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on November 4, 2004

Arteriosclerosis, Thrombosis, and Vascular Biology. 2004
Published online before print November 4, 2004, doi: 10.1161/01.ATV.0000149674.62430.e7
A more recent version of this article appeared on January 1, 2005
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Submitted on August 10, 2004
Accepted on October 7, 2004

Hyperhomocysteinemia Is Inversely Related With Left Ventricular Ejection Fraction and Predicts Cardiovascular Mortality in High-Risk Coronary Artery Disease Hypertensives

Maurizio Cesari ; Mario Zanchetta ; Alberto Burlina ; Luigi Pedon ; Giuseppe Maiolino ; Daniele Sticchi ; Achille C. Pessina ; and Gian Paolo Rossi *

From the Division of Cardiology (M.C., M.Z., L.P.), Cittadella Hospital; and the Department of Pediatrics (A.B.) and Physical Chemistry and DMCS Clinica Medica 4 (G.M., D.S., A.C.P., G.P.R.), University of Padova, Italy.

* To whom correspondence should be addressed. E-mail: gianpaolo.rossi{at}unipd.it.

Objective--The purpose of this study was to investigate the relationship of plasma homocysteine (tHcy) levels with coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) in high-risk patients undergoing coronary angiography for suspected CAD.

Methods and Results--In 936 consecutive patients, we measured LVEF, tHcy, folate levels, and quantified CAD with a modified Duke Index score. We also genotyped patients at the methylen-tetrahydrofolate-reductase 677C->T polymorphism. Hyperhomocysteinemia (HHcy) was defined as tHcy levels ≥15.46 µmol/L; total and cardiovascular mortality was assessed at follow-up that lasted 43 months (median). CAD was confirmed in 75% of patients and ruled out in the rest (non-CAD group). No relationship of HHcy with either arterial hypertension or the CAD score was found. In contrast, there was a significant inverse relationship of tHcy with LVEF in arterial hypertensive but not in normotensive patients, regardless of previous myocardial infarction. At logistic regression, HHcy was the strongest predictor (P=0.001) of a low (<40%) LVEF, followed by type 2 diabetes mellitus and cigarette smoking. At follow-up, HHcy significantly predicted cardiovascular mortality but only in the arterial hypertension subgroup.

Conclusions--In arterial hypertensive but not in normotensive patients, HHcy predicts cardiovascular mortality and a low LVEF, independent of CAD and history of myocardial infarction.
Key words: homocysteine • arterial hypertension • coronary artery disease • survival • MTHFR 677C->T polymorphism • left ventricular ejection fraction




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