Is the effect of antihypertensive drug therapy on blood pressure control and prevalent cardiovascular disease associated with dietary sodium-potassium ratio? A cross-sectional study based on NHANES

Objective To evaluate whether antihypertensive treatment strategy and dietary sodium-to-potassium (Na/K) ratio are associated with blood pressure (BP) control and cardiovascular disease (CVD), and whether Na/K interacts with treatment effects. Methods We analyzed 4,800 treated hypertensive adults (BP control defined as <130/80 mmHg) from NHANES 2009-2018 using survey-weighted logistic models and interaction analyses. Parallel endothelial experiments were performed in HUVECs exposed to normal or high Na/K, Ang II, and antihypertensive drugs. Results Combination therapy was not associated with improved BP control (OR = 0.89; P = 0.214) but was associated with higher CVD prevalence (OR = 2.40; P < 0.001) compared with monotherapy. The Na/K ratio showed no significant association with BP control or CVD across quartiles, and no meaningful interaction with treatment strategy was observed on multiplicative or additive scales. In cell experiments, high Na/K conditions intensified Ang II-induced endothelial injury, while the protective effects of losartan and combination therapy remained comparable under both sodium conditions. Conclusions Pharmacologic treatment intensity and dietary Na/K ratio appeared to influence vascular outcomes independently in treated hypertension. Critically, the lack of dietary Na/K effect modification in the clinical population is biologically explained by the maintained drug efficacy under high Na/K conditions.