👤 Ciaran Kohli-Lynch

Apolipoprotein B (apoB) is a superior marker of residual atherosclerotic cardiovascular disease risk in patients treated with lipid-lowering therapy (LLT) compared with low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). The cost-effectiveness of LDL-C, non-HDL-C, and apoB goals has not been established. To determine the relative cost-effectiveness of intensifying LLT for primary prevention based on LDL-C, non-HDL-C, and apoB goals. This economic evaluation used a computer simulation model to evaluate the cost-effectiveness of intensifying LLT with high-intensity statins or ezetimibe according to LDL-C, non-HDL-C, or apoB goals. A cohort of 250 000 statin-eligible and atherosclerotic cardiovascular disease-free US adults was constructed from 2005 to 2016 National Health and Nutrition Examination Survey participants (N = 4149). Individuals commenced the simulation after lipid screening and received statin therapy based on 2018 American Heart Association/American College of Cardiology guidelines. Model inputs were derived from national survey data, pooled longitudinal cohort studies, and published literature. Uncertainty was explored with traditional and probabilistic sensitivity analysis. Lipid-lowering therapy was intensified if individuals did not achieve treated LDL-C level less than 100 mg/dL, non-HDL-C level less than 118 mg/dL, or apoB level less than 78.7 mg/dL. Lifetime quality-adjusted life-years (QALYs) and costs (in 2025 US dollars), discounted 3.0% annually. The primary outcome was the incremental cost-effectiveness ratio. Strategies were considered cost-effective if they cost less than $120 000 per QALY gained. Compared with an LDL-C goal, 965 QALYs (95% uncertainty interval [UI], -3551 to 5341 QALYs) would be gained with a non-HDL-C goal, alongside a $2.1 million (95% UI, -$94.2 million to $92.0 million) reduction in costs. Compared with a non-HDL-C goal, 1324 QALYs (95% UI, -2602 to 5669 QALYs) would be gained with an apoB goal, alongside a $40.2 million (95% UI, -$43.6 million to $134 million) increase in costs, yielding an incremental cost-effectiveness ratio of $30 300 per QALY gained. At a willingness-to-pay threshold of $120 000 per QALY gained, an apoB goal was optimal in 65% of probabilistic analyses and a non-HDL-C goal was optimal in 25%. The cost of apoB testing was marginal; higher costs reflected longer life expectancy and prolonged preventive treatment. The results of this computer simulation study suggest that apoB can be used as a cost-effective marker to guide primary prevention LLT and improve population health. Show less

Atherogenic lipoprotein exposure during young adulthood increases the risk of atherosclerotic cardiovascular disease (ASCVD) later in life. The relationships between cumulative and usual yearly apolipoprotein B (apoB), low-density lipoprotein particle (LDL-P), and triglyceride-rich lipoprotein particle (TRL-P) exposure in early adult life and incident ASCVD was quantified. Follow-up data of young adults aged 18 to <40 years from the longitudinal population-based Coronary Artery Risk Development in Young Adults (CARDIA) cohort were used. Cumulative early adult exposure of apoB, LDL-P, and TRL-P were defined over a 22-year exposure period (18 to <40 years). 'Usual' exposure to atherogenic lipid particles was calculated by dividing the cumulative exposure to apoB, LDL-P, and TRL-P by 22 years, and the hazard ratio was calculated between a 1 SD higher cumulative lipoprotein exposure with incident ASCVD after age 40 using adjusted Cox regression models. Among 4366 CARDIA participants, there were 241 ASCVD events after age 40 (mean follow-up of 19.3 years). A 1 SD higher cumulative exposure to apoB, LDL-P, and TRL-P was associated with unadjusted HRs of 1.53 [95% confidence interval (CI) 1.36-1.72], 1.54 (95% CI 1.36-1.75), and 1.48 (95% CI 1.30-1.68) for incident ASCVD after age 40, respectively. Adjustment for covariates yielded HRs for each measure of approximately 1.30. The hazard ratio for ASCVD increased after a usual apoB exposure of approximately 75 mg/dL/year from age 18 to <40. Cumulative exposure to atherogenic lipid particles in young adulthood increases the risk for incident ASCVD later in life. Apolipoprotein B concentration <75 mg/dL may represent a goal to maintain low risk in young adults. Show less

Selecting individuals for preventive lipid-lowering therapy is presently governed by the 10-year risk model. Once a prespecified level of cardiovascular disease risk is equaled or exceeded, individuals become eligible for preventive lipid-lowering therapy. A key limitation of this model is that only a small minority of individuals below the age of 65 years are eligible for therapy. However, just under one-half of all cardiovascular disease events occur below this age. Additionally, in many, the disease that caused their events after 65 years of age developed and progressed before 65 years of age. The causal-benefit model of prevention identifies individuals based both on their risk and the estimated benefit from lowering atherogenic apoB lipoprotein levels. Adopting the causal-benefit model would increase the number of younger subjects eligible for preventive treatment, would increase the total number of cardiovascular disease events prevented at virtually the same number to treat, and would be cost-effective. Show less