LIPOPROTEIN(A) INTERACTIONS WITH LIPID AND NONLIPID RISK-FACTORS IN EARLY FAMILIAL CORONARY-ARTERY DISEASE

An interaction between high plasma lipoprotein(a) [Lp(a)], unfavorable plasma lipids, and other risk factors may lead to very high risk for premature CAD. Plasma Lp(a), lipids, and other coronary risk factors w ere examined in 170 cases with early familial CAD and 165 control subj ects to test this hypothesis. In univariate analysis, relative odds fo r CAD were 2.95 (P<.001) for plasma Lp(a) above 40 mg/dL. Nearly all t he risk associated with elevated Lp(a) was found to be restricted to p ersons with historically elevated plasma total cholesterol (6.72 mmol/ L [260 mg/dL] or higher) or with a total/HDL cholesterol ratio >5.8. N onlipid risk factors were also found to at least multiply the risk ass ociated with Lp(a). When Lp(a) was over 40 mg/dL and plasma total/HDL cholesterol >5.8, relative odds for CAD were 25 (P=.0001) in multiple logistic regression. If two or more nonlipid risk factors were also pr esent (including hypertension, diabetes, cigarette smoking, high total homocysteine, or low serum bilirubin), relative odds were 122 (P<1x10 (-12)). The ability of nonlipid risk factors to increase risk associat ed with Lp(a) was dependent on at least a mildly elevated total/HDL ch olesterol ratio. In conclusion, high Lp(a) was found to greatly increa se risk only if the total/HDL cholesterol ratio was at least mildly el evated, an effect exaggerated by other risk factors. Aggressive lipid lowering in those with elevated Lp(a) therefore appears indicated.