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 lowdensity 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 β 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. © 2016 the authors.