Abstract
Nonalcoholic fatty liver disease (NAFLD) is a very common cause of chronic liver disease in the United States. A large proportion of patients with NAFLD have coexisting metabolic syndrome, a major risk factor for cardiovascular disease. A strong association between NAFLD and cardiovascular disease has been long suspected, and recent studies have confirmed that cardiovascular disease is the single most important cause of mortality in this patient population. NAFLD may pose cardiovascular risk beyond the risk conferred by traditional factors such as dyslipidemia, diabetes, and smoking. Health care providers managing patients with NAFLD should recognize this increased cardiovascular risk and should undertake early, aggressive risk factor modification.
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References and Recommended Reading
National Institute of Diabetes and Digestive and Kidney Diseases, Weight-control Information Network: Understanding adult obesity. Available at http://win.niddk.nih.gov/publications/understanding.htm. Accessed October 22, 2008.
Cheung O, Kapoor A, Puri P, et al.: The impact of fat distribution on the severity of nonalcoholic fatty liver disease and metabolic syndrome. Hepatology 2007, 46:1091–1100.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: 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 2001, 285:2486–2497.
Galassi A, Reynolds K, He J: Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. Am J Med 2006, 119:812–819.
Schwimmer JB, Pardee PE, Lavine JE, et al.: Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation 2008, 118:277–283.
Targher G, Arcaro G: Non-alcoholic fatty liver disease and increased risk of cardiovascular disease. Atherosclerosis 2007, 191:235–240.
Jeppesen JA, Hansen TW, Olsen MH, et al.: C-reactive protein, insulin resistance and risk of cardiovascular disease: a population-based study. Eur J Cardiovasc Prev Rehabil 2008, 15:594–598.
Weiss R, Dziura J, Burgert TS, et al.: Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004, 350:2362–2374.
Hamaguchi M, Kojima T, Takeda N, et al.: The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med 2005, 143:722–728.
Okosun IS, Chandra KM, Boev A, et al.: Abdominal adiposity in U.S. adults: prevalence and trends, 1960–2000. Prev Med 2004, 39:197–206.
Tsai C-H, Li T-C, Lin C-C: Metabolic syndrome as a risk factor for nonalcoholic fatty liver disease. South Med J 2008, 101:900–905.
Targher G, Bertolini L, Padovani R, et al.: Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007, 30:1212–1218.
Ioannou GN, Weiss NS, Boyko EJ, et al.: Elevated serum alanine aminotransferase activity and calculated risk of coronary heart disease in the United States. Hepatology 2006, 43:1145–1151.
Ua A, Sa T, Sa B, et al.: Association between nonalcoholic fatty liver disease and coronary artery disease. Coronary Artery Dis 2007, 18:433–436.
Pacifico L, Cantisani V, Ricci P, et al.: Nonalcoholic fatty liver disease and carotid atherosclerosis in children. Pediatr Res 2008, 63:423–427.
Brea A, Mosquera D, Martin E, et al.: Nonalcoholic fatty liver disease is associated with carotid atherosclerosis: a case-control study. Arterioscler Thromb Vasc Biol 2005, 25:1045–1050.
Targher G, Bertolini L, Padovani R, et al.: Relation of nonalcoholic hepatic steatosis to early carotid atherosclerosis in healthy men: role of visceral fat accumulation. Diabetes Care 2004, 27:2498–2500.
Sookoian S, Pirola CJ: Non-alcoholic fatty liver disease is strongly associated with carotid atherosclerosis: a systematic review. J Hepatol 2008, 49:600–607.
Volzke H, Robinson DM, Kleine V, et al.: Hepatic steatosis is associated with an increased risk of carotid atherosclerosis. World J Gastroenterol 2005, 11:1848–1853.
Matteoni CA, Younossi ZM, Gramlich T, et al.: Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999, 116:1413–1419.
Adams LA, Lymp JF, St. Sauver J, et al.: The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005, 129:113–121.
Ekstedt M, Franzén LE, Mathiesen UL, et al.: Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006, 44:865–873.
Dunn W, Xu R, Wingard DL, et al.: Suspected nonalcoholic fatty liver disease and mortality risk in a population-based cohort study. Am J Gastroenterol 2008, 103:2263–2271.
Ong JP, Pitts A, Younossi ZM: Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol 2008, 49:608–612.
Wild SH, Byrne CD, Tzoulaki I, et al.: Metabolic syndrome, haemostatic and inflammatory markers, cerebrovascular and peripheral arterial disease: The Edinburgh Artery Study. Atherosclerosis 2008 Aug 3 (Epub ahead of print).
Targher G, Bertolini L, Zoppini G, et al.: Increased plasma markers of inflammation and endothelial dysfunction and their association with microvascular complications in Type 1 diabetic patients without clinically manifest macroangiopathy. Diabet Med 2005, 22:999–1004.
Wieckowska A, Papouchado BG, Li Z, et al.: Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol 2008, 103:1372–1379.
Moller DE, Kaufman KD: Metabolic syndrome: a clinical and molecular perspective. Annu Rev Med 2005, 56:45–62.
Eckel RH, Grundy SM, Zimmet PZ: The metabolic syndrome. Lancet 2005, 365:1415–1428.
Lumeng CN, Deyoung SM, Saltiel AR: Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins. Am J Physiol Endocrinol Metab 2007, 292:166–174.
Hector J, Schwarzloh B, Goehring J, et al.: TNF-alpha alters visfatin and adiponectin levels in human fat. Horm Metab Res 2007, 39:250–255.
Chandran M, Phillips SA, Ciaraldi T, Henry RR: Adiponectin: more than just another fat cell hormone? Diabetes Care 2003, 26:2442–2450.
Huang MA, Greenson JK, Chao CK, et al.: One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study. Am J Gastroenterol 2005, 100:1072–1081.
Kechagias S, Ernersson A, Dahlqvist O, et al.: Fast-foodbased hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects. Gut 2008, 57:649–654.
Boyd ST, Fremming BA: Rimonabant—a selective CB1 antagonist. Ann Pharmacother 2005, 39:684–690.
Van Gaal LF, Rissanen AM, Scheen AJ, et al.: Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005, 365:1389–1397.
Mallat A, Lotersztajn S: Endocannabinoids and liver disease. I. Endocannabinoids and their receptors in the liver. Am J Physiol Gastrointest Liver Physiol 2008, 294:9–12.
Buse JB, Klonoff DC, Nielsen LL, et al.: Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther 2007, 29:139–153.
Torgerson JS, Hauptman J, Boldrin MN, Sjöström L: XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004, 27:155–161.
Furuya CK Jr, de Oliveira CP, de Mello ES, et al.: Effects of bariatric surgery on nonalcoholic fatty liver disease: preliminary findings after 2 years. J Gastroenterol Hepatol 2007, 22:510–514.
Mummadi R, Kasturi K, Chennareddygari S, Sood G: Effect of bariatric surgery on nonalcoholic fatty liver disease (NAFLD): systematic review and meta-analysis. Clin Gastroenterol Hepatol 2008, 6:1396–1402.
Batsis JA, Romero-Corral A, Collazo-Clavell ML, et al.: Effect of bariatric surgery on the metabolic syndrome: a population-based, long-term controlled study. Mayo Clin Proc 2008, 83:897–907.
Arterburn D, Schauer D, Wise R, et al.: Change in predicted 10-year cardiovascular risk following laparoscopic rouxen-y gastric bypass surgery. Obes Surg 2008 Aug 13 (Epub ahead of print).
Chalasani N, Aljadhey H, Kesterson J, et al.: Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroenterology 2004, 126:1287–1292.
Vuppalanchi R, Teal E, Chalasani N: Patients with elevated baseline liver enzymes do not have higher frequency of hepatotoxicity from lovastatin than those with normal baseline liver enzymes. Am J Med Sci 2005, 329:62–65.
Browning J: Statins and hepatic steatosis: perspectives from the Dallas Heart Study. Hepatology 2006, 44:466–471.
Lewis JH, Mortensen ME, Zweig S, et al.: Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Hepatology 2007, 46:1453–1463.
Albert MA, Danielson E, Rifai N, et al.: Effect of statin therapy on C-reactive protein levels: the Pravastatin Inflammation/CRP Evaluation (PRINCE): a randomized trial and cohort study. JAMA 2001, 286:64–70.
Argo C, Loria P, Caldwell SH, Lonardo A: Statins in liver disease: a molehill, an iceberg, or neither? Hepatology 2008, 48:662–669.
Marchesini G, Forlani G, Cerrelli F, et al.: Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003, 37:917–923.
Perseghin G, Lattuada G, De Cobelli F, et al.: Increased mediastinal fat and impaired left ventricular energy metabolism in young men with newly found fatty liver. Hepatology 2008, 47:51–58.
Senturk O, Kocaman O, Hulagu S, et al.: Endothelial dysfunction in Turkish patients with non-alcoholic fatty liver disease. Intern Med J 2008, 38:183–189.
Yoneda M, Mawatari H, Fujita K, et al.: High-sensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH. J Gastroenterol 2007, 42:573–582.
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Misra, V.L., Khashab, M. & Chalasani, N. Nonalcoholic fatty liver disease and cardiovascular risk. Curr Gastroenterol Rep 11, 50–55 (2009). https://doi.org/10.1007/s11894-009-0008-4
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DOI: https://doi.org/10.1007/s11894-009-0008-4