Mean platelet volume (MPV) as new marker of diabetic macrovascular complications in patients with different glucose homeostasis : Platelets in cardiovascular risk.

BACKGROUND: Platelets play an important role in the development of cardiovascular disease (CVD). Mean platelet volume (MPV) is considered as biological marker of platelets activity and function. The aim of the present study was to evaluate MPV values and its possible correlation with arterial stiffness and subclinical myocardial damage, in normal glucose tolerance patients (NGT), in newly diagnosed type 2 diabetic (T2DM) patients and in individuals with pre-diabetes. METHODS: We enrolled 400 newly diagnosed hypertensive patients. All patients underwent an Oral Glucose Tolerance test (OGTT). Arterial stiffness (AS) was evaluated with the measurement of carotid-femoral pulse wave velocity (PWV), augmentation pressure (AP) and augmentation index (AI). Echocardiographic recordings were performed using an E-95 Pro ultrasound system. RESULTS: Among groups there was an increase in fasting plasma glucose (FPG) (p < 0.0001), fasting plasma insulin (FPI) (p < 0.0001), high sensitivity c reactive protein (hs-CRP) levels (p < 0.0001) and a decrease in renal function as demonstrated by e-GFR values (p < 0.0001). From the NGT group to the T2DM group there was a rise in MPV value (p < 0.0001). Moreover, in the evaluation of arterial stiffness and subclinical myocardial damage, MPV showed a positive correlation with these parameters. CONCLUSIONS: In the present study we highlighted that MPV is significantly increased, not only in newly diagnosed T2DM patients, but also in early stage of diabetes, indicating that subjects with pre-diabetes present increased platelets reactivity. Moreover, our results suggest that MPV is associated with increased arterial stiffness and subclinical myocardial damage, indicating MPV as new marker of CV risk.

Pharmacological treatment of type 2 diabetes in elderly patients with heart failure: randomized trials and beyond.

Heart failure (HF) and type 2 diabetes mellitus (T2DM) represent two important public health problems, and despite improvements in the management of both diseases, they are responsible for high rates of hospitalizations and mortality. T2DM accelerates physiological cardiac aging through hyperglycemia and hyperinsulinemia. Thus, HF and T2DM are chronic diseases widely represented in elderly people who often are affected by numerous comorbidities with important functional limitations making it difficult to apply the current guidelines. Several antidiabetic drugs should be used with caution in elderly individuals with T2DM. For instance, sulfonylureas should be avoided due to the risk of hypoglycemia associated with its use. Insulin should be used with caution because it is associated with higher risk of hypoglycemia, and may determine fluid retention which can lead to worsening of HF. Thiazolindinediones should be avoided due to the increased risk of fluid retention and HF. Biguanides may lead to a slightly increased risk of lactic acidosis in particular in elderly individuals with impaired renal function. Dipeptidyl peptidase 4 (DPP-4) inhibitors are safe having few side effects, minimal risk of hypoglycemia, and a neutral effect on cardiovascular (CV) outcome, even if it has been reported that saxagliptin treatment is associated with increased risk of hospitalizations for HF (hHF). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a CV protection without a significant reduction in hHF. On the other hand, sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown a significant improvement in CV outcome, with a strong reduction of hHF and a positive impact on renal damage progression. However, it is necessary to consider the possible some side effects related to their use in elderly individuals including hypotension, bone fractures, and ketoacidosis.It is important to remark that elderly patients, in particular the very elderly, are not sufficiently represented in the trials; thus, the management and treatment of elderly diabetic patients with HF should be mainly based on the integration of scientific evidence with clinical judgment and patients' condition, with respect to the dignity and quality of life.

Impaired insulin-stimulated myocardial glucose metabolic rate is associated with reduced estimated myocardial energetic efficiency in subjects with different degrees of glucose tolerance.

BACKGROUND: Alterations in myocardial mechano-energetic efficiency (MEEi), which represents the capability of the left ventricles to convert the chemical energy obtained by oxidative metabolism into mechanical work, have been associated with cardiovascular disease. Although whole-body insulin resistance has been related to impaired myocardial MEEi, it is unknown the relationship between cardiac insulin resistance and MEEi. Aim of this study was to evaluate the relationship between insulin-stimulated myocardial glucose metabolic rate (MrGlu) and myocardial MEEi in subjects having different degrees of glucose tolerance. METHODS: We evaluated insulin-stimulated myocardial MrGlu using cardiac dynamic positron emission tomography (PET) with 18F-Fluorodeoxyglucose (18F-FDG) combined with euglycemic-hyperinsulinemic clamp, and myocardial MEEi in 57 individuals without history of coronary heart disease having different degrees of glucose tolerance. The subjects were stratified into tertiles according to their myocardial MrGlu values. RESULTS: After adjusting for age, gender and BMI, subjects in I tertile showed a decrease in myocardial MEEi (0.31 ± 0.05 vs 0.42 ± 0.14 ml/s*g, P = 0.02), and an increase in myocardial oxygen consumption (MVO2) (10,153 ± 1375 vs 7816 ± 1229 mmHg*bpm, P < 0.0001) as compared with subjects in III tertile. Univariate correlations showed that insulin-stimulated myocardial MrGlu was positively correlated with MEEi and whole-body glucose disposal, and negatively correlated with waist circumference, fasting plasma glucose, HbA1c and MVO2. In a multivariate regression analysis running a model including several CV risk factors, the only variable that remained significantly associated with MEEi was myocardial MrGlu (ß 0.346; P = 0.01). CONCLUSIONS: These data suggest that an impairment in insulin-stimulated myocardial glucose metabolism is an independent contributor of depressed myocardial MEEi in subjects without history of CHD.

Association between right ventricular dysfunction and adverse cardiac events in mild COPD patients.

BACKGROUND: Lung hyperinflation and systemic inflammation are currently believed to be the most important causes of right heart alterations in chronic obstructive pulmonary disease (COPD) patients. A multicentre observational study was performed to assess the morphological and functional parameters of right ventricle (RV) in COPD subjects, as well as to evaluate the potential prognostic impact on the development of major cardiovascular adverse events (MACEs). METHODS: For this retrospective study, from 1 January 2010 to 31 December 2021, we enrolled COPD patients on the basis of their airflow limitation. In particular, we selected subjects spanning across GOLD 1 and 2 functional stages. Clinical, laboratory and functional parameters were collected at baseline. Echocardiography was routinely performed in all COPD patients. RV dysfunction was defined on the basis of tricuspid annular plane systolic excursion (TAPSE) values. MACE occurrence (non-fatal ischemic stroke, non-fatal myocardial infarction, cardiac revascularization or coronary bypass surgery and cardiovascular death) was evaluated during a median follow-up of 55 (36-72) months. RESULTS: Among the 749 enrolled patients, 408 subjects had a TAPSE value ≥20 mm, while the remaining 341 had a TAPSE value <20 mm. In patients with TAPSE ≥20 mm the observed MACEs were 1.9 events/100 patient-year, while in the group with a worse right heart function there were 4.2 events/100 patient-year (p < .0001). The multivariate analysis model confirmed the association between RV dysfunction and MACE. Indeed, a 1-mm increase in TAPSE value and the intake of long-acting ß2 -receptor agonists (LABA)/long-acting muscarinic antagonist (LAMA) inhaled therapy were protective factors for the onset of MACE, while the presence of diabetes mellitus and high values of both uric acid (UA) and systolic pulmonary arterial pressure (S-PAP) enhanced the risk of MACE in study participants. CONCLUSIONS: The results of this study showed that in patients with mild COPD there is an association between right heart dysfunction and the risk of MACE during follow-up.

One-hour post-load glucose and subclinical left atrial myocardial dysfunction in hypertensive patients.

BACKGROUND: Recently, studies demonstrated that normal glucose-tolerant subjects (NGT) with 1-h post-load plasma glucose value ≥155 mg/dL during oral glucose tolerance test (OGTT) (NGT ≥ 155) present an impaired cardio-metabolic profile, with subclinical myocardial damage. Atrial morphological and functional alterations, closely related to diastolic dysfunction, are important predictors of atrial fibrillation (AF), cardiovascular (CV) events and mortality in the entire population as well as in diabetic patients. The aim of our study was to evaluate subclinical atrial myocardial damage, assessed with speckle tracking echocardiography, in NGT≥155 mg/dL patients, comparing to NGT < 155 mg/dL subjects, impaired glucose tolerant (IGT) individuals and patients with newly diagnosed type 2 diabetes (T2DM). METHODS: We enrolled 229 Caucasian patients. All subjects underwent anthropometrical and haemodynamic parameters evaluation, OGTT, advanced Colour-Doppler echocardiography with evaluation of main atrial and ventricular parameters. RESULTS: As expected, from first to the fourth group there was a worsening of the metabolic profile as attested by fasting, 1- and 2-h post-load plasma glucose levels, during OGTT. Moreover, from NGT < 155 to T2DM group there was an impairment in reservoir and pump atrial function (PALS and PACS, respectively) (p < .0001). CONCLUSION: Present data demonstrated for the first time that NGT≥155 subjects present subclinical atrial dysfunction. These results may be clinically relevant because they highlight how atrial myopathy occurs early in pre-diabetes stage regardless of fibrotic and morphological alterations of the ventricular myocardium.

Effects of 26 weeks of treatment with empagliflozin versus glimepiride on the myocardial glucose metabolic rate in patients with type 2 diabetes: The randomized, open-label, crossover, active-comparator FIORE trial.

AIM: To determine whether treatment with empagliflozin was able to affect the myocardial glucose metabolic rate, as assessed by cardiac dynamic 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET) combined with euglycaemic-hyperinsulinaemic clamp compared with glimepiride in patients with type 2 diabetes. MATERIALS AND METHODS: To further investigate the cardioprotective mechanism of sodium-glucose co-transporter-2 inhibitors, we performed a 26-week, randomized, open-label, crossover, active-comparator study to determine the effects of empagliflozin 10 mg versus glimepiride 2 mg daily on the myocardial glucose metabolic rate assessed by cardiac dynamic 18 F-FDG-PET combined with euglycaemic-hyperinsulinaemic clamp in 23 patients with type 2 diabetes. We also measured cardiac geometry and myocardial mechano-energetic efficiency, as well as systolic and diastolic function by echocardiography. RESULTS: Compared with glimepiride, treatment with empagliflozin resulted in a greater reduction in the myocardial glucose metabolic rate from baseline to 26 weeks (adjusted difference -6.07 [-8.59, -3.55] µmol/min/100 g; P < .0001). Moreover, compared with glimepiride, empagliflozin led to significant reductions in left atrial diameter, left ventricular end-systolic and end-diastolic volumes, N-terminal pro b-type natriuretic peptide levels, blood pressure, heart rate, stroke work, and myocardial oxygen consumption estimated by the rate pressure product, and increases in ejection fraction, myocardial mechano-energetic efficiency, red blood cells, and haematocrit and haemoglobin levels. CONCLUSIONS: The present study provides evidence that empagliflozin treatment in subjects with type 2 diabetes without coronary artery disease leads to a significant reduction in the myocardial glucose metabolic rate.

Sex-specific differences in left ventricular mass and myocardial energetic efficiency in non-diabetic, pre-diabetic and newly diagnosed type 2 diabetic subjects.

BACKGROUND: Women with type 2 diabetes (T2DM) have a higher excess risk for cardiovascular disease (CVD) than their male counterparts. However, whether the risk for CVD is higher in prediabetic women than men is still debated. We aimed to determine whether sex-related differences exist in left ventricular mass index (LVMI), and myocardial mechano-energetic efficiency (MEEi) in with normal glucose tolerant (NGT), pre-diabetic and newly diagnosed type 2 diabetic subjects. METHODS: Sex-related differences in LVMI and myocardial MEEi, assessed by validated echocardiography-derived measures, were examined among 1562 adults with NGT, prediabetes, and newly diagnosed T2DM, defined according to fasting glucose, 2-h post-load glucose, or HbA1c. RESULTS: Worsening of glucose tolerance in both men and women was associated with an increase in age-adjusted LVMI and myocardial MEEi. Women with newly diagnosed T2DM exhibited greater relative differences in LVMI and myocardial MEEi than diabetic men when compared with their NGT counterparts. Prediabetic women exhibited greater relative differences in myocardial MEEi, but not in LVMI, than prediabetic men when compared with their NGT counterparts. The statistical test for interaction between sex and glucose tolerance on both LVMI (P < 0.0001), and myocardial MEEi (P < 0.0001) was significant suggesting a sex-specific association. CONCLUSIONS: Left ventricle is subject to maladaptive changes with worsening of glucose tolerance, especially in women with newly diagnosed T2DM. The sex-specific increase in LVM and decrease in MEEi, both being predictors of CVD, may have a role in explaining the stronger impact of T2DM on the excess risk of CVD in women than in men.

The TRIB3 R84 variant is associated with increased left ventricular mass in a sample of 2426 White individuals.

BACKGROUND: Prior studies in animal models showed that increased cardiac expression of TRIB3 has a pathogenic role in inducing left ventricular mass (LVM). Whether alterations in TRIB3 expression or function have a pathogenic role in inducing LVM increase also in humans is still unsettled. In order to address this issue, we took advantage of a nonsynonymous TRIB3 Q84R polymorphism (rs2295490), a gain-of-function amino acid substitution impairing insulin signalling, and action in primary human endothelial cells which has been associated with insulin resistance, and early vascular atherosclerosis. METHODS: SNP rs2295490 was genotyped in 2426 White adults in whom LVM index (LVMI) was assessed by validated echocardiography-derived measures. RESULTS: After adjusting for age and sex, LVMI progressively and significantly increased from 108 to 113, to 125 g/m2 in Q84Q, Q84R, and R84R individuals, respectively (Q84R vs. Q84Q, P = 0.03; R84R vs. Q84Q, P < 0.0001). The association between LVMI and the Q84R and R84R genotype remained significant after adjusting for blood pressure, smoking habit, fasting glucose levels, glucose tolerance status, anti-hypertensive treatments, and lipid-lowering therapy (Q84R vs. Q84Q, P = 0.01; R84R vs. Q84Q, P < 0.0001). CONCLUSIONS: We found that the gain-of-function TRIB3 Q84R variant is significantly associated with left ventricular mass in a large sample of White nondiabetic individual of European ancestry.

Neutrophil degranulation biomarkers characterize restrictive echocardiographic pattern with diastolic dysfunction in patients with diabetes.

OBJECTIVE: To investigate the potential association between neutrophil degranulation and patterns of myocardial dysfunction in a cohort of patients with type 2 diabetes mellitus (T2DM). BACKGROUND: Two distinct phenotypes of diabetic cardiomyopathy have been described: a restrictive phenotype with diastolic dysfunction (restrictive/DD) and a dilative phenotype with systolic dysfunction (dilative/SD). However, the underlying determinants of these two patterns are not yet recognized. METHODS: In this single-centre, observational, cross-sectional study, 492 patients were recruited. Ultrasonographic measurements were performed by two experienced sonographers, blinded to the clinical data of the participants. Serum biomarkers of neutrophil degranulation were measured by enzyme-linked immunosorbent sandwich assay (ELISA). RESULTS: After adjustment for confounders, resistin, myeloperoxidase, matrix metalloproteinase 8 and matrix metalloproteinase 9/tissue inhibitor of metalloproteinases 1 complex were positively associated with the restrictive/DD pattern compared with the normal pattern. Similarly, MPO was positively associated with the dilative/SD pattern compared with the normal pattern, and resistin was negatively associated with the dilative/SD pattern compared with the restrictive/DD pattern. CONCLUSIONS: Neutrophil degranulation is associated with the restrictive/DD echocardiographic pattern in patients with T2DM, but not with the normal pattern and dilative/SD patterns. Neutrophils could have a pivotal role in the pathogenesis of myocardial dysfunction, and particularly diastolic dysfunction, in patients with T2DM.

Ferritin modifies the relationship between inflammation and arterial stiffness in hypertensive patients with different glucose tolerance.

BACKGROUND: Ferritin, a crucial element for iron homeostasis, is associated with chronic diseases characterized by subclinical inflammation such as essential arterial hypertension and type 2 diabetes mellitus (T2DM), showing a prognostic value in different clinical settings. We investigated whether ferritin is associated with arterial stiffness (AS), an early indicator of atherosclerosis, and if it could act as effect modifier on the relationship between inflammation and AS in hypertensive patients with different glucose tolerance. METHODS: We enrolled 462 newly diagnosed untreated hypertensive (HT) patients. All subjects underwent an oral glucose tolerance test. Insulin sensitivity was assessed by MATSUDA index and ferritin levels were estimated by immunoradiometric assay. AS was defined by carotid-femoral pulse wave velocity (PWV). RESULTS: Out of 462 patients, 271 showed normal glucose tolerance (HT/NGT), 146 impaired glucose tolerance (HT/IGT) and 45 were diabetic (HT/T2DM). Iron levels significantly decreased and transferrin and ferritin significantly increased from the first to the third group. PWV values were significantly higher in HT/IGT and HT/T2DM patients. PWV was related directly with ferritin, high sensitivity C reactive protein (hs-CRP), transferrin, and inversely with MATSUDA index. Ferritin resulted the strongest determinant of PWV explaining a 14.9% of its variation; moreover it was a strong modifier of the relationship between hs-CRP and PWV. The estimated augmentation in PWV portended by a fixed increase in hs-CRP, was higher across increasing values of ferritin. CONCLUSION: Ferritin represents an independent risk factor of arterial stiffness in our study population and a strong effect modifier on the relationship between inflammation and PWV. However, further studies are needed to fully elucidate the potential role of this biomarker in human atherosclerosis.

Chronic HCV infection increases cardiac left ventricular mass index in normotensive patients.

BACKGROUND & AIMS: Left ventricular hypertrophy (LVH), is an independent predictor for cardiovascular events. We investigated if chronic hepatitis C virus (HCV) infection and the related insulin resistance (IR)/hyperinsulinemia could influence the increase of left ventricular mass (LVM). METHODS: We enrolled 260 outpatients matched for age, body mass index, gender, ethnicity: 52 with never-treated uncomplicated chronic HCV infection (HCV(+)), 104 never-treated hypertensives (HT) and 104 healthy subjects (NT). LVM was calculated according to the Devereux formula and indexed for body surface area. The following laboratory parameters were measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, e-GFR-EPI, HOMA. Quantitative HCV-RNA was assessed by PCR. RESULTS: HCV(+) patients with respect to healthy normotensive subjects had an increased LVMI (100 ± 23 vs. 83 ± 15 g/m(2); p < 0.0001), similar to that observed in HT group (103 ± 25 g/m(2)). Regarding biochemical variables, HCV(+) patients, in comparison with normotensive healthy subjects, had higher triglyceride, creatinine, fasting insulin and HOMA (3.2 ± 1.3 vs. 2.5 ± 1.0; p < 0.0001). At linear regression analysis, the correlation between LVMI and HOMA was similar in HT (r = 0.528, p < 0.0001) and HCV(+) (r = 0.489, p < 0.0001) groups. At multiple regression analysis, HOMA resulted the major determinant of LMVI in all groups, explaining respectively 21.8%, 27.8%, and 23.9% of its variation in NT, HT and HCV(+). At correlational analysis HCV-RNA and HOMA demonstrated a strong and linear relationship between them, explaining the 72.4% of their variation (p = 0.022). CONCLUSIONS: We demonstrated a significant and direct correlation between HOMA and LVMI in patients with chronic HCV infection, similar to that observed in hypertensives.

Gut Permeability and Immune-Mediated Inflammation in Heart Failure.

Heart failure (HF) is characterized by low-grade immune-mediated inflammation due to increased Toll-like receptor (TLR) expression as response to endotoxin increase and dysregulated gut barrier permeability. We investigated TLR expression and possible gut dysbiosis in HF patients compared to a control group. We enrolled 80 Caucasian HF patients and 20 controls. Low-grade immune-mediated inflammation was evaluated by TLR expression, while gut dysbiosis by the detection of zonulin and bacterial endotoxin activity in a semi-quantitative (endotoxin activity assay [EAA]) and quantitative (limulus amebocyte lysate [LAL] test) way. Compared to controls, patients with HF showed significantly higher age and blood pressure values, worse metabolic profile and kidney function, higher inflammatory biomarkers levels, and lower levels of zonulin and endotoxin activity. When dividing failing patients in those with reduced ejection fraction (HF-rEF) and those with preserved ejection fraction (HF-pEF), HF-rEF patients showed significantly higher values of inflammatory biomarkers and TLR expression than HF-pEF patients. Gut permeability biomarkers inversely correlated with the severity of HF and positively with renal function. eGFR was retained as an independent predictor of zonulin variation in all the three groups of failing patients. Present data work to extend current knowledge about the role of gut microbiota in immune-mediated inflammation in HF.

Association between non-dipping blood pressure pattern and different glucometabolic profile during oral glucose tolerance test.

It is known that, a not physiological blood pressure (BP) circadian pattern has been associated with increased risk of organ damage and cardiovascular (CV) event. The aim of this study was to assess the association between circadian BP pattern and glucometabolic phenotypes occurring after oral glucose tolerance test (OGTT). We recruited 810 hypertensive Caucasian patients. All participants underwent to OGTT, laboratory test and 24-h ambulatory BP monitoring (ABPM). The analysis of collected data allowed classifying patients based on nocturnal BP profiles into four categories: dippers, non-dippers, extreme dippers, and reverse dippers. Considering the dipping pattern, the proportion of non-dippers in normal glucose tolerance patients with 1-h glucose ≥ 155 mg/dL (NGT ≥ 155) (36.4%) was higher than NGT < 155 (29.6%) and impaired glucose tolerance (IGT) (34.8%), but lower than type 2 diabetes group (T2DM) (52.6%) (p = 0.001). The proportion of dippers was lower in NGT ≥ 155 (47%) and T2DM (34.6%), when compared with NGT < 155 (53.8%) and IGT (51.2%) (p = 0.017). From logistic regression analysis, 1-h glucose ≥ 155 increased the risk of a pathological nocturnal drop in BP by 74%, (OR = 1.740, 95% CI 1.254-2.415, p < 0.0001). In addition, the improvement in 1 unit of Matsuda was responsible for a 3.5% risk decrease (OR = 0.965, 95% CI 0.958-0.971, p < 0.0001), while e-GFR determined a 0.9% risk reduction of nocturnal BP drop (OR = 0.991, 95% CI 0.984-0.999, p = 0.020). Our data demonstrated the existence, in newly diagnosed hypertensive patients, of an association between circadian BP profile and altered glycemic response during OGTT, in particular NGT ≥ 155 subjects are associated with a non-dipper BP pattern, this is clinically relevant because may explain, at least in part, the increased CV risk in this setting of patients.

Cardiovascular Biomarkers in Cardio-Oncology: Antineoplastic Drug Cardiotoxicity and Beyond.

Serum biomarkers represent a reproducible, sensitive, minimally invasive and inexpensive method to explore possible adverse cardiovascular effects of antineoplastic treatments. They are useful tools in risk stratification, the early detection of cardiotoxicity and the follow-up and prognostic assessment of cancer patients. In this literature review, we aim at describing the current state of knowledge on the meaning and the usefulness of cardiovascular biomarkers in patients with cancer; analyzing the intricate relationship between cancer and cardiovascular disease (especially HF) and how this affects cardiovascular and tumor biomarkers; exploring the role of cardiovascular biomarkers in the risk stratification and in the identification of chemotherapy-induced cardiotoxicity; and providing a summary of the novel potential biomarkers in this clinical setting.

Effect of SGLT2-Inhibitors on Polygraphic Parameters in Elderly Patients Affected by Heart Failure, Type 2 Diabetes Mellitus, and Sleep Apnea.

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.

Metabolic Syndrome and C-reactive Protein are Associated With a Reduced Myocardial Mechano-energetic Efficiency.

CONTEXT: Metabolic syndrome and elevated high-sensitivity C-reactive protein (hsCRP) levels are associated with risk of cardiovascular diseases. A reduced myocardial mechano-energetic efficiency (MEE) has been found to be an independent predictor of cardiovascular disease. OBJECTIVE: To evaluate the association between metabolic syndrome and hsCRP levels with impaired MEE. METHODS: Myocardial MEE was assessed by a validated echocardiography-derived measure in 1975 nondiabetic and prediabetic individuals subdivided into 2 groups according to the presence of metabolic syndrome. RESULTS: Individuals with metabolic syndrome exhibited increased stroke work and myocardial oxygen consumption estimated by rate pressure product, and a reduced MEE per gram of left ventricular mass (MEEi) compared with subjects without metabolic syndrome, after adjusting for age and sex. Myocardial MEEi progressively decreased in parallel with the increase in the number of metabolic syndrome components. In a multivariable regression analysis, both metabolic syndrome and hsCRP contributed to reduced myocardial MEEi independently of sex, total cholesterol, high-density lipoprotein, triglycerides, fasting, and 2-hour postload glucose levels. When the study population was divided into 4 groups by the presence or absence of metabolic syndrome and by hsCRP levels above and below 3 mg/L, hsCRP levels ≥3 mg/L were associated with reduced myocardial MEEi both in subjects with metabolic syndrome and in those without the syndrome. CONCLUSION: Nondiabetic and prediabetic individuals with metabolic syndrome exhibit increased stroke work and myocardial oxygen consumption, and an impaired MEEi, an established predictor of adverse cardiovascular events, and elevated hsCRP levels in combination with metabolic syndrome aggravate the myocardial MEEi impairment.

Short term effect of sacubitril/valsartan on comprehensive geriatric assessment in chronic heart failure: a real life analysis.

Sacubitril/Valsartan (Sac-Val) has improved clinical prognosis in patients affected by heart failure (HF) with reduced ejection fraction (HFrEF). Comorbidities have a crucial impact on clinical presentation and prognosis in HF patients. Cognitive impairment (CoI) and Depression are a very common comorbidity in patients with HF and is widely recognized as a specific determinant of chronic disability, and HF patients with poor physical functional performance in Short physical performance battery (SPPB) showed a worse prognosis. The aim of the present study was to evaluate the potential effects of Sac-Val on functional, humoral, and cognitive aspects, evaluated by performing comprehensive geriatric assessment (CGA), in a cohort of elderly HFrEF. We studied 61 patients (51 men and 10 women, mean age 76.4 ± 5.1 years) suffering from HFrEF. After 6 months follow-up, we observed a significant improvement in humoral and functional parameters of CGA, renal function, NTpro-BNP levels and echocardiographic parameters. In the whole population, multivariate analysis shows that changes of Cardiac Index, NT-proBNP and Respiratory rate contributed for 26.0%, 9.7% and 4.8% to GDS variability, respectively, and the whole model accounted for a 41.1% of GDS variation; moreover changes of Global longitudinal strain, estimated glomerular filtration rate, Cardiac Index and BMI contributed for 23.9%, 11.7%, 5.4% and 4.0% to SPPB variability, respectively, and the whole model accounted for a 45% of SPPB variation. This represents the first real-world study carried out in an elderly population suffering from chronic HFrEF with numerous comorbidities, in which treatment with Sac-Val for 6 months induced important improvements in clinical, humoral, hemodynamic, and functional outcomes, without adverse effects on cognitive performance.

Effects of continuous positive airway pressure on comprehensive geriatric assessment and cognitive function in elderly patients with obstructive sleep apnea syndrome.

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 (SpO2), 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.

New potential biomarkers for early chronic kidney disease diagnosis in patients with different glucose tolerance status.

Background: The purpose of the present study was to investigate the role of oxidative stress, platelet activation, and endocan levels in renal dysfunction in normal glucose tolerance (NGT) patients with 1-h plasma glucose values ≥155 mg/dl (NGT ≥ 155), compared to NGT < 155, impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) newly diagnosed subjects. We enlisted 233 patients subjected to an oral glucose tolerance test (OGTT). Materials and methods: The serum levels of platelet activation (glycoprotein VI and sP-selectin), oxidative stress biomarkers (8-isoprostane and Nox-2), and endocan were evaluated using an ELISA test. Results: Among NGT < 155 patients and the T2DM group, there was a statistically significant increase in 8-isoprostane (p < 0.0001), Nox-2 (p < 0.0001), glycoprotein VI (p < 0.0001), and sP-selectin (p < 0.0001) serum levels. Higher serum endocan levels were found with the worsening of metabolic profile (p < 0.0001); specifically, NGT ≥ 155 patients presented higher serum endocan values when compared to NGT < 155 patients (p < 0.0001). From the multivariate linear regression analysis, 1-h glucose resulted in the major predictor of estimated glomerular filtration rate (e-GFR) justifying 23.6% of its variation (p < 0.0001); 8-isoprostane and Nox-2 added respectively another 6.0% (p < 0.0001) and 3.2% (p = 0.001). Conclusion: Our study confirmed the link between 1-h post-load glucose ≥155 mg/dl during OGTT and the possible increased risk for chronic kidney disease (CKD) in newly diagnosed patients. The novelty is that we demonstrated a progressive increase in oxidative stress, platelet activation, and serum endocan levels with the worsening of metabolic profile, which becomes evident early during the progression of CKD.

Medium-term and long-term renal function changes with direct oral anticoagulants in elderly patients with atrial fibrillation.

Objective: Atrial Fibrillation (AF) and chronic kidney disease frequently coexist in the elderly. Warfarin-like drugs (WLDs) may be associated with a relatively greater decrease of estimated glomerular filtration rate (eGFR) as compared to direct oral anticoagulants (DOACs), but there is no evidence on the medium- and long-term changes. To further elucidate this issue in elderly patients with AF, we investigated the renal function deterioration in the two groups of the study (DOACs or WLDs). Patients and Methods: A total of 420 AF patients were enrolled (mean age: 77.0 ± 6.0 years; 136 on WLDs and 284 on DOACs). These patients underwent three eGFR measurements during the follow-up period. The between-arms difference of eGFR decline over time was investigated by Linear Mixed Models and group-based trajectory model analyses. Results: In the whole study cohort, after a median follow-up of 4.9 years (interquartile range: 2.7-7.0 years), eGFR decreased from 67.4 ± 18.2 to 47.1 ± 14.3 mL/min/1.73 m2 (p < 0.001). Remarkably, patients on DOACs experienced a significantly smaller eGFR decline than WLDs patients (-21.3% vs. -45.1%, p < 0.001) and this was true both in the medium-term (-6.6 vs. -19.9 mL/min/1.73 m2) and in the long-term (-13.5 versus -34.2 mL/min/1.73 m2) period. After stratification into five subgroups according to trajectories of renal function decline over time, logistic regression showed that DOACs patients had from 3.03 to 4.24-fold greater likelihood to belong to the trajectory with less marked eGFR decline over time than WLDs patients. Conclusion: Elderly patients with AF on treatment with DOACs had a relatively smaller decline of eGFR over time compared to those on treatment with WLDs. This is consistent with what was partly reported in the literature.