Alcohol and Atherosclerosis Pilot Study

描述（由申请人提供）：在观察性研究中，适度饮酒一直与冠心病（CHD）风险较低相关。短期试验表明，酒精摄入对心血管危险因素（如HDL-胆固醇）具有潜在的有益作用，酒精在几种动物模型中抑制主动脉粥样硬化。然而，还没有进行过超过几周的酒精摄入试验，并且对临床终点进行长期随机试验的可行性尚不确定。一种可以最大限度地减少这种随机试验的规模和持续时间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，这是一种具有实质性表面有效性的替代结果。这种方法已被证明与更大规模的结局试验具有相似的结果，但需要更少的参与者和更短的观察期，并具有更有利的风险/获益平衡。我们小组最近使用这种方法进行了一项成功的类似的茶摄入量试点研究。我们提出了一项关于长期酒精摄入对动脉粥样硬化影响的原理性初步研究。我们将招募40名年龄在55岁及以上的冠心病高危受试者，并将其随机分配至6个月内，每天饮用150 ml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，磁共振成像是测量动脉斑块大小和壁体积的准确和可重复的方法。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。本可行性研究的主要结局将是饮酒和两次MRI检查的依从性。作为次要结局，我们将测量标准和新的心血管风险标志物，包括炎症标志物和葡萄糖代谢指标。我们将评估酒精摄入对脂蛋白亚类分布的影响，使用核磁共振光谱，并对内皮功能的血清标志物。我们将持续评估安全性，包括重复检测肝酶和血细胞计数、简短问卷和独立的DSMB。如果成功，这项初步研究将形成一个更明确的试验的基础，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，更长期的酒精摄入和心血管事件发生研究的可行性。我们提出了一个试点研究，以确定长期临床试验的可行性，酒精摄入量对动脉粥样硬化，第一步，以确定是否适度饮酒预防心血管疾病，从而了解整个人群的酒精对健康的影响。我们将40名年龄在55岁及以上的参与者随机分为6个月，每天饮用1杯纯酒精（稀释到葡萄酒的强度）或水。在基线和6个月后，我们将测量血液中的几种标准和新的心血管风险标志物，并进行磁共振成像以测量主动脉粥样硬化。

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.