Author + information
- Received April 15, 2016
- Revision received July 5, 2016
- Accepted July 12, 2016
- Published online October 11, 2016.
- S0735109716347982-670d43e09fd8896770ec44deadfc0affNancy R. Cook, ScDa,∗ (, )
- S0735109716347982-5c0dc4f09b3968ac4ca5815a153a6fd7Lawrence J. Appel, MDb and
- S0735109716347982-2e415394709ab3fb8d400b66d03fed96Paul K. Whelton, MDc
- aDivision of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- bWelch Center for Prevention, Epidemiology, and Clinical Research, the Johns Hopkins University, Baltimore, Maryland
- cDepartment of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana
- ↵∗Reprint requests and correspondence:
Dr. Nancy R. Cook, Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, 900 Commonwealth Avenue East, Boston, Massachusetts 02215-1204.
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.
TOHP I and II were supported by National Institutes of Health/National Heart, Lung, and Blood Institute (NHLBI) cooperative agreements HL37849, HL37852, HL37853, HL37854, HL37872, HL37884, HL37899, HL37904, HL37906, HL37907, and HL37924. TOHP Follow-up Study was supported by NHLBI grant HL57915 and American Heart Association (AHA) award 14GRNT18440013. The NHLBI and AHA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
This paper was presented as an oral presentation at the American Heart Association Scientific Sessions on November 10, 2015, in Orlando, Florida.
- Received April 15, 2016.
- Revision received July 5, 2016.
- Accepted July 12, 2016.
- American College of Cardiology Foundation