Improving Lipid Management Strategies in Young Adults

改善年轻人的血脂管理策略

• 批准号: 10639036
• 负责人: Jaejin An
• 金额: $ 78.74万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-05 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10639036
• 关键词: Address; Adolescence; Adult; Adverse event; Age; Age Years; Algorithms; Assessment tool; Atherosclerosis; California; Clinical Trials; Cohort Studies; Data; Databases; Development; Diabetes Mellitus; Disease Outcome; Early Intervention; Economics; Elderly; Equation; Event; Family history of; Future; Goals; Guidelines; Health; Hereditary Disease; Hyperlipidemia; LDL Cholesterol Lipoproteins; Life Style; Life Style Modification; Lipids; Lipoprotein (a); Metabolic syndrome; Myocardial Infarction; Not Hispanic or Latino; Patients; Performance; Persons; Policy Maker; Population; Population Heterogeneity; Prevention; Prevention strategy; Prior Therapy; Qualifying; Recommendation; Risk; Risk Assessment; Risk Estimate; Risk Factors; Selection Bias; Smoking; Smoking History; Statistical Models; Subgroup; Time; age group; aged; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular health; clinically actionable; clinically relevant; cohort; cost; cost effective; emerging adult; enhancing factor; ethnic diversity; experience; follow-up; health equity; health inequalities; healthy aging; high risk; improved; lifestyle intervention; lifetime risk; premature; prevent; racial diversity; randomized trial; risk prediction model; simulation; social health determinants; treatment risk; young adult

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.

低密度脂蛋白胆固醇（LDL-C）是动脉粥样硬化发展的原因 心血管疾病（ASCVD）和降低脂质疗法可以显着降低这种风险。但是，什么时候开始 降低脂质的疗法尚未得到充分了解。尽管美国年轻人的ASCVD发生率增加 在过去的二十年中，年龄在18-39岁的成年人，使用降低脂质疗法的使用量很低，<7％ 患有LDL-C≥160mg/dl的年轻人正在接受治疗（在≥40岁的年龄段为约50％）。据估计 52％的美国年轻人的LDL-C≥100mg/dl，LDL-C≥160mg/dl的LDL-C≥100mg/dl。但是，那里 几乎没有证据表明年轻人的脂质管理。为了进行风险评估，当前的指南 建议使用合并的队列方程（PCE）估算10年ASCVD风险以指导降低脂质 治疗。但是，PCE可能不直接适用于年轻人，因为成年人在成年人中开发了40-- 75岁。为了解决这个问题，当前的准则鼓励估计30年或终生 年轻人的ASCVD风险；但是，这些现有的终身风险算法是从单个队列中得出的 非西班牙裔白人可能会限制其对其他人群的适用性，并已被确定为 当前指南的限制。此外，卫生的社会决定者（SDOH）和其他风险增强因素 当前的风险评估中不包括增加ASCVD风险。对于脂质管理， 年轻人的降低脂质疗法的益处和危害尚不清楚，并且被推断 来自老年人的试验数据。尽管具有硬性ASCVD结果的随机试验将提供确定的 证据，由于高成本和长期随访，在年轻人中进行此类审判可能是不可行的 需要时间。在没有试验的情况下，高质量的观察和模拟研究可以在临床上提供 政策制定者，患者和临床医生的相关证据。 为了解决这些差距，我们建议研究来自4个队列研究的约805,000名年轻人（Cardia， Framingham，HCHS/SOL，JHS）和Kaiser Permanente南加州（1）改善ASCVD风险 通过使用现代和潜水员种群的数据来评估年轻人的准确性，（2）量化 通过大型临床试验模拟临床试验，降低脂质疗法的益处和危害 观察数据库和最新统计模型，以最大程度地减少混杂和选择偏见，以及 （3）比较替代脂质管理的人口规模的健康，经济和健康公平的影响 我们的年轻人的策略在当前的指南中确定，目标1和2。 这项研究的发现将通过确定降低脂质的策略来为未来的准则提供信息 在年轻人中预防ASCVD，通过将治疗引导到高风险亚组来减少健康不平等 目前尚未确定包括SDOH燃烧高的人，并改善心血管健康和 促进我们年轻人的健康衰老。