Abstract
Relationships between fatty liver and coronary heart disease (CHD) and stroke risk remain ill defined. We investigated whether fatty liver is a predictor of CHD and stroke risk. Until December 2000 we followed 2,024 atomic bomb survivors (775 men: 62.0±9.9 years old; 1,249 women: 63.2±8.4 years old) who had basic examinations between November 1990 and October 1992 for clinical and laboratory CHD risk factors and fatty liver and who were initially free of CHD and stroke. Forty-nine cases of CHD and 84 cases of stroke were observed. At the time of the baseline examinations, significant clinical associations were found between fatty liver and obesity (p<0.001), hypertension (p<0.001), dyslipidemia (p<0.001), and glucose intolerance (p<0.001). A slight but nonsignificant association was found between fatty liver and hyperuricemia (p=0.07) as well. By using multiple Cox regression analyses, age (relative risk [RR] 1.05, 95% confidence interval [CI] 1.01–1.08), smoking (RR 2.20, 95% CI 1.02–4.74), hyperuricemia (RR 2.30, 95% CI 1.08–4.89), and fatty liver (RR 2.53, 95% CI 1.06–6.06) were shown to be significant predictors of CHD, whereas age (RR 1.08, 95% CI 1.06–1.10), smoking (RR 2.06, 95% CI 1.14–3.72), and hypertension (RR 2.14, 95% CI 1.38–3.30) predicted stroke risk. Fatty liver, which clusters clinical and laboratory CHD risk factors, is an independent predictor of CHD, but not of stroke. Fatty liver should be followed as a feature of metabolic syndrome, with the aim of preventing CHD.
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Hayashi T, Boyko EJ, Leonetti DL, et al: Visceral adiposity and the prevalence of hypertension in Japanese Americans. Circulation 2003; 108: 1718–1723.
Boyko EJ, Leonetti DL, Bergstrom RW, Newell-Morris L, Fujimoto WY : Visceral adiposity, fasting plasma insulin, and blood pressure in Japanese-Americans. Diabetes Care 1995; 18: 174–181.
Boyko EJ, Leonetti DL, Bergstrom RW, Newell-Morris L, Fujimoto WY : Visceral adiposity, fasting plasma insulin, and lipid and lipoprotein levels in Japanese Americans. Int J Obes Relat Metab Disord 1996; 20: 801–808.
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.
Sattar N, Gaw A, Scherbakova O, et al: Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation 2003; 108: 414–419.
Isomaa B, Almgren P, Tuomi T, et al: Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001; 24: 683–689.
James OF, Day CP : Non-alcoholic steatohepatitis (NASH): a disease of emerging identity and importance. J Hepatol 1998; 29: 495–501.
Bjorntorp P : “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 1990; 10: 493–496.
Akahoshi M, Amasaki Y, Soda M, et al: Correlation between fatty liver and coronary risk factors: a population study of elderly men and women in Nagasaki, Japan. Hypertens Res 2001; 24: 337–343.
Marchesini G, Brizi M, Morselli-Labate AM, et al: Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 1999; 107: 450–455.
Knobler H, Schattner A, Zhornicki T, et al: Fatty liver—an additional and treatable feature of the insulin resistance syndrome. Q J Med 1999; 92: 73–79.
Marchesini G, Brizi M, Bianchi G, et al: Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001; 50: 1844–1850.
Pyorala M, Miettinen H, Halonen P, Laakso M, Pyorala K : Insulin resistance syndrome predicts the risk of coronary heart disease and stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study. Arterioscler Thromb Vasc Biol 2000; 20: 538–544.
Kip KE, Marroquin OC, Kelley DE, et al: Clinical importance of obesity versus the metabolic syndrome in cardiovascular risk in women: a report from the Women's Ischemia Syndrome Evaluation (WISE) study. Circulation 2004; 109: 706–713.
Falck-Ytter Y, Younossi ZM, Marchesini G, McCullough AJ : Clinical features and natural history of nonalcoholic steatosis syndromes. Semin Liver Dis 2001; 21: 17–26.
Sheth SG, Gordon FD, Chopra S : Nonalcoholic steatohepatitis. Ann Intern Med 1997; 126: 137–145.
Bugianesi E, Zannoni C, Vanni E, Marzocchi R, Marchesini G : Non-alcoholic fatty liver and insulin resistance: a cause-effect relationship? Dig Liver Dis 2004; 36: 165–173.
Wannamethee G, Ebrahim S, Shaper AG : Gamma-glutamyltransferase: determinants and association with mortality from ischemic heart disease and all causes. Am J Epidemiol 1995; 142: 699–708.
Ruttmann E, Brant LJ, Concin H, Diem G, Rapp K, Ulmer H : Gamma-glutamyltransferase as a risk factor for cardiovascular disease mortality: an epidemiological investigation in a cohort of 163,944 Austrian adults. Circulation 2005; 112: 2130–2137.
Schindhelm RK, Dekker JM, Nijpels G, et al: Alanine aminotransferase predicts coronary heart disease events: a 10-year follow-up of the Hoorn Study. Atherosclerosis 2007; 191: 391–396.
Targher G, Bertolini L, Poli F, et al: Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes 2005; 54: 3541–3546.
Atomic Bomb Casualty Commission : Research Plan for Joint ABCC-NIH Adult Health Study in Hiroshima and Nagasaki, Atomic Bomb Casualty Commission Technical Report. Hiroshima, Atomic Bomb Casualty Commission, 1962, pp 11–62.
Ikeda Y, Ohno M : Definition, classification and judgment of obesity, and clinical diagnosis of obesity as disease. Nippon Rinsho 1995; 53 ( Suppl): 229–236 ( in Japanese).
Yajima Y, Ohta K, Narui T, Abe R, Suzuki H, Ohtsuki M : Ultrasonographical diagnosis of fatty liver: significance of the liver-kidney contrast. Tohoku J Exp Med 1983; 139: 43–50.
Joseph AE, Saverymuttu SH, al-Sam S, Cook MG, Maxwell JD : Comparison of liver histology with ultrasonography in assessing diffuse parenchymal liver disease. Clin Radiol 1991; 43: 26–31.
Imaizumi M, Akahoshi M, Ichimaru S, et al: Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism. J Clin Endocrinol Metab 2004; 89: 3365–3370.
SAS/STAT Software : Changes and Enhancements, Release 8.1. Cary, SAS Inst. Inc.
Park SH, Kim BI, Yun JW, et al: Insulin resistance and C-reactive protein as independent risk factors for non-alcoholic fatty liver disease in non-obese Asian men. J Gastroenterol Hepatol 2004; 19: 694–698.
Nagahama K, Iseki K, Inoue T, Touma T, Ikemiya Y, Takishita S : Hyperuricemia and cardiovascular risk factor clustering in a screened cohort in Okinawa, Japan. Hypertens Res 2004; 27: 227–233.
Kurata A, Shigematsu Y, Higaki J : Sex-related differences in relations of uric acid to left ventricular hypertrophy and remodeling in Japanese hypertensive patients. Hypertens Res 2005; 28: 133–139.
Lakka HM, Lakka TA, Tuomilehto J, Salonen JT : Abdominal obesity is associated with increased risk of acute coronary events in men. Eur Heart J 2002; 23: 706–713.
Omagari K, Kadokawa Y, Masuda J, et al: Fatty liver in non-alcoholic non-overweight Japanese adults: incidence and clinical characteristics. J Gastroenterol Hepatol 2002; 17: 1098–1105.
Bickel C, Rupprecht HJ, Blankenberg S, et al: Serum uric acid as an independent predictor of mortality in patients with angiographically proven coronary artery disease. Am J Cardiol 2002; 89: 12–17.
Liese AD, Hense HW, Lowel H, Doring A, Tietze M, Keil U : Association of serum uric acid with all-cause and cardiovascular disease mortality and incident myocardial infarction in the MONICA Augsburg cohort. World Health Organization Monitoring Trends and Determinants in Cardiovascular Diseases. Epidemiology 1999; 10: 391–397.
Culleton BF, Larson MG, Kannel WB, Levy D : Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study. Ann Intern Med 1999; 131: 7–13.
Folsom AR, Rasmussen ML, Chambless LE, et al, The Atherosclerosis Risk in Communities (ARIC) Study Investigators : Prospective associations of fasting insulin, body fat distribution, and diabetes with risk of ischemic stroke. Diabetes Care 1999; 22: 1077–1083.
Kernan WN, Inzucchi SE, Viscoli CM, Brass LM, Bravata DM, Horwitz RI : Insulin resistance and risk for stroke. Neurology 2002; 59: 809–815.
Shimizu Y, Pierce DA, Preston DL, Mabuchi K : Studies of the mortality of atomic bomb survivors. Report 12, part II. Noncancer mortality: 1950–1990. Radiat Res 1999; 152: 374–389.
Preston DL, Shimizu Y, Pierce DA, Suyama A, Mabuchi K : Studies of mortality of atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality: 1950–1997. Radiat Res 2003; 160: 381–407.
Neel JV : Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? Am J Hum Genet 1962; 14: 353–362.
Ravussin E : Energy metabolism in obesity. Studies in the Pima Indians. Diabetes Care 1993; 16: 232–238.
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Baba, T., Amasaki, Y., Soda, M. et al. Fatty Liver and Uric Acid Levels Predict Incident Coronary Heart Disease but Not Stroke among Atomic Bomb Survivors in Nagasaki. Hypertens Res 30, 823–829 (2007). https://doi.org/10.1291/hypres.30.823
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DOI: https://doi.org/10.1291/hypres.30.823
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