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Higher dietary sodium intake, estimated by determining daily excretion from at least two 24-hour urine samples, was associated with an increased risk for a cardiovascular event in a meta-analysis of six cohorts.

And higher potassium intake, determined the same way, bromocriptine manufacturer india was associated with a decreased risk for a cardiovascular event, including coronary revascularization, fatal or nonfatal myocardial infarction, and fatal or nonfatal stroke, over 8.8 years among more than 10,000 healthy participants.

Those in the highest quartile for 24-hour sodium excretion had a 60% higher risk for a CV event than those in the lowest quartile (hazard ratios [HR], 1.60; 95% CI, 1.19 – 2.14).

At the same time, participants with the highest 24-hour potassium excretion had a 31% lower risk for a CV event than those with the lowest excretion (HR, 0.69; 95% CI, 0.51 – 0.91).

The study was presented November 13 at the American Heart Association (AHA) Scientific Sessions 2021 and simultaneously published online in the New England Journal of Medicine.

The results “may support reducing sodium intake and increasing potassium intake from current levels,” but the study was observational and thus cannot show cause and effect, lead author Yuan Ma, PhD, explained in an email to theheart.org | Medscape Cardiology.

“Our findings are consistent with those from recent trials, e.g., the SSaSS trial, and current guidance recommendations” for dietary sodium and salt intake, Ma, a research scientist in the Department of Epidemiology, T.H. Chan School of Public Health, Harvard University, Boston, added in an emailed comment.

“Our study, together with consistent evidence from randomized trials,” Ma added, “provides further support for public health policies to reduce sodium intake and increase potassium intake.”

“We hope to see more regulations and actions to implement salt-reduction strategies,” he said, such as “setting salt-reduction targets for the food industry, food labelling, food reformulation, and healthy behavior promotion.”

“Reasonable Na Restriction Warranted”

The researchers pooled data from six cohorts: the Health Professionals Follow-up Study (HPFS); the Nurses’ Health Study (NHS); the Nurses’ Health Study II (NHS II); the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study; and the Trials of Hypertension Prevention (TOHP I and TOHP II) Follow-up Studies.

“Overall, this is a well-conducted study that adds to the literature regarding sodium intake (using 24-h urine sodium collections as a surrogate) and CV outcomes,” Nayan Arora, MD, who was not involved with the research, commented to theheart.org | Medscape Cardiology.

“It did not identify a J-shaped curve, with low urine sodium excretion being associated with higher CV events, which has been described previously in studies with questionable methodology regarding assessment of sodium intake,” Arora added, such as the PURE study in which sodium was determined from spot urines.

It adds to the findings of the TOHP studies, which also failed to show increased risk for CV events at lower levels of sodium intake using 24-h urine collections, said Arora, clinical assistant professor, Department of Nephrology, University of Washington, Seattle.

Study limitations, he added, include the inherent limitations of observational studies, and it was in mainly generally healthy White individuals so it is not generalizable to other populations, which the researchers also acknowledge.

In addition, although there was a dose-response reduction in CV events with reduction in sodium intake in a spline plot of the association, only the difference between quartile 4 (mean daily sodium excretion of 4692 mg) and quartile 1 (2212 mg) was significant; this was also true for potassium.

“I think this study again shows that reasonable levels of sodium restriction are warranted,” Arora summarized, “However, (for me) it still doesn’t answer the question of whether or not such draconian limits as recommended by various health societies are warranted.”

“Increased dietary potassium has been associated with improved outcomes and, although this study does provide further credence for this,” he added, “the SSaSS trial, provides a much stronger case.”

SSaSS was a cluster randomized controlled trial of more than 20,000 individuals at high CV risk (>70% with a history of stroke), in which participants were randomized to either 100% sodium chloride or salt substitution with 75% sodium chloride and 25% potassium chloride, he said.

“This resulted in an impressive reduction in CV events despite only ~ an 8% reduction in sodium, though ~55% increase in potassium, ” he noted.

Controversial Link Between Sodium and CVD

“The relation between sodium intake and cardiovascular disease remains controversial, owing in part to inaccurate assessment of sodium intake,” Ma and colleagues write.

They point to large daily variations in sodium excretion and potential sample collection errors in a single 24-hour urine and errors from estimating 24-hour excretion from a spot urine. Individuals may reduce sodium intake because of pre-existing illness, leading to reverse causation errors.

Therefore, the researchers studied the relation between sodium intake and CVD in healthy individuals who had provided at least two 24-hour urine collections.

The 10,707 participants from the six cohorts had a mean age of 51 years, 54% were women, and 92% were White. On average, they had a mean body mass index (BMI) of 26.6 kg/m2, 2.4% had diabetes, 24% had hypertension, and 30% had hypercholesterolemia.

During a median follow-up of 8.8 years, there were 571 CV events.

Higher sodium excretion, lower potassium excretion, and a higher sodium-to-potassium ratio were all associated with a higher CV risk, after adjustment for confounders (P ≤ .005 for all comparisons).

Each 1000 mg/day increase in sodium excretion was associated with an 18% increase in risk for a CV event (HR, 1.18; 95% CI, 1.08 – 1.29).

And each 1000 mg/day increase in potassium excretion was associated with an 18% decreased risk for a CV event (HR, 0.82; 95% CI, 0.72 – 0.94).

The researchers estimated dietary sodium and potassium intake, assuming that 93% of dietary sodium and 77% of dietary potassium is excreted in the urine.

Overall, the participants in this meta-analysis had an estimated sodium intake of approximately 2000 to 6000 mg/day, and a potassium intake of approximately 2000 to 5000 mg/day.

DASH and Mediterranean Diets

The WHO recommends less than 2 g/day of sodium, and the AHA recommendation for generally healthy adults is less than 2.3 g/day of sodium, Ma noted.

“Our findings were consistent with the data from the dietary intervention trials,” such as the DASH diet and the Mediterranean diet, he said.

To cut salt intake, Ma continued, people can prepare meals from fresh ingredients and add less salt. They can also check food labels and sodium content in grocery stores and choose low-sodium options — noting that to convert 1 g of sodium to 1 g of salt, multiply by 2.5, and 5.8 g of salt is about 1 teaspoon.

Foods that are rich in potassium include fruits, vegetables (such as leafy greens, beans, and squash), nuts, and dairy foods.

“The DASH and Mediterranean diets are excellent options for patients,” Arora agreed, “not simply for sodium restriction, but as a way of providing a multitude of beneficial and necessary nutrients while avoiding processed foods, which play a large role in dietary issues in this country.”

“From a population standpoint, until a true randomized control trial of sodium restriction is performed, I would focus on salt substitution as was done in SSaSS — which provides people an alternative, rather than simply recommending low sodium diets.”

The study was supported by grants from the American Heart Association (AHA) and the National Institute on Aging, National Institutes of Health (NIH). Ma and Arora have no relevant financial disclosures.

N Engl J Med. Published November 13, 2021. Full text

American Heart Association (AHA) Scientific Sessions 2021. Presented November 13, 2021. Poster abstract

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