Replacing device-measured sedentary time with physical activity is associated with lower risk of coronary heart disease regardless of genetic risk.

BACKGROUND: Excess sedentary time (ST) is recognized as an important modifiable risk factor for coronary heart disease (CHD). However, whether the associations of genetic susceptibility with CHD incidence can be modified by replacing wearable-device-measured ST with physical activity (PA) is unknown. OBJECTIVES: To examine the associations of wearable-device-measured ST replaced by PA with incident CHD across strata of genetic susceptibility. METHODS: This study included 77,500 White British (57% female) with valid wrist-worn accelerometry and without prevalent CHD/stroke from UK Biobank. Genetic susceptibility to CHD was quantified through weighted polygenic risk scores for CHD based on 300 single-nucleotide polymorphisms. Wrist-worn accelerometer data were used to derive ST, light PA, and moderate-to-vigorous PA (MVPA). RESULTS: Reallocation of 60 min/day of ST into the same amount of MVPA was associated with approximately 9% lower relative risk of CHD for all participants and across strata of genetic risk: replacement of 1 min/day of ST associated with <1% lower relative risk of CHD. No evidence of interaction (p: 0.784) was found between genetic risk and ST for CHD risk. Reallocating 60 min/day of ST into the same MVPA time was associated with greater absolute CHD risk reductions at high genetic risk (0.27%) versus low genetic risk (0.15%). CONCLUSIONS: Replacing any amount of ST with an equal amount of MVPA time is associated with a lower relative risk of CHD, irrespective of genetic susceptibility to CHD. Reductions in CHD absolute risk for replacing ST with MVPA are greater at high genetic risk versus low genetic risk.

Mode of transport, genetic susceptibility, and incidence of coronary heart disease.

BACKGROUND: Car use has been associated with higher risk of coronary heart disease (CHD). However, whether the associations of transport modes with CHD vary by genetic susceptibility to CHD are unknown. This study aims to investigate the associations of genetic susceptibility and modes of transport with incidence of CHD. METHODS: We included 339,588 white British participants from UK Biobank with no history of CHD or stroke at baseline or within two years of follow-up (52.3% in work). Genetic susceptibility to CHD was quantified through weighted polygenic risk scores derived from 300 single-nucleotide polymorphisms related to CHD risk. Categories of transport mode included exclusive car use and alternatives to the car (e.g., walking, cycling and public transport), separately for non-commuting (e.g., getting about [n=339,588] excluding commuting for work), commuting (in the sub-set in work [n=177,370] who responded to the commuting question), and overall transport (transport mode for both commuting and non-commuting [n=177,370]). We used Cox regression with age as the underlying timescale to estimate hazard ratios (HR) of CHD (n=13,730; median 13.8-year follow-up) and tested the interaction between genetic susceptibility and travel modes with adjustment for confounders. RESULTS: Compared to those using alternatives to the car, hazards of CHD were higher for exclusive use of cars for overall transport (HR: 1.16, 95% confidence interval (CI): 1.08-1.25), non-commuting (HR: 1.08, 95% CI: 1.04-1.12) and commuting (HR: 1.16, 95% CI: 1.09-1.23), after adjusting for confounders plus genetic susceptibility. HRs of CHD were 1.45 (95% CI: 1.38-1.52) and 2.04 (95% CI: 1.95-2.12) for the second and third tertile of genetic susceptibility to CHD, respectively, compared to the first. There was, in general, no strong evidence of interactions between genetic susceptibility and categories of overall, non-commuting and commuting transport. Estimated 10-year absolute risk of CHD was lower for the alternatives to the car across strata of genetic susceptibility, compared with exclusive use of cars for overall, non-commuting and commuting transport. CONCLUSION: Exclusive use of cars was associated with a relatively higher risk of CHD across all strata of genetic susceptibility. Using alternatives to the car should be encouraged for prevention of CHD for the general population including individuals at high genetic risk.

Genetic susceptibility, screen-based sedentary activities and incidence of coronary heart disease.

BACKGROUND: Whether the associations of time spent in screen-based sedentary activities with CHD vary by genetic susceptibility is currently unknown. The objective of this study was to examine the interplay of genetic susceptibility to CHD and two prevalent types of screen-based sedentary activities (television [TV] viewing and computer use) for CHD incidence. METHODS: This prospective cohort study included 373,026 individuals of European ancestry without prevalent CHD/stroke from UK Biobank data. Genetic susceptibility to CHD was assessed using weighted polygenic risk scores, calculated by summing the number of risk-increasing alleles among 300 single-nucleotide polymorphisms, multiplied by their corresponding effect estimates. TV viewing and computer use were assessed through touch-screen questionnaires. CHD incidence (n=9185) was adjudicated over a median 12.6-year follow-up. RESULTS: Compared with ≥4h/day of TV viewing, the hazard ratio of CHD was 0.84 (95% confidence interval [CI] 0.79-0.90) and 0.94 (0.90-0.99) for ≤1h/day and 2-3h/day of TV viewing, respectively, after adjusting for confounders including the genetic risk. CHD hazards were higher for medium and high genetic risk than for low genetic risk. Across all levels of genetic risk including high-genetic risk, ≤1h/day of TV viewing had lower CHD hazards, compared with ≥4h/day: no evidence of interaction between genetic risk and TV viewing (p value: 0.362). Estimates of the population attributable fraction (PAF) suggested that 10.9% (95% CI 6.1-15.3%) of CHD could be prevented if TV viewing time were reduced to ≤1h/day, assuming causality. The PAF values were relatively larger for medium-to-high genetic risk than for low genetic risk, although the CIs were wide and overlapping. No associations were observed for computer use. CONCLUSIONS: Less TV viewing time was associated with lower CHD risk independently of genetic risk. Clinical trials targeted at individuals with high genetic susceptibility should consider reducing TV viewing as as a behavioural target for prevention of an early onset of cardiovascular events.

Incidence of Dementia and Alzheimer's Disease, Genetic Susceptibility, and Grip Strength Among Older Adults.

BACKGROUND: Grip strength has prognostic value for aging-related health outcomes. Whether the associations of grip strength with the risk of dementia and Alzheimer's disease (AD) vary by the genetic risk of AD and related dementias (ADD) is unknown. METHODS: This study included 148 659 older adults of white British ancestry (aged ≥60 years) participating in UK Biobank with no dementia, and self-reported poor health status at baseline. Polygenic risk scores (PRS) for ADD were calculated based on 64 genetic variants. Grip strength was measured by hand dynamometers. RESULTS: The hazard ratios (HR) of dementia (n = 4 963) and AD (n = 2 373) for high genetic risk of ADD were 2.36 (95% confidence interval [CI]: 2.15-2.59) and 3.00 (95% CI: 2.61-3.44), respectively, compared with low genetic risk. Compared with the bottom tertile of grip strength, the top tertile of grip strength had a hazard ratio (HR) of 0.69 (95% CI: 0.64-0.74) for incident dementia, and 0.74 (95% CI: 0.66-0.82) for incident AD, after adjustment for confounders and PRS for ADD. The risk of dementia and AD was lower with the top grip strength tertile within each level of genetic susceptibility to ADD. There was no evidence of multiplicative interaction between grip strength and genetic susceptibility to ADD for both dementia (p value: .241) and AD (p value: .314). CONCLUSIONS: Older adults with higher PRS for ADD are at higher risk of developing dementia and AD. The risk of dementia and AD was lower in individuals with higher grip strength, regardless of their level of genetic susceptibility to ADD.

Adherence to a healthy lifestyle, genetic susceptibility to abdominal obesity, cardiometabolic risk markers, and risk of coronary heart disease.

BACKGROUND: Little is known about whether the association between genetic susceptibility to high waist-to-hip ratio (WHR), a measure of abdominal obesity, and incident coronary heart disease (CHD) is modified by adherence to a healthy lifestyle. OBJECTIVES: To explore the interplay of genetic susceptibility to high WHR and adherence to a healthy lifestyle on incident CHD. METHODS: This study included 282,316 white British individuals from the UK Biobank study. Genetic risk for high WHR was estimated in the form of weighted polygenic risk scores (PRSs), calculated based on 156 single-nucleotide polymorphisms. Lifestyle scores were calculated based on 5 healthy lifestyle factors: regular physical activity, no current smoking, a healthy diet, <3 times/wk of alcohol consumption and 7-9 h/d of sleep. Incident CHD (n = 11,635) was accrued over a median 13.8 y of follow-up, and 12 individual cardiovascular disease risk markers assessed at baseline. RESULTS: Adhering to a favorable lifestyle (4-5 healthy factors) was associated with a 25% (hazard ratio: 0.75, 95% confidence interval: 0.70, 0.81) lower hazard of CHD compared with an unfavorable lifestyle (0-1 factor), independent of PRS for high WHR. Estimated 12-y absolute risk of CHD was lower for a favorable lifestyle at high genetic risk (1.73%) and medium genetic risk (1.67%) than for an unfavorable lifestyle at low genetic risk (2.08%). Adhering to a favorable lifestyle was associated with healthier levels of cardiovascular disease risk markers (except random glucose and high-density lipoprotein), independent of PRS for high WHR. CONCLUSIONS: Individuals who have high or medium genetic risk of abdominal obesity but adhere to a healthy lifestyle may have a lower risk of developing CHD, compared with those who have low genetic risk and an unhealthy lifestyle. Future clinical trials of lifestyle modification could be implemented for individuals at high genetic risk of abdominal obesity for the primary prevention of CHD events.