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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  GENdE r 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.

journal of the american heart association

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