Homocysteine, vitamin status and risk of vascular disease - Effects of gender and menopausal status

Background Elevated plasma total homocysteine (tHcy) is a known risk factor for vascular disease. Gender, age, and circulating levels of folate, vitam ins B-6 and B-12 affect tHcy levels. Objectives To study associations of gender and age with levels of plasma tH cy, and to examine the relationships of tHcy and circulating levels of fola te, vitamins B-6 and B-12 with risk of vascular disease in men and women (p re- and post-menopausal). Material and methods In a multicentre case-control study in Europe, 750 pat ients (544 men, 206 women) with documented vascular disease of the coronary , cerebral, or peripheral vessels and 800 control subjects (570 men, 230 wo men) were enrolled. Plasma tHcy levels (fasting and after methionine loadin g) and circulating levels of the vitamins were measured. Adjustment for age and centre was carried out for all statistical analyses, with additional a djustment for serum creatinine and vitamins for the tHcy comparisons betwee n the sexes and between cases and controls. Risk analyses included adjustme nt 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-menopa usal age category, female post-methionine load tHcy levels surpassed levels of men. Elevation of tHcy (defined as >80th percentile of controls) appear ed 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 B-6 conferred a two- to threefold increased risk of vascular dis ease, 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 v ascular disease in women as men, even before the menopause. Our data indica te that associations of the various tHcy measurements (and the vitamins tha t determine them), with risks of vascular disease may differ between the se xes. The tHcy-independent relationship of vitamin B-6 with vascular disease indicates that it will be advisable to test the effects of vitamin B-6 in clinical trials.