ST. PETER HIV-Alcohol, Protein Biomarkers and Cardiovascular Disease Risk

英石。

• 批准号: 9770731
• 负责人: MATTHEW S FREIBERG
• 金额: $ 19.96万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9770731
• 关键词: Address; Alcohol consumption; Alcoholic Cardiomyopathy; Alcoholic beverage heavy drinker; Alcohols; Biochemical; Biological Markers; Biometry; Brain natriuretic peptide; Cardiac; Cardiovascular Diseases; Caring; Choline; Clinical; Clinical Trials; Collaborations; Collection; Complement; Coronary heart disease; Cytosine; Data; Diet; Disease; Echocardiography; Enrollment; Equilibrium; Event; Food; Frequencies; Funding; Future; General Population; HIV; HIV Infections; Health; Heart failure; Heavy Drinking; Infrastructure; Intervention; Intervention Studies; Intestines; Lead; Life; Link; Measurement; Measures; Mediating; Mediation; Morbidity - disease rate; Natriuretic Peptides; Nature; Observational Study; Organ; Outcome; Pathway interactions; Patient Recruitments; Patient Self-Report; Patients; Persons; Pharmacology; Population; Positioning Attribute; Primary Prevention; Production; Proteomics; Publishing; Questionnaires; Randomized Clinical Trials; Randomized Controlled Trials; Recording of previous events; Reporting; Research; Resources; Risk; Risk Factors; Russia; Smoker; Stretching; Structure; Testing; Ventricular; Virus Diseases; alcohol abuse therapy; alcohol use disorder; biomarker identification; cardiovascular disorder risk; data management; dysbiosis; heart disease risk; heart function; improved; indexing; member; microbial; microbial genome; microbiome; microbiota; mortality; nonhuman primate; peptide B; phosphatidylethanol; protein biomarkers; smoking cessation; treatment strategy; trimethylamine; trimethyloxamine; varenicline

Heavy alcohol use among human immunodeficiency virus infected (HIV+) people is common and associated with heart failure (HF) and coronary heart disease (CHD). An unexplored potential mechanism for this association involves changes in intestinal microbial populations (dysbiosis), which occur with heavy alcohol use or HIV infection. Dysbiosis may shift the balance of microbial genomes (microbiomes) to promote increased trimethylamine N-oxide (TMAO) production. Increased TMAO is associated with cardiovascular disease (CVD) events, including subclinical CHD and HF morbidity and mortality in the general population. Yet, no published studies have assessed the link between alcohol and TMAO or TMAO and subclinical HF among HIV+ people. We hypothesize that among HIV+ heavy drinkers, alcohol use is associated with higher levels of TMAO, and that higher TMAO levels are associated with subclinical measures and biomarkers of HF. We will test these hypotheses in ST. PETER HIV – CVD, an observational study that will be built on and complement St. PETER HIV, a randomized clinical trial (U01AA020780; begins enrollment Winter 2017). The St. PETER HIV clinical trial is testing the effects of varenicline vs. cytosine on simultaneous alcohol reduction and smoking cessation among 400 HIV+ heavy drinkers (≥5 heavy drinking days in prior month) and daily smokers in St. Petersburg, Russia. Major strengths of ST. PETER HIV - CVD are the existing complementary resources/infrastructure of the St. PETER HIV clinical trial including:1) participant recruitment; 2) validated self- report alcohol consumption; 3) biospecimen collection; 4) expertise and strong history of collaboration on alcohol, HIV and CVD research of the U.S. and Russia team members undertaking this study. In ST. PETER HIV – CVD, we propose to collect at baseline and 3 months the following new data: TMAO, echocardiography, B-type natriuretic peptide (BNP; biomarker of ventricular stretching), phosphatidylethanol (PEth; alcohol biomarker) and food frequency questionnaires. Echocardiography will be measured also at 6 months. With these existing and new data, we will be uniquely positioned to complete the following aims: AIM 1: To assess whether heavier alcohol use (Alcohol Use Disorders Identification Test, AUDIT≥20) is: a) cross-sectionally and b) longitudinally associated with TMAO levels among HIV+ heavy drinkers; AIM 2: To assess whether TMAO is associated with cardiac function and BNP in this population; and AIM 3: To explore whether TMAO mediates the association of alcohol use and subclinical HF risk. If confirmed, our hypotheses will identify a biomarker (TMAO) responsive to interventions that reduce alcohol- related CVD risk in HIV+ heavy drinkers. Because heavy alcohol use interventions do not succeed in all, developing new alcohol treatment strategies that reduce alcohol’s negative health impact among HIV+ people are needed. The identification of biomarkers and the pathways they represent (e.g., dysbiosis) could result in new targets for intervention studies and improve CVD risk prediction in HIV+ drinkers.

人类免疫缺陷病毒感染者（HIV+）酗酒很常见，而且 与心力衰竭（HF）和冠心病（CHD）有关。尚未探索的潜在机制 因为这种关联涉及肠道微生物种群的变化（菌群失调），这种变化发生在重度 饮酒或感染艾滋病毒。生态失调可能会改变微生物基因组（微生物组）的平衡，以促进 增加三甲胺 N-氧化物 (TMAO) 的产量。 TMAO 增加与心血管疾病相关 疾病 (CVD) 事件，包括一般人群中亚临床 CHD 和 HF 的发病率和死亡率。然而， 尚未发表的研究评估酒精与 TMAO 或 TMAO 与亚临床心力衰竭之间的联系 艾滋病病毒感染者。我们假设，在 HIV+ 重度饮酒者中，饮酒与较高水平的酒精相关。 TMAO，较高的 TMAO 水平与心力衰竭的亚临床指标和生物标志物相关。我们将 在 ST 中检验这些假设。 PETER HIV – CVD，一项观察性研究，将在此基础上进行补充 St. PETER HIV，一项随机临床试验（U01AA020780；2017 年冬季开始入组）。圣彼得号 HIV 临床试验正在测试伐尼克兰与胞嘧啶对同时减少饮酒和吸烟的影响 圣路易斯 400 名 HIV+ 重度饮酒者（上个月重度饮酒天数≥5 天）和每日吸烟者戒烟 俄罗斯圣彼得堡。 ST的主要优势PETER HIV - CVD 是现有的补充 St. PETER HIV 临床试验的资源/基础设施包括：1) 参与者招募； 2) 自我验证 报告饮酒量； 3）生物标本采集； 4) 专业知识和深厚的合作历史 从事这项研究的美国和俄罗斯团队成员的酒精、艾滋病毒和心血管疾病研究。在ST。彼得 HIV – CVD，我们建议在基线和 3 个月时收集以下新数据：TMAO、超声心动图、 B 型钠尿肽（BNP；心室舒张生物标志物）、磷脂酰乙醇（PEth；酒精 生物标志物）和食物频率问卷。超声心动图也将在 6 个月时进行测量。和 通过这些现有的和新的数据，我们将具有独特的优势来完成以下目标： 目标 1：评估大量饮酒（酒精使用障碍识别测试，AUDIT≥20）是否：a) b) 与 HIV+ 重度饮酒者中 TMAO 水平的横向相关性和纵向相关性； 目标 2：评估 TMAO 是否与该人群的心功能和 BNP 相关；和 目标 3：探讨 TMAO 是否介导饮酒与亚临床心力衰竭风险之间的关联。 如果得到证实，我们的假设将识别出一种生物标志物（TMAO），该标志物对减少酒精的干预措施有反应 HIV+ 重度饮酒者的相关 CVD 风险。因为大量饮酒干预措施并不完全成功， 制定新的酒精治疗策略，减少酒精对艾滋病病毒感染者的负面健康影响 需要。生物标志物及其代表的途径（例如生态失调）的识别可能会导致 干预研究的新目标并改善 HIV+ 饮酒者的 CVD 风险预测。