Abstract
To examine associations of unhealthy lifestyle and genetics with risk of all-cause mortality, cardiovascular disease (CVD) mortality, myocardial infarction (MI) and stroke. We used data on 76,958 adults from the UK Biobank prospective cohort study. Favourable lifestyle included no overweight/obesity, not smoking, physical activity, not sedentary, healthy diet and adequate sleep. A Polygenic Risk Score (PRS) was derived using 300 CVD-related single nucleotide polymorphisms. Cox proportional hazard ratios (HR) were used to model effects of lifestyle and PRS on risk of CVD and all-cause mortality, stroke and MI. New CVD (n = 364) and all-cause (n = 2408) deaths, and stroke (n = 748) and MI (n = 1140) events were observed during a 7.8 year mean follow-up. An unfavourable lifestyle (0–1 healthy behaviours) was associated with higher risk of all-cause mortality (HR: 2.06; 95% CI: 1.73, 2.45), CVD mortality (HR: 2.48; 95% CI: 1.64, 3.76), MI (HR: 2.12; 95% CI: 1.65, 2.72) and stroke (HR:1.74; 95% CI: 1.25, 2.43) compared to a favourable lifestyle (≥4 healthy behaviours). PRS was associated with MI (HR: 1.35; 95% CI: 1.27, 1.43). There was evidence of a lifestyle-genetics interaction for stroke (p = 0.017). Unfavourable lifestyle behaviours predicted higher risk of all-cause mortality, CVD mortality, MI and stroke, independent of genetic risk.
Highlights
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide [1]
Effect sizes were comparable when incident myocardial infarction (MI) and stroke cases within the first 2 years of follow up were excluded and results were congruent when the healthy lifestyle score was treated as a continuous variable (Table S4). This prospective population-based cohort study of more than 76,000 adults aimed to examine the association of an unhealthy lifestyle score based on smoking status, body mass index (BMI), diet quality, physical activity, sleep duration and sedentary time, and a genetic risk score with all-cause and CVD mortality and non-fatal CVD events up to 8 years later
In a population-based cohort study using data from 44,462 US adults and 399,537 United Kingdom (UK) adults, a healthy lifestyle score based on no heavy alcohol consumption, never smoking, being more physical active, and having higher dietary quality was associated with lower risk of all-cause and CVD mortality up to 11 years later [5]
Summary
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide [1]. Risk of CVD is the result of a combination of risk factors, including non-modifiable genetic pre-disposition and a range of modifiable lifestyle behaviours, such as smoking, sleep duration, physical activity and diet [2]. Research from large UK, US and Korean cohorts have shown an additive benefit of maintaining multiple healthy lifestyle behaviours for reducing risk of CVD and all-cause mortality [9,10,11,12]. A paucity of studies has included emerging behavioural risk factors of sedentary time and sleep duration when deriving health behaviour scores [11,13,14].
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