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The Rotterdam Study

Michiel L. Bots, MD, PhD; Lenore J. Launer, PhD; Jan Lindemans, PhD; Arno W. Hoes, MD, PhD; Albert Hofman, MD, PhD; Jacqueline C. M. Witteman, PhD; Peter J. Koudstaal, MD, PhD; Diederick E. Grobbee, MD, PhD

Arch Intern Med. 1999;159:38-44.

Background  Elevated homocysteine level increases vascular disease risk. Most data are based on subjects younger than 60 years; data for the elderly are more limited. We examined the relationship of homocysteine level to incident myocardial infarction and stroke among older subjects in a nested case-control study.

Methods  Subjects were participants in the Rotterdam Study, a cohort study among 7983 subjects residing in the Ommoord district of Rotterdam, the Netherlands. Baseline examinations were performed from March 1, 1990, to July 31, 1993. The analysis is restricted to myocardial infarction and stroke that occurred before December 31, 1994. One hundred four patients with a myocardial infarction and 120 with a stroke were identified with complete data. Control subjects consisted of a sample of 533 subjects drawn from the study base, free of myocardial infarction and stroke. Nonfasting total homocysteine levels were measured.

Results  Results were adjusted for age and sex. The risk of stroke and myocardial infarction increased directly with total homocysteine. The linear coefficient suggested a risk increase by 6% to 7% for every 1-µmol/L increase in total homocysteine. The risk by quintiles of total homocysteine level was significantly increased only in the group with levels above 18.6 µmol/L (upper quintile): odds ratios were 2.43 (95% confidence interval, 1.11-5.35) for myocardial infarction and 2.53 (95% confidence interval, 1.19-5.35) for stroke. Associations were more pronounced among those with hypertension.

Conclusions  The present study, based on a relatively short follow-up period, provides evidence that among elderly subjects an elevated homocysteine level is associated with an increased risk of cardiovascular disease.

From the Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam (Drs Bots, Launer, Hoes, Hofman, Witteman, and Grobbee), Julius Center for Patient Oriented Research, University Medical Center Utrecht, Utrecht (Drs Bots, Hoes, and Grobbee), National Institute of Public Health, Bilthoven (Dr Launer), and Central Clinical Chemical Laboratory (Dr Lindemans) and Department of Neurology (Dr Koudstaal), University Hospital Rotterdam, Rotterdam, the Netherlands. Dr Grobbee is now with the Department of Epidemiology and Biostatistics, Rijksuniversiteit Utrecht.

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