Improving Lipid Management Strategies in Young Adults

低密度脂蛋白胆固醇（LDL-C）是动脉粥样硬化的一个致病因素 心血管疾病（ASCVD），降脂治疗可以显着降低这种风险。然而，何时开始开始 降脂治疗还没有被很好地理解。尽管美国年轻人的ASCVD发病率不断上升， 在过去的二十年中，18-39岁的成年人中，降脂治疗的使用率仍然很低，<7%的 接受治疗的LDL-C ≥160 mg/dL的年轻成人（与年龄≥40岁的患者中约50%相比）。据估计 52%的美国年轻成人非最佳LDL-C ≥100 mg/dL，7%的人LDL-C ≥160 mg/dL。但 很少有证据可以指导年轻人的血脂管理。关于风险评估，现行准则 建议使用汇总队列方程（PCE）估计10年ASCVD风险，以指导降脂治疗 疗法然而，PCE可能不直接适用于年轻人，因为它们是在40岁以下的成年人中开发的。 75岁。为了解决这个问题，目前的指导方针鼓励估计30年或寿命 年轻成人的ASCVD风险;然而，这些现有的终生风险算法来自单一队列 非西班牙裔白人，这可能会限制其适用于其他人群，并已被确定为一个 受现行指导方针的限制。此外，健康的社会决定因素（SDOH）和其他风险增强因素 已知会增加ASCVD风险的药物未纳入当前的风险评估中。对于脂质管理， 年轻人开始降脂治疗的益处和危害尚不清楚， 老年人的试验数据。尽管ASCVD硬结局的随机试验将提供明确的 证据表明，由于成本高和随访时间长，在年轻人中进行此类试验可能不可行 需要时间。在缺乏试验的情况下，高质量的观察和模拟研究可以提供临床 为决策者、患者和临床医生提供相关和可操作的证据。 为了解决这些差距，我们建议对来自4项队列研究（CARDIA， Frachial，HCHS/SOL，JHS）和Kaiser Permanente Southern加州（1）改善ASCVD风险 通过使用当代和不同人群的数据评估年轻人的准确性，（2）量化 通过模拟一项使用大规模的临床试验， 观察性数据库和最先进的统计模型，以尽量减少混淆和选择偏倚，以及 (3)比较替代血脂管理对人群健康、经济和健康公平性的影响 在当前指南和目标1和2中确定的美国年轻人战略。 这项研究的结果将通过确定更有效的降脂策略为未来的指南提供信息 在年轻人中预防ASCVD，通过将治疗导向高危亚组来减少健康不平等 目前没有优先考虑的，包括那些有高负担的SDOH，并改善心血管健康， 促进美国年轻人的健康老龄化。

Low-density lipoprotein cholesterol (LDL-C) is a causative factor in the development of atherosclerotic cardiovascular disease (ASCVD), and lipid-lowering therapy can markedly reduce this risk. Yet, when to begin lipid-lowering therapy has not been well understood. Despite the increasing rates of ASCVD in US young adults aged 18-39 years over the past two decades, use of lipid-lowering therapy remained low, with <7% of young adults with LDL-C ≥160 mg/dL being treated (vs. ~50% in those aged ≥40 years). It is estimated that 52% US young adults have non-optimal LDL-C ≥100 mg/dL and 7% have LDL-C ≥160 mg/dL. However, there is little evidence to guide lipid management in young adults. For risk assessment, current guidelines recommend using the pooled cohort equations (PCEs) to estimate 10-year ASCVD risk to guide lipid-lowering therapy. However, PCEs may not be directly applicable to young adults as they were developed in adults 40- 75 years of age. To address this issue, current guidelines encourage the estimation of 30-year or lifetime ASCVD risk for young adults; however, these existing lifetime risk algorithms were derived from a single cohort of non-Hispanic whites, which may limit their applicability to other populations and has been identified as a limitation by current guidelines. Further, social determinants of health (SDOH) and other risk enhancing factors known to increase ASCVD risk are not included in current risk assessment. For lipid management, the benefits and harms of initiation of lipid-lowering therapy in young adults are unknown and are extrapolated from trial data in older adults. Although randomized trials with hard ASCVD outcomes would provide definitive evidence, it may not be feasible to perform such a trial in young adults due to high costs and long follow-up time needed. In the absence of trials, high quality observational and simulation studies can provide clinically relevant and actionable evidence for policy makers, patients, and clinicians. To address these gaps, we proposes to study ~805,000 young adults from 4 cohort studies (CARDIA, Framingham, HCHS/SOL, JHS) and Kaiser Permanente Southern California to (1) improve ASCVD risk assessment accuracy for young adults by using data from contemporary and diverse populations, (2) quantify the benefits and harms of lipid-lowering therapy among young adults by emulating a clinical trial using a large observational database and state-of-the-art statistical models to minimize confounding and selection bias, and (3) compare the population-scale health, economic, and health equity impact of alternative lipid management strategies for US young adults identified in the current guidelines and Aims 1 and 2. Findings from this study will inform future guidelines by identifying strategies for more effective lipid-lowering and ASCVD prevention in young adults, reduce health inequity by directing treatment to high-risk subgroups not currently prioritized including those with a high burden of SDOH, and improve cardiovascular health and promote healthy aging of US young adults.