Clinical and immunologic factors underlying heart failure with preserved ejection fraction among persons with HIV in South Africa

南非艾滋病毒感染者射血分数保留的心力衰竭的临床和免疫因素

• 批准号: 10685376
• 负责人: Jason V Baker
• 金额: $ 53.1万
• 依托单位: HENNEPIN HEALTHCARE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10685376
• 关键词: Africa South of the Sahara; Age; Aging; Biological; Biological Factors; Biological Response Modifiers; CD4 Lymphocyte Count; COVID-19; Cardiac; Cardiovascular Diseases; Chronic; Clinical; Clinical Research; Clinical Trials; Coronary heart disease; Country; Data; Developing Countries; Diffuse; Diffuse Pattern; Disease; EFRAC; Early identification; Echocardiography; Enrollment; Epidemic; Etiology; Fibrosis; Frequencies; Functional disorder; Goals; HIV; Health; Heart; Heart failure; Hypertension; Immune Targeting; Immunologic Factors; Income; Individual; Infection; Injury; Intervention; Ischemia; Magnetic Resonance; Maps; Methods; Morbidity - disease rate; Mycobacterium tuberculosis; Myocardial; Myocardial Ischemia; Obesity; Organ; Pathogenesis; Pathology; Pathway interactions; Patients; Pattern; Pericardial body location; Persons; Phenotype; Prevalence; Proteomics; Research; Risk; Risk Factors; Sex Differences; South Africa; Standardization; Structure; Subgroup; Target Populations; Ventricular Dysfunction; Viral; Woman; adjudication; antiretroviral therapy; biomarker driven; burden of illness; cardiometabolism; cardiovascular disorder risk; clinically significant; cohort; comorbidity; coronary fibrosis; experience; heart imaging; mortality; multidisciplinary; myocardial injury; point of care; preservation; structural heart disease; substance use; systemic inflammatory response

Premise: HIV associated CVD is a significant cause of clinical morbidity and a barrier to successful aging among persons living with HIV (PWH). To date, HIV-CVD research has emphasized ischemic coronary heart disease. However, nearly 80% of the global CVD burden exists in developing nations and 70% of the HIV epidemic exists in sub-Saharan Africa (SSA) where heart failure (HF) is the predominant CVD manifestation. Data from high income countries (HIC) has established that chronic HIV disease contributes to increased risk for ventricular dysfunction and clinical HF. We have shown that asymptomatic PWH in South Africa (SA) have greater diffuse myocardial fibrosis by CMR, when compared to uninfected controls, representing structural changes that may increase risk for HF with preserved ejection fraction (HFpEF). These findings support our hypothesis that risk for HF will be increased among PWH taking ART in SA, and will manifest predominantly as HFpEF. Unifying mechanistic features of HFpEF have been proposed but the pathogenesis is heavily influenced by the presence of co-morbid end-organ diseases. This has motivated attempts to characterize clinical `phenogroups' of HFpEF based on the profile of comorbid conditions. When compared to HICs, the relative frequencies of co-morbid conditions (e.g., obesity, hypertension) and other risk factors (e.g., mTB, substance use) differs in low-to-middle income countries like SA. The unique risk factor profiles of PWH in SA will then result in distinct HFpEF phenogroups and changes to underlying cardiac structure. Approach: We propose to enroll PWH and uninfected controls, utilize echocardiography to adjudicate HF subgroups, and then identify a cohort of PWH with HFpEF to study clinical and biologic factors in greater detail. The target population includes patients living in Khayelitsha township, outside of Cape Town, SA, who are age ≥40 years and on ART with viral suppression (if living with HIV). Standardized clinical echocardiogram (ECHO) will be used to adjudicate HF status and cardiac magnetic resonance (CMR) will be used to characterize the injury pattern of cardiac fibrosis among those with HF. Our proposal includes following specific aims: Aim 1: Estimate the prevalence of HF due to ventricular dysfunction in SA, as well as the effect of treated-HIV. Aim 2: Determine the clinical phenogroup(s) that define HFpEF among PWH on ART, age ≥40, in SA. Aim 3: Explore immunologic factors that may contribute to myocardial fibrosis and HFpEF risk in PWH. Research and Health Implications: This proposal targets a large unmet need in the HIV-CVD field. HIV associated HF is a clinically significant challenge, and data from HIC do not adequately represent LMIC like SA. In addition, HFpEF can result from heterogeneous pathologies, and HIV disease may influence HFpEF risk through multiple pathways depending on underlying risk. Our proposal will determine the burden of HFpEF among PWH, develop POC approaches for identifying those at risk, and identify clinical and biologic features that may be targeted in HIV-CVD clinical trials within a global region where most of the HIV epidemic resides.

前提：HIV相关的CVD是临床发病率的重要原因，也是成功衰老的障碍 在艾滋病毒（PWH）的人中。迄今为止，HIV-CVD研究强调缺血性冠心病 疾病。但是，几乎80％的全球CVD Burnen存在于发展中国家，艾滋病毒的70％ 流行病存在于撒哈拉以南非洲（SSA），其中心力衰竭（HF）是CVD的主要表现。 高收入国家（HIC）的数据确定，慢性艾滋病毒疾病有助于增加风险 用于心室功能障碍和临床HF。我们已经表明，南非的不对称PWH（SA）有 与未感染的对照相比，CMR的弥漫性心肌纤维化更大，代表结构 使用保留的射血分数（HFPEF）可能会增加HF风险的变化。这些发现支持我们 假设在SA中使用ART的PWH中，HF的风险将增加，并且主要表现为 HFPEF。已经提出了HFPEF的统一机械特征，但发病机理很大 受共临界最终器官疾病的影响。这激发了特征的尝试 HFPEF的临床“现象”基于合并症的特征。与HICS相比 合并条件的相对频率（例如肥胖，高血压）和其他风险因素（例如MTB， 诸如SA之类的低至中收入国家 /地区的药物使用）不同。 SA中PWH的独特风险因素概况 然后，将导致不同的HFPEF现象和对基础心脏结构的变化。 方法：我们建议注册PWH和未感染的控件，利用超声心动图调整HF 亚组，然后确定与HFPEF的PWH队列，以更详细地研究临床和生物学因素。 目标人群包括居住在SA开普敦郊外Khayelitsha镇的患者， ≥40岁，并具有病毒抑制的艺术（如果患有艾滋病毒）。标准临床超声心动图（ECHO） 将用于调整HF状态，心脏磁共振（CMR）将用于表征 HF患者中心脏纤维化的损伤模式。我们的建议包括以下具体目的： 目标1：估计由于SA中心室功能障碍引起的HF的患病率以及治疗HIV的效果。 AIM 2：确定SA中PWH中定义hfpef的临床现象。 AIM 3：探索可能导致PWH中心肌纤维化和HFPEF风险的免疫因素。 研究和健康影响：该提案针对HIV-CVD领域的巨大未满足需求。艾滋病病毒 相关的HF是临床上重要的挑战，HIC的数据不能充分代表LMIC SA。此外，HFPEF可能是由异质性病理引起的，HIV疾病可能会影响HFPEF风险 通过多个途径取决于潜在的风险。我们的建议将决定HFPEF的燃烧 在PWH中，开发POC方法以识别有风险的人并确定临床和生物学特征 这可能是在大多数HIV流行病患者的全球区域内的HIV-CVD临床试验中针对的。