Alcohol and Chronic Disease Among Vulnerable Populations

描述（由申请人提供）：在健康人群中，适度饮酒的好处是有据可查的。然而，超过750万的美国人是心肌梗死（MI）的幸存者，肥胖的流行导致了更大的血脂异常、高血压、低HDL-C和高血糖（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、医生和决策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）中的121,700名妇女（32,826名保存血液样本）和卫生专业人员随访研究（1986-2006年）中的51,529名男性（18,100名保存血液样本）中检查弱势群体中的酒精和慢性病。首先，我们将研究大约3345名女性和2835名男性确诊的非致死性心肌梗死患者的酒精摄入量和死亡风险。其次，我们将使用血脂异常和葡萄糖稳态异常的血液标志物，在一项嵌套病例对照（1:2）研究中，在提供血液样本并随后发展为冠心病的680名女性和534名男性中检测代谢综合征参与者的酒精和冠心病（CHD）。最后，由于所谓的饮酒益处主要归因于HDL-C的增加，我们将研究与调节HDL-C水平的基因中基因-酒精相互作用相关的冠心病风险。具体来说，酒精脱氢酶-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。大量保存有血液样本的女性和男性的研究为阐明酒精对高危患者的健康影响提供了绝佳的机会。此外，了解可能受益于酒精的人群（或高危人群）将有助于了解冠心病的病理生理学，并有助于为日益增长的冠心病高危人群和死亡率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.