Coronary Calcium Score Method and Cardiovascular Disease Events in Two Cohorts

描述(由申请人提供)：计算机断层扫描(CT)上的冠状动脉钙化(CAC)量提供了关于心血管疾病(CVD)风险状态的强大和增量信息，而不是标准的CVD风险因素。阿加斯顿方法是标准的CAC评分方法。对于给定的CAC体积，基于有选择地达到更高的CAC密度切入点，Agatston分数将增加2、3或4倍，从而为更大的CAC密度“增加”Agatston分数。然而，广泛的证据表明，钙化程度较高的冠状动脉斑块可能比钙化程度较低的斑块具有更低的心血管风险。例如，1)只有钙化斑块的人患心血管疾病的风险相对较低；2)不稳定型心绞痛患者的钙化斑块比稳定型心绞痛患者少，3)与安慰剂组相比，他汀类药物治疗可能会提高Agatston评分。在初步研究中，我们小组在两个大的队列中探讨了心血管疾病的风险，即动脉粥样硬化的多种族研究(MESA)和LifeScore研究。MESA和LifeScore的初步分析表明，忽略密度的体积分数比阿加斯顿分数对心血管事件的预测性略高。然后我们创建了一个密度分数，并表明在任何给定的CAC体积下，CAC密度实际上对未来的CVD事件具有保护作用。此外，在LifeScore中关于心血管疾病死亡的病例对照研究中，我们已经表明，在标准胸部CT上测量的简化的未加权分数，即序号分数，比阿加斯顿分数更好地预测，特别是在分数范围的较高端。为了从CT扫描中确定CAC的最佳评分系统，我们建议对MESA和LifeScore研究中的四个CAC评分系统进行比较。前两个分数将是上面讨论的体积分数和序数分数。另外两个分数将在MESA新开发，并在LifeScore中进行验证，两个分数都将采用“反向密度加权”。这两个分数被称为体积-2和序数-2分数，而不是像Agatston分数那样对密度较高的钙化斑块的分数进行“上调”，而是从经验上“下调”密度较大的斑块的CAC分数；也就是说，密度较低的斑块将产生较高的分数，而密度较高的斑块将产生较低的分数，这与Agatston方法相反。容积-2和序数-2评分还将考虑冠状动脉的数量和有CAC的特定冠状动脉。它们将在MESA进行经验开发，并在LifeScore中进行验证。然后，我们将根据风险比率、接收者操作特征曲线下的区域和净重新分类指数的强度和统计意义，比较这四个分数对心血管疾病的预测。最后，在LifeScore研究中，我们将比较心电门控心脏CT扫描和标准胸部CT扫描的分数计算结果。如果在标准胸部CT上测量的CAC与在心脏CT上测量的CAC一样可以预测心血管事件，那么CAC评估可能会变得更广泛、技术上更容易，并且使用更低的辐射剂量进行。

DESCRIPTION (provided by applicant): The amount of coronary artery calcium (CAC) on a computed tomography (CT) scan provides strong and incremental information as to cardiovascular disease (CVD) risk status beyond standard CVD risk factors. The Agatston method is the standard CAC scoring methodology. For a given CAC volume, the Agatston score is increased 2, 3, or 4 fold based on reaching selectively higher CAC density cutpoints, thus "upweighting" the Agatston score for greater CAC density. However, extensive evidence exists that densely calcified coronary plaques may pose a lower CVD risk than less densely calcified plaques. As examples, 1) persons who have only calcified plaques have a relatively low risk of CVD 2) patients with unstable angina have fewer calcified plaques than patients with stable angina, and 3) statin treatment may increase Agatston score compared to a placebo group. In preliminary studies, our group has explored CVD risk in two large cohorts, the Multi-ethnic Study of Atherosclerosis (MESA) and the LifeScore Study. Preliminary analyses in both MESA and LifeScore have shown that the volume score, which ignores density, was slightly more predictive than the Agatston score for CVD events. We then created a density score and have shown that CAC density is actually protective for future CVD events at any given CAC volume. In addition, in a case-control study of CVD death in LifeScore, we have shown that a simplified un-weighted score measured on standard chest CTs, the ordinal score, was a better predictor than the Agatston score, particularly at the higher end of the score range. In order to determine the optimal scoring system or systems for CAC from CT scans, we propose to compare four CAC scoring systems in both the MESA and the LifeScore Study. The first two scores will be the volume and ordinal scores discussed above. The other two scores will be newly developed in MESA and validated in LifeScore and both will employ "reverse density weighting". Rather than "upweighting" the score for more dense calcified plaque as the Agatston score does, these two scores, called the volume-2 and the ordinal-2 scores, will empirically "downweight" the CAC score for denser plaques; that is, less dense plaques will produce a higher score and denser plaques a lower score, the opposite of the Agatston method. The volume-2 and ordinal-2 scores will also consider the number of coronary arteries and the specific coronary arteries with CAC. They will be empirically developed in MESA and validated in LifeScore. We will then compare CVD prediction by these four scores in terms of the strength and statistical significance of the hazard ratios, the areas under Receiver Operating Characteristic curves, and the Net Reclassification Index. Finally, in the LifeScore study we will then compare the results when the scores are calculated on electrocardiographic gated cardiac CT scans vs. standard chest CT scans. If CAC measured on standard chest CTs is equally predictive of CVD events as CAC measured on cardiac CTs, CAC assessment could become more widely available, technically easier, and done with a lower radiation dose.