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(Circulation. 2000;102:605.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Effect of Plasma Homocysteine Concentration on Early and Late Events in Patients With Acute Coronary Syndromes

Peter J. Stubbs, MD, MRCP; Mohamed K. Al-Obaidi, MD, MRCP; Ronan M. Conroy; MusB; Paul O. Collinson, MD; MRCPath; Ian M. Graham, MD; FRCPI; Mark I. M. Noble, DSc, PhD, MD, FRCP

From the Department of Cardiology, Watford General Hospital, Watford (P.J.S.); the National Heart and Lung Institute, Imperial College School of Medicine, Royal Brompton Hospital and Charing Cross Hospital (M.K.A., M.I.M.N.) and the Department of Chemical Pathology, St George’s Hospital (P.O.C.), London, UK; and the Department of Epidemiology and Public Health Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland (R.M.C., I.M.G.).

Correspondence to Dr Mark I.M. Noble, Cardiovascular Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Charing Cross Hospital, Fulham Palace Rd, London W6 8RF, England.

Background—Although a raised plasma homocysteine is a risk factor for vascular disease, it is not known whether it is associated with an adverse cardiac outcome in patients admitted with acute coronary syndromes. We evaluated the relationship between plasma homocysteine and short-term (28 days) and long-term (median 2.5 years) prognosis in acute coronary syndromes.

Methods and Results—We evaluated the relationship of quintiles of homocysteine to fatal and nonfatal coronary disease early (28 days) and late (29 days to a median of 2.5 years) after admission to a single unit of patients with unstable angina (n=204) and myocardial infarction (n=236). The end points studied were cardiac death (n=67) and/or myocardial (re)infarction (n=30). Cox regression and logistic regression were used to estimate the relationship of homocysteine to coronary events. The event rate within the first 28 days (22 cardiac deaths and 5 nonfatal infarctions) was not related to the admission homocysteine level. In the 203 unstable angina and 214 myocardial infarction survivors, an apparent threshold effect was seen on long-term follow-up, with a significant step-up in the frequency of events between the lowest 3 quintiles (14 cardiac deaths and 11 nonfatal infarctions) and the upper 2 quintiles (31 fatal and 12 nonfatal events). Patients in the upper 2 quintiles (>12.2 µmol/L) had a 2.6-fold increase in the risk of a cardiac event (95% CI, 1.5 to 4.3, P<0.001).

Conclusions—Elevated total homocysteine levels on admission strongly predict late cardiac events in acute coronary syndromes.

Key Words: homocysteine • coronary disease

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