Hyperhomocysteinemia and risk of vascular disease in women

Plasma levels of total homocysteine (tHcy), a possible risk factor for vasc ular disease, are generally lower in women than in men and lower in premeno pausal women than in postmenopausal women. This article reviews studies tha t have investigated associations of hyperhomocysteinemia with risk of vascu lar disease among women or that compared risk by stratum of gender or menop ausal status. Seven out of 12 epidemiological studies that included both men and women fo und hyperhomocysteinemia to be a stronger risk factor in women than in men. However, the interaction effect was statistically significant for only 1 s tudy. Three studies observed no risk difference between men and women, and 2 observed a weaker association in women. In addition, 3 studies that consi sted (almost) entirely of women observed direct associations of hyperhomocy steinemia with vascular disease risk, comparable to associations observed i n 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 l imited data indicate that hyperhomocysteinemia is also associated with elev ation of vascular disease risk before the menopause. The stronger association among women in some studies may be explained by as pects of the study design, such as age at inclusion (i.e., women usually su ffer from vascular diseases later in life than do men), or aspects of the d ata analysis, such as use of an overall instead of a gender-specific cutoff point. Of course, one cannot exclude the possibility that women are someho w more susceptible to detrimental effects of tHcy than men are, although th ere is evidence from other studies that estrogens have a "protective" effec t 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 men opause.