Hypertension affects approximately 46% to 48% of US adults, with severe blood pressure elevations (180/110-120 mm Hg or higher) observed in more than 13% of individuals with preexisting hypertension. In the absence of new or worsening target organ damage, this is defined as severe hypertension. Although guidelines provide structured approaches to chronic hypertension management, guidelines for management of acute severe hypertension are limited. In the outpatient setting, medication nonadherence is the most common cause of severe hypertension. This typically requires reinitiating or increasing the dosage of antihypertensive therapy. Out-of-office blood pressure monitoring is recommended, and barriers to adherence should be investigated. In hospitalized patients, transient blood pressure elevations are often triggered by secondary factors such as anxiety, hypervolemia, pain, or withdrawal of home medications. Randomized and observational trials have shown that inpatient treatment of severe hypertension does not improve short-term outcomes but increases the risk of cardiovascular events and acute kidney injury and the length of hospitalization. Use of short-acting or intravenous antihypertensive medications is associated with adverse outcomes and is not recommended. Evaluation for secondary hypertension is recommended in cases of resistant hypertension, progressive blood pressure elevation, age of onset younger than 30 years, or evidence of premature target organ damage.
Primary prevention of hypertension depends on early detection of high-risk individuals. Several useful risk-stratification tools are provided by lipid-glucose-insulin obtained from standard blood testing. This study compared the predictive performance of four indices for incident hypertension: Atherogenic Index of Plasma (AIP), Triglyceride-Glucose (TyG) index, Cholesterol-HDL-Glucose (CHG) index, and Metabolic Score for Insulin Resistance (METS-IR). A total of 1079 adults with initially normal blood pressure were enrolled between January 2016 and January 2019 and followed up until January 2024. Participants were classified according to incident hypertension status during follow-up, the participants were divided into the hypertension group and the non-hypertension group. Multivariable Cox proportional hazards models were used to assess the associations between the four insulin resistance indices and the incidence of hypertension, adjusting for a comprehensive set of clinical and biochemical confounders. Time-dependent receiver operating characteristic (ROC) curve analysis was used to assess predictive accuracy at 12, 36, and 60 months. Among the participants, 297 developed hypertension during follow-up. In the fully adjusted model, only the CHG index maintained a statistically independent association with hypertension risk. Each unit increase in the CHG index was associated with a more than twofold higher risk of hypertension (Hazard Ratio [HR] 2.186, 95% Confidence Interval [CI] 1.269-3.766). However, the AIP, TyG index, and METS-IR index showed no statistical significance after final adjustment. According to time-dependent ROC analysis, both the CHG index and METS-IR showed excellent and consistent discriminative capacity across initial, medium, and long-term follow-up (AUCs consistently >0.71). At the follow up time of 36 and 60 months, the CHG index exhibited the highest AUC values. The TyG index showed intermediate predictive performance, whereas AIP consistently exhibited the lowest predictive power at all intervals. The CHG index demonstrated the most independent association with incident hypertension, better than the AIP, TyG, and METS-IR indices in predictive accuracy.
BackgroundCardiometabolic diseases have become a major cause of morbidity and mortality for people living with HIV (PLWH), and it is not clear if this population is aware of such risk.ObjectiveThe objective of this study is to assess perceived knowledge of cardiometabolic risk among PLWH in an underrepresented US community and explore associations with key demographic characteristics and social determinants of health.MethodsThis study was conducted in urban communities within New Jersey. One-hundred and sixteen participants completed the survey, who were included in the final analytic sample.Results/ConclusionApproximately half of the participants reported being knowledgeable about the long-term effects of hyperlipidemia and diabetes (51.8% and 51.9%, respectively), and 61.6% of participants reported being knowledgeable about the long-term complications of hypertension. An exploratory analysis was conducted to determine if there were any associations related to reported social determinants of health and the primary outcome. Cross-sectional Survey Study Assessing Awareness of Cardiometabolic Risk of People Living With HIV Within an Urban SettingCardiometabolic diseases have become a major cause of sickness and death for people living with HIV. Comorbidities such as heart attacks and heart failure (HF) are doubled in risk in people living with HIV; it is not clear whether people living with HIV are aware of such risk. The objective of this study was to identify whether people living with HIV are aware of their risk of heart disease. This study was done surveying urban communities within New Jersey, focusing on obtaining information from historically underrepresented populations. Overall, nearly 50% of patients agreed or strongly agreed to knowing the long-term effects of uncontrolled blood sugar, high blood pressure, and high cholesterol. We also assessed known risk based on age, race, and gender. Further research should assess opportunities to empower individuals to be their healthiest selves, looking beyond antiretroviral medical care.
Hypertension (HTN) remains a leading global health burden and a key risk factor for cardiovascular disease. While the Dietary Approaches to Stop Hypertension (DASH) diet is an established strategy for blood pressure control, the interplay between dietary patterns and the oral microbiome in the etiology of HTN is not well understood. To investigate the independent and joint associations of genus-level oral microbiome composition and adherence to the DASH diet with hypertension in a nationally representative sample of US adults. We analyzed data from the 2009-2010 and 2011-2012 National Health and Nutrition Examination Survey (NHANES), including 5371 adults with complete oral microbiome, dietary, blood pressure, and covariate data. Genus-level oral microbiome profiles were derived from oral rinse samples using 16S rRNA sequencing and transformed with the centered log-ratio method. DASH adherence was assessed from 24-h dietary recalls using a validated score. Hypertension was defined as self-reported diagnosis, antihypertensive medication use, or measured blood pressure meeting 2017 American College of Cardiology/American Heart Association (ACC/AHA) criteria (systolic ≥130 mmHg or diastolic ≥80 mmHg). Analyses employed a multistage design: differential abundance testing to identify hypertension-associated genera; survey-weighted multivariable logistic regression to examine independent and joint associations, adjusting for demographic, lifestyle, and clinical covariates; subgroup analyses by sex, age, and microbial characteristics; and sensitivity analyses to assess robustness. Greater adherence to the DASH diet was associated with lower odds of hypertension [high vs. low tertile odds ratio (OR) ≈0.62; P < 0.005]. Several oral bacterial genera - Actinomyces, Rothia, Lactobacillus, and Veillonella - showed independent associations with increased hypertension risk (OR range: 1.302-1.468; P < 0.05). Higher Faith's Phylogenetic Diversity was inversely associated with hypertension (OR = 0.742; P = 0.037). Stratified analyses suggested effect modification: the protective DASH-hypertension association was strongest among individuals with low Lactobacillus abundance and intermediate microbial diversity and Rothia abundance, more pronounced in women, and attenuated in adults aged at least 60 years. Sensitivity analyses confirmed these patterns, highlighting the consistent risk associated with Actinomyces and the stability of joint DASH-microbiome associations. Genus-level oral microbiome composition and DASH dietary adherence were independently and jointly associated with hypertension risk. These results support a potential oral-dietary axis in cardiovascular risk and underscore the need for integrated microbiome-dietary approaches to hypertension prevention.
Autoimmune rheumatic diseases (ARDs) are characterized by excessive immune system dysregulation and a significant inflammatory milieu that provokes multiorgan damage. Inflammation holds a key role in the pathophysiology of cardiovascular disease (CVD), thereby explaining the increased cardiovascular risk of patients with ARDs. Among all cardiovascular risk factors, hypertension is the most prevalent one in patients with ARDs. The pathogenesis of hypertension in ARDs is multifactorial and the result of a complex interplay between several traditional cardiovascular risk factors, the sympathetic nervous system, autoimmune disease specific factors and genetic predisposition. Importantly, even though patients with ARDs and hypertension suffer a markedly increased cardiovascular risk, current guidelines lack a widely accepted risk prediction tool to accurately estimate CVD risk and provide a highly individualized approach. This review aims to analyse the prevalence and pathophysiology of hypertension in patients with ARDs and provide an overview of cardiovascular risk assessment in this high-risk group.
To investigate the association between mid-pregnancy serum levels of insulin-like growth factor binding protein-1 (IGFBP-1) and chordin-like 1 (CHRDL1) and the occurrence of fetal growth restriction (FGR) in late pregnancy among women with gestational hypertension (GH). This prospective nested case-control study was conducted within an established cohort of pregnant women with GH from January 2021 to January 2025. A total of 731 singleton pregnant women with GH at 20-24 gestational weeks were enrolled and followed up by dedicated nurses (those lost to follow-up were contacted at least three times) until late pregnancy (≥28 weeks), with 711 completing the entire follow-up. Based on prenatal ultrasound diagnosis, 106 cases of FGR were identified. These cases were individually matched in a 1:2 ratio (matching factors: maternal age, pre-pregnancy body mass index (BMI), and parity) with 212 controls selected from women without FGR, resulting in a final nested case-control sample of 318 participants. Fasting serum samples were collected at 20-24 weeks of gestation, and IGFBP-1 and CHRDL1 levels were measured by enzyme-linked immunosorbent assay (ELISA). FGR occurrence was assessed based on estimated fetal weight (EFW) monitored by B-ultrasound. Spearman's correlation analysis evaluated associations between mid-pregnancy serum concentrations of IGFBP-1 and CHRDL1 with EFW. Conditional logistic regression identified determinants of FGR development in late pregnancy within the GH cohort. The discriminative performance of mid-pregnancy serum IGFBP-1 and CHRDL1 for late-pregnancy FGR prediction was assessed using receiver operating characteristic (ROC) curve analysis. Among 731 pregnant women with GH, 20 (2.74%) were lost to follow-up, and 711 completed the entire follow-up; of these, 106 (14.91%) developed FGR. Following 1:2 matching with 212 controls, 318 participants were included in the nested analysis. Serum levels of IGFBP-1 and CHRDL1 were significantly higher in the FGR group compared with the control group (both p < 0.001). The two biomarkers were positively correlated with each other (r = 0.455, p < 0.05) and negatively correlated with EFW (r = -0.335, -0.304, both p < 0.05). Conditional logistic regression analysis revealed that elevated systolic blood pressure (SBP), diastolic blood pressure (DBP), IGFBP-1, and CHRDL1 were independent risk factors for FGR, while elevated triglycerides (TG) were protective factors. ROC curve analysis demonstrated that the area under the curve (AUC) for IGFBP-1 and CHRDL1 alone in predicting FGR was 0.734 (95%CI: 0.677-0.791) and 0.704 (95%CI: 0.645-0.762), respectively; the combined AUC was 0.801 (95%CI: 0.750-0.852). Elevated serum IGFBP-1 and CHRDL1 levels in mid-pregnancy are independent risk factors for FGR in late pregnancy among women with GH. The combination of these two biomarkers demonstrates favorable predictive value, providing an actionable biomarker panel for early identification of high-risk populations in clinical practice, enabling intensified monitoring and intervention initiation at 20-24 weeks of gestation, and ultimately improving perinatal outcomes.
Cardiovascular-kidney-metabolic (CKM) syndrome has emerged as a major global health burden and driver of cardiovascular disease (CVD), the leading cause of death worldwide. Effective management of CKM depends on timely identification of underlying risk factors. Nevertheless, participation rates in primary care-based screenings are low. Consequently, CKM syndrome oftentimes remains undetected until organ damage is clinically present. Community pharmacies offer an accessible, yet underused, setting to enhance early detection. APOSCREEN-1 evaluates the feasibility and diagnostic yield of a pharmacy-based multi-parametric screening for cardiovascular-kidney-metabolic health. APOSCREEN-1 is a prospective single-arm clinical trial conducted in 20 community pharmacies in the German state of Schleswig-Holstein. Adults (n = 1000) aged ≥ 40 years with predefined risk criteria are included. Participants undergo standardized point-of-care testing (glycated hemoglobin, lipid profile, urinary albumin, blood pressure). Additionally, clinical history is assessed and results are transmitted to the study center via an online platform. Patients meeting pre-defined thresholds of the tested parameters are followed up by confirmatory laboratory testing at the study center or at the participants' general practitioner. Primary outcomes include completion rate, implementation metrics from the pharmacy perspective, and the number needed to screen to detect unknown or insufficiently managed cardiometabolic risk factors. Secondary outcomes comprise participant metrics, diagnostic metrics of the screening, evaluation of the clinical impact. This study aims to address the unmet need for scalable prevention of CVD by identification of CKM syndrome risk factors outside traditional primary care settings. Evidence on feasibility, acceptance, and diagnostic benefit may support the use of community pharmacies as an additional access point for early CKM syndrome detection. Future interventional studies will be required to evaluate structured follow-up pathways and long-term effectiveness. This study was registered with the German trial registry (Deutsches Register klinischer Studien) on 29.01.2026, under trial number DRKS00039149.
Exaggerated blood pressure (BP) response to orthostatic stimuli is indicative of cardiovascular frailty and may be associated with masked and white coat hypertension, which are BP abnormalities associated with cardiovascular outcomes. We aimed to clarify this possible association in a cross-sectional analysis of a large general population. We enrolled 7618 community residents (mean age: 57.7 years). Orthostatic BP change was calculated as the difference between systolic BP measured in a seated position and at 3 min after standing. Orthostatic hypertension and hypotension were defined as >20 mmHg increase or decrease in systolic BP, respectively. Masked and white coat hypertension were defined based on office and home morning BP measurements. The frequency of orthostatic hypotension and hypertension was 1.8% and 1.6%, respectively. A significant association was observed between orthostatic BP change and office-to-home BP differences, that is, the greater the increase in orthostatic BP, the higher the home BP than the office BP. The association between orthostatic hypertension and masked hypertension (crude odds ratio: 3.15; P < 0.001) remained significant even after adjusting for potential covariates, including office seated BP. In addition, orthostatic hypotension was independently associated with white coat hypertension (crude odds ratio: 2.14; P = 0.002). Orthostatic BP change measured at 3 min showed a clearer association with masked and white coat hypertension than that measured at 1 min. We identified a physiological association between exaggerated postural BP variability and office-to-home BP differences, which were previously considered unrelated.
Individuals with chronic obstructive pulmonary disease (COPD) experience a significant decline in their quality of life owing to cardiovascular disease (CVD). This study aimed to develop a predictive framework for evaluating CVD risk in patients with COPD. Data from 1070 COPD patients participating in the 2015 China Health and Retirement Longitudinal Study (CHARLS) were analyzed. To ensure robust feature selection, Least Absolute Shrinkage and Selection Operator (LASSO) regression and the Boruta algorithm were utilized. Subsequently, the predictive performance of six distinct Machine learning (ML) models (Logistic Regression, Random Forest, Support Vector Machine (SVM), Gradient Boosting Machine, XGBoost, and Multi-Layer Perceptron) was comprehensively compared. The Synthetic Minority Oversampling Technique-Nominal Continuous (SMOTE-NC) was applied to the training set to combat class imbalance. An interpretable risk assessment tool was developed using SHapley Additive exPlanations (SHAP). 305 participants (28.50%) had CVD. Seven variables were used to build the six models. The SVM model showed comparatively better performance than the others, with a training Area Under the Receiver Operating Characteristic curve (AUROC) of 0.819 (95% Confidence Interval (CI) 0.793-0.844), accuracy of 74.42%, sensitivity of 75.56%, precision of 74.18%, specificity of 73.26%, and F1 score of 74.86%. In the test set, the AUROC was 0.719 (95% CI, 0.670-0.760), with an accuracy of 68.63%, sensitivity of 64.20%, precision of 66.53%, specificity of 64.96%, and F1 score of 69.36%. This study identified seven key predictors-sex, body weight, hypertension, dyslipidemia, disability, self-rated health, and vision status-that are significantly associated with cardiovascular risk in Chinese patients with COPD. Among the six machine-learning algorithms evaluated, the SVM model demonstrated the most robust performance; however, its predictive capacity remains moderate, reflecting the inherent limitations of cross-sectional survey data and the reliance on self-reported diagnoses. Future prospective studies and rigorous external validation in independent cohorts are essential to refine these predictors and translate this machine-learning approach into reliable clinical decision-support systems for the personalized management of COPD patients.
Cardiometabolic diseases (CMDs) have become the leading cause of mortality and disease burden in low- and middle-income regions, including ethnic minority areas in southwest China. However, population-based epidemiological data on CMDs and their socioeconomic impacts in karst rocky desertification areas remain scarce. This cross-sectional study aimed to investigate the prevalence, population distribution characteristics, and multilevel socioeconomic impacts of CMDs in Qianxinan Buyi and Miao Autonomous Prefecture, Guizhou Province, and to identify associated risk factors. Using multistage stratified cluster sampling, we enrolled 3012 permanent residents aged ≥18 years from Qianxinan Prefecture between January 2023 and December 2024. Data were collected via face-to-face structured questionnaires, standardized physical examinations, the 36-Item Short Form Health Survey, and household income and expenditure verification. CMDs were defined as having at least one of the following: hypertension, type 2 diabetes mellitus, coronary heart disease, or stroke, all diagnosed according to national clinical guidelines. We calculated crude and age-standardized prevalence of CMDs, compared quality of life and household economic burden between CMD patients and non-affected participants, and performed multivariate regression analyses to identify factors associated with CMD prevalence, catastrophic health expenditure (CHE), and poverty due to illness. The age-standardized prevalence of CMDs in the study population was 26.3%, with hypertension (21.5%) being the most prevalent subtype, followed by diabetes (6.8%), coronary heart disease (3.0%), and stroke (1.3%). Higher age-standardized prevalence was observed in adults aged ≥60 years (42.6%), rural residents (29.8%), farmers (32.6%), and those with primary education or below (31.2%). CMD patients had significantly lower 36-Item Short Form Health Survey scores across all dimensions than non-affected participants, especially in the role-physical and role-emotional domains. Households with CMD patients had a significantly higher risk of CHE (27.3% vs 6.8%, P < .001) and poverty due to illness (15.6% vs 3.2%, P < .001) than non-affected households. Multivariate analyses showed that comorbidity of ≥2 CMDs, low household income, and lack of stable medical insurance were independent risk factors for CHE and poverty due to illness. The prevalence of CMDs in Qianxinan Prefecture is higher than the national average, with significant disparities across age, urban-rural, and health literacy subgroups. CMDs are associated with impaired quality of life and increased risks of catastrophic medical expenditure and poverty due to illness.
Upper gastrointestinal bleeding (UGIB) due to portal hypertension (PH) is a severe complication of cirrhosis. No specific score is currently validated to assess prognosis in this setting. We aimed to evaluate the performance of the CAGIB score in predicting recurrence and early mortality following upper gastrointestinal bleedingin in cirrhotic patients. We conducted a retrospective study including cirrhotic patients hospitalized for uppergastrointestinal bleedinginrelatedportal hypertension from 2012 to 2022. The following scores were calculated: CHILD-PUGH, MELD, MELD-Na, MELD 3.0, ALBI, ROCKALL, GBS, NLR, and CAGIB. Their performance in predicting early recurrence (≤5 days), short-term recurrence (≤6 weeks), and early mortality (≤6 weeks) was compared using ROC curves. A total of 105 patients were included (mean age 63 years; F/M ratio 1.05). Bleeding originated from oesophageal varices in 94.3% of cases. Endoscopic treatment was performed in 96 patients (endoscopic band ligation in 90 cases). Short-term recurrence occurred in 20%, early recurrence in 3.8%, and early mortality in 13.3%. The CAGIB score was the best predictor of early recurrence (AUC=0.995; sensitivity=83.3%; specificity=99.6%) and early mortality (AUC=0.891; sensitivity=85.7%; specificity=83.5%) at a threshold ≥ -4.648. The CAGIB score demonstrated superior prognostic performance for early recurrence and mortality following UGIB due to portal hypertension. It appears to be a reliable and reproducible tool for risk stratification in cirrhotic patients.
Clinical management of hypertension in patients with autoimmune rheumatic diseases (ARDs) is challenging. Firstly, the impact on blood pressure (BP) of several antirheumatic drugs varies and the available evidence points towards a wide range of effects. Secondly, management of hypertension in terms of diagnosis, BP thresholds and therapeutic targets currently follows the general recommendations, even though patients with ARDs present a markedly adverse cardiovascular profile. Thirdly, lifestyle interventions in terms of non-pharmaceutical management follow the general recommendations. Notably, it has been shown that they can improve autoimmune disease-specific endpoints, however, their intimate effect on BP has not been fully explored. Finally, the choice of anti-hypertensive medication currently complies with the general antihypertensive therapy recommendations, in the absence of appropriately designed studies in these populations. This review aims to summarize the impact of antirheumatic drugs on BP and present the available data regarding clinical management of hypertension in patients with ARDs.
Hypertension affects almost half of US adults and is a major cause of cardiovascular morbidity and mortality. Although expert guidelines recommend screening for secondary hypertension in patients with treatment-resistant hypertension and other high-risk groups, screening is conducted in <2% of candidates. This study aimed to determine barriers for secondary hypertension screening across US practices. Primary care physicians, cardiologists, nephrologists, and endocrinologists, randomly selected from active members of the American Medical Association, were surveyed on barriers for secondary hypertension screening. Response rate was 67% (425 of 633 response-eligible physicians). The leading reported barriers preventing secondary hypertension screening included visit time constraints (43.5%), poor ancillary support (29.4%), and testing-related logistics (27.5%). Primary care physicians were 10- to 17-fold less likely to be familiar with testing interpretation and subsequent steps than nephrologists and endocrinologists. Physicians in practices covered largely by Medicare were twice more likely to report poor ancillary support than physicians in practices covered primarily by private health insurance. Private practice physicians were more likely to report reimbursement concerns (adjusted odds ratio, 3.4 [95% CI, 1.6-7.7]) and poor ancillary support (adjusted odds ratio, 2.1 [95% CI, 1.3-3.6]) but also more likely to have access to specialists (adjusted odds ratio, 4.0 [95% CI, 1.2-13.5]) than physicians practicing in large medical groups. Our findings call for measures to address critical barriers in secondary hypertension screening. Strategies needed to facilitate personalized hypertension care include optimization of clinic visit duration, ancillary support, education initiatives, and timely access to specialists.
To evaluate the prevalence of hypertension and determine the dose-response relationship between cumulative occupational low-dose ionizing radiation (LDIR) exposure and blood pressure levels among medical radiologists in China. A cross-sectional study was conducted among 5420 medical radiologists in Guangdong Province. Individual cumulative effective doses (CED) were reconstructed based on historical records (1980-2022). Blood pressure was assessed via standardized physical measurements rather than self-reporting. Hypertension was defined according to the 2017 ACC/AHA guidelines (SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg). Multivariable logistic and linear regression analyses were performed to assess associations, adjusting for demographic and lifestyle confounders. The overall prevalence of hypertension was 53.4%. After adjusting for confounders, cumulative effective dose was positively associated with hypertension risk. Compared with the reference group (<1.00 mSv), the adjusted odds ratios (ORs) for hypertension were 1.35 [95% confidence interval (95% CI) 1.06-1.70] for 5.00-9.99 mSv and 1.73 (95% CI 1.27-2.37) for at least 10.00 mSv. Linear regression confirmed that CED was positively associated with both SBP and DBP levels. Stratified analysis revealed gender-specific susceptibility: a significant risk increase was observed at least 5.00 mSv for men, whereas the threshold was at least 10.00 mSv for women. Cumulative occupational LDIR exposure is an independent risk factor for hypertension and elevated blood pressure among medical radiologists, exhibiting a clear dose-response relationship. The findings suggest gender-specific thresholds for vascular damage and advocate for enhanced cardiovascular surveillance in this high-risk population using stricter diagnostic criteria.
Although most progestin-only contraceptives are generally considered safe for most patients at increased risk of arterial and venous thrombosis, patients and clinicians may be wary of their use based on limited studies. Large prospective contraceptive studies with primary data collection would improve the evidence base for people at increased thrombosis risk. We therefore aimed to find solutions for recruitment and long-term retention of representative participants in large prospective studies of contraceptives for patients at increased risk of thrombosis, identify patient- and clinician-prioritized outcomes, and determine patients' and clinicians' preferred dissemination methods for study results. In this formative qualitative study, we conducted semistructured interviews with reproductive-age patients at increased thrombosis risk and clinicians in related fields in New Mexico via telephone and Zoom. Interviews were transcribed and coded deductively using Dedoose qualitative coding software. We categorized emerging themes based on our study aims. We interviewed 16 patients and 11 clinicians from June 2020 to June 2022. Most of the patients (60%) had more than one of the following conditions: hypertension, antiphospholipid antibody syndrome, history of cerebral vascular accident, deep vein thrombosis, pulmonary embolism or myocardial infarction, systemic lupus erythematosus, or a thrombophilia. Clinician specialties included hematology, rheumatology, pulmonology, pharmacy, and women's health. The majority of respondents participated to help others. Although participants highlighted discomfort with reproductive health as a potential barrier to participation, others indicated that they wanted to share their difficult experiences to bring awareness to the topic. Virtual participation in interviews overcame several participation barriers such as scheduling concerns, transportation, and finding childcare. Patients and clinicians both cited effectiveness, safety, side effects, and developing more contraceptive method options as priority research outcomes. All of the participants were interested in receiving the results of the study in which they participated. Clinicians recommended constructing research teams reflecting participant demographics. Altruism may be a strong motivator for contraceptive research participation among medically complex patients. Both patients and clinicians desire new efficacious, safe, low side effect contraceptives for patients at increased thrombosis risk. Virtual participation options address common participant recruitment and, likely, retention barriers. Clinicians anticipate that research teams that reflect participant demographics may lead to better representation of at-risk populations in contraceptive research.
To compare the impacts of persistent social inequality (Palma ratio) and conjunctural economic vulnerability (unemployment) on chronic kidney disease (CKD) burden and to test whether hypertension mediates inequality's association. We analyzed a 68-country panel (1990-2023), modeling the natural log of prevalent CKD cases as a function of the Palma ratio and total unemployment, adjusting for diabetes prevalence, hypertension prevalence, hospital beds per 10,000, and population size. Pooled OLS with HC3 robust standard errors was estimated across lags up to 10 years. To reduce detection bias, we re-estimated models at the 10-year lag within wage-defined income strata; mediation (1,000 bootstraps) was assessed in the high-income stratum. In high-income countries (18 countries, N = 265 observations at the 10-year lag), social inequality was strongly positively associated with the log of total prevalent CKD cases (β = 2.02, 95% CI: 1.32-2.72, p < 0.001), implying that a 1-SD increase in the Palma ratio is associated with a 7.54-fold higher CKD case burden (≈ + 654%), holding covariates constant. Economic vulnerability showed no significant association (β = 0.01, p = 0.871), yielding a 202:1 absolute effect-size ratio. Bootstrap causal mediation indicated a large hypertension pathway (indirect effect = 0.82, 95% CI: 0.34-1.28), corresponding to 78.1% of the total effect. Panel Granger tests suggested that past inequality predicts CKD across tested lags (p < 0.001). We conclude that inequality is the stronger and more consistent upstream determinant of CKD burden, while the effect of unemployment is weaker. The conducted analysis suggests that structural social inequality, quantified by the Palma ratio, has a significantly stronger and more statistically robust correlation with the prevalence of chronic kidney disease compared to economic vulnerability of a conjunctural nature, quantified by the unemployment rate, especially in contexts characterized by adequate diagnostic capacity.
Mice with tamoxifen-inducible endothelium-restricted human endothelin-1 (ET-1) overexpression (ieET-1) exhibited blood pressure elevation after 3  weeks and 3  months, and vascular injury after 3  months. We hypothesised that ET-1 overexpression-induced vascular injury is mediated by gene expression dysregulation. Male ieET-1 mice and mice expressing a tamoxifen-inducible Cre recombinase in endothelial cells were induced with tamoxifen and studied 3-week and 3-month post-treatment. MicroRNA and gene expression were profiled in mesenteric arteries by RNA-sequencing and validated by RT-qPCR. Aorta was used for immunofluorescence microscopy. KH domain containing RNA binding signal transduction associated 3 (Khdrbs3) was the top upregulated gene identified by RNA-sequencing (P = 8x10-12) validated by RT-qPCR (P < 0.001) after 3-week and 3-month ET-1 overexpression. KHDRBS3 protein was increased in aortic endothelial and vascular smooth muscle cells (VSMCs) after 3-month ET-1 overexpression. KHDRBS3 is a splicing regulator of various mRNAs, including human vascular endothelial growth factor A (VEGFA) 165 isoform with exon 7 retention. Three-month ET-1 overexpression upregulated isoforms Vegfa164 containing exon 7 and Vegfa188 retaining exons 6 and 7, and downregulated Vegfa120 isoform lacking both exons (P < 0.05). Analysis of RNA-immunoprecipitation-sequencing of myocardium of patients with dilated cardiomyopathy identified VEGFA and four key VSMC-specific pre-mRNAs as KHDRBS3 targets. Reanalysis of RNA-sequencing data of angiotensin II-infused mice revealed a high correlation between ET-1 (Edn1) and Khdrbs3 mRNAs in mesenteric arteries (r2 = 0.82, P = 3.7 x 10-9). Endothelial human ET-1 overexpression induced RNA splicing via enhanced Khdrbs3 expression, which may play a role in vascular injury, and could represent a therapeutic target in hypertension.
Ferroptosis plays a significant role in pulmonary arterial hypertension (PAH), although its underlying mechanisms and key pathogenic genes remain unclear. Transcriptomic data from human PAH and control lung tissue were obtained from the Gene Expression Omnibus (GEO) database, whereas ferroptosis-related genes (FRGs) were sourced from the MsigDb and FerrDb databases. Differentially expressed FRGs (DE-FRGs) were identified through the intersection of FRGs with differentially expressed genes (DEGs). Functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Key hub genes were identified through Least Absolute Shrinkage and Selection Operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and weighted correlation network analysis (WGCNA). Gene set enrichment analysis (GSEA) was conducted to explore the functional roles and associated pathways of hub genes. The relationship between hub genes and immune infiltration was investigated. Expression levels of potential biomarkers were validated via Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) in two PAH animal models (monocrotaline-induced and Sugen5416 plus hypoxia-induced PAH). Finally, molecular docking was employed to screen potential therapeutic compounds. A total of 133 DE-FRGs were identified, with KEGG and GO analyses highlighting their involvement in intracellular iron homeostasis and ferroptosis. Hub genes, notably FZD7 and NFE2, were identified using LASSO, SVM-RFE, and WGCNA. Immune infiltration analysis suggested that monocytes and neutrophils play key roles in PAH pathogenesis. Validation in PAH animal models showed significant upregulation of Fzd7 and downregulation of Nfe2 in lung tissues of both MCT- and SuHx-induced PAH models. Molecular docking identified tetrachlorodibenzodioxin (TCDD) has good binding affinity. In summary, we investigated two ferroptosis-related biomarkers, FZD7 and NFE2, in PAH using transcriptomics, offering new insights into molecular mechanisms and potential targeted therapies for the disease.
High blood pressure is the dominant risk factor for cardiovascular diseases and death in Australia. The blood pressure control rate in Australia was reported at 32% based on 2017-2018 data, which is substantially lower than other high-income countries. New results from the National Health Survey show an improvement of the crude control rate to 39.6% in the years 2022-2023, though changes in methodology need to be considered in the interpretation. Hypertension prevalence has increased from 33.7 to 39.4%. The prevalence and control rates vary strongly across diverse population groups. The age-standardized prevalence among First Nations peoples is higher than in the general population (37.8 versus 35%), and age-standardized blood pressure control rates are lower (22.2 versus 31.1%). Younger individuals and those in socioeconomically disadvantaged areas have substantially lower control rates, highlighting the need for greater equity to achieve the National Hypertension Taskforce's goal of 70% blood pressure control by 2030.
Chronic thromboembolic pulmonary hypertension (CTEPH) leads to right atrial (RA) dysfunction, which correlates with poor prognosis. However, most studies on RA function in pulmonary hypertension (PH) focus on heterogeneous PH etiologies, with limited data on CTEPH alone. This study aimed to assess RA function in CTEPH patients using standard two-dimensional (2DE) and M-mode echocardiography, and validate the clinical value of RA-related parameters. We enrolled 91 CTEPH patients and 30 healthy controls. RA volume/function parameters (maximal volume index [RAVmaxI], total/passive/active emptying fractions [TotEF/PassEF/ActEF]) and tricuspid annular plane systolic excursion (TAPSE, decomposed into atrial [TAPSEra] and ventricular [TAPSErv] components; TAPSEra% = TAPSEra/TAPSE) were measured via 2DE/M-mode echocardiography. Correlations with clinical (WHO functional class [WHO-FC], 6-min walk distance [6MWD]) and laboratory (NT-proBNP) indices were analyzed; receiver operating characteristic (ROC) curves evaluated predictive value for WHO-FC ≥ III. Compared to controls, CTEPH patients had higher RAVmaxI (43.46 ± 13.34 vs. 22.52 ± 2.89 mL/m2, P < 0.001), lower TotEF (39.45 ± 9.43 vs. 50.07 ± 7.52%, P < 0.001) and PassEF (14.33 ± 6.43 vs. 30.03 ± 5.26%, P < 0.001), and higher ActEV/TotEV (59.76 ± 17.37 vs. 34.05 ± 12.75%, P < 0.001). TAPSEra% was higher in CTEPH patients (58.69 ± 19.54 vs. 30.52 ± 7.92%, P < 0.001). RAVmaxI (≥37.47 mL/m2, AUC = 0.899, sensitivity = 75.4%, specificity = 91.7%) and TAPSEra% (≥45.05%, AUC = 0.849, sensitivity = 90.2%, specificity = 70.0%) effectively predicted WHO-FC ≥ III (both P < 0.001). Impaired RA reservoir and conduit functions are hallmarks of CTEPH, with compensatory active contraction counteracting the reduction in passive filling. Given their noninvasive nature and high reliability, RAVmaxI and TAPSEra% are valuable indices for identifying patients with WHO-FC ≥ III and quantifying CTEPH severity, justifying their integration into standard echocardiographic protocols.