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.

Obstructive sleep apneas (OSAs) and central sleep apneas (CSAs) are the most common comorbidities in Heart Failure (HF) that are strongly associated with all-cause mortality. Several therapeutic approaches have been used to treat CSA and OSA, but none have been shown to significantly improve HF prognosis. Our study evaluated the effects of a 3-months treatment with sodium-glucose cotransporter type 2 inhibitor (SGLT2i) on polygraphic parameters in patients with sleep apnea (SA) and HF, across the spectrum of ejection fraction, not treated with continuous positive air pressure (CPAP). A group of 514 consecutive elderly outpatients with HF, type 2 diabetes mellitus (T2DM) and SA, eligible for treatment with SGLT2i, were included in the investigation before starting any CPAP therapy. The two groups were compared with the t-test and Mann–Whitney test for unpaired data when appropriate. Then, a simple logistic regression model was built using 50% reduction in AHI as the dependent variable and other variables as covariates. A multivariate stepwise logistic regression model was constructed using the variables that linked with the dependent variable to calculate the odds ratio (OR) for the independent predictors associated with the reduction of 50% in AHI. The treated group experienced significant improvements in polygraphic parameters between baseline values and follow-up with reduction in AHI (28.4 ± 12.9 e/h vs. 15.2 ± 6.5 e/h; p < 0.0001), ODI (15.4 ± 3.3 e/h vs. 11.1 ± 2.6 e/h; p < 0.0001), and TC90 (14.1 ± 4.2% vs. 8.2 ± 2.0%; p < 0.0001), while mean SpO₂ improved (91. 3 ± 2.3 vs. 93.8 ± 2.5); p < 0.0001. These benefits were not seen in the untreated population. The use of SGLT2i in patients suffering from HF and mixed-type SA not on CPAP therapy significantly contributes to improving polygraphic parameters.

High-flow nasal cannula (HFNC) has several benefits in patients affected by different forms of acute respiratory failure, based on its own mechanisms. We postulated that HFNC may have some advantages over conventional oxygen therapy (COT) on the heart function in patients with acute-on-chronic respiratory failure with concomitant pulmonary hypertension (PH). We therefore designed this retrospective observational study to assess if HFNC improves the right and left ventricle functions and morphologies, arterial blood gases (ABGs), and patients’ dyspnea, compared to COT. We enrolled 17 hospitalized patients receiving HFNC, matched with 17 patients receiving COT. Echocardiographic evaluation was performed at the time of admission (baseline) and 10 days after (T₁₀). HFNC showed significant improvements in right ventricular morphology and function, and a reduction in sPAP. However, there were no significant changes in the left heart measurements with HFNC application. Conversely, COT did not lead to any modifications in echocardiographic measurements. In both groups, oxygenation significantly improved from baseline to T₁₀ (in the HFNC group, from 155 ± 47 to 204 ± 61 mmHg while in the COT group, from 157 ± 27 to 207 ± 27 mmHg; p < 0.0001 for both comparisons). In conclusion, these data suggest an improvement of oxygenation with both treatments; however, only HFNC was able to improve the right ventricular morphology and function after 10 days from the beginning of treatment in a small cohort of patients with acute-on-chronic respiratory failure with PH.

Background: Obstructive sleep apnoea syndrome (OSAS) is an independent risk factor for cardiovascular morbidity and mortality and has a detrimental effect on vascular function, in particular on arterial stiffness and endothelial function. Continuous positive airway pressure (CPAP) is the gold-standard therapy for OSAS and its effects on arterial stiffness and endothelial function have been demonstrated in non-elderly patients. Objectives: The objective of this study was to evaluate the effect of one year of CPAP treatment on arterial stiffness, through assessment of carotid–femoral pulse wave velocity (cf-PWV), and on endothelial function, through the reactive hyperaemia index (RHi), in a real-life cohort of elderly patients with moderate-to-severe OSAS and several comorbidities. Methods: In this nonrandomised prospective study, we enrolled 469 consecutive elderly patients affected by moderate-to-severe OSAS distributed in two groups: CPAP-treated (n = 225) and untreated patients (n = 244). Results: At one-year follow-up, in the treated group emerged an important improvement in poligraphics (AHI, ODI, TC90, mean SpO₂%), laboratory (HOMA index, eGFR, hs-CRP) and vascular function parameters: cf-PWV. The stepwise multivariate linear regression demonstrated a significant correlation between the delta of the polygraph parameters and the delta of PWV and RHi. Conclusions: Our study confirmed the favourable effects of CPAP therapy in a cohort of elderly patients affected by OSAS and several comorbidities on sleep respiratory parameters and vascular function; early diagnosis and treatment with CPAP might be beneficial to delay or prevent the occurrence of cardiovascular events in these groups of patients.

The ratio of high-sensitivity C-reactive protein (hs-CRP) to Serum albumin (SA) (hs-CRP/SA) is emerging as a new potential biomarker capable of stratifying cardiovascular risk in patients with chronic HF (CHF), particularly the risk of major adverse cardiovascular events (MACEs). Objectives: The aim of this study was to evaluate the long-term prognostic value of the hs-CRP/SA ratio on the risk of MACEs in a population of outpatients with CHF. Methods: In this retrospective observational study, 500 patients were enrolled and were stratified into two groups based on the median value of the hs-CRP/SA ratio: 249 patients with hs-CRP/SA < 1.19 and 251 patients with hs-CRP/SA ≥ 1.19. Results: During median follow-up of 5.2 years, 3.6 MACEs/100 patients/year were detected; patients with hs-CRP/SA ≥ 1.19 had a MACE incidence of 5.9 events per 100 patient-years, compared with 1.2 events per 100 patient-years in those with hs-CRP/AS < 1.19 (p < 0.001). Multivariate analysis confirmed that hs-CRP/SA ≥ 1.19 was associated with an approximately 6.5-fold increased risk of new MACEs (HR 6.513, 95% CI 3.928–10.797; p < 0.001). Conclusions: The hs-CRP/SA ratio is confirmed as a powerful prognostic marker in patients with CHF, associated with a significantly increased risk of MACEs.

Background: Elderly patients with heart failure with reduced ejection fraction (HFrEF) who experience worsening heart failure (wHF) remain at high residual risk despite optimal medical therapy (OMT), and data on cognitive function and comprehensive geriatric assessment (CGA) in this setting are lacking. This study evaluated the association between 12-month treatment with vericiguat and changes in cardiac, functional and geriatric parameters in elderly patients with recent wHF. Methods and results: In this single-center prospective observational study, 55 patients (45 men, mean age 76.4 ± 5.1 years) with HFrEF on OMT and a recent episode of wHF were treated with vericiguat and followed for 12 months. Clinical assessment, CGA and echocardiography including speckle-tracking were performed at baseline, 6, and 12 months. At 12 months, the mean vericiguat dose was 5.5 ± 2.9 mg/day. NT-proBNP levels decreased from 980 (467–2106) to 654 (274–1762) pg/mL (p < 0.0001), while left ventricular ejection fraction increased from 36.8 ± 3.1% to 43.4 ± 5.7% (p < 0.0001). Global longitudinal strain improved from −9.2 ± 1.7% to −11.5 ± 2.1% (p = 0.008), with parallel improvements in right ventricular function and pulmonary pressures. Cognitive performance improved (MMSE 25.1 ± 1.7 to 26.2 ± 2.1 points, p < 0.0001), as did depressive symptoms (GDS 7.8 ± 2.0 to 5.4 ± 1.6 points, p < 0.0001), physical performance (SPPB 6.7 ± 1.1 to 8.4 ± 0.9 points, p < 0.0001), and gait speed (0.70 ± 0.10 to 0.83 ± 0.06 m/s, p < 0.0001). Conley score decreased from 5.2 ± 2.3 to 2.4 ± 1.8 points (p < 0.0001), suggesting a lower risk of falls. Loop diuretic and MRA use were significantly reduced during follow-up. Conclusions: In this elderly HFrEF cohort with recent wHF on contemporary OMT, 12-month treatment with vericiguat was associated with consistent improvements in cardiac structure and function, biomarkers, and multidimensional geriatric status. These hypothesis-generating findings support the integration of CGA into future controlled studies of vericiguat in frail older patients with HFrEF. Given the observational design and lack of a control group, causal inference is not possible.