Cardioprotective Effects of Dietary Flavonoids in the Framingham Offspring Cohort

描述（由申请人提供）：关于食物类黄酮对心血管疾病风险的潜在影响存在很大争议。这在一定程度上是由于直到最近还没有一个完整的食物类黄酮数据库，以及各种类黄酮的潜在差异效应。一些流行病学证据表明，黄烷醇类（包括儿茶素和黄烷酮）可降低心血管疾病的风险。流行病学证据是可用的，虽然变量，黄酮类，黄酮醇和花青素类之间的关联和心血管风险尚未调查。本研究的目的是通过研究不同类黄酮的摄入量与心血管疾病的各种中间标志物之间的关系，进一步了解膳食类黄酮在心血管疾病中的作用。具体来说，我们将研究五类膳食类黄酮之间的关联（黄烷醇、花青素、黄酮、黄酮醇和异黄酮）和以下CVD风险因子：炎症标志物，包括C-反应蛋白、白细胞介素6、单核细胞趋化蛋白-1和肿瘤坏死因子α;纤维蛋白溶解因子，包括纤维蛋白原和P-选择素;脂质，包括高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、总胆固醇和甘油三酯;通过血流介导的扩张（肱动脉反应性）评估的内皮功能;和血压。我们的假设是，黄烷醇类黄酮（包括儿茶素，原花青素和黄烷酮）的摄入量较高与心血管疾病风险的中间标志物的健康状况有关。与黄烷醇相反，其他类黄酮类化合物（花青素、黄酮、黄酮醇和黄酮类化合物）的摄入量预计不会像中间生物标志物所示的那样与较低的CVD风险密切相关。我们计划使用先前收集的和测量的数据来检验这一假设，这些数据来自心脏病研究后代队列的第七次检查。与Fragrance研究人员合作，我们将把增强和更新的类黄酮数据库与食物频率问卷收集的饮食信息联系起来。每种食物类黄酮的量将被输入数据库中的问卷上的每个项目。扩展的数据库将允许比以前更全面地评估类黄酮摄入量。应该注意的是，研究人员在将类黄酮添加到其他食物频率问卷中方面有丰富的经验，因此我们预计完成这项工作不会有问题。该项目提供了一种有效的方法来研究黄酮类化合物与心血管疾病风险之间的潜在关系。有证据表明，某些类黄酮含量高的食物与心血管疾病的代谢风险因素有关，但几乎所有将类黄酮与心血管疾病风险相关的人类证据都是基于对含类黄酮食物的研究，而不是类黄酮摄入量。因此，这一证据可能会被富含类黄酮食物的其他成分所混淆。这项拟议中的研究应有助于澄清的争议和混乱的影响，类黄酮类化合物对心血管疾病的风险，通过检查之间的关系，膳食摄入特定的类黄酮类化合物和心血管疾病的代谢危险因素。

DESCRIPTION (provided by applicant): There is a great deal of controversy about the potential effects of food flavonoids on cardiovascular disease risk. This is, in part, a consequence of the absence, until recently, of a complete food flavonoid database and the potential for differential effects of the various classes of flavonoids. Some epidemiological evidence of cardiovascular disease risk reduction is available for the flavanol class (including catechins and flavanones). Epidemiological evidence is available, though variable, for the flavone, flavonol and isoflavone classes whereas associations between the anthocyanins and cardiovascular risk have not been investigated. The goal of the present study is to further our understanding of the role of dietary flavonoids in cardiovascular disease by examining the relation between intake of the different flavonoid classes and various intermediate markers of cardiovascular disease. Specifically, we will examine the associations between five classes of dietary flavonoids (flavanols, anthocyanins, flavones, flavonols, and isoflavones) and the following CVD risk factors: inflammatory markers including C-reactive protein, interleukin 6, monocyte chemoattractant protein-1, and tumor necrosis factor alpha; fibrinolytic factors including fibrinogen and P-selectin; lipids including high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, and triglycerides; endothelial function by assessed by flow mediated dilation (brachial artery reactivity); and blood pressure. Our hypothesis is that a higher intake of the flavanol class of flavonoids (which includes the catechins, proanthocyanidins, and flavanones) is associated with a healthier profile of intermediate markers of cardiovascular disease risk. In contrast to the flavanols, intakes of other classes of flavonoids (anthocyanins, flavones, flavonols, and isoflavonoids) are not expected to be as strongly associated with lower CVD risk as indicated by intermediate biomarkers. We plan to examine this hypothesis using previously collected and measured data from the seventh examination of Framingham Heart Study Offspring Cohort. Working with the Framingham investigators, we will link an enhanced and updated flavonoid database to dietary information collected with a food frequency questionnaire. Amounts of each food flavonoid will be entered in a database for each item on the questionnaire. The extended database will allow more complete assessment of flavonoid intakes than has previously been possible. It should be noted that the study investigators have extensive experience with addition of flavonoids to other food frequency questionnaires, and therefore we anticipate no problems in accomplishing this. The proposed project presents an efficient and effective means to examine the potential relationship between flavonoids and cardiovascular disease risk. There is evidence that foods high in certain flavonoids are associated with better metabolic risk factors for cardiovascular disease, but almost all of the human evidence relating flavonoids to cardiovascular disease risk is based on studies of flavonoid-containing foods, not flavonoid intake. Consequently, this evidence may be confounded by other components of flavonoid-rich foods. This proposed research should help to clarify the controversy and confusion about the influence of flavonoids on cardiovascular disease risk by examining the relation between dietary intake of specific flavonoids and metabolic risk factors for cardiovascular disease.