Background: Recent studies have raised the possibility of adverse effects of low sodium, particularly <2300 mg/d, on cardiovascular disease; however, these paradoxical findings might have resulted from suboptimal measurement of sodium and potential biases related to indication or reverse causation.
Methods and results: Phases 1 and 2 of the Trials of Hypertension Prevention (TOHP) collected multiple 24-hour urine specimens among prehypertensive individuals. During extended post-trial surveillance, 193 cardiovascular events or cardiovascular disease deaths occurred among 2275 participants not in a sodium reduction intervention with 10 (TOHP II) or 15 (TOHP I) years of post-trial follow-up. Median sodium excretion was 3630 mg/d, with 1.4% of the participants having intake <1500 mg/d and 10% <2300 mg/d, consistent with national levels. Compared with those with sodium excretion of 3600 to <4800 mg/d, risk for those with sodium <2300 mg/d was 32% lower after multivariable adjustment (hazard ratio, 0.68; 95% confidence interval, 0.34-1.37; P for trend=0.13). There was a linear 17% increase in risk per 1000 mg/d increase in sodium (P=0.05). Spline curves supported a linear association of sodium with cardiovascular events, which continued to decrease from 3600 to 2300 and 1500 mg/d, although the data were sparse at the lowest levels. Controlling for creatinine levels had little effect on these results.
Conclusions: Results from the TOHP studies, which overcome the major methodological challenges of prior studies, are consistent with overall health benefits of reducing sodium intake to the 1500 to 2300 mg/d range in the majority of the population, in agreement with current dietary guidelines.
Keywords: cardiovascular diseases; diet; nutrition; primary prevention; sodium chloride, dietary.