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Published in: Digestive Diseases and Sciences 9/2007

01-09-2007 | Original Paper

Association Among C-Reactive Protein, Fatty Liver Disease, and Cardiovascular Risk

Authors: Javier Lizardi-Cervera, Norberto C. Chavez-Tapia, Oliver Pérez-Bautista, Martha H. Ramos, Misael Uribe

Published in: Digestive Diseases and Sciences | Issue 9/2007

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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.
Literature
1.
go back to reference Wanless IR, Lentz JS (1990) Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 12:1106–1110PubMedCrossRef Wanless IR, Lentz JS (1990) Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 12:1106–1110PubMedCrossRef
2.
go back to reference Wang RT, Koretz RL, Yee HF Jr (2003) Is weight reduction an effective therapy for nonalcoholic fatty liver? A systematic review. Am J Med 115:554–559PubMedCrossRef Wang RT, Koretz RL, Yee HF Jr (2003) Is weight reduction an effective therapy for nonalcoholic fatty liver? A systematic review. Am J Med 115:554–559PubMedCrossRef
3.
go back to reference Garcia Monzon C (2001) Non-alcoholic steatohepatitis. Gastroenterol Hepatol 24:395–402PubMed Garcia Monzon C (2001) Non-alcoholic steatohepatitis. Gastroenterol Hepatol 24:395–402PubMed
4.
go back to reference 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 37:909–916PubMedCrossRef 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 37:909–916PubMedCrossRef
5.
go back to reference 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 95:2409–2415PubMedCrossRef 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 95:2409–2415PubMedCrossRef
6.
go back to reference Goldstein BJ, Scalia R (2004) Adiponectin: a novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab 89:2563–2568PubMedCrossRef Goldstein BJ, Scalia R (2004) Adiponectin: a novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab 89:2563–2568PubMedCrossRef
7.
go back to reference Day CP, James OF (1998) Hepatic steatosis:innocent bystander or guilty party? Hepatology 27:1463–1466PubMedCrossRef Day CP, James OF (1998) Hepatic steatosis:innocent bystander or guilty party? Hepatology 27:1463–1466PubMedCrossRef
8.
go back to reference 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) 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)
9.
go back to reference Tolman KG, Fonseca V, Tan MH, Dalpiaz A (2004) Narrative review:hepatobiliary disease in type 2 diabetes mellitus. Ann Intern Med 141:946–956PubMed Tolman KG, Fonseca V, Tan MH, Dalpiaz A (2004) Narrative review:hepatobiliary disease in type 2 diabetes mellitus. Ann Intern Med 141:946–956PubMed
10.
go back to reference Reaven G, Abbasi F, McLaughlin T (2004) Obesity, insulin resistance, and cardiovascular disease. Recent Prog Horm Res 59:207–223PubMedCrossRef Reaven G, Abbasi F, McLaughlin T (2004) Obesity, insulin resistance, and cardiovascular disease. Recent Prog Horm Res 59:207–223PubMedCrossRef
11.
go back to reference 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 40:185–194PubMedCrossRef 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 40:185–194PubMedCrossRef
12.
go back to reference Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J (2004) Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 40:46–54PubMedCrossRef Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J (2004) Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 40:46–54PubMedCrossRef
13.
go back to reference 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) 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)
14.
go back to reference 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 28:675–682PubMedCrossRef 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 28:675–682PubMedCrossRef
15.
go back to reference 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 135:562–566PubMed 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 135:562–566PubMed
16.
go back to reference Rifai N (2005) High-sensitivity C-reactive protein: a useful marker for cardiovascular disease risk prediction and the metabolic syndrome. Clin Chem 51:504–505PubMedCrossRef Rifai N (2005) High-sensitivity C-reactive protein: a useful marker for cardiovascular disease risk prediction and the metabolic syndrome. Clin Chem 51:504–505PubMedCrossRef
17.
go back to reference King DE, Mainous AG 3rd, Taylor ML (2004) Clinical use of C-reactive protein for cardiovascular disease. South Med J 97:985–988PubMedCrossRef King DE, Mainous AG 3rd, Taylor ML (2004) Clinical use of C-reactive protein for cardiovascular disease. South Med J 97:985–988PubMedCrossRef
18.
go back to reference Backes JM, Howard PA, Moriarty PM (2004) Role of C-reactive protein in cardiovascular disease. Ann Pharmacother 38:110–118PubMedCrossRef Backes JM, Howard PA, Moriarty PM (2004) Role of C-reactive protein in cardiovascular disease. Ann Pharmacother 38:110–118PubMedCrossRef
19.
go back to reference 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 123:745–750PubMedCrossRef 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 123:745–750PubMedCrossRef
20.
go back to reference 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 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
21.
go back to reference 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– 1227PubMedCrossRef 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– 1227PubMedCrossRef
22.
go back to reference 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 285:2486–2497CrossRef 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 285:2486–2497CrossRef
23.
go back to reference Hattori K, Becque MD, Katch VL, Rocchini AP, Boileau RA, Slaughter MH, Lohman TG (1987) Fat patterning of adolescents. Ann Hum Biol 14:23–28PubMedCrossRef Hattori K, Becque MD, Katch VL, Rocchini AP, Boileau RA, Slaughter MH, Lohman TG (1987) Fat patterning of adolescents. Ann Hum Biol 14:23–28PubMedCrossRef
24.
go back to reference 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 23:278–282PubMedCrossRef 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 23:278–282PubMedCrossRef
25.
go back to reference Ridker PM (2003) Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 107:363–369PubMedCrossRef Ridker PM (2003) Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 107:363–369PubMedCrossRef
26.
go back to reference 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 18:499–502PubMed 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 18:499–502PubMed
27.
go back to reference 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 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
28.
go back to reference 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 107:499–511PubMedCrossRef 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 107:499–511PubMedCrossRef
30.
go back to reference Mendez-Sanchez N, Chavez-Tapia NC, Uribe M (2004) [Obesity and non-alcoholic steatohepatitis]. Gac Med Mex 140(Suppl 2):S67–S72PubMed Mendez-Sanchez N, Chavez-Tapia NC, Uribe M (2004) [Obesity and non-alcoholic steatohepatitis]. Gac Med Mex 140(Suppl 2):S67–S72PubMed
31.
go back to reference Mendez-Sanchez N, Chavez-Tapia NC, Uribe M (2004) [An update on non-alcoholic fatty liver disease]. Rev Invest Clin 56:72–82PubMed Mendez-Sanchez N, Chavez-Tapia NC, Uribe M (2004) [An update on non-alcoholic fatty liver disease]. Rev Invest Clin 56:72–82PubMed
32.
go back to reference 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 25:193–197PubMed 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 25:193–197PubMed
33.
go back to reference 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 110:380–385PubMedCrossRef 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 110:380–385PubMedCrossRef
34.
go back to reference Ridker PM, Wilson PW, Grundy SM (2004) Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation 109:2818–2825PubMedCrossRef Ridker PM, Wilson PW, Grundy SM (2004) Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation 109:2818–2825PubMedCrossRef
35.
go back to reference 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, 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
36.
go back to reference 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 11:1737–1741PubMed 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 11:1737–1741PubMed
37.
go back to reference 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 19:694–698PubMedCrossRef 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 19:694–698PubMedCrossRef
38.
go back to reference 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 39:206–217PubMedCrossRef 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 39:206–217PubMedCrossRef
Metadata
Title
Association Among C-Reactive Protein, Fatty Liver Disease, and Cardiovascular Risk
Authors
Javier Lizardi-Cervera
Norberto C. Chavez-Tapia
Oliver Pérez-Bautista
Martha H. Ramos
Misael Uribe
Publication date
01-09-2007
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 9/2007
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-006-9262-6

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