Abstract

Introduction: Lipoprotein(a) [Lp(a)] is associated with increased atherosclerotic cardiovascular disease (ASCVD) events. However, whether the optimal Lp(a) threshold for risk-assessment should differ based on baseline ASCVD status is unknown. Hypothesis: To assess the association between Lp(a) and major adverse cardiovascular events (MACE) among patients with and without a history of ASCVD. Methods: Retrospective cohort of patients with Lp(a) measured at two academic medical centers in Boston, MA from 2000-2019. To assess the association of Lp(a) with incident MACE (cardiovascular mortality, myocardial infarction, or ischemic stroke), the following Lp(a) percentile groups were generated: 1 st -50 th (0 - 41 nmol/L; reference), 51 st -70 th (42 - 111 nmol/L), 71 st -90 th (112 - 215 nmol/L), 91 st -100 th (>216 nmol/L). Individuals with severe renal dysfunction or a malignant neoplasm were excluded. Cox proportional hazards modeling was used to assess the association of Lp(a) percentile group with MACE. Results: After applying eligibility criteria, 16,419 patients (median age 60, 41% female) were analyzed with a median follow up of 11.9 years. Patients with ASCVD were older and had higher rates of cardiovascular risk factors. Among the 10,181 (62%) patients with a history of ASCVD, individuals in the 71 st -90 th and 91 st -100 th percentile groups had similarly increased hazards of MACE (adjusted HR = 1.33, p<0.001 and adjusted HR = 1.34, p<0.001 respectively). Among the 6,238 individuals without baseline ASCVD, only individuals in the 91 st -100 th Lp(a) percentile group had a significantly increase hazard of MACE (adjusted HR 2.05, p<0.001), Figure . Conclusions: In a large, contemporary US cohort, elevated Lp(a) is independently associated with long-term MACE among individuals with and without baseline ASCVD. Our results suggest that the Lp(a) threshold for risk assessment may be lower in secondary prevention when compared with primary prevention.

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