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.

人类免疫缺陷病毒感染（HIV+）人的大量饮酒很常见，并且 与心力衰竭（HF）和冠状动脉疾病（CHD）相关。意外的潜在机制 因为这种关联涉及肠道微生物种群的变化（营养不良），这发生在重量 饮酒或艾滋病毒感染。营养不良可能改变微生物基因组（微生物组）的平衡以促进 增加三甲胺N-氧化物（TMAO）的产生。 TMAO增加与心血管有关 疾病（CVD）事件，包括一般人群中的亚临床冠心病和HF发病率和死亡率。然而， 没有发表的研究评估酒精与tmao或tmao与亚临床HF之间的联系 艾滋病毒+人。我们假设在艾滋病毒+饮酒者中，饮酒与较高的水平有关 TMAO，较高的TMAO水平与HF的亚临床测量和生物标志物有关。我们将 在St中检验这些假设。 Peter HIV - CVD，一项将建立和完成的观察性研究 St. Peter HIV，一项随机临床试验（U01AA020780；开始入学率2017年）。圣彼得 HIV临床试验正在测试Varenicline与胞嘧啶对同时减少酒精和吸烟的影响 在400名艾滋病毒+饮酒者中停止（上个月≥5个饮酒日≥5个）和St.的每日吸烟者 俄罗斯彼得斯堡。 ST的主要优势。 Peter HIV -CVD是现有的完整性 圣彼得艾滋病毒临床试验的资源/基础设施包括：1）参与者招募； 2）验证的自我 报告饮酒； 3）Biospecimen Collection; 4）专业知识和强大的合作历史 美国和俄罗斯团队成员进行这项研究的酒精，艾滋病毒和CVD研究。在圣。彼得 HIV - CVD，我们建议在基线和3个月内收集以下新数据：TMAO，超声心动图，， B型亚替肽肽（BNP；心室拉伸的生物标志物），磷脂酰乙醇（Peth；酒精 生物标志物）和食品频率问卷。超声心动图也将在6个月时测量。和 这些现有的和新数据，我们将处于独特的位置，以完成以下目的： 目标1：评估饮酒是否较重（酒精使用障碍识别测试，审计≥20）是：a） 横截面和b）与艾滋病毒+饮酒者之间的TMAO水平相关； 目标2：评估TMAO是否与该人群中的心脏功能和BNP有关；和 目标3：探索TMAO是否介导了酒精使用和亚临床HF风险的关联。 如果得到证实，我们的假设将确定对减少酒精的干预措施的生物标志物（TMAO） 艾滋病毒+饮酒者中相关的CVD风险。因为大量的酒精使用干预措施并非成功，所以 制定新的酒精治疗策略，以减少艾滋病毒+人中酒精的负面影响 需要。生物标志物及其代表的途径的识别（例如，营养不良）可能导致 干预研究的新目标并改善了艾滋病毒+饮酒者的CVD风险预测。