AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Impact of Lipoprotein(a) on Incident Atherosclerotic Cardiovascular Disease Events in Individuals With and Without Diabetes
By Pavade A, Hitti G, Fan Y et al.
Background: Lipoprotein(a) (Lp(a)) is widely recognized as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). However, there are limited data on how the prognostic value of Lp(a) may differ in those with versus without diabetes mellitus (DM). Objective: We examined the comparative association of Lp(a) with incident ASCVD risk among individuals with and without diabetes in a large electronic health record database. Methods: This retrospective cohort study used electronic health record data from the TriNetX Research Network from January 25, 2001, to July 25, 2025, and identified 154,650 adults with a recorded Lp(a) measurement. The index date was defined as each participant’s first available Lp(a) measurement date. We excluded 86,450 adults with ASCVD anytime prior to or within the first 6 months after the index date, leaving 68,200 participants for our analysis. ASCVD events were defined as a composite of nonfatal and fatal MI and stroke, revascularization, and coronary heart disease (CHD) death. Patients with DM (n=5,353) were identified using the ICD-10 code E11. Lp(a) measures were available both in mass and molar units and were categorized: <15 mg/dL or <37.5 nmol/L, 15-29 mg/dL or 37.5-74 nmol/L, 30-49 mg/dL or 75-124 nmol/L, 50-69 mg/dL or 125-174 nmol/L, and > 70 mg/dL or > 175 nmol/L. Incident ASCVD was the primary outcome and was evaluated using unadjusted and multivariable-adjusted Cox models controlling for age, sex, race/ethnicity, hypertension, smoking, BMI, LDL-C, HDL-C, and triglycerides. Participants were required to have at least 1 year of follow-up after the index date. Follow-up extended from the index date to incident ASCVD, death, loss to follow-up, or study end, whichever occurred first. Results: Over a median follow-up of 1.58 years (24.0 years maximum), 6,302 ASCVD events (9.2%) occurred and were greater in those with versus without DM (15.6% vs. 8.7%). In the overall cohort (n=68,200), incident ASCVD risk increased in a graded fashion across Lp(a) categories with adjusted HRs ranging from 1.11 (95% CI 1.02-1.22) to 1.37 (1.27-1.48). Among participants without DM, a similar graded association was observed across Lp(a) categories (HRs 1.11 [1.01-1.23] to 1.39 [1.28-1.51]), whereas among participants with DM, only those with Lp(a) > 70 mg/dL or > 175 nmol/L had increased ASCVD risk (HR 1.24, 95% CI 1.00-1.53). The formal Lp(a) x DM interaction test was not statistically significant (p = 0.558). Conclusions: We demonstrate that ASCVD event rates are consistently higher in those with versus without DM across the range of Lp(a) values; however, the Lp(a)-associated risks of incident ASCVD were similar in those with versus without DM. Further investigation should assess whether Lp(a)-targeted therapies may have a similar impact on ASCVD events in those with versus without DM.