Lipoprotein(a) Identifies Residual Cardiovascular Risk in NIH Randomized Trials
Presenter
Subhash Banerjee, M.D., FSCAI, Baylor Scott & White Heart and Vascular Hospital - Dallas, Dallas, TX
Subhash Banerjee, M.D., FSCAI1, Anand Gupta, MBBS, MPH2, Minseob Jeong, M.D.2, David fernandez-Vazquez, M.D.2, Matthew Wooten, M.D.3, Shivani Reddy, MD3, Victoria Eichten, M.D.4, Vanessa Garcia, BS2, Sally Lewis, PhD5, Jennifer Finholt, MS2, Nicole Minniefield, MD6, Shuaib Abdullah, M.D.7, Vishal Ahuja, PhD8 and Ambarish Pandey, MD9, (1)Baylor Scott & White Heart and Vascular Hospital - Dallas, Dallas, TX, (2)Baylor Scott & White Research Institute, Dallas, TX, (3)Baylor University Medical Center, Arlington, TX, (4)Baylor University Medical Center, Dallas, TX, (5)Tarleton State University, Fort Worth, TX, (6)VA North Texas Health Care System, Dallas, TX, (7)VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, TX, (8)Southern Methodist University, Dallas, TX, (9)University of Texas Southwestern Medical Center, Dallas, TX
Keywords: Pharmacotherapy and Quality
Background
Lipoprotein(a) [Lp(a)] is a genetically determined cardiovascular (CV) risk factor, yet its prognostic relevance across prevention strata remains incompletely defined. We evaluated the independent association between Lp(a) and CV outcomes using biospecimens from three large NIH randomized clinical trials.
Methods
This biorepository analysis included 20,070 participants ≥40 years from ACCORD, PEACE, and SPRINT with available pre-randomization plasma samples obtained through the NIH BioLINCC repository. A dedicated translational laboratory at Baylor Scott & White centrally analyzed all samples using a standardized assay, with Lp(a) quantified in nmol/L. Participants were categorized by Lp(a) level (<75, 75–125, 125–175, ≥175 nmol/L) and classified as primary or secondary CV prevention. The primary outcome was major adverse cardiovascular events (MACE: myocardial infarction (MI), stroke, coronary revascularization, or cardiovascular death). Trial-stratified multivariable Cox models adjusted for demographics, comorbidities, lipids, and therapies.
Results
Mean age was 65.2±8.5 years; 64.9% were male. Over a median 3.98-year follow-up, 1,461 MACE events (7.3%) occurred. Lp(a) ≥175 nmol/L independently associated with higher risk of MACE (HR 1.31, 95% CI 1.10–1.55), cardiovascular death (HR 1.49, 95% CI 1.07–2.06), and stroke (HR 1.64, 95% CI 1.13–2.37), but not MI. Associations were attenuated in primary prevention (HR 1.18, 95% CI 0.90–1.53) and strengthened in secondary prevention (HR 1.30, 95% CI 1.07–1.57). The population attributable fraction for MACE was ~3.6% overall and ~4.8% in secondary prevention.
Conclusions
Across three NIH trials, elevated Lp(a) identifies residual CV risk, particularly in secondary prevention, reinforcing its role as a clinically actionable risk enhancer and therapeutic target in established ASCVD.