Joint association of genetic risk and accelerometer-based step count with cardiovascular disease: a UK-Biobank cohort study.

AimsThis population-based prospective cohort study investigated whether accelerometer-measured step count is associated with incident cardiovascular disease (CVD), independently from genetic risk.MethodsThe study included UK Biobank participants with valid accelerometer and genetic data and without prevalent CVD at baseline. Genetic risk for CVD was categorised as low (1st fifth), moderate (2nd-4th fifths), and high (5th fifth). Median daily step count was categorised as low (<6,500), moderate (6,500-12,499), and high (≥12,500). The association of genetic risk and step count with incident CVD, defined as a composite of coronary artery disease and ischaemic stroke, was examined using adjusted Cox proportional hazards models.ResultsOf 84,286 participants, 4,847 developed CVD during follow-up (median 7.9 years). High genetic risk and low step count were independently associated with higher risk of CVD, with no evidence of a multiplicative interaction (P for interaction = 0.46). Compared with the reference group (low genetic risk and high step count; absolute risk: 62 per 1,000), the highest risk of CVD was observed in participants with high genetic risk and low step count (hazard ratio: 2.81, 95% confidence interval: 2.27-3.46, p < 0.0001; absolute risk: 174 per 1,000). There was an inverse dose-response association between the hazard of CVD and step counts up to 10,000 steps/day, which then plateaued in moderate and high genetic risk groups.ConclusionsHigh daily step count was associated with lower CVD risk in individuals with moderate and high genetic risk, indicating that walking should be encouraged for all, especially those predisposed to CVD.