Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with several metabolic disturbances involving inflammation. Ultrasensitive C-reactive protein (uCRP), a marker of coronary heart disease and other chronic diseases, has not been investigated in NAFLD. We tested the relationship between uCRP and NAFLD in middle-aged asymptomatic subjects, independently of other metabolic disturbances associated with metabolic syndrome and cardiovascular risk. We compared 310 subjects with steatosis visible on ultrasound (cases) with 630 and without (controls). Body mass index (BMI), blood pressure and serum levels of uCRP, glucose, lipids, and lipoproteins were measured in all subjects. Differences between groups and the impact of serum uCRP levels were tested by univariate and multivariate logistic regression analysis. Cases were statistically different from controls in the frequency of metabolic syndrome (66.4% vs. 26.7%; P < 0.001). Cases were significantly older (P < 0.001), and had significantly higher values for BMI, glucose, total cholesterol and triglycerides (P < 0.001), and mean uCRP concentrations (4.5 vs. 2.79 mg/L; P < 0.001). By univariate analysis, variables significantly associated with cases were glucose (OR, 4.09; 95% CI, 2.98–5.61), BMI (OR 5.54; 95% CI, 4.09–7.49), and uCRP (OR 7.06; 95% CI, 4.51–11.02). By multivariate analysis, uCRP levels were associated with hepatic steatosis (OR 5.83; 95% CI, 3.07–11.06). Cardiovascular risk was also higher in subjects with NAFLD (4.7 vs. 2.8). Subjects with hepatic steatosis showed an increased concentration of uCRP independently of other metabolic disturbances; this suggests an increased risk of cardiovascular diseases and could be used as a marker of chronic inflammation.
Similar content being viewed by others
References
Wanless IR, Lentz JS (1990) Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 12:1106–1110
Wang RT, Koretz RL, Yee HF Jr (2003) Is weight reduction an effective therapy for nonalcoholic fatty liver? A systematic review. Am J Med 115:554–559
Garcia Monzon C (2001) Non-alcoholic steatohepatitis. Gastroenterol Hepatol 24:395–402
Musso G, Gambino R, De Michieli F, Cassader M, Rizzetto M, Durazzo M, Faga E, Silli B, Pagano G (2003) Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 37:909–916
Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95:2409–2415
Goldstein BJ, Scalia R (2004) Adiponectin: a novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab 89:2563–2568
Day CP, James OF (1998) Hepatic steatosis:innocent bystander or guilty party? Hepatology 27:1463–1466
Brea A, Mosquera D, Martin E, Arizti A, Cordero JL, Ros E (2005) Nonalcoholic fatty liver disease is associated with carotid atherosclerosis. A case-control study. Arterioscler Thromb Vasc Biol (in press)
Tolman KG, Fonseca V, Tan MH, Dalpiaz A (2004) Narrative review:hepatobiliary disease in type 2 diabetes mellitus. Ann Intern Med 141:946–956
Reaven G, Abbasi F, McLaughlin T (2004) Obesity, insulin resistance, and cardiovascular disease. Recent Prog Horm Res 59:207–223
Feldstein AE, Werneburg NW, Canbay A, Guicciardi ME, Bronk SF, Rydzewski R, Burgart LJ, Gores GJ (2004) Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway. Hepatology 40:185–194
Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J (2004) Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 40:46–54
Schram MT, Chaturvedi N, Schalkwijk CG, Fuller JH, Stehouwer CD (2005) Markers of inflammation are cross-sectionally associated with microvascular complications and cardiovascular disease in type 1 diabetes—the EURODIAB Prospective Complications Study. Diabetologia (in press)
Maumus S, Marie B, Siest G, Visvikis-Siest S (2005) A prospective study on the prevalence of metabolic syndrome among healthy French families: two cardiovascular risk factors (HDL cholesterol and tumor necrosis factor-{alpha}) are revealed in the offspring of parents with metabolic syndrome. Diabetes Care 28:675–682
Lopez-Garcia E, Schulze MB, Meigs JB, Manson JE, Rifai N, Stampfer MJ, Willett WC, Hu FB (2005) Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction. J Nutr 135:562–566
Rifai N (2005) High-sensitivity C-reactive protein: a useful marker for cardiovascular disease risk prediction and the metabolic syndrome. Clin Chem 51:504–505
King DE, Mainous AG 3rd, Taylor ML (2004) Clinical use of C-reactive protein for cardiovascular disease. South Med J 97:985–988
Backes JM, Howard PA, Moriarty PM (2004) Role of C-reactive protein in cardiovascular disease. Ann Pharmacother 38:110–118
Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, Mullen KD, Cooper JN, Sheridan MJ (2002) The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 123:745–750
Aufweber E, Jorup-Ronstrom C, Edner A, Hansson LO (1991) C-reactive protein sufficient as screening test in bacterial vs. viral infections. J Infect 23:216–220
Noack B, Genco RJ, Trevisan M, Grossi S, Zambon JJ, De Nardin E (2001) Periodontal infections contribute to elevated systemic C-reactive protein level. J Periodontol 72:1221– 1227
NCEP (2001) Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285:2486–2497
Hattori K, Becque MD, Katch VL, Rocchini AP, Boileau RA, Slaughter MH, Lohman TG (1987) Fat patterning of adolescents. Ann Hum Biol 14:23–28
Lim SC, Tai ES, Tan BY, Chew SK, Tan CE (2000) Cardiovascular risk profile in individuals with borderline glycemia:the effect of the 1997 American Diabetes Association diagnostic criteria and the 1998 World Health Organization Provisional Report. Diabetes Care 23:278–282
Ridker PM (2003) Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 107:363–369
Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502
Roberts WL, Moulton L, Law TC, Farrow G, Cooper-Anderson M, Savory J, Rifai N (2001) Evaluation of nine automated high-sensitivity C-reactive protein methods: implications for clinical and epidemiological applications. Part 2. Clin Chem 47:418–425
Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Rifai N, Smith SC Jr, Taubert K, Tracy RP, Vinicor F (2003) Markers of inflammation and cardiovascular disease:application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107:499–511
Angulo P (2002) Nonalcoholic fatty liver disease. N Engl J Med 346:1221–1231
Mendez-Sanchez N, Chavez-Tapia NC, Uribe M (2004) [Obesity and non-alcoholic steatohepatitis]. Gac Med Mex 140(Suppl 2):S67–S72
Mendez-Sanchez N, Chavez-Tapia NC, Uribe M (2004) [An update on non-alcoholic fatty liver disease]. Rev Invest Clin 56:72–82
Kerner A, Avizohar O, Sella R, Bartha P, Zinder O, Markiewicz W, Levy Y, Brook GJ, Aronson D (2005) Association between elevated liver enzymes and C-reactive protein: possible hepatic contribution to systemic inflammation in the metabolic syndrome. Arterioscler Thromb Vasc Biol 25:193–197
Rutter MK, Meigs JB, Sullivan LM, D'Agostino RB Sr, Wilson PW (2004) C-reactive protein, the metabolic syndrome, and prediction of cardiovascular events in the Framingham Offspring Study. Circulation 110:380–385
Ridker PM, Wilson PW, Grundy SM (2004) Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation 109:2818–2825
Mendez-Sanchez N, Motola-Kuba D, Bahena-Aponte J, Chavez-Tapia N, Pichardo-Bahena R, Uribe M (2003) Hypertransaminasemia and severe hepatic steatosis without inflammation. A case report. Ann Hepatol 2:183–185
Mendez-Sanchez N, Chavez-Tapia NC, Villa AR, Sanchez-Lara K, Zamora-Valdes D, Ramos MH, Uribe M (2005) Adiponectin as a protective factor in hepatic steatosis. World J Gastroenterol 11:1737–1741
Park SH, Kim BI, Yun JW, Kim JW, Park DI, Cho YK, Sung IK, Park CY, Sohn CI, Jeon WK, Kim H, Rhee EJ, Lee WY, Kim SW (2004) Insulin resistance and C-reactive protein as independent risk factors for non-alcoholic fatty liver disease in non-obese Asian men. J Gastroenterol Hepatol 19:694–698
Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J (2004) Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 39:206–217
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lizardi-Cervera, J., Chavez-Tapia, N.C., Pérez-Bautista, O. et al. Association Among C-Reactive Protein, Fatty Liver Disease, and Cardiovascular Risk. Dig Dis Sci 52, 2375–2379 (2007). https://doi.org/10.1007/s10620-006-9262-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-006-9262-6