Joint associations between exercising and classical cardiometabolic risk factors with all-cause, premature and cardiovascular mortality: a prospective cohort study among Mexican adults.

Background: Cardiovascular diseases are the leading cause of mortality worldwide, with a particularly high burden in low- and middle-income countries such as Mexico. Cardiometabolic risk factors are strongly associated with increased mortality. Although exercise is well established as protective against mortality, evidence on its joint associations with these risk factors in high-risk populations remains limited. This study aimed to examine the joint associations of exercise and classical cardiometabolic risk factors with all-cause, premature, and cardiovascular mortality among Mexican adults. Methods: This prospective cohort study analyzed data from 155156 adults (mean age, 52.3 years; 67.1% women) from the Mexico City Prospective Study. Exercise behavior and cardiometabolic risk factors (hypertension, diabetes, obesity, and smoking) were assessed at baseline. Mortality outcomes (all-cause, premature <75 years, and cardiovascular mortality) were tracked over a median follow-up of 18.26 years. Cox proportional hazards models, adjusted for sociodemographic characteristics and additional risk factors, were used to estimate associations. Joint exposure categories combining exercise with each cardiometabolic risk factor were analyzed. Results: During follow-up, 27510 deaths were recorded, including 13970 premature and 9192 cardiovascular deaths. Individuals who exercised had significantly lower mortality risk compared to non-exercisers. Exercise was associated with a 12-16% reduction in all-cause mortality, 16-20% reduction in premature mortality, and 10-15% reduction in cardiovascular mortality, even in the presence of cardiometabolic risk factors. The joint associations, combining absence of the cardiometabolic risk factor and exercise, showed the greatest risk reduction (HRs ranging from 0.20 to 0.43). Conclusions: Regular exercise is consistently associated with reduced risk of all-cause, premature, and cardiovascular mortality, regardless of the presence of major cardiometabolic risk factors. These findings highlight exercise as a powerful and broadly applicable strategy for reducing mortality risk and support its integration into clinical and public health interventions, particularly in populations with high cardiometabolic burden.