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 是临床发病的重要原因，也是成功老龄化的障碍 迄今为止，HIV-CVD 研究重点关注缺血性心脏病。 然而，全球近 80% 的心血管疾病负担和 70% 的艾滋病毒负担存在于发展中国家。 撒哈拉以南非洲 (SSA) 存在流行病，其中心力衰竭 (HF) 是主要的 CVD 表现。 高收入国家 (HIC) 的数据表明，慢性艾滋病毒会导致风险增加 我们已经证明南非 (SA) 的无症状感染者有心力衰竭。 与未感染的对照相比，CMR 检测显示更大的弥漫性心肌纤维化，代表结构性心肌纤维化 这些变化可能会增加射血分数保留的心力衰竭 (HFpEF) 的风险。 假设在南非接受抗逆转录病毒治疗的感染者中，心力衰竭的风险会增加，并且主要表现为 HFpEF 的统一机制特征已被提出，但发病机制很复杂。 受到共病终末器官疾病的影响，这促使人们尝试表征。 与 HIC 相比，基于合并症概况的 HFpEF 临床“表型”。 共病（例如肥胖、高血压）和其他危险因素（例如结核病、结核病）的相对频率 南澳等中低收入国家的情况有所不同 南澳感染者艾滋病毒感染者的独特风险因素概况。 然后将导致不同的 HFpEF 表型和基础心脏结构的变化。 方法：我们建议纳入 PWH 和未感染对照，利用超声心动图来判定心力衰竭 亚组，然后确定患有 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南澳州开普敦郊外 Khayelitsha 镇的患者，这些患者年龄 ≥40 岁并接受病毒抑制的 ART（如果感染 HIV）。 将用于判定 HF 状态，心脏磁共振 (CMR) 将用于表征 我们的建议包括以下具体目标： 目标 1：估计 SA 中心室功能不全导致心力衰竭的患病率，以及治疗 HIV 的影响。 目标 2：确定在 SA 中接受 ART、年龄≥40 岁的 PWH 中定义 HFpEF 的临床表型。 目标 3：探索可能导致感染者心肌纤维化和 HFpEF 风险的免疫因素。 研究和健康影响：该提案针对的是 HIV-CVD 领域大量未满足的需求。 相关的心力衰竭是临床上的重大挑战，来自 HIC 的数据不能充分代表 LMIC，例如 此外，HFpEF 可能由异质病理引起，HIV 疾病可能会影响 HFpEF 风险。 我们的建议将根据潜在风险通过多种途径确定 HFpEF 的负担。 在 PWH 中，开发 POC 方法来识别高危人群，并确定临床和生物学特征 可能是在全球大多数艾滋病毒流行地区进行艾滋病毒心血管疾病临床试验的目标。