Dietary Etiologies of Heart Disease and Cancer

描述（由申请人提供）：我们建议继续对1986年年龄在40至75岁之间的51，529名男性健康专业人员进行心血管疾病的两年一次的随访，以解决一系列与冠心病和中风风险相关的新饮食假设。我们预计到随访期结束时，将有超过4，000例心肌梗死、致死性冠心病和中风病例。嵌套在这个队列中，超过18，000名参与者在1994年提供了血液样本，我们建议从中研究疾病的几个生物学（血浆和遗传）决定因素。我们将集中讨论与心血管疾病（CVD）的营养和遗传决定因素有关的几个假设。有了这种对与潜在疾病遗传标志物相关的饮食和生活方式特征进行重复评估的特殊资源，我们将前瞻性地评估1）来自鱼类和蔬菜来源的广泛n-3脂肪酸摄入中的n-6脂肪酸与冠心病的关系，2）具有高血糖负荷的食物，特别是在BMI > 25 kg/m^2的男性中，3）蛋白质摄入作为碳水化合物的替代物，以及4）被认为是胰岛素靶点的候选基因中的推定功能变体和单倍型。在这个代谢领域，我们试图确定生活方式的做法，如体育活动或低血糖负荷饮食可以改变潜在的遗传风险。为了进一步研究饮食对CHD介质的影响，我们将研究a）n- 3和n-6脂肪酸对CVD的炎症风险因子之间的相互作用和B）脂联素的血糖负荷以及该脂肪细胞衍生的细胞因子对MI和致死性CHD风险的相关风险。此外，我们建议进一步审查目标1-3关于中风的问题。最后，在一个小的探索性目标，我们建议文件的基本危险因素，充血性心力衰竭，利用创新的方法，我们设计的研究冠心病。正在进行的卫生专业人员随访研究将提供非CVD终点（CA 55075）的随访以及拟定研究的重要协变量信息。总体而言，前瞻性队列的大规模，高随访率，饮食和生活方式信息的重复评估，以及存档血液的可用性，为验证与CVD风险相关的假设提供了独特的成本效益机会。

DESCRIPTION (provided by applicant): We propose to continue the biennial follow-up of cardiovascular disease among 51,529 male health professionals, age 40 to 75 years in 1986, to address a series of new dietary hypotheses related to risk of a coronary heart disease and stroke. We project over 4,000 incident MI, fatal CHD, and stroke cases through the end of the follow-up period. Nested within this cohort, over 18,000 participants provided blood samples in 1994 from which we propose to investigate several biological (plasma and genetic) determinants of disease. We will concentrate on several hypotheses related to nutritional and genetic determinants of cardiovascular disease (CVD). With this exceptional resource of repeated assessments of diet and lifestyle characteristics tied to potential genetic markers of disease, we will prospectively evaluate in relation to coronary heart disease 1) n-6 fatty acids across a wide range of n-3 fatty acid intake from fish and vegetable sources, 2) foods with a high glycemic load, specifically among men with a BMI > 25kg/m^2, 3) protein intake as a replacement for carbohydrate, and 4) putative functional variants and haplotypes in candidate genes thought to be insulin targets. Within this metabolic domain we seek to determine if lifestyle practices such as physical activity or a low glycemic load diet can modify underlying genetic risk. To investigate further the effect of diet on mediators of CHD we will investigate a) the interaction between n- 3 and n-6 fatty acids on inflammatory risk factors for CVD and b) glycemic load on adiponectin and the associated risk of this adipocyte-derived cytokine on risk of MI and fatal CHD. Also, we propose further to examine aims 1-3 with respect to stroke. Finally, within a small exploratory aim, we propose to document basic risk factors for congestive heart failure by utilizing the innovative methods we designed to study coronary heart disease. The ongoing Health Professionals Follow-up Study will provide follow-up of non-CVD endpoints (CA55075) in addition to information on important covariates for the proposed study. Overall, the large size of the prospective cohort, the high follow-up rate, the repeated assessment of dietary and lifestyle information, and the availability of archived bloods provide a unique cost-effective opportunity to test hypotheses related to CVD risk.