Sodium Intake and 20-Year Mortality in Trials of Hypertension Prevention
What is the relationship between well-characterized measures of sodium intake estimated from urinary sodium excretion and long-term mortality?
Two trials were undertaken in TOHP (Trials of Hypertension Prevention), which implemented sodium reduction interventions. The studies included multiple 24-hour urine samples collected from prehypertensive adults 30-54 years of age during the trials. Post-trial deaths were ascertained over a median of 24 years, using the National Death Index. The primary outcome was mortality in the randomized interventions.
Among the 744 participants in TOHP phase I randomized to the sodium reduction intervention or control, the average age was 43, 71% were male, and 20% were African American. Average weight was 191 pounds in men and 160 pounds in women, and average sodium excretion at baseline was 3,839 mg/24 hours in men and 2,948 mg/24 hours in women. Among the 2,382 participants in TOHP phase II, age, gender, and race were similar to TOPH phase I, but weight was higher, with an average of 218 pounds in men and 184 pounds in women. Average sodium excretion at baseline was higher in men (4,576 mg/24 hours) than women (3,541 mg/24 hours) in each group. A total of 251 deaths occurred with an insignificant 15% lower risk in the active intervention (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.66-1.09; p = 0.19). Among 2,974 participants not assigned to an active sodium intervention, 272 deaths occurred. There was a direct linear association between average sodium intake and mortality, with an HR of 0.75, 0.95, and 1.00 and 1.07 (p trend = 0.30) for <2,300, 2,300 to <3,600, 3,600 to <4,800, and ≥4,800 mg/24 hours, respectively; and with an HR of 1.12 per 1,000 mg/24 hour (95% CI, 1.00-1.26; p = 0.05). There was no evidence of a J-shaped or nonlinear relationship. The HR per unit increase in sodium/potassium ratio was 1.13 (95% CI, 1.01-1.27; p = 0.04).
There was an increased risk of mortality for high-sodium intake and a direct relationship with total mortality, even at the lowest levels of sodium intake. These results are consistent with a benefit of reduced sodium and sodium/potassium intake on total mortality over a 20-year period.
Most of the contrary evidence regarding sodium intake and cardiovascular outcomes is due to the lack of 24-hour urinary sodium collections and failure to do repeated measures over time. In contrast, this study measured 24-hour urine electrolytes on seven occasions. The 12% increase in total mortality per 1,000 mg increased intake/24 hours is quite impressive. Salt craving is likely learned early in life and is probably preventable.
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