Joint Effect of Hypertension and Elevated Serum Phosphorus on the Risk of Mortality in National Health and Nutrition Examination Survey-III

BACKGROUND: Elevated serum phosphorus might aggravate the effect of hypertension on mortality. The objective of this study was to examine the joint effect of hypertension and serum phosphorus on the risk of mortality. METHODS AND RESULTS: A large prospective (n=15 833), population-based cohort of participants from the National Health and Nutritional Examination Survey III was examined to test potential synergism between hypertension, elevated serum phosphorus, and the risk of mortality. Interaction on additive scale and multiplicative scale was estimated. After a median follow-up of 14.3 years, 1691 cases of cardiovascular mortality and 3875 cases of all-cause mortality were identified. Interaction was observed between hypertension and elevated serum phosphorus on the additive scale for cardiovascular mortality (relative excess risk due to interaction, 0.99, 95% CI: 0.06; 1.92, adjusted for age, gender, race, and estimated glomerular filtration rate). No statistically significant interaction was found between hypertension and serum phosphorus for all-cause mortality on the additive scale. No significant interaction was detected on the multiplicative scale. In sensitivity analysis, excluding participants who died in first 2 years and adjustment for additional confounders resulted in essentially similar findings. CONCLUSIONS: The joint effect of hypertension and elevated serum phosphorus was larger than the sum of the independent effects on cardiovascular mortality but not on all-cause mortality. Future studies should investigate whether controlling elevated serum phosphorus in hypertensive individuals helps in prevention of extra risk of cardiovascular mortality.