Alcohol and Atherosclerosis Pilot Study

酒精与动脉粥样硬化初步研究

• 批准号: 7385807
• 负责人: KENNETH Jay MUKAMAL
• 金额: $ 22.76万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-05 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7385807
• 关键词: Adherence; Alcohol consumption; Alcohols; Animal Model; Animals; Aorta; Atherosclerosis; Benefits and Risks; Beverages; Blood; Cardiovascular Diseases; Cardiovascular system; Carotid Atherosclerotic Disease; Clinical; Clinical Trials; Consumption; Coronary heart disease; Count; Daily; Data; Development; End Point; Enzymes; Epidemiologic Studies; Equilibrium; Ethanol; Event; Face; Fasting; Feasibility Studies; Genetic; Glass; Glucose; Glycosylated hemoglobin A; Grant; Health; High Density Lipoprotein Cholesterol; Hormones; Individual; Inflammatory; Intake; Intercellular adhesion molecule 1; Interleukin-6; Link; Lipoproteins; Liver; Long-Term Effects; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Methods; NIH Program Announcements; NMR Spectroscopy; National Institute on Alcohol Abuse and Alcoholism; Numbers; Observational Study; Outcome; Outpatients; Participant; Patients; Pilot Projects; Platelet Count measurement; Population; Postmenopause; Prevention program; Prevention strategy; Public Health; Questionnaires; Randomized; Randomized Controlled Clinical Trials; Recruitment Activity; Research; Research Project Grants; Risk; Risk Marker; Safety; Secondary Prevention; Serum Markers; Standards of Weights and Measures; Supplementation; Tea; Testing; Translating; Vascular Cell Adhesion Molecule-1; Vitamin E; Water; Week; White Blood Cell Count procedure; Wine; adiponectin; aged; alcohol effect; base; cardiovascular disorder risk; cardiovascular risk factor; day; design; drinking; glucose metabolism; hazard; human study; mortality; novel; prevent; size; success

DESCRIPTION (provided by applicant): Moderate alcohol consumption has been consistently linked to a lower risk of coronary heart disease (CHD) in observational studies. Short-term trials have shown that alcohol intake has potentially beneficial effects on cardiovascular risk factors, such as HDL-cholesterol, and alcohol inhibits aortic atherosclerosis in several animal models. However, no trial of alcohol intake longer than several weeks has ever been conducted, and the feasibility of a long-term randomized trial on clinical endpoints is uncertain. One approach that could minimize the size and duration of such a randomized trial would be to assess the effect of alcohol on progression of radiologically-defined atherosclerosis, a surrogate outcome with substantial face validity. Such an approach has been shown to give similar results as much larger outcome trials, yet would require fewer participants and a shorter period of observation and have a more favorable risk/benefit balance. Our group recently used this approach to conduct a successful similar pilot study of tea intake. We propose a proof-of-principle pilot study of the effect of longer-term alcohol intake on atherosclerosis. We will recruit and randomize 40 participants aged 55 and older at high risk for CHD to a six-month period of consumption of a single 150 ml glass per day of either 10% ethanol (approximating wine) or water. At baseline and after 6 months, we will assess both aortic and carotid atherosclerosis using magnetic resonance imaging, an accurate and reproducible method for measurement of arterial plaque size and wall volume. We will determine adherence in several ways, including serum markers, dietary recalls, and measurement of unused beverage. The primary outcomes in this feasibility study will be compliance with alcohol intake and the two MRI examinations. As secondary outcomes, we will measure standard and novel cardiovascular risk markers, including inflammatory markers and measures of glucose metabolism. We will assess the effects of alcohol intake on lipoprotein subclass distribution, using NMR spectroscopy, and on serum markers of endothelial function. We will assess safety on a continual basis, including repeated testing of liver enzymes and blood counts, short-form questionnaires, and an independent DSMB. If successful, this pilot study will form the basis for a more definitive trial to determine the effect of alcohol intake on progression of atherosclerosis, which could itself establish the feasibility of even larger, longer- term studies of alcohol intake and occurrence of cardiovascular events. We propose a pilot study to determine the feasibility of a long-term clinical trial of alcohol intake on atherosclerosis, the first step in determining whether moderate drinking prevents cardiovascular disease and hence in understanding the full health effects of alcohol across the population. We will randomize 40 participants aged 55 and older to a six-month period of consumption of 1 glass per day of either pure alcohol (diluted to the strength of wine) or water. At baseline and after 6 months, we will measure several standard and novel cardiovascular risk markers in the blood and will perform magnetic resonance imaging to measure atherosclerosis of the aorta.

描述（由申请人提供）：在观察性研究中，适度饮酒一直与较低的冠心病风险相关。短期试验表明，酒精摄入对心血管危险因素有潜在的有益影响，如高密度脂蛋白胆固醇，酒精在几种动物模型中抑制主动脉粥样硬化。然而，从未进行过超过几周的酒精摄入试验，并且在临床终点上进行长期随机试验的可行性尚不确定。一种可以将此类随机试验的规模和持续时间最小化的方法是评估酒精对放射学定义的动脉粥样硬化进展的影响，这是一种具有实际有效性的替代结果。这种方法已被证明与更大规模的试验结果相似，但需要更少的参与者和更短的观察时间，并且具有更有利的风险/收益平衡。我们的小组最近用这种方法成功地进行了一个类似的关于茶摄入量的试点研究。我们建议对长期饮酒对动脉粥样硬化的影响进行原则性初步研究。我们将随机招募40名年龄在55岁及以上的冠心病高危人群，让他们在6个月的时间里每天喝一杯150毫升的10%乙醇（近似葡萄酒）或水。在基线和6个月后，我们将使用磁共振成像评估主动脉和颈动脉粥样硬化，这是一种精确且可重复的测量动脉斑块大小和壁体积的方法。我们将通过几种方式确定依从性，包括血清标志物、饮食召回和未使用饮料的测量。这项可行性研究的主要结果将是酒精摄入的依从性和两次MRI检查。作为次要结局，我们将测量标准的和新的心血管危险指标，包括炎症指标和葡萄糖代谢指标。我们将评估酒精摄入对脂蛋白亚类分布的影响，使用核磁共振波谱和内皮功能的血清标志物。我们将在持续的基础上评估安全性，包括重复测试肝酶和血细胞计数，简短的问卷调查和独立的DSMB。如果成功，该初步研究将为更明确的试验奠定基础，以确定酒精摄入对动脉粥样硬化进展的影响，这本身就可以建立更大规模、更长期的酒精摄入和心血管事件发生研究的可行性。我们提出了一项初步研究，以确定酒精摄入对动脉粥样硬化的长期临床试验的可行性，这是确定适度饮酒是否能预防心血管疾病的第一步，从而了解酒精对整个人群的健康影响。我们将随机抽取40名年龄在55岁及以上的参与者，让他们在六个月的时间里每天喝一杯纯酒精（稀释到葡萄酒的浓度）或水。在基线和6个月后，我们将测量血液中几种标准的和新的心血管危险标志物，并将进行磁共振成像来测量主动脉动脉粥样硬化。