Sodium-Intake, Mortality Relationship Is Linear: HTN Trial Analysis

Marcia Frellick

October 05, 2016

BOSTON, MA — People with the lowest intake of sodium have the lowest rates of total mortality, according to a study spanning more than 20 years published October 3, 2016 in the Journal of the American College of Cardiology[1].

The findings by Dr Nancy R Cook (Brigham and Women's Hospital, Harvard Medical School, Boston, MA) and colleagues run counter to those of some previous studies that have found a J-curve effect, where people consuming the lowest amounts of sodium seemed also to have increased mortality or sometimes no increased risk.

"Everyone seems to agree that high levels of sodium are bad for you," Cook told heartwire from Medscape, "but there's a lot of controversy about the low end."

In the analysis, for every added 1000 mg/day of sodium (the equivalent of about a half-teaspoon per day), the risk of premature death went up by 12% (95% CI 1.00–1.26; P=0.05).

Dr Dariush Mozaffarian (Tufts University, Medford, MA), who is not connected with the analysis, told heartwire he hopes this study puts the controversy to rest.

"These are the kinds of studies you need to get a more valid answer," he said, adding, "There's not a single national or international organization that believes there's a J shape."

Cook and colleagues calculated mortality over 24 years for the patients in phase 1 (1987–1990) and phase 2 (1990–1995) of the Trials of Hypertension Prevention (TOHP), which analyzed the effect of sodium-reduction interventions on all-cause mortality based on multiple 24-hour urine samples from prehypertensive adults ages 30 to 54 years old.

They found no disadvantage to ingesting the lowest levels of sodium, as reflected by 24-hour urinary sodium excretion, and a direct linear association between average sodium intake and mortality.

Mortality by Levels of Sodium Excretion*

Sodium excretion (mg/d) Hazard ratio (95% CI) P for trend
<2300 0.75 (0.45–1.26)

 

0.30

2300 to <3600 0.95 (0.70–1.29)
3600 to <4800 1.0 (reference)
>4800 1.07 (0.75–1.54)
*Adjusted for age, sex, race/ethnicity, clinic, treatment, assignment, education status, baseline weight, alcohol use, smoking, exercise, potassium excretion (in sodium model), and family history of cardiovascular disease

The findings are the latest evidence in the evolving controversy about how much sodium a person should consume. Current dietary guidelines for Americans recommend levels below 2300 mg a day. This year the US Food and Drug Administration issued draft guidance to ask the food industry to help Americans gradually reduce average intake to 2300 mg, an approach Cook supports.

Why No J Curve?

Cook said there could be several reasons their results were different from some past studies in showing no J curve. First, "we were much less prone to bias. Many of the other studies included people with cardiovascular disease already or with hypertension, and when you've had an MI or stroke you're often advised to go on a low-salt diet or at least to reduce your sodium."

Therefore, they were still at high risk but they may have lowered their sodium, so it may look like there's an uptick at the bottom, she explained.

This study's population was healthy to start with, "which gives a clearer look at the question," she said.

She also pointed to the advantage of the 24-hour excretion samples, considered the gold standard of measuring excretion. The 24-hour samples give a more accurate picture than single excretion or a spot urine test from a morning sample used in other studies, she said.

Mozaffarian says the J-curve controversy is similar to that found in some studies for obesity, when it appeared that being a bit overweight was linked with lower mortality risk. But those studies included smokers and people who lost weight because they were sick.

"But when you got rid of the sick and got rid of the smokers, that J shape goes away. I think that's really what's going on with sodium."

In an accompanying editorial[2], Dr Andrew Mente (McMaster University, Hamilton, ON) and colleagues said that the findings showing no significant difference in mortality in the sodium-reduction groups were "disappointing, given the intensive nature of the dietary behavioral intervention used in the TOHP trials, the anticipated effects of sodium reduction reported by simulation modeling studies, and the emphasis placed on sodium reduction in guidelines."

The results are particularly important because TOPH phase 2 "is the largest clinical trial to evaluate a sodium-reduction intervention," he said.

The lack of J curve in the current study "isn't surprising," they write. "Detecting a nonlinear association between exposure and health outcomes requires much larger sample sizes and larger numbers of events than in the study by Cook et al."

In the future it would be interesting to investigate effects beyond blood pressure, Cook said, adding, "There have to be other effects on the vasculature, other than cardiovascular disease, so that may impact mortality as well."

Mente and others have called for large randomized, controlled trials to compare low vs moderate sodium intake.

But Mozaffarian notes that would be a massive undertaking: "You'd need 30,000 to 40,000 healthy people followed for 6 to 10 years kept on a low-sodium diet vs a regular-sodium diet. . . . I don't know if that's ever going to happen."

The authors and editorialists report that they have no relevant financial relationships. Mozaffarian reports no relevant financial relationships.

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