Epidemiology

ASCVD (atherosclerotic cardiovascular disease) remains the leading cause of death globally. In spite of advances in testing and treatment protocols, patients still continue to suffer from myocardial infarctions, peripheral vascular disease, and stroke needing revascularisation. This, together with rising global trends of risk factors—obesity, hypertension, diabetes and dyslipidaemia—makes it critical to tackle the problem with a cost‑effective and future‑proof strategy (Nedkoff et al., 2023; World Health Organization, 2025).

In this brief report, we focus on the current practice of lipid profiling and additional tests that may improve cost‑effectiveness in the longer term.

Physiology

Cholesterol is a vital substance for cell membranes and hormone synthesis. It travels through the bloodstream in particles called lipoproteins. Low‑density lipoprotein (LDL) particles are the primary carriers of cholesterol in the blood; LDL‑C levels typically track the number of LDL particles and are therefore a useful indicator of cardiovascular risk. However, in people with diabetes, metabolic syndrome or hypertriglyceridaemia, LDL particles can become smaller and carry less cholesterol per particle. In these cases, LDL‑C may underestimate the true atherogenic particle burden (Sniderman et al., 2011; Ference et al., 2017).

For such individuals, measuring the actual number of atherogenic particles via apolipoprotein B‑100 (ApoB‑100)—one molecule per VLDL/IDL/LDL particle—can give a more accurate picture of risk than LDL‑C alone. Two lipoprotein‑related measures of particular interest are ApoB‑100 and lipoprotein(a) [Lp(a)] (Visseren et al., 2021).

Apolipoprotein B‑100 (ApoB‑100)

ApoB‑100 is synthesised in the liver and is essential for the assembly and secretion of VLDL, which are metabolised to IDL and LDL; each VLDL/IDL/LDL particle contains one ApoB‑100, making ApoB a direct proxy for atherogenic particle number. Particle retention in the arterial intima and the subsequent inflammatory cascade drive plaque formation. Thus, particle number (ApoB) better captures risk than cholesterol content alone, which can miss discordant profiles and underestimate ASCVD risk (Sniderman et al., 2011; Ference et al., 2017).

Lipoprotein(a) [Lp(a)]

Lp(a) is an LDL‑like particle whose plasma concentration is largely genetically determined. It contains an apolipoprotein(a) moiety with homology to plasminogen and binds to ApoB‑100, increasing atherothrombotic potential. When Lp(a)‑enriched LDL deposits within the vessel wall, it may trigger inflammatory responses and promote plaque instability, raising the likelihood of rupture and thrombosis (Tsimikas, 2017).

Testing

Current European Society of Cardiology (ESC) guidelines on cardiovascular disease prevention highlight the utility of ApoB testing in patients at risk of ASCVD, particularly in the presence of hypertriglyceridaemia, diabetes, obesity or metabolic syndrome (Visseren et al., 2021).

Cost Effectiveness

Cost‑Benefit Analysis: Precision Lipid Testing (ApoB‑100) vs Basic Lipid Profile in Mixed Dyslipidaemia

Assumptions

• Patient population: 10,000 adults with mixed dyslipidaemia (elevated LDL‑C, triglycerides and low HDL‑C).
• Cardiovascular event rates over 10 years: untreated 15% risk of major CV events (MI, stroke); basic lipid‑guided therapy 30% relative risk reduction (RRR) → 10.5% absolute risk; precision‑guided therapy (ApoB + basic lipids) 45% RRR → 8.25% absolute risk.
• Costs (illustrative U.S. estimates): basic lipid panel $50; ApoB test +$60; statin therapy $5/month; major CV event $150,000 (CTT Collaboration, 2012; Adamson et al., 2022; CMS, 2024; GoodRx, 2024; Luengo‑Fernandez et al., 2021).

Scenario 1: Basic Lipid Profile Only

Testing: 10,000 × $50 = $500,000.

Treatment: 10,000 × $600 = $6,000,000 per year.

Baseline events: 10,000 × 15% = 1,500; avoided with therapy: 450; residual: 1,050.

Total cost: $500,000 + $6,000,000 + (1,050 × $150,000) = $163,550,000.

Scenario 2: Precision Therapy (ApoB + Basic Lipids)

Testing: 10,000 × ($50 + $60) = $1,100,000.

Treatment: 10,000 × $600 = $6,000,000 per year.

Avoided events: 675; residual: 825.

Total cost: $1,100,000 + $6,000,000 + (825 × $150,000) = $130,850,000.

Cost‑Benefit Comparison

Metric	Basic Lipid Profile	Precision Therapy	Difference
Total cost	$163,550,000	$130,850,000	-$32,700,000
Residual CV events	1,050	825	-225 events
Cost per event avoided	$36,345	$25,000	-$11,345
Net savings	—	—	$32.7 million

Conclusion: Precision therapy saves $32.7 million despite higher testing costs, by avoiding 225 additional CV events. Clinical impact: ApoB better predicts residual risk in mixed dyslipidaemia, enabling optimised statin dosing or combination therapy. Key caveats: results assume guideline‑directed statin use; costs vary by country; cost‑effectiveness is greatest in high‑risk populations.

References

Adamson, D.M. et al. 2022, ‘Cost‑effectiveness of generic statins’, JAMA Internal Medicine, vol. n.v., no. n.i., pp. n.p..

Cholesterol Treatment Trialists’ (CTT) Collaboration 2012, ‘Efficacy and safety of more intensive lowering of LDL cholesterol’, The Lancet, vol. 376, no. 9753, pp. 1670–1681.

Ference, B.A. et al. 2017, ‘Low‑density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies’, JAMA Cardiology, vol. 2, no. 12, pp. 1237–1245.

Goff, D.C. et al. 2014, ‘2013 ACC/AHA guideline on the assessment of cardiovascular risk’, Circulation, vol. 129, no. 25 Suppl 2, pp. S49–S73.

GoodRx 2024, ‘U.S. national average pricing for atorvastatin’, GoodRx.

Luengo‑Fernandez, R. et al. 2021, ‘Economic burden of cardiovascular disease’, European Heart Journal – Quality of Care & Clinical Outcomes, vol. 7, no. 2, pp. 159–168.

Centers for Medicare & Medicaid Services (CMS) 2024, ‘Clinical Laboratory Fee Schedule: CPT 80061 (Lipid Panel)’, CMS.

Nedkoff, L., Briffa, T., Zemedikun, D., Herrington, S. & Wright, F.L. 2023, ‘Global trends in atherosclerotic cardiovascular disease’, Clinical Therapeutics, vol. 45, pp. 1087–1091.

Organisation for Economic Co‑operation and Development (OECD) 2024, ‘OECD Health Statistics’, OECD.

Sniderman, A.D. et al. 2011, ‘Apolipoprotein B versus non‑HDL cholesterol as the preferred marker of atherogenic lipoproteins’, Journal of the American College of Cardiology, vol. 58, no. 5, pp. 502–509.

Tsimikas, S. 2017, ‘A test in context: Lipoprotein(a)’, Journal of the American College of Cardiology, vol. 69, pp. 692–711.

Visseren, F.L.J. et al. 2021, ‘2021 ESC Guidelines on cardiovascular disease prevention in clinical practice’, European Heart Journal, vol. 42, pp. 3227–3337.

World Health Organization 2025, ‘World health statistics 2025: monitoring health for the SDGs’, WHO, Geneva.

American Medical Association (AMA) 2024, ‘CPT® Professional Edition: CPT 82145 (Apolipoprotein B)’, AMA.

Tsao, C.W. et al. 2023, ‘Heart disease and stroke statistics—2023 update’, Circulation, vol. 147, no. 8, pp. e93–e621.