Risk Profile and Prognostic Implications of Premature Advanced Coronary Atherosclerotic Disease Among Young to Early Middle-aged Adults: The Coronary Artery Calcium Consortium

Eur J Prev Cardiol. 2025 Jan 16:zwaf019. doi: 10.1093/eurjpc/zwaf019. Online ahead of print.

Authors

Affiliations

¹ Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³ Department of Medicine, MedStar Union Memorial Hospital, Baltimore, Maryland USA.
⁴ Division of Cardiovascular Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
⁵ Division of Cardiovascular Medicine, University of Louisville, Louisville, Kentucky, USA.
⁶ Division of Cardiology, Mount Sinai, St. Luke's Hospital, New York, New York, USA.
⁷ Departments of Imaging and Cardiology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁸ Lundquist Institute, Harbor-UCLA Medical Center, Torrance, California, USA.
⁹ Minneapolis Heart Institute and Foundation, Minneapolis, Minnesota, USA.
¹⁰ Division of Cardiovascular Prevention and Wellness, Houston Methodist DeBakey Heart & Vascular Center, Houston, Texas, USA.
¹¹ Department of Cardiac Imaging, Princeton Longevity Center, Princeton, New Jersey, USA.
¹² Department of Medicine (Cardiology), Icahn School of Medicine at Mount Sinai, New York, New York, USA.

PMID: 39821061
DOI: 10.1093/eurjpc/zwaf019

Abstract

Introduction: Premature advanced subclinical coronary atherosclerosis among young adults is an under-recognized and unique disease phenotype that has not been well characterized.

Methods: We used data from 44,047 participants with no prior CVD history (59.8% male) from the Coronary Artery Calcium (CAC) Consortium. We defined advanced disease as CAC ≥90th percentile for age, sex, and race, and compared risk factor profile of persons with advanced disease to those without CAC and those with CAC <90th percentile. Using multivariable-adjusted Cox proportional hazard and competing risks regression, we assessed the association of premature advanced disease with all-cause, cardiovascular, and CHD mortality.

Results: Of 44,047 participants, 18,561 (42.2%) had CAC. Among those with CAC, 6,680 (36.0%) had CAC ≥90th percentile. Notably, 76.4% of those with CAC ≥90th percentile had multivessel CAC compared to 40.6% of those with CAC <90th percentile. After a mean follow-up of 12.5±3.6 years, the incidence per 1,000 person-years of all-cause (2.93 vs 1.85 vs 1.11), cardiovascular (1.11 vs 0.39 vs 0.21), and CHD mortality (0.65 vs 0.19 vs 0.08) was highest in the advanced disease group compared to CAC <90th percentile and the no CAC group. Persons with CAC ≥90th percentile had a higher multivariable-adjusted risk of all-cause (HR:2.17[1.83-2.57]), cardiovascular (SHR:3.89[2.78-5.44]), and CHD mortality (SHR:5.45[3.38-8.78]), compared to those without CAC. In the subgroup analysis, there was no difference in mortality between men and women with advanced CAC.

Conclusions: Premature advanced atherosclerosis is a distinct clinical phenotype that strongly predicts all-cause and cause-specific mortality. Among persons with CAC at young age, those with scores ≥ 90th percentile have the highest risk of early death and should be identified in future guidelines as a focus for aggressive clinical prevention.

Keywords: Advanced disease; Atherosclerotic cardiovascular disease; Coronary artery calcium; Mortality.

Plain language summary

The findings of our paper show that young and early middle-aged individuals who have high burden of calcifications in their coronary vessels compared to their age, sex, and race-matched counterparts, have higher risk of death from any cause and death from cardiovascular diseases. This implies that we should be more aggressive in our preventive efforts towards this group of young adults.

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