Hypertension Clinical Trials Research Articles

Revisiting sex as a biological variable in hypertension research.

Half of adults in the United States have hypertension as defined by clinical practice guidelines. Interestingly, women are generally more likely to be aware of their hypertension and have their blood pressure controlled with treatment compared with men, yet hypertension-related mortality is greater in women. This may reflect the fact that the female sex remains underrepresented in clinical and basic science studies investigating the effectiveness of therapies and the mechanisms controlling blood pressure. This Review provides an overview of the impact of the way hypertension research has explored sex as a biological variable (SABV). Emphasis is placed on epidemiological studies, hypertension clinical trials, the genetics of hypertension, sex differences in immunology and gut microbiota in hypertension, and the effect of sex on the central control of blood pressure. The goal is to offer historical perspective on SABV in hypertension, highlight recent studies that include SABV, and identify key gaps in SABV inclusion and questions that remain in the field. Through continued awareness campaigns and engagement/education at the level of funding agencies, individual investigators, and in the editorial peer review system, investigation of SABV in the field of hypertension research will ultimately lead to improved clinical outcomes.

Abstract CT278: [DREAM] Double lung transplant registry aimed for lung-limited malignancies - a prospective registry study for medically refractory cancers

Abstract BackgroundAdenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are listed as ‘special circumstances’ for lung transplantation according to a consensus document from the International Society for Heart and Lung Transplantation (ISHLT) (Weill D et al., 2015). Five studies have reported on lung transplantation in carefully selected subsets of patients with multifocal lung adenocarcinoma (Raemdonck DV et al., 2016; Glanville AR et al., 2018). The 5-year survival rate of bilateral sequential lung transplantation was estimated at over 50% in patients with multifocal BAC, invasive adenocarcinoma, and NSCLC (Ahmad U et al., 2012; Paloyan EB et al., 2000; Zorn GL et al., 2003; de Perrot M et al., 2004). Another a case series reported a post-transplant recurrence-free survival of 23 to 56 months in three patients (Garver RI et al., 1999). Moreover, there is an unmet need for patients who have lung-limited metastasis after successful treatment for primary tumors such as sarcomas or colorectal cancer (CRC). As with liver transplantation for CRC patients who have liver-confined metastases (Dueland S et at., 2020; Hernandez-Alejandro R et al., 2022), the applicability of lung transplantation in lung-limited metastatic patients should be explored. There is also an unmet need for patients with respiratory failure with a history of cancer in the last 5 years. MethodsThis is a prospective registration trial to evaluate outcomes of patients who undergo double lung transplantation for the treatment of the select groups of medically refractory cancers (primary lung cancers or metastatic cancers in lungs). Overall survival (OS), disease-free survival (DFS), allograft rejection (AR) and allograft survival (AS) as well as molecular and genetic biomarkers will be monitored to investigate the correlation with prognosis.The study duration will be 10 years including surveillance. Recruitment is to occur during the first 5 years of the study. The goal is to enroll 125 participants through the Northwestern Medicine Clinical Programs.Essential Criteria:1.The tumor should be without any extrapulmonary metastasis as determined by standard of care diagnostic and staging workup.2.All standard of care or experimental oncological treatments known to improve survival should have failed or deemed infeasible 3.Patients should meet the general criteria for lung transplant evaluation and listing Study cohorts:•Cohort A: Primary lung cancers - Examples include, but not limited to, invasive mucinous/non-mucinous non-small cell lung cancers and multifocal carcinomas.•Cohort B: Metastatic cancers to the lung only - Examples include, but not limited to, germ cell tumors, head & neck tumors, colorectal tumors, renal cell tumors, testicular cancers.•Cohort C: Respiratory failure with a history of cancer in the last 5 years- Examples include, but not limited to interstitial lung disease (ILD), pulmonary fibrosis (idiopathic or secondary), advanced chronic obstructive pulmonary disease (COPD), bronchiectasis, emphysema, cystic fibrosis (CF), emphysema due to alpha-1 antitrypsin deficiency, and pulmonary arterial hypertension (PAH) Clinical trial registry number : NCT05671887.Enrollment began November 16, 2022. Trial is open and continues to enroll participants as of Jan 8, 2024. Citation Format: Young Kwang Chae, Liam Il-Young Chung, Rade Tomic, Ankit Bharat. [DREAM] Double lung transplant registry aimed for lung-limited malignancies - a prospective registry study for medically refractory cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT278.

Abstract P446: Community-Engaged Strategies for Recruitment of Black Men at Risk for Hypertension: The CLIP Study

Background: Recruitment of Black participants in research studies is challenging. Mistrust of academic and medical institutions due to historic mistreatment, medical racism, and lack of culturally tailored strategies to engage Black communities as partners, has led to under-representation of Black participants in studies. Black men have higher prevalence of hypertension (HTN) and worse outcomes than other groups. Yet, Black men are underrepresented in HTN clinical trials. The Community-to-Clinic Linkage Program to Prevent Hypertension (CLIP) is a community-engaged cluster randomized trial to test barbershop facilitation to prevent HTN among Black men residing in Staten Island (SI), New York City. Objective: To describe recruitment strategies to engage Black men in CLIP via an academic-community partnership. Methods and Results: Approximately 10% of SI residents identify as Black, of which ~ 90% live in 3 census tracts with the highest prevalence of HTN in the borough. The study team collaborates with Community Health Action of Staten Island (CHASI), a grassroots health organization with > 30 years of community focus on addressing the root causes of health disparities on SI, the Director of Health in SI, a community advisory council (CAC) comprised of local leaders and residents, and the New York American Heart Association providing HTN education materials in an academic-community partnership to implement CLIP. Our recruitment goal is to enroll 84 men across 4-5 Black-owned barbershops over 5 cycles (12 weeks each), total N=418. We did not meet recruitment goals for cycles 1 and 2, (~60% enrolled). In consultation with CHASI and the CAC we adjusted our recruitment strategies to: 1) host bi-monthly community events in or around participating barbershops; 2) offer study incentives at the time of enrollment; 3) leverage existing relationships with faith-based organizations and other stakeholders to promote CLIP; and 4) distribute co-branded promotional flyers with CHASI and other stakeholders to publicize events. Subsequently we exceeded recruitment goals in our last cycle (113% enrolled); current cycle recruitment is ongoing. Several strategies have been successful in improving recruitment of Black men for CLIP: 1) deep community ties of our community health partner; 2) enlisting local community health workers representative of the study population; 3) flexibility and open communication between academic and community staff; 4) trust in the competence of each partner; 5) mutual commitment to the mission of the study. Conclusion: Partnering with engaged and trusted community partners, stakeholders, and local leaders positively impacts recruitment of Black men participants in HTN research studies. Organizations with deep community ties are crucial for establishing trust and identifying flexible solutions to recruitment challenges.

IMPAHCT: A randomized phase 2b/3 study of inhaled imatinib for pulmonary arterial hypertension.

AV-101 (imatinib) powder for inhalation, an investigational dry powder inhaled formulation of imatinib designed to target the underlying pathobiology of pulmonary arterial hypertension, was generally well tolerated in healthy adults in a phase 1 single and multiple ascending dose study. Inhaled Imatinib Pulmonary Arterial Hypertension Clinical Trial (IMPAHCT; NCT05036135) is a phase 2b/3, randomized, double-blind, placebo-controlled, dose-ranging, and confirmatory study. IMPAHCT is designed to identify an optimal AV-101 dose (phase 2b primary endpoint: pulmonary vascular resistance) and assess the efficacy (phase 3 primary endpoint: 6-min walk distance), safety, and tolerability of AV-101 dose levels in subjects with pulmonary arterial hypertension using background therapies. The study has an operationally seamless, adaptive design allowing for continuous recruitment. It includes three parts; subjects enrolled in Part 1 (phase 2b dose-response portion) or Part 2 (phase 3 intermediate portion) will be randomized 1:1:1:1 to 10, 35, 70 mg AV-101, or placebo (twice daily), respectively. Subjects enrolled in Part 3 (phase 3 optimal dose portion) will be randomized 1:1 to the optimal dose of AV-101 and placebo (twice daily), respectively. All study parts include a screening period, a 24-week treatment period, and a 30-day safety follow-up period; the total duration is ∼32 weeks. Participation is possible in only one study part. IMPAHCT has the potential to advance therapies for patients with pulmonary arterial hypertension by assessing the efficacy and safety of a novel investigational drug-device combination (AV-101) using an improved study design that has the potential to save 6-12 months of development time. ClinicalTrials.gov Identifier: NCT05036135.

Retrospective on global pulmonary hypertension clinical trials: 1999-2021.

Data are quite sparse on the comprehensive analyses of pulmonary hypertension (PH) clinical trials worldwide. Information including participating countries (developed or developing), intervention type, trial size, PH categories, sponsorship, study phase, design strategies, and participants' demographic characteristics was extracted from PH trials registered on ClinicalTrials.gov from 1999 to 2021. A total of 203 eligible clinical PH trials were screened, involving 23,402 participants, 67.8% of whom were females. Major clinical trials were designed to test drug interventions (95.6%), sponsored solely by industries in 59.5%, and targeting Group 1 PH patients in 76.3%. A large number of countries participated in PH clinical trials; however, most clinical trials were conducted in developed countries (84.2%). Developing countries were involved in clinical trials with larger sample sizes (P<0.01). Additionally, the differences between developed and developing countries centered on interventions, sponsors, PH groups, and design strategies. Furthermore, developing countries participated in multinational clinical trials with good quality, homogeneity, reliability, and data authenticity. All pediatric participants were diagnosed with Group 1 PH and were only involved in drug intervention trials. Children participated in far fewer clinical trials than adults (P<0.01), and most were enrolled in PH clinical trials in developed countries. Among the entire clinical trial population, younger patients with Group 1 PH had a much higher participation to prevalence ratio (PPR). There was no difference in women's PPRs between developed and developing countries. However, developing countries had higher PPRs for PH Groups I and IV (1.28 vs. 1.22, P<0.01), while developed countries had a lower PPR for Group III (P=0.02). PH is attracting increasing global attention, which is not at the same level of progress in developed and developing countries. Women and children with this disease have unique characteristics and require more attention.

Socioeconomic and Social Determinants of Health: Effects on Pulmonary Arterial Hypertension Care

There is increasing awareness on the significance of socioeconomic status, social determinants of health, and the role of ethnicity and race in clinical outcomes of patients with pulmonary arterial hypertension. However, to date, underrepresentation of minorities in pulmonary hypertension clinical trials and registries remains. In the present review, we summarize the current knowledge on race, ethnicity, traditional and novel socioeconomics and social determinants of health, and its association with clinical outcomes in patients with pulmonary arterial hypertension. We present case examples on the interplay of these factors for specific disease phenotypes and discuss strategies for addressing these variables at the patient care level.

The occurrence of drug-induced side effects in women and men with arterial hypertension and comorbidities.

Women have been underrepresented in large clinical trials in hypertension, and the incidence of adverse drug reactions by sex has been not sufficiently described. The aim of the study was to determine the prevalence of adverse drug reactions in women and men with arterial hypertension and comorbidities and to assess the specific predisposing factors for adverse drug reactions by sex. The study population comprised consecutive hospitalized patients diagnosed with arterial hypertension and patients treated in an outpatient clinic, whose recruitment started in January 2019 aiming to reach 1000 participants. A structured questionnaire was used to gather the patients' demographic and clinical data and current or past cases of adverse drug reactions. The study included 560 women and 440 men, with mean (standard deviation) age of 62.84 (14.96) years. Women were older than men, had a longer hypertension history, and suffered less frequently from other cardiovascular diseases. Women reported more frequently adverse drug reactions. The risk of drug-induced side effects in women increased with age (P = 0.03) and with coexistence of any respiratory disease (P = 0.04). In the case of male sex, the risk of adverse drug reactions increased with the occurrence of hypercholesterolemia (P = 0.03), and coexistence of any analyzed metabolic diseases (P = 0.04). Adverse drug reactions were reported more frequently by women. Older age and the presence of any respiratory disease increased the risk of adverse drug reactions in women, while in men, the risk was increased mainly by the presence of hypercholesterolemia or other metabolic diseases.

Sex differences in hypertension. Do we need a sex-specific guideline?

Hypertension is the most prevalent cardiovascular disorder and the leading cause of death worldwide in both sexes. The prevalence of hypertension is lower in premenopausal women than in men of the same age, but sharply increases after the menopause, resulting in higher rates in women aged 65 and older. Awareness, treatment, and control of hypertension are better in women. A sex-pooled analysis from 4 community-based cohort studies found increasing cardiovascular risk beginning at lower systolic blood pressure thresholds for women than men. Hormonal changes after the menopause play a substantial role in the pathophysiology of hypertension in postmenopausal women. Female-specific causes of hypertension such as the use of contraceptive agents and assisted reproductive technologies have been identified. Hypertensive disorders in pregnancy are associated with increased risk of maternal, fetal, and neonatal morbidity and mortality, as well as with a greater risk of developing cardiovascular disease later in life. Hypertension-mediated organ damage was found to be more prevalent in women, thus increasing the cardiovascular risk. Sex differences in pharmacokinetics have been observed, but their clinical implications are still a matter of debate. There are currently no sufficient data to support sex-based differences in the efficacy of antihypertensive treatment. Adverse drug reactions are more frequently reported in women. Women are still underrepresented in large clinical trials in hypertension, and not all of them report sex-specific results. Therefore, it is of utmost importance to oblige scientists to include women in clinical trials and to consider sex as a biological variable.

Risk assessment tools for survival prognosis: An era of new surrogacy endpoints for clinical outcome measurement in pulmonary arterial hypertension clinical trials?

Developing a new medication in a rare disease indication like pulmonary arterial hypertension (PAH) is very challenging. This is especially true now that clinical trials often employ time to clinical worsening (TTCW) as an endpoint (thus requiring a relatively large and lengthy trial) and since patients are more frequently prescribed combination therapy. During the last few decades, several tools have been developed to predict mortality in PAH and have demonstrated generally good discrimination. The objective of this review article is to assess the available data on the different tools and methods described in the literature and identify potential candidates that could be used as surrogate endpoints in pivotal randomized clinical trials in future. Some of these tools have been validated in various registries and in post-hoc analyses of clinical trial data, but none have been assessed in a prospective clinical trial and we still lack the evidence necessary for endorsement by health authorities. In this review, we identify several promising options that warrant further investigation as potential surrogate endpoints in clinical trials to replace TTCW or 6-minute walk distance. Prospective inclusion of such tools in new clinical trials may help build a stronger surrogacy for prognosis of disease progression and mortality.

A Semi-Automated Term Harmonization Pipeline Applied to Pulmonary Arterial Hypertension Clinical Trials.

Data harmonization is essential to integrate individual participant data from multiple sites, time periods, and trials for meta-analysis. The process of mapping terms and phrases to an ontology is complicated by typographic errors, abbreviations, truncation, and plurality. We sought to harmonize medical history (MH) and adverse events (AE) term records across 21 randomized clinical trials in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. We developed and applied a semi-automated harmonization pipeline for use with domain-expert annotators to resolve ambiguous term mappings using exact and fuzzy matching. We summarized MH and AE term mapping success, including map quality measures, and imputation of a generalizing term hierarchy as defined by the applied Medical Dictionary for Regulatory Activities (MedDRA) ontology standard. Over 99.6% of both MH (N = 37,105) and AE (N = 58,170) records were successfully mapped to MedDRA low-level terms. Automated exact matching accounted for 74.9% of MH and 85.5% of AE mappings. Term recommendations from fuzzy matching in the pipeline facilitated annotator mapping of the remaining 24.9% of MH and 13.8% of AE records. Imputation of the generalized MedDRA term hierarchy was unambiguous in 85.2% of high-level terms, 99.4% of high-level group terms, and 99.5% of system organ class in MH, and 75% of high-level terms, 98.3% of high-level group terms, and 98.4% of system organ class in AE. This pipeline dramatically reduced the burden of manual annotation for MH and AE term harmonization and could be adapted to other data integration efforts.

Decompressive Craniectomy After Traumatic Brain Injury: Incorporating Patient Preferences into Decision-Making

Decompressive craniectomy (DC) is highly effective in relieving intracranial hypertension; however, patient selection, intracranial pressure threshold, timing, and long-term functional outcomes are all subject to controversy. Recently, recommendations were made to update the Brain Trauma Foundation guidelines in regards to the use of DC based on the DECRA (Decompressive Craniectomy in Patients with Severe Traumatic Brain Injury) and RESCUEicp (Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension) clinical trials. Neither the updated recommendations, nor the aforementioned trials, provide a method in incorporating individualized patient or surrogate decision-maker preferences into decision making. In this manuscript, we aimed to redress the gap of not incorporating patient preferences in such value-laden decision making as in the case of DC for refractory post-traumatic intracranial hypertension. We proposed a decision aid based on principles of Decision Theory, and specifically of Expected Utility Theory. We showed that 1) early secondary DC as studied in DECRA, and based on the 1-year outcome data, is associated with decreased expected utility for all possible preference rankings of outcomes; and 2) recommending a late secondary DC versus tier-3 medical therapy, as studied in RESCUEicp, should be informed by individualized patient preference rankings of outcomes as elicited via shared decision-making. The 1-year outcomes from DECRA and RESCUEicp have served as the basis for updated guidelines. However, unaided interpretation of trial data may not be adequate for individualized decision-making; we suggest that the latter can be significantly supported by decision aids such as the one described here and based on expected utility theory.

Global trends in chronic thromboembolic pulmonary hypertension clinical trials and dissemination of results.

Treatment options for chronic thromboembolic pulmonary hypertension (CTEPH) are rapidly expanding. The purpose of this study is to identify trends in CTEPH clinical trials and the publication of results. We performed a worldwide review of completed and ongoing clinical trials through searching the ClinicalTrials.gov database and the World Health Organization International Clinical Trials Registry Platform for “CTEPH” and related terms. Entries were classified as pharmaceutical/procedural interventions (Group 1), all other clinical trials (Group 2) and patient registries (Group 3). Trial characteristics and national affiliation were recorded. PubMed was searched for related publications. There were 117 clinical trials registry entries after removing duplicates and non-target records. Group 1 comprised 29 pharmaceutical, 15 procedural, and four combined interventions starting in 2005, 2010, and 2016, respectively. Riociguat and balloon pulmonary angioplasty were the most frequent pharmaceutical and procedural interventions, respectively. The proportion of procedural trials increased over time from 0% of those in 2005–2009 to 29% in 2010–2014 and 54% in 2015–2020. There were 56 entries in Group 2 and 13 in Group 3. Japan was the most frequent national affiliation and the most frequent participating country, present in 28% of all trials. The proportion of entries with published results was highest with Group 3 (62%) and lowest with Group 1 (27%). Thirty percent of all publications occurred in 2020. In conclusion, CTEPH clinical trials are increasingly procedural based, with growth largely attributable to Japan and balloon pulmonary angioplasty. Most trials have not published, but results from balloon pulmonary angioplasty clinical trials are anticipated soon.

Body mass index prediction rule for mid-upper arm circumference: the atherosclerosis risk in communities study.

Electronic health records (EHR) are a convenient data source for clinical trial recruitment and allow for inexpensive participant screening. However, EHR may lack pertinent screening variables. One strategy is to identify surrogate EHR variables which can predict the screening variable of interest. In this article, we use BMI to develop a prediction rule for arm circumference using data from the Atherosclerosis Risk in Communities (ARIC) Study. This work applies to EHR patient screening for clinical trials of hypertension. We included 11 585 participants aged 52-75 years with BMI and arm circumference measured at ARIC follow-up visit 4 (1996-1998). We selected the following arm circumference cutpoints based on the American Heart Association recommendations for blood pressure (BP) cuffs: small adult (≤26 cm), adult (≤34 cm) and large adult (≤44 cm). We calculated the sensitivity and specificity of BMI values for predicting arm circumference using receiver operating characteristic curves. We report the BMI threshold that maximized Youden's Index for each arm circumference upper limit of a BP cuff. Participants' mean BMI and arm circumference were 28.8 ± 5.6 kg/m2 and 33.4 ± 4.3 cm, respectively. The BMI-arm circumference Pearson's correlation coefficient was 0.86. The BMI threshold for arm circumference≤26 cm was 23.0 kg/m2, arm circumference≤34 cm was 29.2 kg/m2 and arm circumference≤44 cm was 37.4 kg/m2. Only the BMI threshold for arm circumference≤34 cm varied significantly by sex. BMI predicts arm circumference with high sensitivity and specificity and can be an accurate surrogate variable for arm circumference. These findings are useful for participant screening for hypertension trials. Providers can use this information to counsel patients on appropriate cuff size for BP self-monitoring.

Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension - Con Side of the Argument.

Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension - Con Side of the Argument.

Renal denervation in hypertension patients: Proceedings from an expert consensus roundtable cosponsored by SCAI and NKF.

Renal denervation in hypertension patients: Proceedings from an expert consensus roundtable cosponsored by SCAI and NKF.

Features of Chronic Thromboembolic Pulmonary Hypertension Clinical Trials

<h3>Purpose</h3> Innovative research in diagnosis and treatment have led to a rapid evolution in CTEPH care. The purpose of this study is to analyze completed and ongoing CTEPH clinical trials to inform future investigation. <h3>Methods</h3> The ClinicalTrials.gov database and the World Health Organization International Clinical Trials Registry Platform (ICTRP) were searched for "CTEPH" and related terms up to July 2020. PubMed was searched for all trial numbers to identify associated publications. <h3>Results</h3> There were 107 entries in ClinicalTrials.gov and 126 in ICTRP, with 132 total after removing duplicates/non-target entries. 63 trials were pharmaceutical (n=48) and/or procedural (n=19) interventions for treatment of CTEPH, 52% industry-sponsored, and 56% early phase, when specified. The most frequent pharmaceutical interventions were riociguat (35%), macitentan (19%), bosentan (10%), and selexipag (10%). The most frequent procedures were balloon pulmonary angioplasty (63%), pulmonary endarterectomy (16%), and pulmonary artery denervation (11%). Procedural trials were more frequently randomized than pharmaceutical trials. 272 outcomes were listed, 41 unique, with 6-minute walk distance (6MWD) as the most frequent (31/272; 11%). Other trials included investigation of incidence (n=18), imaging (n=8), exercise (n=8), oxygen/ventilation (n=8), registries (n=15), and others (n=12). The most frequent affiliation (country) of the principal investigator, for all 132 entries, was Japan (n=23; 17%). For pharmaceuticals it was USA and procedures it was China. Recruitment targets ranged up to 1301 participants with 41% still recruiting and 2% terminated early. 44 publications, including 27 articles of original research, were identified searching for all 132 trial identifiers. <h3>Conclusion</h3> CTEPH clinical trials are most commonly pharmaceutical, early phase and industry-sponsored with a 6MWD outcome. There is substantial variation in design and regional approach with a minority of trial results found in peer-reviewed literature.

Pulmonary Hypertension Clinical Trials and COVID-19: A Discussion With John Ryan and Roham Zamanian

Pulmonary Hypertension Clinical Trials and COVID-19: A Discussion With John Ryan and Roham Zamanian

Abstract 13135: Starting Beta-blockers in Hypertension is Followed by Excess Loop Diuretic Use: Beta-blocker Induced Heart Failure?

Introduction: Recent investigation has identified that discontinuation of beta-blockers in subjects with normal left ventricular ejection fraction (LVEF) leads to a reduction in natriuretic peptide levels. We investigated whether a similar trend would be seen in a hypertension clinical trial cohort. Methods: In 9,012 subjects hypertensive subjects without a history of symptomatic heart failure, known LVEF &lt;35% or recent heart failure hospitalization enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT), we compared incidence of loop diuretic initiation and time to initiation following start of a new anti-hypertensive medication. The categorical relationship (new antihypertensive class followed by loop-diuretic use) and temporal relationship (time to loop diuretic initiation) were each analyzed. The categorical relationship was assessed using a Pearson’s chi-squared test and the temporal relationship using a Wilcoxon rank sum test. Bonferroni-corrected p-values were utilized for all comparisons. Results: Among the 9,012 subjects analyzed, the incidence of anti-hypertensive initiation and loop diuretic initiation was greatest following start of a beta-blocker (16.6%) compared with other antihypertensive medication classes (calcium channel blocker 13.8%, angiotensin converting enzyme-inhibitor/angiotensin receptor blocker 12.9% and thiazide diuretic 10.2%; p&lt;0.001). In addition, the median time between starting a new antihypertensive medication and loop diuretic was the shortest for beta-blockers and longest for thiazides (both p &lt;0.01). No significant differences in renal function were identified between groups. Conclusion: Compared to other major classes of hypertensive agents, starting beta-blockers was associated with more common and earlier initiation of a loop diuretics in a population without heart failure at baseline. This finding may suggest beta-blocker induced heart failure in a population with a predominantly normal ejection fraction.

Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire: feasibility of utilizing one-day versus seven-day symptom reporting.

Patient-reported outcomes are important measures to include in pulmonary arterial hypertension clinical trials but are not widely utilized in clinical practice. Pulmonary Arterial Hypertension—Symptoms and Impact Questionnaire (PAH-SYMPACT) is the only pulmonary arterial hypertension-specific patient-reported outcomes instrument developed and validated in accordance with the US Food and Drug Administration guidance on patient-reported outcomes development. The PAH-SYMPACT tool measures pulmonary arterial hypertension-related symptoms and impact of pulmonary arterial hypertension on daily life. Symptoms are reported each day for seven consecutive days, and the impact of pulmonary arterial hypertension over one week is recalled and reported on day 7; however, daily symptom reporting may overburden patients and healthcare resources, limiting the practicality of PAH-SYMPACT outside of clinical trials. To determine the practicability of an abridged version of PAH-SYMPACT for which all reporting is completed on one day, symptom data from the SYMPHONY trial (NCT01841762; PAH-SYMPACT validation study) were retrospectively analyzed to assess whether symptoms reported on each day correlated with the weekly average and whether one-day symptom scores were sensitive to disease severity. Correlation coefficients comparing the weekly average and individual day symptom scores were mostly high or very high regardless of the day they were measured. Findings were similar when using either Spearman's rank correlation or weighted kappa method. One-day symptom scores differentiated well between World Health Organization functional classes II and III/IV pulmonary arterial hypertension and were sensitive to change in disease severity as measured by the Patient Global Assessment of Disease Severity. These data suggest that the one-day PAH-SYMPACT is feasible and appropriate for routine implementation in clinical practice.

Association of the genetic ancestry with resistant hypertension in the ReHOT (Resistant Hypertension Optimal Treatment) randomized study

Resistant hypertension (RH) is defined as uncontrolled blood pressure despite treatment with three or more antihypertensive medications, including, if tolerated, a diuretic in adequate doses. It has been widely known that race is associated with blood pressure control. However, intense debate persists as to whether this is solely explained by unadjusted socioeconomical variables or genetic variation. In this scenario, the main aim was to evaluate the association between genetic ancestry and resistant hypertension in a large sample from a multicenter trial of stage II hypertension, the ReHOT study. Samples from 1,358 patients were analyzed, of which 167 were defined as resistant hypertensive. Genetic ancestry was defined using a panel of 192 polymorphic markers. The genetic ancestry was similar in resistant (52.0% European, 36.7% African and 11.3% Amerindian) and nonresistant hypertensive patients (54.0% European, 34.4% African and 11.6% Amerindian) (p > 0.05). However, we observed a statistically suggestive association of African ancestry with resistant hypertension in brown patient group. In conclusion, increased African genetic ancestry was not associated with RH in Brazilian patients from a prospective randomized hypertension clinical trial.