Hypertension Research Articles

A cohort study on the association between blood pressure trajectories and variability in adolescence and subsequent target organ damage

Objective: To investigate the relationship between blood pressure trajectories and blood pressure variability with the risk of target organ damage in Chinese population from childhood to middle age. Methods: This study is a population-based, long-term follow-up cohort study. Participants who had their blood pressure measured at least 5 times in the Hanzhong Adolescent hypertension cohort from 1987 to 2023 were included in this study. Group-based trajectory modeling was used to identify different systolic and diastolic blood pressure trajectories, and the subjects were divided into low-increasing group, moderate-increasing group and high-increasing group according to blood pressure trajectories. Blood pressure variability was assessed using standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Target organ damage was evaluated during the final follow-up in 2023 (middle age). Logistic regression models were used to analyze the relationship between blood pressure trajectories and blood pressure variability with the risk of target organ damage. Results: A total of 2 447 subjects were included, with a median age of 48 years, of whom 1 373 were male (56.1%). Based on systolic blood pressure, 868 were in the low-increasing group, 1 238 in the moderate-increasing group, and 341 in the high-increasing group. For diastolic blood pressure, the distribution was 894, 1 263 and 290, respectively. Compared with the low-increasing group of systolic blood pressure, the moderate-increasing group (arteriosclerosis: OR=4.14, 95%CI 2.96-5.79; proteinuria: OR=2.06, 95%CI 1.38-3.07; left ventricular hypertrophy: OR=1.68, 95%CI 1.00-2.82) and high-increasing group (arterial stiffness: OR=15.44, 95%CI 10.14-23.50; proteinuria: OR=5.80, 95%CI 3.63-9.29; left ventricular hypertrophy: OR=2.93, 95%CI 1.55-5.53) had a higher risk of target organ damage (all P<0.005). The moderate-increasing group of diastolic blood pressure had a higher incidence of arterial stiffness (OR=3.72, 95%CI 2.69-5.12) and proteinuria (OR=1.67, 95%CI 1.15-2.42) than the low-increasing group (all P<0.005), while the high-increasing group had a significantly higher risk of all type of target organ damage compared to the low-increasing group (arterial stiffness: OR=10.84, 95%CI 7.08-16.61; proteinuria: OR=3.72, 95%CI 2.31-5.99; left ventricular hypertrophy: OR=2.38, 95%CI 1.23-4.59; all P<0.005). Additionally, higher systolic blood pressure variability was associated with an increased incidence of arterial stiffness (SD: OR=2.25, 95%CI 1.96-2.57; VIM: OR=1.64, 95%CI 1.45-1.86; ARV: OR=1.70, 95%CI 1.50-1.93) and proteinuria (SD: OR=1.65, 95%CI 1.44-1.89; VIM: OR=1.41, 95%CI 1.22-1.63; ARV: OR=1.45, 95%CI 1.26-1.67; all P<0.005). The results for diastolic blood pressure variability indicators were similar to those for systolic blood pressure. Conclusion: Early-life blood pressure trajectories are predictive of target organ damage risk in middle age. Higher blood pressure variability is related to an increased risk of arterial stiffness and proteinuria, but was less associated with left ventricular hypertrophy. Focusing on the risk of high blood pressure early in life can help prevent the occurrence of target organ damage in middle age.

Patterns of Non-Communicable Disease Comorbidities among Older Persons in Bangladesh

Comorbidity among older adults is a significant public health concern in Bangladesh. This study investigated the patterns and correlates of non- communicable disease comorbidities among older persons in Bangladesh through a cross-sectional study carried out in Dhaka and Chittagong divisions among people aged 60 years and above who suffered from any non-communicable disease in the past three months of the survey. Data was collected from 474 respondents. Descriptive statistics, chi-squared tests, and independent sample t- tests were used to explore the non-communicable disease comorbidities among respondents. The findings showed that the majority of the respondents were suffering from diabetes (39.2 percent), arthritis (38 percent), high blood pressure (34.6 percent), ulcer (26.4 percent), asthma (20.9 percent), and kidney diseases (20.3 percent) and were significantly suffering from several comorbidities like arthritis and ulcer (16.5 percent), arthritis and high blood pressure (15.6 percent), high blood pressure and diabetes (24.5 percent), and diabetes and asthma (11.8 percent) at the same time. Results showed that comorbidity of high blood pressure and diabetes was higher among the 60-70 age group, comorbidity of arthritis and ulcer was higher among rural respondents, comorbidity of diabetes and asthma was higher among males, comorbidity of arthritis and ulcer was higher among educated respondents, and comorbidity of high blood pressure and diabetes was higher among those who had a monthly income source. The study suggests that the government should improve primary healthcare by integrating non-communicable disease-related services and developing physical and human resources, focusing on promoting healthy lifestyles among older persons. Social Science Review, Vol. 41(1), June 2024, Page 1-16.

Hábitos alimenticios e hipertensión en pacientes ambulatorios de un Hospital en Honduras

Eating habits play an important role in the prevention and management of high blood pressure. The World Health Organization demonstrated that poor eating habits trigger arterial hypertension, which is a chronic increase in blood pressure with values ​​equal to or greater than 140 millimeters of mercury (MmHg) systolic pressure and 90 mmHg. diastolic pressure. The general objective of this study was to identify the eating habits of patients with high blood pressure who attended the outpatient clinic at the Gabriela Alvarado Hospital in Danlí, Honduras, in the period January-March 2024. It was a descriptive, cross-sectional study; The study data was obtained through a structured questionnaire addressed to each of the participants. Among the results found, the eating habits of the 81 participating patients reflect that 86.4% eat 3 times a day, with lunch being the most substantial with 88.9%, in which they mainly consume more fruits and vegetables, 35.8% consume 4 to 6 glasses of water a day, have eating habits that include healthy aspects according to their health status.

Descriptive Analysis of Oxygen Dependency and Hemodynamic Changes Following Pulmonary Thromboendarterectomy in Chronic Thromboembolic Pulmonary Hypertension Patients

Descriptive Analysis of Oxygen Dependency and Hemodynamic Changes Following Pulmonary Thromboendarterectomy in Chronic Thromboembolic Pulmonary Hypertension Patients

Assessment of the Potential Clinical and Economic Impact of Weight Loss in the Adult Population with Obesity and Associated Comorbidities in Spain.

Obesity and its complications are associated with high morbidity/mortality and a significant healthcare cost burden in Spain. It is therefore essential to know the potential clinical and economic benefits of reducing obesity. The objective of this study is to predict the decrease in rates of onset of potential complications associated with obesity and the cost savings after a weight loss of 15% over 10years in Spain. Data were combined in an adapted version of a weight loss benefit simulation model. Sources with demographic information on the Spanish population and the distribution of obesity and type 2 diabetes mellitus (T2DM) were used to obtain the data for the model. In addition, use was made of prevalence data on obesity-associated complications from a cohort of patients with obesity in the United Kingdom (UK). These data were combined by age and sex to create a Spanish synthetic cohort. The simulation showed that, for a cohort of 100,000 individuals with a body mass index (BMI) of 30-50kg/m2, a weight loss of 15% is estimated to lead to relevant relative risk reductions in obstructive sleep apnoea (OSA) (-56.4%), T2DM (-39.2%), asthma (-20.2%) and arterial hypertension (-18.7%). The estimated overall savings were €105 million for a cohort of 100,000 individuals, mainly resulting from the decrease in T2DM and arterial hypertension (23% and 22% of the total savings at year 10, respectively), as well as osteoarthritis and chronic kidney disease (CKD) (16% and 13%, respectively). Sustained weight loss could significantly reduce the burden derived from future complications associated to obesity in Spain, as well as the excess economic cost associated with its treatment.

Effect of Balloon-Dilated Restenosis on Exercise Performance and Cardiac Function in Children After Coarctation Repair.

Restenosis occurs commonly after aortic coarctation (CoA) repair, usually requiring treatment by balloon dilation. Its effect on physical exercise performance is not documented. A retrospective analysis of exercise testing and echocardiographic assessment was performed in children after CoA repair. A group without restenosis (= group 1) and a group with recoarctation, treated by single balloon dilation (= group 2) were compared by matching for age and gender at a 2:1 ratio. Group 1 included 40 children and group 2 comprised 21 children, with mean age of 12.3 ± 2.3y and 11.9 ± 2.9y (p = 0.536) at evaluation. Group 2 children were younger at CoA repair (group 1: median 32.0d (11.0-188.0)-group 2: 9.0d (5.5-19.0), p = 0.011). Arterial hypertension was frequently noticed (group 1: 23(57.5%)-group 2: 7(33.3%), p = 0.106). Echocardiography revealed comparable cardiac function properties, showing more left ventricular (LV) hypertrophy in all CoA patients compared to their peers (Posterior wall thickness z-value: 1.03 ± 1.65, p < 0.001)). Exercise results were generally comparable, despite small differences in favor of group 1 (predicted % peak VO2 = group 1: 95.2 ± 21.4%-group 2: 82.3 ± 10.5%, p = 0.024; peak VO2/kg = group 1: 38.9 ± 9.5ml/min/kg-group 2: 33.8 ± 6.9ml/min/kg, p = 0.034; VO2/WR slope = group 1: 12.6 ± 2.0ml/min/watt-group 2: 11.3 ± 1.7ml/min/watt, p = 0.018). Compared to uncomplicated coarctation patients, children developing a surgical restenosis after CoA repair, and treated effectively by balloon dilation, had lower-but still acceptable-oxygen uptake during exercise. As intrinsic cardiovascular function characteristics were similar, further study to evaluate the impact of non-disease-specific factors is mandatory.

The association of dietary approaches to stop hypertension measured by the food frequency questionnaire with metabolic syndrome and some inflammatory biomarkers in adolescents with obesity: a case-control study

BackgroundGlobally, obesity trends are a serious public health concern. Adolescent obesity is associated with cardiometabolic risk and metabolic disorders in adolescence and may persist into adulthood. The current study was designed to explore the Dietary Approaches to Stop Hypertension (DASH) in adolescents and its relationship with obesity, insulin resistance, metabolic syndrome (MetS), and some inflammatory biomarkers.MethodsA total of 90 adolescents with obesity and 90 adolescents with normal weight, participated in the study. Data from a validated 168-item semi-quantitative food frequency questionnaire were used to calculate the DASH score. The association of DASH score with cardiometabolic risk factors was estimated using multivariable logistic regression models. To assess the correlation between the DASH score and dietary factor, the Pearson correlation coefficient (r) was used.ResultsAdolescents with a high DASH score had significantly higher intakes of potassium, magnesium, vitamin C, and vitamin K and lower intakes of sodium compared with those with a low DASH score (P < 0.05 ). There were no significant differences in the DASH score and its components between adolescents with and without metabolic syndrome. Adolescents with metabolic syndrome had significantly higher concentrations of triglycerides, low HDL-C, and high blood pressure compared with those without metabolic syndrome (P < 0.05). There were no significant associations between DASH score and MetS and other cardiometabolic risk factors in crude and multivariate-adjusted models. In addition, the DASH score was positively associated with potassium, magnesium, sodium, vitamins D and C, docosahexaenoic acid, and soluble fiber (P < 0.05).ConclusionIn the current study, there was no significant association between adherence to the DASH diet and odds of metabolic syndrome, and other cardiometabolic risk factors in adolescent. Further prospective studies are needed to confirm these findings.Trial registrationEthics approval was obtained from the research ethics committee of Tabriz University of Medical Sciences (IR.TBZMED.REC.1397.179.).

Sotatercept in pulmonary hypertension and beyond.

Sotatercept binds free activins by mimicking the extracellular domain of the activin receptor type IIA (ACTRIIA). Additional ligands are BMP/TGF-beta, GDF8, GDF11 and BMP10. The binding with activins leads to the inhibition of the signalling pathway and the deactivation of the bone morphogenic protein (BMP) receptor type 2. In this way, sotatercept activates an antiproliferative signalling to the cells of the pulmonary arteries and arterioles with the aim of rebalancing the proliferative and antiproliferative pathway that characterizes the pulmonary arterial hypertension (PAH). Sotatercept is indicated for the treatment of group 1 PAH in combination with drugs that act through the endothelin receptor, nitric oxide or prostacyclin. Its effects, demonstrated in the STELLAR study, are the improvement of exercise capacity and the FC-WHO functional class, together with the reduction of the risk of clinical worsening events. In addition to its antiremodeling effects on the pulmonary circulation, sotatercept has several haematological effects that could suggest its use in the treatment of some blood disorders other than PAH. In this review, we will discuss the effects of the drug on PAH and in parallel provide an in-depth overview of its application in haematological disorders, focusing on clinical and preclinical studies.

Factors of progression to severity and death in COVID-19 patients at two health care sites in Bamako, Mali

ObjectivesTo analyze the clinical and biological characteristics and to evaluate the risk factors associated with the mortality of patients with COVID-19 in Commune IV of the District of Bamako.MethodsThe cohort consisted of COVID-19 patients managed from March 2020 to June 2022 at the Bamako Dermatology Hospital and the Pasteur Polyclinic in Commune IV in Bamako. The studied variables were sociodemographic, clinical, and biological. For the analysis of deaths, explanatory variables were grouped into sociodemographic factors, comorbidities and symptoms. Binomial logistic regression models were used to identify mortality associated risk factors.ResultsAmong the 1319 included patients, 38.4% were asymptomatic, 46% and 15.5% developed moderate or severe COVID-19 respectively. The predominant signs were cough (48.5%), respiratory difficulty (24.6%) and headache (19.7%). Male were more common (58.2%). High blood pressure (19.9%) and diabetes (10%) were the main comorbidities. D-dimers < 0.5 μg/l was found in 53.3% of cases and the mean hemoglobin level was 12.9 ± 1.7 g/l. The case fatality rate was 3.71% in our series. In bivariate analysis, age > 60 years, high blood pressure, diabetes, clinical severity, D-dimers < 0.5 μg/l were associated with death. Using binomial logistic regression method, age > 60 years, increased heart rate, disease severity level and mainly acute respiratory distress syndrome (polypnea, difficulty breathing) were the factors found associated with death. After adjusting for all the assessed factors, age < 60 years [aHR = 0.15 (0.06–0.35)] and administration of azithromycin [aHR = 0.31 (0.1–0.97)] were protective factors while higher respiratory rate [aHR = 1.14 (1.07–1.22)] and difficulty breathing [aHR = 3.06 (1.03–9.13)] were risk factors associated with death.ConclusionThese main findings elucidate the factors associated with severity and lethality external of health care system constraints. Advanced age, higher heart rate and the development of respiratory distress were the factors significantly associated with increased fatalities.

Renal nerves and hypertension contribute to impaired proximal tubule megalin-mediated albumin uptake in renovascular hypertensive rats.

Proteinuria, especially albuminuria, serves as an independent risk factor for progression in cardiovascular and renal diseases. Clinical and experimental studies have demonstrated that renal nerves contribute to renal dysfunction in arterial hypertension (AH). This study hypothesizes that renal nerves mediate the mechanisms of protein endocytosis by proximal tubule epithelial cells (PTEC) and glomerular function; with dysregulation of the renal nerves contributing to proteinuria in Wistar rats with renovascular hypertension (2-kidney, 1-clip model, 2K-1C). Reduced albumin uptake and increased internalization of endocytic receptor megalin in PTEC were found in both the clipped and contralateral kidneys of 2K-1C rats. Renal denervation (DNx) or hydralazine treatment restored these parameters. Moreover, DNx, but not hydralazine, reduced serum creatinine and recovered podocyte numbers in the contralateral kidney of 2K-1C rats. Thus, our data suggest that renal nerves and high arterial pressure contribute to decreased albumin reabsorption by cellular redistribution of megalin in PTEC, while renal nerves remarkably drive glomerular dysfunction in renovascular hypertension, independently of their effect on blood pressure. Created with BioRender.com.

Blood pressure control with active ultrafiltration measures and without antihypertensives is essential for survival in hemodiafiltration and hemodialysis programs for patients with CKD: a prospective observational study

BackgroundHigh blood pressure is a prevalent condition in patients with chronic kidney disease on hemodialysis. Adequate control of high blood pressure is essential to reducing deaths in this group. The present study aimed to observe mortality prospectively in a group of patients in hemodialysis and hemodiafiltration programs in whom the use of antihypertensives was optimized with the point-of-care dry weight (POC-DW) technique.MethodsThe present observational, prospective study was carried out at the Pafram hemodiafiltration unit in Morona Santiago, Ecuador, and the hemodialysis unit of the Fundación Renal del Ecuador in Guayaquil, Ecuador, from August 2019 to December 2023. Patients who were receiving hemodiafiltration were included. Weight was optimized with POC-DW for eight weeks. In Group 1, patients whose use of antihypertensive drugs was not required to control systolic blood pressure with a value less than 150 mmHg predialysis, less than 130 mmHg postdialysis, and a peridialytic blood pressure (defined as post-HD minus pre-HD SBP) between 0 and − 20 mmHg were analyzed. In Group 2, patients who required antihypertensive drugs for not meeting the aims of systolic blood pressure were included. The variables included clinical, demographic, mortality, description of the treatment, and routine laboratory tests in dialysis programs. The sample was nonprobabilistic. Survival analysis was performed for the study groups. The log-rank test (Mantel-Cox) was used for survival comparisons.ResultsThe study included 106 patients. Optimal blood pressure control without antihypertensive treatment was achieved in 52 patients (49.1%) (Group 1). In 54 patients (50.9%), antihypertensive agents were required (Group 2). There was more significant mortality in the group that received antihypertensives: 11 patients in group 1 (21.2%) versus 25 patients in group 2 (46.3%) (P = 0.005). Survival was more significant in group 1, with an HR of 2.2163 (1.125–4.158) (P = 0.0243).ConclusionIn hemodiafiltration and hemodialysis programs, blood pressure control with active ultrafiltration measures and without using antihypertensives is essential for survival in patients with CKD.

Prevalence, Awareness, Treatment and Control of Hypertension in Residents’ Sample of Luanda, Angola

Hypertension (HTN) is an important risk factor for cardiovascular complications and is considered a public health problem worldwide. We aimed to evaluate the prevalence, awareness, treatment and control of HTN in a population sample in Luanda, Angola. A cross-sectional study was carried out which included 1480 individuals, between May 2018 and June 2019; we recruited participants at three different points of the city. Blood pressure (BP) was measured with semi-automatic device (Omron®, EM-7131-E). For each participant, three BP measurements were taken after 5 minutes resting and the mean of the two last measurements was used for systolic and diastolic BP. HTN was defined as BP ≥140/90 mmHg or use of antihypertensive drugs. The sample included mostly young people (39.7±11.6 years old) and male (69.3%). HTN prevalence was 34.9%; 47.4% of patients were aware of their condition; 36.8% were taking medication and of these only 35.8% had BP under control. There was a positive correlation between BP and age. The prevalence of HTN was high, almost half of the patients were unaware and, among the hypertensive patients who were under medication, most of them did not have their BP under control. HTN prevalence was high; awareness, treatment and control were low.

Deciphering the Role of Calcium Signaling Pathway-Associated Single Nucleotide Variants in Susceptibility to Hypertension.

As a complex disease, hypertension (HTN) is influenced by both genetic and environmental factors and their interaction. The calcium signaling pathway is known to be involved in the regulation of blood pressure, and dysfunction in this pathway may contribute to the development of hypertension. Genome-wide association studies (GWAS) have identified several genes in the calcium signaling pathway associated with susceptibility to HTN, including PLCB1, ATP2B1, and ADRB1. The aim of this study was to investigate the possible association between single nucleotide variants (SNVs) in the calcium signaling pathway and HTN. We genotyped three SNVs: rs1801253 (ADRB1), rs6108168 (PLCB1), and rs17249754 (ATP2B1) in a population of 131 patients with hypertension and 115 healthy controls from Kermanshah province, Iran. Our results showed a strong and significant association between the G allele and the GG and CG genotypes of the rs1801253 variant in the ADRB1 gene and susceptibility to hypertension. However, no significant association was found for the other two SNVs. In addition, the presence of the GCG haplotype (alleles from left to right: rs1801253, rs6108168, and rs17249754) appeared to confer a protective role against HTN. This study has made a significant contribution towards enhancing the comprehension of hypertension development, as well as the early identification of individuals who are at risk.

The long-term effects of cardiometabolic risk factors on mortality and life expectancy: evidence from a health check-up cohort study

ObjectiveCardiometabolic risk factors significantly contribute to disease burden. This study explored the effects of hypertension (HTN), diabetes mellitus (DM), and hyperlipidemia (HLP) on mortality. It stratified findings by age group and comorbidity severity using the Charlson Comorbidity Index (CCI) score. Additionally, it assessed the compounded effects of comorbid conditions to estimate life expectancy (LE) and years of life lost (YLL) in individuals with various cardiometabolic risk factor combinations.MethodsUsing data from the MJ Health Check-up Database (2002–2017), linked with the National Health Insurance Research Database (2000–2017) and the Death Registry (2002–2019), this study employed Cox proportional hazards models to determine mortality risk associated with various cardiometabolic risk factors. Adjusted Kaplan–Meier curves were constructed to evaluate survival rates across different risk factors and CCI scores. Survival rates were extrapolated to estimate confounder-adjusted LE and YLL for age-comorbidity combinations.ResultsAmong the three age groups (20–39, 40–59, 60–79), HLP was the most common single risk factor, followed by HTN. In participants with dual risk factors, HTN and HLP were the most frequent pair, with diabetes and HLP second. An increased number of cardiometabolic risk factors elevated mortality risk, particularly in the 20–39 age group. LE, adjusted for confounders, declined with age, higher CCI scores, and more risk factors. YLL decreased with age but increased with higher CCI scores and more risk factors.ConclusionsPromoting health awareness, early disease detection, and timely medical access can reduce cardiometabolic risk factors and associated comorbidities, thereby alleviating disease burden.

Blood Pressure Management Strategies and Podocyte Health.

Hypertension (HTN) is one of the key global cardiovascular risk factors, which is tightly linked to kidney health and disease development. Podocytes, glomerular epithelial cells that play a pivotal role in maintenance of the renal filtration barrier, are significantly affected by increased glomerular capillary pressure in HTN. Damage or loss of these cells causes proteinuria, which marks the initiation of the HTN-driven renal damage. It goes without saying that effective blood pressure (BP) management should not only mitigate cardiovascular risks but also preserve renal function by protecting podocyte integrity. This review offers a comprehensive examination of current BP management strategies and their implications for podocyte structure and function and emphasizes strategies for the reduction of proteinuria in HTN. We explore primary and secondary antihypertensive agents, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, and diuretics, as well as newer therapies (sodium-glucose cotransporter-2 blocking and endothelin receptor antagonism), emphasizing their mechanistic roles in safeguarding podocytes and curtailing proteinuria.

The Effect of Risk Factors and Clinical Complications of Chronic Kidney Disease (CKD) on Renal Arterial Resistive Index (RRI).

Chronic Kidney Disease (CKD) is a known risk factor for End-Stage Renal Disease (ESRD) and Cardiovascular Diseases (CVD). Renal Doppler Ultrasound (RDU) can detect early renal involvement in CKD using the Renal Resistive Index (RRI). This study aimed to investigate the effects of risk factors and clinical complications associated with CKD on RRI among patients with different stages of CKD. In this analytical cross-sectional study, 186 patients referred to Poursina Hospital for RDU were categorized into six groups (normal and five stages of CKD). We analyzed the impact of demographic factors and clinical complications on RRI across all groups. Our findings indicated that CKD prevalence was particularly high among older patients and those with CVD, type 2 diabetes mellitus (DM), and hypertension (HTN). Elevated RRI in CKD patients was significantly associated with age, CKD stage, CVD, and HTN (p < 0.05). Furthermore, RRI was higher in CKD patients with elevated serum phosphorus (P) levels, higher low-density lipoproteins (LDL), and lower calcium (Ca) and hemoglobin (Hb) levels. Based on a multivariate regression model, CVD, lower Ca, high LDL, and proteinuria were identified as independent predictors of elevated RRI (p < 0.05). This study concludes that elevated RRI is associated with the severity of CKD and its clinical complications, suggesting that RRI can serve as a reliable indicator for assessing CKD patients, managing treatment, and preventing early death complications.

Medical Problems of Chronic Hypoxia in Highlanders Living on the Tibetan Plateau.

Ri-Li Ge. Medical problems of chronic hypoxia in highlanders living on the tibetan plateau. High Alt Med Biol. 00:00-00, 2024.-Health issues at high altitudes arise due to the lower atmospheric pressure and subsequent reduction in the partial pressure of oxygen in ambient air. While much research has been published on health problems of lowlanders who move to high altitudes, less is known about the medical challenges faced by long-term and permanent high-altitude residents, especially in the Qinghai-Tibetan plateau. In this review, we briefly summarized the chronic hypoxia-related health issues in highlanders, focusing on the specific population of the Qinghai-Tibetan plateau. It deals with important health problems for highlanders, including the main disease categories, from chronic mountain sicknesses and pulmonary hypertension (PH) to kidney, neurocognitive impairments, perinatal problems, and congenital heart defect. However, the most hallmark of disorders is excessive erythrocytosis associated with specific symptoms and signs, and high-altitude heart disease is characterized by excessive PH, right ventricular hypertrophy, and right heart failure. We also provide information on potential treatment strategies, including some traditional Tibetan medical practices and also a combination of Western medicine and traditional Chinese medicine to prevent and treat these conditions effectively. This mini-review is heavily based on a couple of decades of research carried out by Chinese high-altitude medical research groups at the Qinghai-Tibetan Plateau. We believe that this review will provide valuable perspective to researchers whose study interest and base lie in high altitude.

Peroxiredoxin 5 Acts as a Negative Regulator of the Sodium-Chloride Cotransporter Involved in Alleviating Angiotensin II-Induced Hypertension

Chronic kidney disease (CKD) and hypertension are interconnected, worsening each other. Recent studies have shown that the reduction of peroxiredoxin 5 (Prdx5) accelerates kidney fibrosis, a hallmark of CKD. This study aims to observe whether the deficiency of Prdx5 also contributes to the worsening of CKD-related hypertension. Angiotensin II (Ang II, 1000 ng/kg/day) was infused into Prdx5 wild-type (WT) and Prdx5 knock out (KO) mice (each group; n = 6). The blood pressure was higher in the Ang-II-infused Prdx5 KO mice than in the WT mice. Ang-II-induced ROS/RNS generation and fibrotic marker expressions were also higher in the Prdx5 KO mice. In particular, the expression of the sodium-chloride cotransporter (NCC), an ion transport protein important for sodium retention in the distal convoluted tubule, and the NCC’s phosphorylation at Thr53 were increased in the kidney of Ang-II-infused Prdx5 KO. The activity of an WNK4-SPAK/OSR1, upstream activator of the NCC, was also increased. In 209/mDCT cells, the knockdown of Prdx5 (siPrdx5) increased the activity of Ang-II-mediated WNK4-SPAK/OSR1-NCC signaling and Ang-II-mediated ROS generation, whereas Prdx5 overexpression showed opposite results. In conclusion, Prdx5 negatively regulates the WNK4-SPAK/OSR1-NCC signaling axis, indicating its potential as a candidate for antihypertensive drug development through NCC regulation.

Das Update der EULAR-Empfehlungen für die systemische Sklerose zeigt Fortschritt zumindest bei der Lungenbeteiligung

Objectives: To update the 2017 European Alliance of Associations for Rheumatology (EULAR) recommendations for treatment of systemic sclerosis (SSc), incorporating new evidence and therapies. Methods: An international task force was convened in line with EULAR standard operating procedures. A nominal group technique exercise was performed in two rounds to define questions underpinning a subsequent systematic literature review. The evidence derived was discussed and overarching principles, recommendations and future research agenda were iteratively developed with voting rounds. Results: The task force agreed on 22 recommendations covering 8 clinical/organ domains including Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, scleroderma renal crisis, skin fibrosis, interstitial lung disease (ILD), gastrointestinal manifestations and arthritis. Most new recommendations are related to skin fibrosis and ILD. These included novel recommendations for the use of mycophenolate mofetil, nintedanib, rituximab and tocilizumab for the treatment of these crucial disease manifestations. The recommendations also included first-line and second-line interventions, providing increased utility for rheumatology practitioners. Important additions to the future research agenda included consideration of novel interventions for the management of vascular, musculoskeletal and gastrointestinal manifestations and calcinosis, as well as for the local management of digital ulcers. Conclusion: These updated recommendations include the first set of synthetic and biological targeted therapies recommended for key fibrotic manifestations of SSc as well as first-line combination treatment for newly diagnosed pulmonary artery hypertension and prioritise a new research agenda for the coming years.

Safety and Efficacy of Selexipag for Pediatric Pulmonary Arterial Hypertension in Japanese Patients - An Open-Label Phase 2 Study.

Selexipag, an oral prostacyclin (PGI2) receptor agonist, is approved for adult patients with pulmonary arterial hypertension (PAH). This study evaluated the efficacy and safety of selexipag for Japanese pediatric patients with PAH. The study enrolled 6 patients who received selexipag twice daily at an individualized dose based on body weight; maintenance doses were determined for each patient by 12 weeks after starting administration. Efficacy, including pulmonary hemodynamics, was evaluated after 16 weeks, and efficacy and safety were further evaluated 52 weeks after treatment was initiated in the last enrolled patient. The mean (±SD) change in the pulmonary vascular resistance index from baseline to Week 16 (the primary endpoint of the study) was -5.55±6.88 Wood units·m2; improvements were also seen in other pulmonary hemodynamic parameters. The 6-min walk distance increased and N-terminal pro-B-type natriuretic peptide decreased up to Week 64, but the between-subject variability was large. The World Health Organization functional class was improved in 1 of 6 patients at Week 16 and in 2 of 4 patients at Week 64. No patient worsened. The major side effects of selexipag were those characteristic of PGI2, and the safety profile of selexipag was similar to that in adult patients. The efficacy and safety of selexipag in Japanese pediatric patients with PAH were demonstrated.