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

英石。

• 批准号: 9349871
• 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 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9349871
• 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; Intervention; Intervention Studies; Intestines; Lead; Life; Link; Measurement; Measures; Mediating; Mediation; Morbidity - disease rate; Natriuretic Peptides; Nature; Observational Study; Organ; Outcome; Participant; Pathway interactions; 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; Recruitment Activity; Reporting; Research; Research Infrastructure; Resources; Risk; Risk Factors; Russia; Smoker; Stretching; Structure; Testing; Ventricular; alcohol abuse therapy; alcohol use disorder; biomarker identification; cardiovascular disorder risk; data management; heart disease risk; 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.

在人类免疫缺陷病毒感染者（HIV+）中大量饮酒是常见的， 与心力衰竭（HF）和冠心病（CHD）相关。一种未被探索的潜在机制 因为这种联系涉及肠道微生物群的变化（生态失调），这与重金属中毒有关。 酗酒或感染艾滋病毒。生态失调可能会改变微生物基因组的平衡， 增加的三甲胺N-氧化物（TMAO）产生。TMAO增加与心血管疾病有关 疾病（CVD）事件，包括一般人群中的亚临床CHD和HF发病率和死亡率。然而， 没有发表的研究评估酒精和TMAO或TMAO和亚临床HF之间的联系， 艾滋病毒阳性者。我们假设，在HIV+重度饮酒者中，饮酒与更高水平的 较高的TMAO水平与HF的亚临床指标和生物标志物相关。我们将 在圣彼得HIV - CVD中测试这些假设，这是一项观察性研究， 圣PETER HIV，一项随机临床试验（U 01 AA 020780; 2017年冬季开始入组）。圣彼得 HIV临床试验正在测试伐尼克兰与胞嘧啶对同时减少酒精和吸烟的影响 400名HIV+重度饮酒者（前一个月≥5个重度饮酒日）和每日吸烟者在St. 俄罗斯，彼得堡。圣彼得HIV - CVD的主要优势是现有的互补性 圣彼得HIV临床试验的资源/基础设施，包括：1）参与者招募; 2）经过验证的自我验证; 报告酒精消费; 3）生物标本采集; 4）专业知识和强大的合作历史， 酒精，艾滋病毒和CVD研究的美国和俄罗斯的团队成员进行这项研究。在圣彼得 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型利钠肽（BNP;心室伸展的生物标志物）、磷脂酰乙醇（PEth;酒精 生物标志物）和食物频率问卷。还将在6个月时测量超声心动图。与 这些现有的和新的数据，我们将处于独特的地位，以完成以下目标： 目的1：评估重度饮酒（酒精使用障碍识别测试，AUDIT≥20）是否：a） B）与HIV+重度饮酒者的TMAO水平纵向相关; 目的2：评估TMAO是否与该人群的心功能和BNP相关; 目的3：探讨氧化三甲胺是否介导饮酒与亚临床心力衰竭风险之间的关系。 如果得到证实，我们的假设将确定一种对减少酒精的干预措施有反应的生物标志物（TMAO）- HIV+重度饮酒者的CVD风险。因为酗酒的干预措施并不总是成功的， 制定新的酒精治疗策略，减少酒精对艾滋病毒阳性人群健康的负面影响 是必要的。生物标志物及其代表的途径的鉴定（例如，生态失调）可能导致 为干预研究提供新的目标，并改善HIV+饮酒者的CVD风险预测。