Association of elevated lipoprotein(a) with future major adverse cardiovascular events in recurrent ASCVD patients: analysis of a large US electronic health record database

Abstract Background Elevated lipoprotein(a) (Lp(a)) is a genetic, independent, and causal driver of atherosclerotic cardiovascular disease (ASCVD) risk. Evidence has shown association between elevated Lp(a) and increased risk of recurrent ASCVD. Purpose To describe the prevalence of elevated Lp(a) among patients with recurrent ASCVD and its association with future major adverse cardiovascular events (MACE). Methods A retrospective cohort study was performed using the Optum de-identified Electronic Health Record data set (Optum EHR) between 01 January 2014 – 30 June 2023. The study cohort included adults (≥18 years) with recurrent ASCVD who had an Lp(a) measurement in nmol/L. Recurrent ASCVD was defined as having two consecutive myocardial infarction (MI), ischemic stroke and/or peripheral artery disease related events or procedures, the second event occurring within two years of the first event. The index date is defined as the date of the second event. MACE (MI, ischemic stroke, coronary revascularization, and all-cause death) occurrence during the post-index follow-up period was described for the study cohort stratified by Lp(a) 65 nmol/L and ≥150 nmol/L. Cumulative incidence rates of MACE, i.e., the total number of MACE over the entire follow-up period, were calculated per 100 person-years. Cumulative incidence rate ratios (CIRR) and hazard ratios (HR), comparing Lp(a) ≥150 nmol/L to 65 nmol/L, were generated using Poisson and Cox proportional hazard models, respectively; both models adjusted for age and sex. Results The study identified 4,528 recurrent ASCVD patients, mean age 62.6 years, 60.6% male, 76.3% Caucasian, 62.7% had hypertension, 20.8% diabetes, and 12.9% heart failure. Mean LDL-C was 93.1 (SD: 42.9) mg/dL, median Lp(a) was 47 (IQR: 118.3) nmol/L with 25.4% having Lp(a) ≥150 nmol/L. Over a median of 3.75 years of follow-up, 37.7% vs 32.5% (p0.05) had a subsequent MACE in patients with Lp(a) ≥150 nmol/L and 65nmol/L, respectively (Table 1). Compared to those with Lp(a) 65 nmol/L, patients with Lp(a) ≥150 nmol/L were significantly associated with 14%, and 26% greater risk of a subsequent MACE (HR=1.14, 95% CI: 1.03-1.26, p=0.012) and MI (HR=1.14, 95% CI: 1.10-1.43, p0.001) (Table 1). Additionally, Lp(a) ≥150 nmol/L was associated with 38%, 27%, and 13% greater number of MI, coronary revascularization, and MACE over the study period compared to Lp(a) 65 nmol/L (Table 1). Conclusions Among patients with recurrent ASCVD, elevated Lp(a) increased not only the risk of an immediate subsequent event but also the total number of events, demonstrating the growing cumulative event burden related to elevated Lp(a). Knowing Lp(a) levels in patients with recurrent ASCVD events is important to properly manage this high-risk population in the secondary prevention setting.Table 1 - HR and CIRR of MACE