Lipoprotein(a) Interactions With Low-Density Lipoprotein Cholesterol and Other Cardiovascular Risk Factors in Premature Acute Coronary Syndrome (ACS)

Background-Current recommendations for lipoprotein(a) (Lp[ a]) focus on the control of other risk factors, including lowering low-density lipoprotein cholesterol (LDL-C), with little evidence to support this approach. Identifying interactions between Lp(a) and other risk factors could identify individuals at increased risk for Lp(a)-mediated disease. Methods and Results-We used a case-only study design and included 939 participants (median age=49 years, interquartile range 46-53, women=33.1%) from the GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-Premature Acute Coronary Syndrome (GENESIS-PRAXY) study, a multicenter prospective cohort study of premature acute coronary syndrome. There was a higher prevalence of elevated Lp(a) levels (> 50 mg/dL; 80th percentile) in PRAXY participants as compared to the general population (31% versus 20%; P<0.001). Lp(a) was strongly associated with LDL-C (adjusted beta 0.17; P<0.001). Individuals with high Lp(a) were more likely to have LDL-C > 2.5 mmol/L, indicating a synergistic interaction (adjusted odds ratio 1.51; 95% CI 1.08-2.09; P=0.015). The interaction with high Lp(a) was stronger at increasing LDL-C levels (LDL-C > 3.5, adjusted odds ratio 1.87; LDL-C > 4.5, adjusted odds ratio 2.72). In a polytomous logistic model comparing mutually exclusive LDL-C categories, the interaction with high Lp(a) became attenuated at LDL-C <= 3.5 mmol/L (odds ratio 1.16; 95% CI 0.80-1.68, P=0.447). Other risk factors were not associated with high Lp(a). Conclusions-In young acute coronary syndrome patients, high Lp(a) is more prevalent than in the general population and is strongly associated with high LDL-C, suggesting that Lp(a) confers greater risk for acute coronary syndrome when LDL-C is elevated. Individuals with high Lp(a) and LDL-C > 3.5 mmol/L may warrant aggressive LDL-C lowering.