Clinical Context

Guidelines have suggested that persons with heart failure (HF) reduce their consumption of sodium to from less than 1.5 to less than 3 g/day. However, there is evidence from animal studies that a low-sodium diet may reduce cardiac output and increase peripheral resistance. Moreover, clinical trials have even demonstrated potential harm associated with sodium restriction among persons with HF. A study by Ezekowitz and colleagues, published in the April 9, 2022, issue of the Lancet, is enlightening.^[1]

This trial included patients with heart failure with reduced ejection fraction and heart failure with preserved ejection fraction (HFpEF), but many previous studies of diet and HF have excluded patients with HFpEF. The current study evaluates the effects of salt consumption on patients with HFpEF.

Study Synopsis and Perspective

Cutting out almost all salt when preparing meals was associated with a worse prognosis in patients with HFpEF, according to the results of a new study.

Results from a post hoc analysis of the TOPCAT trial show that those with a cooking salt score of zero were at significantly higher risk for the primary outcome of cardiovascular (CV) death, HF hospitalization, and aborted cardiac arrest than those whose score was above zero. Survival was similar in both groups.

"Some patients restrict dietary salt intake as least as possible according to their physicians' words or their own understanding. However, the present study found that, in patients with [HFpEF], overstrict salt restriction could lead to poor prognosis -- mainly heart failure hospitalization," explained Professor Chen Liu, MD, and Weihao Liang, MD, Sun Yat-sen University First Affiliated Hospital, Guangzhou, Guangdong, China.

"Thus, when giving salt restriction advice to patients with heart failure with preserved ejection fraction, physicians should be careful instead of just saying 'as least as possible,' " the authors said in an email to theheart.org | Medscape Cardiology.

The study was published online July 18 in Heart.^[2]

The authors note that HF guidelines recommend reduced salt intake, but that there is a lack of high-quality evidence to support those recommendations and no consensus on how low to go.

Previous studies have shown that reduced dietary sodium intake was associated with worse survival and higher readmission rate in patients with HF, whereas the SODIUM HF trial reported earlier this year that dietary sodium intake of less than 100 mmol (1500 mg) per day did not improve 1-year clinical outcomes, but moderately improved quality of life and New York Heart Association functional class.

"In daily clinical practice, we noticed that some physicians advised patients with heart failure to take salt as least as possible, but it could lead to hyponatremia and loss of appetite, which has been frequently reported to be associated with poor prognosis. Thus, we wanted to investigate the potential effect of overstrict salt restriction," Dr Liu and Dr Liang explained.

The investigators examined data from 1713 participants aged 50 years and older with HFpEF (left ventricular ejection fraction 45% or greater) in the phase 3 TOPCAT trial, excluding those from Russia and Georgia. Patients self-reported how much salt they added to cooking staples, such as rice, pasta, potatoes, soup, meat, and vegetables, and were scored as: 0 (none), 1 (1/8 tsp), 2 (1/4 tsp), and 3 (1/2 tsp or more) points. Median follow-up was 2.9 years.

TOPCAT failed to show that spironolactone improved CV outcomes over placebo, but regional differences in data from Russia/Georgia and the Americas have raised concerns about its validity.

In the present analysis, almost half the participants (n=816) had a cooking salt score of zero, 56.4% were male, and 80.8% were White. These participants were more likely than participants with a salt score greater than zero to have a previous HF hospitalization, diabetes, poor renal function, and a lower ejection fraction (57% vs 60%). Half were randomly assigned to spironolactone.

Compared with patients with a cooking salt score of zero, patients with a cooking salt score greater than zero had significantly lower risks for the primary outcome (hazard ratio [HR], 0.760; P=.002) and HF hospitalization (HR, 0.737; P=.003), but not all-cause (HR, 0.838) or CV (HR, 0.782) death.

The findings were consistent after full adjustment, with HRs of 0.834 (P=.046), 0.791 (P=.024), 0.944 (P=.583), and 0.872 (P=.320), respectively.

Results of subgroup analyses suggested that patients aged 70 years or younger) and those of Black and other ethnicities were at greater risk for the primary outcome from aggressive restriction of cooking salt.

"It was an interesting but unproved finding," Dr Liu and Dr Liang observed. "One possible explanation is the difference in [renin-angiotensin-aldosterone system] physiology and its response to salt restriction among races, and the other is the difference in accustomed food, because the cooking salt score only accounted for sodium added during cooking, but not sodium from ingredients."

Spearman correlation analyses showed that the cooking salt score correlated significantly with systolic and diastolic blood pressure, serum sodium, and chloronium levels, but not with plasma volume status, suggesting that low sodium intake did not have an intravascular volume contraction effect on patients with HFpEF.

The authors pointed out that the salt score was self-reported, hemodynamic parameters were seldom acquired in TOPCAT, and reverse causation between low dietary sodium intake and worse HF might still exist, despite a propensity score-matching sensitivity analysis.

Reached for comment, Mary Norine Walsh, MD, medical director of heart failure and cardiac transplantation, Ascension St. Vincent Heart Center, Indianapolis, Indiana, said in an email that the authors appropriately excluded patients enrolled from Russia and Georgia because of concerns about the representativeness of patients with HFpEF in these 2 countries, which has been previously demonstrated.

"What limits the importance of the authors' findings, which they acknowledge, is that the sodium intake for each patient was self-reported," she said. "No confirmatory testing was done, and recall bias could clearly have played a role."

"Last, many patients with HFpEF have significant volume overload and dyspnea, and appropriate sodium restriction is needed to help address symptoms and achieve a euvolemic state," added Dr Walsh, a past president of the American College of Cardiology.

Future trials are needed to determine an optimal salt restriction range for patients with heart failure, Dr Liu and Dr Liang suggested. "A randomized controlled trial may be hard to achieve because it is difficult to set a perfect control group. Therefore, an analysis using real-world data with a dose-response curve could be ideal."

The study was funded by the National Natural Science Foundation of China, Guangdong Natural Science Foundation, and China Postdoctoral Science Foundation. The authors have disclosed no relevant financial relationships.

Heart. Published July 18, 2022.

Clinical Implications

• In a previous randomized trial of a low-sodium diet vs usual care among adults with HF, there was no difference between the 2 groups in the primary composite outcome of emergency department or hospital visits for cardiovascular causes or all-cause mortality. There were also no significant differences in the low-sodium vs usual care groups in the individual outcomes of the composite.
• In the current study of adults with HFpEF, adding some salt to food in cooking was associated with a lower risk for HF hospitalization, although sodium consumption did not affect mortality outcomes.

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