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BACKGROUND: Aldosterone excess chronically induces oxidative stress and cell proliferation. Previously, a single study investigated primary aldosteronism (PA) in patients with papillary thyroid cancer (PTC), albeit without a matched control group. METHODS: We conducted a propensity score matched case-control study to investigate the association between PA and PTC in individuals with arterial hypertension (HT). PA was investigated in 137 patients with PTC and HT. The control group included 137 (1:1) age, sex-, and body mass index (BMI)-matched individuals with HT. We conducted a secondary analysis in which the controls were also matched according to HT stage. RESULTS: The prevalence of PA was 29.20% (95% confidence interval [CI], 21.91%-37.68%) in the PTC group and 20.44% (95% CI, 14.22%-28.35%) in the controls not matched for HT stage (p = 0.093). Although the PA prevalence was similar in both groups, the frequency of severe HT (stage III or resistant) was significantly lower in the PTC group (23%) compared to the hypertensive controls (73%, p < 0.001). After matching the controls by HT stage, the prevalence of PA in the PTC group was significantly higher compared to the hypertensive controls (9.56%; 95% CI, 5.39%-16.1%, p < 0.0001). In the multivariable analysis, PTC was independently associated with PA in both unmatched hypertensive individuals (odds ratio [OR] 4.74; 95% CI, 2.26-10.55; p< 0.001) and in those matched for HT stage (OR 5.88, 95% CI, 2.79-13.37; p< 0.001). CONCLUSION: PTC was an independent variable associated with a diagnosis of PA in hypertensive individuals. Therefore, we propose the association between PTC and HT as a new recommendation for PA screening regardless of HT severity.

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BACKGROUND: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). METHODS: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI + Veh (infarcted, treated with vehicle); and AMI + PY (infarcted, treated with the cholinesterase inhibitor, pyridostigmine bromide (PY)-40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. The clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. RESULTS: Seven days post-surgery, the AMI + PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI + Veh group. Furthermore, there was a notable downregulation in pro-inflammatory gene expression and an upregulation in anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers, indicative of subclinical kidney injury. CONCLUSIONS: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

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INTRODUCTION: High blood pressure in hypertensive smokers is affected by nicotine consumption. This study aimed to evaluate the effect of smoking cessation treatments on blood pressure in hypertensive smokers. METHODS: A total of 113 hypertensive smokers on antihypertensives during smoking cessation treatment in the randomized controlled trial GENTSMOKING were considered for analysis. At Baseline (T0) and Week 12 (T12), systolic and diastolic blood pressure (SBP and DBP), and heart rate (HR) were measured using a semi-automated digital oscillometric device. Mean arterial pressure (MAP) and delta differences for SBP, DBP, HR, and MAP were calculated. Smoking cessation was confirmed by measuring carbon monoxide (CO) in exhaled air. RESULTS: After 12 weeks of treatment, 72 participants ceased smoking (cessation group) and 41 did not (no cessation group). At T0, there was no statistically meaningful difference between groups with respect to age, body mass index, CO, and daily cigarette consumption. At T12, daily cigarette consumption and CO had decreased in both groups (p<0.001). The cessation group showed decreased SBP (131 ± 2 vs 125 ± 2 mmHg, p=0.004), DBP (79 ± 1 vs 77 ± 1 mmHg, p=0.031), MAP (96 ± 1 vs 93 ± 1 mmHg, p=0.005), and HR (79 ± 1 vs 74 ± 1 beats/min, p=0.001), and increased body weight (77.4 ± 2.1 vs 79.2 ± 2.2 kg, p<0.001). No significant differences were seen for these variables in the no cessation group. Decrease in blood pressure was significantly higher among hypertensive participants with SBP ≥130 mmHg: SBP (145 ± 2 vs 132 ± 2 mmHg, p<0.001), DBP (85 ± 2 vs 80 ± 1 mmHg, p=0.002), MAP (105 ± 1 vs 97 ± 1 mmHg, p<0.001), and HR (81 ± 2 vs 74 ± 2 beats/min, p=0.002). A positive correlation was found between HR and CO (r=0.34; p=0.001). CONCLUSIONS: Smoking cessation treatment reduced blood pressure in hypertensive smokers, allowing them to reach therapeutic targets for hypertension management. Smoking cessation has a positive impact on hypertension treatment; therefore, it should be encouraged in clinical practice. CLINICALTRIALSGOV IDENTIFIER: NCT03362099.

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Resumo Fundamento: A rigidez arterial aumentada é considerada atualmente um fator de risco independente para fibrilação atrial. No entanto, os mecanismos fisiopatológicos dessa arritmia ainda constituem uma lacuna no conhecimento a ser explorada. Objetivos: Investigar a existência de uma associação entre rigidez arterial e densidade de extrassístoles atriais em indivíduos hipertensos sem fibrilação atrial. Métodos: Estudo transversal com pacientes hipertensos sem fibrilação atrial diagnosticada, que foram estudados com ecocardiografia speckle-tracking para avaliar o strain do átrio esquerdo e velocidade de onda de pulso carótido-femoral (VOPcf) para avaliar a rigidez arterial. Todos os pacientes foram submetidos ao Holter de 24 horas e exames laboratoriais. O nível de significância adotado foi de p<0,05. Resultados: Setenta pacientes de um único centro sem doença cardiovascular evidente foram incluídos. A VOPcf correlacionou-se com uma maior densidade de extrassístoles atriais no Holter de 24 horas, independentemente da massa ventricular esquerda [1,48 (1,08- 2,03), p = 0,005]. Uma VOPcf aumentada correlacionou-se com valores reduzidos de strain atrial esquerdo, com coeficientes de correlação de Spearman de −0,27 (p= 0,027) e −0,29 (p = 0,018) para strains bidimensionais de reservatório e de conduto, respectivamente. Conclusão: Neste estudo com pacientes hipertensos, foi possível demonstrar uma associação entre rigidez arterial e maior densidade de arritmias atriais. Além disso, a rigidez arterial associou-se com valores mais baixos de strain atrial esquerdo das funções de reservatório e de conduto.

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Abstract Background: Increased arterial stiffness is currently an independent risk factor for atrial fibrillation, but the pathophysiological mechanisms of this arrhythmia remain an area of knowledge gap to be explored. Objectives: To investigate the existence of an association between arterial stiffness and the density of premature atrial contractions (PACs) in hypertensive individuals without atrial fibrillation. Methods: Cross-sectional study with hypertensive patients without diagnosed atrial fibrillation, who were studied with speckle-tracking echocardiography to assess left atrial (LA) strain and carotid-femoral pulse wave velocity (cfPWV) to assess arterial stiffness. All patients underwent 24h-ECG Holter and laboratory tests. Significance level was set at p<0.05. Results: Seventy participants from a single centre without overt cardiovascular disease were included. The cfPWV was correlated with higher density of PACs in 24h-Holter monitoring, independently of LV mass index (1.48 [1.08-2.03], p-value 0.005). Increased cfPWV was correlated with decreased LA strain values, with Spearman correlation coefficients of −0.27 (p-value 0.027) and −0.29 (p-value 0.018) for reservoir and conduit 2D Strain, respectively. Conclusions: In this study with hypertensive patients, it was possible to demonstrate an association between arterial stiffness and higher density of atrial arrhythmias. Furthermore, arterial stiffness was associated with lower left atrial strain values for reservoir and conduit functions.

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Previous studies show that COVID-19 survivors have elevated muscle sympathetic nerve activity (MSNA), endothelial dysfunction, and aortic stiffening. However, the neurovascular responses to mental stress and exercise are still unexplored. We hypothesized that COVID-19 survivors, compared with age- and body mass index (BMI)-matched control subjects, exhibit abnormal neurovascular responses to mental stress and physical exercise. Fifteen severe COVID-19 survivors (aged: 49 ± 2 yr, BMI: 30 ± 1 kg/m2) and 15 well-matched control subjects (aged: 46 ± 3 yr, BMI: 29 ± 1 kg/m2) were studied. MSNA (microneurography), forearm blood flow (FBF), and forearm vascular conductance (FVC, venous occlusion plethysmography), mean arterial pressure (MAP, Finometer), and heart rate (HR, ECG) were measured during a 3-min mental stress (Stroop Color-Word Test) and during a 3-min isometric handgrip exercise (30% of maximal voluntary contraction). During mental stress, MSNA (frequency and incidence) responses were higher in COVID-19 survivors than in controls (P < 0.001), and FBF and FVC responses were attenuated (P < 0.05). MAP was similar between the groups (P > 0.05). In contrast, the MSNA (frequency and incidence) and FBF and FVC responses to handgrip exercise were similar between the groups (P > 0.05). MAP was lower in COVID-19 survivors (P < 0.05). COVID-19 survivors exhibit an exaggerated MSNA and blunted vasodilatory response to mental challenge compared with healthy adults. However, the neurovascular response to handgrip exercise is preserved in COVID-19 survivors. Overall, the abnormal neurovascular control in response to mental stress suggests that COVID-19 survivors may have an increased risk to cardiovascular events during mental challenge.

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COVID-19 , Fuerza de la Mano , Adulto , Humanos , Persona de Mediana Edad , Presión Sanguínea/fisiología , Hemodinámica , Ejercicio Físico/fisiología , Frecuencia Cardíaca/fisiología , Sistema Nervioso Simpático , Antebrazo/irrigación sanguínea , Músculo Esquelético/inervación

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BACKGROUND: There is emerging evidence that the nervous system regulates immune and metabolic alterations mediating Metabolic syndrome (MetS) pathogenesis via the vagus nerve. This study evaluated the effects of transcutaneous auricular vagus nerve stimulation (TAVNS) on key cardiovascular and inflammatory components of MetS. METHODS: We conducted an open label, randomized (2:1), two-arm, parallel-group controlled trial in MetS patients. Subjects in the treatment group (n = 20) received 30 min of TAVNS with a NEMOS® device placed on the cymba conchae of the left ear, once weekly. Patients in the control group (n = 10) received no stimulation. Hemodynamic, heart rate variability (HRV), biochemical parameters, and monocytes, progenitor endothelial cells, circulating endothelial cells, and endothelial micro particles were evaluated at randomization, after the first TAVNS treatment, and again after 8 weeks of follow-up. RESULTS: An improvement in sympathovagal balance (HRV analysis) was observed after the first TAVNS session. Only patients treated with TAVNS for 8 weeks had a significant decrease in office BP and HR, a further improvement in sympathovagal balance, with a shift of circulating monocytes towards an anti-inflammatory phenotype and endothelial cells to a reparative vascular profile. CONCLUSION: These results are of interest for further study of TAVNS as treatment of MetS.

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CONTEXT: Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277-415.5 pmol/L) using immunoassay. OBJECTIVE: To evaluate intra-individual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening. METHODS: A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least 2 screenings. RESULTS: The median intra-individual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level <15 ng/dL, 19.9% had at least 2 aldosterone levels <15 ng/dL, and 16.2% had mean aldosterone levels <15 ng/dL. A lower cutoff of 10 ng/dL was associated with false negative rates for PA screening of 14.3% for a single aldosterone measurement, 4.6% for 2 aldosterone measurements, and only 2.3% for mean aldosterone levels. Considering the minimum aldosterone, true positive rate of aldosterone thresholds was 85.7% for 10 ng/dL and 61.6% for 15 ng/dL. An A/DRC >2 ng/dL/µIU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on 1 or 2 assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering antihypertensive medications, PA lateralization, hypokalemia, age, and number of hormone measurements. CONCLUSION: Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negatives in a single screening for PA. Therefore, PA screening should be based on at least 2 screenings with concomitant aldosterone and renin measurements.

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Hiperaldosteronismo , Hipertensión , Humanos , Aldosterona , Hiperaldosteronismo/diagnóstico , Renina , Inmunoensayo/métodos , Presión Sanguínea

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AIMS: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of JNC 7 Stage I hypertension in patients with type 2 diabetes mellitus. METHODS: In an a priori subgroup analysis of a randomized, double-blind, controlled trial, volunteers aged 30-70 years, with stage I hypertension and diabetes mellitus, were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 47) or 50 mg of losartan (N = 50), and followed for 18 months in 21 clinical centers. If BP remained uncontrolled after three months, study medication dose was doubled, and if uncontrolled after six months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg BID) were added as open label drugs in a progressive fashion. RESULTS: Systolic BP decreased to a greater extent in participants allocated to diuretics compared to losartan (P < 0.001). After 18 months of follow-up, systolic BP was 128.4 ± 10.3 mmHg in the diuretic group versus 133.5 ± 8.0 in the losartan group (P < 0.01). In the diuretic group, 36 out of 43 participants (83.7%) had a JNC 7 normal BP, compared to 31/47 (66%) in the losartan group (P = 0.089). Serum cholesterol was higher in the diuretic arm at the end of the trial. Other biochemical parameters and reports of adverse events did not differ by treatment. CONCLUSIONS: Treatment of hypertension based on a combination of chlorthalidone and amiloride is more effective for BP lowering compared to losartan in patients with diabetes mellitus and hypertension. TRIAL REGISTRATION: Clinical trials registration number: NCT00971165.

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Amilorida/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Clortalidona/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Losartán/administración & dosificación , Adulto , Anciano , Amilorida/efectos adversos , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Brasil , Clortalidona/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/patología , Losartán/efectos adversos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del Tratamiento

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BACKGROUND Kommerell diverticulum with a right-sided aortic arch is a rare congenital anatomical condition most often observed in adults. A possible etiology of the subclavian artery's anomalous origin would be an abnormality in regression of the fourth primitive aortic arch during embryonic development. CASE REPORT We report on the case of a 16-year-old female patient presenting with complaints of occasional tachycardia and mild non-specific dyspnea after anxiety crises. Physical examination revealed lower amplitude of the pulses in the left upper limb compared to the right upper limb, and difference in blood pressure (BP) values of 80×60 mmHg, and 100×60 mmHg, respectively. Different radiological imaging modalities were performed to elucidate a possible vascular abnormality. Multislice detector computed tomography angiography of the thoracic aorta and supra-aortic trunks showed a right-sided aortic arch and an aberrant origin of the left subclavian artery with a retroesophageal course and dilation of its emergence (Kommerell diverticulum), as well as duplicity of the right vertebral artery (RVA). Considering the actual small diameter of the diverticulum and the absence of dysphagia or severe external esophageal compression analyzed by the esophagogram, vascular surgery was not indicated. Since complications have been described in the literature, the patient must be kept under observation in the future. CONCLUSIONS Congenital vascular alterations, including Kommerell diverticulum with right-sided aortic arch and the aberrant origin of the left subclavian artery, should be suspected in otherwise asymptomatic young patients with few clinical manifestations. Investigation with different imaging methods helps to clarify the vascular abnormalities, to support a possible surgical procedure indication, and to monitor the patients in follow-up.

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Aorta Torácica/anomalías , Divertículo/congénito , Divertículo/diagnóstico por imagen , Arteria Subclavia/anomalías , Arteria Vertebral/anomalías , Adolescente , Aorta Torácica/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Femenino , Humanos , Tomografía Computarizada Multidetector , Arteria Subclavia/diagnóstico por imagen , Arteria Vertebral/diagnóstico por imagen

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OBJECTIVES: The aim of this study was to determine if carvedilol improved structural and functional changes in the left ventricle and reduced mortality in patients with hypertensive heart disease. METHODS: Blood pressure, heart rate, echocardiographic parameters, and laboratory variables, were assessed pre and post treatment with carvedilol in 98 eligible patients. RESULTS: Carvedilol at a median dose of 50 mg/day during the treatment period in hypertensive heart disease lowered blood pressure 10/10 mmHg, heart rate 10 beats/min, improved left ventricular ejection fraction from baseline to follow-up (median: 6 years) (36%-47%)) and reduced left ventricular end-diastolic and end-systolic dimensions (62 vs 56 mm; 53 vs 42 mm, respectively, all p-values <0.01). Left ventricular ejection fraction increased in 69% of patients. Patients who did not have improved left ventricular ejection fraction had nearly six-fold higher mortality than those that improved (relative risk; 5.7, 95% confidence interval: 1.3-25, p = 0.022). CONCLUSION: Carvedilol reduced cardiac dimensions and improved left ventricular ejection fraction and cardiac remodeling in patients with hypertensive heart disease. These treatment-related changes had a favorable effect on survival.

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Physical exercise is one of the most important factors improving quality of life, but it is not feasible for patients with morbidity or limited mobility. Most previous studies focused on high-intensity or long-term exercise that causes metabolic stress or physiological adaption, respectively. Here, we studied how moderate-intensity swimming affects systemic inflammation in 6-8 week old C57BL/6J male mice during endotoxemia. One-hour swimming prevented hypokalemia, hypocalcemia, attenuated serum levels of inflammatory cytokines, increased anti-inflammatory cytokines but affected neither IL6 nor glycemia before or after the endotoxic challenge. Exercise attenuated serum TNF levels by inhibiting its production in the spleen through a mechanism mediated by the subdiaphragmatic vagus nerve but independent of the splenic nerve. Exercise increased serum levels of dopamine, and adrenalectomy prevented the potential of exercise to induce dopamine and to attenuate serum TNF levels. Dopaminergic agonist type-1, fenoldopam, inhibited TNF production in splenocytes. Conversely, dopaminergic antagonist type-1, butaclamol, attenuated exercise control of serum TNF levels. These results suggest that vagal induction of dopamine may contribute to the anti-inflammatory potential of physical exercise.

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Dopamina/metabolismo , Condicionamiento Físico Animal/fisiología , Nervio Vago/fisiología , Animales , Antiinflamatorios/farmacología , Citocinas/metabolismo , Dopamina/sangre , Endotoxemia/terapia , Inflamación/terapia , Lipopolisacáridos/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Sepsis/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo

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Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Cardiología/tendencias , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/diagnóstico por imagen , Insuficiencia Cardíaca/epidemiología , Enfermedades de las Válvulas Cardíacas/prevención & control

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We previously reported that cholinergic stimulation with pyridostigmine (PY) induces anti-inflammatory cell recruitment soon after myocardial infarction (MI). In this study, we evaluated the anti-inflammatory effects of PY during the proliferative phase of cardiac repair by analyzing the infiltration of macrophages, Treg lymphocytes, oxidative stress and inflammatory cytokines. Wistar rats underwent control sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated (untreated infarcted group, I) or to receive PY (30 mg·kg(-1)·day(-1)) in the supplied water (infarcted treated group, I + PY). Blood pressure and heart rate variability were registered at day 5 post-MI. The animals were euthanized 7 days after thoracotomy, when the hearts were removed and processed for immunohistochemistry (CD68, CD206, FOXP3), cytokines (IL-1ß, IL-6, IL-10, TNF-α) and oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, lipidic and protein peroxidation). PY treatment increased parasympathetic modulation, M2 macrophages and the anti-oxidant enzyme activity but reduced protein oxidation (carbonyls) and the concentration of IL-1ß, IL-6, TNF-α and IL-10. Cholinergic stimulation induces parasympathetic neuro-immune modulation and anti-inflammatory cell enrollment as well as prevents oxidative stress and cytokine production after MI.

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Cardiotónicos/farmacología , Inhibidores de la Colinesterasa/farmacología , Inflamación/tratamiento farmacológico , Infarto del Miocardio/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Bromuro de Piridostigmina/farmacología , Animales , Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Hemodinámica/efectos de los fármacos , Inflamación/metabolismo , Inflamación/patología , Masculino , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Estrés Oxidativo/fisiología , Distribución Aleatoria , Ratas Wistar

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BACKGROUND: Metabolic syndrome (MetS) is an obesity-driven condition of pandemic proportions that increases the risk of type 2 diabetes and cardiovascular disease. Pathophysiological mechanisms are poorly understood, though inflammation has been implicated in MetS pathogenesis. The aim of this study was to assess the effects of galantamine, a centrally acting acetylcholinesterase inhibitor with antiinflammatory properties, on markers of inflammation implicated in insulin resistance and cardiovascular risk, and other metabolic and cardiovascular indices in subjects with MetS. METHODS: In this randomized, double-blind, placebo-controlled trial, subjects with MetS (30 per group) received oral galantamine 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo. The primary outcome was inflammation assessed through plasma levels of cytokines and adipokines associated with MetS. Secondary endpoints included body weight, fat tissue depots, plasma glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol (total, HDL, LDL), triglycerides, BP, heart rate, and heart rate variability (HRV). RESULTS: Galantamine resulted in lower plasma levels of proinflammatory molecules TNF (-2.57 pg/ml [95% CI -4.96 to -0.19]; P = 0.035) and leptin (-12.02 ng/ml [95% CI -17.71 to -6.33]; P < 0.0001), and higher levels of the antiinflammatory molecules adiponectin (2.71 µg/ml [95% CI 1.93 to 3.49]; P < 0.0001) and IL-10 (1.32 pg/ml, [95% CI 0.29 to 2.38]; P = 0.002) as compared with placebo. Galantamine also significantly lowered plasma insulin and HOMA-IR values, and altered HRV. CONCLUSION: Low-dose galantamine alleviates inflammation and insulin resistance in MetS subjects. These findings support further study of galantamine in MetS therapy. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02283242. FUNDING: Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, and the NIH.

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AIMS: The aim of this study was to determine the rate of major clinical events and its determinants in patients with previous cardiovascular event or not, and with or without diabetes from a middle-income country. METHODS: REACT study is a multicenter registry conducted between July 2010 and May 2013 in Brazil. Patients were eligible if they were over 45years old and high cardiovascular risk. Patients were followed for 12months; data were collected regarding adherence to evidence-based therapies and occurrence of clinical events (all-cause mortality, non-fatal cardiac arrest, myocardial infarction, or stroke). RESULTS: A total of 5006 subjects was included and analyzed in four groups: No diabetes and no previous cardiovascular event, n=430; diabetes and no previous cardiovascular event, n=1138; no diabetes and previous cardiovascular event, n=1747; and diabetes and previous cardiovascular event, n=1691. Major clinical events in one-year follow-up occurred in 332 patients. A previous cardiovascular event was associated with a higher risk of having another event in the follow-up (HR 2.31 95% CI 1.74-3.05, p<0.001), as did the presence of diabetes (HR 1.28 95% CI 1.10-1.73, p=0.005). In patients with diabetes,failure to reach HbA1c targetswas related topoorer event-free survival compared to patients with good metabolic control (HR 1.70 95% CI 1.01-2.84, p=0.044). CONCLUSIONS: In Brazil, diabetes confers high risk for major clinical events, but this condition is not equivalent to having a previous cardiovascular event. Moreover, not so strict targets for HbA1c in patients with diabetes and previous cardiovascular events might be considered.

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Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 2/etiología , Brasil , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/patología , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Factores de Riesgo , Clase Social

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Whether sex influences the association of obstructive sleep apnea (OSA) with markers of cardiovascular risk in patients with hypertension is unknown. In this study, 95 hypertensive participants underwent carotid-femoral pulse wave velocity, 24-hour ambulatory blood pressure monitoring, echocardiogram, and polysomnography after a 30-day standardized treatment with hydrochlorothiazide plus enalapril or losartan. OSA was present in 52 patients. Compared with non-OSA patients, pulse wave velocity values were higher in the OSA group (men: 11.1±2.2 vs 12.7±2.4 m/s, P=.04; women: 11.8±2.4 vs 13.2±2.2 m/s, P=.03). The proportion of diastolic dysfunction was significant in men and women with OSA. Compared with non-OSA patients, nondipping systolic blood pressure in OSA was higher in men (14.3% vs 46.4%) and in women (41.4% vs 65.2%). OSA was independently associated with pulse wave velocity (ß=1.050; P=.025) and nondipping systolic blood pressure (odds ratio, 3.03; 95% confidence interval, 1.08-8.55; P=.035) in the regression analysis. In conclusion, OSA is independently associated with arterial stiffness and nondipping blood pressure in patients with hypertension regardless of sex.

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Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/epidemiología , Hipertensión/complicaciones , Apnea Obstructiva del Sueño/complicaciones , Rigidez Vascular/fisiología , Adulto , Anciano , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Monitoreo Ambulatorio de la Presión Arterial/métodos , Brasil/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Diuréticos/normas , Diuréticos/uso terapéutico , Ecocardiografía/métodos , Enalapril/administración & dosificación , Enalapril/uso terapéutico , Femenino , Humanos , Hidroclorotiazida/administración & dosificación , Hidroclorotiazida/normas , Hidroclorotiazida/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Hipertensión/fisiopatología , Losartán/administración & dosificación , Losartán/uso terapéutico , Masculino , Persona de Mediana Edad , Polisomnografía/métodos , Análisis de la Onda del Pulso/métodos , Factores de Riesgo , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/fisiopatología

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Introduction: Recurrent hypoxia (HPX), a hallmark of the obstructive sleep apnea (OSA), impairs autonomic balance, and increases arterial blood pressure (BP). Oxidative stress is one of the mechanisms involved in these alterations. The cumulative effect of acute intermittent HPX and the chronicity may determine whether the response crosses the threshold from having protective value to pathology. However, the impact of acute intermittent HPX-reoxygenation on markers of oxidative stress in healthy individuals remains to be fully understood. Objective: To analyze the effects of the acute intermittent HPX on the generation of neutrophil-derived superoxide, sympathovagal balance, and vascular function in healthy subjects. Methods: We applied six cycles of intermittent HPX (10% O2 and 90% N2) for 5 min followed by 2 min of room-air in 15 healthy volunteers (34 ± 2 years; 22.3 ± 0.46 kg/m2), without OSA (polysomnography), during wakefulness. During the experimental protocol, we recorded O2 saturation, end-tidal CO2, heart rate (HR), systolic, and diastolic BP, cardiac output (CO) and peripheral resistance (PR). Cardiac sympathovagal balance was determined by HR variability analysis (low frequency and high frequency bands, LF/HF). Superoxide generation in polymorphonuclear neutrophil cells were established using relative luminescence units (PMNs RLU) at baseline (pre-HPX) and immediately after hypoxia induction (post-HPX6). Results: The studied subjects had normal levels of BP, plasma glucose, lipid profile, and inflammatory marker (C-reactive protein). Acute intermittent HPX increased HR, systolic BP, CO, and decreased PR. Additionally, acute intermittent HPX increased PMNs RLU, measured post-HPX6 (470 ± 50 vs. 741 ± 135, P < 0.05). We found a similar increase in LF/HF post-HPX6 (0.91 ± 0.11 vs. 2.85 ± 0.40, P < 0.05). PR was diminished from pre-HPX to post-HPX6 (1.0 ± 0.03 vs. 0.85 ± 0.06, P < 0.05). Further analysis showed significant association between O2 saturation and PMNs RLU (R = -0.62, P = 0.02), and with LF/HF (R = -0.79, P = 0.02) post-HPX6. In addition, an association was found between PMNs RLU and PR post-HPX6 (R = 0.58, P = 0.04). Conclusion: Acute exposure to intermittent HPX not only increased superoxide generation in neutrophils, but also impaired cardiac sympathovagal balance in healthy subjects. These data reinforce the role of intermittent HPX in superoxide generation on neutrophils, which may lead to an impairment in peripheral vascular resistance.

RESUMEN

BACKGROUND: The effects of exercise training (ET) associated with pyridostigmine bromide (PYR) treatment on cardiac and autonomic function, as well as on inflammatory profile after myocardial infarction (MI), are unclear. METHODS: Male Wistar rats were randomly assigned to: control (C); sedentary+infarcted (I); sedentary+infarcted treated with PYR (IP); infarcted submitted to aerobic exercise training (IT); and infarcted submitted to treatment with PYR and aerobic exercise training (ITP). After 12weeks of ET (50-70% maximal running speed; 1h a day, 5days a week) and/or PYR treatment (0.14mg/mL on drink water), hemodynamic, autonomic and cytokines expression were performed. RESULTS: We observed that both aerobic ET, associated or not with PYR treatment in MI animals, were able to: reduced MI area, improved systolic and diastolic function, baroreflex sensitivity, cardiovascular autonomic modulation, and tonic activity of the sympathetic and parasympathetic nervous system. Also, they led to a reduction of inflammatory profile measured at plasma, left ventricle and soleus skeletal muscle. However, additional effects were observed when ET and PYR were associated, such as an increase in vagal tonus and modulation, reduction of MI area, interferon-γ and tumor necrosis factor-α (TNF-α), as well as an increase of interleukin-10/TNF-α ratio on left ventricle. CONCLUSION: These data suggest that associating ET and PYR promotes some additional benefits on cardiovascular autonomic modulation and inflammatory profile in infarcted rats.

Asunto(s)

Mediadores de Inflamación/sangre , Infarto del Miocardio/sangre , Infarto del Miocardio/terapia , Condicionamiento Físico Animal , Bromuro de Piridostigmina/uso terapéutico , Animales , Barorreflejo/fisiología , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/uso terapéutico , Mediadores de Inflamación/antagonistas & inhibidores , Masculino , Condicionamiento Físico Animal/métodos , Bromuro de Piridostigmina/farmacología , Distribución Aleatoria , Ratas , Ratas Wistar , Resultado del Tratamiento

RESUMEN

AIMS:The aim of this study was to determine the rate of major clinical events and its determinants in patients with previous cardiovascular event or not, and with or without diabetes from a middle-income country.METHODS:REACT study is a multicenter registry conducted between July 2010 and May 2013 in Brazil. Patients were eligible if they were over 45years old and high cardiovascular risk. Patients were followed for 12months; data were collected regarding adherence to evidence-based therapies and occurrence of clinical events (all-cause mortality, non-fatal cardiac arrest, myocardial infarction, or stroke).

Asunto(s)

Humanos , Masculino , Femenino , Persona de Mediana Edad , Diabetes Mellitus/etiología , Diabetes Mellitus/mortalidad , Diabetes Mellitus/patología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/patología