Hyperhomocysteinemia and risk of vascular disease in women

Plasma levels of total homocysteine (tHcy), a possible risk factor for vascular disease, are generally lower in women than in men and lower in premenopausal women than in postmenopausal women. This article reviews studies that have investigated associations of hyperhomocysteinemia with risk of vascular disease among women or that compared risk by stratum of gender or menopausal status. Seven out of 12 epidemiological studies that included both men and women found hyperhomocysteinemia to be a stronger risk factor in women than in men. However, the interaction effect was statistically significant for only 1 study. Three studies observed no risk difference between men and women, and 2 observed a weaker association in women. In addition, 3 studies that consisted (almost) entirely of women observed direct associations of hyperhomocysteinemia with vascular disease risk, comparable to associations observed in male populations. Hyperhomocysteinemia was associated with increased risk in populations of both young and elderly women, but only few studies have compared risks among premenopausal and postmenopausal women. However, the limited data indicate that hyperhomocysteinemia is also associated with elevation of vascular disease risk before the menopause. The stronger association among women in some studies may be explained by aspects of the study design, such as age at inclusion (i.e., women usually suffer from vascular diseases later in life than do men), or aspects of the data analysis, such as use of an overall instead of a gender-specific cutoff point. Of course, one cannot exclude the possibility that women are somehow more susceptible to detrimental effects of tHcy than men are, although there is evidence from other studies that estrogens have a "protective" effect on the vascular wall and a favorable effect on hemostasis. In conclusion, we should consider hyperhomocysteinemia as a potential risk factor for vascular disease in both men and women, before and after the menopause.