Abstract Body (Do not enter title and authors here): Background: Atherosclerotic cardiovascular disease (ASCVD) is considered premature if diagnosed before age 55 years in men or 65 years in women. Elevated Lp(a) is an independent, causal risk driver for cardiovascular (CV) events. Due to low Lp(a) testing rates in the US, studies assessing the association of Lp(a) with subsequent ASCVD events is limited in patients with premature onset of disease.

Objectives: To evaluate the association between Lp(a) levels and the risk of CV events in patients with premature ASCVD.

Methods: Patients with premature ASCVD were identified from Medicare, Medicaid, and commercial insurance claims between 2017–2022. Lp(a) levels from lab data were linked at the patient level and categorized: <30 mg/dL (<75 nmol/L), 30–<50 mg/dL (75–<125 nmol/L), 50–<70 mg/dL (125–<175 nmol/L), and ≥70 mg/dL (≥175 nmol/L). Cox proportional hazards models, adjusted for demographics, comorbidities, LDL-C, and other risk factors, were utilized to evaluate the association between Lp(a) levels and ASCVD events defined as a composite of myocardial infarction, ischemic stroke, and revascularization requiring hospitalization.

Results: Among 17 million ASCVD patients, 97,775 (0.55%) had Lp(a) measures. Overall, 17,594 (18%) had premature ASCVD and 80,181 (82%) had non-premature ASCVD. Premature ASCVD patients were 23.2 years younger (mean±SD age 50.9±10.1 vs. 74.1±8.7 years, p<0.05) and more likely female (68.9% vs. 44.1%, p<0.05) compared to non-premature ASCVD patients. Premature ASCVD patients had their index premature event most frequently observed at age 45-54 years (40.3%) followed by 35-44 years (14.9%), 25-34 years (4.1%), and 18-24 years (1.0%). Lp(a) levels ≥50mg/dL and ≥70 mg/dL were more prevalent in premature ASCVD patients (26.8% vs. 24.3% and 18.8% vs. 16.5%, both p<0.05). Across Lp(a) strata, both premature and non-premature ASCVD groups exhibited a steadily increase in ASCVD event risk along with increasing Lp(a) levels: adjusted hazard ratios (HR) being 1.04-1.05 (30–<50 mg/dL), 1.08-1.08 (50–<70 mg/dL) and 1.15-1.16 (≥70 mg/dL) compared to Lp(a)<30 mg/dL. (Figure 1)

Conclusions: Despite being over 20 years younger, patients with premature ASCVD were more likely to have elevated Lp(a) and exhibited Lp(a)-driven CV risk similar to that of older non-premature patients. These findings highlight the important role of Lp(a) in early onset of disease and the urgent need for testing high-risk patients, particularly premature ASCVD patients.