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(Circulation. 2004;109:601-606.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Serum Homocysteine in Relation to Mortality and Morbidity From Coronary Heart Disease

A 24-Year Follow-Up of the Population Study of Women in Gothenburg

Dimitri Edin Zylberstein, MD; Calle Bengtsson, MD, PhD; Cecilia Björkelund, MD, PhD; Sverre Landaas, MD, PhD; Valter Sundh, BSc; Dag Thelle, MD, PhD; Lauren Lissner, PhD

From the Department of Primary Health Care (D.E.Z., C. Bengtsson, C. Björkelund, V.S., L.L.) and Institute of Cardiovascular Research (D.T.), Sahlgrenska Academy, Göteborg University, Göteborg, Sweden; Department of Laboratory Medicine (S.L.), Ullevål University Hospital, Oslo University, Oslo, Norway; and Nordic School of Public Health (L.L.), Göteborg, Sweden.

Correspondence to Dimitri Edin Zylberstein, MD, Sahlgrenska Academy at Göteborg University, Department of Primary Health Care, PO Box 454, SE 405 30 Göteborg, Sweden. E-mail dimitri.zylberstein{at}allmed.gu.se

Received March 26, 2003; de novo received September 1, 2003; revision received November 11, 2003; accepted November 18, 2003.

Background— Elevated serum total homocysteine (tHcy) is an established risk factor for cardiovascular disease (CVD), especially in men. However, there are few prospective population studies on female cohorts, and none of these has been longer than 13 years.

Methods and Results— The Population Study of Women in Gothenburg began in 1968/1969, at which time a representative population-based cohort of women aged 38, 46, 50, 54, and 60 years was recruited. The present cohort is a prospective follow-up of 1368 women in the original cohort for whom blood samples were stored and who were free of previous acute myocardial infarction (AMI) at the 1968/1969 baseline. Homocysteine was analyzed in 2001 with frozen serum from the baseline study and related to AMI incidence and mortality during 24 years of follow-up. Cox regression analyses were used with adjustment for age, traditional risk factors, and tHcy modifiers. For the fifth tHcy quintile, relative risk was 1.86 (95% CI 1.06 to 3.26) for AMI and 5.14 (95% CI 2.22 to 11.92) for death due to AMI. Age-standardized Kaplan-Meier plots for the fifth tHcy quintile versus others showed significant differences both for AMI and for death due to AMI that were apparent after 15 years of follow-up.

Conclusions— Homocysteine in middle-aged women is an independent risk factor for myocardial infarction and in particular mortality due to myocardial infarction. The study illustrates that long-term prospective studies might be necessary to show effects of homocysteine levels on AMI morbidity and mortality in women.

Key Words: homocysteine • women • myocardial infarction

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