Sodium Intake and All-Cause Mortality Over 20 Years in the Trials of Hypertension Prevention

Abstract

Background: The relationship between lower sodium intake and total mortality remains controversial.

Objectives: This study examined the relationship between well-characterized measures of sodium intake estimated from urinary sodium excretion and long-term mortality.

Methods: Two trials, phase I (1987 to 1990), over 18 months, and phase II (1990 to 1995), over 36 months, were undertaken in TOHP (Trials of Hypertension Prevention), which implemented sodium reduction interventions. The studies included multiple 24-h urine samples collected from pre-hypertensive adults 30 to 54 years of age during the trials. Post-trial deaths were ascertained over a median 24 years, using the National Death Index. The associations between mortality and the randomized interventions as well as with average sodium intake were examined.

Results: Among 744 phase I and 2,382 phase II participants randomized to sodium reduction or control, 251 deaths occurred, representing a nonsignificant 15% lower risk in the active intervention (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.66 to 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 (references) 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 h, respectively; and with an HR of 1.12 per 1,000 mg/24 h (95% CI: 1.00 to 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 to 1.27; p = 0.04).

Conclusions: We found 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.

Keywords: diet; mortality; nutrition; potassium; sodium.

Figure 1

Cumulative total mortality by randomized sodium intervention group in TOHP I (left) and TOHP II (right). Each shows a lower but non-significant reduction in mortality in the active sodium reduction group (see Table 1).

Central Illustration

Spline plot of average sodium intake based on multiple 24hr excretions and total mortality in observational analysis of usual intake. Shown is the hazard ratio for total mortality over more than 20 years as a function of usual sodium intake averaged over 3-7 urine collections over 1-3 years at baseline. Mortality is lowest among those with usual sodium intake less than 2300 mg/24hr and highest among those with levels above 6000 mg/24hr. There is a significant direct linear effect of sodium with mortality (p=0.048) with no evidence of non-linearity (p=0.90) in spline analysis.