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(Circulation. 2007;115:180-187.)
© 2007 American Heart Association, Inc.

Epidemiology

Elevated Homocysteine Is Associated With Reduced Regional Left Ventricular Function

The Multi-Ethnic Study of Atherosclerosis

Khurram Nasir, MD, MPH; Michael Tsai, PhD; Boaz D. Rosen, MD; Veronica Fernandes, MD; David A. Bluemke, MD, PhD; Aaron R. Folsom, MD, MPH; João A.C. Lima, MD

From the Division of Cardiology (K.N., B.D.R., V.F., J.A.C.L.), Department of Medicine, and the Department of Radiology (D.A.B.), Johns Hopkins University, Baltimore, Md, and the Department of Laboratory Medicine and Pathology (M.T.) and the Division of Epidemiology and Community Health (A.R.F.), University of Minnesota, Minneapolis, Minn.

Correspondence to Dr João A.C. Lima, Cardiology Division, Blalock 524, Johns Hopkins Hospital, 600 N. Wolfe St, Baltimore, MD 21287–0409. E-mail jlima{at}jhmi.edu

Received June 23, 2006; accepted October 13, 2006.

Background— An elevated homocysteine (Hcy) level has been reported to be a risk factor for the development of congestive heart failure in individuals free of myocardial infarction. In this study, we aim to investigate the relationship between Hcy levels and regional left ventricular function in an asymptomatic population.

Method and Results— Regional peak systolic midwall circumferential strains were calculated from 1178 tagged magnetic resonance imaging studies in participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Left ventricular regions were defined by coronary territories (left anterior descending, left circumflex, right coronary artery). For the 1178 study participants (66±10 years of age, 58% males), the median (interquartile range) of Hcy was 9.1 (9.0 to 9.3). After adjustment for traditional risk factors, race, height, weight, left ventricular end-diastolic mass/volume, serum creatinine, and measures of atherosclerosis, reduced regional myocardial circumferential shortening across sex-specific quartiles of plasma Hcy in the left anterior descending (P=0.038) and left circumflex (P=0.009) regions persisted, which indicated an important association of reduced function with elevated Hcy. Multiple linear regression analyses confirmed that circumferential systolic dysfunction was associated with log transformed Hcy levels in the left anterior descending (P=0.004) and left circumflex (P=0.0002) regions. In the fully adjusted model, the odds ratio for left ventricular strains below the 10^th percentile with 1 SD increases in log-transformed Hcy was 1.33 (95% confidence interval, 1.04 to 1.70; P=0.022) for the left anterior descending, 1.28 (95% confidence interval, 1.00 to 1.64; P=0.046) for the left circumflex, and 1.32 (95% confidence interval, 1.03 to 1.69; P=0.025) for the right coronary artery region.

Conclusion— In this asymptomatic population, an elevated Hcy level is associated with reduced regional left ventricular systolic function detected by tagged magnetic resonance imaging.

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