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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.

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.)

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.

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

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.

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.

Many public health policies in Latin America target an optimized sodium and potassium intake. The aims of this study were to assess the sodium and potassium intake using 24-hour urinary analysis and to study their association with blood pressure in a Uruguayan population cohort using cluster analysis. A total of 149 participants (aged 20-85 years) were included in the study, and office blood pressure, anthropometric measurements, biochemical parameters in the blood, and 24-hour urine samples were obtained. The overall mean sodium and potassium excretion was 152.9 ± 57.3 mmol/day (8.9 ± 3.4 g/day of salt) and 55.4 ± 19.6 mmol/day, respectively. The average office systolic/diastolic blood pressure was 124.6 ± 16.7/79.3 ± 9.9 mmHg. Three compact spherical clusters were defined in untreated participants based on predetermined attributes, including blood pressure, age, and sodium and potassium excretion. The major characteristics of the three clusters were (1) high systolic blood pressure and moderate sodium excretion, (2) moderate systolic blood pressure and very high sodium excretion, and (3) low systolic blood pressure and low sodium excretion. Participants in cluster three had systolic blood pressure values that were 23.9 mmHg (95% confidence interval: -29.5 to -1.84) lower than those in cluster one. Participants in cluster two had blood pressure levels similar to those in cluster one (P = 0.32) and worse metabolic profiles than those in cluster one and three (P < 0.05). None of the clusters showed high blood pressure levels and high sodium excretion. No linear association was found between blood pressure and urinary sodium excretion (r < 0.14; P > 0.47). An effect of sodium and potassium intake on blood pressure levels was not found at the population level using regression or cluster analysis. ispartof: INTERNATIONAL JOURNAL OF HYPERTENSION vol:2018 ispartof: location:United States 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

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.

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.

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 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.

Contains fulltext : 80922.pdf (Publisher’s version ) (Closed access) AIMS: In patients with pulmonary hypertension (PH), elevated endothelin-1 levels are associated with prolonged duration of right ventricular (RV) contraction, which induces leftward ventricular septal bowing with impaired left diastolic filling. We hypothesized that baseline RV contraction duration predicts efficacy of endothelin receptor antagonist, bosentan. METHODS AND RESULTS: Eighteen PH patients (age 57, range 35-79 years, 33% male) received bosentan. Six minute walk distance (6-MWD) and echocardiography were performed at baseline and after 1 year follow-up. After 1 year of treatment, 6-MWD increased (mean 60 +/- 41 m) in 67% of patients (responders). Baseline RV contraction duration was longer in responders, compared with non-responders (612 +/- 66 vs. 514 +/- 23 ms; P < 0.01). A baseline RV contraction duration >550 ms was associated with improved 6-MWD (sensitivity 83%, specificity 83%; P < 0.01). CONCLUSION: An improvement of 6-MWD during bosentan treatment was associated with a decrease in RV contraction duration and could be predicted by a baseline RV contraction duration >550 ms.

Blood pressure ( BP) control remains unsatisfactory worldwide. Better knowledge of BP management in clinical practice is needed to develop more effective improving strategies. Using a large Italian primary care database, we selected the subjects diagnosed with hypertension, and extracted the diagnosis of myocardial infarction, angina pectoris/coronary disease, stroke/transitory ischemic attack (TIA), heart failure, atrial fibrillation, peripheral arterial disease, diabetes mellitus, the serum total cholesterol, HDL cholesterol, triglycerides, creatinine, BP, electrocardiogram, weight, height and the prescription of cardiovascular ( CV) drugs. Hypertension was recorded in 119.065 individuals (prevalence 19.3%), 19.134 (16%) had no ambulatory visit and 33.183 (27.8%) had no BP value recorded. Overall, 14.594 (21.9%) had at least one recorded diagnosis showing high CV risk. BP was controlled (mean of BP values

Contains fulltext : 81439.pdf (Publisher’s version ) (Closed access) The prevalence and incidence of systemic sclerosis (SSc) in The Netherlands is unknown. The same holds true for its leading causes of death: pulmonary fibrosis and pulmonary arterial hypertension (PAH), for which effective treatment options have recently become available. OBJECTIVE: To establish the prevalence and incidence of SSc and its pulmonary complications. METHODS: Detailed information on patients in the POEMAS registry, "Pulmonary Hypertension Screening, a Multidisciplinary Approach in Scleroderma", consisting of 819 patients, was combined with a nationwide questionnaire. RESULTS: By combining the two sources the prevalence of SSc was found to be 8.9 per 100 000 adults. The incidence was 0.77 patients per 100 000 per year. PAH was diagnosed in 9.9% of SSc patients. The prevalence of interstitial lung disease in SSc varied from 19% to 47% depending on the definition used. CONCLUSION: This study clarifies the epidemiology of SSc in The Netherlands and confirms the frequent occurrence of pulmonary complications, based on 654 cases. This can and will be studied further in the ongoing POEMAS study.

Erythropoietin (EPO) mobilises endothelial progenitor cells and promotes neovascularisation in heart failure. The present authors studied the effects of EPO on pulmonary vascular and cardiac remodelling in a model for flow-associated pulmonary arterial hypertension (PAH). PAH was induced in adult male Wistar rats by the injection of monocrotaline combined with an abdominal aortocaval shunt 1 week later (PAH or experimental group). Immediately afterwards, rats were randomised into those who received treatment with EPO (PAH+EPO group) and controls. Pulmonary and systemic haemodynamics, and right ventricular and pulmonary vascular remodelling were evaluated 3 weeks later. Vascular occlusion of the intra-acinar pulmonary vessels (13.4 +/- 0.7 versus 16.7 +/- 1.3% in PAH+EPO and PAH, respectively) and medial wall thickness of the pre-acinar arteries (wall-to-lumen ratio 0.13 +/- 0.01 versus 0.17 +/- 0.01 in PAH+EPO and PAH, respectively) decreased after treatment with EPO. Moreover, right ventricular capillary density was increased by therapy (2,322 +/- 61 versus 2,100 +/- 63 capillaries mm(-2) in PAH+EPO and PAH, respectively). Increased mean pulmonary arterial pressure and decreased right ventricular contractility in the model were not altered by EPO treatment. In this rat model of flow-associated pulmonary arterial hypertension, erythropoietin treatment beneficially affected pulmonary vascular and cardiac remodelling. These histopathological effects were not accompanied by significantly improved haemodynamics.

This editorial refers to ‘Contrasting mortality risks among subgroups of treated hypertensive patients developing new-onset diabetes’[†][1], by S. Lip et al ., on page 968. Arterial hypertension and type 2 diabetes mellitus are well known cardiovascular (CV) risk factors, which are often associated.1 In a large, prospective cohort study including 12 550 adults, the development of type 2 diabetes was almost 2.5 times as likely in patients with hypertension than in their normotensive counterparts. It is common knowledge that prevalent and new-onset diabetes in hypertensive patients are associated with a two- to three-fold higher risk of CV disease.2 Furthermore, a recent analysis of the Framingham data showed that the population with prevalent hypertension at the time of diagnosis of diabetes mellitus had higher rates of all-cause and CV mortality, thus suggesting that much of this excess risk is attributable to co-existent hypertension.3 This strong piece of evidence led to the classification of hypertensive patients with diabetes mellitus automatically at very high CV risk by ESC/ESH Guidelines.4 For that reason, in the past years lower blood pressure (BP) targets had been recommended for this subgroup of patients,5 although no evidence from randomized clinical trials supported this suggestion. Indeed, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study failed to demonstrate a significant reduction in incidence of CV events when lowering … [1]: #fn-2

Background Pulmonary hypertension (PH) is a common finding in patients with chronic fibrosing idiopathic interstitial pneumonias (IIP). Little is known about the response to pulmonary vasodilator therapy in this patient population. COMPERA is an international registry that prospectively captures data from patients with various forms of PH receiving pulmonary vasodilator therapies. Methods We retrieved data from COMPERA to compare patient characteristics, treatment patterns, response to therapy and survival in newly diagnosed patients with idiopathic pulmonary arterial hypertension (IPAH) and PH associated with IIP (PH-IIP). Results Compared to patients with IPAH (n = 798), patients with PH-IIP (n = 151) were older and predominantly males. Patients with PH-IIP were treated predominantly with phosphodiesterase-5 inhibitors (88% at entry, 87% after 1 year). From baseline to the first follow-up visit, the median improvement in 6MWD was 30 m in patients with IPAH and 24.5 m in patients with PH-IIP (p = 0.457 for the difference between both groups). Improvements in NYHA functional class were observed in 22.4% and 29.5% of these patients, respectively (p = 0.179 for the difference between both groups). Survival rates were significantly worse in PH-IIP than in IPAH (3-year survival 34.0 versus 68.6%; p

BACKGROUND: The Fontan circulation is a palliation for patients with a functionally univentricular heart. It is characterized by gradual attrition over time. An increase in pulmonary vascular resistance could be a key factor in the long-term failure of the Fontan circulation. In this study we aimed to identify pulmonary vascular remodeling in patients with a Fontan circulation.METHODS: Pulmonary vascular histomorphometric analysis and immunohistochemistry were performed in lung tissue obtained at autopsy from 12 Fontan patients. These patients had died either penoperatively (Group A: death during or 5 years after Fontan completion; n = 7). Two age-matched control groups (n = 10 and n = 14, respectively) were included.RESULTS: Intra-acinar pulmonary vessels in the Fontan Group B patients showed decreased medial thickness (p = 0.028) compared with age-matched controls, whereas intimal thickness was increased (p = 0.002). Infimal thickness in the Fontan Group B patients correlated with age at death (r = 0.964, p CONCLUSIONS: We observed a unique pattern of adverse pulmonary vascular remodeling in patients with a long-standing Fontan circulation who had died during follow-up. This remodeling pattern may play a major role in long-term attrition of the Fontan circulation. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved.

Introduction: Beneficial effects of treprostmil, a stable prostacyclin analogue, were demonstrated in patients with pulmonary arterial hypertension (PAH). Although regression of pulmonary vascular remodeling has been suggested as therapeutic mechanism, its mode of action remains unknown.Methods: Flow-associated PAH was created in rats by injection of monocrotaline (60 mg/kg) combined with an abdominal aortocaval shunt. Subsequently, rats were treated with subcutaneous treprostinil (50 ng/kg/min, treated; n = 8) or saline (untreated; n = 9). A control group underwent sham-surgery (n = 8). Animals were sacrificed at symptoms of cardiac failure, together with their matched controls.Results: Dyspnea and weight loss determined the moment of sacrifice in 8/9 untreated animals (89%) versus in one of eight treated animals (13%; log-rank test survival curves; P = 0.02). Mean pulmonary arterial pressure increased in the model (42 +/- 2 mm Hg in untreated vs. 18 +/- 1 in controls; P Conclusions: Treprostinil treatment improved clinical course and ameliorated symptoms of heart failure in a model of advanced PAR However, beneficial effects were not associated with reversed structural remodelling of the pulmonary vasculature.

In a subgroup of patients with systemic sclerosis (SSc), vasospasm affecting the pulmonary circulation may contribute to worsening respiratory symptoms, including dyspnea. Noninvasive assessment of pulmonary blood flow (PBF), utilizing inert-gas rebreathing (IGR) and dual-energy computed-tomography pulmonary angiography (DE-CTPA), may be useful for identifying pulmonary vasospasm. Thirty-one participants (22 SSc patients and 9 healthy volunteers) underwent PBF assessment with IGR and DE-CTPA at baseline and after provocation with a cold-air inhalation challenge (CACh). Before the study investigations, participants were assigned to subgroups: group A included SSc patients who reported increased breathlessness after exposure to cold air (n = 11), group B included SSc patients without cold-air sensitivity (n = 11), and group C patients included the healthy volunteers. Median change in PBF from baseline was compared between groups A, B, and C after CACh. Compared with groups B and C, in group A there was a significant decline in median PBF from baseline at 10 minutes (−10%; range: −52.2% to 4.0%; P < 0.01), 20 minutes (−17.4%; −27.9% to 0.0%; P < 0.01), and 30 minutes (−8.5%; −34.4% to 2.0%; P < 0.01) after CACh. There was no significant difference in median PBF change between groups B or C at any time point and no change in pulmonary perfusion on DE-CTPA. Reduction in pulmonary blood flow following CACh suggests that pulmonary vasospasm may be present in a subgroup of patients with SSc and may contribute to worsening dyspnea on exposure to cold.

BACKGROUND Patients with pulmonary arteriovenous malformations (PAVMs) are unusual because hypoxemia results from right-to-left shunting and not airway or alveolar disease. Their surprisingly well-preserved exercise capacity is not generally appreciated. METHODS To examine why exercise tolerance is preserved, cardiopulmonary exercise tests were performed while breathing room air in 21 patients with radiologically proven PAVMs, including five restudied 3 to 12 months after embolization when their PAVMs had regressed. Where physiologic matching was demonstrable, comparisons were made with 12 healthy control subjects. RESULTS The majority of patients achieved their predicted work rate despite a resting arterial oxygen saturation (Sao 2 ) of 80% to 96%. Peak work rate and oxygen consumption ( V ˙ o 2 ) were no lower in patients with more hypoxemia. Despite higher Sao 2 following embolization (median, 96% and 90%; P = .009), patients achieved similar work rates and similar peak V ˙ o 2 . Strikingly, treated patients reset to virtually identical peak oxygen pulses (ie, V ˙ o 2 per heart beat) and in many cases to the same point on the peak oxygen pulse/work rate plot. The 21 patients had increased minute ventilation ( V ˙ e) for given increases in CO 2 production ( V ˙ e/ V ˙ co 2 slope), but perceived dyspnea was no greater than in the 12 control subjects or in the same patients before compared to after embolization comparison. Overall, work rate and peak V ˙ o 2 were associated not with oxygenation parameters but with V ˙ e/ V ˙ co 2 slope, BMI, and anaerobic threshold. CONCLUSIONS Patients with hypoxemia and PAVMs can maintain normal oxygen delivery/ V ˙ o 2 during peak exercise. Following improvement of Sao 2 by embolization, patients appeared to reset compensatory mechanisms and, as a result, achieved similar peak V ˙ o 2 per heart beat and peak work rates.

Aims: We studied the unclear question whether blood pressure (BP) lowering reduces cardiovascular disease (CVD) in elderly individuals with systolic BP

In the present paper we studied the role of nitric oxide radicals (NO) on platelet aggregation, fibrinogen deposition, superoxide formation, peroxynitrite formation, hemodynamics, and leukocyte migration in the Thy-1 model of glomerulonephritis. To first study the baseline kinetics of these parameters, groups of anti-Thy-l-treated rats were sacrificed at 1 h, 4 h, 24 h, 3 days, 7 days, and 14 days and compared to controls. Urinary protein excretion was significantly elevated in Thy-1 nephritis at 3 and 7 days. Glomerular macrophages, PMNs, and superoxide anion-positive cells were significantly increased in Thy-1 nephritis. Nitrotyrosine immunoreactivity was absent during the entire study period. Glomerular platelet aggregation was significantly increased in anti-Thy-1 injected rats at 1 h, 4 h, 24 h, and 3 days. Glomerular fibrinogen deposition was significantly elevated at all time points. To elucidate the role of NO in this process, additional groups of anti-Thy-l-injected rats were treated with the NOS inhibitor L-NAME and studied at 24 h. Urinary protein excretion was significantly higher in L-NAME treated Thy-1 rats compared to nontreated Thy-1 rats. Plasma and urine nitrite/nitrate levels were significantly lower in L-NAME-treated Thy-1 rats compared to nontreated Thy-1 rats. Compared to nontreated Thy-1 rats, there were no differences in intraglomerular leukocyte accumulation after treatment with L-NAME. In contrast, we observed a marked increase in platelet aggregation following L-NAME treatment. From these data we conclude that the inflammatory infiltrate in Thy-1 nephritis develops independent of NO radical production, whereas NO radicals prevent the accumulation of platelet aggregates. (C) 2001 Elsevier Science.

An excessive blood pressure (BP) reduction might be dangerous in high-risk patients with cardiovascular disease. In the Studio Italiano Sugli Effetti CARDIOvascolari del Controllo della Pressione Arteriosa SIStolica (Cardio-Sis), 1111 nondiabetic patients with systolic BP ≥150 mm Hg were randomly assigned to a systolic BP target P for interaction=0.82). The main secondary end point, a composite of cardiovascular events and all-cause death, occurred less frequently in the tight than in the standard control group both in patients without (1.47 versus 3.68 patient-years; P =0.016) and with (7.87 versus 11.22 patient-years; P =0.049) previous cardiovascular disease. In a multivariable Cox model, allocation to tight BP control reduced the risk of cardiovascular events to a similar extent in patients with or without overt cardiovascular disease at randomization ( P for interaction=0.43). In conclusion, an intensive treatment aimed to lower systolic BP

Introduction: Erythropoiesis-Stimulating Agents (ESA) are hypothesized to increase cardiovascular mortality in patients with chronic kidney disease. One of the proposed mechanisms is the elevation of blood pressure (BP) by ESA. Therefore, we aimed to determine whether the use of ESA was associated with antihypertensive treatment and higher BP.Materials and Methods: In this cohort 502 incident pre-dialysis patients were included who started specialized pre-dialysis care in 25 clinics in the Netherlands. Data on medication including ESA use and dose, co-morbidities and BP were routinely collected every 6 months. Antihypertensive treatment and BP were compared for patients with and without ESA at baseline. Differences in antihypertensive medication and BP during pre-dialysis care were estimated with linear mixed models adjusted for age, sex, body mass index, cardiovascular disease, diabetes mellitus and estimated glomerular filtration rate.Results: At baseline, 95.6% of patients with ESA were treated with antihypertensive medication and 73.1% of patients without ESA. No relevant difference in BP was found. During pre-dialysis care patients with ESA used 0.77 (95% CI 0.63; 0.91) more classes of antihypertensive drugs. The adjusted difference in systolic blood pressure (SBP) was -0.3 (95% CI -22.7;2.0) mmHg and in diastolic blood pressure (DBP) was -1.0 (95% CI -2.1; 0.3) mmHg for patients with ESA compared to patients without ESA. Adjusted SBP was 3.7 (95% CI -1.6; 9.0) mmHg higher in patients with a high ESA dose compared to patients with a low ESA dose.Conclusions: Our study confirms the hypertensive effect of ESA, since ESA treated patients received more antihypertensive agents. However, no relevant difference in BP was found between patients with and without ESA, thus the increase in BP seems to be controlled for by antihypertensive medication.