Improving Lipid Management Strategies in Young Adults

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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.