Lipoprotein(a) interactions with lipid and non-lipid risk factors in patients with early onset coronary artery disease results from the NHLBI family heart study

Background: A positive interaction between high plasma lipoprotein(a) [Lp(a)] and unfavorable plasma lipid levels has been reported to result in very high risk for premature coronary artery disease (CAD). We further examined this issue for men and women with early onset CAD. We also examined potential interactions betweeh Lp(a) and non-lipid risk factors. Methods and results: In 338 men and women with early onset CAD (most with a positive family history of early CAD) and 480 general population controls, we measured Lp(a), lipids and other risk factors. In univariate analysis, relative odds for CAD was 1.7 (P = 0.002) for plasma Lp(a) > 50 mg/dl. Elevated Lp(a) level was found to interact with adjusted plasma total/high density lipoprotein (HDL) cholesterol such that when Lp(a) was over 50 mg/dl and adjusted plasma total/HDL cholesterol > 5.8, relative odds for CAD were 8.0-9.6 (P < 0.0001) in multiple logistic regression. Non-lipid risk factors were generally found to multiply the risk associated with Lp(a) (as predicted by logistic regression) without evidence for interaction. Conclusions: We find evidence that Lp(a) does interact positively with adjusted plasma total/HDL cholesterol ratio. Aggressive risk factor intervention, especially for lipids, in those with elevated Lp(a) therefore appears indicated.