Joint associations of 25-hydroxyvitamin D and physical activity with hypertension: Evidence from the ELSA study and genome-wide data

The interaction between 25-hydroxyvitamin D 25(OH)D and physical activity (PA) in influencing hypertension remains underexplored. This study aimed to examine their independent and joint associations with hypertension risk among 5,327 participants aged ≥50 years from the English Longitudinal Study of Ageing. Participants were categorized by 25(OH)D status (sufficient, ≥50 nmol/L; insufficient, ≥30 to <50 nmol/L; deficient, <30 nmol/L) and self-reported PA levels. Multivariable logistic regression, adjusting for the season of measurement and sociodemographic confounders, showed that sufficient 25(OH)D (OR = 0.66, 95% CI: 0.56-0.78) and higher PA (OR = 0.82, 95% CI: 0.71-0.94) were independently associated with reduced hypertension prevalence. In joint analyses, the group combining higher PA and sufficient 25(OH)D exhibited the lowest odds of hypertension (OR = 0.55, 95% CI: 0.43-0.70) compared to the lower PA and deficient group. A significant synergistic interaction was identified, indicating that the combined protective effect of these factors was greater than the sum of their individual associations. These results were corroborated by Mendelian randomization analysis, which identified inverse causal associations between genetically predicted 25(OH)D, vigorous PA, and hypertension risk across independent datasets. These findings emphasize that vitamin D sufficiency acts in synergy with an active lifestyle to enhance cardiovascular protection. This relationship underscores the critical importance in nutritional science of integrating micronutrient status with physical activity to develop more effective, multifaceted lifestyle-based strategies for hypertension management in middle-aged and older populations.