Clinical Research in CardiologyNov 5, 2026, 13:14 GMT

Lower blood chloride linked to worse heart failure outcomes

Patients in the lowest fifth for both sodium and chloride had 1.3- to 1.7-fold higher heart failure event and death rates than those with higher levels of both.

Paper by João Pedro Ferreira, Faiez Zannad, Gerasimos Filippatos, +4Milton Packer

Figure 1 from Clinical Research in Cardiology — Figure 1. Ferreira et al.

Our read

Interventions

Studied:: Cohort study of 9,718 outpatients with heart failure (Placebo-controlled)
What changed:: Heart failure event and death rates were 1.3- to 1.7-fold higher with low versus higher sodium and chloride
The catch:: Greater loop-diuretic use in patients with low mineral levels could confound the outcome comparison
In the record:: The 148th paper on empagliflozin with results in people; 415 on record in all.
Why it’s aging research:: It studies an intervention with evidence of extending healthy life.

Editor of record: Boris Djordjevic · AgingResearch.News

Paper

Among 9,718 outpatients with heart failure, a pooled analysis of clinical trial data examined blood sodium and chloride levels, health outcomes and the effects of empagliflozin, a heart failure drug. Patients in the lowest fifth for both minerals had sodium below 140 mmol/L and chloride below 99 mmol/L.

Lower chloride was associated with higher death rates regardless of sodium levels. Lower sodium was associated with poorer outcomes only when chloride was also relatively low. Empagliflozin’s benefits did not vary with either mineral’s level. Compared with placebo, the drug slightly increased sodium and chloride by an average of 0.1 mmol/L each, particularly from week 32 onward. It also reduced bicarbonate, another blood electrolyte, by an average of 0.2 mmol/L.

Why it matters

Heart failure often affects older adults. The analysis addresses whether blood mineral measurements can help assess risk and inform expectations of drug benefit.

Caveats

The risk comparisons grouped patients by their starting blood levels, rather than testing whether changing those levels improved outcomes. Patients with lower levels of both minerals more often took loop diuretics, drugs that remove excess fluid.