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
-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;
< 0.0001), ODI (15.4 ± 3.3 e/h vs. 11.1 ± 2.6 e/h;
< 0.0001), and TC90 (14.1 ± 4.2% vs. 8.2 ± 2.0%;
< 0.0001), while mean SpO
improved (91. 3 ± 2.3 vs. 93.8 ± 2.5);
< 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.
•In a cohort of elderly hospitalized patients suffering from Non-valvular Atrial Fibrillation on therapy with DOACs, women and men differed in the CHA2DS2VASc score: 5.3 ± 1.3 vs 4.2 ± 1.4 points (p ...< 0.0001) and in the HAS-BLED score: 2.5 ± 0.7 vs 2.3 ± 0.8 points (p = 0.009), which was significantly higher in women.•In this population Cognitive Impairment (CoI) and functional disabilities are widely represented.•Female sex increases the risk of being affected by CoI by approximately 3-fold, while improving functional limitations reduces this risk by approximately 15 %.•Furthermore, CoI and depressive symptoms increase the risk of functional impairment by approximately 2-fold and 28 %, respectively, while antihypertensive and antidiabetic therapy reduce this risk by 54 % and 43 %, respectively.
Atrial fibrillation (AF) represents the most common supraventricular arrhythmia, with a prevalence of 1–3 % in the world population. Growing evidences show that AF plays an important role as a risk factor for the development of cognitive impairment (CoI) and dementia, depression and functional limitation. The purpose of the study is to evaluate, in a large cohort of elderly hospitalized patients with nonvalvular AF (NVAF) on direct oral anticoagulants (DOACs) therapy, the prevalence of CoI, depression, and functional limitation, and to assess the different variables that may be detrimental or protective on the risk of CoI or functional limitation. 1004 elderly patients were enrolled, 384 men and 620 women, with a mean age of 84±7.1 years. The two groups were comparable for the main study variables, except for age, prevalence of hypertension and CKD, which were higher in women, while ischemic heart disease was higher in men. In addition, the two groups differed in the CHA2DS2VASc score 5.3 ± 1.3 vs 4.2 ± 1.4 pts (p < 0.0001) and HAS-BLED score 2.5 ± 0.7 vs 2.3 ± 0.8 pts (p = 0.009) that were significantly higher in women. Our study revealed that in a cohort of elderly patients hospitalized with AF taking DOACs, CoI and disability are widely represented, and female sex increases the risk of being affected by CoI by about 3-fold, while improvement of functional limitations reduce this risk by about 15 %. In addition, CoI and depressive symptoms increase the risk of functional impairment about 2-fold and 28 % respectively, while antihypertensive and anti-diabetic therapy reduce this risk.
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.
Background
Hypoalbuminemia is common in heart failure (HF) patients; however, there are no data regarding the possible long-term prognostic role of serum albumin (SA) in the younger population with ...chronic HF without malnutrition. The aim of this study was to examine the long-term prognostic role of SA levels in predicting major adverse cardiac events (MACE) in middle-aged outpatients with chronic HF.
Methods
In the present retrospective analysis, 378 subjects with HF were enrolled. MACE (non-fatal ischemic stroke, non-fatal myocardial infarction, cardiac revascularization or coronary bypass surgery, and cardiovascular death), total mortality, and HF hospitalizations (hHF) occurrence were evaluated during a median follow-up of 6.1 years.
Results
In all population, 152 patients had a SA value < 3.5 g/dL and 226 had a SA value ≥ 3.5 g/dL. In patients with SA ≥ 3.5 g/dL, the observed MACE were 2.1 events/100 patient-year; while in the group with a worse SA levels, there were 7.0 events/100 patient-year (
p
< 0.001). The multivariate analysis model confirmed that low levels of SA increase the risk of MACE by a factor of 3.1. In addition, the presence of ischemic heart disease, serum uric acid levels > 6.0 mg/dL, chronic kidney disease, and a 10-year age rise, increased the risk of MACE in study participants. Finally, patients with SA < 3.5 g/dl had a higher incidence of hHF (
p
< 0.001) and total mortality (
p
< 0.001) than patients with SA ≥ 3.5 g/dl.
Conclusions
Patients with chronic HF that exhibits low SA levels show a higher risk of MACE, hHF and total mortality.
Obstructive sleep apnea syndrome (OSAS) can lead to cognitive impairment and depression affecting memory, attention, and executive functions. Continuous positive airway pressure (CPAP) treatment ...seems to be able to revert changes in brain networks and neuropsychological tests correlated to OSAS. The aim of the present study was to evaluate the effects of a 6-month treatment with CPAP on functional, humoral and cognitive parameters in a cohort of elderly OSAS patients with several comorbidities. We enrolled 360 elderly patients suffering from moderate to severe OSAS and indication for nocturnal CPAP. At baseline the Comprehensive Geriatric Assessment (CGA) revealed a borderline Mini-Mental State Examination (MMSE) score that improved after 6-month treatment with CPAP (25.3 ± 1.6 vs 26 ± 1.5;
p
< 0.0001), as well as the Montreal Cognitive Assessment (MoCA) showed a mild improvement (24.4 ± 2.3 vs 26.2 ± 1.7;
p
< 0.0001). Moreover, functionality activities increased after treatment, as documented by a short physical performance battery (SPPB) (6.3 ± 1.5 vs 6.9 ± 1.4;
p
< 0.0001). Reduction of the Geriatric Depression Scale (GDS) from 6.0 ± 2.5 to 4.6 ± 2.2 (
p
< 0.0001) was also detected. Changes of homeostasis model assessment (HOMA) index, oxygen desaturation index (ODI), sleep-time spent with saturation below 90% (TC90), peripheral arterial oxyhaemoglobin saturation (SpO
2
), apnea–hypopnea index (AHI) and estimation of glomerular filtration rate (eGFR), contributed, respectively, to 27.9%, 9.0%, 2.8%, 2.3%, 1.7% and 0.9% of MMSE variability for a total of 44.6% of MMSE variations. GDS score changes were due to the improvement of AHI, ODI and TC90, respectively, for 19.2%, 4.9%, 4.2% of the GDS variability, cumulative responsible for 28.3% of GDS modifications. The present real-world study shows that CPAP treatment is able to improve cognition and depressive symptoms in OSAS elderly patients.
Abstract
Aim
Heart failure (HF) is associated to endothelial dysfunction, a pathological condition characterized by imbalance between the production of vasoconstrictor and vasodilator factors, ...increase in the production of cytokines, down-regulation of eNOS, platelets activation and increased oxidative stress. Furthermore, endothelial dysfunction promotes the increase of arterial stiffness, augmenting myocardial damage. Sacubitril/Valsartan (sac/val) is used in the treatment of HF reduced ejection fraction (HFrEF) and has been proven effective in reducing CV disease progression and all-cause mortality in HFrEF patients. The aim of the study was to evaluate the effect of sac/val on endothelial dysfunction and arterial stiffness in patients with HFrEF, at baseline and after 6 months of treatment. Moreover, we evaluated the effects of sac/val on oxidative stress levels and platelets activation.
Materials Methods
We enrolled 46 Caucasian patients (mean age 70.1±7.1), suffering from HFrEF. Inclusion criteria were LVEF<35, functional class NYHA II or III. All clinical evaluation and laboratory tests were performed at baseline and after 6 months of treatment. The serum values of the markers of oxidative stress (8-isoprostane, NOX-2) and platelets activation (Sp-selectin, GPVI) were assessed with ELISA sandwich. Endothelial function was estimated with the measurement of the reactive hyperemia index (RHI); arterial stiffness (AS) was evaluated with the measurement of carotid-femoral pulse wave velocity (PWV), augmentation pressure (AP) and augmentation index (AI).
Results
The mean dose of sac/val was 180.5±110 mg without serious adverse events. At 6 months, data showed a significant improvement in in hemodynamic and clinical parameters such as heart rate (HR) (p<0.0001), NT-ProBNP (p<0.0001), fasting plasma glucose (FPG) (p<0.0001). Furthermore, there was a significant reduction in oxidative stress, platelets activation and inflammatory indices. We observed a significant improvement in PWV (p<0.0001), AI (p<0.0001), AP (p<0.0001) and RHI (p<0.0001). A linear correlation analysis was performed to assess the association between vascular parameters and different covariates expressed as Δ variation between baseline and follow-up. ΔPWV was directly correlated with ΔHOMA (p=0.037), ΔIL-6 (p=0.034), ΔTNF-α (p=0.001), Δ8-isoprostane (p=0.016), ΔNox-2 (p=0.01), ΔGP6 (p=0.018), ΔSp-selectin (p=0.023); ΔRHI was inversely correlated with ΔHOMA (p=0.003), ΔIL-6 (p=0.004), ΔTNF-α (p=0.023), ΔCRP (p=0.011), Δ8-isoprostane (p=0.012), ΔNox-2 (p=0.01), ΔGP6 (p=0.014), ΔSp-selectin (p=0.015). From stepwise multivariate linear regression model, ΔTNF-α was the stronger predictor of ΔPWV, justifying 48.5% of its variation and ΔSp-selectin was the major predictor of ΔRHI explaining 23.2% of its variation.
Conclusion
The treatment with sac/val improved endothelial dysfunction and arterial stiffness, due to reduced levels of oxidative stress, platelet activation and inflammation.
Abstract
Aim
Atrial fibrillation (AF) is the most common cardiac arrhythmia globally and is associated with a five-fold increased risk of stroke compared with patients without AF. Although large ...clinical trials have demonstrated the noninferiority of NOACs to VKAs in preventing stroke and systemic thromboembolism and their use is recommended by the guidelines, the role of antithrombotic therapies on the risk of major adverse cardiac events (MACE) in a high-risk population, such as the elderly, is still controversial (2). The aim of this work is to evaluate any differences on the occurrence of MACE among NOACs-treated patients versus VKAs in an elderly population with AF and other critical comorbidities.
Materials and Methods
420 caucasian patients with non-valvular AF, aged ≥65 years were enrolled, 136 in treatment with VKAs and 284 with NOACs, with mean age 76.7±5.7. A clinical-instrumental and laboratory evaluation was performed for a follow-up of 93.9 months. Statistical analysis was performed with Wicoxon's test, Student's t-test, log rank test, univariate and multivariate Cox regression model in order to calculate the hazard ratio (HR) for independent predictors associated with the incidence of MACE.
Results
The two groups were overlappings for sex, smoking, T2DM. NOACs group had a higher prevalence of: HF (110 vs 32, p=0.002), COPD (127 vs 39 p = 0.001), arterial hypertension (266 vs 112, p = 0.0003) and they were older than VKAs group (78.4±4.7 vs 73.2±5.9 years; p<0.0001). In the whole general population at baseline, the following values were detected: estimated glomerular filtration rate (eGFR) 64.6 ± 18.2 ml/min/1.73 m2, Systolic blood pressure (BP)132.5±11.6 mmHg, diastolic BP 76.6±9.5 mmHg, BMI 29.4±4.8 Kg/m2. In patients treated with NOACs, MACEs observed were 44 (2.4 events /100 patient-years), while in the group treated with VKAs were 76 (7.2 events/100 patient-years) (p <0.0001). A multivariate analysis model showed that an enhancement of 1g/dl of albuminemia value (HR 0.565, p=0.033), taking a therapy with β-blockers (HR 0.621, p=0.013), ACE inhibitors or ARBs (HR 0.695, p=0.024) were protective factors for the onset of MACE, while VKAs therapy (HR 2.596, p<0.0001) and HF (HR 1.471, p<0.0001) increased the risk of MACE in patients with AF.
Conclusions
The data of present study confirm a better safety profile of NOACs compared to VKAs on the occurrence of MACE in an elderly population with critical comorbidities, even though patients treated with NOACs were older and had a greater burden of comorbidities that negatively affect the risk of MACE such as: arterial hypertension, COPD and heart failure.
Abstract
Aim
Non Valvular Atrial fibrillation (NVAF) is an independent predictor of cardiovascular (CV) mortality and morbidity. The incidence and prevalence increase in proportion to age and ...comorbidity burden. Non vitamin K oral anticoagulants (NOACs) are as effective as VKAs with a better safety profile, ensuring a lower incidence of major bleeding. NVAF and Chronic Kidney Disease (CKD) are mutually connected and often coexist in the elderly patient. NVAF is a risk factor for the progression of CKD, the prevalence and incidence of NVAF increase with decrease in renal function, CKD also increases the risk of bleeding and thromboembolism, making risk stratification and treatment difficult. All available NOACs are partially eliminated by the kidneys therefore, renal function inevitably influences our therapeutic strategies. The aim of this work is to evaluate any differences between VKAs versus NOACs patient's on the decline of renal function in elderly population with NVAF and important comorbidities.
Materials and Methods
We enrolled 411 Caucasian patients aged ≥70 years, affected by NVAF with important comorbidities; 135 patients receiving VKAs and 276 receiving NOACs, median age was 77.2 years (IQR 72.7-81.6). Patients underwent clinical-instrumental and laboratory evaluation for a follow-up of 6.9±2.5 years. Patients with severe hepatic impairment or ClCr <15 mL/min were excluded from this study. Rapid decline in renal function was defined as annual loss ≥5 mL/min/1.73 m2 and estimated as events/year. Data were expressed as mean and standard deviation or as median and interquartile range (IQR) when appropriate.
Results
During an average follow-up of 6.9±2.5 years there were statistically significantly differences between NOACs and VKAs in: eGFR values 48.2 (IQR 40.3-58.6) vs. 39.7 (IQR 32.4-47.8) ml/min/1.73 m2, p=0.0001; Delta eGFR -9.1 (IQR -14.3/-5.2) vs -29.8 (IQR -40.9/-18.9) ml/min/1.73 m2, p=0.0001; Delta eGFR/year -1.6 (IQR -2.6/-0.9) vs 2.9 (IQR -5.0/-2.0) ml/min/1.73 m2, p=0.0001; and in glycaemia (p<0.0001), systolic blood pressure (SBP) (p<0.0001), haemoglobin (HB) (p<0.0001), number events/year 35/135 (25.9%) vs 36/276 (13.0%), p=0.001). In the NOACs group, a linear correlation analysis was performed between eGFR and different covariates expressed as variation (Δ) between baseline and follow-up. ΔeGFR was significantly correlated with diastolic blood pressure (ΔDBP), ΔSBD, ΔBMI and ΔHb. From stepwise model, ΔHb was the major predictor of ΔeGFR, justifying 18.0% of its variation.
Conclusions
The data from the present study confirm a better safety profile of NOACs compared with VKAs on the occurrence of rapid decline in renal function in an elderly population with numerous comorbidities, despite the NOACs group having lower baseline eGFR values than VKAs.
Abstract
Aim
Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) is mainly produced by the liver, but it is also expressed in the heart. It plays a key role in cholesterol's metabolism. Recent ...studies suggest its possible role in cardiovascular (CV) diseases, promoting vascular inflammation, reactive oxygen species generation and atherosclerotic plaque formation. Global longitudinal strain (GLS), global myocardial work efficiency (GWE), reservoir (PALS) and pump (PACS) atrial function evaluated by speckle-tracking echocardiography are able to identify early subclinical ventricular and atrial myopathy. In the last years PCSK9 inhibitors have been introduced as innovative therapies for LDL plasma levels's reduction. The aim of our study was to investigate PCSK9 inhibitors's effects in secondary prevention's patients, equally assigned to Alirocumab or Evolocumab, who were statin-intolerant and/or not reaching the target of LDL-C <55 mg/dl using the maximum tolerated drugs’ dosage at basal time and on semestral follow-up.
Methods
We selected 30 patients (24 males and 6 females, mean age 66+8 years old), having several comorbidities: hypertension (97%), ICM (90%), CKD II-III stage (70%), polidistrectual atherosclerosis (67%), T2DM (50%), OSAS-COPD (20%), HF NYHA class II-III (20%). They underwent anthropometrical evaluation, biochemical analysis, oxidative stress markers assessment, liver elastography, and advanced echocardiogram at basal time and after six months of therapy. NOX-2 and Sp-selectin were assessed with ELISA sandwich. Data were analyzed with ANOVA, post-hoc Bonferroni's test and Chi-square. Linear correlation analysis was performed for variables whose variation were statistically significant.
Results
As expected, lipid profile was greatly improved in all the subjects, reaching the target of LDL-C <55 mg/dl. We obtained a statistically significant reduction of total-cholesterol (32%, p<0,0001), LDL-C (60%, p<0,0001), TG (26%, p<0,0001), TG/HDL ratio (27%, p<0,0001); an increase of HDL-C (9%, p=0.001) and an improvement of glomerular filtrate evaluated by CKD-EPI (6%, p=0.007). We observed a statistically significant reduction of NOX-2 (27%, p<0,0001) and Sp-selectin (36%, p<0,0001). We obtained a statistically significant increase of PALS (16.9%, p<0,0001), PACS (21%, p<0,0001), GWE (9.7%, p<0,0001), GLS (24%, p<0,0001) and a statistically significant reduction of global wasted work (GWW; 15%, p<0,0001), left atrial volume index (LAVI; 8%, p<0,0001) and E/e’ ratio (19%, p<0,0001). The results of linear correlation analysis showed that PACS was significantly and inversely correlated with TG/HDL (r=-0.406, p=0.013) and NOX-2 (r=-0.416, p=0.011); PALS was significantly and inversely correlated with TG/HDL (r=-0.473, p=0.004) and NOX-2 (r=-0.435, p=0.008); E/e’ was significantly and directly correlated with TG/HDL (r=0.654, p<0.0001) and NOX-2 (r=0.438, p=0.008); GWE was inversely correlated with NOX-2 (r=-0.422, p=0.01).
Conclusions
Our study demonstrated for the first time that PCSK9 inhibitors are able to reduce left ventricular filling pressure, to increase atrial function (reservoir and pump), global cardiac performance (GLS and GWE), and eGFR after six months of treatment in high CV risk population. Our results could be partially explained with a reduction of oxidative stress markers, inflammation and cardio-lipotoxicity, probably linked to a modulation of PCSK9's heart expression and its toxic effect on CV and renal function. In addition, we observed a TG/HDL ratio's reduction, related to cardiometabolic and lipid profile improvement. Further studies are necessary to better investigate systemic benefit in a larger population with longer follow-up.
