Abstract Background Atherosclerotic cardiovascular disease (ASCVD) is the world’s leading cause of death. While most ASCVD and major adverse cardiovascular events (MACE) occur later in life, a significant proportion of the younger population are at-risk. Elevated lipoprotein(a) (Lp(a)), a genetic, independent, and causal driver of ASCVD risk, has been shown to be associated with premature ASCVD. Purpose This study aims to evaluate the prevalence of elevated Lp(a) and its impact on subsequent MACE among premature ASCVD patients, in a US population. Methods A retrospective cohort study was performed using the Optum de-identified Electronic Health Record data set (Optum EHR) in the US between 01 January 2014 – 30 June 2023. The study cohort included adult (≥18 years) premature ASCVD patients with an Lp(a) measurement in nmol/L. Premature ASCVD was defined as having either a myocardial infarction (MI), ischemic stroke or peripheral artery disease related event or procedure before the age of 55 years for males and 65 years for females. MACE was defined as a composite of MI, ischemic stroke, coronary revascularization, and all-cause death. Incidence rates (IR) were calculated per 100 person-years. Incidence rate ratios (IRR) 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 2,684 premature ASCVD patients. Among these, 57.7% were female, mean LDL-C was 114.7 (SD: 44.9) mg/dL, median Lp(a) was 50 (IQR: 137.07) nmol/L. One-in-three (29.7%) premature ASCVD patients had elevated Lp(a) ≥125 nmol/L, and 25.3% had Lp(a) ≥150 nmol/L. Over a median follow-up of 3.75 years, 38.8% (1,041/2,684) of premature ASCVD patients had a subsequent MACE. Whereas 42.7% (291/682) of those with Lp(a) ≥150 nmol/L had a subsequent MACE (Table 1). IRs were significantly higher among patients with Lp(a) ≥150 nmol/L than those with Lp(a) 65 nmol/L for MACE, MI, coronary revascularization, but not all-cause death (Table 1). Compared to Lp(a) 65 nmol/L, Lp(a) ≥150 nmol/L was significantly (p0.05) associated with higher IRRs and with 20%, 19 %, 23% greater risk of MACE, MI, and coronary revascularization: HR=1.20, 1.19, 1.23, respectively (Table 1). Conclusions The study demonstrated that elevated Lp(a) is prevalent among premature ASCVD patients and Lp(a) ≥150 nmol/L is significantly associated with an increased risk of subsequent MACE. This highlights the importance of Lp(a) testing in premature ASCVD patients for early identification and optimization of cardiovascular risk management.Table 1 - IR, IRR, and HR of MACE
Byrne et al. (Sat,) studied this question.