Alcohol and Atherosclerosis Pilot Study

描述(由申请人提供)：在观察性研究中，适度饮酒一直与较低的冠心病(CHD)风险有关。短期试验表明，酒精摄入对心血管风险因素(如高密度脂蛋白-胆固醇)具有潜在的有益影响，并且酒精可以抑制几种动物模型的动脉粥样硬化。然而，从未进行过饮酒超过几周的试验，在临床终点进行长期随机试验的可行性尚不确定。一种可以将这种随机试验的规模和持续时间降至最低的方法是评估酒精对放射定义的动脉粥样硬化进展的影响，这是一种具有相当表面有效性的替代结果。这种方法已经被证明给出了与更大的结果试验类似的结果，但需要更少的参与者和更短的观察期，并且具有更有利的风险/收益平衡。我们小组最近使用这种方法成功地进行了一项关于茶摄入量的类似试点研究。我们建议对长期饮酒对动脉粥样硬化的影响进行一项原则验证的初步研究。我们将招募40名55岁及以上的冠心病高危参与者，并将其随机分配到6个月的时间内，每天喝一杯150毫升的10%乙醇(相当于葡萄酒)或水。在基线和6个月后，我们将使用磁共振成像来评估主动脉和颈动脉粥样硬化，这是一种测量动脉斑块大小和管壁体积的准确和可重复性的方法。我们将通过几种方法确定依从性，包括血清标记物、饮食召回和对未使用的饮料的测量。这项可行性研究的主要结果将是酒精摄入的依从性和两项MRI检查。作为次要结果，我们将测量标准的和新的心血管风险标记物，包括炎症标记物和葡萄糖代谢的测量。我们将使用核磁共振波谱来评估酒精摄入对脂蛋白亚类分布的影响，以及对内皮功能的血清标记物的影响。我们将持续评估安全性，包括肝酶和血细胞计数的重复测试、简短的问卷调查和独立的DSMB。如果成功，这项先导性研究将为一项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，这本身可能建立起对酒精摄入和心血管事件发生的更大、更长期研究的可行性。我们建议进行一项试点研究，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可以预防心血管疾病，从而了解酒精对整个人群的全面健康影响的第一步。我们将随机选择40名55岁及以上的参与者，每天饮用1杯纯酒精(稀释到葡萄酒的强度)或水，为期6个月。在基线和6个月后，我们将测量血液中几个标准的和新的心血管风险标记物，并将进行磁共振成像来测量主动脉的动脉粥样硬化。

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.