Author + information
- Received October 26, 2018
- Revision received January 18, 2019
- Accepted February 27, 2019
- Published online April 17, 2019.
- Allison W. Peng, BSa,
- Mohammadhassan Mirbolouk, MDa,
- Olusola A. Orimoloye, MBBS, MPHa,
- Albert D. Osei, MD, MPHa,
- Zeina Dardari, MSa,
- Omar Dzaye, MD, PhDa,
- Matthew J. Budoff, MDb,
- Leslee Shaw, PhDc,
- Michael D. Miedema, MD, MPHd,
- John Rumberger, MD, PhDe,
- Daniel S. Berman, MDf,
- Alan Rozanski, MDg,
- Mouaz H. Al-Mallah, MDh,
- Khurram Nasir, MD, MPHi and
- Michael J. Blaha, MD, MPHa,∗ ()
- aJohns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins School of Medicine, Baltimore, Maryland
- bDepartment of Medicine, Harbor-UCLA Medical Center, University of California Los Angeles, Los Angeles, California
- cDivision of Cardiology, Emory University School of Medicine, Atlanta, Georgia
- dMinneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota
- ePrinceton Longevity Center, Princeton, New Jersey
- fDepartment of Imaging, Cedars-Sinai Medical Center, Los Angeles, California
- gDivision of Cardiology, Mount Sinai St. Luke’s Hospital, New York, New York
- hCardiovascular Imaging Department, Houston Methodist Hospital, Houston, Texas
- iSection of Cardiovascular Medicine, Center for Outcomes Research and Evaluation, Yale University School of Medicine, New Haven, Connecticut
- ↵∗Address for correspondence:
Dr. Michael J. Blaha, Director of Clinical Research, Ciccarone Center for the Prevention of Heart Disease, Blalock 524D1, 600 North Wolfe Street, Baltimore, Maryland 21287.
Objectives This study thoroughly explored the demographic and imaging characteristics, as well as the all-cause and cause-specific mortality risks of patients with a coronary artery calcium (CAC) score ≥1,000 in the largest dataset of this population to date.
Background CAC is commonly used to quantify cardiovascular risk. Current guidelines classify a CAC score of >300 or 400 as the highest risk group, yet little is known about the potentially unique imaging characteristics and mortality risk in individuals with a CAC score ≥1,000.
Methods A total of 66,636 asymptomatic adults were included from the CAC consortium, a large retrospective multicenter clinical cohort. Mean patient follow-up was 12.3 ± 3.9 years for patients with cardiovascular disease (CVD), coronary heart disease (CHD), cancer, and all-cause mortality. Multivariate Cox proportional hazards regression models adjusted for age, sex, and conventional risk factors were used to assess the relative mortality hazard of individuals with CAC ≥1,000 compared with, first, a CAC reference of 0, and second, with patients with a CAC score of 400 to 999.
Results There were 2,869 patients with CAC ≥1,000 (86.3% male, mean 66.3 ± 9.7 years of age). Most patients with CAC ≥1,000 had 4-vessel CAC (mean: 3.5 ± 0.6 vessels) and had greater total CAC area, higher mean CAC density, and more extracoronary calcium (79% with thoracic artery calcium, 46% with aortic valve calcium, and 21% with mitral valve calcium) than those with CAC scores of 400 to 999. After full adjustment, those with CAC ≥1,000 had a 5.04- (95% confidence interval [CI]: 3.92 to 6.48), 6.79- (95% CI: 4.74 to 9.73), 1.55- (95% CI:1.23 to 1.95), and 2.89-fold (95% CI: 2.53 to 3.31) risk of CVD, CHD, cancer, and all-cause mortality, respectively, compared to those with CAC score of 0. The CAC ≥1,000 group had a 1.71- (95% CI: 1.41 to 2.08), 1.84- (95% CI: 1.43 to 2.36), 1.36- (95% CI:1.07 to 1.73), and 1.51-fold (95% CI: 1.33 to 1.70) increased risk of CVD, CHD, cancer, and all-cause mortality compared to those with CAC scores 400 to 999. Graphic analysis of CAC ≥1,000 patients revealed continued logarithmic increase in risk, with no clear evidence of a risk plateau.
Conclusions Patients with extensive CAC (CAC ≥1,000) represent a unique very high-risk phenotype with mortality outcomes commensurate with high-risk secondary prevention patients. Future guidelines should consider CAC ≥1,000 patients to be a distinct risk group who may benefit from the most aggressive preventive therapy.
Dr. Blaha is supported by U.S. National Institutes of Health/National Heart Lung and Blood Institute grant L30 HL110027. Dr. Budoff has received a grant from General Electric. Dr. Nasir is a member of the advisory board of Regeneron. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received October 26, 2018.
- Revision received January 18, 2019.
- Accepted February 27, 2019.
- 2019 American College of Cardiology Foundation
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