Adolescent Cardiorespiratory Fitness and the Trade-Off Between Atrial Fibrillation Risk and Cardiovascular Benefits: A Nationwide Sibling-Controlled Cohort Study

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Abstract
BACKGROUND: Young athletes and adolescents with high cardiorespiratory fitness appear to have a higher risk of atrial fibrillation (AF), but the extent to which this reflects causal effects or shared genetic, behavioral, and environmental factors remains uncertain. METHODS: This cohort study with sibling control analysis comprised Swedish men who participated in mandatory military conscription examinations from 1972 to 1995 and completed cardiorespiratory fitness testing. The outcomes were AF and non-AF cardiovascular disease (CVD; eg, stroke and ischemic heart disease), defined as a composite end point of diagnosis or death in the National Patient Register and the Cause of Death Register, until December 31, 2023. Flexible parametric regressions estimated standardized cumulative risk differences (RDs) by deciles of fitness. RESULTS: Among 1 124 049 men (mean age, 18.3 years), 45 179 (4.0%) experienced an AF event and 96 404 (8.6%) had a non-AF CVD event at a median age of 54.8 and 54.4 years. In population-wide analysis controlling for measured confounders, compared with the lowest decile of fitness, the highest decile had a small excess in AF that exceeded the reduction in non-AF CVD during early adulthood, whereas the reduction in non-AF CVD became larger from 45 years of age onwards. In full-sibling comparisons controlling for shared familial factors, the age-dependent trade-off disappeared entirely, leaving no age window with a net cardiovascular disadvantage. Already from 35 years of age, the reduction in non-AF CVD was larger (RD, −0.11% [95% CI, −0.21% to −0.01%]) than the excess in AF (RD, 0.06% [95% CI, −0.01% to 0.12%]). By 65 years of age, the gap further widened, with an even larger reduction in non-AF CVD (RD, −3.91% [95% CI, −5.40% to −2.42%]) compared with the excess in AF (RD, 2.30% [95% CI, 1.15%–3.45%]). CONCLUSIONS: High adolescent cardiorespiratory fitness is associated with a small excess in AF risk during early adulthood that is outweighed by larger reductions in non-AF CVD after controlling for familial confounders. These findings support population-level efforts to improve youth cardiorespiratory fitness and provide reassurance about the safety and benefits of high fitness levels.

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