Hyperhomocysteinemia predicts total and cardiovascular mortality in high-risk women

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Abstract
The impact of homocysteine on cardiovascular disease can be more detrimental in women than in men, but it is unknown whether this applies to high-risk women. We therefore investigated the association of hyperhomocysteinemia with coronary artery disease (CAD) and cardiovascular mortality in high-risk women referred for CAD, both in the total population and in the hypertensive and normotensive cohorts. A prospective study cohort. A tertiary centre. Inclusion criteria: 262 consecutive Caucasian postmenopausal women referred for coronary angiography. Exclusion criteria: acute myocardial infarction and vitamin supplementation. We assessed total plasma homocysteine (tHcy), folate levels, and the MTHFR677C→T polymorphism. CAD was defined as a modified Duke Index score greater than 0; hyperhomocysteinemia as tHcy levels of 15 μmol/l or greater. The primary study outcome was cardiovascular mortality at follow-up. Mild/moderate and severe hyperhomocysteinemia was found in 15.1 and 1.6% of women, respectively, without differences between CAD and non-CAD women. By the ATPIII criteria, 92.2% of the women were in the highest risk class and 55% had CAD; however, no association of tHcy with the CAD score was found. After a median follow-up of 3.6 years, 23 women (9.1%) had died, 15 (6%) of cardiovascular causes. Women with high tHcy levels showed the worst all-cause and cardiovascular death-free survival at Kaplan–Meier and Cox regression analysis. Moreover, in the hypertensive cohort only women with hyperhomocysteinemia showed increased cardiovascular mortality. Hyperhomocysteinemia is common in high-risk women and adversely affects their prognosis, although it is unrelated to the CAD atherosclerotic burden.