Vasculometabolic effects in patients with congenital growth hormone deficiency with and without GH replacement therapy during adulthood.

PURPOSE: To evaluated the metabolic profiles and vascular properties in congenital growth hormone (GH) deficiency (GHD) and its replacement in adults. PATIENTS AND METHODS: Cross-sectional study conducted in a single tertiary center for pituitary diseases. Eighty-one adult subjects were divided into three groups: (1) 29 GHD patients with daily subcutaneous GH replacement therapy (GHRT) during adulthood; (2) 20 GHD patients without GHRT during adulthood and (3) 32 controls. Only patients with adequate adherence to others pituitary hormone deficiencies were included. Anthropometric parameters, body composition by dual-energy X-ray absorptiometry, metabolic profiles and vascular properties (carotid intima media thickness, pulse wave velocity and flow-mediated dilation) were compared among the groups. RESULTS: Waist-to-height ratio (WHR), body fat percentages and fat mass index (FMI) were lower in patients with GHRT than patients without GHRT during adulthood (0.49 ± 0.06 vs. 0.53 ± 0.06 p = 0.026, 30 ± 10 vs. 40 ± 11 p = 0.003 and 7.3 ± 4 vs. 10 ± 3.5 p = 0.041, respectively). In addition, association between longer GHRT and lower body fat percentage was observed (r = - 0.326, p = 0.04). We found higher triglyceride (113.5 ± 62 vs. 78 ± 36, p = 0.025) and lower HDL cholesterol (51 ± 17 vs. 66 ± 23, p = 0.029) levels in patients without GHRT during adulthood in comparison to controls. No statistical differences were observed for vascular properties among the groups. CONCLUSIONS: No differences in vascular properties were observed in congenital GHD adult patients with or without GHRT despite patients without GHRT had an unfavorable body composition. GHRT currently remains an individualized decision in adults with GHD and these findings bring new insight into the treatment and follow-up of these patients.

May Measurement Month 2019: an analysis of blood pressure screening results from Brazil.

The aim of this study is to describe the results of the May Month Measurement (MMM) campaign implemented in Brazil, in 2019. Questionnaire data were collected and three measures of blood pressure (BP) were performed. The sample consisted of 13 476 individuals, 58.2% were white, 60.8% were women. The average age was 46.3 (18.6) years. Of all 13 476 participants, 6858 (50.9%) had hypertension defined as a systolic BP ≥140 mmHg or a diastolic BP ≥90 mmHg or being on anti-hypertensive medication. Of those with hypertension, 68.8% were aware of their diagnosis, 65.3% were on antihypertensive medication, and 36.1% had controlled BP (<140/90 mmHg). In addition, of 4479 participants on anti-hypertensive medication, 55.2% had controlled BP. The use of anti-hypertensive medication was associated with higher systolic (P < 0.001) and diastolic BP (P < 0.001) and having diabetes with higher systolic BP (P < 0.001). Previous hypertension in pregnancy was associated with higher systolic (P = 0.038) and diastolic BP (P = 0.003), and smoking was associated with higher systolic BP (P < 0.001). Lastly, obese and overweight individuals showed significantly higher systolic (P < 0.001) and diastolic (P < 0.001) BP. The Brazilian MMM19 data demonstrate that strategies to increase awareness of hypertension and a better control of the risk factors are still needed.

[São Paulo call to action for the prevention and control of high blood pressure: 2020Llamado a la acción de San Pablo para la prevención y el control de la hipertensión arterial, 2020]. / Chamado à ação de São Paulo para prevenção e controle da hipertensão arterial, 2020.

About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke).There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring.Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated.Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks.Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care.Urgent sustained action is needed is needed for effective public policies and health system changes to prevent and control hypertension.

Cerca de una cuarta parte de los adultos tienen hipertensión, el principal factor de riesgo de muerte (inclusive la causada por cardiopatía y accidente cerebrovascular).Existen políticas eficaces que podrían ayudar a las personas a elegir opciones saludables para prevenir el aumento de la presión arterial; si se las aplicara plenamente, se podría evitar en gran medida el desarrollo de hipertensión.La hipertensión es fácil de detectar y tratar, PERO solo alrededor de 50% de los adultos que presentan dicha afección son conscientes de su situación y solamente 1 de cada 7 de ellos recibe el tratamiento adecuado.La prevención y el control de la hipertensión es el mecanismo principal para prevenir y controlar las enfermedades no transmisibles y un modelo para evitar otros riesgos de presentar dichas enfermedades.La adopción de un modo de vida saludable y el tratamiento farmacológico efectivo podrían prevenir y controlar la hipertensión en la mayoría de las personas si se implementaran de manera sistemática en la población; en todos los entornos es posible aplicar intervenciones sencillas, que pueden usarse para mejorar la atención primaria.Es urgente adoptar medidas sostenidas para introducir cambios eficaces en las políticas públicas y los sistemas de salud pública con miras a prevenir y controlar la hipertensión.

[São Paulo call to action for the prevention and control of high blood pressure: 2020Chamado à ação de São Paulo para prevenção e controle da hipertensão arterial: 2020]. / Llamado a la acción de San Pablo para la prevención y el control de la hipertensión arterial, 2020.

About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke).There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring.Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated.Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks.Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care.Urgent sustained action is needed is needed for effective public policies and health system changes to prevent and control hypertension.

Cerca de » dos adultos têm hipertensão arterial, que é o fator de risco isolado mais importante para morte (incluídas as mortes por cardiopatia e acidente vascular cerebral).Existem políticas eficazes que poderiam facilitar escolhas pessoais saudáveis para evitar a elevação da pressão arterial e, se plenamente implementadas, podem prevenir a ocorrência da hipertensão arterial.É fácil rastrear e tratar a hipertensão, MAS somente cerca de 50% dos adultos hipertensos estão cientes de sua condição, e apenas cerca de 1 em cada 7 é tratado adequadamente.A prevenção e controle da hipertensão é o principal mecanismo de prevenção e controle das doenças não transmissíveis e um modelo para outros riscos de doenças não transmissíveis.Tratamentos eficazes com mudanças de estilo de vida e medicamentos poderiam prevenir e controlar a hipertensão arterial na maioria das pessoas se aplicados sistematicamente à população; as intervenções simples são viáveis em todos os ambientes e podem melhorar a atenção primária.É necessária a ação continuada e urgente a fim de obter mudanças efetivas nas políticas públicas e no sistema de saúde para prevenir e controlar a hipertensão arterial.

Safety of Atorvastatin in Patients With Stable Systemic Autoimmune Myopathies: A Pilot Longitudinal Study.

BACKGROUND/OBJECTIVE: Patients with systemic autoimmune myopathies (SAMs) have high prevalence of dyslipidemia and, consequently, possible endothelial dysfunction and vascular stiffness. Our objective was to evaluate the possible benefits on endothelial function and vascular stiffness, as well as adverse effects of atorvastatin in SAMs. METHODS: A pilot longitudinal, double-blind, randomized, placebo-controlled study was conducted. Twenty-four of 242 patients were randomized at a 2:1 ratio to receive atorvastatin (20 mg/d) or placebo for a period of 12 weeks. Demographic data, comorbidities, and clinical and laboratory parameters, as well as endothelial function and arterial stiffness, were evaluated. RESULTS: Of the 24 randomized patients, 4 patients were excluded, with remaining 20 patients (14 in the atorvastatin group and 6 in the placebo group). The mean age of the patients was 49.0 years, and 75% of the patients were female. At baseline, the demographic data, disease status, treatment, cardiovascular comorbidities, and risk factors were comparable between the atorvastatin and placebo groups. After 12 weeks of follow-up of atorvastatin therapy, no improvements were observed for endothelial function and arterial stiffness in either group (p > 0.05). As expected, a significant reduction in total and low-density lipoprotein cholesterol levels was observed. During the study, no clinical intercurrences or disease relapses were observed in either group. CONCLUSIONS: The atorvastatin drug attenuated low-density lipoprotein cholesterol without worsening clinical outcomes in SAMs. No change was observed for endothelial function and arterial stiffness. Additional studies, with long-term follow-up time and different atorvastatin dosage, are needed to corroborate the results of this study.

Gender differences of aortic wave reflection and influence of menopause on central blood pressure in patients with arterial hypertension.

BACKGROUND: Evidences suggest that central hemodynamics indexes are independent predictors of future cardiovascular events and all-cause mortality. Multiple factors have been pointed to have potential influence on central aortic function: height, heart rate, left ventricular ejection duration and blood pressure level. Data related to the influence of gender and postmenopausal status on aortic waveform reflection is scarce. We aim to evaluate the impact of gender and menopause on central blood pressure of hypertensive patients. METHODS: In a cross sectional study 122 hypertensive patients (52 men and 70 women) were studied. Hypertension was defined as blood pressure (BP) levels ≥140/90 mmHg or use of antihypertensive drugs. Central arterial pressure, augmentation index (AIx) and augmentation index normalized to 75 bpm (AIx75) were obtained using applanation tonometry. Menopause and postmenopause history were accessed by a direct series of questions. Postmenopause was defined as at least one year since last menstruation. Patients were paired by age, gender and menopausal status, and the data were compared considering gender and menopausal status. RESULTS: Height and weight were significantly lower in women than in men at the same age. Conversely, AIx (32.7 ± 9.8% vs. 20.1 ± 11.7%, p < 0.01), AIx75 (29.6 ± 6.7% vs. 18.3 ± 9.4%, p < 0.01) and central systolic blood pressure (136 ± 30 vs. 125 ± 23 mmHg, p = 0.03) were higher in women than men. The menopausal women (mean age of menopause = 48 years) had the worst indexes of aortic wave reflection, compared to men at the same age and younger women. CONCLUSION: Hypertensive women had both higher reflected aortic pressure waveform and central blood pressure indexes than hypertensive men, and these findings were worsened by the menopausal status.

A real-world analysis of outcomes and healthcare costs of patients on perindopril/indapamide/amlodipine single-pill vs. multiple-pill combination in Italy.

OBJECTIVES: This analysis compared adherence, cardiovascular (CV) events and all-cause mortality incidence, and healthcare costs among hypertensive patients treated with perindopril (PER)/indapamide (IND)/amlodipine (AML) in single-pill combination (SPC) vs. multiple-pill combination, in a real-world setting in Italy. METHODS: In this observational retrospective analysis of Italian administrative databases, adult patients treated with PER/IND/AML between 2010 and 2020 were divided into two cohorts: single-pill vs. multiple-pill. Patient data were available for at least one year before and after index date. Propensity score matching (PSM) was applied to reduce selection bias. Adherence was defined as proportion of days covered: non-adherence, <40%; partial adherence, 40-79%, and adherence ≥80%. Mortality incidence and CV events as single, or composite, endpoints were evaluated after first year of follow-up. Healthcare cost analyses were performed from the perspective of the Italian National Health Service. RESULTS: Following PSM, the single-pill cohort included 12 150 patients, and the multiple-pill cohort, 6105. The SPC cohort had a significantly higher percentage of adherent patients vs. the multiple-pill cohort (59.9% vs. 26.9%, P  < 0.001). Following the first year of follow-up, incidence of all-cause mortality, and combined endpoint of all-cause mortality and CV events were lower in the SPC cohort compared with multiple-pill cohort. Average annual direct healthcare costs were lower in the single-pill cohort (€2970) vs. multiple-pill cohort (€3642); cost of all drugs and all-cause hospitalizations were major contributors. CONCLUSION: The SPC of PER/IND/AML, compared with multiple-pill combination, is associated with higher adherence to medication, lower incidence of CV events and mortality, and reduced healthcare costs.

Coronary Artery Disease Assessment and Cardiovascular Events in Middle-Aged Patients on Hemodialysis.

OBJECTIVE: To explore whether, in younger patients on dialysis with longer life expectancy, assessment of coronary artery disease (CAD) could identify individuals at higher risk of events and revascularization might improve outcomes in selected patients contrary to what had been observed in elderly patients. METHODS: From August 1997 to January 2019, 2265 patients with stage 5 chronic kidney disease were prospectively referred for cardiovascular assessment. For this study, we selected 1374 asymptomatic patients aged between 18 and 64 years. After clinical risk stratification and cardiac scintigraphy by single-photon emission computed tomography, 866 patients underwent coronary angiography. The primary end point was the composite incidence of nonfatal/fatal major adverse cardiovascular events during a follow-up period of 0.1 to 189.7 months (median, 26 months). The secondary end point was all-cause mortality. RESULTS: The primary end point occurred in 327 (23.8%) patients. Clinically stratified high-risk patients had a 3-fold increased risk of the primary end point. The prevalence of abnormal findings on perfusion scans was 29.2% (n=375), and significant CAD was found in 449 (51.8%) of 866 patients who underwent coronary angiography. An abnormal finding on myocardial perfusion scan and the presence of CAD were significantly associated with a 74% and 22% increased risk of cardiovascular events, respectively. In patients undergoing percutaneous coronary intervention or coronary artery bypass grafting (n=99), there was an 18% reduction in the risk of all-cause death relative to patients receiving medical treatment (P=.03). CONCLUSION: In this cohort of middle-aged, asymptomatic patients on dialysis, assessment of CAD identified individuals at higher risk of events, and coronary intervention was associated with reducing the risk of death in selected patients.

Cardiovascular risk in women with nonclassical congenital adrenal hyperplasia.

CONTEXT: The outcomes related to cardiovascular risk (CVR) in patients with nonclassical form of congenital adrenal hyperplasia (NCAH) are unknown, especially those related to therapeutic options, including low doses of glucocorticoids (GCs) or oral contraceptive pills. OBJECTIVES: to analyze CVR by markers of atherosclerosis in females with nonclassical form according to therapeutic options. DESIGN AND SETTING: a cross-sectional study at a tertiary center. PATIENTS AND METHODS: Forty-seven females with NCAH (33.4 ± 10 years) were subdivided into: G1 (n = 28) treated with dexamethasone (0.14 ± 0.05 mg/m2/day); G2 (n = 19) with oral contraceptive pills; and G3 (30 matched controls). CVR was analyzed through serum lipids, HOMA-IR, inflammatory cytokines levels and quantitative image evaluations (pulse wave velocity-PWV, endothelial function by flow mediated dilatation-FMD, carotid intima media thickness-CIMT and visceral fat-VAT by abdominal tomography. RESULTS: There were no statistically significant differences in BMI, HOMA-IR, HDL-cholesterol, or triglyceride levels among groups (p > 0.05). Serum interleukin-6 levels ​​were higher in G1 than in G2 (p = 0.048), and interleukin-8 levels were higher in G1 than in G2/3 (p = 0.008). There were no statistically significant differences in VAT, PWV, FMD or CIMT among groups (p > 0.05). In multivariable regression analysis, there was no statistically significant association between glucocorticoid dose and evaluated outcomes. CONCLUSION: Adult females with NCAH did not show increased CVR using methodologies for detection of precocious atherosclerosis. Although patients receiving dexamethasone therapy had increased IL-6 and 8 levels, these data were not associated with radiological markers of atherosclerosis. Our cohort was composed of young adults and should be reevaluated in a long-term follow-up.

Cutoff Values of Aldosterone and the Aldosterone-Renin Ratio for Predicting Primary Aldosteronism in Patients with Resistant Hypertension: A Real-Life Study.

Primary aldosteronism (PA) is commonly associated with resistant hypertension. Biochemical tests can be clinically useful in the screening and diagnosis of primary aldosteronism. This study aimed to identify the cutoff values of aldosterone levels (A) and the aldosterone-renin ratio (ARR) for an accurate prediction of PA in patients with apparent resistant hypertension in a real-life scenario. This database-based study included a historical cohort of male and female patients with apparent resistant hypertension, aged 18 years or older and surveyed for PA in a specialized center from 2008 to 2018. Aldosterone and plasma renin activity (PRA) or the plasma renin concentration (PRC) were measured in the treated hypertensive patients. The patients with positive screening results were subsequently referred to the endocrinology department for confirmatory tests. The patients with confirmed PA were included in the case group, and the others remained as controls. Receiver-operating characteristic (ROC) curves were used to identify the cutoff points for aldosterone and the ARR, thereby analyzing their sensitivity and specificity for confirmed PA. Among the 3464 patients (59 ± 13 years old, 41% male) who had apparent resistance hypertension screened, PA was confirmed in 276 individuals (8%). A ≥ 16.95 ng/dL (95% CI: 0.908-0.933) had an odds ratio of 6.24 for PA, while A/PRA ≥ 29.88 (95% CI: 0.942-0.984) or an A/PRC ≥ 2.44 (95% CI: 0.978-0.990) had an odds ratio of 216.17 for PA diagnoses. Our findings suggest that a positive PA screening with aldosterone ≥ 17 ng/dL associated with A/PRA ≥ 29.88 or an A/PRC ratio of ≥2.44 should be sufficient to confirm the diagnosis of PA without confirmatory testing.

Severity of sleep apnea impairs adipose tissue insulin sensitivity in individuals with obesity and newly diagnosed obstructive sleep apnea.

Introduction: Obstructive sleep apnea (OSA) is a common sleep disorder associated with increased risk for the development of type 2 diabetes. While studies have examined the effects of sleep on whole-body insulin sensitivity, little is known about the effects of sleep on adipose tissue insulin sensitivity in patients with OSA. We analyzed if the severity of OSA, measured by apnea-hypopnea index (AHI), is associated with adipose tissue insulin sensitivity. Methods: We examined the relationship between sleep parameters and adipose tissue insulin sensitivity in non-diabetic participants with obesity and newly diagnosed OSA who underwent overnight polysomnography and a 2 h oral glucose tolerance test during which circulating free fatty acids were measured. In total, 16 non-diabetic participants with obesity and newly diagnosed OSA (sex, 81.3% males; mean age, 50.9 ± 6.7 y; BMI, 36.5 ± 2.9 kg/m2; AHI, 43 ± 20 events/h) were included in the analysis. Results: In our study participants, AHI is inversely associated with free-fatty acid suppression during oral glucose challenge (R = -0.764, p = 0.001). This relationship persisted even after statistical adjustment for age (R = -0.769, p = 0.001), body mass index (R = -0.733, p = 0.002), waist-to-hip ratio (R = -0.741, p = 0.004), or percent body fat mass (R = -0.0529, p = 0.041). Furthermore, whole-body insulin sensitivity as determined by the Matsuda index was associated with percent REM sleep (R = 0.552, p = 0.027) but not AHI (R = -0.119, p = 0.660). Conclusion: In non-diabetic patients with OSA, the severity of sleep apnea is associated with adipose tissue insulin sensitivity but not whole-body insulin sensitivity. The impairments in adipose tissue insulin sensitivity may contribute to the development of type 2 diabetes.

Adherence to Triple Single-Pill Combination of Perindopril/Indapamide/Amlodipine: Findings from Real-World Analysis in Italy.

INTRODUCTION: Single-pill combination therapy for hypertension is recognized to improve adherence to treatment. However, less is known about the benefits of triple single-pill combinations. This retrospective observational analysis aimed to assess changes in adherence when treatment was switched from perindopril (PER)/indapamide (IND) + amlodipine (AML) to PER/IND/AML single-pill combination, in Italian clinical practice. METHODS: This analysis used data extracted from administrative databases of Italian healthcare entities. Adult patients receiving PER/IND/AML were selected, and the prescription date was considered as the index date. Among them, those who had a prescription for PER/IND + AML during the 12 months before the index date and a prescription of PER/IND/AML during 6 months of follow-up were included. Adherence was calculated as the proportion of days covered (PDC: PDC < 40%, non-adherent; PDC = 40-79%, partially adherent; PDC ≥ 80%, adherent). RESULTS: Among the identified patients, 158 were exposed users and were included in the analysis. When patients were compared before and after switch to triple single-pill combination, the proportion of adherent patients was significantly higher with PER/IND/AML single-pill combination (75.3%) than with PER/IND + AML combination (44.3%) (P < 0.05). Conversely, the proportion of non-adherent patients was lower with the PER/IND/AML single-pill combination (14.6%) vs PER/IND + AML (17.7%) (P < 0.001). CONCLUSION: This real-world analysis showed that switching to a triple single-pill combination could offer an opportunity to improve adherence to antihypertensive treatment in real-life clinical practice.

Medication adherence is defined by the World Health Organization as the "extent to which a person's behavior (in taking medication) corresponds with agreed recommendations from a healthcare provider". Low levels of medication adherence in hypertension have been linked with increased disease burden and with higher costs for patients. Patients with hypertension whose blood pressure is poorly controlled often need to receive more than one pill. Nevertheless, having to take many pills may result in poor adherence, i.e., patients not taking their treatment as prescribed. Combining multiple drugs into a single pill for the management of hypertension is known to improve adherence; however, limited evidence exists about the benefits of triple single-pill combinations compared with equivalent free combinations in real clinical practice. This analysis evaluated changes in adherence before and after patients switched from a three-drug therapy of perindopril/indapamide single-pill + amlodipine (PER/IND + AML) to perindopril/indapamide/amlodipine (PER/IND/AML) taken as a single pill. In this analysis, real-world data from Italian administrative databases covering around 11% of the Italian population were used. Overall, 158 patients were included. More patients were found to be adherent after switch to PER/IND/AML single pill (75.3% vs 44.3% of PER/IND + AML combination). Partially adherent and poorly adherent patients were fewer with PER/IND/AML single-pill combination (10.1% and 14.6%, respectively) compared to PER/IND + AML combination (38.0% and 17.7%, respectively). These findings indicate that switching to a simplified therapy in which all three drugs are taken in one pill may offer an opportunity for increasing the number of patients that are adherent to their medication.

Computerized working memory training for hypertensive individuals with executive function impairment: a randomized clinical trial.

Background: Hypertension is associated with working memory (WM) impairment. However, the benefits of Cogmed WM training for the hypertensive population are unknown. Therefore, we aimed to evaluate Cogmed's effects on the WM performance of hypertensive individuals with executive function (EF) impairment. Methods: We included 40 hypertensive patients (aged 40-70 years, 68% female) with EF impairment. They were randomized in a 1:1 ratio to receive 10 weeks of adaptive Cogmed training or a non-adaptive control training based on online games. The primary outcome was the WM performance. The secondary outcomes were verbal memory, visuospatial ability, executive function, global cognition, and the neuronal activity measured using functional magnetic resonance imaging (fMRI) under two WM task conditions: low (memorization of 4 spatial locations) and high (memorization of 6 spatial locations). An intention-to-treat (ITT) and per-protocol (PP) analysis were performed. Results: Cogmed did not show a significant effect on WM or any other cognitive outcome post-training. However, under the WM-low load and WM-high load conditions of the fMRI, respectively, the Cogmed group had an activation decrease in the right superior parietal lobe (ITT and PP analyses) and left inferior frontal lobe (PP analysis) in comparison to the control group. Conclusion: The Cogmed showed no effects on the WM performance of hypertensive individuals with EF impairment. However, activation decreases were observed in frontoparietal areas related to the WM network, suggesting a more efficient neuronal activity after training.

Measurement of resistance-area product by transcranial Doppler: An alternative tool for cognitive screening in hypertensive on drug treatment?

Introduction: Arterial hypertrophy and remodeling are adaptive responses present in systemic arterial hypertension that can result in silent ischemia and neurodegeneration, compromising brain connections and cognitive performance (CP). However, CP is affected differently over time, so traditional screening methods may become less sensitive in assessing certain cognitive domains. The study aimed to evaluate whether cerebrovascular hemodynamic parameters can serve as a tool for cognitive screening in hypertensive without clinically manifest cognitive decline. Methods: Participants were allocated into groups: non-hypertensive (n = 30) [group 1], hypertensive with systolic blood pressure (SBP) < 140 and diastolic blood pressure (DBP) < 90 mmHg (n = 54) [group 2] and hypertensive with SBP ≥ 140 or DBP ≥ 90 (n = 31) [group 3]. Measurements of blood pressure and middle cerebral artery blood flow velocity were obtained from digital plethysmography and transcranial Doppler. For the cognitive assessment, the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and a broad neuropsychological battery were applied. Results: Patients in groups 2 and 3 show no significant differences in most of the clinical-epidemiological variables or pulsatility index (p = 0.361), however compared to group 1 and 2, patients in group 3 had greater resistance-area product [RAP] (1.7 [±0.7] vs. 1.2 [±0.2], p < 0.001). There was a negative correlation between RAP, episodic memory (r = -0.277, p = 0.004) and cognitive processing speed (r = -0.319, p = 0.001). Conclusion: RAP reflects the real cerebrovascular resistance, regardless of the direct action of antihypertensive on the microcirculation, and seems to be a potential alternative tool for cognitive screening in hypertensive.

Arterial Stiffness in Transgender Men Receiving Long-term Testosterone Therapy.

Context: The effects of androgen therapy on arterial function in transgender men (TM) are not fully understood, particularly concerning long-term androgen treatment. Objective: To evaluate arterial stiffness in TM receiving long-term gender-affirming hormone therapy by carotid-femoral pulse wave velocity (cf-PWV). Methods: A cross-sectional case-control study at the Gender Dysphoria Unit of the Division of Endocrinology, HC-FMUSP, Sao Paulo, Brazil. Thirty-three TM receiving intramuscular testosterone esters as regular treatment for an average time of 14 ± 8 years were compared with 111 healthy cisgender men and women controls matched for age and body mass index. Aortic stiffness was evaluated by cf-PWV measurements using Complior device post-testosterone therapy. The main outcome measure was aortic stiffness by cf-PWV as a cardiovascular risk marker in TM and control group. Results: The cf-PWV after long-term testosterone therapy was significantly higher in TM (7.4 ± 0.9 m/s; range 5.8-8.9 m/s) than in cisgender men (6.6 ± 1.0 m/s; range 3.8-9.0 m/s, P < .01) and cisgender women controls (6.9 ± .9 m/s; range 4.8-9.1 m/s, P = .02). The cf-PWV was significantly and positively correlated with age. Analysis using blood pressure as a covariate showed a significant relationship between TM systolic blood pressure (SBP) and cf-PWV in relation to cisgender women but not to cisgender men. Age, SBP, and diagnosis of hypertension were independently associated with cf-PWV in the TM group. Conclusion: The TM group on long-term treatment with testosterone had higher aging-related aortic stiffening than the control groups. These findings indicate that aortic stiffness might be accelerated in the TM group receiving gender-affirming hormone treatment, and suggest a potential deleterious effect of testosterone on arterial function. Preventive measures in TM individuals receiving testosterone treatment, who are at higher risk for cardiovascular events, are highly recommended.

Population health impact and economic evaluation of the CARDIO4Cities approach to improve urban hypertension management.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, with 80% of that mortality occurring in low- and middle-income countries. Hypertension, its primary risk factor, can be effectively addressed through multisectoral, multi-intervention initiatives. However, evidence for the population-level impact on cardiovascular (CV) event rates and mortality, and the cost-effectiveness of such initiatives is scarce as long-term longitudinal data is often lacking. Here, we model the long-term population health impact and cost-effectiveness of a multisectoral urban population health initiative designed to reduce hypertension, conducted in Ulaanbaatar (Mongolia), Dakar (Senegal), and in the district of Itaquera in São Paulo (Brazil) in collaboration with the local governments. We based our analysis on cohort-level data among hypertensive patients on treatment and control rates from a real-world effectiveness study of the CARDIO4Cities approach (built on quality of care, early access, policy reform, data and digital, Intersectoral collaboration, and local ownership). We built a decision tree model to estimate the CV event rates during implementation (1-2 years) and a Markov model to project health outcomes over 10 years. We estimated the number of CV events averted and quality-adjusted life-years gained (QALYs through the initiative and assessed its cost-effectiveness based on the costs reported by the funder using the incremental cost effectiveness ratio (ICER) and published thresholds. A one-way sensitivity analysis was performed to assess the robustness of the results. The modelled patient cohorts included 10,075 patients treated for hypertension in Ulaanbaatar, 5,236 in Dakar, and 5,844 in São Paulo. We estimated that 3.3-12.8% of strokes and 3.0-12.0% of coronary heart disease (CHD) events were averted during 1-2 years of implementation in the three cities. We estimated that over the subsequent 10 years, 3.6-9.9% of strokes, 2.8-7.8% of CHD events, and 2.7-7.9% of premature deaths would be averted. The estimated ICER was USD 748 QALY gained in Ulaanbaatar, USD 3091 in Dakar, and USD 784 in São Paulo. With that, the intervention was estimated to be cost-effective in Ulaanbaatar and São Paulo. For Dakar, cost-effectiveness was met under WHO-CHOICE standards, but not under more conservative standards adjusted for purchasing power parity (PPP) and opportunity costs. The findings were robust to the sensitivity analysis. Our results provide evidence that the favorable impact of multisector systemic interventions designed to reduce the hypertension burden extend to long-term population-level CV health outcomes and are likely cost-effective. The CARDIO4Cities approach is predicted to be a cost-effective solution to alleviate the growing CVD burden in cities across the world.

Arterial stiffness and atrial fibrillation: A review.

Arterial stiffness has been investigated as part of the physiopathology of arterial hypertension since the 1970s. Its role in increasing the "pulsatile load" imposed over the Left Ventricle (LV) has been intensely studied recently and has helped in understanding the mechanisms of Atrial Fibrillation (AF) in hypertensive patients. This paper aims to review the main evidence on this issue and establish possible mechanisms involved in the development of AF in patients with arterial stiffness. A PubMed search was performed, and selected articles were searched for references focusing on this topic. In the long term, lower blood pressure levels allow for arterial wall remodeling, leading to a lower stiffness index. To this day, however, there are no available treatments that directly promote the lowering of arterial wall stiffness. Most classes of anti-hypertensive drugs ‒ with stronger evidence for beta-blockers and diuretics ‒ could be effective in reducing arterial stiffness. There is strong evidence demonstrating an association between arterial stiffness and AF. New studies focusing on arterial stiffness and pre-fibrillatory stages would strengthen this causality relation.

Incor Residency Program in Adult Cardiology in 2022: 40 Years Preparing Cardiologists for the Demands in Brazil. / Programa de Residência Médica em Cardiologia de Adultos do InCor em 2022: 40 Anos Formando Cardiologistas para as Demandas do Brasil.

BACKGROUND: Considering demographic data related to the cardiologist's fields of work in Brazil, the administrative board of the InCor medical residency program decided for an update of its curriculum content, to adapt the educational process to the cardiologist's work reality. OBJECTIVE: This article aimed to describe the recent updates applied to the InCor medical residency program. METHODS: In the article, we described the recent updates on the InCor residency program, and compared the current curriculum track with the previous one. We also presented the rationale for these changes, based on the literature on the participation of cardiologists in the labor market. RESULTS: There was a reduction in the working hours of residents in training in the intensive care unit, and an increase in the outpatient activities of primary and secondary prevention. Also, the didactic content was reformulated and became organized by the corresponding division. CONCLUSION: The update of the curriculum track of the InCor medical residency program was required in order to adapt it to the Brazilian labor market. The commission in charge of this update is aware that this is a dynamic process that may need changes over time.

FUNDAMENTO: Diante de dados demográficos referentes às áreas de atuação dos cardiologistas no Brasil, a coordenação do Programa de Residência Médica em Cardiologia do Instituto do Coração (PRM INCOR) entendeu a necessidade de uma atualização de seu conteúdo programático, a fim de adaptar o processo de formação à realidade profissional do cardiologista. OBJETIVO: O presente artigo tem como objetivo descrever à comunidade científica as atualizações recentemente implementadas no PRM INCOR. MÉTODOS: No artigo, descrevemos as atualizações recentes do PRM INCOR, comparando a grade teórica pregressa e a atual. Expomos também o racional por trás de tais mudanças com dados de literatura relacionados à atuação do médico cardiologista no mercado de trabalho. RESULTADO: Houve uma redução da carga horária destinada a estágios de terapia intensiva, e um incremento nas atividades ambulatoriais relacionadas a medidas de prevenção primária e secundária. Além disso, o programa passou por uma reformulação de seu conteúdo didático, organizado agora por núcleos de competência. CONCLUSÃO: A atualização da grade curricular decorre da necessidade de adequar o PRM INCOR à realidade atual do mercado de trabalho brasileiro. O grupo envolvido na atualização está ciente que se trata de um processo dinâmico e que pode exigir modificações no decorrer do tempo.

The Cholinergic Drug Galantamine Alleviates Oxidative Stress Alongside Anti-inflammatory and Cardio-Metabolic Effects in Subjects With the Metabolic Syndrome in a Randomized Trial.

Background: The metabolic syndrome (MetS) is an obesity-associated disorder of pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered neural autonomic regulation, are important components and drivers of pathogenesis. Galantamine, an acetylcholinesterase inhibitor and a cholinergic drug that is clinically-approved (for Alzheimer's disease) has been implicated in neural cholinergic regulation of inflammation in several conditions characterized with immune and metabolic derangements. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS. Trial Design and Methods: The effects of galantamine treatment, 8 mg daily for 4 weeks or placebo, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n = 22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment. Results: Galantamine treatment significantly increased antioxidant enzyme activities, including SOD [+1.65 USOD/mg protein, [95% CI 0.39-2.92], P = 0.004] and CAT [+0.93 nmol/mg, [95% CI 0.34-1.51], P = 0.01], decreased lipid peroxidation [thiobarbituric acid reactive substances [log scale 0.72 pmol/mg, [95% CI 0.46-1.07], P = 0.05], and systemic nitrite levels [log scale 0.83 µmol/mg protein, [95% CI 0.57-1.20], P = 0.04] compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment. Conclusion: Low-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates neural autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with the cholinergic drug galantamine to ameliorate MetS.

Systemic arterial hypertension and cognition in adults: effects on executive functioning.

BACKGROUND: Central nervous system changes associated to systemic arterial hypertension (SAH) are progressive and may cause negative effects on cognitive performance. The objective of this study was to investigate the relation between SAH and the components of executive functions (EF), inhibitory control (IC), updating and shifting, comparing a control group (without SAH) to patients with SAH, in two levels of severity. METHODS: The protocol included the following tests to evaluate EF components: T.O.V.A. Test (IC), Backward Digit Span from Wechsler Adults Intelligence Scale (WAIS-III), Phonemic and Semantic Verbal Fluency (updating), and Trail Making Test Part B (shifting). RESULTS: A total of 204 participants was included: 56 from the Control Group (CG), 87 SAH stage 1, and 61 SAH stage 2. The groups were not different for age (52.37±12.29) and education (10.98±4.06). As to controlled blood pressure (BP), duration of hypertension treatment and number of drugs, the SAH 2 group had a worse BP control, longer duration of hypertension treatment and use of more drugs when compared to the SAH 1. The findings revealed that patients with more severe hypertension presented worse performance in updating (Backward Digit Span, phonemic and semantics VF) and shifting (Trail Making Test Part B). CONCLUSION: The results suggest that patients with SAH have a significant impairment in EF, more specifically in updating and shifting. Besides that, such damage may be directly proportional to the severity of SAH. It is suggested that future studies include neuroimaging exams to exclude possible cerebrovascular diseases.