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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:115.)
© 2005 American Heart Association, Inc.

Vascular Biology

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; Gian Paolo Rossi

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

Correspondence to Prof Gian Paolo Rossi, MD, FACC, FAHA, Department of Clinical and Experimental Medicine, Clinica Medica 4 University Hospital, via Giustiniani, 2, 35126 Padova, Italy. 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 677CT 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.

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. 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 677CT polymorphism • left ventricular ejection fraction

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