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Original Investigation
January 12, 2009

Joint Effects of Sodium and Potassium Intake on Subsequent Cardiovascular Disease: The Trials of Hypertension Prevention Follow-up Study

Author Affiliations

Author Affiliations: Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (Drs Cook, Buring, and Rexrode); Division of Prevention and Population Sciences, National Heart, Lung, and Blood Institute, Bethesda (Drs Obarzanek and Cutler), and Department of Medicine, The Johns Hopkins School of Medicine, The Johns Hopkins University, Baltimore (Dr Appel), Maryland; Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia (Dr Kumanyika); and Loyola University Health System, Loyola University Medical Center, Maywood, Illinois (Dr Whelton).

Arch Intern Med. 2009;169(1):32-40. doi:10.1001/archinternmed.2008.523

Background  Previous studies of dose-response effects of usual sodium and potassium intake on subsequent cardiovascular disease (CVD) have largely relied on suboptimal measures of intake.

Methods  Two trials of sodium reduction and other interventions collected 24-hour urinary excretions intermittently during 18 months from September 17, 1987, to January 12, 1990 (Trials of Hypertension Prevention [TOHP] I), and during 36 months from December 18, 1990, to April 7, 1995 (TOHP II), among adults with prehypertension aged 30 to 54 years. Among adults not assigned to an active sodium reduction intervention, we assessed the relationship of a mean of 3 to 7 twenty-four–hour urinary excretions of sodium and potassium and their ratio with subsequent CVD (stroke, myocardial infarction, coronary revascularization, or CVD mortality) through 10 to 15 years of posttrial follow-up.

Results  Among 2974 participants, follow-up information was obtained on 2275 participants (76.5%), with 193 CVD events. After adjustment for baseline variables and lifestyle changes, there was a nonsignificant trend in CVD risk across sex-specific quartiles of urinary sodium excretion (rate ratio [RR] from lowest to highest, 1.00, 0.99, 1.16, and 1.20; P = .38 for trend) and potassium excretion (RR, 1.00, 0.94, 0.91, and 0.64; P = .08 for trend) but a significant trend across quartiles of the sodium to potassium excretion ratio (RR, 1.00, 0.84, 1.18, and 1.50; P = .04 for trend). In models containing both measures simultaneously, linear effects were as follows: RR, 1.42; 95% confidence interval (CI), 0.99 to 2.04 per 100 mmol/24 h of urinary sodium excretion (P = .05); and 0.67; 0.41 to 1.10 per 50 mmol/24 h of urinary potassium excretion (P = .12). A model containing the sodium to potassium excretion ratio (RR, 1.24; 95% CI, 1.05-1.46; P = .01) had the lowest Bayes information criterion (best fit).

Conclusion  A higher sodium to potassium excretion ratio is associated with increased risk of subsequent CVD, with an effect stronger than that of sodium or potassium alone.