Inflammation
Elevated Lp(a) independently predicts ventricular arrhythmias, even after adjusting for ASCVD, TriNetX cohort of over 116,000 patients finds (Heart Rhythm O2 2025)
Original title: Increased lipoprotein(a) levels independently predict a higher incidence of ventricular arrhythmias: A comprehensive retrospective cohort study
This retrospective cohort study used the TriNetX research network to identify adults with Lp(a) measurements, stratified into low (75 nmol/L or below, 75,655 patients) and high (above 75 nmol/L, 40,860 patients) groups, testing whether Lp(a) independently predicts ventricular arrhythmia (VA, defined as ventricular tachycardia, fibrillation, flutter, or cardiac arrest of cardiac cause) beyond its known role in atherosclerotic disease. After propensity score matching (39,414 patients per cohort), VA occurred in 889 low-Lp(a) and 718 high-Lp(a) patients over a mean follow-up of 3.35 and 1.90 years respectively; the high-Lp(a) group had lower VA-free survival (84.30% vs. 86.06%, P < .01), with a hazard ratio of 0.855 (95% CI 0.771-0.922, P = .045) for VA-free survival. The authors conclude elevated Lp(a) is independently associated with higher VA incidence even after adjusting for ASCVD and its downstream consequences, implicating pathways beyond cholesterol, such as endothelial dysfunction, thrombogenesis and inflammation, in arrhythmogenesis.
Original abstract
Background: Lipoprotein(a) (Lp(a)) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and has been linked to ventricular arrhythmias (VA). Beyond its role in cholesterol metabolism, Lp(a) promotes endothelial dysfunction, thrombogenesis, and inflammation, which may contribute to arrhythmogenesis independent of ASCVD.
Objective: This study aimed to evaluate the association between Lp(a) levels and the incidence of VA in a large, population-based cohort.
Methods: Adults aged ≥18 years with available Lp(a) measurements were identified from the TriNetX research network. Patients were stratified into low (≤75 nmol/L) and high Lp(a) groups (>75 nmol/L). The primary outcome was the incidence of VA, defined as ventricular tachycardia, fibrillation, flutter, or cardiac arrest owing to cardiac causes. Propensity score matching was used to adjust for demographics, ASCVD risk factors, and comorbidities. Kaplan-Meier survival analysis and Cox proportional hazards models were performed after matching.
Results: Before propensity score matching, 75,655 patients were in the low Lp(a) group and 40,860 in the high Lp(a) group. After matching, each cohort included 39,414 patients. VA occurred in 889 patients in the low and 718 in the high Lp(a) cohort. Mean follow-up was 3.35 years [low Lp(a)] and 1.90 years [high Lp(a)]. The high Lp(a) group had lower VA-free survival (84.30% vs 86.06%, P < .01). High Lp(a) was associated with increased VA risk (hazard ratio 0.855, 95% confidence interval 0.771-0.922, P = .045).
Conclusion: Elevated Lp(a) levels are independently associated with a higher incidence of VA, even after adjusting for ASCVD and its downstream consequences. Future research should explore mechanisms and therapeutic implications.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.