentrations in human portal and peripheral blood. J Clin Invest 1975; 55: 1278–83

    Article  PubMed  CAS  Google Scholar 

  436. Hollenbeck C, Reaven GM. Variations in insulin-stimulated glucose uptake in healthy individuals with normal glucose tolerance. J Clin Endocrinol Metab 1987; 64: 1169–73

    Article  PubMed  CAS  Google Scholar 

  437. Gerstein HC, Yusuf S. Dysglycaemia and risk of cardiovascular disease. Lancet 1996; 347: 949–50

    Article  PubMed  CAS  Google Scholar 

  438. Stamler R, Stamler J, editors. Asymptomatic hyperglycemia and coronary heart disease: a series of papers by the International Collaborative Group, based on studies in fifteen populations. J Chronic Dis 1979; 32: 683–837

    Article  Google Scholar 

  439. Fuller J, Shipley M, Rose G, et al. Mortality from coronary heart disease and stroke in relation to degree of glycaemia: the Whitehall Study. BMJ 1983; 287: 867–70

    Article  PubMed  CAS  Google Scholar 

  440. Eschwege E, Richard J, Thibult N, et al. Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels: the Paris Prospective Study, ten years later. Horm Metab Res 1985; 15 Suppl.: 41–6

    CAS  Google Scholar 

  441. Burchfield CM, Curb JD, Rodriguez BL, et al. Glucose intolerance and 22-year stroke incidence: the Honolulu Heart Program. Stroke 1994; 25: 951–7

    Article  Google Scholar 

  442. Curb JD, Rodriguez B, Burchfield CM, et al. Sudden death, impaired glucose tolerance, and diabetes in Japanese American men. Circulation 1995; 91: 2591–5

    Article  PubMed  CAS  Google Scholar 

  443. Donahue R, Abbott R, Reed D, et al. Post-challenge glucose concentration and coronary heart disease in men of Japanese ancestry. Diabetes 1987; 36: 689–92

    Article  PubMed  CAS  Google Scholar 

  444. Barrett-Connor E, Wingard D, Criqui MH, et al. Is borderline fasting hyperglycaemia a risk factor for cardiovascular death. J Chronic Dis 1984; 37: 773–9

    Article  PubMed  CAS  Google Scholar 

  445. Scheidt-Nave C, Barrett-Connor E, Wingard DL, et al. Sex differences in fasting glycaemia as a risk factor for ischaemic heart disease death. Am J Epidemiol 1991; 133(6): 565–76

    PubMed  CAS  Google Scholar 

  446. Singer DE, Nathan DM, Anderson KM, et al. Association of HbA1c with prevalent cardiovascular disease in the original cohort of the Framingham study. Diabetes 1992; 41: 202–8

    Article  PubMed  CAS  Google Scholar 

  447. Cerami A, Vlassara H, Brownlee M. Role of advanced glycosylation products in complications of diabetes. Diabetes Care 1988; 11 Suppl. 1:73–9

    PubMed  Google Scholar 

  448. Yki-Järvinen H. Glucose toxicity. Endocr Rev 1992; 13: 415–31

    PubMed  Google Scholar 

  449. Wolff SP. Diabetes mellitus and free radicals. Br Med Bull 1993; 49: 642–52

    PubMed  CAS  Google Scholar 

  450. Brownlee M. Glycation products and the pathogenesis of diabetic complications. Diabetes Care 1992; 15: 1835–43

    Article  PubMed  CAS  Google Scholar 

  451. Gerlach H, Esposito C, Stern DM. Modulation of endothelial hemostatic properties: an active role in the host response. Annu Rev Med 1990; 41: 15–24

    Article  PubMed  CAS  Google Scholar 

  452. Waine H, Fieden E, Caplan H. Metabolic effects of Enovid in rheumatoid patients. Arthritis Rheum 1963; 6: 796–7

    Article  Google Scholar 

  453. Beck P. Effects of gonadal hormones and contraceptive steroids on glucose and insulin metabolism. In: Salhanick HA, Kipnis DM, Van de Wiele RL, editors. Metabolic effects of gonadal hormones and contraceptive steroids. New York (NY): Plenum Press, 1969

    Google Scholar 

  454. Spellacy WN. A review of carbohydrate metabolism and the oral contraceptives. Am J Obstet Gynecol 1969; 104: 448–60

    PubMed  CAS  Google Scholar 

  455. Kalkhoff R. Effects of oral contraceptive agents on carbohydrate metabolism. J Steroid Biochem 1975; 6(6): 949–56

    Article  PubMed  CAS  Google Scholar 

  456. Furman B. Impairment of glucose tolerance produced by diuretics and other drugs. Pharmacol Ther 1981; 12: 613–49

    Article  PubMed  CAS  Google Scholar 

  457. Gaspard UJ. Metabolic effects of oral contraceptives. Am J Obstet Gynecol 1987; 157: 1029–41

    PubMed  CAS  Google Scholar 

  458. Godsland I, Crook D, Wynn V Low-dose oral contraceptives and carbohydrate metabolism. Am J Obstet Gynecol 1990; 163: 348–53

    PubMed  CAS  Google Scholar 

  459. Stamp J, Date J, Deckert T. Serum insulin and intravenous glucose tolerance in oral contraception. Acta Endocrinol 1968; 58: 537–44

    Google Scholar 

  460. Vermeulen A, Daneels R, Thiery M. Effects of oral contraceptives on carbohydrate metabolism. Diabetologia 1970; 6: 519–23

    Article  PubMed  CAS  Google Scholar 

  461. Pyorälä K, Pyorälä T, Lampinen V. Sequential oral contraceptive treatment and intravenous glucose tolerance. Lancet 1967; II: 776–7

    Article  Google Scholar 

  462. Godsland IF, Crook D, Stevenson J, et al. Estrogen/progestin combinations and carbohydrate metabolism. Int Proc J 1989; 1:74–80

    Google Scholar 

  463. Russell-Briefel R, Ezzati TM, Perlman JA, et al. Impaired glucose tolerance in women using oral contraceptives: United States, 1976–1980. J Chronic Dis 1987; 40: 3–11

    Article  PubMed  CAS  Google Scholar 

  464. Wynn V. Effect of duration of low-dose oral contraceptive administration on carbohydrate metabolism. Am J Obstet Gynecol 1982; 142: 739–46

    PubMed  CAS  Google Scholar 

  465. Godsland IF, Crook D. Update on the metabolic effects of steroidal contraceptives and their relationship to cardiovascular disease risk. Am J Obstet Gynecol 1994; 170: 1528–36

    PubMed  CAS  Google Scholar 

  466. Thomas J. Modification of glucagon-induced hyperglycaemia by various steroidal agents. Metabolism 1963; 12: 207–12

    PubMed  CAS  Google Scholar 

  467. Kalkhoff RK, Kim H-J. Effects of pregnancy on insulin and glucagon secretion by perifused rat pancreatic islets. Endocrinology 1978; 102: 623–31

    Article  PubMed  CAS  Google Scholar 

  468. Ahmed-Sorour H, Bailey CJ. Role of ovarian hormones in the long-term control of glucose homeostasis: interaction with insulin, glucagon and epinephrine. Horm Res 1980; 13: 396–403

    Article  PubMed  CAS  Google Scholar 

  469. Faure A, Sutter-Dub M-T, Sutter B, et al. Ovarian-adrenal interactions in regulation of endocrine pancreatic function in the rat. Diabetologia 1983; 24: 122–7

    Article  PubMed  CAS  Google Scholar 

  470. Mandour T, Kissebah A, Wynn V. Mechanism of oestrogen and progesterone effects on lipid and carbohydrate metabolism: alteration in the insulin: glucagon molar ratio and hepatic enzyme activity. Eur J Clin Invest 1977; 7: 181–7

    Article  PubMed  CAS  Google Scholar 

  471. Watanabe RN, Azen CG, Roy S, et al. Defects in carbohydrate metabolism in oral contraceptive users without apparent metabolic risk factors. J Clin Endocrinol Metab 1994; 79: 1277–83

    Article  PubMed  CAS  Google Scholar 

  472. Ducimetiere P, Eschwege E, Papoz L, et al. Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease in a middle-aged population. Diabetologia 1980; 19: 205–10

    Article  PubMed  CAS  Google Scholar 

  473. Pyörälä K, Savolainen E, Kaukola S, et al. Plasma insulin as coronary heart disease risk factor: relationship to other risk factors and predictive value during 91/2 yearfollow-up of the Helsinki Policemen Study population. Acta Med Scand 1985; 701 Suppl.: 38–52

    Google Scholar 

  474. Després J-P, Lamarche B, Mauriège P, et al. Hyperinsulinaemia as an independent risk factor for ischaemic heart disease. N Engl J Med 1996; 334: 952–7

    Article  PubMed  Google Scholar 

  475. Folsom AR, Szklo M, Stevens J, et al. A prospective study of coronary heart disease in relation to fasting insulin, glucose and diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care 1997; 20: 935–42

    Article  PubMed  CAS  Google Scholar 

  476. Fontbonne A, Tchobroutsky G, Eschwege E, et al. Coronary heart disease mortality risk: plasma insulin level is a more sensitive marker than hypertension or abnormal glucose tolerance in overweight males: the Paris Prospective Study. Int J Obes 1988; 12: 557–65

    PubMed  CAS  Google Scholar 

  477. Ley C, Swan J, Godsland I, et al. Insulin resistance, lipids, body fat and coagulation factors in males with suspected angina and normal or abnormal coronary angiograms. J Am Coll Cardiol 1994; 23: 377–83

    Article  PubMed  CAS  Google Scholar 

  478. Swan JW, Walton C, Godsland IF, et al. Insulin resistance in chronic heart failure. Eur Heart J 1994; 15: 1528–32

    PubMed  CAS  Google Scholar 

  479. Dean JD, Jones CJH, Hutchinson SJ, et al. Hyperinsulinaemia and microvascular angina (‘syndrome X’). Lancet 1991; 337: 456–7

    Article  PubMed  CAS  Google Scholar 

  480. Godsland IF, Crook D, Stevenson JC, et al. The insulin resistance syndrome in postmenopausal women with cardiological syndrome X. Br Heart J 1995; 74: 47–52

    Article  PubMed  CAS  Google Scholar 

  481. Stout R, Bierman E, Ross R. Effect of insulin on the proliferation of cultured primate arterial smooth muscle cells. Circ Res 1975; 36: 319–27

    Article  PubMed  CAS  Google Scholar 

  482. Stout R. Insulin and atheroma: 20-yr perspective. Diabetes Care 1990; 13:631–54

    Article  PubMed  CAS  Google Scholar 

  483. Stamler J, Pick R, Katz LN. Effect of insulin in the induction and regression of atherosclerosis in the chick. Circ Res 1960; 8: 572–6

    Article  PubMed  CAS  Google Scholar 

  484. Kooistra T, Bosnia P, Töns H, et al. Plasminogen activator inhibitor 1: biosynthesis and mRNA level are increased by insulin in cultured human hepatocytes. Thromb Haemost 1989; 62: 723–8

    PubMed  CAS  Google Scholar 

  485. Topping D, Mayes P. The immediate effect of insulin and fructose on the metabolism of the perfused liver. Biochem J 1972; 126:295–311

    CAS  Google Scholar 

  486. Reaven GM, Lithell H, Landsberg L. Hypertension and associated metabolic abnormalities: the role of insulin resistance and the sympoathoadrenal system. N Engl J Med 1996; 334: 374–81

    Article  PubMed  CAS  Google Scholar 

  487. Baynes C, Henderson AD, Richmond W, et al. The response of hepatic lipase and serum lipoproteins to acute hyperinsulinaemia in type 2 diabetes. Eur J Clin Invest 1992; 22: 341–6

    Article  PubMed  CAS  Google Scholar 

  488. Knudsen P, Eriksson J, Lahdenperä S, et al. Changes in lipolytic enzymes cluster with insulin resistance syndrome. Diabetologia 1995; 38: 344–50

    Article  PubMed  CAS  Google Scholar 

  489. Godsland IF, Crook D, Walton C, et al. Influence of insulin resistance, secretion, and clearance on serum cholesterol, triglycerides, lipoprotein cholesterol, and blood pressure in healthy men. Arterioscler Thromb 1992; 12: 1030–5

    Article  PubMed  CAS  Google Scholar 

  490. Galli G, Casini A, Cresci B, et al. Effects of insulin and glucose on the growth and the release of extracellular matrix components by bovine bone endothelial cells. Endocrine 1994; 2: 559–66

    CAS  Google Scholar 

  491. Ferri C, Pittoni V, Piccoli A, et al. Insulin stimulates endothelin-1 secretion from human endothelial cells and modulates its circulating levels in vivo. J Clin Endocrinol Metab 1995; 80: 829–35

    Article  PubMed  CAS  Google Scholar 

  492. Jarrett RJ. Why is insulin not a risk factor for coronary heart disease? Diabetologia 1994; 37: 945–7

    Article  PubMed  CAS  Google Scholar 

  493. Wingard DL, Barrett-Connor EL, Ferrara A. Is insulin really a heart disease risk factor? Diabetes Care 1995; 18: 1299–304

    PubMed  CAS  Google Scholar 

  494. Godsland IF, Stevenson JC. Insulin resistance: syndrome or tendency? Lancet 1995; 346: 100–3

    Article  PubMed  CAS  Google Scholar 

  495. McKeigue P, Davey G. Associations between insulin levels and cardiovascular disease are confounded by comorbidity. Diabetes Care 1995; 18: 1294–8

    PubMed  CAS  Google Scholar 

  496. Dahlgren E, Johansson S, Lapidus L, et al. Polycystic ovary syndrome and risk of myocardial infarction: evaluation from a risk factor model based on a prospective population study of women. Acta Obstet Gynecol Scand 1992; 71: 599–604

    Article  PubMed  CAS  Google Scholar 

  497. Spellacy W, Carlson K. Plasma insulin and blood glucose levels in patients taking oral contraceptives. Am J Obstet Gynecol 1966; 95: 474–9

    PubMed  CAS  Google Scholar 

  498. Wynn V, Adams P, Godsland I, et al. Comparison of the effects of different combined oral-contraceptive formulations on carbohydrate and lipid metabolism. Lancet 1979; I: 1045–9

    Article  Google Scholar 

  499. Adams PW, Godsland IF, Melrose J, et al. The influence of oral contraceptive formulation on carbohydrate and lipid metabolism. J Pharmacother 1980; 3: 54–63

    PubMed  CAS  Google Scholar 

  500. Godsland IF, Walton C, Felton C, et al. Insulin resistance, secretion and metabolism in users of oral contraceptives. J Clin Endocrinol Metab 1992; 74: 64–70

    Article  PubMed  CAS  Google Scholar 

  501. Godsland I, Crook D, Wynn V. Coronary heart disease risk markers in users of low-dose oral contraceptives. J Reprod Med 1991; 36 Suppl.: 226–37

    PubMed  CAS  Google Scholar 

  502. Godsland IF. Sex steroids and changes in the cardiovascular system: carbohydrate metabolism. Gynecol Endocrinol 1996; 10 Suppl. 2: 59–64

    Article  Google Scholar 

  503. Després J-P, Marette A. Relation of components of insulin resistance syndrome to coronary disease risk. Curr Opin Lipidol 1994; 5: 274–89

    Article  PubMed  Google Scholar 

  504. Hopkins PN, Hunt SC, Wu LL, et al. Hypertension, dyslipidemia, and insulin resistance: links in a chain or spokes on a wheel? Curr Opin Lipidol 1996; 7: 241–53

    Article  PubMed  CAS  Google Scholar 

  505. Yarnell JWG, Patterson CC, Bainton D, et al. Is metabolic syndrome a discrete entity in the general population? Evidence from the Caerphilly and Speedwell population studies. Heart 1998; 79: 248–52

    PubMed  CAS  Google Scholar 

  506. Spencer CP, Godsland IF, Stevenson JC. Is there a menopausal metabolic syndrome? Gynecol Endocrinol 1997; 11: 341–55

    Article  PubMed  CAS  Google Scholar 

  507. Singh BM, Nattrass M. Use of combined oral contraceptive preparations alters the insulin sensitivity of fatty acid and ketone metabolism. Clin Endocrinol 1989; 30: 561–70

    Article  CAS  Google Scholar 

  508. Skouby S, Andersen O, Saurbrey N, et al. Oral contraception and insulin sensitivity: in vivo assessment in normal women and women with previous gestational diabetes. J Clin Endocrinol Metab 1987; 64: 519–23

    Article  PubMed  CAS  Google Scholar 

  509. Skouby SO, Anderson O, Petersen KR, et al. Mechanism of action of oral contraceptives on carbohydrate metabolism at the cellular level. Am J Obstet Gynecol 1990; 163: 343–8

    PubMed  CAS  Google Scholar 

  510. Kasdorf G, Kalkhoff R. Prospective studies of insulin sensitivity in normal women receiving oral contraceptive agents. J Clin Endocrinol Metab 1988; 66: 846–52

    Article  PubMed  CAS  Google Scholar 

  511. Russell RW. How does blood pressure cause stroke? Lancet 1975; II: 1283–5

    Article  Google Scholar 

  512. Woods J. Oral contraceptives and hypertension. Lancet 1967; II: 653–4

    Article  Google Scholar 

  513. Laragh J, Sealey J, Ledingham J, et al. Oral contraceptives, renin, aldosterone and high blood pressure. JAMA 1967; 201: 918–22

    Article  PubMed  CAS  Google Scholar 

  514. Tyson J. Oral contraception and elevated blood pressure. Am J Obstet Gynecol 1968; 100: 875–6

    PubMed  CAS  Google Scholar 

  515. Weinberger M, Collins D, Dowdy A, et al. Hypertension induced by oral contraceptives containing estrogen and gestagen: effects on plasma renin activity and aldosterone excretion. Ann Intern Med 1969; 71: 891–902

    PubMed  CAS  Google Scholar 

  516. Weir R, Briggs E, Mack A, et al. Blood pressure in women after one year of oral contraception. Lancet 1971; I: 467–70

    Article  Google Scholar 

  517. Clezy T, Foy B, Hodge R, et al. Oral contraceptives and hypertension. Br Heart J 1972; 34: 1238–43

    Article  PubMed  CAS  Google Scholar 

  518. Fisch I, Frank J. Oral contraceptives and blood pressure. JAMA 1977; 237: 2499–503

    Article  PubMed  CAS  Google Scholar 

  519. Kunin C, McCormack R, Abernathy J. Oral contraceptives and blood pressure. Arch Intern Med 1969; 123: 362–5

    Article  PubMed  CAS  Google Scholar 

  520. Greenblatt D, Koch-Weser J. Oral contraceptives and hypertension: a report from the Boston Collaborative Drug Surveillance Program. Obstet Gynecol 1974; 44: 412–7

    PubMed  CAS  Google Scholar 

  521. Blumenstein B, Douglas M, Dallas-Hall W. Blood pressure changes and oral contraceptive use: a study of 2676 black women in the Southeastern United States. Am J Epidemiol 1980; 112:539–52

    PubMed  CAS  Google Scholar 

  522. Wallace R, Barrett-Connor E, Criqui M, et al. Alterations in blood pressures associated with combined alcohol and oral contraceptive use: the Lipid Research Clinics Prevalence Study. J Chronic Dis 1982; 35(4): 251–7

    Article  PubMed  CAS  Google Scholar 

  523. Goldhaber S, Hennekens C, Spark R, et al. Plasma renin substrate, renin activity and aldosterone levels in a sample of oral contraceptive users from a community survey. Am Heart J 1984; 107: 119–22

    Article  PubMed  CAS  Google Scholar 

  524. Dieben TO, van Beek A. Desogestrel-containing oral contraceptives and blood pressure. Arzneimittelforschung 1986; 36: 1678–80

    PubMed  CAS  Google Scholar 

  525. Weijers MJ. Clinical trial of an oral contraceptive containing desogestrel and ethinyl estradiol. Clin Ther 1982; 4: 359–66

    PubMed  CAS  Google Scholar 

  526. Rekers H. Multicenter trial of a monophasic oral contraceptive containing ethinyl estradiol and desogestrel. Acta Obstet Gynecol Scand 1988; 67: 171–4

    Article  PubMed  CAS  Google Scholar 

  527. Khaw K-T, Peart W Blood pressure and contraceptive use. BMJ 1982; 285: 403–7

    Article  PubMed  CAS  Google Scholar 

  528. Task Force on Oral Contraceptives. The WHO multicentre trial of the vasopressor effects of combined oral contraceptives: 2. Lack of effect of estrogen. Contraception 1989; 40: 147–56

    Article  Google Scholar 

  529. Nichols M, Robinson G, Bounds W, et al. Effect of four combined oral contraceptives on blood pressure in the pill-free interval. Contraception 1993; 47: 367–76

    Article  PubMed  CAS  Google Scholar 

  530. Godsland IF, Crook D, Devenport M, et al. Relationships between blood pressure, oral contraceptive use and metabolic risk markers for cardiovascular disease. Contraception 1995; 52: 143–9

    Article  PubMed  CAS  Google Scholar 

  531. Ulstein M, Svendsen E, Steier A, et al. Clinical experience with a triphasic oral contraceptive. Acta Obstet Gynecol Scand 1984; 63: 233–6

    Article  PubMed  CAS  Google Scholar 

  532. Wouterez TB, Korba VD. Five-year multicenter study of a triphasic, low-dose, combination oral contraceptive. Int J Fertil 1988; 33: 406–10

    Google Scholar 

  533. Yabur JA, Alvarado M, Brito V. Clinical evaluation of a new combined oral contraceptive desogestrel-ethinylestradiol. Adv Contracept 1989; 5: 57–70

    Article  PubMed  CAS  Google Scholar 

  534. Hoppe G. Gestodene, an innovative progestagen. Adv Contracept 1987; 3: 159–66

    Article  PubMed  CAS  Google Scholar 

  535. Düsterberg B, Brill K. Clinical acceptability of monophasic gestodene. Am J Obstet Gynecol 1990; 163: 1398–404

    PubMed  Google Scholar 

  536. Crane M, Harris J, Winsor WI. Hypertension, oral contraceptive agents, and conjugated estrogens. Ann Intern Med 1971; 74: 13–21

    PubMed  CAS  Google Scholar 

  537. Weir R, Briggs E, Mack A, et al. Blood pressure in women taking oral contraceptives. BMJ 1974; 1: 533–5

    Article  PubMed  CAS  Google Scholar 

  538. Petitti DB, Klatsky AL. Malignant hypertension in women aged 15 to 44 years and its relation to cigarette smoking and oral contraceptives. Am J Cardiol 1983; 52: 297–98

    Article  PubMed  CAS  Google Scholar 

  539. Tsai CC, Williamson HO, Kirkland BH, et al. Low-dose oral contraception and blood pressure in women with a past history of elevated blood pressure. Am J Obstet Gynecol 1985; 151: 28–32

    PubMed  CAS  Google Scholar 

  540. Emmons K, Weidner G. The effects of cognitive and physical stress on cardiovascular reactivity among smokers and oral contraceptive users. Psychophysiology 1988; 25: 166–71

    Article  PubMed  CAS  Google Scholar 

  541. Davis M, Matthews K. Cigarette smoking and oral contraceptive use influence women’s lipid, lipoprotein, and cardiovascular responses during stress. Health Psychol 1990; 9: 717–36

    Article  PubMed  CAS  Google Scholar 

  542. Armitage P, Rose GA. The variability of measurement of casual blood pressure: I. A laboratory study. Clin Sci 1966; 30: 325–35

    PubMed  CAS  Google Scholar 

  543. Carey R, Reid R, Ayers C, et al. The Charlottesville blood pressure survey: value of repeated blood-pressure measurements. JAMA 1976; 236: 847–51

    Article  PubMed  CAS  Google Scholar 

  544. Fisch I, Freedman S, Myatt A. Oral contraceptives, pregnancy and blood pressure. In: Ramcharan S, editor. The Walnut Creek Contraceptive Drug Study: a Prospective Study of the Side Effects of Oral Contraceptives. Vol. I. Washington (DC): National Institutes of Health, 1974: publication no.: 74-562

    Google Scholar 

  545. Meade T, Haines A, North W, et al. Haemostatic, lipid and blood pressure profiles of women on oral contraceptives containing 50 micrograms or 30 micrograms of oestrogen. Lancet 1977; II: 948–51

    Article  Google Scholar 

  546. Straneva P, Hinderliter A, Wells E, et al. Smoking, oral contraceptives, and cardiovascular reactivity to stress. Obstet Gynecol 2000; 95: 78–83

    Article  PubMed  CAS  Google Scholar 

  547. Spellacy W, Birk S. The effect of intrauterine devices, oral contraceptives, estrogens and progestogens on blood pressure. Am J Obstet Gynecol 1972; 112: 912–9

    PubMed  CAS  Google Scholar 

  548. Fakeye O. The effect of low-dose oral contraceptives and Norplant on blood pressure and body weight in Nigerian women. Adv Contracept 1992; 8: 27–32

    Article  PubMed  CAS  Google Scholar 

  549. Thorn G, Harrop G. The ‘sodium-retaining’ effect of the sex hormones. Science 1937; 86: 40–1

    Article  PubMed  CAS  Google Scholar 

  550. Preedy J, Aitken E. Effect of estrogen on water and electrolyte metabolism; normal. J Clin Invest 1956; 35: 423–9

    Article  PubMed  CAS  Google Scholar 

  551. Laidlaw J, Ruse J, Gornall A. The influence of estrogen and progesterone on aldosterone excretion. J Clin Endocrinol 1962; 22: 161–77

    Article  CAS  Google Scholar 

  552. Crane M, Harris J. Plasma renin activity and aldosterone excretion rate in normal subjects: I. Effect of ethinyl estradiol and medroxyprogesterone acetate. J Clin Endocrinol 1969; 29: 1550–7

    Google Scholar 

  553. Crane M, Harris J. Plasma renin activity and aldosterone excretion rate in normal subjects: II. Effect of oral contraceptive agents. J Clin Endocrinol 1969; 29: 558–62

    Article  CAS  Google Scholar 

  554. Walters W, Lim Y. Haemodynamic changes in women taking oral contraceptives. J Obstet Gynecol Brit Commonw 1970; 77(11): 1007–12

    Article  CAS  Google Scholar 

  555. Hollenberg N, Williams G, Burger B, et al. Renal blood flow and its response to angiotensin II: an interaction between oral contraceptive agents, sodium intake, and the renin-angiotensin system in healthy young women. Circ Res 1976; 38: 35–40

    Article  PubMed  CAS  Google Scholar 

  556. Weir R, Davies D, Fraser R, et al. Contraceptive steroids and hypertension. J Steroid Biochem 1975; 6: 961–4

    Article  PubMed  CAS  Google Scholar 

  557. Walters WA, Lim YL. Cardiovascular dynamics in women receiving oral contraceptive therapy. Lancet 1969; II: 879–81

    Article  Google Scholar 

  558. Lehtovirta P. Haemodynamic effects of combined oestrogen/progestogen oral contraceptives. J Obstet Gynaecol Br Commonw 1974; 81: 517–25

    Article  PubMed  CAS  Google Scholar 

  559. Littler WA, Bojorges-Bueno R, Banks J. Cardiovascular dynamics in women during the menstrual cycle and oral contraceptive therapy. Thorax 1974; 29: 567–70

    Article  PubMed  CAS  Google Scholar 

  560. Derkx FHM, Stuenkel C, Schalekamp MPA, et al. Immunoreactive renin, prorenin, and enzymatically active renin in plasma during pregnancy and in women taking oral contraceptives. J Clin Endocrinol Metab 1986; 63: 1008–15

    Article  PubMed  CAS  Google Scholar 

  561. Saruta T, Saade G, Kaplan N. A possible mechanism for hypertension induced by oral contraceptives. Arch Intern Med 1970; 126: 621–6

    Article  PubMed  CAS  Google Scholar 

  562. Heritage A, Stumpf W, Sar M, et al. Brainstem catecholamine neurons are target sites for sex steroid hormones. Science 1980; 207: 1377–9

    PubMed  CAS  Google Scholar 

  563. Eggena P, Hidaka H, Barrett J, et al. Multiple forms of human plasma renin substrate. J Clin Invest 1978; 62: 367–72

    Article  PubMed  CAS  Google Scholar 

  564. Ahluwalia BS, Curry CL, Crocker CL, et al. Evidence of higher ethinyl estradiol blood levels in human hypertensive oral contraceptive users. Fertil Steril 1977; 28: 627–30

    PubMed  CAS  Google Scholar 

  565. Blum M, Zacharovich D, Gelernter I, et al. Influence of oral contraceptive treatment on blood pressure and 24-hour urinary catecholamine excretion in smoking as compared with non-smoking women. Adv Contracept 1988; 4: 143–9

    Article  PubMed  CAS  Google Scholar 

  566. Paffenberg Jr R, Wolf P, Notkin J, et al. Chronic disease in former college students: 1. Early precursors of fatal coronary heart disease. Am J Epidemiol 1966; 83: 314–28

    Google Scholar 

  567. Kannel W, Wolf P, Verter J, et al. Epidemiological assessment of the role of blood pressure in stroke. JAMA 1970; 214: 301–10

    Article  PubMed  CAS  Google Scholar 

  568. Prentice RL. On the ability of blood pressure effects to explain the relation between oral contraceptives and cardiovascular disease. Am J Epidemiol 1988; 127: 213–9

    PubMed  CAS  Google Scholar 

  569. Prentice RL, Thomas DB. Epidemiology of oral contraceptives and disease. Adv Cancer Res 1987; 49: 285–401

    Article  PubMed  CAS  Google Scholar 

  570. Prentice RL, Shimizu Y, Lin CH, et al. Serial blood pressure measurements and cardiovascular disease in a Japanese cohort. Am J Epidemiol 1982; 116: 1–28

    PubMed  CAS  Google Scholar 

  571. Cook NR, Scherr PA, Evans DA, et al. Regression analysis of changes in blood pressure with oral contraceptive use. Am J Epidemiol 1985; 121: 530–40

    PubMed  CAS  Google Scholar 

  572. Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med 1998; 338: 1042–50

    Article  PubMed  CAS  Google Scholar 

  573. Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet 1999; 354: 407–13

    Article  PubMed  CAS  Google Scholar 

  574. Christen WG, Ajani UA, Glynn RJ, et al. Blood levels of homocysteine and increased risks of cardiovascular disease: causal or casual? Arch Intern Med 2000; 160: 422–34

    Article  PubMed  CAS  Google Scholar 

  575. Finkelstein JD. Methionine metabolism in mammals. J Nutr Biochem 1990; 1: 228–37

    Article  PubMed  CAS  Google Scholar 

  576. Ueland PM, Refsum H, Stabler SP, et al. Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem 1993; 39: 1764–79

    PubMed  CAS  Google Scholar 

  577. Jacobsen DW, Gatautis VJ, Green R, et al. Rapid HPLC determination of total homocysteine and other thiols in serum and plasma: sex differences and correlation with cobalamin and folate concentrations in healthy subjects. Clin Chem 1994; 40: 873–81

    PubMed  CAS  Google Scholar 

  578. Kang SS, Zhou J, Wong PWK, et al. Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet 1988; 43: 414–21

    PubMed  CAS  Google Scholar 

  579. Malinow MR, Nieto FJ, Kruger WD, et al. The effects of folic acid supplementation on plasma total homocysteine are modulated by multivitamin use and methylenetetrahydrofolate reductase genotypes. Arterioscler Thromb Vasc Biol 1997; 17: 1157–62

    Article  PubMed  CAS  Google Scholar 

  580. Ubbink JB, Vermaak WJH, van der Merwe A, et al. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994; 124: 1927–33

    PubMed  CAS  Google Scholar 

  581. Brattström LE, Israelsson B, Jeppson J-O, et al. Folic acid: an innocuous means to reduce plasma homocysteine. Scand J Clin Lab Invest 1988; 48: 215–21

    Article  PubMed  Google Scholar 

  582. Brattström LE, Israelsson B, Norrving B, et al. Impaired homocysteine metabolism in early-onset cerebral and periperal occlusive arterial disease: effects of pyridoxine and folic acid treatment. Atherosclerosis 1990; 81: 51–60

    Article  PubMed  Google Scholar 

  583. Saltzman E, Mason JB, Jacques PF, et al. B vitamin supplementation lowers homocysteine levels in heart disease [abstract]. Clin Res 1994; 42: 172A

    Google Scholar 

  584. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969; 56: 111–28

    PubMed  CAS  Google Scholar 

  585. Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol 1996; 27: 517–27

    Article  PubMed  CAS  Google Scholar 

  586. Boushey CJ, Beresford SAA, Omenn GS, et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intake. JAMA 1995; 274: 1049–57

    Article  PubMed  CAS  Google Scholar 

  587. Ray JG. Meta-analysis of hyperhomocysteinaemia as a risk factor for venous thromboembolic disease. Arch Intern Med 1998; 158:2101–16

    Article  PubMed  CAS  Google Scholar 

  588. Pancharuniti N, Lewis CA, Sauberlich HE, et al. Plasma homocyst(e)ine, folate and vitamin B12 concentrations and risk for early-onset coronary artery disease. Am J Clin Nutr 1994; 59: 940–8

    PubMed  CAS  Google Scholar 

  589. Rinehart JF, Greenberg LD. Arteriosclerotic lesions in pyridoxine-deficient monkeys. Am J Pathol 1949; 25: 481–91

    PubMed  CAS  Google Scholar 

  590. Frosst P, Blom HJ, Milos R, et al. Acandidate genetic risk factor for vascular disease: a common mutation in methylenetetra-hydrofolate reductase. Nat Genet 1995; 10: 111–3

    Article  PubMed  CAS  Google Scholar 

  591. Starkebaum G, Harlan JM. Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. J Clin Invest 1986; 77: 1370–6

    Article  PubMed  CAS  Google Scholar 

  592. Loscalzo J. The oxidant stress of hyperhomocyst(e)inaemia. J Clin Invest 1996; 98: 5–7

    Article  PubMed  CAS  Google Scholar 

  593. Celermajer DS, Sorensen K, Ryalls M, et al. Impaired endothelial function occurs in the systemic arteries of children with homozygous homocystinuria but not in their heterozygous parents. J Am Coll Cardiol 1993; 22: 854–8

    Article  PubMed  CAS  Google Scholar 

  594. Chambers JC, McGregor A, Jean-Marie J, et al. Acute hyperhomocysteinaemia and endothelial dysfunction. Lancet 1998; 351: 36–7

    Article  PubMed  CAS  Google Scholar 

  595. Di Minno G, Davi G, Margaglione M, et al. Abnormally high thromboxane biosynthesis in homozygous homocystinuria. J Clin Invest 1993; 92: 1400–6

    Article  PubMed  Google Scholar 

  596. Rodgers GM, Kane WH. Activation of endogenous factor V by a homocysteine-induced vascular endothelial cell activator. J Clin Invest 1986; 77: 1909–16

    Article  PubMed  CAS  Google Scholar 

  597. Lentz SR, Sadler JE. Inhibition of thrombomodulin surface expression and protein C activation by the thrombogenic agent homocysteine. J Clin Invest 1991; 88: 1906–14

    Article  PubMed  CAS  Google Scholar 

  598. Giltay EJ, Hoogeveen EK, Elbers JMH, et al. Effects of sex steroids on plasma total homocysteine levels: a study in transsexual males and females. J Clin Endocrinol Metab 1998; 83: 550–3

    Article  PubMed  CAS  Google Scholar 

  599. Giri S, Thompson PD, Taxel P, et al. Oral estrogen improves serum lipids, homocysteine and fibrinolysis in elderly men. Atherosclerosis 1998; 137: 359–66

    Article  PubMed  CAS  Google Scholar 

  600. Green TJ, Houghton LA, Donovan U, et al. Oral contraceptives did not affect biochemical folate indexes and homocysteine concentrations in adolescent females. J Am Diet Assoc 1998; 98: 49–55

    Article  PubMed  CAS  Google Scholar 

  601. Wong PWK, Kang S-S. Accelerated atherosclerosis. Am J Med 1988; 84: 1093–4

    Article  PubMed  CAS  Google Scholar 

  602. Beaumont V, Malinow MR, Sexton G, et al. Hyperhomocyst(e)inemia, anti-estrogen antibodies and other risk factors for thrombosis in women on oral contraceptives. Atherosclerosis 1992; 94: 147–52

    Article  PubMed  CAS  Google Scholar 

  603. Adams PW, Wynn V, Folkard J, et al. Influence of oral contraceptives, pyridoxine (vitamin B6), and tryptophan on carbohydrate metabolism. Lancet 1976; I: 759–64

    Article  Google Scholar 

  604. Rose DP. Aspects of tryptophan metabolism in health and disease: a review. J Clin Pathol 1972; 25: 17–25

    Article  PubMed  CAS  Google Scholar 

  605. Webb JL. Nutritional effects of oral contraceptives. J Reprod Med 1980; 25: 150–6

    PubMed  CAS  Google Scholar 

  606. Peng F, Triplett D, Barna L, et al. Pulmonary embolism and premature labor in a patient with both factor V Leiden mutation and methylenetetrahydrofolate reductase gene C677T mutation. Thromb Res 1996; 83: 243–51

    Article  PubMed  CAS  Google Scholar 

  607. Beaumont JL, Lemort N, Lorenzelli-Edouard L, et al. Anti-ethinyloestradiol antibody activities in oral contraceptive users. Clin Exp Immunol 1979; 38: 445–52

    PubMed  CAS  Google Scholar 

  608. Beaumont V, Lorenzelli-Edouard L, Lemort N, et al. Detection and composition of circulating immune complexes in oral contraceptive. Biomedicine 1979; 30: 256–60

    PubMed  CAS  Google Scholar 

  609. Beaumont JL, Lemort N, Beaumont V, et al. Detection of pill-induced antiethinylestradiol antibodies [in French]. Ann Biol Clin (Paris) 1981; 39(2): 69–74

    CAS  Google Scholar 

  610. Beaumont JL, Lemort N. Oral contraceptive, pulmonary artery thrombosis and anti-ethinyl-oestradiol monoclonal IgG. Clin Exp Immunol 1976; 24: 455–63

    PubMed  CAS  Google Scholar 

  611. Plowright C, Adam SA, Thorogood M, et al. Immunogenicity and the vascular risk of oral contraceptives. Br Heart J 1985; 53: 556–61

    Article  PubMed  CAS  Google Scholar 

  612. Beaumont V, Lemort N, Beaumont JL. Oral contraception, circulating immune complexes, anti-ethinyloestradiol antibodies and thrombosis. Am J Reprod Immunol 1982; 2: 8–12

    PubMed  CAS  Google Scholar 

  613. Bucala R, Lahita G, Fishman J, et al. Antiestrogen antibodies in users of oral contraceptives and in patients with systemic lupus erythematosus. Clin Exp Immunol 1987; 67: 167–75

    PubMed  CAS  Google Scholar 

  614. Beaumont V, Lemort N, Beaumont JL. Oral contraceptives, sex steroid-induced antibodies and vascular thrombosis: results from 1318 cases. Eur Heart J 1991; 12: 1219–24

    Article  PubMed  CAS  Google Scholar 

  615. van den Brule FA, Coibon M, Hendrick JC, et al. Antisteroid immune complexes and vascular thrombosis during steroid hormone therapy. Contraception 1994; 49: 571–7

    Article  PubMed  Google Scholar 

  616. Bolton CH, Hampton JR, Mitchell JRA. Effect of oral contraceptive agents on platelets and plasma-phospholipids. Lancet 1968; I: 1336–41

    Article  CAS  Google Scholar 

  617. Poller L, Priest CM, Thomson JM. Platelet aggregation during oral contraception. BMJ 1969; 4: 273–4

    Article  PubMed  CAS  Google Scholar 

  618. LeCompte F, Renaud S. Influence of pregnancy and oral contraceptives on platelets in relation to coagulation and aggregation. Thromb Haemost 1973; 30: 510–7

    Google Scholar 

  619. Bierenbaum ML, Fleischman AI, Stier A, et al. Increased platelet aggregation and decreased high-density lipoprotein cholesterol in women on oral contraceptives. Am J Obstet Gynecol 1979; 134: 638–41

    PubMed  CAS  Google Scholar 

  620. Poller L, Thomson JM, Thomas W, et al. Blood clotting and platelet aggregation during oral progestagen contraception: a follow-up study. BMJ 1971; 1: 705–7

    Article  PubMed  CAS  Google Scholar 

  621. Fogh M, Knudsen JB, Gormsen J. Effect of cyproterone acetate on platelet aggregability, fibrinolytic activity and fibrinolytic capacity in normal men. Acta Endocrinol 1980; 94: 430–2

    PubMed  CAS  Google Scholar 

  622. Singh K, Viegas OAC, Koh SCL, et al. Effects of Norplant-2 rods on haemostatic function. Contraception 1992; 46: 71–81

    Article  CAS  Google Scholar 

  623. Kuhl H. Effects of progestogens on haemostasis. Maturitas 1996; 24: 1–19

    Article  PubMed  CAS  Google Scholar 

  624. Ciavatti M, Michel G, Renaud S. Modification by oral contraceptives in rat of 14C incorporation into platelet lipids. Horm Metab Res 1979; 11:441–4

    Article  PubMed  CAS  Google Scholar 

  625. Ciavatti M, Dumont E, Benoit C, et al. Oral contraceptives, lanosterol and platelet hyperactivity in rat. Science 1980; 210: 642–4

    Article  PubMed  CAS  Google Scholar 

  626. Ciavatti M, Blache D, Renaud S. Dietary fats modulate hormonal contraceptive induced changes in platelet aggregation, composition and lipid biosynthesis in female rats. Nutr Res 1987; 7: 589–99

    Article  CAS  Google Scholar 

  627. Ciavatti M, Blache D, Renaud S. Hormonal contraceptive increases plasma lipid peroxides in female rats: relationship to platelet aggregation and lipid biosynthesis. Arteriosclerosis 1989; 9: 84–9

    Article  PubMed  CAS  Google Scholar 

  628. Ciavatti M, Renaud S. Oxidative status and oral contraceptive: its relevance to platelet abnormalities and cardiovascular risk. Free Radic Biol Med 1991; 10: 325–38

    Article  PubMed  CAS  Google Scholar 

  629. Renaud S, Ciavetti M, Perrot L, et al. Influence of vitamin E administration on platelet functions in hormonal contraceptive users. Contraception 1987; 36: 347–58

    Article  PubMed  CAS  Google Scholar 

  630. Tangeney CC, Driskell JA. Vitamin E status of young women on combined-type oral contraceptives. Contraception 1978; 17:499–512

    Article  Google Scholar 

  631. Gray E, Barrowcliffe TW. Inhibition of antithrombin III by lipid peroxides. Thromb Res 1985; 37: 241–50

    Article  PubMed  CAS  Google Scholar 

  632. Nordoy A, Svensson B, Haycraft D, et al. The influence of age, sex and use of oral contraceptives on inhibitory effects of endothelial cells and PGI2 on platelet function. Scand J Haematol 1978; 21: 177–87

    Article  PubMed  CAS  Google Scholar 

  633. Ylikorkala O, Puolakka J, Vinika L. The effects of oral contraceptives on antiaggregatory prostacyclin and proaggregatory thromboxane A2 in humans. Am J Obstet Gynecol 1982; 142: 573–6

    PubMed  CAS  Google Scholar 

  634. Pan JQ, Hall ER, Wu KK. Alteration of platelet responses to metabolites of arachidonic acid by oral contraceptives. Br J Haematol 1984; 58: 317–23

    Article  PubMed  CAS  Google Scholar 

  635. Ylikorkala O, Kuusi T, Tikkanen MJ, et al. Desogestrel- and levonorgestrel-containing oral contraceptives have different effects on urinary excretion of prostacyclin metabolites and serum high density lipoproteins. J Clin Endocrinol Metab 1987; 65: 1238–42

    Article  PubMed  CAS  Google Scholar 

  636. Mileikowsky GN, Nadler JL, Huey F, et al. Evidence that smoking alters prostacyclin formation and platelet aggregation in women who use oral contraceptives. Am J Obstet Gynecol 1988; 159: 1547–52

    PubMed  CAS  Google Scholar 

  637. Berg G, Kohlmeier L, Brenner H. Use of oral contraceptives and serum beta-carotene. Eur J Clin Nutr 1997; 51: 181–7

    Article  PubMed  CAS  Google Scholar 

  638. Bauer KA, Rosenberg RD. The pathophysiology of the prethrombotic state in humans: insights gained from studies using markers of hemostatic system activation. Blood 1987; 70: 343–50

    PubMed  CAS  Google Scholar 

  639. Mazur EM. Megakaryocytes and megakaryocytopoiesis. In: Loscalzo J, Schafer AI, editors. Thrombosis and hemorrhage. Oxford: Blackwell Scientific, 1994: 161–94

    Google Scholar 

  640. Greenberg CS. Fibrin formation and stabilization. In: Loscalzo J, Schafer AI, editors. Thrombosis and hemorrhage. Oxford: Blackwell Scientific, 1994: 107–26

    Google Scholar 

  641. Rabbani LE, Loscalzo J. The relationship between thrombosis and atherosclerosis. In: Loscalzo J, Schafer AI, editors. Thrombosis and hemorrhage. Oxford: Blackwell Scientific, 1994: 769–90

    Google Scholar 

  642. Meade TW. Epidemiology of thrombosis. In: Loscalzo J, Schafer AI, editors. Thrombosis and hemorrhage. Oxford: Black-well Scientific, 1994: 791–808

    Google Scholar 

  643. Bauer KA. Inherited hypercoagulable states. In: Loscalzo J, Schafer AI, editors. Thrombosis and hemorrhage. Oxford: Blackwell Scientific, 1994: 809–34

    Google Scholar 

  644. Gilbert GE. The xase complex. In: Loscalzo J, Schafer AI, editors. Thrombosis and hemorrhage. Oxford: Blackwell Scientific, 1994: 37–56

    Google Scholar 

  645. Broze Jr GJ. The tissue factor pathway of coagulation. In: Loscalzo J, Schafer AI, editors. Thrombosis and hemorrhage. Oxford: Blackwell Scientific, 1994: 57–86

    Google Scholar 

  646. Dahlbäck B. The protein C anticoagulant system: inherited defects as basis for venous thrombosis. Thromb Res 1995; 77: 1–43

    Article  PubMed  Google Scholar 

  647. Hanss M, Collen D. Secretion of tissue-type plasminogen activator and plasminogen activator inhibitor by cultured human endothelial cells: modulation by thrombin, endotoxin and histamine. J Lab Clin Med 1987; 109: 97–104

    PubMed  CAS  Google Scholar 

  648. Francis CW, Marder VJ. Physiologic regulation and pathologie disorders of fibrinolysis. In: Coleman RW, Hirsh J, Marder VJ, et al., editors. Hemostasis and thrombosis. 2nd ed. Philadelphia (PA): Lippincott Williams & Wilkins, 1987: 358–79

    Google Scholar 

  649. Kluft C, Dooijewaard G, Emeis JJ. Role of the contact system in fibrinolysis. Semin Thromb Hemost 1987; 13: 50–68

    Article  PubMed  CAS  Google Scholar 

  650. Siegel RJ, Ariani M, Fishbein MC, et al. Histopathologic validation of angioscopy and intravascular ultrasound. Circulation 1991; 84: 109–17

    Article  PubMed  CAS  Google Scholar 

  651. Ehrenford S, Aggören-Pürsüm V, Hach-Wunderle V, et al. Prevalence of elevated histidine-rich glycoprotein in patients with thrombophilia: a study of 695 patients. Thromb Haemost 1994; 71: 160–1

    Google Scholar 

  652. Collen D, Wiman B. Turnover of antiplasmin, the fast-acting plasmin inhibitor of plasma. Blood 1979; 53: 313–24

    PubMed  CAS  Google Scholar 

  653. Kluft C. Disorders of the hemostatic system and the risk of the development of thrombotic and cardiovascular dissease: limitation of laboratory diagnosis. Am J Obstet Gynecol 1990; 163: 305–12

    PubMed  CAS  Google Scholar 

  654. Kluft C, Jie AFH. Comparison of specificities of antigen assays for plasminogen activator inhibitor 1 (PAI-1). Fibrinolysis 1990; 4: 136–7

    Article  CAS  Google Scholar 

  655. Schafer AI. The hypercoagulable states. Ann Intern Med 1985; 102: 814–28

    PubMed  CAS  Google Scholar 

  656. UH Winkler. Thromboembolierisiko, hormonelle Kontrazeption und östrogensubstitution. Gynäkologe 1997; 30: 341–51

    Article  Google Scholar 

  657. Pabinger I, Cyrle PA, Heistinger M, et al. The risk of thromboembolism in asymptomatic patients with protein C and protein S deficiency: a prospective cohort study. Thromb Haemost 1994; 71: 441–5

    PubMed  CAS  Google Scholar 

  658. Mammen EF. Oral contraceptives and blood coagulation: a critical review. Am J Obstet Gynecol 1982; 142: 781–90

    PubMed  CAS  Google Scholar 

  659. Koster T, Rosendaal FR, Briet E, et al. Protein C deficiency in a controlled series of unselected outpatients: an infrequent but clear risk factor for venous thrombosis: Leiden Thrombophilia Study. Blood 1995; 85: 2756–61

    PubMed  CAS  Google Scholar 

  660. Pabinger I, Schneider B. Thrombotic risk of women with hereditary antithrombin II-, protein C- and protein S-deficiency taking oral contraceptive medication: the GTH Study Group on Natural Inhibitors. Thromb Haemost 1994; 71(5): 548–52

    PubMed  CAS  Google Scholar 

  661. The British Committee for Standard in Haematology. Guidelines on the investigation and management of thrombophilia. J Clin Pathol 1990; 49: 703

    Google Scholar 

  662. Juhan-Vague I, Vague P. Interrelations between carbohydrates, lipids, and the hemostatic system in relation to the risk of thrombotic and cardiovascular disease. Am J Obstet Gynecol 1990; 163: 313–5

    PubMed  CAS  Google Scholar 

  663. Dawson S, Henney A. The status of PAI-1 as a risk factor for arterial and thrombotic disease: a review. Atherosclerosis 1992; 95: 105–17

    Article  PubMed  CAS  Google Scholar 

  664. Schulman S, Wiman B. The significance of the hypofibrinolysis for the risk of recurrence of venous thromboembolism: duration of anticoagulation (DURAC) Trial Study Group. Thromb Haemost 1996; 75(4): 607–11

    PubMed  CAS  Google Scholar 

  665. Hamsten A, de Faire U, Walldius G, et al. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; II: 3–9

    Article  Google Scholar 

  666. Hennis BC, Boomsma DI, Fijnvandraat K, et al. Estrogens reduce plasma histidine-rich glycoprotein (HRG) levels in a dose dependent way. Thromb Haemost 1995; 73: 484–7

    PubMed  CAS  Google Scholar 

  667. Jespersen J, Kluft C. Decreased levels of histidine-rich glycoprotein (HRG) and increased levels of free plasminogen in women on oral contraceptives low in estrogen. Thromb Haemost 1982; 48: 283–5

    PubMed  CAS  Google Scholar 

  668. Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognised mechanism characterised by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci U S A 1993; 90: 1004–8

    Article  PubMed  Google Scholar 

  669. Faioni EM, Franchi F, Asti D, et al. Resistance to activated protein C in nine thrombophilic families: interference in a protein S functional assay. Thromb Haemost 1993; 70: 1067–71

    PubMed  CAS  Google Scholar 

  670. Griffin JH, Evatt B, Wideman C, et al. Anticoagulant protein C pathway defective in majority of thrombophilic patients. Blood 1993; 82: 1989–93

    PubMed  CAS  Google Scholar 

  671. Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517–22

    Article  PubMed  CAS  Google Scholar 

  672. Koster T, Rosendaal FR, de Ronde H, et al. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet 1993; 342: 1503–6

    Article  PubMed  CAS  Google Scholar 

  673. Dahlbäck B, Hildebrand B. Inherited resistance to activated protein C is corrected by anticoagulant cofactor activity found to be a property of factor V. Proc Natl Acad Sci U S A 1994; 91(4): 1396–400

    Article  PubMed  Google Scholar 

  674. Sun X, Evatt B, Griffith JH. Blood coagulation factor Va abnormality associated with resistance to activated protein C in venous thrombophilia. Blood 1994; 83: 3120–5

    PubMed  CAS  Google Scholar 

  675. Bertina RM, Koeleman RPC, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64–7

    Article  PubMed  CAS  Google Scholar 

  676. Greengard JS, Sun X, Xu X, et al. Activated protein C resistance caused by Arg506Gln mutation in factor Va. Lancet 1994; 343: 1361–2

    Article  PubMed  CAS  Google Scholar 

  677. Voorberg J, Roeise J, Koopman R, et al. Association of idiopathic venous thromboembolism with single point mutation of arg506 of factor V. Lancet 1994; 343: 1535–6

    Article  PubMed  CAS  Google Scholar 

  678. Zöller B, Dahlbäck B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 1994; 343: 1536–8

    Article  PubMed  Google Scholar 

  679. Zöller B, Svensson PJ, He X, et al. Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C. J Clin Invest 1994; 94: 2521–4

    Article  PubMed  Google Scholar 

  680. Rees CR, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133–4

    Article  PubMed  CAS  Google Scholar 

  681. Zöller B, Nordlund L, Leskell H, et al. High prevalence of the FVR506Q mutation causing APC resistance in a region of southern Sweden with a high incidence of venous thrombosis. Thromb Res 1996; 83: 475–7

    Article  PubMed  Google Scholar 

  682. Hellgren M, Svenson PJ. Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives. Am J Obstet Gynecol 1995; 172: 210–3

    Article  Google Scholar 

  683. de Ronde H, Bertina RM. Laboratory diagnosis of APC resistance: a critical evaluation of the test and of the development of diagnostic criteria. Thromb Haemost 1994; 72: 880–6

    PubMed  Google Scholar 

  684. Henkens CM, Bom VJ, Seinen AJ, et al. Sensitivity to activated protein C: influence of oral contraceptives and sex. Thromb Haemost 1995; 73: 402–4

    PubMed  CAS  Google Scholar 

  685. Vasse M, Leduc O, Borg J-Y, et al. Resistance to activated protein C: evaluation of three functional assays. Thromb Res 1994; 76: 47–59

    Article  PubMed  CAS  Google Scholar 

  686. Mathonnet F, de Mazancourt P, Bastenaire B, et al. Activated protein C sensitivity ratio in pregnant women at delivery. Br J Haematol 1996; 92: 244–6

    Article  PubMed  CAS  Google Scholar 

  687. Walker MC, Garner PR, Keely EJ, et al. Changes in activated protein C resistance during normal pregnancy. Am J Obstet Gynecol 1997; 177: 162–9

    Article  PubMed  CAS  Google Scholar 

  688. Cumming AM, Tait RC, Fildes S, et al. Development of resistance to activated protein C during pregnancy. Br J Haematol 1995; 90(3): 725–7

    Article  PubMed  CAS  Google Scholar 

  689. Lowe GDO, Rumley A, Woodward M, et al. Oral contraceptives and venous thromboembolism. Lancet 1997; 349(9065): 1623

    Article  PubMed  CAS  Google Scholar 

  690. Spannagl M, Dick A, Assmann A, et al. Resistance to activated protein C in women using oral contraceptives. Semin Thromb Hemost 1998; 24: 423–30

    Article  PubMed  CAS  Google Scholar 

  691. Olivieri O, Friso S, Manzato F, et al. Resistance to activated protein C in healthy women taking oral contraceptives. Br J Haematol 1995; 91: 465–70

    Article  PubMed  CAS  Google Scholar 

  692. Tripodi A, Negri B, Bertina RM, et al. Screening for FV-Q506 mutation: evaluation of thirteen plasma-based methods for their diagnostic efficacy in comparison with DNA analysis. Thromb Haemost 1997; 77: 436–9

    PubMed  CAS  Google Scholar 

  693. Hemker HC, Willems GM, Béguin S. A computer assisted method to obtain the prothrombin activation velocity in whole plasma independent of the thrombin decay processes. Thromb Haemost 1986; 56: 9–17

    PubMed  CAS  Google Scholar 

  694. Hemker HC, Wielders S, Kessels H, et al. Continuous registration of thrombin generation in plasma: its use for the determination of the thrombin potential. Thromb Hemost 1993; 70: 617–24

    CAS  Google Scholar 

  695. Hemker HC, Béguin S. Thrombin generation in plasma: its assessment via the endogenous thrombin potential. Thromb Haemost 1995; 74: 134–8

    PubMed  CAS  Google Scholar 

  696. Duchemin J, Pittet J, Tartary M, et al. A new method based on thrombin generation inhibition to detect both protein C and protein S deficiencies in plasma. Thromb Haemost 1994; 71: 331–8

    PubMed  CAS  Google Scholar 

  697. Rosing J, Tans G, Nicolaes GAF, et al. Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second- and third-generation oral contraceptives. Br J Haematol 1997; 97: 233–8

    Article  PubMed  CAS  Google Scholar 

  698. Nicolaes GA, Thomassen MC, Tans G, et al. Effect of activated protein C on thrombin generation and on the thrombin potential in plasma of normal and APC-resistant individuals. Blood Coagul Fibrinolysis 1997; 8: 28–38

    Article  PubMed  CAS  Google Scholar 

  699. Heinemann LAJ, Assman A, Spannagl M, et al. Normalised activated protein C ratio itself not associated with increased risk of venous thromboembolism. Contraception 1998; 58: 321–2

    Article  PubMed  CAS  Google Scholar 

  700. Tans G, Rosendaal FR, Curvers J, et al. APC resistance determined with the endogenous thrombin generation potential is associated with venous thrombosis: a blinded clinical evaluation [abstract]. 17th Congress of the International Society for Thrombosis and Haemostasis: 1999 Aug 14–21; Washington (DC)

  701. Sugimura M, Kobayashi T, Kanayama N, et al. Detection of marked reduction of sensitivity to activated protein C prior to the onset of thrombosis during puerperium as detected by endogenous thrombin potential-based assay. Thromb Haemost 1999; 82: 1364–5

    PubMed  CAS  Google Scholar 

  702. de Visser MCH, Rosendaal FR, Bertina RM. A reduced sensitivity for activated protein C in the absence of factor V Leiden increases the risk of venous thrombosis. Blood 1999; 93: 1271–6

    PubMed  Google Scholar 

  703. Bloemenkamp KW, Rosendaal FR, Heimerhorst FM, et al. Hemostatic effects of oral contraceptives in women who developed deep-vein thrombosis while using oral contraceptives. Thromb Haemost 1998; 80: 382–7

    PubMed  CAS  Google Scholar 

  704. Astrup T. The biological significance of fibrinolysis. Lancet 1956; II: 565–8

    Article  Google Scholar 

  705. Bauer KA, Kass BL, ten Cate H, et al. Detection of factor X activation in humans. Blood 1989; 74: 2007–15

    PubMed  CAS  Google Scholar 

  706. Bauer KA, Mannuci PM, Gringeri A, et al. Factor IXa and Factor Villa cell surface complex does not contribute to the basal activation of the coagulation mechanism in-vivo. Blood 1992; 79: 2039–47

    PubMed  CAS  Google Scholar 

  707. Heinrich J, Sandkamp M, Kokott R, et al. Relationship of lipoprotein (a) to variables of coagulation and fibrinolysis in a healthy population. Clin Chem 1991; 37: 1950–4

    PubMed  CAS  Google Scholar 

  708. Mari D, Mannucci PM. Hypercoagulability in centenarians: the paradox of successful aging. Blood 1995; 85: 3144–9

    PubMed  CAS  Google Scholar 

  709. Falanga A, Ofosu FA, Delaini F, et al. The hypercoagulable state in cancer patients: evidence for impaired thrombin inhibitions. Blood Coagul Fibrinolysis 1994; 5: 19–23, 596–601

    Article  Google Scholar 

  710. Rickles FR, Levine M, Edwards RL. Hemostatic alterations in cancer patients. Cancer Metastasis Rev 1992; 11: 237–48

    Article  PubMed  CAS  Google Scholar 

  711. Leone G, Gugliotta L, Mazzucconi MG, et al. Evidence of a hypercoagulable state in patients with acute lymphoblastic leukemia treated with low dose of E coli L-asparaginase: a GIMEMA study. Thromb Haemost 1993; 69: 12–5

    PubMed  CAS  Google Scholar 

  712. Kakkar AK, DeRuvo N, Chinswangwatanakul V, et al. Extrinsic-pathway activation in cancer with high factor Vlly and tissue factor. Lancet 1995; 346: 1004–5

    Article  PubMed  CAS  Google Scholar 

  713. van Wersch JWJ, Peters C, Ubachs HMH. Haemostasis activation markers in plasma of patients with benign and malignant gynaecological tumours: pilot study. Eur J Clin Chem Clin Biochem 1995; 33: 225–9

    PubMed  Google Scholar 

  714. Zurborn KH, Gram J, Delbruck K, et al. Influence of cytostatic treatment on the coagulation sytem and fibrinolysis in patients with non-Hodgkin’s lymphomas and acute leukemias. Eur J Haematol 1991; 47: 55–9

    Article  PubMed  CAS  Google Scholar 

  715. Ginsberg JS, Deniers C, Brill-Edwards P, et al. Increased thrombin generation and activity in patients with systemic lupus erythematosus and anticarioloipin antibodies: evidence for a prothrombotic state. Blood 1993; 81: 2958–63

    PubMed  CAS  Google Scholar 

  716. van Wersch JWJ, De Vries Hanje JC, Oosterbos C. Coagulation activation and reactive fibrinolysis in patients receiving oral anticoagulation after total hip or knee replacement. Blood Coagul Fibrinolysis 1994; 5: 605–8

    PubMed  Google Scholar 

  717. Reiter W, Ehrensberger H, Steinbruckner B, et al. Parameters of haemostasis during acute venous thrombosis. Thromb Haemost 1995; 74: 596–601

    PubMed  CAS  Google Scholar 

  718. Koster T, Blann AD. Role of clotting factor VIII in effect of von Willebrand factor on occurence of deep-vein thrombosis. Lancet 1995; 345: 152–5

    Article  PubMed  CAS  Google Scholar 

  719. Koster T, Rosendaal FR, Reitsma PH, et al. Factor VII and fibrinogen levels as risk factors for venous thrombosis. Thromb Haemost 1994; 71: 719–22

    PubMed  CAS  Google Scholar 

  720. Meade T, Brozovic M, Chakrabarti R, et al. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; II: 533–7

    Article  Google Scholar 

  721. Hamsten A, Iselius L, de Faire U, et al. Genetic and cultural inheritance of plasma fibrinogen concentration. Lancet 1987; II: 988–91

    Article  Google Scholar 

  722. Ernst E. Plasma fibrinogen: an independent cardiovascular risk factor. J Intern Med 1990; 227: 365–7

    Article  PubMed  CAS  Google Scholar 

  723. Di Minno G, Mancini M. Measuring plasma fibrinogen to predict stroke and myocardial infarction. Atherosclerosis 1990; 10: 1–7

    Google Scholar 

  724. Haverkate F. Low-grade acute-phase reactions in arteriosclerosis and the consequences for haemostatic risk factors. Fibrinolysis 1992; 6: 17–8

    Google Scholar 

  725. Cook NS, Ubben D. Fibrinogen as a major risk factor in cardiovascular disease. Trends Pharmacol Sci 1990; 11: 444–8

    Article  PubMed  Google Scholar 

  726. Wilhelmsen L, Svärdsudd K, Korsan-Bengtsen K, et al. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 311: 501–5

    Article  PubMed  CAS  Google Scholar 

  727. Stone MC, Thorp JM. Plasma fibrinogen: a major coronary risk factor. J R Coll Gen Pract 1985; 35: 565–70

    PubMed  CAS  Google Scholar 

  728. Heinrich J, Schulte H, Balleisin L, et al. Predictive value of haemostatic variables in the PROCAM study. Thromb Haemost 1991; 65: 815–9

    Google Scholar 

  729. Kannel WB, Wolf PA, Castelli WP, et al. Fibrinogen and risk of cardiovascular disease. JAMA 1987; 258: 1183–7

    Article  PubMed  CAS  Google Scholar 

  730. Benchimol D, Dartigues JF. Predictive value of hemostatic factors for sudden death in patients with stable angina pectoris. Am J Cardiol 1995; 76: 241–4

    Article  PubMed  CAS  Google Scholar 

  731. Pedersen OD, Gram J, Jespersen J. Plasminogen activator inhibitor type-1 determines plasmin formation in patients with ischaemic heart disease. Thromb Haemost 1995; 73: 835–40

    PubMed  CAS  Google Scholar 

  732. Hamsten A, Wiman B, DeFaire U, et al. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med 1985; 313: 1557–63

    Article  PubMed  CAS  Google Scholar 

  733. Rapold JH, Grimaudo V, Deslerck PJ, et al. Plasma levels of plasminogen activator inhibitor type I, beta-thromboglobulin, and fibrinopeptide A before, during, and after treatment of acute myocardial infarction with alteplase. Blood 1991; 78: 1490–5

    PubMed  CAS  Google Scholar 

  734. Weissberger AJ, Ho KKY, Lazarus. Contrasting effects of oral and transdermal routes of estrogen replacement therapy on 24-hour growth hormone (GH) secretion, insulin like growth factor 1, and GH-binding protein in postmenopausal women. J Clin Endocrinol Metab 1991; 72: 374–81

    Article  PubMed  CAS  Google Scholar 

  735. Gray RP, Mohamed Ali V, Patteron DL, et al. Determinants of plasminogen activator inhibitor-1 activity in survivors of myocardial infarction. Thromb Haemost 1995; 73: 261–7

    PubMed  CAS  Google Scholar 

  736. Mennen LI, Schouten EG, Grobbee DE, et al. Coagulation factor VII, dietary fat and blood lipids: a review. Thromb Haemost 1996; 76: 492–9

    PubMed  CAS  Google Scholar 

  737. Bara L, Vicaud V. Expression of a paternal history of premature myocardial infarction on fibrinogen, factor VIIc and PAI-1 in European offspring: the European Atherosclerosis Research Study (EARS) Group. Thromb Haemost 1994; 71: 434–40

    PubMed  CAS  Google Scholar 

  738. Ruddock V, Meade TW. Factor VII activity and ischaemic heart disease: fatal and non-fatal events. Q J Med 1994; 87: 403–6

    CAS  Google Scholar 

  739. Austin MA. Plasma triglyceride as a risk factor for coronary heart disease. Am J Epidemiol 1989; 129: 249–59

    PubMed  CAS  Google Scholar 

  740. Gurfinkel E, Bozovich G, Cerda M, et al. Time significance of acute thrombotic reactant markers in patients with and without silent myocardial ischemia and overt unstable angina pectoris. Am J Cardiol 1995; 76: 121–4

    Article  PubMed  CAS  Google Scholar 

  741. Heinrich J, Schulte H, Schönfeld R, et al. Association of variables of coagulation, fibrinolysis and acute-phase with atherosclerosis in coronary and peripheral arteries and those supplying the brain. Thromb Haemost 1995; 73: 374–9

    PubMed  CAS  Google Scholar 

  742. Kruskal JB, Commerford PJ, Franks JJ, et al. Fibrin and Fibrinogen-related antigens in patients with stable and unstable coronary artery disease. N Engl J Med 1987; 317: 1361–5

    Article  PubMed  CAS  Google Scholar 

  743. van Hulsteijn H, Kolff J, Briet E, et al. Fibrinopeptide A and beta thromboglobulin in patients with angina pectoris and acute myocardial infarction. Am Heart J 1984; 107: 39–45

    Article  PubMed  Google Scholar 

  744. Eisenberg P, Sherman LA, Schechtmann K, et al. Fibrinopeptide A: a marker for acute coronary thrombosis. Circulation 1985; 71: 912–8

    Article  PubMed  CAS  Google Scholar 

  745. Mombelli G, Im Hof V, Haeberli A, et al. Effect of heparin on plasma fibrinopeptide A in patients with acute myocardial infarction. Circulation 1984; 69: 684–9

    Article  PubMed  CAS  Google Scholar 

  746. Kienast J, Thompson SG, Raskino C, et al. Prothrombin activation fragment 1+2 and thrombin antithrombin III complexes in patients with angina pectoris: relation to the presence and severity of coronary atherosclerosis. Thromb Haemost 1993; 70: 550–3

    PubMed  CAS  Google Scholar 

  747. Kluft C, Lansink M. Effect of oral contraceptives on haemostasis variables. Thromb Haemost 1997; 78: 315–26

    PubMed  CAS  Google Scholar 

  748. Winkler UH. Blood coagulation and oral contraceptives: a critical review. Contraception 1998; 57: 203–9

    Article  PubMed  CAS  Google Scholar 

  749. Winkler UH. Effects on haemostatic variables of desogestrel- and gestodene-containing oral contraceptives in comparison with (levo)norgestrel-containing oral contraceptives: a review. Am J Obstet Gynecol 1998; 179: S51–61

    Article  PubMed  CAS  Google Scholar 

  750. Harris GM, Stendt CL, Vollenhoven BJ, et al. Decreased plasma tissue factor pathway inhibitor in women taking combined oral contraceptives. Am J Hematol 1999; 60: 175–80

    Article  PubMed  CAS  Google Scholar 

  751. Bloemenkamp KWM, de Maat MPM, Dersjant-Roorda MC, et al. Genetic polymorphisms modify the response of factor VII to oral contraceptive use: an example of genotype-environment interaction [abstract]. 17th Congress of the International Society for Thrombosis and Haemostasis: 1999 Aug 14–21; Washington (DC)

  752. Mann DEJ, Kessel ER, Mullins DL, et al. ischemic colitis and acquired resistance to activated protein C in a woman using oral contraceptives. Am J Gastroenterol 1998; 93: 1960–2

    Article  PubMed  Google Scholar 

  753. Henkens CMA, Bom VJJ, van der Meer J. Lowered APC-sensitivity ratio related to increased factor VIII-clotting activity [letter]. Thromb Haemost 1995; 74: 1198

    PubMed  CAS  Google Scholar 

  754. Schramm W, Heineman LAJ. Oral contraceptives and venous thromboembolism: acquired APC resistance? Br J Haematol 1997; 98: 491–2

    PubMed  CAS  Google Scholar 

  755. Curvers J, Thomassen MCLGD, Nicolaes GAF, et al. Acquired APC resistance and oral contraceptives: differences between two functional tests. Br J Haematol 1999; 105: 88–94

    Article  PubMed  CAS  Google Scholar 

  756. Kluft C, de Maat MPM, Heinemann LAJ, et al. Importance of levonorgestrel dose in oral contraceptives for effects on coagulation. Lancet 1999; 354: 832–3

    PubMed  CAS  Google Scholar 

  757. Thomassen MCLGD, Curvers J, Rimmer JE, et al. Influence of hormone replacement therapy, oral contraceptives and pregnancy on APC resistance [abstract]. 17th Congress of the International Society for Thrombosis and Haemostasis: 1999 Aug 14–21; Washington (DC)

  758. Rosing J, Middeldorp S, Curvers J, et al. Low-dose oral contraceptives and acquired resistance to activated protein C: a randomised cross-over study. Lancet 1999; 354: 2036–40

    Article  PubMed  CAS  Google Scholar 

  759. Winkler UH, Schindler AE, Endrikat J, et al. A comparitive study of the effects on the hemostatic system of two monophasic gestodene oral contraceptives containing 20 μg and 30 μg ethinylestradiol. Contraception 1996; 53: 75–84

    Article  PubMed  CAS  Google Scholar 

  760. Winkler UH. Menopause, hormone replacement therapy and cardiovascular disease: a review of haemostaseological findings. Fibrinolysis 1992; 6 Suppl. 3: 5–10

    Article  Google Scholar 

  761. Winkler UH. Hormone replacement therapy and hemostasis: principles of acomplex interaction. Maturitas 1996; 24: 131–45

    PubMed  CAS  Google Scholar 

  762. Caine YG, Bauer KA, Barzegar E, et al. Coagulation activation following estrogen administration to postmenopausal women. Thromb Haemost 1992; 68: 392–5

    PubMed  CAS  Google Scholar 

  763. Inauen W, Stocker G, Haeberli A, et al. Effects of low and high dose oral contraceptives on blood coagulation and thrombogenesis induced by vascular subendothelium exposed to flowing human blood. Contraception 1991; 43: 435–46

    Article  PubMed  CAS  Google Scholar 

  764. Bloemenkamp KWM, Heimerhorst FM, Rosendaal FR, et al. Venous thrombosis, oral contraceptives and high factor VIII levels. Thromb Haemost 1999; 82: 1024–7

    PubMed  CAS  Google Scholar 

  765. Westhoff C. Oral contraceptives and venous thromboembolism: should epidemiologic associations drive clinical decision making? Contraception 1996; 54: 1–3

    Article  PubMed  CAS  Google Scholar 

  766. Lauritzen C. Comments on desogestrel and Gestoden (3rd generation progestogens) and the incidence of thromboembolism. Horm Metab Res 1996; 28: 245–7

    Article  PubMed  CAS  Google Scholar 

  767. Schwingl PJ, Shelton J. Modeled estimates of myocardial infarction and venous thromboembolic disease in users of second and third generation oral contraceptives. Contraception 1997; 55: 125–9

    Article  PubMed  CAS  Google Scholar 

  768. Martin R, Hilton S, Kerry S. The impact of the October 1995 ‘pill scare’ on oral contraceptive use in the United Kingdom: analysis of a general practice automated database. Fam Pract 1997; 14: 279–84

    Article  PubMed  CAS  Google Scholar 

  769. Lidegaard Ø. Oral contraceptives and venous thromboembolism: an epidemiological review. Eur J Contracept Reprod Health Care 1996; 1: 13–20

    Article  PubMed  CAS  Google Scholar 

  770. Farley TMM, Meirik O, Poulter NR, et al. Oral contraceptives and thrombotic diseases: impact of new epidemiological studies. Contraception 1996; 54: 193–5

    Article  PubMed  CAS  Google Scholar 

  771. Heimerhorst FM, Bloemenkamp KW, Rosendaal FR, et al. Oral contraceptives and thrombotic disease: risk of venous thromboembolism. Thromb Haemost 1997; 78: 327–33

    Google Scholar 

  772. Crook D. Do different oral contraceptives differ in their effects on cardiovascular disease? Br J Obstet Gynaecol 1997; 104: 516–20

    Article  PubMed  CAS  Google Scholar 

  773. Vandenbroucke JP, Heimerhorst FM, Bloemenkamp KWM, et al. Third-generation oral contraceptive and deep venous thrombosis: from epidemiologic controversy to new insights in coagulation. Am J Obstet Gynecol 1997; 177: 887–91

    Article  PubMed  CAS  Google Scholar 

  774. Spitzer WO. The 1995 pill scare revisited: anatomy of a non-epidemic. Hum Reprod 1997; 12: 2347–57

    Article  PubMed  CAS  Google Scholar 

  775. Walker AM. Newer oral contraceptives and the risk of venous thromboembolism. Contraception 1998; 57: 169–81

    Article  PubMed  CAS  Google Scholar 

  776. Spitzer WO. Bias versus causality: interpreting recent evidence of oral contraceptive studies. Am J Obstet Gynecol 1998; 179: S43–50

    Article  PubMed  CAS  Google Scholar 

  777. Westhoff CL. Oral contraceptives and thrombosis: an overview of study methods and results. Am J Obstet Gynecol 1998; 179: S38–42

    Article  PubMed  CAS  Google Scholar 

  778. Lewis MA. Myocardial infarction and stroke in young women: what is the impact of oral contraceptives. Am J Obstet Gynecol 1998; 179: S68–77

    Article  PubMed  CAS  Google Scholar 

  779. Weiss G. Risk of venous thromboembolism with third-generation oral contraceptives: a review. Am J Obstet Gynecol 1999; 180: S295–301

    Article  CAS  Google Scholar 

  780. Lidegaard Ø, Bygdeman M, Milsom I, et al. Oral contraceptives and thrombosis. Acta Obstet Gynecol Scand 1999; 78: 142–9

    Article  PubMed  CAS  Google Scholar 

  781. Edwards RG, Cohen J. Reproductive choices in 2000: the relative safety of current oral contraceptives. Hum Reprod Update 1999; 5: 565–620

    Article  PubMed  CAS  Google Scholar 

  782. Watson C. Scare over oral contraceptives: doctors should take warning seriously. BMJ 1995; 311: 1638

    Article  PubMed  CAS  Google Scholar 

  783. MacRae K, Kay C. Third generation oral contraceptive pills. BMJ 1995; 311: 1112

    Article  PubMed  CAS  Google Scholar 

  784. Reijnen HBM, Atsma WJ. Scare over oral contraceptives: risk is highest during first months of use [letter]. BMJ 1995; 311: 1639

    Article  PubMed  CAS  Google Scholar 

  785. Guillebaud J. Scare over oral contraceptives: if a woman has not had a thrombotic event in years of use she is unlikely to have one now. BMJ 1995; 311: 1638–9

    Article  PubMed  CAS  Google Scholar 

  786. Guillebaud J. Advising women on which pill to take. BMJ 1995; 311: 1111–2

    Article  PubMed  CAS  Google Scholar 

  787. Spitzer WO. Data from transnational study of oral contraceptives have been misused [letter]. BMJ 1995; 311: 1162

    Article  PubMed  CAS  Google Scholar 

  788. Vasilakis C, Jick S, Jick H. The risk of venous thromboembolism in users of postcoital contraceptive pills. Contraception 1999; 59: 79–83

    Article  PubMed  CAS  Google Scholar 

  789. Farmer R. Safety of modern oral contraceptives. Lancet 1996; 347: 259

    PubMed  CAS  Google Scholar 

  790. Parkin L, Skegg DCG, Wilson M, et al. Oral contraceptives and pulmonary embolism. Lancet 2000; 355: 2133–4

    Article  PubMed  CAS  Google Scholar 

  791. Todd J-C, Lawrenson R, Fanner RDT, et al. Venous thromboembolic disease and combined oral contraceptives: a re-analysis ofthe MediPlus database. Hum Reprod 1999; 14: 1500–5

    Article  PubMed  CAS  Google Scholar 

  792. Farmer RDT, Todd J-C, MacRae KD, et al. Oral contraception was not associated with venous thromboembolic disease in recent study. BMJ 1998; 316: 1090–1

    Article  PubMed  CAS  Google Scholar 

  793. Farmer RD, Lawrenson RA, Todd JC, et al. Acomparison of the risks of venous thromboembolic disease in association with different combined oral contraceptives. Br J Clin Pharmacol 2000; 49: 580–90

    Article  PubMed  CAS  Google Scholar 

  794. Fanner RDT, Todd J-C, Lewis M, et al. The risks of venous thromboembolic disease among German women using oral contraceptives: a database study. Contraception 1998; 57: 67–70

    Article  Google Scholar 

  795. Søgaard Andersen B, Olsen J, Nielsen GL, et al. Third generation oral contraceptives and heritable thrombophilia as risk factors of non-fatal venous thromboembolism. Thromb Haemost 1998; 79: 28–31

    Google Scholar 

  796. Bennet L, Odeberg H. Resistance to activated protein C, highly prevalent amongst users of oral contraceptives with venous thromboembolism. J Intern Med 1998; 244: 27–32

    Article  PubMed  CAS  Google Scholar 

  797. de Bruijn SFTM, Stam J, Vandenbroucke JP. Increased risk of cerebral venous sinus thrombosis with third-generation oral contraceptives. Lancet 1998; 351: 1404

    Article  PubMed  Google Scholar 

  798. Farmer RDT, Williams U, Simpson EL, et al. Effect of 1995 pill scare on rates of venous thromboembolism among women taking combined oral contraceptives: analysis of General Practice Research Database. BMJ; 2000: 477–9

  799. Suissa S, Spitzer WO, Rainville B, et al. Recurrent use of newer oral contraceptives and the risk of venous thromboembolism. Hum Reprod 2000; 15: 817–21

    Article  PubMed  CAS  Google Scholar 

  800. Vandenbroucke JP, Helmerhorst FM, Bloemenkamp KWM, et al. Third-generation oral contraceptives and venous thrombosis [letter]. Lancet 1997; 349: 731

    Article  PubMed  CAS  Google Scholar 

  801. Jick H, Jick SS, Wald Myers M, et al. Third generation oral contraceptives and thrombosis [letter]. Lancet 1997; 349: 731–2

    Article  PubMed  CAS  Google Scholar 

  802. Poulter NR, Chang CL, Mannot M, et al. Third-generation oral contraceptives and thrombosis. Lancet 1997; 349: 732–3

    Article  PubMed  CAS  Google Scholar 

  803. Fanner RDT, Lawrenson RA. Third-generation oral contraceptives and venous thrombosis [letter]. Lancet 1997; 349: 733

    Article  Google Scholar 

  804. Vandenbroucke JP, Bloemenkamp KWM, Helmerhorst FM, et al. Mortality from venous thromboembolism and myocardial infarction in young women in the Netherlands. Lancet 1996; 348: 401

    Article  PubMed  CAS  Google Scholar 

  805. Thomas SHL. Mortality from venous thromboembolism and myocardial infarction in young adults in England and Wales. Lancet 1996; 348: 402

    Article  PubMed  CAS  Google Scholar 

  806. Mellemkjaer L, Sørensen HT, Dreyer L, et al. Admission for and mortality from primary venous thromboembolism in women of fertile age in Denmark, 1977–95. BMJ 1999; 319: 820–1

    Article  PubMed  CAS  Google Scholar 

  807. Goldacre MJ, Roberts S, Yeates D, et al. Hospital admission and mortality rates for venous thromboembolism in Oxford region, UK, 1975–1978. Lancet 2000; 355: 1968–9

    Article  PubMed  CAS  Google Scholar 

  808. Farmer RDT, Lawrenson R. Utilisation patterns of oral contraceptives in UK general practice. Contraception 1996; 53: 211–5

    Article  PubMed  CAS  Google Scholar 

  809. Heinemann LAJ, Lewis MA, Assman A, et al. Could preferential prescribing and referral behaviour of physicians explain the elevated thrombosis risk found to be associated with third generation oral contraceptives. Phannacoepidemiol Drug Saf 1996; 5: 285–94

    Article  CAS  Google Scholar 

  810. Jamin C, De Mouzon J. Selective prescribing of third generation oral contraceptives (OCs). Contraception 1996; 54: 55–6

    Article  PubMed  CAS  Google Scholar 

  811. Van Lunsen HW Recent oral contraceptive use patterns in four European countries: evidence for selective prescribing of oral contraceptives containing third generation progestogens. Eur J Contracept Reprod Health Care 1996; 1: 39–45

    Article  PubMed  Google Scholar 

  812. Herings RMC, Boer DA, Urquhart J, et al. Non-causal explanations for the increased risk of venous thromboembolism among users of third-generation oral contraceptives [abstract]. Phannacoepidemiol Drug Saf 1996; 5: S88

    Google Scholar 

  813. Lidegaard Ø. The influence of thrombotic risk factors when oral contraceptives are prescribed. Acta Obstet Gynaecol Scand 1997; 76: 252–60

    CAS  Google Scholar 

  814. Farley TMM, Meirik O, Mannot MG, et al. Oral contraceptives and risk of venous thromboembolism: impact of duration of use [letter]. Contraception 1998; 57: 61–4

    Article  PubMed  CAS  Google Scholar 

  815. Suissa S, Spitzer WO. Methodological limitations in comparing the risks of newer oral contraceptives. Contraception 1998; 57: 64–5

    Article  Google Scholar 

  816. Jick H, Jick SS, Wald Myers M, et al. Risk of acute myocardial infarction and low-dose combined oral contraceptives. Lancet 1996; 347: 627–8

    Article  PubMed  CAS  Google Scholar 

  817. Lidegaard Ø. Oral contraceptives and acute myocardial infarction: a case control study [abstract]. Eur J Contracept Reprod Health Care 1996; 1:74

    Article  Google Scholar 

  818. Lidegaard Ø. Smoking and use of oral contraceptives: impact on thrombotic diseases. Am J Obstet Gynecol 1999; 180: S357–63

    Article  PubMed  CAS  Google Scholar 

  819. Poulter NR, Chang CL, Farley TMM, et al. Effect on stroke of different progestagens in low oestrogen dose oral contraceptives. Lancet 1999; 354: 301–2

    Article  PubMed  CAS  Google Scholar 

  820. Jick SS, Myers MW, Jick H. Risk of idiopathic cerebral haemorrhage in women on oral contraceptives with differing progestagen components. Lancet 1999; 354: 302–3

    Article  PubMed  CAS  Google Scholar 

  821. de Lignieres B. Safety of combined oral contraceptive pills [letter]. Lancet 1996; 347: 549

    Article  Google Scholar 

  822. Vandenbroucke JP, Bloemenkamp KWM, Helmerhorst FM, et al. Safety of combined oral contraceptive pills [letter]. Lancet 1996; 347: 547–8

    Article  Google Scholar 

  823. Vandenbroucke JP, Rosendaal FR. End of the line for “thirdgeneration-pin” controversy? Lancet 1997; 349: 1113–4

    Article  PubMed  CAS  Google Scholar 

  824. Alexandre JM, Strandberg K. EMEA and third-generation oral contraceptives. Lancet 1997; 350: 290

    Article  PubMed  CAS  Google Scholar 

  825. Olivieri O, Friso S, Manzato F, et al. Resistance to activated protein C, associated with oral contraceptive use; effect of formulations, duration of assumption, and doses of oestroprogestins. Contraception 1996; 54: 149–52

    Article  PubMed  CAS  Google Scholar 

  826. Nicolaes GAF, MCLGD Thomassen, van Oerle R, et al. A prothombinase-based assay for detection of resistance to activated protein C. Thromb Haemost 1996; 76: 404–10

    PubMed  CAS  Google Scholar 

  827. Middeldorp S, Meijers JCM, van den Ende AE, et al. Effects on coagulation of levonorgestrel and desogestrel containing low dose oral contraceptives. Thromb Haemost 2000; 84: 4–8

    PubMed  CAS  Google Scholar 

  828. Meijers JCM, Middeldorp S, Tekelenburg W, et al. Increased fibrinolytic activity during use of oral contraceptives is counteracted by an enhanced factor XI-independent down regulation of fibrinolysis: a randomized cross-over study of two low-dose oral contraceptives. Thromb Haemost 2000; 84: 9–14

    PubMed  CAS  Google Scholar 

  829. Tans G, Curvers J, Middeldorp S, et al. A randomized crossover study of the effects of levonorgestrel- and desogestrel-containing oral contraceptives on the anticoagulantpathways. Thromb Haemost 2000; 84: 15–21

    PubMed  CAS  Google Scholar 

  830. The Oral Contraceptive and Haemostasis Study Group. An open label, randomized study to evaluate the effects of seven monophasic oral contraceptive regimens on haemostatic variables. Contraception 1999; 59: 345–55

    Article  Google Scholar 

  831. van Tilburg NH, Rosendaal FR, Bertina RM. Thrombin activ-atable fibrinolysis inhibitor and the risk for deep vein thrombosis. Blood 2000;95: 2855–9

    PubMed  Google Scholar 

  832. Herkert O, Kuhl H, Busse R, et al. Thrombin receptor upregulation by progestagens in cultured vascular smooth muscle cells. Abstracts of the First European Meeting on Vascular Biology and Medicine: 1999 Sep 29–Oct 1: Nürnberg

  833. Hannaford PC. Some observations on last year’s pill scare. Br J Cardiol 1996; 3: 203

    Google Scholar 

  834. Hannaford PC, Owen-Smith V. Using epidemiological data to guide clinical practice: review of studies on cardiovascular disease and use of combined oral contraceptives. BMJ 1998; 316: 984–7

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The work of Dr Godsland is funded by the Heart Disease and Diabetes Research Trust (HDDRT). The present work was partly funded by a grant from NV Organon, manufacturer of steroid hormones, for the provision of a detailed overview of all issues relating to oral contraceptives and cardiovascular disease. Over the past 5 years he has received payments from manufacturers of oral contraceptives for lecturing (5 occasions) and legal consultation (2 occasions) regarding oral contraceptives and cardiovascular disease.

Dr Winkler has, over the past 5 years, been principal investigator in several multicentre trials of the haemostatic effects of oral contraceptive, funded by NV Organon and Wyeth-Ayerst, and has received occasional payments for lecturing on the haemostatic effects of sex steroids from manufacturers of oral contraceptives.

The work of Prof. Lidegaard is largely supported by public Danish health funds. He has recently been in receipt of a grant from the companies NV Organon, Wyeth-Ayerst and Schering for work on the epidemiology of cardiovascular disease in oral contraceptive users, and has received occasional payments for lecturing, and for legal consultancy on behalf of both manufacturers and users of steroid hormones (for more detailed discussion of these involvements and conflict of interest issues, see British Medical Journal website: http://www.bmj.com/).

Dr Crook has a consultancy arrangement with and receives research funding from NV Organon in connection with the metabolic effects of steroid hormones. Over the past 5 years, he has received honoraria and hospitality from various manufacturers of steroid hormones for lecturing on the subject of steroid hormones and cardiovascular risk, as well as ad hoc payments for advice given in connection with legal actions and regulatory authority hearings concerning the subject of steroid hormones and cardiovascular risk.

We thank Professor Victor Wynn for his role in initiating this project and his comments on the manuscript

Authors’ note:

Reviews on a scale such as this are generally in edited form, with distinct aspects of the subject being covered in separate chapters, each with its own author or panel of authors. In the present work, we have attempted a broadly synthetic approach in which different aspects of the issues are discussed in the context of a single, jointly-authored, review. Nevertheless, a breakdown of each author’s principal input is given here so that questions or comments on specific aspects of the review can be directed to the appropriate individual. Section 2 on the epidemiology of occlusive vascular disease in oral contraceptive users was assembled by Drs Lidegaard and Godsland, section 4.9 on the haemostatic system by Dr Winkler, and section 4.3 on lipid and lipoprotein metabolism by Dr Crook, who also contributed substantially to section 5.6 on progestogen effects on myocardial infarction risk and undertook detailed editing. Dr Godsland was responsible for all other sections.

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Authors and Affiliations

  1. Wynn Department of Metabolic Medicine, Division of Medicine, Imperial College School of Medicine, London, England

    Ian F. Godsland

  2. Department of Obstetrics and Gynaecology, Friedrich-Ebert-Krankenhaus Neumünster, Neumünster, Germany

    Ulrich Winkler

  3. Department of Obstetrics and Gynaecology, Herlev Hospital, University of Copenhagen, Herlev, Denmark

    Øjvind Lidegaard

  4. Department of Cardiovascular Biochemistry, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, London, England

    David Crook

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  1. Ian F. Godsland
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  2. Ulrich Winkler
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  3. Øjvind Lidegaard
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  4. David Crook
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Godsland, I.F., Winkler, U., Lidegaard, Ø. et al. Occlusive Vascular Diseases in Oral Contraceptive Users. Drugs 60, 721–869 (2000). https://doi.org/10.2165/00003495-200060040-00003

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