Profiling Cardiovascular Events and Biomarkers in the Very Old to Improve Personalized Approaches for the Prevention of Cardiac and Vascular Disease

尽管老年人发生心血管疾病(CVD)事件的绝对风险最高，但美国 胆固醇和血压指南建议对这种高强度、低侵袭性的患者进行治疗 风险人群基于有限的临床试验数据和潜在的更多副作用。当前的风险预测 等式不包括79岁的人，也不包括心力衰竭(HF)，这是一种更常见的疾病 比心肌梗塞或中风年龄更大的个体发生心血管事件。最近的试验表明， 老年高危参与者心血管疾病风险的绝对降低，强调了改善风险的必要性 评估，以便为治疗决策和有关治疗的患者-医生讨论提供信息。心脏 生物标志物已被证明可以识别高危个体，并改进对心力衰竭风险的预测 社区动脉粥样硬化风险(ARIC)研究中中年成年人的传统危险因素。在 建议的工作，我们将开发动脉粥样硬化性心血管疾病和心力衰竭的风险预测工具，为高龄老年人量身定做， 包括心脏生物标志物测量，以提供更全面的心血管疾病风险评估，并允许 更准确地评估治疗的潜在益处和风险，以及中年生活方式、人口统计、 以及导致心血管健康老化的临床因素。除了关于传统风险因素和 来自ARIC的心血管事件，我们建议测量心脏损伤、应激、纤维化和炎症的生物标记物 在参加最近一次访问的所有ARIC参与者中(访问5：2011年至2013年；大多数年龄≥70岁)和 即将到来的访问(访问6：N=4,214,2016-2017，大多数年龄为75岁的≥；访问7：N=3,827,2018-2019年)以解决 我们的目标：1：评估动脉粥样硬化性心血管疾病合并队列方程风险计算器的性能 开发一种改进的风险计算器，使用最好的循环生物标志物和风险 因素小组；2：量化和比较心力衰竭与动脉粥样硬化性心血管疾病的风险，开发风险预测工具 对于高龄成年人发生的心力衰竭，以及对心力衰竭、心肌梗死和中风的综合治疗工具 预防；3：找出导致“健康的心血管衰老”的主要中年因素，定义为 无临床心血管事件和心脏生物标志物升高。

Although older individuals have the highest absolute risk for cardiovascular disease (CVD) events, U.S. cholesterol and blood pressure guidelines recommend lower-intensity, less-aggressive treatment in this high- risk population based on limited clinical trial data and potential for more side effects. The current risk prediction equation does not include individuals aged >79 years, nor does it include heart failure (HF), a more common CVD event in older individuals than myocardial infarction or stroke. Recent trials have demonstrated greater absolute CVD risk reduction in older high-risk participants, underscoring the need for improved risk assessment to inform treatment decisions and patient–physician discussions regarding therapy. Cardiac biomarkers have been shown to identify higher-risk individuals and to improve HF risk prediction beyond traditional risk factors in middle-aged adults in the Atherosclerosis Risk in Communities (ARIC) Study. In the proposed work, we will develop risk prediction tools for atherosclerotic CVD and HF tailored for very old adults, including cardiac biomarker measurements, to provide more comprehensive CVD risk assessment and to allow more precise assessment of potential benefits and risks of therapy as well as midlife lifestyle, demographic, and clinical factors that lead to healthy cardiovascular aging. In addition to data on traditional risk factors and CVD events from ARIC, we propose to measure biomarkers of cardiac injury, stress, fibrosis, and inflammation in all ARIC participants who attended the most recent visit (visit 5: 2011–2013; most aged ≥70 years) and the upcoming visits (visit 6: n=4,214, 2016–2017, most aged ≥75 years; visit 7: n=3,827, 2018–2019) to address our aims: 1: To assess the performance of the Pooled Cohort Equation risk calculator for atherosclerotic CVD in very old adults and to develop an improved risk calculator using the best circulating biomarkers and risk factor panel; 2: To quantify and compare risk of HF versus atherosclerotic CVD, develop risk prediction tools for incident HF in very old adults and a comprehensive tool for HF, myocardial infarction, and stroke for primary prevention; 3: To identify major midlife factors leading to “healthy cardiovascular aging,” defined as the absence of clinical CVD events and elevated cardiac biomarkers.