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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.
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Biomarcadores , Diabetes Mellitus Tipo 2 , Evaluación Geriátrica , Insuficiencia Cardíaca , Estrés Oxidativo , Activación Plaquetaria , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Volumen Sistólico , Humanos , Anciano , Estrés Oxidativo/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/sangre , Femenino , Masculino , Activación Plaquetaria/efectos de los fármacos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Anciano de 80 o más Años , Evaluación Geriátrica/métodos , Dinoprost/análogos & derivados , Dinoprost/sangreRESUMEN
BACKGROUND: Uric acid (UA) is an independent prognostic factor for cardiovascular events, but there are no data demonstrating a different risk profile between women and men. Thus, we tested whether UA is associated with a possible sex-related difference in fatal and non-fatal cardiovascular events. METHODS: In this prospective population-based study we enrolled 1,650 never-treated Caucasian hypertensive outpatients referred to Catanzaro University Hospital (Italy). Inclusion criteria were newly diagnosed hypertensive patients, aged 20 years or more. Exclusion criteria were secondary form of hypertension, previous cardiovascular events, rheumatic and non-rheumatic valvular heart disease, prosthetic valves, cardiomyopathies, type-2 diabetes, chronic kidney disease, malignant diseases, gout arthritis and secondary forms of hyperuricemia, liver diseases, peripheral vascular diseases, and heart failure. Anthropometric, clinical, and biochemical parameters were measured. UA prognostic role was investigated by Cox regression analyses. Receiver-operating characteristic curve analyses and area under the curve were used to determine the predictive validity and the optimal cut-off point of UA. We investigated following endpoints: coronary events (fatal and nonfatal myocardial infarction, unstable angina, coronary revascularization procedures, coronary death); fatal and nonfatal stroke; all-cause mortality and major adverse cardiovascular events (MACE). RESULTS: We enrolled 830 males and 820 females aged 52.2 ± 11.3 years. During 9.5 ± 3.1 years follow-up, there were 424 new clinical events (2.71%): 250 coronary (1.59%), 118 (0.75%) cerebrovascular, and 56 (0.40%) deaths. Comparison between groups demonstrated a higher and significant difference in incidence rate in females for MACE (3.08 vs 2.33%, P = 0.001), coronary (1.82 vs 1.36%, P = 0.014) and cerebrovascular events (0.93 vs 0.57%, P = 0.006). UA at multiple Cox regression analysis resulted a strong and significant predictor of coronary events (HR = 1.493;95% CI 1.375-1.621), cerebrovascular events (HR = 1.256;95% CI 1.109-1.423), MACE (HR = 1.415;95% CI 1.328- 53 1.508), and all-cause mortality (HR = 1.469;95% CI 1.237-1.745) in the whole population and in both groups with a HR higher in females. The best estimated cut-off values of uric acid for males and females predicted these endpoints equally well, but it was always lower in females than males. CONCLUSIONS: We demonstrate, that UA operates with a sex-related impact and best cut-off value in predicting cardiovascular outcomes and all-cause mortality, reflecting a possible sex difference in disease pathophysiology.
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Hipertensión , Ácido Úrico , Humanos , Masculino , Femenino , Estudios Prospectivos , Factores de Riesgo , Caracteres Sexuales , Hipertensión EsencialRESUMEN
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.
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Enfermedad Pulmonar Obstructiva Crónica , Disfunción Ventricular Derecha , Humanos , Estudios Retrospectivos , Pronóstico , Ecocardiografía/métodos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Función Ventricular Derecha/fisiología , Volumen Sistólico/fisiologíaRESUMEN
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.
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Fibrilación Atrial , Diabetes Mellitus Tipo 2 , Intolerancia a la Glucosa , Hipertensión , Resistencia a la Insulina , Humanos , Glucemia , Glucosa , MiocardioRESUMEN
Inflammation plays a key role in the pathogenesis/progression of atherosclerosis, and inflammatory molecules contribute to the progression of cardiovascular disease. Subjects with normal post-load glucose tolerance and 1-h post-load plasma glucose >155 mg/dL have an increased risk of subclinical target organ damage and incident diabetes. We aimed to test possible differences in immune-mediated inflammatory parameters in newly-diagnosed hypertensives with or without 1-h post-load hyperglycemia. We enrolled 25 normotensives (NGT) and 50 hypertensives normotolerant on oral glucose tolerance test, further divided into two groups based on 1-h post-load plasma glucose: NGT 1-h ≥ 155 (n = 25) and NGT 1-h < 155 (n = 25). We measured toll-like receptor (TLR) 2, TLR4, nuclear factor kß (NF-kß), interleukin (IL)-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α. Hypertensives showed significantly worse metabolic and lipid profiles, and higher values of body mass ass index (BMI), creatinine, and inflammatory parameters, compared to controls. NGT 1-h ≥ 155 had a worse glycometabolic profile and higher values of TLR2 (9.4 ± 4.2 vs. 5.9 ± 2.6 MFI), TLR4 (13.1 ± 3.9 vs. 7.8 ± 2.3 MFI), NF-kß (0.21 ± 0.07 vs. 0.14 ± 0.04), IL-1ß (6.9 ± 3.4 vs. 3.2 ± 2.1 pg/mL), IL-6 (10.8 ± 2.6 vs. 4.1 ± 1.6 pg/mL), IL-8 (27.6 ± 9.3 vs. 13.3 ± 5.6 pg/mL), TNF-α (6.4 ± 2.9 vs. 3.3 ± 1.4 pg/mL), and high-sensitivity C-reactive protein (hs-CRP) (4.8 ± 1.5 vs. 2.7 ± 1.0 mg/dL) in comparison with NGT 1-h < 155. Matsuda-index and 1-h post-load glycemia were retained as major predictors of TLRs and NF-kß. These results contribute to better characterizing cardiovascular risk in hypertensives.
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Hiperglucemia , Hipertensión , Glucemia/metabolismo , Proteína C-Reactiva/metabolismo , Creatinina , Humanos , Hiperglucemia/complicaciones , Inflamación , Interleucina-10 , Interleucina-6 , Interleucina-8 , Lípidos , Receptor Toll-Like 2 , Receptor Toll-Like 4 , Factor de Necrosis Tumoral alfaRESUMEN
Vitamin D is an important micronutrient involved in several processes. Evidence has shown a strong association between hypovitaminosis D and cardio-metabolic diseases, including obesity. A ketogenic diet has proven to be very effective for weight loss, especially in reducing fat mass while preserving fat-free mass. The aim of this study was to investigate the effect of a ketogenic diet-induced weight loss on vitamin D status in a population of obese adults. We enrolled 56 obese outpatients, prescribed with either traditional standard hypocaloric Mediterranean diet (SHMD) or very low-calorie ketogenic diet (VLCKD). Serum 25(OH)D concentrations were measured by chemiluminescence. The mean value of serum 25-hydroxyvitamin D (25(OH)D) concentrations in the whole population at baseline was 17.8 ± 5.6 ng/mL, without differences between groups. After 12 months of dietetic treatment, in VLCKD patients serum 25(OH)D concentrations increased from 18.4 ± 5.9 to 29.3 ± 6.8 ng/mL (p < 0.0001), vs 17.5 ± 6.1 to 21.3 ± 7.6 ng/mL (p = 0.067) in the SHMD group (for each kilogram of weight loss, 25(OH)D concentration increased 0.39 and 0.13 ng/mL in the VLCKD and in the SHMD groups, respectively). In the VLCKD group, the increase in serum 25(OH)D concentrations was strongly associated with body mass index, waist circumference, and fatty mass variation. In a multiple regression analysis, fatty mass was the strongest independent predictor of serum 25(OH)D concentration, explaining 15.6%, 3.3%, and 9.4% of its variation in the whole population, in SHMD, and VLCKD groups, respectively. We also observed a greater reduction of inflammation (evaluated by high-sensitivity C reactive protein (hsCRP) values) and a greater improvement in glucose homeostasis, confirmed by a reduction of HOMA values, in the VLCKD versus the SHMD group. Taken together, all these data suggest that a dietetic regimen, which implies a great reduction of fat mass, can improve vitamin D status in the obese.
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Dieta Cetogénica , Obesidad/etiología , Obesidad/metabolismo , Vitamina D/metabolismo , Pérdida de Peso , Adulto , Biomarcadores , Dieta Cetogénica/efectos adversos , Femenino , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Vitamina D/sangreRESUMEN
Metabolic syndrome (MS) is characterized by an increased risk of incident diabetes and cardiovascular (CV) events, identifying insulin resistance (IR) and endothelial dysfunction as key elements. Moreover, non-alcoholic fatty liver disease (NAFLD) is bidirectionally linked with MS as a consequence of metabolic and inflammatory abnormalities. We addressed the question if the evolution in NAFLD might worsen endothelium-dependent vasodilating response in MS hypertensives. We recruited 272 Caucasian newly-diagnosed never-treated hypertensive outpatients divided into three groups according to the presence/absence of MS alone or in combination with NAFLD. MS and NAFLD were defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and non-invasive fatty liver index, respectively. We determined IR by using the homeostasis model assessment (HOMA) index. Vascular function, as forearm blood flow (FBF), was determined through strain-gauge plethysmography after intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside. MS+NAFLD+ group showed worse metabolic, inflammatory and vascular profiles compared with MS-NAFLD- and MS+NAFLD-. HOMA resulted in being the strongest predictor of FBF both in the MS+NAFLD- and in the MS+NAFLD+ groups, accounting for 20.5% and 33.2% of its variation, respectively. In conclusion, we demonstrated that MS+NAFLD+ hypertensives show a worse endothelium-dependent vasodilation compared with MS+NAFLD-, allowing for consideration of NAFLD as an early marker of endothelial dysfunction in hypertensives.
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Endotelio Vascular/fisiología , Hipertensión/patología , Síndrome Metabólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Acetilcolina/farmacología , Adulto , Presión Sanguínea/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Femenino , Humanos , Hipertensión/complicaciones , Resistencia a la Insulina , Modelos Lineales , Masculino , Persona de Mediana Edad , Nitroprusiato/farmacología , Flujo Sanguíneo Regional/efectos de los fármacos , Vasodilatadores/farmacologíaRESUMEN
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.
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Hepatitis C Crónica , Homeostasis , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda , Resistencia a la Insulina , Adulto , Glucemia/análisis , Presión Sanguínea , Índice de Masa Corporal , Superficie Corporal , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Hepatitis C Crónica/sangre , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/fisiopatología , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/fisiopatología , Insulina/sangre , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estadística como Asunto , Triglicéridos/sangreRESUMEN
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.
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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.
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Diabetes Mellitus Tipo 2 , Hipertensión , Humanos , Presión Sanguínea/fisiología , Prueba de Tolerancia a la Glucosa , Diabetes Mellitus Tipo 2/complicaciones , Ritmo Circadiano/fisiología , Hipertensión/complicaciones , Monitoreo Ambulatorio de la Presión Arterial , GlucosaRESUMEN
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.
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Insuficiencia Cardíaca , Albúmina Sérica , Humanos , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/complicaciones , Masculino , Estudios Retrospectivos , Pronóstico , Persona de Mediana Edad , Albúmina Sérica/análisis , Anciano , Biomarcadores/sangre , Enfermedad Crónica , Factores de RiesgoRESUMEN
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.
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Insulin resistance and endothelial dysfunction are associated with heart failure (HF). Our objective was to investigate whether endothelial dysfunction and insulin resistance are independent predictors of incident HF and if a possible interaction exists between them. We enrolled 705 white never-treated hypertensives. Endothelium-dependent vasodilation was investigated by intra-arterial infusion of acetylcholine. During the follow-up [median: 117 months (range: 31-211)], we documented 223 new cases of HF (3.3 events/100 patient-years). We stratified the study population into progressors and non-progressors; progressors showed an older age and a higher prevalence of females, as well as higher mean values of baseline glucose, insulin, homeostasis model assessment (HOMA), creatinine, and high-sensitivity C-reactive protein (hs-CRP), whereas the estimated glomerular filtration rate (e-GFR) and endothelium-dependent vasodilation were lower. In the multiple Cox regression analysis, serum hs-CRP (HR = 1.362, (95% CI = 1.208-1.536), HOMA (HR = 1.293, 95% CI = 1.142-1.465), maximal acetylcholine (Ach)-stimulated forearm blood flow (FBF) (100% increment, HR = 0.807, 95% CI = 0.697-0.934), and e-GFR (10 mL/min/1.73 m2 increment, HR = 0.552, 95% CI = 0.483-0.603) maintained an independent association with incident HF. HOMA and endothelial dysfunction interact between them in a competitive manner (HR = 6.548, 95% CI = 4.034-10.629), also showing a mutual effect modification. Our findings demonstrate that both endothelial dysfunction and HOMA are independent and strong predictors of incident HF in hypertensives, these two risk factors interact between them with a competitive mechanism.
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Chronic kidney disease is a risk factor for cardiovascular events. Smoking and chronic obstructive pulmonary disease (COPD) are risk factors for renal impairment. The aim of this study was to test the combined effect of smoking and COPD on renal function decline in hypertensives. We enrolled 1728 hypertensives stratified by smoking status and presence/absence of COPD. To test the mutual effect modification by both smoking and COPD and e-GFR, we performed crude and adjusted linear regression analyses, these latter taking into account potential confounders. Smokers displayed significantly lower e-GFR values than non-smokers (90 ± 24 vs. 121 ± 35 ml/min/1.73 m2); this difference was confirmed when comparing e-GFR values between patients with/without COPD (81 ± 17 vs. 109 ± 32 ml/min/1.73 m2). Smoking and COPD were directly and significantly interrelated (Cramer's V coefficient = 0.200; P = < 0.001). At interaction analyses, smoking significantly modified the effect of COPD on e-GFR and COPD significantly modified the effect of smoking on e-GFR, indicating a competitive interaction between smoking and COPD in the appearance of renal damage. e-GFR was 35 ml/min/1.73 m2 lower in patients with COPD than in those without; this reduction was of higher magnitude than that found between COPD and COPD-free patients among smokers (19 ml/min/1.73 m2). Smoking and COPD competitively interact in the appearance of renal function decline. These results suggest to screen for kidney damageboth smokers and COPD patients, especially those with both conditions.
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Hipertensión , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Fumar/efectos adversos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Factores de Riesgo , Hipertensión/complicaciones , Hipertensión/epidemiología , Riñón/fisiologíaRESUMEN
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.
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Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Humanos , Glucemia/metabolismo , Prueba de Tolerancia a la Glucosa , Biomarcadores , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/complicacionesRESUMEN
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.
Asunto(s)
Presión de las Vías Aéreas Positiva Contínua , Apnea Obstructiva del Sueño , Humanos , Anciano , Evaluación Geriátrica , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/terapia , Apnea Obstructiva del Sueño/diagnóstico , Cognición , SíndromeRESUMEN
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.
Asunto(s)
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Insuficiencia Cardíaca , Valsartán , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Aminobutiratos/efectos adversos , Antagonistas de Receptores de Angiotensina/efectos adversos , Combinación de Medicamentos , Evaluación Geriátrica , Insuficiencia Cardíaca/tratamiento farmacológico , Volumen Sistólico , Tetrazoles/efectos adversos , Valsartán/uso terapéuticoRESUMEN
BACKGROUND: In normoglucose-tolerant subjects (NGT), 1-h post-load plasma glucose value ≥155 mg/dL, during an oral glucose tolerance test (OGTT), is associated with an increased risk of type-2 diabetes (T2D) and subclinical organ damage. Insulin-like growth factor-1 (IGF-1) is involved in the pathogenesis of insulin resistance (IR) and T2D. Moreover, hypertensives have different degrees of IR and different levels of IGF-1. Actually, there are no data supporting the association between post-load glucose and IGF-1; thus, the aim of the study was to investigate this relationship. MATERIALS AND METHODS: We enrolled 1126 never-treated hypertensive subjects who underwent an OGTT and clinical characterization. Insulin sensitivity was assessed by the Matsuda index. IGF-1 was measured by a sensitive immunoradiometric assay. RESULTS: Among participants, 764 had NGT, 263 had impaired glucose tolerance (IGT) and 99 had T2D. According to the 1-h post-load plasma glucose cut-off point of 155 mg/dL, we divided NGT subjects into NGT < 155 mg/dL and NGT ≥ 155 mg/dL. NGT ≥ 155 in comparison with NGT < 155 had significantly reduced insulin sensitivity and IGF-1 levels. At multiple regression analysis, IGF-1 was the major determinant of 1-h post-load glucose in NGT ≥ 155 subjects, IGT and diabetics, accounting for 20·9%, 17·7% and 15·5% of its variation in the respective models. CONCLUSIONS: In hypertensive NGT ≥ 155 subjects, IGF-1 results strongly associated with 1-h post-load glucose, similarly to that observed in IGT and diabetics. This finding has clinical relevance because both low IGF-1 levels and 1-h post-load glucose in NGT subjects are associated with subclinical organ damage, an independent predictor of cardiovascular events.
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Hipertensión/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Adulto , Anciano , Glucemia/metabolismo , Estudios Transversales , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores de Tiempo , Población BlancaRESUMEN
Immediate implant rehabilitation of edentulous arches may be somewhat problematic because of anatomic situations involving insufficient bone thickness or height and tooth position. The aim of this report was to present a retrospective case series of dental implants placed into augmented sites (split crest or sinus augmentation) that were stabilized with an intraorally welded framework at the time of immediate provisionalization. An intraoral welding unit was used to join and stabilize implants as an orthopedic splint to break down forces applied on provisional restorations during healing and osseointegration. This approach allows for the immediate provisionalization of implants in bone-defective areas where multiple implant systems have been enacted. Forty-eight implants in 16 patients were inserted, welded together to a titanium framework, and immediately provisionalized during the same surgery in which split-crest or sinus augmentation procedures were performed. After removing the welded frameworks, 1 of 48 implants failed; the failed implant was associated with a sinus augmentation procedure. Intraoral welding stabilization may be a predictable procedure to allow immediate loading in augmented areas during healing time and to stabilize implants against nonaxial forces, thereby reducing the number of surgical and prosthetic sessions and making patients comfortable and accustomed to immediate fixed provisional and definitive restorations.
Asunto(s)
Aumento de la Cresta Alveolar/métodos , Implantes Dentales , Prótesis Dental de Soporte Implantado , Soldadura Dental/métodos , Adulto , Anciano , Materiales Dentales/química , Diseño de Prótesis Dental , Retención de Prótesis Dentales/instrumentación , Fracaso de la Restauración Dental , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Oseointegración/fisiología , Osteogénesis por Distracción/métodos , Estudios Retrospectivos , Elevación del Piso del Seno Maxilar/métodos , Férulas (Fijadores) , Titanio/química , Cicatrización de Heridas/fisiologíaRESUMEN
Heart failure (HF) is associated to endothelial dysfunction that promotes the increase of arterial stiffness thus augmenting myocardial damage. Sacubitril/Valsartan is used in the treatment of HF reduced ejection fraction (HFrEF) and has been proven effective in reducing cardiovascular disease (CVD) progression and all-cause mortality. The aim of this study was to evaluate the effect of Sacubitril/Valsartan on endothelial dysfunction, arterial stiffness, oxidative stress levels and platelets activation in patients with HFrEF, at baseline and after 6 months of treatment. We enrolled 100 Caucasian patients. Endothelial function was evaluated by the reactive hyperemia index (RHI) and arterial stiffness (AS) by the measurement of carotid-femoral pulse wave velocity (PWV), augmentation pressure (AP) and augmentation index (AI). At baseline, among enrolled outpatients, 43% showed a NYHA class II and 57% a NYHA class III. At 6 months, there was a significant improvement of several hemodynamic, clinical and metabolic parameters with a significant reduction in oxidative stress indices such as 8-isoprostane (p < 0.0001) and Nox-2 (p < 0.0001), platelets activity biomarkers such as sP-selectin (p < 0.0001) and Glycoprotein-VI (p < 0.0001), and inflammatory indices. Moreover, we observed a significant improvement in arterial stiffness parameters and in endothelial function indices. Our study demonstrated that 6 months treatment with Sacubitril/Valsartan, in patients with HFrEF, improves endothelial dysfunction and arterial stiffness, by reducing oxidative stress, platelet activation and inflammation circulating biomarkers, without adverse effects.