Hypertension: protective effects of physical exercise on cognition function, arterial function and brain health

Systemic Arterial Hypertension (SAH) is a chronic condition that requires clinical treatment and is associated with increased risk of cognitive impairment and dementia. Therefore, strategies with fewer side effects and less invasive procedures are required. Evidence supports that Physical Exercise (PE) has antihypertensive effects and has proven to be an efficient and complementary tool for managing hypertension, reducing cardiovascular disease risk factors, and improving cerebral perfusion in the majority of healthy populations. Much of this cardiovascular-protective effect of PE is probably due to pluripotent effects on the vasculature, including regulation of vascular tone, energy metabolism, microvascular recruitment, and endothelial function (reducing oxidative stress and preserving NO availability). These factors are speculated to work synergistically, thereby reducing systolic and diastolic blood pressure and are directly related to improved cerebrovascular function. However, few studies have specifically examined the potential positive effects of PE on the brain in hypertensive individuals. In this brief review, we discuss the potential effect of different PE modalities (aerobic, resistance, and combined) that may act as an effective preventive or therapeutic strategy for reducing blood pressure in hypertensives and, consequently, mitigate the association between hypertension, cognitive impairment and risk of dementia

Early Vascular Ageing (EVA): Definitions and Clinical Applicability.

Arterial stiffness has been accumulating evidence as an intermediate cardiovascular endpoint. It has been established as an independent risk marker for cardiovascular disease, and reflects the dissociation between chronologic and biologic age of large arteries-attributing earlier the risk that a normal vascular ageing process had installed to occur several years later. The concept of Early Vascular Ageing (EVA) is developed to establish primordial prevention, identifying individuals whose ageing path has been accelerated either by inherent features, interaction with the environment or arterial exposure to several types of insults that evolve to medial layer morphological changes. Understanding the pathophysiology of vascular ageing, its consequences and therapeutic opportunities is therefore an advantage that could be translated in time of prevention and survival free of cardiovascular disease. As the EVA construct is advancing, new features appear as interesting to better translate it into clinical practice.(undefined)info:eu-repo/semantics/publishedVersio

Skin autofluorescence–indicated advanced glycation end products as predictors of cardiovascular and all-cause mortality in high-risk subjects: a systematic review and meta-analysis

Background Chronic deposits of advanced glycation end products produced by enzymatic glycation have been suggested as predictors of atherosclerotic-related disorders. This study aimed to estimate the relationship between advanced glycation end products indicated by skin autofluorescence levels and the risk of cardiovascular and all-cause mortality based on data from observational studies. Methods and Results We systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the Web of Science databases from their inceptions until November 2017 for observational studies addressing the association of advanced glycation end products by skin autofluorescence levels with cardiovascular and all-cause mortality. The DerSimonian and Laird random-effects method was used to compute pooled estimates of hazard ratios and their respective 95% confidence intervals for the risk of cardiovascular and all-cause mortality associated with levels of advanced glycation end products by skin autofluorescence. Ten published studies were included in the systematic review and meta-analysis. Higher skin autofluorescence levels were significantly associated with a higher pooled risk estimate for cardiovascular mortality (hazard ratio: 2.06; 95% confidence interval, 1.58-2.67), which might not be important to moderate heterogeneity (I2=34.7%; P=0.163), and for all-cause mortality (hazard ratio: 1.91; 95% confidence interval, 1.42-2.56) with substantial heterogeneity (I2=60.8%; P=0.0.18). Conclusions Our data suggest that skin autofluorescence levels could be considered predictors of all-cause mortality and cardiovascular mortality in patients at high and very high risk.Cavero-Redondo and Martínez-Hortelano are supported by a grant from the Universidad de Castilla-La Mancha (FPU13/ 01582 and PREDUCLM16/14, respectively). Soriano-Cano is supported by a grant from Spanish Ministry of Economy, Industry, and Competitiveness (Fi 17/332). Garrido-Miguel and Berlanga-Macías are supported by a grant from the Spanish Ministry of Education, Culture, and Sport (FPU15/ 03847 and FPU16/02380, respectively).info:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Estudo para determinar o risco cardiovascular da população de Guimarães/Vizela, incluindo a prevalência de rigidez arterial e de envelhecimento vascular precoce

Tese de Doutoramento em Medicina.A doença cardiovascular (DCV) é a principal causa de morte em Portugal, um dos 10 países do mundo em que as taxas de mortalidade por AVC são maiores do que as por doença coronária isquémica, e aquele que apresenta a mais alta incidência de acidente vascular cerebral (AVC) da Europa Ocidental. Neste contexto, pretendemos compreender as características existentes na comunidade respeitantes ao risco CV (RCV) e às manifestações de DCV, usando um rigoroso método de fenotipagem. O nosso objectivo nuclear é o de contribuir para uma melhor estratégia de identificação precoce dos sujeitos em risco e promover um início atempado de medidas. Os principais objectivos foram: i) estabelecer a prevalência de factores de RCV tradicionais e não tradicionais; ii) avaliar a distribuição dos valores médios de velocidade de onda de pulso (VOP) e de pressão arterial central (PAC) na população e reconhecer sinais existentes de envelhecimento vascular precoce (EVP) ou rigidez arterial; iii) estabelecer a distribuição da população pelas diferentes classes de RCV, seguindo diferentes estratégias de estimativa de risco e analisando a dimensão da reclassificação conseguida através de uma cuidadosa fenotipagem; iv) avaliar a prevalência de DCV e doença renal estabelecidas, bem como de lesão em órgão alvo (LOA). Num estudo de cohort com uma amostra aleatoriamente seleccionada da população de duas cidades, observamos os sujeitos em duas ocasiões, registando história clínica, características biológicas, medidas hemodinâmicas centrais e periféricas e recolhendo ainda amostras de sangue e urina. Cada característica fenotípica foi atribuída a um indivíduo se verificada concordantemente em ambas as visitas. 4000 sujeitos foram randomizados, 3038 incluídos e 2542 completaram as duas visitas, constituindo uma amostra equilibrada com idade média de 45.5 anos e 55.1% de mulheres. Os nossos resultados principais foram: 1) A confirmação de uma sobre e/ou subestimação da prevalência de características de RCV, quando utilizada apenas uma avaliação desses parâmetros; 2) A prevalência de várias características de RCV é elevada, particularmente em faixas etárias mais jovens, e os riscos mínimos de exposição para o desenvolvimento de DCV são amplamente ultrapassados (glicose, pressão arterial (PA), índice de massa corporal); 3) Apesar da evolução positiva no número de sujeitos hipertensos tratados e controlados na última década, os actuais valores médios de PA posicionam-se entre os mais elevados da Europa; as tendências nacionais de declínio na prevalência de hipertensão e dos níveis de PA, não foram verificadas; 4) Diferentes estratégias de estratificação de RCV, permitiram reclassificar 18.2% da população para risco mais elevado; 38.5% dos sujeitos com risco Moderado foi reclassificada para classes de risco Alto e Muito Alto; a classe de Muito Alto risco aumentou cerca de 32 vezes. 62.7% dos hipertensos foram classificados como de Alto/Muito Alto risco; apenas 43% recebiam tratamento anti-lipídico: só 14.3% dos hipertensos de Muito Alto Risco atingiam alvos terapêuticos. 5) A prevalência de EVP foi de 12.5%; 26.1% dos sujeitos com menos de 30 anos apresentavam EVP. 18.7% da população apresentava valores de VOP > 10m/s, predominantemente no sexo masculino. Modelos de regressão logística indicam que as mulheres apresentam a mesma probabilidade de atingir valores de VOP> 10m/s, 10 anos mais tarde que os homens; 6) A PAC Sistólica (PACS) e a Pressão de Pulso Central (PPC) excederam em 10 a 20 mmHg o valor médio esperado, em várias faixas etárias. O ratio médio da Amplificação da PPC (PPCA) foi 1.32. 37.5% da população/72.4% dos hipertensos apresentaram valores de PACS > percentil 90 (P90); PPC> P90 foi documentada em 23.7/51.5% da população/dos hipertensos. Em hipertensos tratados e controlados, 33.9/20.5% dos sujeitos apresentavam valores de PACS/PPC> P90. LOA foi significativamente mais prevalente em sujeitos com PACS/PCC>P90 (2 a 4 vezes). O Sal apresentou-se como uma variável independente explicativa da PACS e da PPCA em análise de regressão multivariada, e como factor de risco para valores de PACS > P90. Achados congruentes permitem estabelecer a imagem de uma população com risco mais elevado que o esperado para o desenvolvimento de DCV, começando por alterações fenotípicas que favorecem a doença, desde idades jovens.Cardiovascular (CV) disease (CVD) is the leading cause of death in Portugal. The northern region registers the highest incidence of stroke in Western Europe; paradoxically, this country is one of the ten nations in the world where standardized mortality rates by stroke are higher than for coronary heart disease. In this setting, we wanted to better understand the community dwelling characteristics concerning CV risk (CVR) and CVD manifestations by using a more strict method to phenotype subjects. Our goal was to contribute to a better strategy of pinpointing earlier subjects at risk, and promote subsequent earlier initiation of measures to decrease the development of CVD. Our main aims were to: i) establish the prevalence of traditional and non-traditional CVR factors; ii) evaluate the distribution of pulse wave velocity (PWV) and central blood pressure values in the population and recognize the existing signs of early vascular aging (EVA) or pathologic arterial stiffness; iii) establish the distribution of the population by the different CV risk classes, following different risk estimation strategies, and analyse the reclassification of risk achieved through thorough phenotyping; iv) evaluate the prevalence of established CV and renal disease and target organ damage (TOD). We established a cohort study, with a randomly selected sample of the population of two adjacent cities. Subjects were observed in a two visit plan where clinical history, biologic characteristics, peripheral and central hemodynamic variables were recorded and blood and urine samples collected. A phenotypic characteristic would be attributable to an individual if it was concordantly verified in the two visits. Four thousand subjects were randomized, 3038 were included and 2542 completed the two visit plan, constituting a balanced sample with 45.5 years of mean age and 55.1% of women. Our main results were: 1) The confirmation of an over and/or underestimation of the prevalence of CVR characteristics usually obtained with a single evaluation of those parameters; 2) The prevalence of several CVR features is elevated, particularly in younger age groups, and theoretical minimum risk exposure for the development of CVD are largely surpassed (glucose, blood pressure (BP), body mass index); 3) In spite of the positive evolution on the number of treated and controlled hypertensive subjects over the last decade, current mean BP levels rank amongst the highest in European countries; the reported national trends of BP levels and hypertension prevalence decline have not been confirmed; 4) Using different CVR stratification strategies, 18.2% of the population was reclassified into higher risk classes; 38.5% of Moderate risk subjects were reclassified into High and Very/High risk categories, increasing the number of Very High risk subjects by 32 times. 62.7% of hypertensives were classified with High or Very High risk; only 43% of them were receiving anti-lipidic treatment and only 14.3% of the Very High Risk group achieved treatment targets. 5) The overall prevalence of EVA was 12.5%; 26.1% of individuals under 30 years presented this feature. 18.7% of the population exhibited PWV values above 10 m/s, with male predominance. Logistic regression models indicated gender differences concerning the risk of developing large artery damage, with women having the same odds, of reaching PWV>10m/s, 10 years later than men. 6) Central Systolic Blood Pressure (CSBP) and Central Pulse Pressure (CPP) exceeded 10 - 20 mmHg the expected mean values for healthy subjects, in several age groups. CPP Amplification (CPPA) mean ratio was 1.32. 37.5% of the population and 72.4% of hypertensives presented CSBP>90th percentile (90thp); CPP>90thp was registered in 23.7 of the population and in 51.5% of hypertensives. In treated and controlled hypertensives, 33.9/20.5% of the subjects persist with CSBP/CPP values >90thp. TOD was significantly more prevalent in subjects above CSBP/CPP 90thp (2 to 4 times). Salt was an independent explanatory variable of CSBP and CPPA in multivariate regression analysis, and it increased the risk of having CSBP >90thp. Congruent findings construct a snapshot of a population with higher than expected risk for the development of CVD, starting with phenotypic changes favouring disease at young ages

Concept of extremes in vascular aging: from early vascular aging to supernormal vascular aging

[Excerpt] With advancing age, changes in the arterial wall contribute to what has been called vascular aging, and in some prematurely affected subjects even early vascular aging (EVA).1–5 Several years ago,1 we listed various components of EVA, including arteriosclerosis, atherosclerosis, and excess vasoconstriction, with their clinical expression: arterial stiffening and increased central pulse pressure, carotid intima media thickening and endothelial dysfunction, and increased total peripheral resistance, respectively.[...]This review was funded by INSERM, Paris Descartes University; Lund University, the Swedish Research Council; and the Minho Universit