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Regulating dietary sodium may not be the only way to attack hypertension, and for most of the world it may not even be the best way, according to new data published this week in the New England Journal of Medicine.

Only a very small proportion of the worldwide population consumes a low-sodium diet. In these people, sodium intake is not uniformly related to blood pressure, wrote authors of the Prospective Urban Rural Epidemiology (PURE) study.

The PURE findings were reported in two analyses, which were published along with results from the NUTRICODE study -- three papers dealt with sodium.

PURE, a prospective epidemiologic study that gathered data from 157,543 people ages 35 to 70 years in 18 low-, middle- and high-income countries, captured the broad range of sodium intake on a global scale, study author , clinical epidemiology and biostatistics assistant professor at McMaster University in Hamilton, Ontario, told 番茄社区.

"Previous studies looked at restricted geographic areas and a narrow range of sodium intake," Mente said.

These findings, along with results from NUTRICODE, a modeling of the effect of sodium consumption on cardiovascular mortality, question "the feasibility and usefulness of reducing dietary sodium as a population-based strategy for reducing blood pressure," wrote , Director of the Vascular Biology and Hypertension Program at the University of Alabama School of Medicine in Birmingham, Ala., in an accompanying editorial.

Encouraging diets high in potassium may be an alternative approach to reducing blood pressure and cardiovascular events, she added.

"Rather than focusing on sodium restriction, we're better off focusing on lifestyle changes, such as not smoking, and an overall healthy diet," said Mente.

"This confirms what we have known for a long time," , a cardiologist and professor of medicine at the University of California San Francisco and at Stanford, told 番茄社区. "I hope this changes recommendations, because nobody is following them."

But the data may not change guidelines due to limitations of these new studies.

"The major weaknesses of the PURE study, inherent in its study design and scope, include the absence of direct measurement of 24-hour urinary excretion on multiple occasions, which is the accepted model for assessing electrolyte intake," Oparil wrote.

Instead, the authors estimated 24-hour sodium and potassium excretion from a single fasting morning urine specimen.

There is evidence that sodium and potassium excretion may not even accurately represent dietary intake, , an internist and Director of the Welch Center for Prevention, Epidemiology and Clinical Research at Johns Hopkins School of Medicine, told 番茄社区.

"We don't have a good biomarker for potassium intake. It turns out that urinary excretion of potassium varies enormously," Appel said. "There are lots of factors, including race."

Urinary Sodium and Blood Pressure

PURE investigators compiled data from 102,216 participants from the PURE study, each with a valid baseline fasting morning urine sample.

They used the Kawasaki formula, which they validated using 1,083 people, to estimate 24-hour urinary excretion of sodium and potassium from the morning specimen and used these estimates as surrogates for sodium and potassium intake.

Mean estimated sodium and potassium excretion were calculated for the entire cohort, and adjustments were done for covariates known to be associated with blood pressure (including age, sex, educational level, body-mass index, alcohol intake, and geographic region).

Overall, 43.5% of the population had an estimated sodium excretion of more than 5 g per day, 45.9% between 3 and 5 g per day, and 10.6% less than 3 g per day.

Only 3.3% had an excretion of less than 2.3 g per day and 0.6%, less than 1.5 g per day.

Current recommend a maximum sodium intake of 1.5 to 2.4 g per day.

Estimated sodium excretion was higher in rural areas than in urban areas (P<0.001), whereas estimated potassium excretion was higher in urban areas (P<0.001).

Mean estimated sodium excretion ranged from 3.78 g per day in Malaysia to 5.59 g per day in China.

Mean estimated potassium excretion ranged from 1.70 g per day in South Asia to 2.46 g per day in Canada and Europe.

There was a positive but non-uniform association between estimated sodium excretion and blood pressure:

• A steep slope for the association among participants with sodium excretion of more than 5 g per day (2.58 mm Hg per gram of sodium; 95% CI 2.38-2.78)
• A modest association among those with sodium excretion to 3 to 5 g per day (1.74 mm Hg per gram; 95% CI 1.29-2.19)
• No significant association among those with sodium excretion of less than 3 g per day (0.74 mm Hg per gram; 95% CI minus 0.36-1.84)

The positive relationship between sodium excretion and blood pressure was observed in all geographic regions, but the slope of the association was less steep in the Middle East.

There was a significant inverse association between estimated potassium excretion and systolic blood pressure, with a stronger relationship in China.

After adjustment for covariates, a strong and linear association was observed between the estimated sodium-to-potassium ratio and systolic and diastolic blood pressures (P<0.001 for trend for both).

The highest blood pressures were observed in the group with the highest estimated sodium excretion and the lowest estimated potassium excretion.

The findings are consistent with previous trials, including INTERSALT and DASH, authors wrote.

"These findings suggest that the effect of sodium on blood pressure is dependent on the background diet," they added.

Mortality, and Cardiovascular Events

In the second analysis from PURE, the authors compiled data from a cohort of 101,945 participants who had a valid baseline fasting morning urine sample. Again, they used the Kawasaki formula to estimate sodium and potassium intake.

The mean duration of follow-up was 3.7 years.

The primary composite outcome of death or a major cardiovascular event occurred in 3,317 participants (3.3%): 1,976 participants died (650 from cardiovascular causes), 857 had myocardial infarction, 872 had stroke, and 261 had heart failure. Participants may have had more than one cardiovascular event.

The mean systolic and diastolic blood pressures were higher among participants with a higher estimated sodium excretion (P<0.001).

The lowest risk of death and cardiovascular events was seen among participants with an estimated sodium excretion between 3 g per day and 6 g per day.

As compared with an estimated sodium excretion of 4.00 to 5.99 g per day, estimated excretion of 7.00 g per day or more was associated with increased risks of the primary composite outcome (odds ratio, 1.15; 95% confidence interval [CI], 1.02-1.30) and death from any cause (odds ratio, 1.25; 95% CI 1.07-1.48).

But when adjustment for blood pressure or diagnosis of prior hypertension was made, only death from any cause remained significantly associated with high sodium excretion.

Estimated excretion of less than 3.00 g per day was also associated with increased risks of the primary composite outcome (odds ratio, 1.27; 95% CI 1.12-1.44) and death from any cause (odds ratio, 1.38; 95% CI 1.15-1.66).

These associations remained significant after adjustment for blood pressure or prior diagnosis of hypertension, which suggested that mechanisms other than blood-pressure effects may play a role in morbidity, authors noted.

As compared with an estimated potassium excretion of less than 1.50 g per day, a higher estimated excretion of potassium was associated with a reduction in the risks of death and cardiovascular events.

Global Sodium Consumption and Death From Cardiovascular Causes

In the third NEJM paper -- the NUTRICODE study -- researchers collected data from surveys conducted between March 2008 and December 2011 on sodium intake as determined by urinary excretion and diet in people from 66 countries (accounting for 74.1% of adults in the world) to quantify the global consumption of sodium according to age, sex, and country.

In 2010, the mean level of consumption of sodium worldwide was 3.95 g per day, and regional means ranged from 2.18 to 5.51 g per day.

Overall, 181 of 187 countries (99.2% of the adult population in the world) had estimated mean levels of sodium intake exceeding the World Health Organization recommendation of 2.0 g per day, and 119 countries (88.3% of the adult population in the world) exceeded this recommended level by more than 1.0 g per day.

Researchers also calculated the effects of sodium on blood pressure and cardiovascular mortality from data in a meta-analysis of 107 randomized interventions in 103 trials.

They found a linear dose-response relationship between reduced sodium intake and blood pressure.

Although estimated sodium-associated cardiovascular mortality was highest in Central Asia, it was high in all regions studied. There were more than 750 deaths per 1 million adults who were 70 years of age or older.

"Globally, 1.65 million annual deaths from cardiovascular causes (95% uncertainty interval [confidence interval], 1.10 million-2.22 million) were attributed to sodium intake above the reference level," they wrote.

The estimated number of proportional sodium-associated deaths was also high, approaching or exceeding 15% of premature deaths from cardiovascular causes in most regions.

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