The Use of Metabolomes in Risk Stratification of Heart Failure Patients: Protocol for a Scoping Review.

BACKGROUND: Heart failure (HF) is a significant health problem that is often associated with major morbidity and mortality. Metabolic abnormalities occur in HF and may be used to identify individuals at risk of developing the condition. Furthermore, these metabolic changes may play a role in the pathogenesis and progression of HF. Despite this knowledge, the utility of metabolic changes in diagnosis, management, prognosis, and therapy for patients with chronic HF has not been systematically reviewed. OBJECTIVE: This scoping review aims to systematically appraise the literature on metabolic changes in patients with HF, describe the role of these changes in pathogenesis, progression, and care, and identify knowledge gaps to inform future research. METHODS: This review will be conducted using a strategy based on previous reports, the JBI Manual for Evidence Synthesis, and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) guidelines. A comprehensive search of electronic databases (Medline, EBSCOhost, Scopus, and Web of Science) will be conducted using keywords related to HF, myocardial failure, metabolomes, metabonomics, and analytical chemistry techniques. The search will include original peer-reviewed research papers (clinical studies conducted on humans and systematic reviews with or without a meta-analysis) published between January 2010 and September 2023. Studies that include patients with HF younger than 18 years or those not published in English will be excluded. Two authors (UGA and MB) will screen the titles and abstracts independently and perform a full-text screen of the relevant and eligible papers. Relevant data will be extracted and synthesized, and a third author or group will be consulted to resolve discrepancies. RESULTS: This scoping review will span from January 2010 to September 2023, and the results will be published in a peer-reviewed, open-access journal as a scoping review in 2024. The presentation of the findings will use the PRISMA-ScR flow diagram and descriptive and narrative formats, including tables and graphical displays, to provide a comprehensive overview of the extracted data. CONCLUSIONS: This review aims to collect and analyze the available evidence on metabolic changes in patients with HF, aiming to enhance our current understanding of this topic. Additionally, this review will identify the most commonly used and suitable sample, analytical method, and specific metabolomes to facilitate standardization, reproducibility of results, and application in the diagnosis, treatment, and risk stratification of patients with HF. Finally, it is hoped that this review's outcomes will inspire further research into the metabolomes of patients with HF in low- and middle-income countries. TRIAL REGISTRATION: Open Science Framework; https://osf.io/sp6xj. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53905.

Cardiac and Renal Comorbidities in Aging People Living With HIV.

Contemporary World Health Organization data indicates that ≈39 million people are living with the human immunodeficiency virus. Of these, 24 million have been reported to have successfully accessed combination antiretroviral therapy. In 1996, the World Health Organization endorsed the widespread use of combination antiretroviral therapy, transforming human immunodeficiency virus infection from being a life-threatening disease to a chronic illness characterized by multiple comorbidities. The increased access to combination antiretroviral therapy has translated to people living with human immunodeficiency virus (PLWH) no longer having a reduced life expectancy. Although aging as a biological process increases exposure to oxidative stress and subsequent systemic inflammation, this effect is likely enhanced in PLWH as they age. This narrative review engages the intricate interplay between human immunodeficiency virus associated chronic inflammation, combination antiretroviral therapy, and cardiac and renal comorbidities development in aging PLWH. We examine the evolving demographic profile of PLWH, emphasizing the increasing prevalence of aging individuals within this population. A central focus of the review discusses the pathophysiological mechanisms that underpin the heightened susceptibility of PLWH to renal and cardiac diseases as they age.

ß-blockers are not all the same: pharmacologic similarities and differences, potential combinations and clinical implications.

ß-blockers are a heterogeneous class, with individual agents distinguished by selectivity for ß1- vs. ß2- and α-adrenoceptors, presence or absence of partial agonist activity at one of more ß-receptor subtype, presence or absence of additional vasodilatory properties, and lipophilicity, which determines the ease of entry the drug into the central nervous system. Cardioselectivity (ß1-adrenoceptor selectivity) helps to reduce the potential for adverse effects mediated by blockade of ß2-adrenoceptors outside the myocardium, such as cold extremities, erectile dysfunction, or exacerbation of asthma or chronic obstructive pulmonary disease. According to recently updated guidelines from the European Society of Hypertension, ß-blockers are included within the five major drug classes recommended as the basis of antihypertensive treatment strategies. Adding a ß-blocker to another agent with a complementary mechanism may provide a rational antihypertensive combination that minimizes the adverse impact of induced sympathetic overactivity for optimal blood pressure-lowering efficacy and clinical outcomes benefit.

Efficacy of beta-blockers on blood pressure control and morbidity and mortality endpoints in hypertensives of African ancestry: an individual patient data meta-analysis.

Introduction: Compared with first-line antihypertensives, beta-blockers (BB) have been reported to lower the central aortic blood pressure suboptimally and are associated with increased stroke risk. This observation has not been investigated in hypertensives of African ancestry. We hypothesised that an individual patient data meta-analysis (IPD-MA) on the efficacy of second- or third-generation beta-blockers (STGBBs) in hypertensives of African descent may provide new insights. Methods: A single-stage IPD-MA analysed the efficacy of STGBB in lowering the mean arterial blood pressure and reducing the composite outcomes: cardiovascular death, stroke, and myocardial infarction. Results: A total of 11,860 participants from four randomised control trials were included in the analysis. Second- or third-generation beta-blockers reduced the mean arterial pressure by 1.75 mmHg [95% confidence interval (CI):1.16-2.33; P < 0.001] in all participants included in the analysis, and by 1.93 mmHg (95% CI: 0.86-3.00; P < 0.001) in hypertensive Africans. In patients with established cardiovascular disease, where the benefits of BB therapy are well established, STGBBs were associated with an adjusted odds ratio of 1.33 (95% CI: 1.06-1.65; P = 0.015) of the composite outcome, most likely due to confounding. Similarly, the risk of total myocardial infarction was 1.76 times higher (95% CI: 1.15-2.68; P = 0.008) in hypertensives of African ancestry on STGBBs. Conclusion: The STGBBs reduced the mean arterial pressure comparably to other antihypertensives, and they were not associated with an increased risk of stroke.