Inflammatory markers and improving CHD risk assessment

描述(由申请人提供)： 此应用程序响应RFA中提到的实验室、分析和协作组件。具体地说，我们建议利用现有的数据集和存储的生物标本，将流行病学风险因素信息与决策分析方法相结合，并在FHS、波士顿大学医学中心、波士顿大学数学系和塔夫茨大学人类营养老龄研究中心之间建立多学科合作。目的1.探讨同型半胱氨酸(THcy)(待测)、C反应蛋白(CRP)、脂蛋白(A)[Lp(A)](已测定)对冠心病(CHD)的预测作用。这些标记物的水平将通过嵌套病例队列设计来确定，利用一项基线检查，其中包括已经获得的关于弗雷明翰后代的传统风险因素的信息和心血管疾病事件的12年随访。高敏C反应蛋白的新测量将在弗雷明翰实验室进行，同型半胱氨酸将由雅各布·塞尔休博士在塔夫茨大学进行。目的2.检测新因素(tHcy、CRP和Lp[a])在不同水平的冠状动脉危险中的评估能力，单独使用传统危险因素，考虑冠状动脉事件的0-6%、6-20%和20%的初始风险。将估计新的风险测量方法用于预测在预先指定的绝对风险水平下冠状动脉事件的绝对风险增加的效用。目的3.开发新的冠心病风险预测方程，该方程将结合CRP和同型半胱氨酸的测量来评估冠心病的风险。这一目标将包括对第二代后代超过12年的冠心病风险的估计，并将纳入来自较老的第一代队列的数据，在这些队列中，已经测量了同型半胱氨酸和C反应蛋白，还可以对冠状动脉疾病事件进行12年的随访。

DESCRIPTION (provided by applicant): This application responds to laboratory, analytical, and collaborative components mentioned in the RFA. Specifically, we propose to integrate epidemiological risk factor information with a decision analytical approach, using existing data sets and stored biological specimens, and establishing a multidisciplinary collaboration between the FHS, Boston University Medical Center, Boston University Mathematics Department and the Tufts University Human Nutrition Research Center on Aging. Aim 1. To test the utility of homocysteine (tHcy) (to be measured), C-reactive protein (CRP) (to be measured), lipoprotein (a) [Lp(a] (already determined) as predictors of coronary heart disease (CHD) over and above traditional risk factor measures. Levels of these markers will be determined with a nested case cohort design, utilizing a baseline examination that includes already obtained information on conventional risk factors for the Framingham Offspring and 12 years of follow up for cardiovascular disease events. New measurements of hsCRP will be made in the Framingham laboratory and homocysteine will be done at Tufts University by Dr. Jacob Selhub. Aim 2. To test the ability of new factors (tHcy, CRP and Lp[a]) at different levels of coronary risk as assessed by using the traditional risk factors alone, considering 0-6%, 6-20% and >20% initial risk of a coronary event. The utility of newer risk measures to predict an increase in the absolute risk of coronary events at pre-specified absolute levels of risk will be estimated. Aim 3. To develop new CHD risk prediction equations that will incorporate CRP and homocysteine measurements to assess the risk of coronary heart disease. This aim will include estimates of CHD risk over 12 years for the second generation Offspring and will incorporate data from the older first generation cohort where homocysteine and CRP have already been measured and 12 years of follow up for coronary disease events is also available.