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.

Vitamin D represents a group of secosteroids involved in the calcium and phosphate metabolism. The active form of vitamin D, 1,25-dihydroxylcalciferol, exerts its biological mechanisms via the VDR (vitamin D receptor) which acts as a regulator of several target genes. Hypovitaminosis D is associated with many diseases, which are not only limited to the metabolism of the skeleton, but growing evidence links the deficit of vitamin D to cardiovascular, metabolic, immune, and neoplastic diseases. In regard to the cardiovascular system, current evidence shows the presence of VDR in endothelial cells. Moreover, both in vitro and animal experimental models demonstrated that the deficit of vitamin D can promote endothelial dysfunction and atherosclerosis development. Vitamin D can interfere with vascular functions also by affecting the production of vasodilator mediators. VDR is also expressed in left ventricle cardiomyocytes, and hypovitaminosis D can relate to cardiac hypertrophy and heart failure. Randomized clinical trials (RCT) designed to prove the therapeutic role of vitamin D supplementation have been inconclusive to date. The aim of this review is to highlight the main interactions between vitamin D metabolism and cardiovascular diseases; thus, focusing on pathogenic mechanisms and related clinical manifestations.