Abstract 11843: Population Effects of Clinical, Laboratory, and Genetic Risk Factors for Incident CAD: A Cohort Study in the UK Biobank

Abstract

Background: Modifiable clinical risk factors are estimated to account for the majority of population attributable risk (PAR) for first myocardial infarction (MI). Hypothesis: Novel biomarkers and genetic factors additionally contribute to the risk for first MI. Methods: We determined incident coronary artery disease (CAD), defined as first-time MI or revascularization, in the UK Biobank. Exposures included laboratory (ApoB/A1, lipoprotein(a) [Lp(a)], C reactive protein [CRP]), genetic (CAD polygenic risk score [PRS], heterozygous familial hypercholesterolemia [HeFH]), and clinical (waist/hip ratio, hypertension, diabetes, diet, exercise, smoking, Townsend deprivation index) risk factors. We fitted multivariable logistic regression models with clinical risk factors alone, then added CAD PRS, HeFH, CRP and Lp(a). Results: Among 98 387 participants, 5 408 had incident CAD (5.5%). Compared to a model with clinical risk factors alone (PAR 82.3%, 95% CI 77.6-86.9%), adding novel biomarkers (Lp(a), CRP) and genetic risk raised total PAR to 89.0% (95% CI 86.4-91.5%). Novel risk factors Lp(a) > 125 nmol/L (OR 1.22, PAR 2.5%), CRP > 2.0 mg/L (OR 1.22, PAR 8.0%), HeFH (OR 1.52, PAR 0.1%), and high CAD PRS (OR 2.48 for top vs lowest decile, PAR 37.4%) were significantly associated with incident CAD controlling for clinical risk factors. In combination with novel risk factors, smoking (OR 1.25 for current + former vs never, PAR 11.3%), ApoB/A1 ratio (OR 1.60 for top vs lowest quintile, PAR 16.6%), hypertension (OR 2.17, PAR 31.9%), waist-to-hip ratio (OR 1.21 for top vs lowest tertile, PAR 13.3%), diabetes (OR 1.59, PAR 5.6%), diet (OR 1.42, PAR 7.8%), exercise (OR 1.12, PAR 7.1%) and Townsend index (OR 1.34 for top vs lowest decile, PAR 8.6%) were significantly associated with incident CAD at α=0.05. Conclusions: The novel cardiovascular risk factors Lp(a), CRP, CAD PRS, and HeFH contribute significant risk for first-time CAD, with PAR for CAD PRS exceeding conventional risk factors.