Optimize Risk Assessment for Incident and Recurrent Atherosclerotic Cardiovascular Disease

最近的美国心脏协会(AHA)和美国心脏病学会(ACC)的胆固醇指南 将动脉粥样硬化性心血管疾病(ASCVD)风险评估置于 启动和剂量降脂治疗，包括他汀类药物、依折麦布和PCSK9抑制剂。 尽管如此，关于该指南如何有效地将药物引导到那些 世卫组织将获得一大笔ASCVD风险降低的绝对好处。对于初级预防，2018年AHA/Access 指引引入了风险提升因素的概念，以识别风险高于 由集合队列方程(PCE)预测。风险增加因素的存在支持决定 对处于边缘和中等风险的患者启动或加强他汀类药物治疗。然而，指导方针确实做到了 不量化风险增加因素在多大程度上改变个人10年的风险，做出治疗的决定 治疗或不知情的风险增加因素最终是主观的。健康的社会决定因素 (SDOH)是ASCVD的重要危险因素。PCE系统性地低估了以下个人的风险 社会上被剥夺的；然而，SDOH不包括在PCE中，或被视为 目前的指导方针。此外，PCE的表现在拉美裔和亚裔中是有问题的 美国增长最快的少数族裔群体。对于二级预防，2018年指南建议高- 用依折麦布和PCSK9强化他汀类药物治疗2400万美国成年ASCVD患者 推荐用于ASCVD复发风险非常高的子集的抑制剂，其定义为多发性 重大ASCVD事件或一个具有多个高危条件的重大事件。然而，最近的证据表明， 这一定义可能会将太多的个人(&gt；50%)归类为具有非常高的风险。此外，女性， 少数族裔和SDOH阴性的人ASCVD复发的风险更高，但那些 目前的指南在定义非常高的ASCVD复发风险时没有考虑这些因素。 为了解决文献和指南中的这些差距，我们的研究建议1)量化 每个风险增加因素(包括SDOH、西班牙裔和亚洲亚群)的存在或不存在 它们的组合改变了PCE预测之外的10年ASCVD风险；2)确定了 优化对复发ASCVD事件的高危个体的识别；以及3)比较 选择降脂个体对美国成年人的健康、经济和健康公平的影响 根据目标1和2中确定的方法与2018年胆固醇指南中确定的方法进行治疗。 这项研究将开发提高美国成年人胆固醇治疗指南精确度的方法， 并帮助直接治疗有不良SDOH高负担的种族亚群和群体，他们有 ASCVD风险很高，但根据当前的国家胆固醇指南，可能不建议进行治疗。发现 这项研究将为未来的指导方针提供参考，改善心血管结果，缩小健康不平等的范围。

Recent American Heart Association (AHA) and American College of Cardiology (ACC) cholesterol guidelines put atherosclerotic cardiovascular disease (ASCVD) risk assessment at the center of decision-making for initiating and dosing of lipid-lowering therapies including statins, ezetimibe, and PCSK9 inhibitors. Nonetheless, there remains controversy regarding how efficiently this guideline directs medication to those who will receive a large absolute ASCVD risk reduction benefit. For primary prevention, the 2018 AHA/ACC guideline introduced the concept of risk-enhancing factors to identify individuals who have a risk higher than predicted by the pooled cohort equations (PCE). The presence of risk-enhancing factors supports a decision to initiate or intensify statin therapy in patients with borderline and intermediate risk. However, the guideline did not quantify how much a risk-enhancing factor changes an individual's 10-year risk, making decisions to treat or not to treat informed by the risk-enhancing factors ultimately subjective. Social determinants of health (SDOH) are important ASCVD risk factors. The PCE systematically underestimates risk for individuals who are socially deprived; however, SDOH are not included in the PCE or considered as risk-enhancing factors in the current guidelines. Additionally, the PCE's performance is questionable in Hispanics and Asians, the two fastest growing minority groups in the US. For secondary prevention, the 2018 guideline recommends high- intensity statin therapy for the 24 million US adults with established ASCVD, with ezetimibe and PCSK9 inhibitors recommended for a subset with a very high risk for recurrent ASCVD, defined by a history of multiple major ASCVD events or one major event with multiple high-risk conditions. However, recent evidence suggests that this definition may classify too many individuals (>50%) as having very high risk. Additionally, women, racial/ethnic minorities, and those with adverse SDOH may have a higher risk for recurrent ASCVD, but those factors were not considered in the current guideline when defining very high risk of recurrent ASCVD. To address these gaps in the literature and guidelines, our study proposes to 1) quantify how much the presence or absence of each risk-enhancing factor (including SDOH and Hispanic and Asian subgroups) and their combinations change 10-year ASCVD risk beyond PCE predictions; 2) determine the algorithm that optimizes the discrimination of individuals at very high risk for a recurrent ASCVD event; and 3) compare the health, economic, and health equity impact among US adults of selecting individuals for lipid-lowering therapies according to approaches identified in Aims 1 and 2 vs. in the 2018 cholesterol guideline. This study will develop approaches that improve the precision of cholesterol treatment guidelines in US adults, and help direct treatment to ethnic subgroups and groups with a high burden of adverse SDOH who have a high ASCVD risk but may not be recommended treatment by current national cholesterol guidelines. Findings from this study will inform future guidelines, improve cardiovascular outcomes, and narrow health inequities.