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)是动脉粥样硬化的致病因素 心血管疾病(ASCVD)和降脂治疗可以显著降低这一风险。然而，何时开始呢？ 降脂疗法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 18-39岁的成年人在过去20年中，降脂治疗的使用率仍然很低，只有7%的人 低密度脂蛋白-C-≥为160mgdL的青壮年患者正在接受治疗(40岁的≥患者的这一比例约为50%)。据估计， 52%的美国青年低密度脂蛋白胆固醇≥为100 mg/dL，7%的美国青年低密度脂蛋白≥为160 mg/dL。然而，在那里 几乎没有证据可以指导年轻人的血脂管理。对于风险评估，当前指南 建议使用集合队列方程(PCE)来估计10年ASCVD风险，以指导降脂 心理治疗。然而，PCE可能不直接适用于年轻人，因为它们是在成年人中发展起来的40- 现年75岁。为了解决这个问题，目前的指导方针鼓励对30年或一生的估计 年轻人的ASCVD风险；然而，这些现有的终生风险算法是从单个队列中得出的 非西班牙裔白人，这可能会限制他们对其他人群的适用性，并已被确定为 受当前指导方针的限制。此外，健康的社会决定因素(SDOH)和其他风险增加因素 已知会增加ASCVD风险的风险不包括在当前的风险评估中。对于血脂管理， 在年轻人中开始降脂治疗的好处和坏处是未知的，也是推断的 来自老年人的试验数据。尽管具有硬ASCVD结果的随机试验将提供明确的 证据表明，在年轻人身上进行这样的试验可能不可行，因为费用高，随访时间长。 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在临床上提供 政策制定者、患者和临床医生的相关和可操作的证据。 为了解决这些差距，我们建议研究来自4个队列研究的约80.5万名年轻人(CARDIA， Framingham，HCHS/SOL，JHS)和Kaiser Permanente Southern California(1)改善ASCVD风险 使用当代和不同人群的数据对年轻人进行评估的准确性，(2)量化 通过模拟一项临床试验，在年轻人中进行降脂治疗的利与弊 观察性数据库和最先进的统计模型，以最大限度地减少混淆和选择偏差，以及 (3)比较替代脂类管理对人群规模健康、经济和健康公平的影响 目前的指导方针和目标1和2确定了针对美国年轻人的战略。 这项研究的发现将通过确定更有效的降脂策略来为未来的指南提供参考 在年轻人中预防ASCVD，通过指导高危亚群的治疗来减少健康不平等 目前未被优先考虑的包括SDOH负担较高的人，并改善心血管健康和 促进美国年轻人的健康老龄化。