Lipoprotein(a) and Homocysteine Potentiate the Risk of Coronary Artery Disease in Male Subjects

Abstract

Lipoprotein (Lp(a)) and homocysteine (Hcy) are independent risk factors for coronary artery disease (CAD). Hcy promotes the release of free apo(a) from Lp(a). The high fibrin affinity of free apo(a) inhibits plasminogen binding and plasmin generation. Hyperhomocysteinemia can result from a less active variant of methylene tetrahydrofolate reductase (variant C677T). Because the C677T genotype is estimated to be present in 32.2% of the Mexican population, we took advantage of this prevalence to determine the possible potentiating effect between high plasma Lp(a) and Hcy for increasing the risk of CAD in male patients. First, 222 male patients admitted for coronary angiography were recruited and classified as CAD+ or CAD-. Anthropometric measurements, traditional risk factors, and plasma total Hcy (tHcy) and Lp(a) levels were recorded in both groups. We performed a conditional logistic regression model adjusted for conventional risk factors of CAD and it became clear that Lp(a) ≥30mg/dl was a risk factor for CAD (odds ratio [OR] 5.06, 95% confidence interval [CI] 1.88-13.51, P=0.001), whereas Hcy was not related to CAD (OR 0.44, 95% CI 0.63-2.90, P=0.44). However, when both factors were considered together in an interaction model, high tHcy and high Lp(a) plasma concentrations showed a potentiated effect (OR 10.52, 95% CI 2.18-50.71, P=0.003). The combination of high Lp(a) and Hcy levels synergistically increases the likelihood of developing CAD in male patients.