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Hyperhomocystinemia
A Risk Factor or a Consequence of Coronary Heart Disease?
Paul Knekt, PhD;
Antti Reunanen, MD, PhD;
Georg Alfthan, PhD;
Markku Heliövaara, MD, PhD;
Harri Rissanen;
Jukka Marniemi, PhD;
Arpo Aromaa, MD, PhD
Arch Intern Med. 2001;161:1589-1594.
Background Mild hyperhomocystinemia has been suggested as an indicator of an increased
risk of cardiovascular disease.
Objective To examine whether serum homocysteine concentration is a predictor of
coronary heart disease (CHD) events.
Methods A case-control study, nested in a population-based cohort study was
used. During a follow-up of 13 years, 166 major coronary events (death from
CHD or nonfatal myocardial infarction) occurred in men with evidence of heart
disease at baseline and 272 events in men without a history of heart disease.
Two controls per case were selected by individual matching.
Results Among men with known heart disease at baseline, the relative risk (95%
confidence interval) of CHD events adjusted for age, smoking, hypertension,
diabetes mellitus, serum cholesterol level, body mass index, and alcohol consumption
was 2.23 (95% confidence interval, 1.03-4.85) in the highest serum homocysteine
quintile compared with the lowest quintile. Among the men free of heart disease
at baseline, the corresponding relative risk was 0.90 (95% confidence interval,
0.51-1.60).
Conclusions This prospective study does not support the hypothesis that a high concentration
of serum homocysteine is a risk factor for coronary events in a population
free of heart disease. However, it does suggest that mild hyperhomocystinemia
predicts secondary coronary events in men with heart disease, possibly as
a consequence of atherosclerotic changes.
From the National Public Health Institute, Helsinki, Finland (Drs Knekt,
Reunanen, Alfthan, Heliövaara, and Aromaa and Mr Rissanen); and the Social
Insurance Institution, Turku, Finland (Dr Marniemi).
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