CAC for Risk Stratification Among Individuals With Hypertriglyceridemia Free of Clinical Atherosclerotic Cardiovascular Disease

Miguel Cainzos-Achirica, Renato Quispe, Ramzi Dudum, Philip Greenland, Donald Lloyd-Jones, Jamal S. Rana, Joao A.C. Lima, Henrique Doria de Vasconcellos, Parag H. Joshi, Amit Khera, Colby Ayers, Raimund Erbel, Andreas Stang, Karl Heinz Jöckel, Nils Lehmann, Sara Schramm, Börge Schmidt, Peter P. Toth, Kershaw V. Patel, Michael J. BlahaMarcio Bittencourt, Khurram Nasir

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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 (NNT5) to prevent 1 event was estimated among IPE-eligible participants, assuming a 21.8% relative risk reduction with IPE. In exploratory analyses, the NNT5 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 NNT5 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.

Original languageEnglish (US)
Pages (from-to)641-651
Number of pages11
JournalJACC: Cardiovascular Imaging
Issue number4
StatePublished - Apr 2022


  • cardiovascular disease
  • coronary artery calcium
  • hypertriglyceridemia
  • icosapent ethyl
  • prevention
  • primary prevention
  • risk
  • Predictive Value of Tests
  • Risk Assessment
  • Cardiovascular Diseases/epidemiology
  • Humans
  • Risk Factors
  • Coronary Artery Disease/diagnostic imaging
  • Vascular Calcification/diagnostic imaging
  • Hypertriglyceridemia/diagnosis
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
  • Atherosclerosis/diagnostic imaging

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Radiology Nuclear Medicine and imaging


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