Strict Limits on Salt Intake May Increase Negative Outcomes in HFpEF

Cautions to restrict salt intake should be tempered for patients with heart failure with preserved ejection fraction (HFpEF), according to an analysis of data from more than 1700 patients with this form of the condition.

Researchers found specifically that overly strict limitations on salt used in cooking by patients with HFpEF was significantly associated with higher risks of a composite of cardiovascular death, HF hospitalization, and aborted cardiac arrest. Their findings were published online July 18 in the journal Heart.

Salt restriction is a common recommendation in evidence-based heart failure guidelines but patients with HFpEF are often excluded from studies of the disease, investigators point out. This has been the case for decades, they state, even though HFpEF has gradually accounted for a higher proportion of the HF population and now accounts for half of all cases.

Despite these years of research as well as links to lower mortality associated with reduced sodium intake in the general population, “there is a lack of high-quality evidence to support salt intake restriction in patients with HF,” write the authors, from the Department of Cardiology Sun Yat-sen University First Affiliated Hospital, in China.

“As salt intake could significantly affect volume status and neurohormonal status, which might play a role in the response to treatment in HFpEF, we aimed to explore the effect of cooking salt restriction in patients with HFpEF."

“As salt intake could significantly affect volume status and neurohormonal status, which might play a role in the response to treatment in HFpEF, we aimed to explore the effect of cooking salt restriction in patients with HFpEF."

To do so, lead author Weihao Liang and colleagues tapped data from the TOPCAT (Aldosterone Antagonist Therapy for Adults with Heart Failure and Preserved Systolic Function) trial.

TOPCAT was a phase 3 randomized, double-blind, placebo-controlled trial assessing efficacy of spironolactone for symptomatic HFpEF. Investigators enrolled 3445 patients aged ≥50 years with left ventricular ejection fraction (LVEF) ≥45% who were then randomized to receive spironolactone or placebo.

From this original cohort, after exclusion for missing data and other concerns, investigators had a total of 1713 participants for inclusion in the current post-hoc analysis.

TOPCAT participants had completed a food questionnaire that was used to calculate individual “cooking salt scores" based on how much salt they routinely added per serving to staple homemade foods and expressed as points: 0=no salt, 1=1/8 tsp, 2=1/4 tsp, and 3=1/2 tsp+. A final cooking score summed these 4 scores for different types of foods.

The primary end point for the analysis was a composite of cardiovascular (CV) death, HF hospitalization, and aborted cardiac arrest; the secondary end points were CV death, all-cause death, and HF hospitalization.

Findings

Researchers divided participants into 2 cohorts: cooking salt score of 0 (n=816) and cooking salt score >0 (n=897). Median (IQR) ages were equivalent in the groups, at 72 (63-79) and 73 (64-79) years, respectively. The majority of participants in both groups were White (80.8% and 76.9%), had a previous HF hospitalization (62.6% and 55.1%), had hypertension (90.0% and 90.2%), and were taking diuretics (92.2% and 86.8%). All cooking salt scores were self-reported.

After a median follow-up of 2.4 years, participants with a cooking salt score of 0 compared to those with cooking salt scores >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).
• Were significantly heavier (97.34±25.81 kg vs 91.08±23.76 kg; P<.001)
• Had lower diastolic blood pressure (70.20±11.28 mmHg vs 72.35±11.61 mmHg; P<.001); systolic BP was similar.

When investigators analyzed the association of cooking salt score with primary and secondary outcomes, they found participants in the group with a cooking salt score >0 had a 24% reduced risk of the composite endpoint of CV death, HF hospitalization, and aborted cardiac arrest (HR, 0.76; 95% CI, 0.638-0.906; P=.002). This group also had a 26% reduced risk of HF hospitalization (HR, 0.737; 95% CI, 0.603-0.900; P = .003), a component of the secondary outcome.

Survival was not found to be significantly better, however, for participants with a cooking salt score >0 for the outcomes of all-cause death, at a reduction of 16% (HR, 0.838; 95% CI, 0.684-1.027; P=.088) or CV death, with a reduction of 22% (HR, 0.782; 95% CI, 0.598-1.020; P=.071).

In highlighting findings from subgroup analyses, investigators note that participants aged ≤70 years had significantly greater benefits from adding salt when cooking compared to those >70 years old as well as for the composite primary endpoint and HF hospitalization. Additionally, they observed that the benefits of adding cooking salt appeared greater for patients of non-White race with regard to the primary endpoint, although the result was not statistically significant. Finally, they report they found no significant difference in the association of cooking salt score and risks of outcomes between subgroups according to gender, previous HF hospitalization, and diuretics use.

“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.

Reference: Li J, Zhen Z, Huang P, Dong YG, Lie C, Liang W. Salt restrictions and risk of adverse outcomes in heart failure with preserved ejection fraction. Heart. Published online July 18, 2022. doi:10.1136/heartjnl-2022-321167