Cardiovascular fitness in young males and risk of unprovoked venous thromboembolism in adulthood

Background: Whether high cardiovascular fitness is associated with reduced risk of venous thromboembolism (VTE) is unknown. The present study aims to determine whether high cardiovascular fitness reduces the risk of VTE. Methods: A Swedish cohort of male conscripts (n=773,925) born in 1954-1970 with no history of previous VTE were followed from enlistment (1972-1990) until 2010. Data on cardiovascular fitness using a cycle ergonometric test (maximal aerobic workload in Watt [W-max]) at conscription were linked with national hospital register data and the Multi-Generation Register. We identified all full-siblings and first-cousin pairs discordant for maximal aerobic workload. This co-relative design allows for adjustment for familial resemblance. Results: In total, 3005 (0.39%) males were affected by VTE. Cardiovascular fitness estimated with W-max was not associated with VTE risk when adjusted for body mass index (BMI). However, cardiovascular fitness estimated with W-max/kg and adjusted for BMI was associated with reduced risk for VTE (Hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.78-0.85 per standard deviation compared with mean W-max/kg). The association was weaker over time and also when examining discordant first cousins and full-sibling pairs. Conclusions: These results suggest that there is a relationship between cardiovascular fitness and weight that is important for future VTE risk.