Self-reported walking pace, polygenic risk scores and risk of coronary artery disease in UK biobank

Background and aims: Both polygenic risk scores (PGS) and self-reported walking pace have been shown to predict cardiovascular disease; whether combining both factors produces greater risk differentiation is, however, unknown. Methods and results: We estimated the 10-year absolute risk of coronary artery disease (CAD), adjusted for traditional risk factors, and the C-index across nine PGS and self-reported walking pace in UK Biobank study participants between Mar/2006–Feb/2021. In 380,693 individuals (54.8% women), over a median (5th, 95th percentile) of 11.9 (8.3, 13.4) years, 2,603 (1.2%) CAD events occurred in women and 8,259 (4.8%) in men. Both walking pace and genetic risk were strongly associated with CAD. The absolute 10-year risk of CAD was highest in slow walkers at high genetic risk (top 20% of PGS): 2.72% (95% CI: 2.30–3.13) in women; 9.60% (8.62–10.57) in men. The risk difference between slow and brisk walkers was greater at higher [1.26% (0.81–1.71) in women; 3.63% (2.58–4.67) in men] than lower [0.76% (0.59–0.93) and 2.37% (1.96–2.78), respectively] genetic risk. Brisk walkers at high genetic risk had equivalent (women) or higher (men) risk than slow walkers at moderate-to-low genetic risk (bottom 80% of PGS). When added to a model containing traditional risk factors, both factors separately improved risk discrimination; combining them resulted in the greatest discrimination: C-index of 0.801 (0.793–0.808) in women; 0.732 (0.728–0.737) in men. Conclusion: Self-reported slow walkers at high genetic risk had the greatest risk of CAD, identifying a potentially important population for intervention. Both PGS and walking pace contributed to risk discrimination.