Alcohol and Chronic Disease Among Vulnerable Populations

描述（由申请人提供）：在健康人群中，适度饮酒的益处已得到充分证明。然而，超过750万美国人是心肌梗死（MI）的幸存者，并且肥胖症的流行已经引起了甚至更大的具有血脂异常、高血压、低HDL-C和高血糖症（即代谢综合征）的不健康人群。酒精对这些“高危”人群预后的影响对于患者、医生和政策制定者做出明智的决策至关重要。我们建议在护士健康研究（1976 - 2006年）中对121 700名妇女（32 826名储存了血液样本）和卫生专业人员随访研究（1986-2006年）中的51 529名男子（18 100名储存了血液样本）进行酒精和慢性病的脆弱人群调查。首先，我们将研究酒精摄入量和死亡风险，估计有3，345名女性和2，835名男性确诊为非致命性MI事件。其次，使用血脂异常和血糖稳态异常的血液标志物，我们将在一项巢式病例对照（1：2）研究中检查代谢综合征参与者中的酒精和冠心病（CHD），该研究包括680名女性和534名男性，他们提供了血液样本，随后发展为CHD。最后，由于饮酒的益处主要归因于HDL-C升高，我们将研究与调节HDL-C水平的基因中的基因-酒精相互作用相关的CHD风险。具体而言，醇脱氢酶-3、肝脂肪酶、脂蛋白脂肪酶、胆固醇酯转运蛋白和内皮脂肪酶。具有良好特征的大量储存血液样本的女性和男性队列提供了一个无与伦比的机会来阐明酒精对高危患者健康的影响。此外，了解可能受益于酒精（或处于最大风险）的人群将有助于了解CHD的病理生理学，并有助于为日益增长的冠心病和死亡风险人群制定更完整的临床指南。

DESCRIPTION (provided by applicant): Among healthy populations, the benefits of moderate alcohol consumption are well documented. However, more than 7.5 million Americans are survivors of myocardial infarction (MI) and the epidemic of obesity has given rise to an even larger unhealthy population with dyslipidemia,hypertension, low HDL-C, and hyperglycemia (i.e. metabolic syndrome). The influence that alcohol has on prognosis among these "at risk" groups is crucial for informed decision-making by patients, physicians, and policy-makers. We propose to examine alcohol and chronic disease in vulnerable populations among 121,700 women (32,826 with stored blood samples) in the Nurses' Health Study (1976-2006) and 51,529 men (18,100 with stored blood samples) in the Health Professionals Follow-up Study (1986-2006). First, we will study alcohol intake and risk of mortality among an estimated 3,345 women and 2,835 men with confirmed incident non-fatal MI. Secondly, using blood markers of dyslipidemia and abnormal glucose homeostasis, we will examine alcohol and coronary heart disease (CHD) among participants with metabolic syndrome in a nested case control (1:2) study among the projected 680 women and 534 men who provided blood samples and subsequently developed CHD. Finally, because the purported benefit of alcohol consumption is attributed principally to increased HDL-C, we will examine CHD risk associated with gene-alcohol interactions in genes that modulate HDL-C levels. Specifically, alcohol dehydrogenase-3, hepatic lipase, lipoprotein lipase, cholesteryl ester transport protein, and endothelial lipase. The well characterized large cohorts of women and men with stored blood samples provide an unparalleled opportunity to elucidate the health effects of alcohol among high risk patients. Furthermore, knowledge of populations that may benefit from alcohol (or be at greatest risk) will help in the understanding of the pathophysiology of CHD and aid in the development of more complete clinical guidelines for the growing population of individuals at risk for coronary disease and mortality.