Homocysteine and lipoprotein(a) interact to increase CAD risk in young menand women

A biochemical link between homocysteine (tHcy) and lipoprotein(a) [Lp(a)] r elated to fibrin binding has been proposed. This hypothesis has not been sp ecifically examined in human subjects. We sought to determine in a clinical setting whether these risk factors would interact to increase coronary art ery disease (CAD) risk. We performed a cross-sectional analysis of 750 men and 403 women referred to a preventive cardiology clinic at the Cleveland C linic Foundation, in whom baseline tHcy and Lp(a) data were available. Logi stic regression after adjusting for standard cardiovascular risk factors wa s used to estimate the relative risk of CAD in patients with an Lp(a) great er than or equal to 30 mg/dL and a tHcy greater than or equal to 17 mu mol/ L. Neither isolated high tHcy (odds ratio [OR]=1.06, P=0.89) nor isolated h igh Lp(a) (OR=1.15, P=0.60) appeared to be associated with CAD in women. Ho wever, strong evidence of an association was seen when both risk factors we re present (OR=4.83, P=0.003). Moreover, this increased risk showed evidenc e of an interactive effect beyond that attributable to either additive or m ultiplicative effects of tHcy and Lp(a) (P=0.03). In contrast, both elevate d tHcy (OR=1.93, P=0.05) and elevated Lp(a) (OR=1.87, P=0.01) showed eviden ce of being independent risk factors for CAD in men. The presence of both r isk factors in men did not appear to confer additional risk (OR=2.00, P=0.0 9), even though ORs as high as 12.4 were observed within specific age inter vals. Consistent with prior studies, tHcy and Lp(a) are risk factors, eithe r independently or in concert, for CAD in this clinical population. More si gnificantly, we found evidence that when both risk factors were present in women, the associated risk was greater than what would be expected if the 2 risks were simply acting independently. The absence of such an interactive effect in men may be due to the confounding effects of age manifested as " survivor bias." These clinical findings provide insights into the potential roles of both tHcy and Lp(a) in the pathogenesis of atherosclerosis.