Cardiovascular Disease and All-Cause Mortality in Male Twins With Discordant Cardiorespiratory Fitness: A Nationwide Cohort Study

Abstract

Whether genetic and familial factors influence the association between cardiorespiratory fitness (CRF) and cardiovascular disease (CVD) is unknown. Two cohorts were formed based on 1,212,295, 18-year-old men that conscripted for military service in Sweden 1972-1996. The first comprised 4,260 twin pairs where twins in each pair had different CRF (≥1 Watt). The second comprised 90,331 non-sibling pairs with different CRF and matched on birth year and year of conscription. Incident CVD and all-cause mortality were identified using national registers. During follow-up (median 32 years), there was no difference in CVD and mortality between fitter twins and less fit twins (246 vs 251 events; hazard ratio [HR] = 1.00, 95% confidence interval [CI]: 0.83, 1.20). The risks were similar in twin pairs with ≥60 Watt difference in CRF (HR = 0.96, 95% CI: 0.57, 1.64). In contrast, in the non-sibling cohort, fitter men had a lower risk of the outcomes than less fit men (4444 vs 5298 events; HR = 0.87, 95% CI: 0.83, 0.92). The association was stronger in pairs with ≥60 Watt difference in CRF (HR = 0.65, 95% CI: 0.59, 0.71). These findings indicate that genetic and familial factors influence the association of CRF with CVD and mortality.

Does exercise prevent major non‐communicable diseases and premature mortality? A critical review based on results from randomized controlled trials

“…Furthermore, although one twin study has found a single estimate of self-reported physical activity to be associated with reduced risk of all-cause and cardiovascular mortality in monozygotic twin pairs with discordant levels of physical activity [84], several other twin studies have shown other results. For instance, studies that have used either repeated estimates of self-reported physical activity or a single measure of objectively measured physical fitness have found no beneficial associations in relation to major NCDs or mortality in twin pairs with discordant levels of physical activity/fitness [85][86][87], further suggesting that genetic pleiotropy may influence the strong associations of physical activity with various diseases and mortality found in observational studies.…”

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“… 254 Moreover, genetic factors may confound the observed association between low levels of physical activity and higher disease and mortality risk. 255 , 256 , 257 …”

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“…It is to some extent an integrated measure of several factors with negative effects on cardiovascular health such as obesity, T2D, smoking, and sedentary activity, but there are genetic factors that contribute to individual variations of CRF. These familiar and genetic factors are also of major importance for the association between CRF and disease in young males [ 66 ].…”