Associations of genetic susceptibility and healthy lifestyle with incidence of coronary heart disease and stroke in individuals with hypertension

Aims: This study explored the associations of genetic susceptibility and adherence to a healthy lifestyle with incident coronary heart disease (CHD) and stroke in individuals with hypertension.

Methods and results: This study included 258 531 European descendants with hypertension at baseline from UK Biobank. Genetic risk of CHD and stroke was estimated using polygenic risk scores derived from 300 and 87 single-nucleotide polymorphisms, respectively. Lifestyle scores were calculated based on 4 lifestyle components (no obesity, no current smoking, regular physical activity and healthy diet). Cox regression with age as the underlying timescale was fit for incident CHD (n = 7470) and stroke (n = 5015), separately. A favourable lifestyle (3-4 lifestyle components) was associated with 37% and 30% lower hazards of CHD (95% confidence intervals, 32-42%) and stroke (23-37%), compared with an unfavourable lifestyle (0-1 lifestyle component), at all levels of genetic risk. Evidence of interaction between genetic susceptibility and lifestyle adherence was found for stroke (P = 0.036): no evidence of interaction for CHD (P = 0.524). A favourable lifestyle at high genetic risk had lower 12-year absolute risk of CHD and stroke, compared with an unfavourable lifestyle at low-to-intermediate genetic (exception: an unfavourable lifestyle at low CHD genetic risk).

Conclusion: Adhering to a healthy lifestyle is associated with lower CHD and stroke risk regardless of genetic risk among individuals with hypertension. Risk of CHD and stroke for those at high genetic risk but adhering to a healthy lifestyle was generally lower than for those at low-to-intermediate genetic risk but adhering to an unhealthy lifestyle.