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Turner syndrome is caused by complete or partial X monosomy in some or all cells. Cardiovascular complications are dominant, including increased blood pressure (BP), leading to early-onset hypertension. The aim is to describe the debut, development, and treatment of hypertension in Turner syndrome during a 12-year pragmatic interventional study to help identify risk factors associated with hypertension. One hundred and two women (aged 38±11 years, range: 18–62 years) with Turner syndrome verified by karyotyping (45, X: n=58 [57%]) were included consecutively. Ambulatory BPs were recorded over 24 hours with oscillometric measurements every 20 minutes. Antihypertensive treatment was recommended if the BP was above 135/85 mm Hg during the daytime. Overall, systolic BP, diastolic BP, and pulse pressure increased during the study, while heart rate decreased. The number of patients treated with antihypertensive medicine increased from 29 (28.71%) at baseline to 34 (53.13%) at the end of study. Twenty-four–hour systolic BP and 24-hour pulse pressure increased significantly with age, while 24-hour heart rate decreased with age, and diastolic BP was insignificantly affected by age. Antihypertensive treatment lowered systolic BP (24-hour: −5 mm Hg), diastolic BP (24-hour: −5 mm Hg), and diminished the pulse pressure (24-hour: −6 mm Hg) but did not affect nighttime systolic BP. Antihypertensive treatment did not affect heart rate. Our study showed that both systolic and diastolic BP increases significantly in women with Turner syndrome resulting in an increased risk of cardiovascular comorbidities. This increment should be considered of multifactorial origin with many contributing factors which is supported by our results.

Background Hypertension has become an important public health concern in the developing world owing to rising prevalence and its adverse impact on ailing health systems. Despite being a modifiable risk factor for cardiovascular disease, hypertension has not received the needed attention in Ghana as a result of various competing interests for scarce health resources. This systematic review and meta-analysis provides a comprehensive and updated summary of the literature on the prevalence of hypertension in Ghana. Methods Major databases such as MEDLINE, EMBASE, and Google Scholar and local thesis repositories were accessed to identify population-based studies on hypertension among Ghanaians. Data extracted from retrieved reports were screened independently by two reviewers. The quality of eligible studies was evaluated and reported. A reliable pooled estimate of hypertension prevalence was calculated utilizing a random-effects model and reported according to the GRADE framework. Additionally, a meta-regression analysis was performed to analyze the contribution of study-level variables to variance in hypertension prevalence. Results In general, a total of 45,470 subjects (n = 22,866 males and 22,604 females) were enrolled from urban (n = 12), rural (n = 8), and mixed populations (n = 7). Blood pressure (BP) was measured across studies according to a validated and clinically approved protocol by trained field workers or healthcare workers including nurses and physicians. A combined total of 30,033 participants across twenty studies reporting on the population prevalence of hypertension were pooled with 10,625 (35.4%) identified to satisfy study criteria for elevated BP. The pooled prevalence across 24 studies was 30.3% (95% CI 26.1–34.8%) after fitting a random effects model. Prevalence of hypertension was 30.1% (95% CI 25.6–36.0%) among females and 34.0% (95% CI 28.5–40.0%) among males. Significant differences in pooled estimates across regions emerged from subgroup comparisons of regional estimates with an increasing trend in the north-to-south direction and with increasing age. Compared to rural settings, the burden of hypertension in urban populations was significantly higher. Age structure and population type accounted for 65.0% of the observed heterogeneity in hypertension estimates. Conclusions The prevalence of hypertension in Ghana is still high. The gap in hypertension prevalence between rural and urban populations is closing especially in elderly populations. These findings must claim the attention of public health authorities in Ghana to explore opportunities to reduce rural hypertension. Systematic review registration The protocol for this review has been published previously with PROSPERO (CRD42020215829).

ispartof: CONGENITAL HEART DISEASE vol:15 issue:2 pages:69-78 status: published

BACKGROUND The prevalence of hypertension among black African patients is high, and these patients usually need two or more medications for blood-pressure control. However, the most effective two-drug combination that is currently available for blood-pressure control in these patients has not been established. METHODS In this randomized, single-blind, three-group trial conducted in six countries in sub-Saharan Africa, we randomly assigned 728 black patients with uncontrolled hypertension (≥140/90 mm Hg while the patient was not being treated or was taking only one antihypertensive drug) to receive a daily regimen of 5 mg of amlodipine plus 12.5 mg of hydrochlorothiazide, 5 mg of amlodipine plus 4 mg of perindopril, or 4 mg of perindopril plus 12.5 mg of hydrochlorothiazide for 2 months. Doses were then doubled (10 and 25 mg, 10 and 8 mg, and 8 and 25 mg, respectively) for an additional 4 months. The primary end point was the change in the 24-hour ambulatory systolic blood pressure between baseline and 6 months. RESULTS The mean age of the patients was 51 years, and 63% were women. Among the 621 patients who underwent 24-hour blood-pressure monitoring at baseline and at 6 months, those receiving amlodipine plus hydrochlorothiazide and those receiving amlodipine plus perindopril had a lower 24-hour ambulatory systolic blood pressure than those receiving perindopril plus hydrochlorothiazide (between-group difference in the change from baseline, −3.14 mm Hg; 95% confidence interval [CI], −5.90 to −0.38; P=0.03; and −3.00 mm Hg; 95% CI, −5.8 to −0.20; P=0.04, respectively). The difference between the group receiving amlodipine plus hydrochlorothiazide and the group receiving amlodipine plus perindopril was −0.14 mm Hg (95% CI, −2.90 to 2.61; P=0.92). Similar differential effects on office and ambulatory diastolic blood pressures, along with blood-pressure control and response rates, were apparent among the three groups. CONCLUSIONS These findings suggest that in black patients in sub-Saharan Africa, amlodipine plus either hydrochlorothiazide or perindopril was more effective than perindopril plus hydrochlorothiazide at lowering blood pressure at 6 months. (Funded by GlaxoSmithKline Africa Noncommunicable Disease Open Lab; CREOLE ClinicalTrials.gov number, NCT02742467. opens in new tab.)

BACKGROUND: Pulmonary arterial hypertension (PAH) is common in congenital heart disease (CHD). Because clinical-trial data on PAH associated with CHD (PAH-CHD) remain limited, registry data on the long-term course are essential. This analysis aimed to update information from the COMPERA-CHD registry on management strategies based on real-world data. METHODS: The prospective international pulmonary hypertension registry COMPERA has since 2007 enrolled more than 10,000 patients. COMPERA-CHD is a sub-registry for patients with PAH-CHD. RESULTS: A total of 769 patients with PAH-CHD from 62 specialized centers in 12 countries were included into COMPERA-CHD from January 2007 through September 2020. At the last follow-up in 09/2020, patients [mean age 45.3±16.8 years; 512 (66%) female] had either post-tricuspid shunts (n=359; 46.7%), pre-tricuspid shunts (n=249; 32.4%), complex CHD (n=132; 17.2%), congenital left heart or aortic valve or aortic disease (n=9; 1.3%), or miscellaneous CHD (n=20; 2.6%). The mean 6-minute walking distance was 369±121 m, and 28.2%, 56.0%, and 3.8% were in WHO functional class I/II, III or IV, respectively (12.0% unknown). Compared with the previously published COMPERA-CHD data, after 21 months of follow-up, the number of included PAH-CHD patients increased by 91 (13.4%). Within this group the number of Eisenmenger patients rose by 39 (16.3%), the number of "Non-Eisenmenger PAH" patients by 45 (26.9%). Currently, among the 674 patients from the PAH-CHD group with at least one follow-up, 450 (66.8%) received endothelin receptor antagonists (ERA), 416 (61.7%) PDE-5 inhibitors, 85 (12.6%) prostacyclin analogues, and 36 (5.3%) the sGC stimulator riociguat. While at first inclusion in the COMPERA-CHD registry, treatment was predominantly monotherapy (69.3%), this has shifted to favoring combination therapy in the current group (53%). For the first time, the nature, frequency, and treatment of significant comorbidities requiring supportive care and medication are described. CONCLUSIONS: Analyzing "real life data" from the international COMPERA-CHD registry, we present a comprehensive overview about current management modalities and treatment concepts in PAH-CHD. There was an trend towards more aggressive treatment strategies and combination therapies. In the future, particular attention must be directed to the "Non-Eisenmenger PAH" group and to patients with complex CHD, including Fontan patients. TRIAL REGISTRATION: www.clinicaltrials.gov, study identifier: Clinicaltrials.gov NCT01347216. ispartof: CARDIOVASCULAR DIAGNOSIS AND THERAPY vol:11 issue:6 pages:1255-1268 ispartof: location:China status: published

Statement of remit: To align with its mission to reduce the global burden of raised blood pressure (BP), the International Society of Hypertension (ISH) has developed worldwide practice guidelines for the management of hypertension in adults, aged 18 years and older. The ISH Guidelines Committee extracted evidence-based content presented in recently published extensively reviewed guidelines and tailored ESSENTIAL and OPTIMAL standards of care in a practical format that is easy-to-use particularly not only in low-resource settings but also in high-resource settings- by clinicians, but also nurses and community health workers, as appropriate. Although distinction between low-resource and high-resource settings often refers to high (HIC) and low-income and middle-income countries (LMIC), it is well established that in HIC, there are areas with low-resource settings, and vice versa. Herein optimal care refers to evidence-based standard-of-care articulated in recent guidelines [1,2] and summarized here, whereas essential standards recognize that optimal standards would not always be possible. Hence, essential standards refer to minimum standards of care. To allow specification of essential standards of care for low-resource settings, the Committee was often confronted with the limitation or absence in clinical evidence, and thus applied expert opinion. In the Guidelines, differentiation between optimal and essential standards were not always possible, and were made in sections where it was most practical and sensible. The Guidelines Committee is also aware that some recommended essential standards may not be feasible in low-resource settings, for example, out-of-office BP measurements, the requirement of multiple visits for the diagnosis of hypertension, or advising the use of single pill combination therapy. Although challenging to implement, these guidelines may aid in local initiatives to motivate policy changes and serve as an instrument to drive local improvements in standards of care. Every effort should be made to achieve essential standards of care to reduce hypertension-induced cardiovascular morbidity and mortality.

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An increase in pulmonary artery pressure is a common observation in adult mammals exposed to global alveolar hypoxia. It is considered a maladaptive response that places an increased workload on the right ventricle. The mechanisms initiating and maintaining the elevated pressure are of considerable interest in understanding pulmonary vascular homeostasis. There is an expectation that identifying the key molecules in the integrated vascular response to hypoxia will inform potential drug targets. One strategy is to take advantage of experiments of nature, specifically, to understand the genetic basis for the inter-individual variation in the pulmonary vascular response to acute and chronic hypoxia. To date, detailed phenotyping of highlanders has focused on haematocrit and oxygen saturation rather than cardiovascular phenotypes. This review explores what we can learn from those studies with respect to the pulmonary circulation. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc.

Background and Purpose— Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage. If clinical signs of DCI occur, induced hypertension is a plausible but unproven therapeutic intervention. There is clinical equipoise if the use of hypertension induction is useful or not with the consequence that this strategy is irregularly used. We explored the effect of blood pressure augmentation in preventing cerebral infarction in patients with clinical signs of DCI. Methods— We performed a retrospective observational study, totaling 1647 patients with aneurysmal subarachnoid hemorrhage admitted at 3 academic hospitals in the Netherlands between 2006 and 2015. To study the primary outcome DCI related cerebral infarcts, we only included patients with no cerebral infarct at the time of onset of clinical signs of DCI. Cox regression was used to test the association between induced hypertension after onset of clinical signs of DCI and the occurrence of DCI related cerebral infarcts. Logistic regression was used to relate hypertension induction with poor outcome after 3 months, defined as a modified Rankin score >3. Results were adjusted for treatment center and baseline characteristics. Results— Clinical signs of DCI occurred in 479 (29%) patients of whom 300 without cerebral infarction on computed tomography scan at that time. Of these 300 patients, 201 (67%) were treated with hypertension induction and 99 were not. Of the patients treated with hypertension induction, 41 (20%) developed a DCI related cerebral infarct compared with 33 (33%) with no induced hypertension: adjusted hazard ratio, 0.59; 95% CI, 0.35 to 0.99. Hypertension induction also prevented poor outcome: adjusted odds ratio, 0.27; 95% CI, 0.14 to 0.55. Conclusions— Hypertension induction seems an effective strategy for preventing DCI related cerebral infarcts if not already present at the time of onset of clinical signs of DCI. This may lead to a reduction in poor clinical outcome.

Background: Pulmonary hypertension (PH) is prevalent in Africa and is still often diagnosed only at an advanced stage, therefore it is associated with poor quality of life and survival rates. In resource-limited settings, we assessed the diagnostic utility of standard 12-lead electrocardiograms (ECG) to detect abnormalities indicating PH.Methods: Sixty-five patients diagnosed with PH were compared with 285 heart disease-free subjects. The prevalence and diagnostic performance of ECG features indicative of PH and right heart strain were calculated.Results: Compared to the control group, all abnormalities were more frequent in the PH cohort where no patient had a completely normal ECG. The most prevalent (cases vs control) ECG abnormalities were: pathological Q wave in at least two contiguous peripheral leads (47.7 vs 6.7%), left ventricular hypertrophy (38.5 vs 9.8%) and p-pulmonale (36.9 vs 20.7%) (all p = 100 degrees), and highest (100%) for QRS axis >= +100 degrees combined with R/S ratio in V1 >= 1 or R in V1 > 7 mm.Conclusion: When present, signs of PH on ECG strongly indicated disease, but a normal ECG cannot rule out disease. ECG patterns focusing on the R and S amplitude in V1 and right-axis deviation had good specificity and negative predictive values for PH, and warrant further investigation with echocardiography.

Objective: People with psychotic disorders have an increased metabolic risk and a shortened life expectancy compared to the general population. Two large studies showed that metabolic disorders were untreated in a majority of the patients. Since then, guidelines have urged monitoring of metabolic health. This study examined the course of metabolic disorders over time in people with psychotic disorders and investigated current treatment rates. Methods: A total of 1, 259 patients with psychotic disorders, as defined by the DSM-IV, from 4 Dutch mental health institutions participated in 3 yearly assessments of the Pharmacotherapy Monitoring and Outcome Survey (PHAMOUS) between 2006 and 2014. Patients' metabolic parameters were measured, and the use of pharmacologic treatment for hypertension (systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg), dyslipidemia (5% ≤ Systematic COronary Risk Evaluation [SCORE] risk < 10% and low-density lipoprotein [LDL] cholesterol level ≥ 2.5 mmol/L or SCORE risk ≥ 10% and LDL cholesterol level ≥ 1.8 mmol/L and/or triglycerides ≥ 2.3 mmol/L), and hyperglycemia (hemoglobin A1c concentration > 7% and/or fasting glucose concentration ≥ 7.2 mmol/L) was recorded. Results: Prevalence of the metabolic syndrome, as defined by the National Cholesterol Education Program criteria, was > 50% at each assessment. On the basis of the European Society of Cardiology guidelines, pharmacotherapy for metabolic disorders was recommended for 52%-59% of the patients at each assessment. Treatment rates with antihypertensive (from 31% to 38%, P

Despite advancements in lowering blood pressure, the best approach to lower it remains controversial because of the lack of information on the molecular basis of hypertension. We, therefore, performed plasma proteomics of plasma from patients with hypertension to identify molecular determinants detectable in these subjects but not in controls and vice versa. Plasma samples from hypertensive subjects (cases; n=118) and controls (n=85) from the InGenious HyperCare cohort were used for this study and performed mass spectrometric analysis. Using biostatistical methods, plasma peptides specific for hypertension were identified, and a model was developed using least absolute shrinkage and selection operator logistic regression. The underlying peptides were identified and sequenced off-line using matrix-assisted laser desorption ionization orbitrap mass spectrometry. By comparison of the molecular composition of the plasma samples, 27 molecular determinants were identified differently expressed in cases from controls. Seventy percent of the molecular determinants selected were found to occur less likely in hypertensive patients. In cross-validation, the overall R 2 was 0.434, and the area under the curve was 0.891 with 95% confidence interval 0.8482 to 0.9349, P P

Different treatment options for pulmonary hypertension have emerged in recent years, and evidence-based management strategies have improved quality of life and survival in adults. In children with pulmonary vascular disease, therapeutic algorithms are not so clearly defined; this study determined current treatment initiation in children with pulmonary hypertension in participating centres of a registry.Through the multinational Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension registry, patient demographics, diagnosis, and treatment as judged and executed by the local physician were collected. Inclusion criteria were >3 months and 2, and mean pulmonary capillary wedge pressure ⩽12 mmHg).At diagnostic catheterisation, 217/244 patients (88.9%) were treatment naïve for pulmonary hypertension-targeted therapy. Targeted therapy was initiated after catheterisation in 170 (78.3%) treatment-naïve patients. A total of 19 patients received supportive therapy, 28 patients were not started on therapy, and 26 patients (10.7%) were on targeted treatment before catheterisation. Among treatment-naïve subjects, treatment was initiated with one targeted drug (n=112, 51.6%), dual therapy (n=39, 18%) or triple-therapy (n=5, 2.3%), and calcium channel blockers with one targeted medication in one patient (0.5%). Phosphodiesterase inhibitors type 5 were used frequently; some patients with pulmonary hypertension related to lung disease received targeted therapy.There is a diverse therapeutic approach for children with pulmonary hypertension with a need of better-defined treatment algorithms based on paediatric consensus for different aetiologies including the best possible diagnostic workup.

The present study had the purpose of evaluating the proportion of subjects with hypertension, treatment, control rates, and the relationship between blood pressure (BP) with body mass index and abdominal circumference in a cross-sectional study, as part of a worldwide study designed by International Society of Hypertension, performed during May 2017. After the protocol´s approval by the local Ethical Committee, 64 sites were included from eight Venezuelan regions. A short questionnaire was completed for each participant, including knowledge of taking antihypertensive treatment, diabetes, previous myocardial infarction or stroke, alcohol intake, and smoking. BP was measured in the sitting position three times after resting for 5 minutes, one minute apart, using mainly oscillometric devices. Height, weight and abdominal circumference were measured. Data analyses were performed by the MMM central team. 21644 individuals were screened. After multiple imputations, 10584 individuals [48.9% (50.7% male; 47.7% female)] had hypertension. Of subjects not receiving antihypertensive medication, 1538 (12.2%) were hypertensives. Of hypertensive individuals receiving antihypertensive medication, 2974 (32.9%) had uncontrolled BP. 15.6% of our sample had obesity according to their body mass index; 43.8% of women and 20.7% of men had abdominal obesity. BP was positively correlated with BMI and abdominal circumference. In this largest BP screening carried out in Venezuela, 48.9% of the individuals had elevated BP and 12.2% did not know that they had hypertension, and in one third of those with hypertension on treatment, BP was not controlled. 15.6% had obesity by BMI, and 35.1% abdominal obesity. Screening such as the MMM17 can evaluate the association between hypertension and obesity and therefore may help to inform control programs.

IMPORTANCE In addition to biochemical cure, clinical benefits after surgery for primary aldosteronism depend on the magnitude of decrease in blood pressure (BP) and use of antihypertensive medications with a subsequent decreased risk of cardiovascular and/or cerebrovascular morbidity and drug-induced adverse effects.OBJECTIVE To evaluate the change in BP and use of antihypertensive medications within an international cohort of patients who recently underwent surgery for primary aldosteronism.DESIGN, SETTING, AND PARTICIPANTS A cohort study was conducted across 16 referral medical centers in Europe, the United States, Canada, and Australia. Patients who underwent unilateral adrenalectomy for primary aldosteronism between January 2010 and December 2016 were included. Data analysis was performed from August 2017 to June 2018. Unilateral disease was confirmed using computed tomography, magnetic resonance imaging, and/or adrenal venous sampling. Patients with missing or incomplete preoperative or follow-up data regarding BP or corresponding number of antihypertensive medications were excluded.MAIN OUTCOMES AND MEASURES Clinical success was defined based on postoperative BP and number of antihypertensive medications. Cure was defined as normotension without antihypertensive medications, and clear improvement as normotension with lower or equal use of antihypertensive medications. In patients with preoperative normotensivity, improvement was defined as postoperative normotension with lower antihypertensive use. All other patients were stratified as no clear success because the benefits of surgery were less obvious, mainly owing to postoperative, persistent hypertension. Clinical outcomes were assessed at follow-up closest to 6 months after surgery.RESULTS On the basis of inclusion and exclusion criteria, a total of 435 patients (84.6%) from a cohort of 514 patients who underwent unilateral adrenalectomy were eligible. Of these patients, 186 (42.3%) were women; mean (SD) age at the time of surgery was 50.7 (11.4) years. Cure was achieved in 118 patients (27.1%), clear improvement in 135 (31.0%), and no clear success in 182 (41.8%). In the subgroup classified as no clear success, 166 patients (91.2%) had postoperative hypertension. However, within this subgroup, the mean (SD) systolic and diastolic BP decreased significantly by 9 (22) mm Hg (P CONCLUSIONS AND RELEVANCE In this study, for most patients, adrenalectomy was associated with a postoperative normotensive state and reduction of antihypertensive medications. Furthermore, a significant proportion of patients with postoperative, persistent hypertension may benefit from adrenalectomy given the observed clinically relevant and significant reduction of BP and antihypertensive medications.

The function of the right ventricle determines the fate of patients with pulmonary hypertension. Since right heart failure is the consequence of increased afterload, a full physiological description of the cardiopulmonary unit consisting of both the right ventricle and pulmonary vascular system is required to interpret clinical data correctly. Here, we provide such a description of the unit and its components, including the functional interactions between the right ventricle and its load. This physiological description is used to provide a framework for the interpretation of right heart catheterisation data as well as imaging data of the right ventricle obtained by echocardiography or magnetic resonance imaging. Finally, an update is provided on the latest insights in the pathobiology of right ventricular failure, including key pathways of molecular adaptation of the pressure overloaded right ventricle. Based on these outcomes, future directions for research are proposed., SCOPUS: ar.j, info:eu-repo/semantics/published

Experimental models are critical for the understanding of lung health and disease and are indispensable for drug development. However, the pathogenetic and clinical relevance of the models is often unclear. Further, the use of animals in biomedical research is controversial from an ethical perspective.The objective of this task force was to issue a statement with research recommendations about lung disease models by facilitating in-depth discussions between respiratory scientists, and to provide an overview of the literature on the available models. Focus was put on their specific benefits and limitations. This will result in more efficient use of resources and greater reduction in the numbers of animals employed, thereby enhancing the ethical standards and translational capacity of experimental research.The task force statement addresses general issues of experimental research (ethics, species, sex, age,ex vivoandin vitromodels, gene editing). The statement also includes research recommendations on modelling asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung infections, acute lung injury and pulmonary hypertension.The task force stressed the importance of using multiple models to strengthen validity of results, the need to increase the availability of human tissues and the importance of standard operating procedures and data quality.

Background: Hypertension is a major risk factor for cardiovascular disease and is responsible for 14% of all annual deaths globally. The prevalence of hypertension varies across occupational groups, possibly affected by differences in the working environment. One work-related factor that might impose a risk for hypertension is lifting due to the acute large increases in blood pressure (BP) during lifting. Objective: The aim of this study is to explore associations between heavy occupational lifting and hypertension in the Copenhagen City Heart Study. Methods: This study will use data from the third, fourth, and fifth examination of the Copenhagen City Heart Study. The dataset contains person-based information on health as well as a large variety of biological, environmental, and lifestyle-related factors. Using a cross-sectional design, we will investigate the association between heavy occupational lifting and hypertension, defined as using antihypertensive drugs or having a measured systolic BP (SBP) =140 mm Hg or diastolic BP (DBP) =90 mm Hg. Furthermore, in a prospective design, we will investigate the association between heavy occupational lifting and risk of becoming an SBP case, defined as the shift from not using antihypertensive drugs in examination n to use of antihypertensive drugs in examination n+1 or an above median delta value of SBP (SBP in examination n+1-SBP in examination n). Results: In the third examination in 1991-1994, 10,135 out of 16,560 participants attended (61.20%), in the fourth examination in 2001-2003, 6237 out of 12,599 participants attended (49.50%), and in the fifth examination in 2011-2015, 4550 out of 9765 participants attended (46.59%). On the basis of the inclusion criteria of answering to the level of occupational physical activity, 5031 observations were excluded from examination 3, 2600 from examination 4, and 1621 from examination 5. Hence, the final populations for the cross-sectional and prospective analysis are assumed to include less than 7166 participants in the cross-sectional analysis and less than 1850 participants in the prospective analysis due to the additional inclusion criteria of measured BP and use of antihypertensive drugs. Conclusions: One-third of the workforce in Europe reports to carry or move heavy loads regularly during working hours (6th survey in Eurofound). Thus, if this study shows occupational lifting to increase the risk for hypertension, the prevention for hypertension can be improved.

Purpose: Hand-held vital microscopes (HVMs) were introduced to observe sublingual microcirculatory alterations at the bedside in different shock states in critically ill patients. This consensus aims to provide clinicians with guidelines for practical use and interpretation of the sublingual microcirculation. Furthermore, it aims to promote the integration of routine application of HVM microcirculatory monitoring in conventional hemodynamic monitoring of systemic hemodynamic variables.Methods: In accordance with the Delphi method we organized three international expert meetings to discuss the various aspects of the technology, physiology, measurements, and clinical utility of HVM sublingual microcirculatory monitoring to formulate this consensus document. A task force from the Cardiovascular Dynamics Section of the European Society of Intensive Care Medicine (with endorsement of its Executive Committee) created this consensus as an update of a previous consensus in 2007. We classified consensus statements as definitions, requirements, and/or recommendations, with a minimum requirement of 80% agreement of all participants.Results: In this consensus the nature of microcirculatory alterations is described. The nature of variables, which can be extracted from analysis of microcirculatory images, is presented and the needed dataset of variables to identify microcirculatory alterations is defined. Practical aspects of sublingual HVM measurements and the nature of artifacts are described. Eleven statements were formulated that pertained to image acquisitions and quality statements. Fourteen statements addressed the analysis of the images, and 13 statements are related to future developments.Conclusion: This consensus describes 25 statements regarding the acquisition and interpretation of microcirculatory images needed to guide the assessment of the microcirculation in critically ill patients.

Background The TOPP Registry has been designed to provide epidemiologic, diagnostic, clinical, and outcome data on children with pulmonary hypertension (PH) confirmed by heart catheterisation (HC). This study aims to identify important characteristics of the haemodynamic profile at diagnosis and HC complications of paediatric patients presenting with PH. Methods and results HC data sets underwent a blinded review for confirmation of PH (defined as mean pulmonary arterial pressure≥25mmHg, pulmonary capillary wedge pressure≤12mmHg and pulmonary vascular resistance index [PVRI] of >3WU×m 2 ). Of 568 patients enrolled, 472 who fulfilled the inclusion criteria and had sufficient data from HC were analysed. A total of 908 diagnostic and follow-up HCs were performed and complications occurred in 5.9% of all HCs including five (0.6%) deaths. General anaesthesia (GA) was used in 53%, and conscious sedation in 47%. Complications at diagnosis were more likely to occur if GA was used (p=0.04) and with higher functional class (p=0.02). Mean cardiac index (CI) was within normal limits at diagnosis when analysed for the entire group (3.7L/min/m 2 ; 95% confidence interval 3.4–4.1), as was right atrial pressure despite a severely increased PVRI (16.6WU×m 2, 95% confidence interval 15.6–17.76). However, 24% of the patients had a CI of 2 at diagnosis. A progressive increase in PVRI and decrease in CI was observed with age (p Conclusion In TOPP, haemodynamic assessment was remarkable for preserved CI in the majority of patients despite severely elevated PVRI. HC-related complication incidence was 5.9%, and was associated with GA and higher functional class.

Objective/backgroundTo investigate experimentally the arterial wall/device compliance mismatch of four stent-graft devices and a multilayer flow modulator within the supra- and infrarenal locations for the treatment of abdominal aortic aneurysms (AAA).MethodsFive devices (MFM, EndurantII, Excluder, Zenith, and Fortron) were tested under physiological flow conditions within a flow simulator system comprising of a patient-specific thin-walled flexible AAA perfusion model with replicated intraluminal thrombus, supported by the spinal column. Devices were submitted to circumferential force tests and implanted in the perfusion model for circumferential arterial pressure/diameter measurements. Parameters, including radial resistive force, supra-/infrarenal compliance, pulsatile arterial energy loss (PAEL), pulse wave velocity (PWV), and wave reflection coefficient (Γ), were computed to characterise the devices' performance.ResultsThe Zenith and EndurantII devices had the highest radial resistive force (up to 3 N/cm), while the Fortron device had the lowest (0.11 N/cm). Supra- and infrarenal compliance varied between 6.9–5.1 × 10−4/mmHg and 4.8–5.4 × 10−4/mmHg, respectively. Two devices (EndurantII and Excluder) significantly decreased infrarenal compliance by 13–26% (p

Item does not contain fulltext Increased serotonin serum levels have been proposed to play a key role in pulmonary arterial hypertension (PAH) by regulating vessel tone and vascular smooth muscle cell proliferation. An intact serotonin system, which critically depends on a normal function of the serotonin transporter (SERT), is required for the development of experimental pulmonary hypertension in rodents exposed to hypoxia or monocrotaline. While these animal models resemble human PAH only with respect to vascular media remodeling, we hypothesized that SERT is likewise required for the presence of lumen-obliterating intima remodeling, a hallmark of human PAH reproduced in the Sugen hypoxia (SuHx) rat model of severe angioproliferative pulmonary hypertension. Therefore, SERT wild-type (WT) and knockout (KO) rats were exposed to the SuHx protocol. SERT KO rats, while completely lacking SERT, were hemodynamically indistinguishable from WT rats. After exposure to SuHx, similar degrees of severe angioproliferative pulmonary hypertension and right ventricular hypertrophy developed in WT and KO rats (right ventricular systolic pressure 60 vs. 55 mmHg, intima thickness 38 vs. 30%, respectively). In conclusion, despite its implicated importance in PAH, SERT does not play an essential role in the pathogenesis of severe angioobliterative pulmonary hypertension in rats exposed to SuHx.

Contains fulltext : 154708.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To analyse the predicted 10- and 30-year risk scores for cardiovascular disease (CVD) in patients who experienced preeclampsia (PE) 5-10 years previously compared with healthy parous controls. DESIGN: Observational study. SETTING: Tertiary referral hospital in the Netherlands. POPULATION: One hundred and fifteen patients with a history of PE and 50 controls. PE patients were categorised into two groups, hypertensive (n = 21) and normotensive (n = 94), based on use of antihypertensive medication, and next categorised into subgroups based on the onset of PE: early-onset PE (n = 39) and late-onset PE (n = 76). METHODS: All participants underwent cardiovascular risk screening 5-10 years after index pregnancy. We measured body mass, height and blood pressure. Blood was analysed for fasting glucose, insulin and lipid levels. All participants completed a validated questionnaire. The 10- and 30-year Framingham risk scores were calculated and compared. MAIN OUTCOME MEASURES: Estimated Framingham 10- and 30-year risk scores for CVD. RESULTS: The overall 10- and 30-year CVD median risks weighing subjects' lipids were comparable between formerly PE women and controls; 1.6 versus 1.5% (P = 0.22) and 9.0 versus 9.0% (P = 0.49), respectively. However, hypertensive formerly PE women have twice the CVD risk as normotensive formerly PE women: 10- and 30-year CVD median risks were 3.1 versus 1.5% (P < 0.01) and 19.0% versus 8.0% (P < 0.01), respectively. Risk estimates based on BMI rather than lipid profile show comparable results. Early-onset PE clustered more often in the hypertensive formerly PE group and showed significantly higher 10- and 30-year CVD risk estimates based on lipids compared with the late-onset PE group: 1.7 versus 1.3% (P < 0.05) and 10.0 versus 7.0% (P < 0.05), respectively. CONCLUSIONS: Women who are hypertensive after preeclampsia, have a twofold risk of developing CVD in the next 10-30 years. Formerly PE women who are normotensive in the first 10 years after their preeclamptic pregnancy have a comparable future cardiovascular risk to healthy controls.

The aim of the study was to evaluate the role of conventional and new markers of early cardiac organ damage (OD) on 12-lead electrocardiography (ECG) in 25 outpatients with newly diagnosed untreated essential hypertension compared with 15 normotensive, otherwise healthy individuals. Each participant underwent ECG, echocardiographic, and blood pressure (BP) measurements. Conventional and new ECG indexes for cardiac OD (Tp-Te interval, ventricular activation time, and P-wave analysis) were also measured. Clinic and 24-hour ambulatory BP levels as well as left ventricular mass indexes were significantly higher in hypertensive than in normotensive patients. No significant differences were found between the two groups for ECG and echocardiographic markers of OD. Only Tp-Te interval was higher in hypertensive than in normotensive individuals (3.06 mm vs 2.24 mm; P

This analysis is aimed to determine blood pressure (BP) levels and BP control rates in a large population of hypertensive patients in Italy. Data were taken from two large and inclusive cross-sectional surveys, which covered two distinct and subsequent time periods (2000-2005 and 2005-2011, respectively). Observational clinical studies and surveys, which reported average systolic/diastolic clinic BP levels, proportions of treated/untreated and controlled/uncontrolled patients, and prevalence of cardiovascular risk factors in hypertensive patients followed in either outpatient clinics, hypertension centres or general practice, were considered for the analyses. The overall sample included 211 591 hypertensive patients (119 997 (56.7%) women, age 57.0±10.0 years, body mass index 26.9±4.0 kg m(-2), BP levels 146.9±16.7/88.7±9.6 mm Hg). BP levels were 148.2±15.4/87.5±9.3 mm Hg in patients followed by general practitioners (n=168 313, 79.5%), 148.1±17.3/90.1±9.7 mm Hg in those followed by hypertension centres (n=28 180, 13.3%), and 142.4±17.6/86.6±9.8 mm Hg in those followed by outpatient clinics and hospital divisions (n=15 098, 7.1%). Among treated hypertensive patients (n=128 079; 60.5%), 43 008 (33.6%) were reported to have controlled BP levels. Over one decade of observation, we reported that ~60% of hypertensive patients were treated and among these only 33% achieved effective BP control. These findings highlight the need for more effective interventions to improve management of hypertension in Italy.

© 2018 Journal of Thoracic Disease. All rights reserved. 2018 has seen important steps forward in the field of pulmonary vascular diseases. Risk stratification in both acute pulmonary embolism and PAH sees a move towards improving care by individualising patient therapy; whist the advent of interventional procedures provides a potential novel non-pharmacological technique for the treatment of PAH. ispartof: JOURNAL OF THORACIC DISEASE vol:10 issue:Suppl 25 pages:S3029-S3033 ispartof: location:China status: published

Objective The aim of our study was to investigate clinical importance of neutrophil/ lymphocyte ratio in patients with Chronic thromboembolic pulmonary hypertension. Methods 125 consecutive patients with a diagnosis of Chronic thromboembolic pulmonary hypertension were operated pulmonary thromboendarterectomy in our center between February 2011 and August 2013. 106 patients included into the study due to limitations. The patients were classified into two groups as patients discharged alive (Group 1) and those dying in the hospital (Group 2). Baseline neutrophil/lymphocyte ratio level was measured by dividing neutrophil count to lymphocyte count. Results 84 patients (79%) were in Group 1, 22 patients (21%) were in Group 2. Patients with higher neutrophil/lymphocyte ratio in admission have a significantly higher mortality rate and postoperative pulmonary vascular resistance was found statistically significant variable to predict the mortality. Receiver operator characteristic (ROC) analysis revealed that using a cut-off point of 2.54, admission neutrophil/lymphocyte ratio predicts mortality. Also, correlation analysis showed a significant correlation between preoperative pulmonary vascular resistance and neutrophil/lymphocyte ratio. Conclusion The neutrophil/lymphocyte ratio level may be a useful and noninvasive biomarker for operative risk stratification for mortality after pulmonary thromboendarterectomy.

Recent trends in use of antihypertensive drugs are unknown. From Danish nationwide prescription data, we obtained information on primary care use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, aldosterone receptor antagonists, and calcium channel blockers. During 1999 to 2015, the use of antihypertensive drugs per 1,000 inhabitants/day increased from 184 to 379 defined daily doses (DDD), corresponding to a rise in the prevalence proportion of users from approximate to 20% to approximate to 35%. From 1999 to 2015, a notable increase was observed for angiotensin-converting enzyme inhibitors (from 29 to 105 DDD per 1,000 inhabitants/day approximate to 260%) and angiotensin H receptor blockers (from 13 to 73 DDD per 1,000 inhabitants/day approximate to 520%). For diuretics the use remained stable, with a slight decrease (from 89 to 81 DDD per 1,000 inhabitants/day approximate to-10%). The use of aldosterone receptor antagonists increased until 2007 and remained unchanged at around 3.5 DDD per 1,000 inhabitants/day thereafter (average change approximate to 65%). The use of beta blockers doubled during the study period (from 17 to 34 DDD per 1,000 inhabitants/day approximate to 100%), entirely driven by increasing use of metoprolol. Similar trends.were observed for calcium channel blockers (from 34 to 82 DDD per 1,000 inhabitants/day approximate to 140%), where amlodipine drove the overall increase. In conclusion, antihypertensive drug use has increased remarkably during the past 2 decades. (C) 2017 Elsevier Inc. All rights reserved.

Albuminuria development in hypertensive patients is an indicator of higher cardiovascular (CV) risk and renal damage. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control but it does not prevent from albuminuria development. We pursued the identification of protein indicators in urine behind albuminuria development in hypertensive patients under RAS suppression. Urine was collected from 100 patients classified in three groups according to albuminuria development: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Quantitative analysis was performed in a first discovery cohort by isobaric labeling methodology. Alterations of proteins of interest were confirmed by target mass spectrometry analysis in an independent cohort. A total of 2416 proteins and 1223 functional categories (coordinated protein responses) were identified. Immune response, adhesion of immune and blood cells, and phagocytosis were found significantly altered in patients with albuminuria compared to normoalbuminuric individuals. The complement system C3 increases, while Annexin A1, CD44, S100A8 and S100A9 proteins showed significant diminishment in their urinary levels when albuminuria is present. This study reveals specific links between immune response and controlled hypertension in patients who develop albuminuria, pointing to potential protein targets for novel and future therapeutic interventions. The authors acknowledge Lucia Guerrero and Maria Cruz Casal from Hospital 12 de Octubre for their participation in samples collection. Instituto de Salud Carlos III co- supported by FEDER grants (PI11/01401, PI13/01873, PI14/01650, PI16/01334, CPII15/00027, PT13/0001/0013, IF08/3667-1, PI11/02239, PI11/02432, PI14/0917, PI14/01841, PIE13/00045, CP15/00129, PI13/01746, REDinREN (RD12/0021/0001, RD12/0042/0071 and RD16/0009)), and Fundacion SENEFRO. These results are lined up with the Spanish initiative on the Human Proteome Project (SpHPP). Sí

Item does not contain fulltext Cardiac magnetic resonance (CMR) imaging is the preferred method to measure right ventricular (RV) volumes and ejection fraction (RVEF). This study aimed to determine the impact of excluding trabeculae and papillary muscles on RV volumes and function in patients with RV pressure and/or volume overload and healthy controls and its reproducibility using semi-automatic software. Eighty patients (pulmonary hypertension, transposition of the great arteries after arterial switch operation and after atrial switch procedure and repaired Tetralogy of Fallot) and 20 controls underwent short-axis multislice cine CMR. End diastolic volume (EDV), end systolic volume (ESV), RV mass and RVEF were measured using 2 methods. First, manual contour tracing of RV endo- and epi-cardial borders was performed. Thereafter, trabeculae were excluded from the RV blood volume using semi-automatic pixel-intensity based software. Both methods were compared using a Student T test and 25 datasets were re-analyzed for reproducibility. Exclusion of trabeculae resulted in significantly decreased EDV; ranging from -5.7 +/- 1.7 ml/m(2) in controls to -29.2 +/- 6.6 ml/m(2) in patients after atrial switch procedure. RVEF significantly increased in all groups, ranging from an absolute increase of 3.4 +/- 0.8 % in healthy controls to 10.1 +/- 2.3 % in patients after atrial switch procedure. Interobserver agreement of method 2 was equal to method 1 for RVEDV, RVESV and RVEF and superior for RV mass. In patients with overloaded RVs exclusion of trabeculae from the blood volume results in a significant change in RV volumes, RVEF and RV mass. Exclusion of trabeculae is highly reproducible when semi-automatic pixel-intensity based software is used.

ObjectivePatients with repaired coarctation (RCoA) remain at higher risk of cardiac dysfunction, initially often only detected during exercise. In this study, haemodynamics of isometric handgrip (HG) and bicycle ergometry (BE) were compared in patients with RCoA and matched controls (MCs).MethodsCase–control study of 19 children with RCoA (mean age 12.9±2.3 years; mean age of repair 7 months) compared with 20 MC. HG with echocardiography followed by BE was performed in both groups.ResultsDuring HG (blood pressure) BP increased from 114±11/64±4 mm Hg to 132±14/79±7 mm Hg, without significant differences. During HG as well as BE, HR increased less in patients with RCoA. There were no significant differences in (left ventricle) LV dimensions or LV mass.The RCoA group had diastolic dysfunction: both at rest and during HG they had significantly higher transmitral E and A velocities and lower tissue Doppler E′ and A′ velocities. E/E′ was higher, reaching statistical significance during HG (pConventional parameters of systolic function (FS and EF) were similar at rest and HG. More sensitive tissue Doppler S′ was significantly lower at rest in CoA subjects (5.1±1.5 cm/s vs 6.5±1±1 cm/s; pConclusionsWe provide first evidence that HG with echocardiography is feasible, easy and patient-friendly. A decreased systolic (tissue Doppler) and impaired diastolic LV function was measured in the RCoA group, a difference that tended to increase during HG.

Item does not contain fulltext Pulmonary arterial hypertension (PAH) and renal thrombotic microangiopathy (rTMA) are rare diseases in childhood, frequently leading to death and end-stage renal disease, respectively. Their combined occurrence has been reported anecdotally. We investigated the clinical, biochemical, and genetic aspects of 5 children with the rare combination of PAH and rTMA. Onset of disease ranged from 1.5 to 14 years of age. The 2 youngest patients presented with concomitant pulmonary and renal disease; in the older patients, PAH was preceded by rTMA from age 2.5 to 7 years. Three patients presenting at A or G>T) at nucleotide 276 in addition to frame-shift mutations. One patient had homozygous nonsense mutations of MMACHC. We established cblC deficiency as the denominator in the rare combination of PAH and rTMA in these children. Early recognition of cblC deficiency and vigorous treatment with hydroxocobalamin may beneficially affect the course of this devastating disease. 01 augustus 2013

Resistant hypertension is highly prevalent, and is the form of arterial hypertension that is most difficult to treat. Many patients diagnosed with this disease do not have resistant hypertension, but rather have mismanaged primary hypertension. In many cases blood pressure can be controlled by directly addressing underlying causes such as primary aldosteronism, obstructive sleep apnoea, or excessive neurogenic stimulation. Clinicians should ensure that appropriate blood-pressure measurements are used to diagnose resistant hypertension, explore a variety of drug combinations, and battle clinical inertia. Patients should comply with medication schedules and dietary modifications. Correction of these factors will greatly diminish the prevalence of 'resistant' hypertension and avoid the consequences of a persistently elevated blood pressure in these patients.

Bone morphogenetic protein (BMP) signaling regulates vascular smooth muscle maturation, endothelial cell proliferation, and tube formation. The endogenous BMP antagonist Follistatin-like 1 (Fstl1) is highly expressed in pulmonary vascular endothelium of the developing mouse lung, suggesting a role in pulmonary vascular formation and vascular homeostasis. The aim of this study was to investigate the role of Fstl1 in the pulmonary vascular endothelium. To this aim, Fstl1 was conditionally deleted from endothelial and endothelial-derived cells using Tie2-cre driven Fstl1-KO mice (Fstl1-eKO mice). Endothelial-specific Fstl1 deletion was postnatally lethal, as ∼70% of Fstl1-eKO mice died at three weeks after birth. Deletion of Fstl1 from endothelium resulted in a reduction of right ventricular output at three weeks after birth compared with controls. This was associated with pulmonary vascular remodeling, as the percentage of actin-positive small pulmonary vessels was increased at three weeks in Fstl1-eKO mice compared with controls. Endothelial deletion of Fstl1 resulted in activation of Smad1/5/8 signaling and increased BMP/Smad-regulated gene expression of Jagged1, Endoglin, and Gata2 at one week after birth compared with controls. In addition, potent vasoconstrictor Endothelin-1, the expression of which is driven by Gata2, was increased in expression, both on the mRNA and protein levels, at one week after birth compared with controls. At three weeks, Jagged1 was reduced in the Fstl1-eKO mice whereas Endoglin and Endothelin-1 were unchanged. In conclusion, loss of endothelial Fstl1 in the lung is associated with elevated BMP-regulated genes, impaired small pulmonary vascular remodeling, and decreased right ventricular output.

International audience; Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited genetic vascular disorder with an estimated prevalence of 1 in 6,000, characterized by recurrent epistaxis, cutaneous telangiectasia, and arteriovenous malformations (AVMs) that affect many organs including the lungs, gastrointestinal tract, liver, and brain. Its diagnosis is based on the Curacao criteria, and is considered definite if at least 3 of the 4 following criteria are fulfilled: (1) spontaneous and recurrent epistaxis, (2) telangiectasia, (3) a family history, and (4) pulmonary, liver, cerebral, spinal, or gastrointestinal AVMs. The focus of this review is on delineating how HHT affects the lung.

Introduction: The causes of intradialytic hypertension (IDHyper) are not well understood and this condition can complicate the clinical management of hemodialysis (HD) patients. Aim: To evaluate the potential role of intradialytic sodium gradient (NaG) on blood pressure values and IDHyper during HD. Patients and Methods: 206 prevalent HD patients on 3 times weekly HD treatment for at least 6 months (dialytic vintage 6-240 months) followed at our institution were studied. Mean age was 68 ± 14 years, 129 were men. For 2 consecutive months (24 HD sessions) after the start of observation, the following variables were evaluated in predialysis after the long interdialysis interval: pre-HD plasma sodium (pNa, mmol/l) and potassium (pK, mmol/l) concentrations (mean value of 8 determinations), pre- and post-HD systolic (SBP, mm Hg) and diastolic (DBP, mm Hg) blood pressure, dry body weight (dBW, kg), interdialytic weight gain (IDWG, kg), ultrafiltration rate (UFR, ml/kg/h), dialysis dose (Kt/V), protein catabolic rate (PCRn, g/kg/day), hemoglobin (Hb, g/dl). SBP, DBP, IDWG, UFR are the mean values of the 24 HD sessions. 76% of patients were on antihypertensive therapy, 171 patients were on bicarbonate HD, and 35 on HDF. Dialysate Na concentration was set at 140 mmol/l in all patients. Duration of HD and the blood and dialysate flow rate were kept constant during observation. Statistical Analysis: Data are expressed as mean ± SD; linear and multiple regression analysis and t test for unpaired data were employed. Significant differences were defined as p < 0.05. Results: Pre-HD pNa was 138.1 ± 2.3 mmol/l, pK 5.0 ± 0.4 mmol/l, dBW 67 ± 14 kg, IDWG 2.9 ± 0.8 kg, UFR 11.2 ± 3.7 ml/kg/h, Kt/V 1.43 ± 0.18, PCRn 1.13 ± 0.17 g/kg/day, and Hb 11.2 ± 0.8 g/dl. Pre- and post-HD SBP values were 139 ± 13 and 134 ± 12 mm Hg (p < 0.0001); pre- and post-HD DBP did not change significantly. A dialysis Na gradient (NaG) (dialysate Na - pre-HD pNa) was calculated, as well as the delta of SBP (ΔSBP) (post-HD SBP - pre-HD SBP). IDHyper was defined as ΔSBP >0. A significant direct correlation was found between NaG and ΔSBP (p < 0.0001) and multiple regression analysis with ΔSBP as dependent variable confirmed the strong correlation with NaG (p < 0.00001). According to ΔSBP behavior, 171 patients (83%) had a decrease or no change in post-HD SBP (group 1; no IDHyper); 35 patients (17%) increased their post-HD SBP (group 2; IDHyper). NaG values were significantly greater in patients in group 2 (group 1: 1.5 ± 2.2 vs. group 2: 3.3 ± 2.5, p < 0.0001). Conclusions: This study shows that the intradialytic ΔSBP is independently and strongly associated with the dialytic NaG. The more positive the NaG (net intradialytic Na gain), the more positive the ΔSBP and IDHyper.

Resumen Introducción .En enfermería ha destacado la inclusión de medicina tradicional y alternativa como disciplina para prevenir, diagnosticar, tratar y rehabilitar al paciente con técnicas de masaje y acupuntura. En la revista Salud Mundial la OMS enlista enfermedades que pueden ser tratadas con dicha medicina, disminuyendo las repercusiones de patologías que ocupan los primeros lugares de morbimortalidad en México. Objetivo.Conocer si la acupuntura y el masaje son tratamientos alternativos auxiliares en la HTA y DM2 en usuarios del centro de salud de Cuitláhuac, Tacotalpa, Tab. Método . Estudio cuantitativo, transversal, cuasiexperimental, en 28 pacientes con DM2 y HTA, conmediciones antes y después del tratamiento alternativo. Resultado. Con el tratamiento alternativo, la glicemia bajó de 131 a 124 mg y la presión arterial de 140/79 a 123/83 mmHg (p ≤ 0.05). Conclusión. La acupuntura y masajemuestran ser auxiliares altratar enfermedades crónicas, no se cuenta con resultados más específicos en población indígena mexicana y es necesario realizar estudios con diseños más robustos para determinar su eficacia. Abstract Introduction. Nursing has highlighted the inclusion of traditional and alternative medicine as a discipline to prevent, diagnose, treat and rehabilitate the patient with acupuncture and massage techniques. In the WHO Global Health magazine lists diseases that can be treated with this medicine, reducing the impact of diseases that are at the top of morbidity and mortality in Mexico. Objective. Know if acupuncture and massage are alternative treatments aids in hypertension and DM2 users Cuitláhuac health center, Tacotalpa, Tab. Method. Quantitative, transversal, quasi-experimental, in 28 patients with type 2 diabetes and hypertension, with measurements before and after alternative treatment study. Result. With alternative treatment, blood glucose levels dropped from 131 to 124 mg and blood pressure of 140/79 to 123/83 mmHg (p ≤ 0.05). Conclusion. Acupuncture and massage shown to be ancillary to treat chronic diseases, do not have more specific results in Mexico's indigenous population and studies are needed with more robust designs for their effectiveness. Resumo Introdução. Enfermagemdestacou a inclusão da medicinatradicional e alternativacomoumadisciplinaparaprevenir, diagnosticar, tratar e reabilitar o paciente com técnicas de acupuntura e massagem. Na revista WHO Global Health lista de doençasquepodemsertratadascomestemedicamento, reduzindo o impacto de doençasqueestão no topo de morbidade e mortalidade no México. Objectivo. Saber se aacupuntura e massagemsãoajudartratamentosalternativosnahipertensão e usuários de DM2 centro de saúdeCuitláhuac, Tacotalpa, Tabasco. Método . Quantitativa, transversal, quasi-experimental, em 28 pacientes com diabetes tipo 2 e hipertensão, com medições antes e depois de estudo de tratamentoalternativo. Resultado . Com tratamentoalternativo, osníveis de glicose no sanguecaiu de 131 para 124 mg e pressão arterial de 140/79 a 123/83 mmHg (p ≤ 0,05). Conclusão. Acupuntura e massagemdemonstrouserauxiliar no tratamento de doençascrônicas, nãotêmresultadosmaisespecíficosemestudospopulacionais e indígenas do México sãonecessárioscomdesenhosmaisrobustospara a suaeficácia.

Background Circulating angiopoietin-1 (Ang-1) has been linked to pulmonary hypertension (PH) in experimental studies. However, the clinical relevance of Ang-1 as a biomarker in PH remains unknown. We aimed to investigate the prognostic and clinical significance of Ang-1 in PH using data from the prospectively recruiting Giessen PH Registry. Methods Patients with suspected PH (without previous specific pulmonary arterial hypertension [PAH] therapy) who underwent initial right heart catheterization (RHC) in our national referral center between July 2003 and May 2012 and who agreed to optional biomarker analysis were included if they were diagnosed with idiopathic PAH, connective tissue disease-associated PAH (CTD-PAH), PH due to left heart disease (PH-LHD), or chronic thromboembolic PH (CTEPH), or if PH was excluded by RHC (non-PH controls). The association of Ang-1 levels with disease severity (6-minute walk distance and pulmonary hemodynamics) was assessed using linear regression, and the impact of Ang-1 levels on transplant-free survival (primary endpoint) and clinical worsening was assessed using Kaplan—Meier curves, receiver operating characteristic (ROC) analyses, and Cox regression. Results 151 patients (39, 39, 32, and 41 with idiopathic PAH, CTD-PAH, PH-LHD, and CTEPH, respectively) and 41 non-PH controls were included. Ang-1 levels showed no significant difference between groups (p = 0.8), and no significant associations with disease severity in PH subgroups (p ≥ 0.07). In Kaplan—Meier analyses, Ang-1 levels (stratified by quartile) had no significant impact on transplant-free survival (p ≥ 0.27) or clinical worsening (p ≥ 0.51) in PH subgroups. Regression models found no significant association between Ang-1 levels and outcomes (p ≥ 0.31). ROC analyses found no significant cut-off that would maximize sensitivity and specificity. Conclusions Despite a strong pathophysiological association in experimental studies, this first comprehensive analysis of Ang-1 in PH subgroups suggests that Ang-1 is not a predictive and clinically relevant biomarker in PH.

Rationale: Enhanced proliferation and impaired apoptosis of pulmonary arterial vascular smooth muscle cells (PAVSMCs) are key pathophysiologic components of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH).Objectives: To determine the role and therapeutic relevance of HIPPO signaling in PAVSMC proliferation/apoptosis imbalance in PAH.Methods: Primary distal PAVSMCs, lung tissue sections from unused donor (control) and idiopathic PAH lungs, and rat and mouse models of SU5416/hypoxia-induced pulmonary hypertension (PH) were used. Immunohistochemical, immunocytochemical, and immunoblot analyses and transfection, infection, DNA synthesis, apoptosis, migration, cell count, and protein activity assays were performed in this study.Measurements and Main Results: Immunohistochemical and immunoblot analyses demonstrated that the HIPPO central component large tumor suppressor 1 (LATS1) is inactivated in small remodeled pulmonary arteries (PAs) and distal PAVSMCs in idiopathic PAH. Molecular- and pharmacology-based analyses revealed that LATS1 inactivation and consequent up-regulation of its reciprocal effector Yes-associated protein (Yap) were required for activation of mammalian target of rapamycin (mTOR)-Akt, accumulation of HIFl alpha, Notch3 intracellular domain and beta-catenin, deficiency of proapoptotic Bim, increased proliferation, and survival of human PAH PAVSMCs. LATS1 inactivation and up-regulation of Yap increased production and secretion of fibronectin that up regulated integrin-linked kinase 1 (ILK1). ILK1 supported LATS1 inactivation, and its inhibition reactivated LATS1, down-regulated Yap, suppressed proliferation, and promoted apoptosis in PAH, but not control PAVSMCs. PAVSM in small remodeled PAs from rats and mice with SU5416/hypoxia-induced PH showed down regulation of LATS1 and overexpression of ILK1. Treatment of mice with selective ILKinhibitor Cpd22 at Days 22-35 of SU5416/hypoxia exposure restored LATS1 signaling and reduced established pulmonary vascular remodeling and PH.Conclusions: These data report inactivation of HIPPO/LATS1, self-supported via Yap-fibronectin-ILK1 signaling loop, as a novel mechanism of self-sustaining proliferation and apoptosis resistance of PAVSMCs in PAH and suggest a new potential target for therapeutic intervention.

Hypoxic pulmonary vasoconstriction is correlated with pulmonary vascular remodeling. The hypoxia-inducible transcription factors (HIFs) HIF-1α and HIF-2α are known to contribute to the process of hypoxic pulmonary vascular remodeling; however, the specific role of pulmonary endothelial HIF expression in this process, and in the physiological process of vasoconstriction in response to hypoxia, remains unclear. Here we show that pulmonary endothelial HIF-2α is a critical regulator of hypoxia-induced pulmonary arterial hypertension. The rise in right ventricular systolic pressure (RVSP) normally observed following chronic hypoxic exposure was absent in mice with pulmonary endothelial HIF-2α deletion. The RVSP of mice lacking HIF-2α in pulmonary endothelium after exposure to hypoxia was not significantly different from normoxic WT mice and much lower than the RVSP values seen in WT littermate controls and mice with pulmonary endothelial deletion of HIF-1α exposed to hypoxia. Endothelial HIF-2α deletion also protected mice from hypoxia remodeling. Pulmonary endothelial deletion of arginase-1, a downstream target of HIF-2α, likewise attenuated many of the pathophysiological symptoms associated with hypoxic pulmonary hypertension. We propose a mechanism whereby chronic hypoxia enhances HIF-2α stability, which causes increased arginase expression and dysregulates normal vascular NO homeostasis. These data offer new insight into the role of pulmonary endothelial HIF-2α in regulating the pulmonary vascular response to hypoxia.

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive and debilitating diseases characterized by gradual obstruction of the pulmonary vasculature, leading to elevated pulmonary artery pressure (PAP) and increased pulmonary vascular resistance (PVR). If untreated, they can result in death due to right-sided heart failure. Riociguat is a novel soluble guanylate cyclase (sGC) stimulator that is approved for the treatment of PAH and CTEPH. We describe in detail the role of the nitric oxide-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway in the pathogenesis of PAH and CTEPH and the mode of action of riociguat. We also review the preclinical data associated with the development of riociguat, along with the efficacy and safety data of riociguat from initial clinical trials and pivotal phase III randomized clinical trials in PAH and CTEPH.

In patients with left ventricular heart failure (HF), the development of pulmonary hypertension (PH) and right ventricular (RV) dysfunction are frequent and have important impact on disease progression, morbidity, and mortality, and therefore warrant clinical attention. Pulmonary hypertension related to left heart disease (LHD) by far represents the most common form of PH, accounting for 65-80% of cases. The proper distinction between pulmonary arterial hypertension and PH-LHD may be challenging, yet it has direct therapeutic consequences. Despite recent advances in the pathophysiological understanding and clinical assessment, and adjustments in the haemodynamic definitions and classification of PH-LHD, the haemodynamic interrelations in combined post- and pre-capillary PH are complex, definitions and prognostic significance of haemodynamic variables characterizing the degree of pre-capillary PH in LHD remain suboptimal, and there are currently no evidence-based recommendations for the management of PH-LHD. Here, we highlight the prevalence and significance of PH and RV dysfunction in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), and provide insights into the complex pathophysiology of cardiopulmonary interaction in LHD, which may lead to the evolution from a 'left ventricular phenotype' to a 'right ventricular phenotype' across the natural history of HF. Furthermore, we propose to better define the individual phenotype of PH by integrating the clinical context, non-invasive assessment, and invasive haemodynamic variables in a structured diagnostic work-up. Finally, we challenge current definitions and diagnostic short falls, and discuss gaps in evidence, therapeutic options and the necessity for future developments in this context., SCOPUS: re.j, info:eu-repo/semantics/published

IF 8.332; International audience; A case of pulmonary hypertension associated with ponatinib therapy in a chronic myelogenous leukaemia patient.

Background: Pulmonary arterial hypertension (PAH) is a progressive angioproliferative disease with high morbidity and mortality. Although the histopathology is well described, its pathogenesis is largely unknown. We previously identified the increased presence of mast cells and their markers in a rat model of flow-associated PAH. The aim of this study was to test the effect of mast cell stabilization on pulmonary vascular remodeling in experimental PAH.Methods: Rats with flow-associated PAR created by monocrotaline and an aorto-caval shunt were treated with the mast cell stabilizer cromolyn and compared with untreated rats and control rats. Further, we treated a group of rats with PAR with an inhibitor (TY-51469) of chymase, one of the mast cell proteases. The effects on pulmonary vascular remodeling and hemodynamics were assessed.Results: Rats with PAR had increased mast cells, chymase activity, and inflammatory markers. Treatment with mast cell stabilizer attenuated pulmonary vascular remodeling but not hemodynamics. A lower pulmonary chymase activity correlated with more favorable pulmonary vascular remodeling as well as hemodynamics and inflammatory markers.Conclusions: We showed in rats with PAH that mast cell stabilization attenuated pulmonary vascular remodeling and that a lower chymase activity correlated with more favorable hemodynamics and pulmonary vascular remodeling. The results of this experimental study support the concept of the use of antiinflammatory therapy by mast cell stabilizers, a group of drugs already licensed for clinical use, to attenuate disease progression in PAH. CHEST 2012; 141(3):651-660

Women with pulmonary hypertension have a high risk of morbidity and mortality during pregnancy. The inability to increase cardiac output leads to heart failure while further risks are introduced with hypercoagulability and decrease in systemic vascular resistance. There is no proof that new advanced therapies for pulmonary hypertension decrease the risk, though some promising results have been reported. However, pregnancy should still be regarded as contraindicated in women with pulmonary hypertension. When pregnancy occurs and termination is declined, pregnancy and delivery should be managed by multidisciplinary services with experience in the management of both pulmonary hypertension and high-risk pregnancies.

In flow-associated pulmonary arterial hypertension (PAH), increased pulmonary blood flow is an essential trigger for neointimal formation. Using microarray analysis, we recently found that the early growth response protein 1 (Egr-1) transcription factor is increased in experimental flow-associated end-stage PAH. Its role in PAH development is unknown. Here, we assessed the spatiotemporal expression of Egr-1 during neointimal development in flow-associated PAH. Flow-associated PAH was produced in rats by combining monocrotaline administration with an aortocaval shunt. Animals were sacrificed 1 day before or 1 day, 1 week, or 4 to 5 weeks after flow addition. Egr-1 expression was spatiotemporally assessed using laser microdissection, quantitative real-time PCR and immunohistochemistry. In addition, Egr-1 expression was assessed in a non-neointimal pulmonary hypertension model and in human PAH associated with congenital shunt. In 4 to 5 weeks, rats subjected to increased flow developed PAH with neointimal lesions. Egr-1 mRNA was increased 1 day after flow addition and in end-stage PM!, whereas monocrotaline only did not result in increased Egr-1 mRNA. Directly after flow addition, Egr-1 was expressed in endothelial cells. During disease development, Egr-1 protein expression increased and migrated throughout the vessel wall. In PM! patients, Egr-1 was expressed in vessels with media hypertrophy and neointimal lesions, including plexiform lesions. Thus, Egr-1 may be an important regulator in the development of pulmonary neointimal lesions induced by increased pulmonary blood flow. (Am J Pathol 2011, 179:2199-2209; DOI: 10.1016/j.ajpath.2011.07.030)

Background The benefits of reducing blood pressure are well established, but there remains uncertainty about whether the magnitude of the effect varies with the initial blood pressure level. The objective was to compare the risk reductions achieved by different blood pressure-lowering regimens among individuals with different baseline blood pressures. Methods Thirty-two randomized controlled trials were included and seven comparisons between different types of treatments were made. For each comparison, the primary prespecified analysis included calculation of summary estimates of effect using random-effects meta-analysis for major cardiovascular events in four groups defined by baseline SBP (= 180 mmHg). Results There were 201 566 participants among whom 20 079 primary outcome events were observed. There was no evidence of differences in the proportionate risk reductions achieved with different blood pressure-lowering regimens across groups defined according to higher or lower levels of baseline SBP (all P for trend >0.17). This finding was broadly consistent for comparisons of different regimens, for DBP categories, and for commonly used blood pressure cut-points. Conclusion It appears unlikely that the effectiveness of blood pressure-lowering treatments depends substantively patients in the trials contributing to these overviews had a history of hypertension or were receiving background blood pressure-lowering therapy, the findings suggest that additional blood pressure reduction in hypertensive patients meeting initial blood pressure targets will produce further benefits. More broadly, the data are supportive of the utilization of blood pressure-lowering regimens in high-risk patients with and without hypertension. J Hypertens 29: 4-16 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.