Abstract
To the Editor,
We read with interest the population-based study by Holm et al 1 on physical activity, carotid-femoral pulse wave velocity (cfPWV), cardiovascular disease, and death in men and women. The authors should be commended for linking a behavioral exposure with an objective vascular-aging marker and registry-based outcomes in an older community cohort. Their finding that arterial stiffness partly explained the association between physical activity and adverse outcomes, particularly in men, adds useful mechanistic detail to the prevention literature.
Several points may help refine the interpretation of these findings. First, physical activity was assessed by self-report, whereas cfPWV was measured objectively. This imbalance in exposure and mediator measurement may have introduced non-differential misclassification and attenuated the estimated physical activity-outcome association. Future studies using accelerometry or wearable-derived activity profiles would better distinguish total volume, sedentary time, intensity distribution, and long-term activity patterns.
Second, the interval between physical activity assessment and cfPWV measurement deserves careful consideration. Arterial stiffness is not a fixed trait; it may change with aging, blood pressure, metabolic status, medication use, and sustained exercise habits. A single cfPWV assessment therefore captures only 1 point in a dynamic vascular-aging process. Repeated cfPWV measurements could determine whether physical activity slows vascular stiffening or whether lower arterial stiffness simply identifies individuals with more favorable baseline cardiovascular health. 2
Third, the sex-specific results are clinically important but should be interpreted cautiously. The absence of a significant physical activity-outcome association in women may reflect differences in menopausal status, hormonal milieu, lifetime activity patterns, body composition, reporting behavior, or statistical power. These possibilities are not mutually exclusive. Stratification by menopausal status, hormone therapy, physical function, and activity intensity could clarify whether the apparent sex difference is biological, methodological, or partly due to residual confounding. 3
Finally, arterial stiffness explained only a modest proportion of the protective association. This finding should not weaken the importance of cfPWV; rather, it supports the concept that exercise-related cardiovascular protection is mediated through multiple parallel pathways, including endothelial function, inflammation, autonomic regulation, glycemic control, body composition, and lipid metabolism. A multi-mediator framework may therefore be more informative than testing arterial stiffness alone.4,5
Overall, Holm et al provide valuable evidence that vascular aging may be 1 pathway linking physical inactivity to adverse cardiovascular outcomes in older adults. Future prospective studies should combine objective physical activity monitoring, serial cfPWV assessment, and sex-specific mediation analyses to identify which vascular and metabolic targets are most responsive to intervention.
