Pasquale Mone (1), Maria Luisa D'Onghia (1), Germano Guerra (1), Gaetano Santulli (2)

(1) Università degli Studi del Molise.
(2) Albert Einstein College of Medicine

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Background: Heart failure with preserved ejection fraction (HFpEF) is prevalent among patients with multiple comorbidities, particularly older adults, and is associated with an increased risk of frailty. Since frail older adults with HFpEF often experience multiple chronic conditions and are at risk for major complications, we reasoned that SHR may serve as a valuable prognostic marker in this vulnerable population. We investigated the relationship between SHR and cognitive impairment in a population of frail older adults with HFpEF.

Methods: We conducted a prospective observational study enrolling consecutive frail older adults with a prior diagnosis of HFpEF admitted to the local health unit of the Italian Ministry of Health (ASL) in Avellino, Southern Italy, between March 2021 and March 2022. Inclusion criteria were: age >65 years, confirmed diagnoses of frailty and HFpEF, and a Montreal Cognitive Assessment (MoCA) score <26.

Results: We screened 295 patients but 204 patients successfully completed the study. Participants were categorized into two groups based on SHR values: ≤1 or >1. Notably, patients in the SHR >1 group exhibited significantly lower global cognitive function compared to those in the SHR ≤1 group (MoCA in SHR ≤1: 21.06 ± 2.8 vs. MoCA in SHR >1: 19.52 ± 3.9; p = 0.0014). Through peripheral blood immunophenotyping, we detected significantly higher levels of Natural Killer T (NKT) cells in patients with SHR≤1 compared to SHR>1; in contrast, (PD-1, Programmed cell Death Protein 1), a key regulator of NKT cell activity,5 was more expressed in the SHR>1 group.

Discussion: Our findings suggest that SHR may serve as a new marker of cognitive impairment in this population, independent of diabetes status, as our cohort included individuals with diabetes, prediabetes, and normal glycemia. Additionally, NKT cells in patients with SHR≤1 might be associated with controlled immune responses, while the higher PD-1 expression in SHR>1 could be involved in the regulation of inflammation in the settings of HFpEF and its associated complications.