Proteomic analysis identifies lipoprotein(a)-associated proteins linked to incident atherosclerotic cardiovascular disease events

作者：Tiffany R. Bellomo, Seyedmohammad Saadatagah, Jiwoo Lee, Emily E. Bramel, Layla A. Abushamat, Anika Misra, Tetsushi Nakao, Satoshi Koyama, Aniruddh P. Patel, Sarah Urbut, Christie M. Ballantyne, Pradeep Natarajan · 发表于：medRxiv · 年份：2025 · DOI：10.64898/2025.12.16.25342337 · 被引用次数：2 · 研究领域：Lipoproteins and Cardiovascular Health、Atherosclerosis and Cardiovascular Diseases、Adipokines, Inflammation, and Metabolic Diseases

ABSTRACT Background The pathways linking lipoprotein(a) (Lp[a]) to atherosclerotic cardiovascular disease (ASCVD) are unclear. This study aimed to discover Lp(a)-associated plasma proteins and estimate their associations with incident ASCVD. Methods We analyzed 48,859 UK Biobank participants with measured Lp(a) and proteomic profiles, with replication in 9,416 individuals in the Atherosclerosis Risk in Communities (ARIC) study cohort utilizing a separate proteomic platform. Linear models assessed associations between Lp(a) and protein concentrations adjusted for age, sex, cigarette smoking, diabetes diagnosis, body mass index, systolic blood pressure, hypertension, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, estimated glomerular filtration rate, statin prescription, and the first 10 components of genetic ancestry. Multiple testing correction was performed using the Benjamini-Hochberg FDR method (P < 0.05). We examined how the protein effect sizes from the primary analysis using the outcome of Lp(a) aligned with those for the outcomes of an LPA genetic risk score (GRS) and LDL-C. Cox proportional hazards models quantified hazard ratios (HRs) for protein associations with incident ASCVD. Results Participants were a mean age of 57 years (SD 8.22), 93.9% European, and 53.8% male, with median follow-up of 8.9 years (IQR 8.3–9.7). Of 1,459 circulating proteins, 164 were significantly associated with Lp(a) after FDR correction...