Associations of genetic risk and adherence to a healthy lifestyle with incidence of Stroke and Coronary Heart Disease in individuals with Hypertension: The UK Biobank Study
Creators: name: Wang, Mengyao
name: Lun Au Yeung, Shiu
name: Luo, Shan
name: Kim, Youngwon
Publisher: name: The Health & Fitness Journal of Canada
Year: 2022

description: Background: Individuals with hypertension have increased risk of coronary heart disease (CHD) and stroke. A key prevention strategy for CHD and stroke in hypertensive individuals has been promotion of a healthy lifestyle. However, whether a healthy lifestyle acts as a potential effect modifier in the association between genetic susceptibility and risk of CHD and stroke in hypertensive individuals remains unknown. Purpose: This study explored the associations of genetic risk for CHD and stroke and adherence to a healthy lifestyle with incident CHD and stroke in hypertensive individuals. Methods: This study included 260,037 hypertensive individuals of European ancestry without CHD and stroke at baseline from UK Biobank. Each individual’s genetic risk for CHD and stroke was estimated through quantification of weighted polygenic risk scores calculated based on uncorrelated 300 and 87 single nucleotide polymorphisms (SNPs), respectively. Three categories of genetic risk (low, middle and high) were generated according to the tertiles of calculated polygenic risk scores. Following an established methodology, we used 4 healthy lifestyle components (no obesity [BMI &lt;30kg/m2], no current smoking, regular physical activity [³150minutes/week of moderate, ³75minutes/week of vigorous physical activity or an equivalent combination of both] and a healthy diet [sufficient vegetable, fruit and fish intake, and appropriate processed and red meat intake]) to define compliance with a healthy lifestyle. Three categories of adherence to a healthy lifestyle (favorable [3-4 healthy lifestyle factors], intermediate [2 healthy factors] and unfavorable [0-1 healthy factor]) were then created. Incidence of CHD (n=7,867) and stroke (n=5,031) was defined based on death and hospital admission records accrued over a median 11.9 and 12.0 years of follow-up, respectively. Cox regression models using age as the underlying timescale were used to estimate hazard ratio (HR) for incident CHD and stroke, and multiplicative interaction between genetic risk and adherence to a healthy lifestyle. Results: Hypertensive individuals with high genetic risk for CHD and stroke had 107% (HR: 2.07; 95%CI: 1.95-2.19) and 28% (HR: 1.28; 95%CI: 1.20-1.37) higher hazards of CHD and stroke, respectively, compared with those with low genetic risk, after adjusting for all confounders. A favorable lifestyle was associated with 37% (HR: 0.63; 95% CI: 0.59-0.68) and 34% (HR: 0.66; 95% CI: 0.60-0.73) lower hazards of CHD and stroke, respectively, compared with an unfavorable lifestyle after adjusting for genetic risk and confounders. At all genetic risk strata, a favorable lifestyle had consistently lower hazards of CHD and stroke, compared with an unfavorable lifestyle. There was no evidence of interaction between genetic risk and adherence to a healthy lifestyle for CHD (p-value= 0.526) and stroke (p-value= 0.078). Estimates of 12-year absolute risk were lower for hypertensive individuals with high genetic risk but a favorable lifestyle (3.19% for CHD; 1.66% for stroke), compared with those with high genetic risk and an unfavorable lifestyle (6.46% for CHD; 2.50% for stroke). Conclusions: Hypertensive individuals who adhered to a more favorable lifestyle had reduced risk of developing CHD and stroke, regardless of their genetic susceptibility. Our study informs implementation of clinical trials aimed at promoting a healthy lifestyle for prevention of cardiovascular events through early identification of and interventions with hypertensive individuals whose genetic risk is high. Funding: Strengthened Start-up Funds for New Staff at The University of Hong Kong Li Ka Shing Faculty of Medicine. This research has been conducted using the UK Biobank Resource under Application Number 43528.
description: The Health &amp; Fitness Journal of Canada, Vol. 14 No. 3 (2021): Proceedings from the 8th International Society for Physical Activity and Health Congress