June 28, 2026
Sodium Intake and All-Cause Mortality Over 20 Years in the Trials of Hypertension Prevention
Key Result
Sodium reduction was associated with a nonsignificant reduction in long-term mortality (HR 0.85; 95% CI 0.66-1.09; p=0.19), while higher average sodium intake directly increased mortality risk.
Key Points
- To examine the long-term relationship between measured sodium intake and total mortality, using urinary sodium excretion data.
- Conducted two trials of sodium reduction interventions in pre-hypertensive adults aged 30-54.
- Collected multiple 24-hour urine samples and tracked mortality over a median of 24 years.
- Compared mortality rates between participants with different average sodium intakes.
- Among 744 Phase I and 2382 Phase II participants, no significant reduction in mortality was seen with active intervention (HR=0.85, p=0.19).
- A direct linear association was found: HR=1.12 per 1000 mg sodium increase, indicating risk increases with higher sodium intake (p=0.05).
- No evidence of a J-shaped curve or non-linear relationship was observed for sodium intake and mortality.
Study Design
Type
RCT (n=3,126)
Randomization
randomized
Structured PICO
Does sodium reduction reduce long-term all-cause mortality in pre-hypertensive adults?
P
Population
3,126 pre-hypertensive adults aged 30-54 randomized to sodium reduction or control, followed for a median of 24 years for mortality.
I
Intervention
Sodium reduction intervention (Phase I over 18 months, Phase II over 36 months) and lower average sodium intake estimated from multiple 24-hour urinary sodium excretions.
C
Comparator
Control group and higher average sodium intake.
O
Outcome
Long-term all-cause mortality ascertained via the National Death Index over a median 24 years.hard clinical
Long-term follow-up demonstrates a direct linear relationship between higher sodium intake and increased all-cause mortality, supporting the benefits of sodium reduction and challenging the existence of a J-shaped curve.
Main Result
Hazard Ratio: 0.85 (95% CI 0.66–1.09)
p-value: p=0.19
Abstract
Background While several studies suggest beneficial effects of lower sodium on cardiovascular disease, the relationship with total mortality remains controversial. Some have reported a J-shaped curve, but this may be due to poor quality measurement of sodium or confounding bias. Objective To examine the relationship of well-characterized measures of sodium intake, estimated from urinary sodium excretion, with long-term mortality. Methods Two trials Phase I (1987-90) over 18 month and Phase II (1990-5) over 36 months in the Trials of Hypertension Prevention implemented sodium reduction interventions. Multiple 24-hour urines were collected from pre-hypertensive adults aged 30-54 during these trial periods. Post-trial deaths were ascertained over a median 24 years through December 31, 2013 using the National Death Index. The association of mortality with both the randomized intervention and average sodium intake was examined. Results Among 744 Phase I and 2382 Phase II participants randomized to sodium reduction or control, 251 deaths occurred, with a nonsignificant 15% lower risk in the active intervention (hazard ratio (HR)=0.85, 95% 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 of average sodium intake with mortality, with HR=0.75, 0.95, 1.00 (reference), and 1.07 (p-trend = 0.30) for =4800 mg/24hr, respectively, with HR=1.12 per 1000 mg/24hr (95% CI = 1.00-1.26, p=0.05) and no evidence of a J-shape or nonlinear relation. The HR per unit increase in sodium/potassium ratio was 1.13 (95% CI = 1.01-1.27, p=0.04). Conclusions This study, with carefully characterized measures of sodium intake, found an increased risk at high sodium intake and a direct relation with total mortality even at the lowest levels of sodium intake. Overall, these results are consistent with a benefit of reduced sodium and sodium/potassium on total mortality over a period of over 20 years.
Expert Takes4 quotes
1/4
“Sodium is an essential nutrient. It's not tobacco. Without sodium, you die. The body needs sodium. The optimal level of tobacco is zero, but with sodium, it's not zero. The question is, how much sodium? Every essential nutrient in the body tends to have the so-called U-shaped relationship with mortality—calcium, magnesium, vitamin D, and so on and so forth. Why would sodium be any different? The researchers are making it seem like there's a linear relationship when in fact it violates the laws of biology. It doesn't make any sense.”
Andrew Mente, Epidemiologist, McMaster University/Population Health Research InstituteMcMaster Universityauto_pipelineView source