CAC for Risk Stratification Among Individuals With Hypertriglyceridemia Free of Clinical Atherosclerotic Cardiovascular Disease
Open accessAbstract
Objectives In this study, we sought to evaluate whether the coronary artery calcium (CAC) score can enhance current paradigms for risk stratification among individuals with hypertriglyceridemia in primary prevention. The eligibility criteria for icosapent ethyl (IPE) were used as case example. Background Recent trials of atherosclerotic cardiovascular disease (ASCVD) risk-reduction therapies for individuals with hypertriglyceridemia without clinical ASCVD restricted enrollment to participants with diabetes or various other risk factors. These criteria were mirrored in the Food and Drug Administration product label for IPE. Methods We pooled 2,345 participants with triglycerides 150 to <500 mg/dL (or >178-<500 mg/dL if not on a statin) and without clinical ASCVD from MESA, CARDIA, the Dallas Heart Study, and the Heinz Nixdorf Recall study. We evaluated the incidence of ASCVD events overall, by IPE eligibility (as defined in the product label), and further stratified by CAC scores (0, >0-100, >100). The number needed to treat for 5 years (NNT 5) to prevent 1 event was estimated among IPE-eligible participants, assuming a 21.8% relative risk reduction with IPE. In exploratory analyses, the NNT 5 was also estimated among noneligible participants. Results There was marked heterogeneity in CAC burden overall (45% CAC 0; 24% CAC >100) and across IPE eligibility strata. Overall, 17% of participants were eligible for IPE and 11.9% had ASCVD events within 5 years. Among participants eligible for IPE, 38% had CAC >100, and their event rates were markedly higher (15.9% vs 7.2%) and the NNT 5 2.2-fold lower (29 vs 64) than those of the 25% eligible participants with CAC 0. Among the 83% participants not eligible for IPE, 20% had CAC >100, and their 5-year incidence of ASCVD (13.9%) was higher than the overall incidence among IPE-eligible participants. Conclusions CAC can improve current risk stratification and therapy allocation paradigms among individuals with hypertriglyceridemia without clinical ASCVD. Future trials of risk-reduction therapies in hypertriglyceridemia could use CAC >100 to enroll a high-risk study sample, with implications for a larger target population.
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In individuals with hypertriglyceridemia, coronary artery calcium scoring improves risk stratification and therapy allocation.
“In individuals with HTG, CAC scoring improves risk stratification and therapy allocation, underscoring the utility of subclinical plaque measurement in this phenotype [30].”
From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [30]
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- Authors
- Cainzos-Achirica, M., Quispe, R., Dudum, R., Greenland, P., Lloyd-Jones, D., Rana, J. S., Lima, J. A. C., Doria de Vasconcellos, H., Joshi, P. H., Khera, A., Ayers, C., Erbel, R., Stang, A., Jöckel, K.-H., Lehmann, N., Schramm, S., Schmidt, B., Toth, P. P., Patel, K. V., Blaha, M. J., Bittencourt, M., & Nasir, K.
- Affiliations
- Johns Hopkins University (US)
- Stanford Medicine (US)
- Northwestern University (US)
- Kaiser Permanente (US)
- The University of Texas Southwestern Medical Center (US)
- University of Duisburg-Essen (DE)
- Boston University (US)
- Houston Methodist (US)
- ORCID
- Venue
- JACC: Cardiovascular Imaging
- Publisher
- Elsevier BV
- Published
- 2022-04
- Volume
- 15
- Issue
- 4
- Pages
- 641-651
- ISSN
- 1876-7591 (ISSN-L)
- 1936-878X
- OpenAlex
- W4200587761
- Cited by
- 24
- References
- 36
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 2 · 2023: 9 · 2022: 4
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- JACC. Cardiovascular imaging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- GlaxoSmithKline
- Roche
- ResMed Foundation
- Philips
- AstraZeneca
- Merck KGaA
- Novo Nordisk
- Sanofi
- Universität Duisburg-Essen
- National Center for Advancing Translational Sciences
- Boston Scientific Corporation
- Janssen Pharmaceuticals
- Ministry of Science Research and Technology
- Heinz Nixdorf Stiftung
- Volkswagen Foundation (5T32HL007227)
- National Institutes of Health (HHSN268201800003I, UL1TR001105)
- U.S. Food and Drug Administration
- University Hospitals
- Kulturstiftung Essen
- European Commission
- Deutsche Forschungsgemeinschaft (10-1, 6-2, EI 969/2-3, ER 155/6-1, HO 3314/2-1, INST 58219/32-1, JO 170/8-1, KN 885/3-1, PE 2309/2-1, SI 236/8-1)
- Bundesministerium für Bildung und Forschung (01EG0401, 01ER1001D, 01GI0205, 01GI0856, 01GI0860)
- Else Kröner-Fresenius-Stiftung (2015_A119)
- Deutsche Gesetzliche Unfallversicherung (FF-FP295)
- American Heart Association
- Amgen
- Amgen Foundation
- National Heart, Lung, and Blood Institute (UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881)
- National Aeronautics and Space Administration
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Health Promotion and Cardiovascular Prevention
- Keywords
- coronary artery calcium score, hypertriglyceridemia, icosapent ethyl, primary prevention, number needed to treat, atherosclerosis burden, statin eligibility, MESA, gastric cardia, Dallas Heart Study
- MeSH terms
- Cardiovascular Diseases, Coronary Artery Disease, Humans, Predictive Value of Tests, Risk Factors, Hypertriglyceridemia, Risk Assessment, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Atherosclerosis, Vascular Calcification
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