Does urinary Na/K ratio predict future development of hypertension in the general population?

Abstract Background/Introduction Excess dietary salt intake is an important risk of developing hypertension and a close association between dietary sodium intake and blood pressure (BP) has been reported. Recently, the urinary sodium-to-potassium (Na/K) ratio has been reported to be more strongly associated with BP than either sodium or potassium levels alone. Purpose The present study was designed to investigate whether urinary Na/K ratio predicts the development of hypertension in the general population. Methods Urinary Na/K ratio was calculated using a spot urine sample in 23014 participants (male=13525, 51.4±13.2 year-old) who visited our hospital for a yearly medical checkup from April 2010 to March 2023. Data obtained at their first visit during the period were used for a cross-sectional analysis where the relationship between urinary Na/K ratio and hypertension was examined. Then, after excluding participants with hypertension, 12483 normotensive participants (male=7087, 48.7±11.9 year-old) were followed up until March 2024 (median 1788 days) with the endpoint being the development of hypertension. Hypertension was defined as systolic BP ≥140mmHg, diastolic BP ≥90mmHg or the use of antihypertensive medication. Results Cross-sectional analysis revealed that urinary Na/K ratio was higher in male than female participants (4.71±2.66 vs. 4.35±2.47, p0.001) and higher in hypertensive than normotensive participants (n=6039; 5.05±2.85 vs. n=16975; 4.39±2.47, p0.001). After the exclusion of participants with antihypertensives, urinary Na/K ratio was significantly associated with systolic and diastolic BP (p0.001). In the follow-up study, 4056 participants (58.9 per 1000 person-year) developed hypertension. The incident hypertension was more frequent in male than female participants (68.5 vs. 46.5 per 1000 person-year, p0.001), and increased across the quartiles of baseline urinary Na/K ratio (50.9, 54.5, 62.2, and 67.9 per 1000 person-years in the first, second, third, and fourth quartiles, respectively). Non-adjusted hazard ratio (HR) (95% confidence interval CI) of urinary Na/K ratio for the new onset of hypertension was 1.041 (1.029-1.053). Multivariate Cox hazard analysis adjusted for age, sex, body mass index, pulse rate, serum creatinine, uric acid, HbA1c, LDL-cholesterol, HDL-cholesterol, frequent alcohol consumption and family history of hypertension showed that urinary Na/K ratio was a significant predictor for the future development of hypertension (HR=1.028, 95%CI=1.016-1.041), while the statistical significance was disappeared after additional adjustment for baseline systolic BP (HR=1.008, 95%CI=0.996-1.020). Conclusions Urinary Na/K ratio is associated with BP levels and an increased urinary Na/K ratio predicts future development of hypertension in the general population. The prediction of hypertension may at least partially be attributable to mild increase in baseline BP in participants with increased urinary Na/K ratio.