Dietary Etiologies of Heart Disease and Cancer

描述(由申请人提供)：我们建议在1986年继续对51,529名年龄在40岁至75岁之间的男性健康专业人员进行两年一次的心血管疾病随访，以解决一系列与冠心病和中风风险有关的新饮食假设。我们预计在随访期结束时会有超过4,000例突发心肌梗死、致命的冠心病和中风病例。在这个队列中，超过18,000名参与者在1994年提供了血液样本，我们建议从这些样本中调查疾病的几个生物学(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相关的几个假设。有了这一特殊的资源，反复评估饮食和生活方式特征与潜在的疾病遗传标记物相关，我们将前瞻性地评估1)来自鱼类和蔬菜的各种n-3脂肪酸摄入量中的n-6脂肪酸，2)高血糖负荷的食物，尤其是BMI&GT；25 kg/m^2)蛋白质摄入量作为碳水化合物的替代品，以及4)被认为是胰岛素靶标的候选基因的可能功能变异和单倍型。在这个代谢领域，我们试图确定生活方式实践，如体力活动或低血糖负荷饮食是否可以改变潜在的遗传风险。为了进一步研究饮食对冠心病介质的影响，我们将研究a)n-3和n-6脂肪酸之间的相互作用对心血管疾病炎症危险因素的影响，b)血糖负荷对脂联素的影响，以及这种脂肪细胞来源的细胞因子对心肌梗死和致死性冠心病风险的相关风险。此外，我们还建议进一步研究卒中的目标1-3。最后，在一个小的探索性目标内，我们建议通过利用我们设计的研究冠心病的创新方法来记录充血性心力衰竭的基本危险因素。正在进行的卫生专业人员跟踪研究将提供对非心血管疾病终点(CA55075)的跟踪，以及关于拟议研究的重要协变量的信息。总体而言，未来队列的庞大规模、高随访率、对饮食和生活方式信息的重复评估以及可获得的存档血液，为检验与心血管疾病风险相关的假设提供了一个独特的经济高效的机会。

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.