Published Online
on November 24, 2008

A more recent version of this article appeared on December 9, 2008

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Submitted on May 29, 2008
Accepted on September 29, 2008

Plasma Fetuin-A Levels and the Risk of Myocardial Infarction and Ischemic Stroke

Cornelia Weikert MD, MPH^*, Norbert Stefan MD, Matthias B. Schulze DrPH, Tobias Pischon MD, MPH, Klaus Berger MD, MSc, MPH, Hans-Georg Joost MD, Hans-Ulrich Häring MD, Heiner Boeing PhD, MSPH, and Andreas Fritsche MD

From the Departments of Epidemiology (C.W., M.B.S., T.P., H.B.) and Pharmacology (H.J.), German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute for Social Medicine, Epidemiology, and Health Economics, Charité University Medicine Berlin, Berlin, Germany (C.W.); Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease, and Clinical Chemistry, University of Tübingen, Tübingen, Germany (N.S., H.H., A.F.); Public Health Nutrition Unit, Technische Universität München, München, Germany (M.B.S.); and Institute of Epidemiology and Social Medicine, University of Muenster, Muenster, Germany (K.B.).

^* To whom correspondence should be addressed. E-mail: Weikert{at}dife.de.

Background—Fetuin-A, a protein almost exclusively secreted by the liver, induces insulin resistance and subclinical inflammation in rodents. Circulating fetuin-A levels are elevated in humans with metabolic syndrome and insulin resistance, conditions that are associated with increased risk of cardiovascular disease.

Methods and Results—We investigated the association between fetuin-A levels and the risk of future myocardial infarction (MI) and ischemic stroke (IS) in a case-cohort study based on the European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam Study comprising 27 548 middle-aged subjects of the general population. Fetuin-A levels were measured in plasma of 227 individuals who developed MI, in 168 who developed IS, and in 2198 individuals who remained free of cardiovascular events during a mean follow-up of 8.2±2.2 years. Individuals in the highest compared with the lowest quintile of plasma fetuin-A had significantly increased risks of MI (relative risk, 3.80; 95% confidence interval, 2.37 to 6.10; P for trend <0.0001) and IS (relative risk, 3.93; 95% confidence interval, 2.17 to 7.12; P for trend <0.0001) after adjustment for sex and age. Additional adjustment for smoking status, body mass index, waist circumference, alcohol consumption, educational attainment, physical activity, hypertension, diabetes mellitus, total and high-density lipoprotein cholesterol, and C-reactive protein only moderately attenuated these risks (MI: relative risk, 3.25; 95% confidence interval, 2.01 to 5.28; P for trend <0.0001; IS: relative risk, 3.78; 95% confidence interval, 2.06 to 6.94; P for trend <0.0001).

Conclusions—Our data provide evidence for a link between high plasma fetuin-A levels and an increased risk of MI and IS. Therefore, more research is warranted to determine the role of fetuin-A in the pathophysiology of cardiovascular disease.

Key words: atherosclerosis • cerebral infarction • coronary disease • risk factors

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