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. 2024 Aug 13;25(16):8811.
doi: 10.3390/ijms25168811.

Effects of SGLT2-Inhibitors on Comprehensive Geriatric Assessment, Biomarkers of Oxidative Stress, and Platelet Activation in Elderly Diabetic Patients with Heart Failure with Preserved Ejection Fraction

Marcello Magurno  1 , Velia Cassano  1 , Francesco Maruca  1 , Carlo Alberto Pastura  1 , Marcello Divino  1 , Federica Fazio  1 , Giandomenico Severini  1 , Elvira Clausi  1 , Giuseppe Armentaro  2 , Sofia Miceli  2 , Raffaele Maio  2 , Egidio Imbalzano  3 , Francesco Andreozzi  1   4 , Marta Letizia Hribal  1   4 , Angela Sciacqua  1   2   4
Affiliations

Effects of SGLT2-Inhibitors on Comprehensive Geriatric Assessment, Biomarkers of Oxidative Stress, and Platelet Activation in Elderly Diabetic Patients with Heart Failure with Preserved Ejection Fraction

Marcello Magurno et al. Int J Mol Sci. .

Abstract

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) represents a major comorbidity in the elderly and is associated with cognitive impairment (CoI) and type 2 diabetes mellitus (T2DM). In this context, there is an increase in oxidative stress and platelet activation biomarkers. The aim of this study was to evaluate the effects of 6 months' treatment with SGLT2i on functional, mood-related, and cognitive aspects, assessed by performing a comprehensive geriatric assessment (CGA), and on oxidative stress and platelet activation biomarkers, in a cohort of HFpEF elderly patients with T2DM. We recruited 150 elderly outpatients (mean age 75.8 ± 7.4 years).

Results: At six-month follow-up, there was a significant improvement in MMSE (p < 0.0001), MoCA (p < 0.0001), GDS score (p < 0.0001), and SPPB (p < 0.0001). Moreover, we observed a significant reduction in Nox-2 (p < 0.0001), 8-Isoprostane (p < 0.0001), Sp-Selectin (p < 0.0001), and Gp-VI (p < 0.0001). Considering ΔMMSE as the dependent variable, ΔE/e', ΔNox-2, ΔHOMA, Δ8-Isoprostane, and ΔUricemia were associated for 59.6% with ΔMMSE. When ΔMoCA was considered as the dependent variable, ΔHOMA, ΔE/e', Δ8-Isoprostane, ΔNox-2 and ΔUricemia were associated for 59.2%. Considering ΔGDS as the dependent variable, ΔHOMA, ΔNox-2, Δ8-Isoprostane, and ΔUricemia were associated with 41.6% of ΔGDS variation. Finally, ΔHOMA was the main predictor of ΔSPPB, which was associated with 21.3% with ΔSPPB, Δ8-Isoprostane, ΔNox-2, ΔE/e', and ΔUricemia added another 24.1%.

Conclusion: The use of SGLT2i in elderly patients with T2DM and HFpEF significantly contributes to improving CGA scales and biomarkers of OS and PA.

Keywords: SGLT2i; T2DM; cognitive impairment; elderly; oxidative stress.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Changes in oxidative stress biomarkers and platelet activation biomarkers between baseline and follow-up. Abbreviations: Nox-2: NAPDH Oxidase 2.
Figure 2
Figure 2
Changes in echocardiographic parameters between baseline and follow-up. Abbreviations: LAVI: left atrial volume index, E/e’: between wave E and wave e’ (reliable estimate of changes in end-diastolic blood pressure); s-PAP: systolic pulmonary arterial pressure; GLS: global longitudinal strain.
Figure 3
Figure 3
Changes in cognitive and functional parameters between baseline and follow-up. Abbreviations: MMSE: Mini-Mental state examination; MoCA: Montreal cognitive assessment; GDS: Geriatric Depression Scale; SPPB: short performance physical battery.
See this image and copyright information in PMC

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