Separating the effects of 24-hour urinary chloride and sodium excretion on blood pressure and risk of hypertension: Results from PREVEND

Abstract

Objective: Research into dietary factors associated with hypertension has focused on the sodium component of salt. However, chloride has distinct physiological effects that may surpass the effect of sodium on blood pressure. This study aims to separate the specific effects of chloride and sodium intake on blood pressure.

Methods: We studied 5673 participants from the Prevention of Renal and Vascular End-Stage Disease(PREVEND) study. Urinary chloride(uCl) and sodium(uNa) were measured in two 24-hour collections. We used generalized-linear-regression to evaluate the relation of uCl and uNa with baseline blood pressure and Cox-proportional-hazards-analysis to assess the association with hypertension. Multicollinearity was assessed with Ridge regression.

Results: Baseline 24-hour uCl was 135±39mmol and uNa was 144±54mmol. The correlation between uCl and uNa was high (Pearson's r = 0.96). UCl and uNa had similar non-significant positive and linear associations with blood pressure. In 3515 normotensive patients, 1021 patients developed hypertension during a median follow-up of 7.4 years. UCl and uNa had a comparable but non-significant J-shaped effect on the risk of hypertension. Adding both uCl and uNa to the same model produced instability, demonstrated by Ridge coefficients that converged or changed sign. The single index of uNa minus uCl showed a non-significant higher risk of hypertension of 2% per 10mmol/24-hour difference (HR1.02, 95%CI 0.98-1.06).

Conclusion: UCl and uNa had similar positive but non-significant associations with blood pressure and risk of hypertension and their effects could not be disentangled. Hence, the alleged adverse effects of high salt intake could be due to sodium, chloride or both. This encourages further study into the effect of chloride in order to complement dietary recommendations currently focused on sodium alone.

Fig 1. Correlation between urinary sodium and chloride excretion.

Fig 2. 24-h urinary chloride excretion in relation to blood pressure at baseline, with density plot.

Adjusted for age and sex (left) and after additional adjustment (right) for age, sex, urinary creatinine, urinary potassium, smoking, body-mass index, history of diabetes, family history of premature cardiovascular disease, educational attainment, alcohol and estimated glomerular filtration rate. SBP, systolic blood pressure; DBP, diastolic blood pressure.

Fig 3. Urinary chloride excretion and the risk of hypertension.

Adjusted for age and sex (left) and fully adjusted model (right) for urinary creatinine, urinary potassium, smoking, body-mass index, history of diabetes, family history of premature cardiovascular disease, educational attainment, alcohol and estimated glomerular filtration rate. HR, hazard ratio.

Fig 4

Urinary chloride (left) and sodium (right) excretion and the risk of hypertension incorporated in the same model. Age and sex adjusted. HR, hazard ratio.

Fig 5

Difference in urinary sodium and chloride excretion and the risk of hypertension (left) and after further adjustment (right). Adjusted for urinary creatinine, urinary potassium, smoking, body-mass index, history of diabetes, family history of premature cardiovascular disease, educational attainment, alcohol and estimated glomerular filtration rate (right). HR, hazard ratio.