European Primary Care Cardiovascular Society

High genetic risk for CVD may be modified by physical activity

Associations of Fitness, Physical Activity, Strength, and Genetic Risk With Cardiovascular Disease: Longitudinal Analyses in the UK Biobank Study

Tikkanen E, Gustafsson S, Ingelsson E, et al. - Circulation 2018: published online ahead of print

Introduction and methods

Physical exercise is a cost-effective method for CVD prevention, but fitness and physical activity are difficult to measure accurately and consistently on a large scale [1,2]. Additionally, it is not clear to which extent exercise can compensate the genetic CVD risk.

In this analysis of the UK Biobank, the associations of fitness and physical activity with incident CVD and all-cause death were evaluated, and it was assessed whether these associations are modified by genetic risk. For this purpose, objective and subjective measures of fitness and physical activity together with information of CVD risk factors and genomics in relation to prospective CVD disease events and all-cause death were analyzed, in 502,635 individuals.

The UK Biobank [3] is a longitudinal cohort study that enrolled more than 500,000 individuals aged 40-69 years between 2006 and 2010. The measures of fitness and physical activity were grip strength, total physical activity by means of the short form of the IPAQ questionnaire [4], and cardiorespiratory fitness (CRF), assessed with net oxygen consumption [5]. Available genome-wide genetic data of 468,095 individuals was used and Genetic Risk Score (GRS) for CHD and AF was calculated as the weighted sum of the risk alleles by using effect sizes from the reference genome-wide association study as weights [6,7]. The disease outcomes were coronary heart disease (CHD), stroke, heart failure (HF), atrial fibrillation (AF), and death. The median follow-up was 6.1 years (interquartile range: 5.4–6.8 years).

Main results


In a large population based analysis, different measures of fitness and physical activity were inversely associated with future CVD events and all-cause death. Among those at high, intermediate, or low genetic predisposition for CHD and AF, there was a graded inverse association with these parameters among each stratum of genetic risk, suggesting that elevated genetic risk for CVD can be compensated for by exercise.


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Find this article online at Circulation