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Long-Term All-Cause and Cause-Specific Mortality in Asymptomatic Patients With CAC ≥1,000: Results From the CAC
Allison W Peng1, Mohammadhassan Mirbolouk1, Olusola A Orimoloye1
1Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins School of Medicine, Baltimore, Maryland.
Insights
Patients with a coronary artery calcium (CAC) score of 1,000 or higher have significantly increased mortality risks for cardiovascular disease, cancer, and all causes. This very high-risk group warrants consideration for aggressive preventive therapies.
Area of Science:
- Cardiology
- Preventive Medicine
- Medical Imaging
Background:
- Coronary artery calcium (CAC) scoring is vital for cardiovascular risk assessment.
- Current guidelines define high CAC scores (>300-400) but lack clarity on scores ≥1,000.
- Limited data exists on the unique characteristics and mortality risks associated with extremely high CAC scores (≥1,000).
Purpose of the Study:
- To investigate the demographic and imaging features of patients with CAC scores ≥1,000.
- To evaluate the all-cause and cause-specific mortality risks in this extreme CAC score group.
- To compare mortality risks of CAC ≥1,000 patients against those with CAC 0 and CAC 400-999.
Main Methods:
- Analysis of a large retrospective multicenter cohort (66,636 asymptomatic adults) from the CAC consortium.
- Inclusion of patients with CAC scores ≥1,000 (n=2,869) and comparison groups (CAC 0 and CAC 400-999).
- Utilized multivariate Cox proportional hazards regression, adjusting for age, sex, and conventional risk factors.
Main Results:
- Patients with CAC ≥1,000 exhibited distinct imaging characteristics, including multi-vessel calcification and higher prevalence of extracoronary calcium.
- Fully adjusted analyses revealed significantly elevated risks: CVD (5.04x), CHD (6.79x), cancer (1.55x), and all-cause mortality (2.89x) compared to CAC 0.
- Compared to CAC 400-999, CAC ≥1,000 showed increased risks: CVD (1.71x), CHD (1.84x), cancer (1.36x), and all-cause mortality (1.51x).
- Risk continued to increase logarithmically with no apparent plateau.
Conclusions:
- Patients with CAC scores ≥1,000 represent a unique, very high-risk phenotype.
- Their mortality outcomes are comparable to patients undergoing secondary prevention for high-risk conditions.
- Future guidelines should establish CAC ≥1,000 as a distinct risk category warranting aggressive preventive strategies.
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.
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