From Pages to Practice

By Leslie Chang, MD

Published January 5, 2022


Aaron is a 31-year-old male intern in an internal medicine residency program. For him, one of the best parts of intern year has been the free food. Every day, his residency program provides residents with a free catered meal at the noon conference lecture. His favorite day is Wednesday — Chinese food day —and he dreads Monday when salads are served. As good as the Chinese take-out tastes, Aaron is worried about the high sodium levels in the lo mein and the long-term effects on his cardiovascular health.

In the past decade, several studies have endeavored to uncover the association between high-sodium intake and cardiovascular disease. However, these studies are limited by methodological issues and the results have been inconsistent. One limitation is the inaccurate assessment of sodium intake. To overcome this limitation, Ma et al. analyzed individual-level 24-hour urinary sodium and potassium excretion over several days in six cohorts of healthy adults. These measurements are considered the most accurate surrogate for sodium and potassium intake.

Among the 10,709 participants included in this study, the overall daily sodium and potassium intakes based on urinary excretion were approximately 3500 mg and 3300 mg, respectively. After a median follow-up of nearly 9 years, higher sodium excretion, lower potassium excretion, and higher sodium-to-potassium ratio were associated with higher cardiovascular risk in a dose-response manner, after controlling for confounding factors. Each daily increment of 1000 mg in sodium excretion correlated with an 18% increase in cardiovascular risk. Conversely, each daily increment of 1000 mg in potassium excretion was associated with an 18% decrease in risk. 

The evidence from this study leans the pendulum in support of an association between a high-sodium diet and increased cardiovascular risk. As delicious as Chinese take-out may be, Aaron might want to consider adopting a low-sodium diet, favoring salad day over Chinese food day. 

The following NEJM Journal Watch Summary provides more details of the study.


Further Evidence to Support a Low-Sodium, High-Potassium Diet

Allan S. Brett, MD, reviewing Ma Y et al. N Engl J Med 2021 Nov 13

Studies with various limitations generally have shown that high sodium intake and low potassium intake are associated with higher risk for hypertension and adverse cardiovascular (CV) events. To provide more-robust evidence, researchers combined data from six prospective cohort studies in which multiple 24-hour urine collections for sodium and potassium (average, 3–4 collections per participant) were used to estimate intake. Nearly 11,000 adults (mean age, 52) with no evidence of CV or kidney disease were followed for a median of 9 years.

The primary CV outcome (i.e., myocardial infarction, stroke, or coronary revascularization) occurred in about 6% of participants. In analyses adjusted for potentially confounding variables, this outcome was associated — in significant dose-response relations — with higher sodium excretion, lower potassium excretion, and higher sodium-to-potassium ratio. For example:

  • Participants in the highest quartile of sodium excretion (median, 4.7 g/24 hours) had a hazard ratio of 1.60 for an adverse CV event compared with those in the lowest quartile (median, 2.2 g/24 hours); this represented roughly 2 to 3 more CV events per 100 people.

  • Participants in the highest quartile of potassium excretion (median, 3.5 g/24 hours) had a hazard ratio of 0.69 for a CV event compared with those in the lowest quartile (median, 1.8 g/24 hours); this represented roughly 1 fewer CV event per 100 people.

  • Hazard ratios were similar in older (age, ≥65) and younger (age, <65) subgroups and in people with or without hypertension at baseline.

Comment: In a recent randomized trial, use of a potassium-containing salt substitute was associated with a lower incidence of adverse CV events (NEJM JW Gen Med Oct 1 2021; p. 151 and N Engl J Med 2021; 385:1067). Those findings, in combination with these new results, make a strong case for emphasizing moderate sodium restriction and high potassium intake for primary prevention of adverse CV events in middle-aged and older patients with normal renal function.

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Leslie is a 2021-2022 NEJM Editorial Fellow and a hospitalist at Massachusetts General Hospital. She graduated from Duke University School of Medicine in 2018 and completed her internal medicine residency at Massachusetts General Hospital in 2021.
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