No limit to benefits of exercise in reducing risk of CVD — UK Biobank cohort study

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There is no upper threshold to the benefits of exercise in reducing the risk of cardiovascular disease (CVD), found the largest ever cohort study of its kind, conducted over five-years and led by the University of Oxford.

Cardiovascular disease is the leading cause of death globally, claiming around 17.9m lives each year. Until now, it has been difficult to quantify the protective effect of physical activity, since previous studies have typically measured this using questionnaires. These methods are crude, subject to poor recall and cannot accurately record all activity that takes place throughout the day. This has made it difficult to assess whether increasing physical activity always gives an additional benefit in reducing the risk of cardiovascular disease, or if there is an upper limit on improvements to cardiovascular health from exercise.

A new, large-cohort study led by the University of Oxford has resolved this by using accelerometers (wrist-worn devices) to accurately record the activity of over 90,000 participants followed over five years. This found that physical activity is not only associated with lower risk of developing cardiovascular disease, but the greatest benefit is seen for those who are active at the highest level.

Over the five-year follow up period, 3,617 of the participants were diagnosed with cardiovascular disease (3,305 nonfatal and 312 fatal). This included 2,220 men and 1,397 women. In the participants, as the amount of moderate and vigorous physical activity increased, cases of cardiovascular disease decreased, with no threshold where the effects of exercise stopped improving cardiovascular health.

The protective effect of physical activity against cardiovascular disease was:
48%-57% for those in the top quarter of all physical activity
49%-59% for those in the top quarter of moderate-intensity activity
54%-63% for those in the top quarter of vigorous-intensity activity.

Associate Professor Aiden Doherty, from the University of Oxford’s Nuffield department of population health and one of the lead authors of the study, said: ‘This is the largest ever study of device-measured physical activity and cardiovascular disease. It shows that physical activity is probably even more important for the prevention of cardiovascular disease than we previously thought. Our findings lend further weight to the new World Health Organisation (WHO) guidelines on physical activity which recommend at least 150 to 300 minutes of moderate to vigorous aerobic activity per week for all adults’.

Professor Terry Dwyer, from the University of Oxford’s Nuffield department of women’s & reproductive health and lead author of the study, said: ‘The results of this study enhance confidence that physical activity is likely to be an important way of preventing cardiovascular disease. The potential risk reduction estimated in those engaging in relatively high levels of activity is substantial and justifies a greater emphasis on measures to increase levels of physical activity in the community.’

The results of the study were similar for men and women, although the benefits of vigorous exercise appeared to be particularly strong for women. Although those who exercised more were also more likely to not smoke, to have a healthy BMI and a moderate alcohol intake, the researchers adjusted for these factors and found that the association between increased exercise and a decrease in cardiovascular disease was still strong. These results demonstrate, therefore, that exercise alone has a significant effect on cardiovascular disease risk.

The study was based on 90,211 healthy participants in the UK Biobank, from across England, Wales, and Scotland. They were sent wrist-worn accelerometers to record their activity over a seven-day period in 2013-2015. The participants were followed up over five years after the seven-day period when they wore the accelerometers. The researchers recorded the number of first hospital admissions or death caused by cardiovascular disease. These were obtained from national Hospital Episode Statistics and the national death index.

Dr Rema Ramakrishnan, from the University of Oxford's Nuffield department of women's & reproductive health and the first author of this study said: "We are confident about the study findings because physical activity was objectively assessed by a more valid tool that can capture frequency, intensity, and duration of physical activity rather than self-reported by the participants. We were also fortunate to have access to data from the UK Biobank study, a rich data source that could answer this question."

Why was this study done?

There is an inverse association between self-reported physical activity (PA) and occurrence of cardiovascular disease (CVD). However, there is uncertainty about the strength of this association as self-reported questionnaires are subject to differential measurement error.

Accelerometers are small lightweight motion sensors that are typically worn on the wrist. They more reliably measure PA status and thus could improve understanding of associations with CVD.

What did the researchers do and find?

We used data from 90,211 UK Biobank participants without prior CVD who agreed to wear an accelerometer to measure their PA status over 7 days.

Higher levels of PA were associated with lower risk for CVD that was similar across total, moderate- and vigorous-intensity PA.

What do these findings mean?

Our findings suggest that individuals who engage in higher levels of PA have lower risk for CVD throughout the range of PA measured.

The lowest risk for CVD in the UK Biobank cohort is seen at the highest level of PA, whether total, moderate-intensity, or vigorous-intensity.

Source: University of Oxford


Study details

Accelerometer measured physical activity and the incidence of cardiovascular disease: Evidence from the UK Biobank cohort study

Rema Ramakrishnan, Aiden Doherty, Karl Smith-Byrne, Kazem Rahimi, Derrick Bennett, Mark Woodward, Rosemary Walmsley, Terence Dwyer

Published in PLOS Medicine on 12 January 2021


Higher levels of physical activity (PA) are associated with a lower risk of cardiovascular disease (CVD). However, uncertainty exists on whether the inverse relationship between PA and incidence of CVD is greater at the highest levels of PA. Past studies have mostly relied on self-reported evidence from questionnaire-based PA, which is crude and cannot capture all PA undertaken. We investigated the association between accelerometer-measured moderate, vigorous, and total PA and incident CVD.

Methods and findings
We obtained accelerometer-measured moderate-intensity and vigorous-intensity physical activities and total volume of PA, over a 7-day period in 2013–2015, for 90,211 participants without prior or concurrent CVD in the UK Biobank cohort. Participants in the lowest category of total PA smoked more, had higher body mass index and C-reactive protein, and were diagnosed with hypertension. PA was associated with 3,617 incident CVD cases during 440,004 person-years of follow-up (median (interquartile range [IQR]): 5.2 (1.2) years) using Cox regression models. We found a linear dose–response relationship for PA, whether measured as moderate-intensity, vigorous-intensity, or as total volume, with risk of incident of CVD. Hazard ratios (HRs) and 95% confidence intervals for increasing quarters of the PA distribution relative to the lowest fourth were for moderate-intensity PA: 0.71 (0.65, 0.77), 0.59 (0.54, 0.65), and 0.46 (0.41, 0.51); for vigorous-intensity PA: 0.70 (0.64, 0.77), 0.54 (0.49,0.59), and 0.41 (0.37,0.46); and for total volume of PA: 0.73 (0.67, 0.79), 0.63 (0.57, 0.69), and 0.47 (0.43, 0.52). We took account of potential confounders but unmeasured confounding remains a possibility, and while removal of early deaths did not affect the estimated HRs, we cannot completely dismiss the likelihood that reverse causality has contributed to the findings. Another possible limitation of this work is the quantification of PA intensity-levels based on methods validated in relatively small studies.

In this study, we found no evidence of a threshold for the inverse association between objectively measured moderate, vigorous, and total PA with CVD. Our findings suggest that PA is not only associated with lower risk for of CVD, but the greatest benefit is seen for those who are active at the highest level.


PLOS Medicine study (Open access)




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