Departamento Administrativo de Ciencia, Tecnología e Innovación (COLCIENCIAS), National Health and Medical Research Council, Nestlé Nutrition (Nestec), Metagenics, and AXA.

BackgroundBeing overweight or obese is associated with an increased risk of cardiovascular disease (CVD). Physical activity might reduce the risk associated with overweight and obesity. We examined the association between overweight and obesity and CVD risk as a function of physical activity levels in a middle-aged and elderly population.DesignThe study was a prospective cohort study.MethodsThe study included 5344 participants aged 55 years or older from the population-based Rotterdam Study. Participants were classified as having high or low physical activity based on the median of the population. Normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2) and obese participants (≥30 kg/m2) were categorized as having high or low physical activity to form six categories. We assessed the association of the six categories with CVD risk using Cox proportional hazard models adjusted for confounders. High physical activity and normal weight was used as the reference group.ResultsDuring 15 years of follow-up (median 10.3 years, interquartile range 8.2–11.7 years), 866 (16.2%) participants experienced a CVD event. Overweight and obese participants with low physical activity had a higher CVD risk than normal weight participants with high physical activity. The HRs and 95% confidence intervals (CIs) were 1.33 (1.07–1.66) and 1.35 (1.04–1.75), respectively. Overweight and obese participants with high physical activity did not show a higher CVD risk (HRs (95%CIs) 1.03 (0.82–1.29) and 1.12 (0.83–1.52), respectively).ConclusionsOur findings suggest that the beneficial impact of physical activity on CVD might outweigh the negative impact of body mass index among middle-aged and elderly people. This emphasizes the importance of physical activity for everyone across all body mass index strata, while highlighting the risk associated with inactivity even among normal weight people.

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PA and sedentary behavior in the elderly differed by sex, age, BMI, prevalence of chronic disease, and disability, whereas there were no clear patterns for sleep. On average, our participants spent up to 79.5% of their time awake being sedentary and 7%-8% in moderate-to-vigorous PA. Replacing sedentary behavior with light PA would be a good starting point for those with the lowest level of PA. Older adults, those with high BMI and worse health could benefit from targeted interventions to increase PA.

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.