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Excessive Salt Restriction Could Increase Risk of Negative Outcomes in HFpEF

A posthoc analysis of patients in the Americas from the TOPCAT trial provides insight into the relationship between excessive dietary salt restriction and risk of adverse outcomes in patients with heart failure with preserved ejection fraction.

An analysis of data from more than 1700 patients with heart failure with preserved ejection fraction (HFpEF) is highlighting the risk of excessive salt restriction among this patient population.

Despite links to lower mortality and event risk in the general population, results of the study, which was a posthoc analysis leveraging food questionnaire data from the TOPCAT trial, demonstrate those with the lowest levels of had a greater risk of events and heart failure hospitalization than their HFpEF counterparts with reporting other levels of salt intake.

“Results of the present study suggested that an overstrict cooking salt restriction was significantly associated with higher risks of the composite primary endpoint of cardiovascular death, heart failure hospitalization and aborted cardiac arrest in patients with HFpEF,” wrote investigators. “Additionally, an overstrict cooking salt restriction was also significantly associated with a higher risk of heart failure hospitalization but not cardiovascular or all-cause mortality.”

Although recommendations regarding salt intake are common, guideline-based recommendations among patients with heart failure are based on observational data. With more data emerging on the topic, including the SODIUM-HF trial, the current study was conducted by a team at the Sun Yat-sen University with an interest in further exploring associations between salt intake restriction and risk of adverse outcomes in patients with HFpEF.

A phase 3, randomized, double-blind, placebo-controlled trial, the TOPCAT trial randomized 3445 patients aged 50 years or older with a left ventricular ejection fraction of 45% or greater to spironolactone or placebo therapy. The trial’s primary outcome of interest was a composite of cardiovascular death, aborted cardiac arrest, or hospitalization for heart failure. After exclusion of those with missing data and due to location, investigators identified a cohort of 1713 patients for inclusion in their analyses.

In the food questionnaire, trial participants were asked how much salt they routinely added to the cooking of homemade food items, including rice, pasta, and potatoes, as well as soup, meat, and vegetables. For the purpose of analysis, these were scored as with 0 points for ‘none’, 1 point for ‘1/8 tsp’, 2 points for ‘1/4 tsp’, and 3 points for ‘more than 1/2 tsp’. The sum of these numbers was used as a final cooking salt score.

The primary outcome of interest for the study was a composite endpoint of cardiovascular death, heart failure hospitalization, and aborted cardiac arrest. Secondary outcomes of interest included all-cause mortality, cardiovascular mortality, and heart failure hospitalization. Investigators noted Cox proportional hazards model and subdistribution hazards model were used to estimate associations between salt intake and outcomes of interest.

Of the 1713 included in the analysis, 816 had cooking salt score of 0. Compared to those with cooking salt scores greater than 0, those with a cook salt score of 0 were more likely to be male (56.4% vs 44.7%; P <.001) and of white race (80.8% vs 76.9%; P=.013). These individuals were also significantly heavier (97.34±25.81 kg vs 91.08±23.76 kg; P <.001) and had lower diastolic blood pressure (70.20±11.28 mmHg vs 72.35±11.61 mmHg; P <.001) than their counterparts with cook salt scores greater than 0.

Upon analysis, investigators found those with a cook salt score greater than 0 had significantly lower risks of the primary endpoint (HR, 0.760 [95% CI, 0.638-0.906]; P=.002) and heart failure hospitalization (HR, 0.737 [95% CI, 0.603-0.900]; P=.003), but not all-cause (HR, 0.838 [95% CI, 0.684-1.027]; P=.088) or cardiovascular mortality (HR, 0.782 [95% CI, 0.598-1.020]; P=.071). Investigators noted similar results were observed in propensity score-matched analyses and among those who prepared meals mostly at home. Additional subgroups analyses suggested the association between overstrict salt restriction and poor outcomes was more predominant in patients aged 70 years or less and of non-white race.

“Overstrict dietary salt intake restriction could harm patients with HFpEF and is associated with worse prognosis. Physicians should reconsider giving this advice to patients with HFpEF. High-quality trials are needed to determine the optimal salt intake range for patients with HFpEF,” investigators added.

This study, “Salt restriction and risk of adverse outcomes in heart failure with preserved ejection fraction,” was published in Heart.