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1.
Artigo em Inglês | MEDLINE | ID: mdl-32052315

RESUMO

BACKGROUND AND AIMS: Increased ß-amyloid and decreased mitochondrial-derived peptide (MOTS-c), are reported in diabetes. We investigated their additive value to high on-clopidogrel platelet reactivity (HPR) for adverse outcome in type 2 diabetics after recent revascularization. PATIENTS AND METHODS: In 121 type II diabetics, treated with clopidogrel and aspirin, (93 males, mean age 67.2 years) we measured: (a) maximum platelet aggregation to adenosine diphosphate (ADP) by light transmission aggregometry (LTAmax), (b) malondialdehyde (MDA), as oxidative stress marker, (c) MOTS-c, (d) ß-amyloid blood levels. Cardiac death and acute coronary syndromes (MACE) were recorded during 2 years of follow-up. RESULTS: Out of 121 patients, 32 showed HPR (LTAmax > 48%,). At baseline, HPR was associated with ß-amyloid > 51 pg/ml (p = 0.006) after adjusting clinical variables, HbA1c, MOTS-c, MDA and medication. During follow-up, 22 patients suffered a MACE. HPR, ß-amyloid > 51 pg/ml and MOTS-c < 167 ng/ml were predictors of MACE (relative risk 3.1, 3.5 and 3.8 respectively, p < 0.05) after adjusting for confounders and medication. There was significant interaction between HPR and ß-amyloid or MOTS-c for the prediction of MACE (p < 0.05). Patients with HPR and ß-amyloid > 51 mg/dl or HPR and MOTS-c concentration < 167 ng/ml had a fourfold higher risk for MACE than patients without these predictors (relative risk 4.694 and 4.447 respectively p < 0.01). The above results were confirmed in an external validation cohort of 90 patients with diabetes and CAD. CONCLUSIONS: Increased ß-amyloid or low MOTS-c are additive predictors to high on-clopidogrel platelet reactivity for adverse outcome in diabetics with CAD during 2-years follow-up. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT04027712.

2.
J Neurol Sci ; 409: 116628, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31862517

RESUMO

Although intracerebral hemorrhage (ICH) score is used to provide an estimate on the probability of mortality following spontaneous ICH of any cause, its utility has not been exclusively tested in ICH patients with history of treatment with vitamin K antagonists (VKAs) or non-vitamin K oral anticoagulants (NOACs). The aim of the present report is to investigate the utility of ICH score for mortality prognostication of VKA-ICH and NOAC-ICH patients. We used receiver operating characteristic curve analyses to estimate the accuracy parameters for the different values of ICH score in the prognosis of mortality within 30-days after the onset of NOAC-ICH or VKA-ICH. We analyzed data from 108 NOAC-ICH and 241 VKA-ICH patients (median age 76 years, 58% males, median NIHSS score 11 points, median ICH-score 2 points). ICH score of 4 points was uncovered to be the most favorable threshold for the prediction of 30-day mortality both after NOAC-ICH (sensitivity: 57.7%, specificity: 98.8%) or VKA-ICH (sensitivity: 42.1%, specificity: 92.6%). However, comparison of the areas under the curve (AUC) suggested a cumulatively higher (p = .001) predictive value of ICH-score in the prognostication of 30-day mortality after ICH related to the use of NOACs (AUC: 0.92, 95%CI: 0.86-0.98) compared to the ICH related to the use of VKAs (AUC: 0.77, 95%CI: 0.70-0.83). In conclusion, ICH score seems to have an adequate predictive utility in the prognostication of 30-day mortality following an ICH related to the use of oral anticoagulants, with better yield in ICH cases associated with the use of NOACs.

3.
J Clin Hypertens (Greenwich) ; 21(9): 1386-1392, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31465154

RESUMO

Wave reflection at central arteries consists of a major component of left ventricular afterload. Central augmentation index (AIx) is the most widely used surrogate of wave reflection. Recent technological developments now provide the ability to obtain, non-invasively, aortic, or carotid pressure waves and measure AIx based on various algorithms of pulse wave analysis. The aim of this study was to compare AIx measurements performed by the Arteriograph, Complior, and Mobil-O-Graph apparatuses. Recordings by each device in randomized order were performed with 5-minute interval at 211 individuals (age 55.1 ± 14.1 years, 67.8% males) who underwent diagnostic cardiovascular assessment. All measurements were obtained at the supine position, and AIx was calculated using the formula AIx = 100 × (Augmentation pressure)/(Pulse Pressure). Bland-Altman analysis was performed. Mean difference (bias) ± one standard deviation of difference (with limits of agreement) of AIx between different devices was as follows: (a) Mobil-O-Graph vs Complior: -2.1 ± 14.8% (-31.1% to 26.9%), (b) Arteriograph vs Complior: 12.9 ± 14.6% (-15.7% to 41.5%), and (c) Mobil-O-Graph vs Arteriograph: -10.8 ± 16.9% (-43.9% to 22.3%). The three examined devices exerted significant differences in central AIx estimation which makes the three devices non-interchangeable for wave reflection assessment. However, the Mobil-O-Graph device showed the highest agreement (lowest bias) with the Complior system as regards to the AIx measurement.

4.
Thromb Haemost ; 119(11): 1860-1868, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31421641

RESUMO

BACKGROUND AND PURPOSE: Cardioembolism is a postulated mechanism of embolic stroke of undetermined source (ESUS). We investigated endothelial glycocalyx, aortic elastic properties, oxidative stress, and their association with left atrial (LA) function in ESUS and healthy individuals. METHODS: In 90 ESUS patients (age 50.4 ± 13.2) and 90 controls with similar risk factors, we measured: (1) perfused boundary region (PBR) of the sublingual arterial microvessels (range 5-25 µm), a marker inversely related with glycocalyx thickness, (2) pulse wave velocity (PWV), central systolic blood pressure (cSBP), and augmentation index (AIx), (3) LA volume and strain using speckle-tracking imaging, and (4) malondialdehyde (MDA) and protein carbonyls (PCs), as oxidative stress markers. RESULTS: Compared with controls, ESUS had higher PWV, PBR, MDA, and PC levels as well as higher LA volume and reduced reservoir LA strain (p < 0.05). PBR > 1.2 µm of microvessel ranging from 5 to 9 µm and PWV > 10.2 m/s were associated with ESUS on multivariable analysis (odds ratio: 2.374 and 5.429, p < 0.05, respectively) and increased the c-statistic of the initial model from 0.54 to 0.71. In ESUS, glycocalyx damage (increased PBR) was related with increased PWV (p < 0.01) which was linked with LA reservoir strain after controlling for age, sex, and risk factors (p = 0.03). Increased MDA and PC were related with glycocalyx damage, increased PWV (r = 0.67 and r = 0.52), AIx, cSBP, and aortic atheroma (p < 0.01). CONCLUSION: Arterial function and endothelial glycocalyx are severely impaired in ESUS and are linked to LA dysfunction suggesting their contribution to ESUS pathogenesis. CLINICAL TRIAL REGISTRATION: URL-http://www.clinicaltrials.gov. Unique identifier: NCT03609437.

5.
Postgrad Med ; 131(7): 423-437, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31382796

RESUMO

Hyperglycemia on hospital admission is a common phenomenon in acute ischemic stroke patients and represents an independent predictor of poor clinical outcome with or without acute recanalization therapies (systemic thrombolysis or mechanical thrombectomy). Effective restoration of normoglycemia is considered to be beneficial, but conclusive evidence from randomized controlled clinical trials and specific recommendations are lacking. In addition, aggressive glucose control can be complicated by hypoglycemia leading to early neurological deterioration. We conducted a systematic literature review with the aim of addressing several questions: timing of glucose control, target range, type of insulin delivery, duration and practicability of glucose-lowering protocols. Special issues regarding mechanical thrombectomy and glycemic variability can then be investigated in future trials which are also being considered.


Assuntos
Isquemia Encefálica/terapia , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Acidente Vascular Cerebral/terapia , Glicemia/metabolismo , Isquemia Encefálica/complicações , Isquemia Encefálica/metabolismo , Hospitalização , Humanos , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Hipoglicemia/induzido quimicamente , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/metabolismo , Trombectomia , Terapia Trombolítica
6.
Artigo em Inglês | MEDLINE | ID: mdl-31322077

RESUMO

BACKGROUND: Obesity is a global epidemic which is associated with several cardiometabolic comorbidities and is characterized by chronic, low grade systemic inflammation. Numerous biomarkers have been implicated in the pathophysiology of the disease, including transcription factors and coregulators. Steroid Receptor Coactivator (SRC)-family represent the master regulators of metabolic pathways and their dysregulation is strongly associated with numerous metabolic disorders. METHODS: 50 morbidly obese patients participated in the present study. Biopsies were collected from visceral adipose tissue, subcutaneous adipose tissue, skeletal muscle, extramyocellular adipose tissue and liver. We evaluated the differential protein expression of NFATc1, SRC-2/TIF-2, SRC-3/AIB-1 and inflammatory biomarkers CD68 and CD3 by immunohistochemistry. The current study was designed to determine any correlations between the transcription factor NFATc1 and the SRC coregulators, as well as any associations with the inflammatory biomarkers. RESULTS: We identified SRC-3 as a hepatic NFATc1 coactivator and we demonstrated its role in energy homeostasis and lipid metabolism. Moreover, we revealed a complex and extensive inter- and intra-tissue network among the three main investigated proteins and the inflammatory biomarkers, suggesting their participation in the obesity-induced inflammatory cascade. CONCLUSIONS: Steroid receptor coactivators are critical regulators of human metabolism with pleiotropic and tissue-specific actions. We believe that our study will contribute to the better understanding of the complex multi-tissue interactions that are disrupted in obesity and can therefore lead in numerous cardiometabolic diseases. Further on, present findings suggest that SRC-3/AIB-1 could constitute possible future drug targets.

7.
J Clin Med ; 8(7)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284526

RESUMO

BACKGROUND: Poor glycaemic control affects myocardial function. We investigated changes in endothelial function and left ventricular (LV) myocardial deformation in poorly controlled type 2 diabetics before and after glycaemic control intensification. METHODS: In 100 poorly-controlled diabetic patients (age: 51 ± 12 years), we measured at baseline and at 12 months after intensified glycaemic control: (a) Pulse wave velocity (PWV, Complior); (b) flow-mediated dilatation (FMD, %) of the brachial artery; (c) perfused boundary region (PBR) of the sublingual arterial micro-vessels (side-view dark-field imaging, Glycocheck); (d) LV global longitudinal strain (GLS), peak twisting (pTw), peak twisting velocity (pTwVel), and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography, where the ratio of PWV/GLS was used as a marker of ventricular-arterial interaction; and (e) Malondialdehyde (MDA) and protein carbonyls (PCs) plasma levels. RESULTS: Intensified 12-month antidiabetic treatment reduced HbA1c (8.9 ± 1.8% (74 ± 24 mmol/mol) versus 7.1 ± 1.2% (54 ± 14 mmol/mol), p = 0.001), PWV (12 ± 3 versus 10.8 ± 2 m/s), PBR (2.12 ± 0.3 versus 1.98 ± 0.2 µm), MDA, and PCs; meanwhile, the treatment improved GLS (-15.2 versus -16.9%), PWV/GLS, and FMD% (p < 0.05). By multi-variate analysis, incretin-based agents were associated with improved PWV (p = 0.029), GLS (p = 0.037), PBR (p = 0.047), and FMD% (p = 0.034), in addition to a reduction of HbA1c. The patients with a final HbA1c ≤ 7% (≤ 53 mmol/mol) had greater reduction in PWV, PBR, and markers of oxidative stress, with a parallel increase in FMD and GLS, compared to those who had HbA1c > 7% (> 53 mmol/mol). CONCLUSIONS: Intensified glycaemic control, in addition to incretin-based treatment, improves arterial stiffness, endothelial glycocalyx, and myocardial deformation in type 2 diabetes after one year of treatment.

8.
Diabetes ; 68(9): 1861-1869, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31217175

RESUMO

Available data from observational studies on the association of admission hyperglycemia (aHG) with outcomes of patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) are contradictory, especially when stratified by diabetes mellitus (DM) history. We assessed the association of aHG (≥144 mg/dL) with outcomes stratified by DM history using propensity score-matched (PSM) data from the SITS-ISTR. The primary safety outcome was symptomatic intracranial hemorrhage (SICH); 3-month functional independence (FI) (modified Rankin Scale [mRS] scores 0-2) represented the primary efficacy outcome. Patients with and without aHG did not differ in baseline characteristics both in the non-DM (n = 12,318) and DM (n = 6,572) PSM subgroups. In the non-DM group, patients with aHG had lower 3-month FI rates (53.3% vs. 57.9%, P < 0.001), higher 3-month mortality rates (19.2% vs. 16.0%, P < 0.001), and similar symptomatic intracerebral hemorrhage (SICH) rates (1.7% vs. 1.8%, P = 0.563) compared with patients without aHG. Similarly, in the DM group, patients with aHG had lower rates of 3-month favorable functional outcome (mRS scores 0-1, 34.1% vs. 39.3%, P < 0.001) and FI (48.2% vs. 52.5%, P < 0.001), higher 3-month mortality rates (23.7% vs. 19.9%, P < 0.001), and similar SICH rates (2.2% vs. 2.7%, P = 0.224) compared with patients without aHG. In conclusion, aHG was associated with unfavorable 3-month clinical outcomes in patients with and without DM and AIS treated with IVT.

9.
Blood Press ; 28(2): 107-113, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30668163

RESUMO

PURPOSE: Pulse wave velocity (PWV) is a marker of arterial stiffness with major prognostic value. We compared Arteriograph and Complior devices with the Mobil-O-Graph for assessment of PWV and central systolic blood pressure (cSBP). MATERIALS AND METHODS: We studied 316 consecutive subjects (age: 55 ± 14 years). For each individual, we measured PWV and cSBP with Arteriograph, Complior and Mobil-O-Graph and compared the readings. Differences in values among three devices were calculated for each measurement. We used Bland-Altman analysis, intraclass correlation coefficient (ICC) and coefficient of variation (CV). RESULTS: Bland-Altman analysis indicated a mean difference for PWV: i.0.5 m/s (limits of agreement -1.4-2.4) between Complior and Mobil-O-Graph, ii.0.6 m/s (limits of agreement -1.4-2.6) between Arteriograph and Mobil-O-Graph. cSBP mean difference was 3.8 mmHg between Complior and Mobil-O-Graph (limits of agreement -12.5-20.1) and 9.2 mmHg between Arteriograph and Mobil-O-Graph (limits of agreement -7.6-26). ICC for PWV was 0.86 between Arteriograph and Mobil-O-Graph, 0.87 between Complior and Mobil-O-Graph and for cSBP 0.92 and 0.91 respectively. CV for PWV was 9.5% between Arteriograph and Mobil-O-Graph, 8.8% between Complior and Mobil-O-Graph. Respective values for cSBP were 6.8% and 5.1%. CONCLUSION: Our study shows acceptable agreement among the three devices regarding pulse wave analysis markers though Mobil-O-Graph appears to underestimate the values of these markers. Further studies are needed to explore the agreement between the 3 devices in various clinical settings and patient populations.


Assuntos
Análise de Onda de Pulso/instrumentação , Adulto , Idoso , Pressão Sanguínea , Determinação da Pressão Arterial/instrumentação , Humanos , Pessoa de Meia-Idade , Análise de Onda de Pulso/normas , Rigidez Vascular
10.
Diabetes Obes Metab ; 21(3): 517-524, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30242948

RESUMO

AIMS: To assess the effect of liraglutide on 24-hour ambulatory blood pressure and heart rate in patients with hypertension (pre- and stage 1 hypertension) and inadequately controlled Type 2 diabetes (glycated haemoglobin 7%-10% [53-86 mmol/mol]). MATERIALS AND METHODS: Eligible patients for this investigator-initiated, parallel-group, randomized, double-blind trial were on stable background antihyperglycaemic therapy excluding insulin, glucagon-like peptide-1 receptor agonists and dipeptidyl-peptidase-4 inhibitors. Participants were centrally randomized in a 1:1 ratio to daily liraglutide 0.6 mg, titrated to 1.2 mg after the first week, or placebo for 5 weeks. The primary outcome was change in 24-hour ambulatory systolic blood pressure (SBP), and secondary outcomes included change in ambulatory diastolic blood pressure (DBP) and heart rate. We also assessed renal sodium handling. RESULTS: Of 87 patients assessed for eligibility, 62 (66.1% men) with a mean age of 60.2 years were randomized to liraglutide (n = 31) or placebo (n = 31). All participants received background therapy with metformin, whilst 35.5% were treated concomitantly with sulphonylureas and 14.5% with pioglitazone. Compared with placebo, liraglutide reduced 24-hour SBP by -5.73 mm Hg (95% confidence interval [CI] -9.81 to -1.65) and had a neutral effect on 24-hour DBP (mean difference - 1.42 mm Hg; 95% CI -4.25 to 1.40), whilst increasing 24-hour heart rate by 6.16 beats/min (95% CI 3.25 to 9.07). Findings were consistent for daytime and night-time measurements. Liraglutide did not increase urine sodium excretion. CONCLUSION: Based on 24-hour ambulatory measurements, short-term treatment with liraglutide had a favourable effect on SBP whilst increasing heart rate.

11.
Curr Vasc Pharmacol ; 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31889495

RESUMO

The endothelial glycocalyx is a complex mesh of proteoglycans, glycoproteins and other soluble components which covers the vascular endothelium. It is considered to play an important role in many physiological processes including vascular permeability, transduction of shear stress and interaction of blood cells and other molecules with the vascular wall. Its complicate structure makes the precise assessment of the latter challenging, and many different visualization techniques have been implemented with various results. Diabetes, one of the main disease models where disorders of the glycocalyx are involved, causes degradation of the glycocalyx through a variety of molecular pathways and especially through oxidative stress with the action of reactive oxygen species. As the glycocalyx has been primarily studied in the glomerular endothelium, more and more evidence points towards a vital role in albumin handling and, consequently, to diabetic nephropathy. Therefore, the maintenance or restoration of the integrity of the glycocalyx seems a promising therapeutic target. In this review, we present the structural and functional capacities of the endothelial glycocalyx, and the available methods for its evaluation. Then, we describe the mechanisms through which diabetes leads to glycocalyx degradation and albuminuria, the current data on the field and possible treatment options targeting the glycocalyx.

12.
J Musculoskelet Neuronal Interact ; 18(4): 509-524, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30511955

RESUMO

OBJECTIVES: Obesity is characterized by a chronic, low grade, systemic inflammation. However, little is known about the role of skeletal muscle, which represents an active metabolic organ whose activities need to be determined. The purpose of our study was to detect relationships between skeletal muscle and adipose tissue inflammation with nonalcoholic fatty liver disease (NAFLD) and diabetes, as well as to explore associations with clinicopathological parameters. METHODS: Our study population consisted of 50 morbidly obese patients undergoing planned bariatric surgery. Biopsies were taken from visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), skeletal muscle (SM), extramyocellular adipose tissue (EMAT) and liver. The expression of CD68 and CD3 was assessed by immunohistochemistry. RESULTS: Our findings suggest a complex inter- and intra-tissue co-expression network that links obesity-induced inflammation in adipose depots and skeletal muscle with NAFLD. A novel finding is the intricate cross-talk between SM, EMAT and the liver and the probable correlation between SM, EMAT inflammation and the presence of liver fibrosis. CONCLUSIONS: Although the mechanisms of obesity-induced inflammation and its association with NAFLD and liver fibrosis are incompletely understood, our findings indicate an extensive and complex tissue network that needs to be further investigated.


Assuntos
Tecido Adiposo/patologia , Mediadores da Inflamação/sangue , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Músculo Esquelético/patologia , Obesidade Mórbida/sangue , Obesidade Mórbida/diagnóstico , Tecido Adiposo/metabolismo , Adulto , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/epidemiologia , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Obesidade Mórbida/epidemiologia , Adulto Jovem
13.
Nutrients ; 10(12)2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30518065

RESUMO

The role of nutrition in the pathogenesis of cardiovascular disease has long been debated. The established notion of the deleterious effects of fat is recently under question, with numerous studies demonstrating the benefits of low-carbohydrate, high-fat diets in terms of obesity, diabetes, dyslipidemia, and metabolic derangement. Monounsaturated and polyunsaturated fatty acids, especially n-3 PUFAs (polyunsaturated fatty acids), are the types of fat that favor metabolic markers and are key components of the Mediterranean Diet, which is considered an ideal dietary pattern with great cardioprotective effects. Except for macronutrients, however, micronutrients like polyphenols, carotenoids, and vitamins act on molecular pathways that affect oxidative stress, endothelial function, and lipid and glucose homeostasis. In relation to these metabolic markers, the human gut microbiome is constantly revealed, with its composition being altered by even small dietary changes and different microbial populations being associated with adverse cardiovascular outcomes, thus becoming the target for potential new treatment interventions. This review aims to present the most recent data concerning different dietary patterns at both the macro- and micronutrient level and their association with atherosclerosis, obesity, and other risk factors for cardiovascular disease.


Assuntos
Doenças Cardiovasculares , Dieta com Restrição de Carboidratos , Dieta Hiperlipídica , Gorduras na Dieta , Aterosclerose , Humanos , Nutrientes , Obesidade , Risco
14.
Hellenic J Cardiol ; 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30138744

RESUMO

OBJECTIVE: PGC-1α is already known as a significant regulator of mitochondrial biogenesis, oxidative phosphorylation and fatty acid metabolism. Our study focuses on the role of PGC1α in morbid obesity, in five different tissues, collected from 50 severely obese patients during planned bariatric surgery. METHODS: The investigated tissues included subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), skeletal muscle (SM), extramyocellular adipose tissue (EMAT) and liver. PGC1α expression was investigated with immunohistochemistry and evaluated with microscopy. RESULTS: Our findings highlighted significant positive inter-tissue correlations regarding PGC-1α expression between several tissue pairs (VAT-SAT, VAT-SM, VAT-EMAT, SAT-SM, SAT-EMAT, SM-EMAT). Moreover, we found significant negative correlations between PGC1α expression in VAT with CD68 expression in skeletal muscle and EMAT, implying a possible protective role of PGC1α against obesity-induced inflammation. CONCLUSION: Unmasking the inter-tissue communication networks regarding PGC-1α expression in morbid obesity, will give more insight into its significant role in obesity-induced diseases. PGC1α could potentially represent a future preventive and therapeutic target against obesity-induced disease, probably through enhancing mitochondrial biogenesis and metabolism.

15.
Stroke ; 49(8): 1992-1995, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29991656

RESUMO

Background and Purpose- Scarce data indicate that statin pretreatment (SP) in patients with acute cerebral ischemia because of large artery atherosclerosis may be related to lower risk of recurrent stroke because of a decreased incidence of microembolic signals (MES) during transcranial Doppler monitoring. Methods- We performed a systematic review and meta-analysis of available observational studies reporting MES presence/absence or MES burden, categorized according to SP status, in patients with acute cerebral ischemia because of symptomatic (≥50%) large artery atherosclerosis. In studies with partially-published data, authors were contacted for previously unpublished information. We also performed a sensitivity analysis of studies with data on MES burden categorized according to SP status, and an additional subgroup analysis in patients receiving higher-dose SP (atorvastatin 80 mg or rosuvastatin 40 mg daily). Results- Seven eligible study protocols were identified (610 patients, 54% with SP). SP was associated with a reduced risk of MES detection during transcranial Doppler monitoring (risk ratio=0.67; 95% CI, 0.45-0.98), with substantial heterogeneity between studies ( I2=52%). In studies reporting MES burden (n=4), a significantly lower number of MES were identified in patients with compared with those without SP (mean difference=-0.92; 95% CI, -1.64 to -0.19), with no evidence of heterogeneity between studies ( I2=49%). Subgroup analysis revealed that higher-dose SP reduced the risk of detecting MES (risk ratio=0.23; 95% CI, 0.06-0.88), with no evidence of heterogeneity between studies ( I2=0%). Conclusions- SP seems to be associated with a lower incidence and burden of MES in patients with acute cerebral ischemia because of large artery atherosclerosis.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Arteriosclerose Intracraniana/diagnóstico por imagem , Embolia Intracraniana/diagnóstico por imagem , Microvasos/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Humanos , Arteriosclerose Intracraniana/tratamento farmacológico , Embolia Intracraniana/tratamento farmacológico , Microvasos/efeitos dos fármacos
16.
Heart Fail Rev ; 23(3): 337-346, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29524067

RESUMO

The prevalence of heart failure (HF) in the diabetic population has rapidly increased over the past 2 decades, triggering research about the impact of oral anti-diabetic medications on it. Unfortunately, not all success at the bench in preclinical experiments has translated to success at the bedside. On the other hand, recent promising clinical data from oral SGLT2 inhibitors mainly lack mechanistic explanation from experimental studies. Hence, it is critical to understand the lessons learned from prior translational studies to gain a better knowledge of the mechanisms of oral anti-diabetic drugs in HF. This review aims to summarize the results from preclinical studies regarding the interaction between oral anti-diabetic medications and heart failure development and/or exacerbation. Although there is a wide spectrum of controversial results, the underlying hope is that the clinical success rate will improve and the adverse events during ineffective targeted therapy will be limited.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Hipoglicemiantes/administração & dosagem , Administração Oral , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Saúde Global , Insuficiência Cardíaca/etiologia , Humanos , Incidência
17.
Heart Fail Rev ; 23(3): 377-388, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29383638

RESUMO

Diabetes mellitus is a leading cause of cardiovascular morbidity and mortality worldwide. Traditional antidiabetic therapies targeting hyperglycemia reduce diabetic microvascular complications but have minor effects on macrovascular complications, including cardiovascular disease. Instead, cardiovascular complications are improved by antidiabetic medications (metformin) and other therapies (statins, antihypertensive medications) ameliorating insulin resistance and other associated metabolic abnormalities. Novel classes of antidiabetic drugs have proven efficacious in improving glycemia, while at the same time exert beneficial effects on pathophysiologic mechanisms of diabetes-related cardiovascular disease. In the present review, we will present current evidence of the cardiovascular effects of two new classes of antidiabetic medications, glucagon-like peptide 1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP4) inhibitors, focusing from mechanistic preclinical and clinical investigation to late-phase clinical testing.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/sangue , Inibidores da Dipeptidil Peptidase IV/farmacologia , Peptídeo 1 Semelhante ao Glucagon/agonistas , Hipoglicemiantes/farmacologia , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Saúde Global , Humanos , Morbidade/tendências
18.
Cardiovasc Diabetol ; 17(1): 8, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29310645

RESUMO

BACKGROUND: Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. We investigated the changes in arterial stiffness and left ventricular (LV) myocardial deformation after 6-month treatment with the GLP-1 analogue liraglutide in subjects with newly diagnosed T2DM. METHODS: We randomized 60 patients with newly diagnosed and treatment-naive T2DM to receive either liraglutide (n = 30) or metformin (n = 30) for 6 months. We measured at baseline and after 6-month treatment: (a) carotid-femoral pulse wave velocity (PWV) (b) LV longitudinal strain (GLS), and strain rate (GLSR), peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography. LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO (%dpTw-UtwMVO), at peak (%dpTw-UtwPEF) and end of early LV diastolic filling (%dpTw-UtwEDF) (c) Flow mediated dilatation (FMD) of the brachial artery and percentage difference of FMD (FMD%) (d) malondialdehyde (MDA), protein carbonyls (PCs) and NT-proBNP. RESULTS: After 6-months treatment, subjects that received liraglutide presented with a reduced PWV (11.8 ± 2.5 vs. 10.3 ± 3.3 m/s), MDA (0.92 [0.45-2.45] vs. 0.68 [0.43-2.08] nM/L) and NT-proBNP (p < 0.05) in parallel with an increase in GLS (- 15.4 ± 3 vs. - 16.6 ± 2.7), GLSR (0.77 ± 0.2 vs. 0.89 ± 0.2), pUtwVel (- 97 ± 49 vs. - 112 ± 52°, p < 0.05), %dpTw-UtwMVO (31 ± 10 vs. 40 ± 14), %dpTw-UtwPEF (43 ± 19 vs. 53 ± 22) and FMD% (8.9 ± 3 vs. 13.2 ± 6, p < 0.01). There were no statistically significant differences of the measured markers in subjects that received metformin except for an improvement in FMD. In all subjects, PCs levels at baseline were negatively related to the difference of GLS (r = - 0.53) post-treatment and the difference of MDA was associated with the difference of PWV (r = 0.52) (p < 0.05 for all associations) after 6-month treatment. CONCLUSIONS: Six-month treatment with liraglutide improves arterial stiffness, LV myocardial strain, LV twisting and untwisting and NT-proBNP by reducing oxidative stress in subjects with newly diagnosed T2DM. ClinicalTrials.gov Identifier NCT03010683.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Incretinas/uso terapêutico , Liraglutida/uso terapêutico , Contração Miocárdica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Rigidez Vascular/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Adulto , Biomarcadores/sangue , Fenômenos Biomecânicos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/fisiopatologia , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Grécia , Humanos , Hipoglicemiantes/efeitos adversos , Incretinas/efeitos adversos , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Fatores de Tempo , Resultado do Tratamento
19.
Stroke ; 48(8): 2285-2288, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28596449

RESUMO

BACKGROUND AND PURPOSE: Even though current guidelines suggest that noninvasive ventilatory correction (NIVC) could be considered for acute ischemic stroke patients with obstructive sleep apnea, available evidence is conflicting, with no adequately powered randomized clinical trial being available to date. METHODS: We conducted a systematic review and meta-analysis of all available literature data evaluating the effect of NIVC on neurological improvement (based on decrease in National Institutes of Health Stroke Scale score), vascular events (recurrent stroke, transient ischemic attack, myocardial infarction and unstable angina), and mortality during the follow-up period. RESULTS: We identified 4 randomized clinical trials and 1 prospectively matched observational cohort, comprising a total of 389 patients (59.8% males, mean age: 64.4 years). The risk of both performance and detection bias was considered high in most of the included randomized clinical trials because of the lack of blinding in participants, personnel and/or outcome assessors. The mean decrease in National Institutes of Health Stroke Scale scores during the first (≤30) days of acute ischemic stroke was found to be greater in NIVC-treated patients in comparison to controls (standardized mean difference, 0.38; 95% confidence interval, 0.11-0.66; P=0.007). However, no significant differences were detected between NIVC-treated acute ischemic stroke patients and controls on both the risk of vascular events (risk ratio, 0.53; 95% confidence interval, 0.25-1.14; P=0.11) and mortality (risk ratio, 0.71; 95% confidence interval, 0.37-1.36; P=0.30). No evidence of heterogeneity (I2=0%; P for Cochran Q>0.50) or publication bias were detected in all analyses. CONCLUSIONS: NIVC seems to be associated with greater short-term neurological improvement in acute ischemic stroke patients with obstructive sleep apnea. This finding deserves further investigation within the settings of an adequately powered, sham-control, randomized clinical trial.


Assuntos
Isquemia Encefálica/terapia , Pressão Positiva Contínua nas Vias Aéreas/métodos , Apneia Obstrutiva do Sono/terapia , Acidente Vascular Cerebral/terapia , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Pressão Positiva Contínua nas Vias Aéreas/tendências , Humanos , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia
20.
Int J Cardiol ; 233: 105-112, 2017 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-28096045

RESUMO

BACKGROUND: First-degree relatives of type-2 diabetes patients (FDR) present insulin resistance. We investigated whether FDR and dysglycaemic subjects demonstrate abnormal endothelial glycocalyx and LV deformation during postprandial hyperglycemia. METHODS: We studied 40 FDR with normal oral glucose test (OGTT), 40 subjects with abnormal OGTT (dysglycaemic) and 20 subjects with normal OGTT without parental history of diabetes (normoglycaemic). At 0 and 120min of OGTT we measured: a) LV longitudinal strain (LS) of subendocardial, mid-myocardial and subepicardial layers, global LS (GLS), peak twisting (pTw), untwisting velocity (pUtwVel), by speckle tracking echocardiography b) perfused boundary region (PBR) of the sublingual arterial microvessels; high PBR values represent reduced glycocalyx thickness. Insulin resistance was evaluated using insulin sensitivity index (ISI). RESULTS: ISI was related with baseline PBR, GLS and pTw in all subjects (p<0.05). Compared to normoglycaemics, FDR and dysglycaemics had higher PBR, lower ISI, GLS (-18.4±2.6 and -16.8±2.0 vs. -19.2±2.4%), subendocardial LS (-19.0±4.2 and -17.9±3.0 vs. -20.1±3.4%), pTw (14.4±4.4 and 15.6±6.4 vs. 16.9±6.5deg) and pUtwVel (p<0.05 for all comparisons). A GLS<-18% identified FDR with LV dysfunction (p=0.016). Post-OGTT, GLS and the subendocardial LS decreased while pTw and pUtwVel increased in FDR and dysglycaemics (p<0.05) indicating prevalence of the motion of the subepicardial over a dysfunctioning subendocardial myocardial helix. Increased PBR was related with impaired deformation markers at baseline and 120min of OGTT (p<0.05). CONCLUSION: First-degree relatives and dysglycaemics have reduced glycocalyx thickness related with impaired LV longitudinal, twisting-untwisting function. Postprandial hyperglycemia when combined with insulin resistance causes LV longitudinal dysfunction leading to increased LV twisting.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Diagnóstico Precoce , Ecocardiografia/métodos , Endotélio Vascular/metabolismo , Glicocálix/metabolismo , Resistência à Insulina/fisiologia , Disfunção Ventricular Esquerda/diagnóstico , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Endotélio Vascular/fisiopatologia , Família , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Miocárdio/metabolismo , Disfunção Ventricular Esquerda/genética , Disfunção Ventricular Esquerda/metabolismo , Função Ventricular Esquerda/fisiologia
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