Cardiovascular Dynamics in HIV: The Influence of Adrenal Function and Nutritional Status.

This interdisciplinary review explores the intricate nexus between HIV infection, nutrition, adrenal gland function, and cardiovascular health, highlighting a critical aspect of HIV management often overlooked in current literature. With the advent of antiretroviral therapy, the life expectancy of people living with HIV has dramatically improved, transforming HIV into a manageable chronic condition. However, this success brings forth new challenges, notably an increased risk of cardiovascular diseases among people living with HIV. We examine the normal physiology of the adrenal gland, including its role in mineral metabolism, a crucial facet of nutrition. We discuss the evolution of knowledge tying adrenal pathology to cardiovascular disease. We explore the impact of HIV on adrenal gland findings from a gross pathology perspective, as well as the clinical impact of adrenal insufficiency in HIV. The review further elucidates the role of nutrition in this context, considering the double burden of undernutrition and obesity prevalent in regions heavily affected by HIV. By aggregating findings from longitudinal studies and recent clinical trials, the review presents compelling evidence of increased cardiovascular disease among people living with HIV compared with people without HIV. It highlights the critical role of the adrenal glands in regulating nutrient metabolism and its implications for cardiovascular health, drawing attention to the potential for dietary interventions and targeted therapies to mitigate these risks. This review urges a paradigm shift in the management of HIV, advocating for a holistic approach that incorporates nutritional assessment and interventions into routine HIV care to address the complex interplay between HIV, adrenal function, and cardiovascular health. Through this lens, we offer insights into novel therapeutic strategies aimed at reducing cardiovascular risk in people living with HIV, contributing to the ongoing efforts to enhance the quality of life and longevity in this population.

Responsible, practical genomic data sharing that accelerates research.

Data sharing anchors reproducible science, but expectations and best practices are often nebulous. Communities of funders, researchers and publishers continue to grapple with what should be required or encouraged. To illuminate the rationales for sharing data, the technical challenges and the social and cultural challenges, we consider the stakeholders in the scientific enterprise. In biomedical research, participants are key among those stakeholders. Ethical sharing requires considering both the value of research efforts and the privacy costs for participants. We discuss current best practices for various types of genomic data, as well as opportunities to promote ethical data sharing that accelerates science by aligning incentives.

Testing for Primary Aldosteronism and Mineralocorticoid Receptor Antagonist Use Among U.S. Veterans : A Retrospective Cohort Study.

BACKGROUND: Primary aldosteronism is a common cause of treatment-resistant hypertension. However, evidence from local health systems suggests low rates of testing for primary aldosteronism. OBJECTIVE: To evaluate testing rates for primary aldosteronism and evidence-based hypertension management in patients with treatment-resistant hypertension. DESIGN: Retrospective cohort study. SETTING: U.S. Veterans Health Administration. PARTICIPANTS: Veterans with apparent treatment-resistant hypertension (n = 269 010) from 2000 to 2017, defined as either 2 blood pressures (BPs) of at least 140 mm Hg (systolic) or 90 mm Hg (diastolic) at least 1 month apart during use of 3 antihypertensive agents (including a diuretic), or hypertension requiring 4 antihypertensive classes. MEASUREMENTS: Rates of primary aldosteronism testing (plasma aldosterone-renin) and the association of testing with evidence-based treatment using a mineralocorticoid receptor antagonist (MRA) and with longitudinal systolic BP. RESULTS: 4277 (1.6%) patients who were tested for primary aldosteronism were identified. An index visit with a nephrologist (hazard ratio [HR], 2.05 [95% CI, 1.66 to 2.52]) or an endocrinologist (HR, 2.48 [CI, 1.69 to 3.63]) was associated with a higher likelihood of testing compared with primary care. Testing was associated with a 4-fold higher likelihood of initiating MRA therapy (HR, 4.10 [CI, 3.68 to 4.55]) and with better BP control over time. LIMITATIONS: Predominantly male cohort, retrospective design, susceptibility of office BPs to misclassification, and lack of confirmatory testing for primary aldosteronism. CONCLUSION: In a nationally distributed cohort of veterans with apparent treatment-resistant hypertension, testing for primary aldosteronism was rare and was associated with higher rates of evidence-based treatment with MRAs and better longitudinal BP control. The findings reinforce prior observations of low adherence to guideline-recommended practices in smaller health systems and underscore the urgent need for improved management of patients with treatment-resistant hypertension. PRIMARY FUNDING SOURCE: National Institutes of Health.

Angiotensin Receptor Blockers and the Risk of Cancer: Insights from Clinical Trials and Recent Drug Recalls.

PURPOSE OF REVIEW: The purpose of this review is to familiarize readers with issues surrounding angiotensin receptor blockers (ARBs) and the risk of cancer, both from the perspective of clinical trial data and the more recent concerns about impurities in certain ARB products. RECENT FINDINGS: Approximately 45.6% of adults in the USA have hypertension. ARB-containing medications are widely used in the USA, with tens of millions of prescriptions written yearly. Whether exposure to certain ARB drug products contributes to the development of cancer has been the topic of a series of publications. Nonetheless, ARBs' link to cancer, if any, remains inconclusive. Any mechanistic link between ARBs and cancer is poorly understood, with a variety of basic science studies suggesting that ARBs should exert a protective effect. Due to the presence of potentially carcinogenic nitrosamine impurities in certain ARB products, a series of large recalls in the USA and in countries around the world has occurred since 2018. These recalls have occurred in the context of two recent trends affecting antihypertensive drugs: nearly ubiquitous reliance on generic drugs and increased use of manufacturing facilities in China and India to supply the USA. Despite substantial efforts directed toward understanding whether ARBs have the potential to cause cancer, the available studies do not provide a consistent answer, and a causal link remains speculative. The principal conclusion must be that there is not a definitive signal for cancer associated with ARB exposure, although the possibility has not been fully excluded. The problem of nitrosamine impurities in certain ARB products (and some other drug products) is in need of further investigation, so that the risks can be mitigated by eliminating these impurities from the drug supply chain.

Extracellular Vesicles in Essential Hypertension: Hidden Messengers.

PURPOSE OF REVIEW: Hypertension affects about half of all Americans, yet in the vast majority of cases, the factors causing the hypertension cannot be clearly delineated. Developing a more precise understanding of the molecular pathogenesis of HTN and its various phenotypes is therefore a pressing priority. Circulating and urinary extracellular vesicles (EVs) are potential novel candidates as biomarkers and bioactivators in HTN. EVs are a heterogeneous population of small membrane fragments shed from various cell types into various body fluids. As EVs carry protein, RNA, and lipids, they also play a role as effectors and novel cell-to-cell communicators. In this review, we discuss the diagnostic, functional, and regenerative role of EVs in essential HTN and focus on EV protein and RNA cargo as the most extensively studied EV cargo. RECENT FINDINGS: The field of EVs in HTN is still a young one and earlier studies have not used the novel EV detection tools currently available. More rigor and transparency in EV research are needed. Current data suggest that EVs represent potential novel biomarkers in HTN. EVs correlate with HTN severity and possibly end-organ damage. However, it has yet to be discerned which specific subtype(s) of EV reflects best HTN pathophysiology. Evolving studies are also showing that EVs might be novel regulators in vascular and renal tubular function and also be therapeutic. RNA in EVs has been studied in the context of hypertension, largely in the form of studies of miRNA, which are reviewed herein. Beyond miRNAs, mRNA in urinary EVs changed in response to sodium loading in humans. EVs represent promising novel biomarkers and bioactivators in essential HTN. Novel tools are being developed to apply more rigor in EV research including more in vivo models and translation to humans.

Hypertension.

Recent guidelines on diagnosis and management of high blood pressure (BP) include substantial changes and several new concepts compared with previous guidelines. These are reviewed and their clinical implications are discussed in this article. The goal is to provide a practical reference to assist clinicians with up-to-date management of patients with high BP. Important issues include new diagnostic thresholds, out-of-office BP monitoring, intensified treatment goals, and a different approach to resistant hypertension. Finally, differences among guidelines, the persistent controversies that have led to them, and their implications for clinical practice are discussed.

Primary Aldosteronism: Practical Approach to Diagnosis and Management.

Primary aldosteronism (PA) is the most common form of secondary hypertension. In many cases, somatic mutations in ion channels and pumps within adrenal cells initiate the pathogenesis of PA, and this mechanism might explain why PA is so common and suggests that milder and evolving forms of PA must exist. Compared with primary hypertension, PA causes more end-organ damage and is associated with excess cardiovascular morbidity, including heart failure, stroke, nonfatal myocardial infarction, and atrial fibrillation. Screening is simple and readily available, and targeted therapy improves blood pressure control and mitigates cardiovascular morbidity. Despite these imperatives, screening rates for PA are low, and mineralocorticoid-receptor antagonists are underused for hypertension treatment. After the evidence for the prevalence of PA and its associated cardiovascular morbidity is summarized, a practical approach to PA screening, referral, and management is described. All physicians who treat hypertension should routinely screen appropriate patients for PA.

Personalized Medicine and the Treatment of Hypertension.

PURPOSE OF REVIEW: The purpose of this review is to discuss the implications of personalized medicine for the treatment of hypertension, including resistant hypertension. RECENT FINDINGS: We suggest a framework for the personalized treatment of hypertension based on the concept of a trade-off between simplicity and personalization. This framework is based on treatment strategies classified as low, medium, or high information burden personalization approaches. The extent to which a higher information burden is justified depends on the clinical scenario, particularly the ease with which the blood pressure can be controlled. A one-size-fits-many treatment strategy for hypertension is efficacious for most people; however, a more personalized approach could be useful in patients with subtypes of hypertension that do not respond as expected to treatment. Clinicians seeing patients with unusual hypertension phenotypes should be familiar with emerging trends in personalized treatment of hypertension.

Blood pressure, heart rate, and mortality in chronic obstructive pulmonary disease: the SUMMIT trial.

Aims: To characterize the relationship between blood pressure (BP) or heart rate and mortality and morbidity in chronic obstructive pulmonary disease (COPD). Methods and results: We performed post hoc analysis of baseline BP or heart rate and all-cause mortality and cardiovascular events in the SUMMIT trial. SUMMIT was a randomized double-blind outcome trial of 16 485 participants (65 ± 8 years, 75% male, and 47% active smokers) enrolled at 1368 sites in 43 countries. Participants with moderate COPD with or at risk for cardiovascular disease (CVD) were randomized to placebo, long-acting beta agonist, inhaled corticosteroid, or their combination. All-cause mortality increased in relation to high systolic [≥140 mmHg; hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.12-1.45] or diastolic (≥90 mmHg; HR 1.35, 95% CI 1.14-1.59) BP and low systolic (<120 mmHg; HR 1.36, 95% CI 1.13-1.63) or diastolic (<80 mmHg; HR 1.15, 95% CI 1.00-1.32) BP. Higher heart rates (≥80 per minute; HR 1.39, 95% CI 1.21-1.60) and pulse pressures (≥80 mmHg; HR 1.39, 95% CI 1.07-1.80) were more linearly related to increases in all-cause mortality. The risks of cardiovascular events followed similar patterns to all-cause mortality. Similar findings were observed in subgroups of patients without established CVD. Conclusion: A 'U-shaped' relationship between BP and all-cause mortality and cardiovascular events exists in patients with COPD and heightened cardiovascular risk. A linear relationship exists between heart rate and all-cause mortality and cardiovascular events in this population. These findings extend the prognostic importance of BP to this growing group of patients and raise concerns that both high and low BP may pose health risks.

Reach Out Churches: A Community-Based Participatory Research Pilot Trial to Assess the Feasibility of a Mobile Health Technology Intervention to Reduce Blood Pressure Among African Americans.

Innovative strategies are needed to reduce the hypertension epidemic among African Americans. Reach Out was a faith-collaborative, mobile health, randomized, pilot intervention trial of four mobile health components to reduce high blood pressure (BP) compared to usual care. It was designed and tested within a community-based participatory research framework among African Americans recruited and randomized from churches in Flint, Michigan. The purpose of this pilot study was to assess the feasibility of the Reach Out processes. Feasibility was assessed by willingness to consent (acceptance of randomization), proportion of weeks participants texted their BP readings (intervention use), number lost to follow-up (retention), and responses to postintervention surveys and focus groups (acceptance of intervention). Of the 425 church members who underwent BP screening, 94 enrolled in the study and 73 (78%) completed the 6-month outcome assessment. Median age was 58 years, and 79% were women. Participants responded with their BPs on an average of 13.7 (SD = 10.7) weeks out of 26 weeks that the BP prompts were sent. All participants reported satisfaction with the intervention. Reach Out, a faith-collaborative, mobile health intervention was feasible. Further study of the efficacy of the intervention and additional mobile health strategies should be considered.

Anxiety in the "age of hypertension".

In the USA, hypertension affects one in three adults, and anxiety disorders are the most commonly diagnosed mental health disorders. Both hypertension and anxiety have been studied extensively. Yet, a full understanding of anxiety's relationship to hypertension has been elusive. In this review, we discuss the spectrum of anxiety disorders. In addition, we consider the evidence for acute and long-term effects of anxiety on blood pressure. We review the effect on blood pressure of several "real-world" stressors, such as natural disasters. In addition, we review the effect of anxiety treatments on blood pressure. We explain the American Heart Association's recent recommendations regarding meditation and other relaxation methods in the management of hypertension. We conclude that novel research methods are needed in order to better elucidate many aspects of how anxiety relates to hypertension.

The contribution of the ACCOMPLISH trial to the treatment of stage 2 hypertension.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommended a thiazide-like diuretic, alone or in combination with other antihypertensive drug classes, as initial therapy for hypertension. JNC 7, however, did not specify preferred combinations. The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial was completed five years after the JNC 7 and demonstrated a 20 % advantage in cardiovascular risk reduction when blood pressure was lowered using the single-pill combination of benazepril-amlodipine compared to benazepril-hydrochlorothiazide (Jamerson et al. 359(23):2417-28 [1]). This new and significant finding provided compelling evidence that the long-standing preference for diuretics as initial therapy could be refuted, but it may also be relevant to the lower-than-expected reduction in coronary disease related events (compared to stroke) observed for decades prior to the ACCOMPLISH approach to therapy. The JNC 8 panel members recently published their recommendations, and while the group did not recommend benazepril-hydrochlorothiazide over other combinations, they did highlight the findings of ACCOMPLISH, rating the primary ACCOMPLISH paper as "good." The American Society of Hypertension position paper and the European Hypertension Society guidelines endorse such combinations as a first-line agent for patients with stage 2 hypertension. We review the current position of ACCOMPLISH in the guidelines regarding treatment of stage 2 hypertension.

Data quality of an electronic health record tool to support VA cardiac catheterization laboratory quality improvement: the VA Clinical Assessment, Reporting, and Tracking System for Cath Labs (CART) program.

BACKGROUND: Electronic health records (EHRs) have been identified as a key tool for quality improvement (QI) in health care. However, EHR data must be of sufficient quality to support QI efforts. In 2005, the Department of Veterans Affairs (VA) began using a novel EHR tool-the CART Program-to support QI in cardiac catheterization laboratories. We evaluated whether data collected by the CART Program were of sufficient quality to support QI. METHODS: We evaluated the data validity, completeness, and timeliness of CART Program data using a random sample of 200 coronary procedures performed in 10 geographically diverse VA medical centers. RESULTS: Of 1690 observations in the CART Program data repository, 1664 (98.5%) were valid, as compared to the VA medical record. The CART Program reports were more complete than cardiac catheterization laboratory reports generated prior to CART Program implementation (79% vs. 63.1%, P < .001). Finally, there was a trend toward earlier availability of completed procedure reports to treating providers after CART Program implementation, with 75% of CART Program reports available within 1 day compared to 4 days for reports generated prior to CART Program implementation (P = .06). CONCLUSIONS: Cardiac catheterization reports generated by the VA's CART Program demonstrate excellent data validity, superior completeness, and a trend toward more timely availability to referring providers relative to cardiac catheterization laboratory reports generated prior to CART Program implementation. This demonstration of data quality is a key step in realizing CART Program's aim of supporting QI efforts in VA catheter laboratories.

Ontology-Based Classification and Analysis of Adverse Events Associated With the Usage of Chloroquine and Hydroxychloroquine.

Multiple methodologies have been developed to identify and predict adverse events (AEs); however, many of these methods do not consider how patient population characteristics, such as diseases, age, and gender, affect AEs seen. In this study, we evaluated the utility of collecting and analyzing AE data related to hydroxychloroquine (HCQ) and chloroquine (CQ) from US Prescribing Information (USPIs, also called drug product labels or package inserts), the FDA Adverse Event Reporting System (FAERS), and peer-reviewed literature from PubMed/EMBASE, followed by AE classification and modeling using the Ontology of Adverse Events (OAE). Our USPI analysis showed that CQ and HCQ AE profiles were similar, although HCQ was reported to be associated with fewer types of cardiovascular, nervous system, and musculoskeletal AEs. According to EMBASE literature mining, CQ and HCQ were associated with QT prolongation (primarily when treating COVID-19), heart arrhythmias, development of Torsade des Pointes, and retinopathy (primarily when treating lupus). The FAERS data was analyzed by proportional ratio reporting, Chi-square test, and minimal case number filtering, followed by OAE classification. HCQ was associated with 63 significant AEs (including 21 cardiovascular AEs) for COVID-19 patients and 120 significant AEs (including 12 cardiovascular AEs) for lupus patients, supporting the hypothesis that the disease being treated affects the type and number of certain CQ/HCQ AEs that are manifested. Using an HCQ AE patient example reported in the literature, we also ontologically modeled how an AE occurs and what factors (e.g., age, biological sex, and medical history) are involved in the AE formation. The methodology developed in this study can be used for other drugs and indications to better identify patient populations that are particularly vulnerable to AEs.