Prognostic Value of Coronary Artery Calcium in the PROMISE Study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain)

Circulation. 2017 Nov 21;136(21):1993-2005. doi: 10.1161/CIRCULATIONAHA.117.030578. Epub 2017 Aug 28.

Abstract

Background: Coronary artery calcium (CAC) is an established predictor of future major adverse atherosclerotic cardiovascular events in asymptomatic individuals. However, limited data exist as to how CAC compares with functional testing (FT) in estimating prognosis in symptomatic patients.

Methods: In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain (or dyspnea) and intermediate pretest probability for obstructive coronary artery disease were randomized to FT (exercise electrocardiography, nuclear stress, or stress echocardiography) or anatomic testing. We evaluated those who underwent CAC testing as part of the anatomic evaluation (n=4209) and compared that with results of FT (n=4602). We stratified CAC and FT results as normal or mildly, moderately, or severely abnormal (for CAC: 0, 1-99 Agatston score [AS], 100-400 AS, and >400 AS, respectively; for FT: normal, mild=late positive treadmill, moderate=early positive treadmill or single-vessel ischemia, and severe=large ischemic region abnormality). The primary end point was all-cause death, myocardial infarction, or unstable angina hospitalization over a median follow-up of 26.1 months. Cox regression models were used to calculate hazard ratios (HRs) and C statistics to determine predictive and discriminatory values.

Results: Overall, the distribution of normal or mildly, moderately, or severely abnormal test results was significantly different between FT and CAC (FT: normal, n=3588 [78.0%]; mild, n=432 [9.4%]; moderate, n=217 [4.7%]; severe, n=365 [7.9%]; CAC: normal, n=1457 [34.6%]; mild, n=1340 [31.8%]; moderate, n=772 [18.3%]; severe, n=640 [15.2%]; P<0.0001). Moderate and severe abnormalities in both arms robustly predicted events (moderate: CAC: HR, 3.14; 95% confidence interval, 1.81-5.44; and FT: HR, 2.65; 95% confidence interval, 1.46-4.83; severe: CAC: HR, 3.56; 95% confidence interval, 1.99-6.36; and FT: HR, 3.88; 95% confidence interval, 2.58-5.85). In the CAC arm, the majority of events (n=112 of 133, 84%) occurred in patients with any positive CAC test (score >0), whereas fewer than half of events occurred in patients with mildly, moderately, or severely abnormal FT (n=57 of 132, 43%; P<0.001). In contrast, any abnormality on FT was significantly more specific for predicting events (78.6% for FT versus 35.2% for CAC; P<0.001). Overall discriminatory ability in predicting the primary end point of mortality, nonfatal myocardial infarction, and unstable angina hospitalization was similar and fair for both CAC and FT (C statistic, 0.67 versus 0.64). Coronary computed tomographic angiography provided significantly better prognostic information compared with FT and CAC testing (C index, 0.72).

Conclusions: Among stable outpatients presenting with suspected coronary artery disease, most patients experiencing clinical events have measurable CAC at baseline, and fewer than half have any abnormalities on FT. However, an abnormal FT was more specific for cardiovascular events, leading to overall similarly modest discriminatory abilities of both tests.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550.

Keywords: calcium; coronary artery disease; diagnostic tests; prognosis; routine.

Publication types

  • Multicenter Study
  • Pragmatic Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Angina Pectoris / etiology*
  • Angina, Unstable / etiology
  • Comparative Effectiveness Research
  • Computed Tomography Angiography*
  • Coronary Angiography / methods*
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / diagnosis*
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / mortality
  • Diagnosis, Differential
  • Disease Progression
  • Dyspnea / etiology*
  • Echocardiography, Stress / methods*
  • Electrocardiography / methods*
  • Exercise Test*
  • Female
  • Hospitalization
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multidetector Computed Tomography*
  • Myocardial Infarction / etiology
  • North America
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Time Factors
  • Vascular Calcification / complications
  • Vascular Calcification / diagnosis*
  • Vascular Calcification / diagnostic imaging
  • Vascular Calcification / mortality

Associated data

  • ClinicalTrials.gov/NCT01174550