Copyright © 1999 by the European Society of Cardiology.
Homocysteine, vitamin status and risk of vascular disease; effects of gender and menopausal status
Wageningen Centre for Food Sciences and Wageningen University, Division of Human Nutrition and Epidemiology, Wageningen, The Netherlands
Department of Cardiology, Adelaide-Meath Hospital incorporating the National Children's Hospital, Dublin, Ireland
Department of Public Health Medicine and Epidemiology, University College Dublin, Dublin, Ireland
Department of Epidemiology and Preventive Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A.
Department of Medicine, University Hospital Nijmegen, Nijmegen, The Netherlands
revised December 18, 1998; accepted January 5, 1999
Abstract
Background Elevated plasma total homocysteine (tHcy) is a known risk factor for vascular disease. Gender, age, and circulating levels of folate, vitamins B6and B12affect tHcy levels.
Objectives To study associations of gender and age with levels of plasma tHcy, and to examine the relationships of tHcy and circulating levels of folate, vitamins B6and B12with risk of vascular disease in men and women (pre- and post-menopausal).
Material and methods In a multicentre case-control study in Europe, 750 patients (544 men, 206 women) with documented vascular disease of the coronary, cerebral, or peripheral vessels and 800 control subjects (570 men, 230 women) were enrolled. Plasma tHcy levels (fasting and after methionine loading) and circulating levels of the vitamins were measured. Adjustment for age and centre was carried out for all statistical analyses, with additional adjustment for serum creatinine and vitamins for the tHcy comparisons between the sexes and between cases and controls. Risk analyses included adjustment for creatinine and traditional risk factors. Relationships between age, gender and tHcy were studied among control subjects only.
Results Fasting tHcy levels were lower in women than in men. Levels of tHcy showed a positive association with age, for both sexes. In the post-menopausal age category, female post-methionine load tHcy levels surpassed levels of men. Elevation of tHcy (defined as >80th percentile of controls) appeared to be at least as strong a risk factor for vascular disease in women as in men, even before the menopause. For post-methionine load tHcy, there was a 40% stronger association with vascular disease in women than in men. In both sexes, but especially in pre-menopausal women, low circulating levels of vitamin B6conferred a two- to threefold increased risk of vascular disease, independent of tHcy. In men, but not in women, low (defined as <20th percentile of controls) circulating folate levels were associated with a 50% increased risk of vascular disease.
Conclusions Elevation of tHcy appears to be at least as strong a risk for vascular disease in women as men, even before the menopause. Our data indicate that associations of the various tHcy measurements (and the vitamins that determine them), with risks of vascular disease may differ between the sexes. The tHcy-independent relationship of vitamin B6with vascular disease indicates that it will be advisable to test the effects of vitamin B6in clinical trials.
Key Words: Homocysteine, vitamins, gender, menopause, vascular disease
f1 Correspondence: Dr Petra Verhoef, Wageningen Centre for Food Sciences and Wageningen University, Division of Human Nutrition and Epidemiology, Wageningen, The Netherlands.
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