Long-Term All-Cause and Cause-Specific Mortality in Asymptomatic Patients With CAC ≥1,000: Results From the CAC Consortium

JACC Cardiovasc Imaging. 2020 Jan;13(1 Pt 1):83-93. doi: 10.1016/j.jcmg.2019.02.005. Epub 2019 Mar 15.

Abstract

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.

Keywords: cardiovascular imaging; coronary artery calcium; high risk; primary prevention; risk scoring.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Asymptomatic Diseases
  • Cause of Death
  • Computed Tomography Angiography
  • Coronary Angiography
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / mortality*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • United States
  • Vascular Calcification / diagnostic imaging
  • Vascular Calcification / mortality*