Cardioprotective Effects of Dietary Flavonoids in the Framingham Offspring Cohort

描述(申请人提供)：关于食物类黄酮类物质对心血管疾病风险的潜在影响，有很大的争议。这在一定程度上是因为，直到最近，还没有一个完整的食品类黄酮数据库，以及不同类别的类黄酮可能产生不同的影响。黄烷醇类药物(包括儿茶素和黄烷酮)具有降低心血管疾病风险的流行病学证据。黄酮类、黄酮醇类和异黄酮类的流行病学证据是可用的，尽管变量不同，但花青素和心血管风险之间的关联尚未被调查。本研究的目的是通过研究摄入不同种类的类黄酮与心血管疾病的各种中间标记物之间的关系，进一步了解膳食中类黄酮在心血管疾病中的作用。具体地说，我们将研究五类饮食类黄酮(黄烷醇、花青素、黄酮类、黄酮醇和异黄酮类)与下列心血管危险因素之间的关系：炎症标记物，包括C-反应蛋白、白介素6、单核细胞趋化蛋白-1和肿瘤坏死因子α；纤溶因子，包括纤维蛋白原和P-选择素；脂类，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(臂动脉反应性)评估内皮功能；以及血压。我们的假设是，黄烷醇类类黄酮(包括儿茶素、原花青素和黄烷酮)的摄入量越高，心血管疾病风险的中间标志物越健康。与黄烷醇相反，摄入其他类别的黄酮类(花青素、黄酮类、黄酮醇和异黄酮类)并不像中间生物标志物所表明的那样与较低的心血管疾病风险密切相关。我们计划使用之前从Framingham心脏研究后代队列第七次检查中收集和测量的数据来检验这一假设。与弗雷明翰研究人员合作，我们将把增强和更新的类黄酮类数据库与通过食物频率问卷收集的饮食信息联系起来。每种食物的类黄酮量将被输入问卷上每一项的数据库中。扩展的数据库将允许对类黄酮摄入量进行比以前更全面的评估。应该指出的是，研究调查人员在向其他食物频率问卷中添加类黄酮方面拥有丰富的经验，因此我们预计完成这一任务不会有任何问题。该项目为研究类黄酮类化合物与心血管疾病风险之间的潜在关系提供了一种有效的手段。有证据表明，某些类黄酮含量较高的食物与心血管疾病的代谢风险因素更好相关，但几乎所有与类黄酮有关的人类证据都是基于对含有类黄酮的食物的研究，而不是类黄酮摄入量。因此，这一证据可能会被富含类黄酮的食物的其他成分混淆。这项拟议的研究应该有助于澄清关于类黄酮对心血管疾病风险的影响的争议和困惑，通过研究特定类黄酮的饮食摄入量与心血管疾病的代谢危险因素之间的关系。

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.