Quantifying cardiovascular calcification at very old age for personalized risk classification

摘要：量化高龄患者的心血管钙化以进行个性化风险分类 预测风险是动脉粥样硬化性心血管疾病一级预防决策的核心 （ASCVD）。然而，对≥75岁的老年人进行风险分类仍然极具挑战性。通过放置重 根据年龄加权，现有的风险预测模型普遍分配高风险状态，因此建议 几乎所有老年人的治疗，引起了人们对过度用药，药物相互作用和缺乏治疗的担忧。 个性化。其他疾病引起的死亡率和发病率的竞争风险（例如，癌症，肺病， 和痴呆症）是这一人群的另一个问题，需要在预防心血管疾病和 准确的风险预测与其他合并症的管理。不幸的是，这种准确的风险预测 在老年人中一次性评估传统的心血管危险因素是无法实现的， 这一方法并不包括累积的终生接触和个人的易感性。 在这种情况下，冠状动脉钙（CAC）是有前途的，因为它直接量化了累积的 暴露和个人对风险因素的易感性。事实上，高CAC分数是最有效的方法之一， ASCVD的预测因子。最近，零和低CAC已被证明是有用的“去风险”，确定 绝对风险低的个体，预防性治疗可能不会产生净效益。最近 研究还表明冠状动脉外钙（ECC）（即，主动脉根/瓣膜、二尖瓣环和胸主动脉 在常规CAC扫描上检测到的主动脉）提供了CAC以外的风险信息。然而，患病率和 非常年老的成年人中CAC和ECC的预后数据令人惊讶地稀少。因此，我们建议执行 动脉粥样硬化风险研究中约3，100名参与者的非对比心脏门控计算机断层扫描， 在2017-19年即将到来的访问期间进行社区（ARIC）研究，并制定专门的CVD风险 纳入CAC和ECC的≥75岁老年人分类工具。为了最大限度地利用我们的 心血管疾病风险分类工具，我们将开发结合我们的预测模型和患者 两个代表性方案的偏好，预防性他汀类药物和阿司匹林药物治疗。 目的1：建立75岁及以上人群心血管疾病风险的风险分类模型。 目的2：评价30年累积暴露与CAC/ECC之间的相互作用，以评估 健康的血管老化（例如，低或零CAC）和CVD预后的估计。 目的3：评价预防性治疗偏好和基于CAC/ECC的风险信息对 ≥75岁成人预防性药物治疗的获益和危害平衡。 该项目将根据已确定的风险因素为CVD提供准确的风险分类工具， CAC/ECC适用于75岁及以上人群。30年累积风险因素暴露与 CAC/ECC将具有临床和生物学价值。我们的获益-危害图表将直接告知基于证据的 75岁及以上老年人在CVD一级预防方面的共同决策。

ABSTRACT: Quantifying cardiovascular calcification at very old age for personalized risk classification Predicted risk is central to decision-making in primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, classifying risk in older adults ≥75 years remains extremely challenging. By placing heavy weight on age, existing risk prediction models universally assign high risk status and therefore recommend treatment for nearly all older adults, raising concerns about overmedication, drug-drug interactions, and lack of personalization. Competing risk of mortality and morbidity due to other conditions (e.g., cancer, lung disease, and dementia) is another issue in this population, requiring a fine balance between prevention of CVD based on accurate risk prediction vs. management of other comorbidities. Unfortunately, such accurate risk prediction is not achievable with one-time assessment of traditional cardiovascular risk factors at older ages because this approach does not capture cumulative lifetime exposures and individuals' susceptibility. In this context, coronary artery calcium (CAC) is promising, as it directly quantifies a composite of cumulative exposure and an individual's susceptibility to risk factors. Indeed, a high CAC score is one of the most potent predictors of ASCVD. Recently, zero and low CAC has been shown to be useful for “de-risking”, identifying individuals who are at low absolute risk in whom preventive therapy may not result in net benefit. Recent studies also demonstrate that extra-coronary calcium (ECC) (i.e., aortic root/valve, mitral annulus, and thoracic aorta) detected on a routine CAC scan provides risk information beyond CAC. However, prevalence and prognostic data for CAC and ECC among very old adults are surprisingly sparse. Thus, we propose to perform non-contrasted cardiac-gated computed tomography among ~3,100 participants in the Atherosclerosis Risk in Communities (ARIC) Study during forthcoming visits between 2017-19 and to develop a dedicated CVD risk classification tool incorporating CAC and ECC for older adults ≥75 years. To maximize the usefulness of our CVD risk classification tool, we will develop benefit-harm charts incorporating our prediction models and patient preferences for two representative scenarios, preventive statin and aspirin pharmacotherapy. Aim 1: To develop risk classification models for CVD risk in the 75-and-older population. Aim 2: To evaluate the interplay between 30-year cumulative exposures and CAC/ECC for assessment of healthy vascular aging (e.g., low or zero CAC) and estimation of CVD prognosis. Aim 3: To evaluate the effect of preventive treatment preferences and CAC/ECC-based risk information on the balance of benefits and harms of preventive pharmacotherapy in adults ≥75 years of age. This project will deliver accurate risk classification tools for CVD based on established risk factors and CAC/ECC for the 75-and-older population. The comparison of 30-year cumulative risk factor exposures vs. CAC/ECC will be of value clinically and biologically. Our benefit-harm charts will directly inform evidence-based shared decision-making in the context of primary prevention of CVD among older adults aged 75 and older.