Incremental prognostic value of coronary computed tomographic angiography over coronary artery calcium score for risk prediction of major adverse cardiac events in asymptomatic diabetic individuals.
BACKGROUND
Coronary artery disease (CAD) diagnosis by coronary computed tomographic angiography (CCTA) is useful for identification of symptomatic diabetic individuals at heightened risk for death. Whether CCTA-detected CAD enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring (CACS) remains unexplored.


METHODS
From a prospective 12-center international registry of 27,125 individuals undergoing CCTA, we identified 400 asymptomatic diabetic individuals without known CAD. Coronary stenosis by CCTA was graded as 0%, 1-49%, 50-69%, and ≥70%. CAD was judged on a per-patient, per-vessel and per-segment basis as maximal stenosis severity, number of vessels with ≥50% stenosis, and coronary segments weighted for stenosis severity (segment stenosis score), respectively. We assessed major adverse cardiovascular events (MACE) - inclusive of mortality, nonfatal myocardial infarction (MI), and late target vessel revascularization ≥90 days (REV) - and evaluated the incremental utility of CCTA for risk prediction, discrimination and reclassification.


RESULTS
Mean age was 60.4 ± 9.9 years; 65.0% were male. At a mean follow-up 2.4 ± 1.1 years, 33 MACE occurred (13 deaths, 8 MI, 12 REV) [8.25%; annualized rate 3.4%]. By univariate analysis, per-patient maximal stenosis [hazards ratio (HR) 2.24 per stenosis grade, 95% confidence interval (CI) 1.61-3.10, p < 0.001], increasing numbers of obstructive vessels (HR 2.30 per vessel, 95% CI 1.75-3.03, p < 0.001) and segment stenosis score (HR 1.14 per segment, 95% CI 1.09-1.19, p < 0.001) were associated with increased MACE. After adjustment for CAD risk factors and CACS, maximal stenosis (HR 1.80 per grade, 95% CI 1.18-2.75, p = 0.006), number of obstructive vessels (HR 1.85 per vessel, 95% CI 1.29-2.65, p < 0.001) and segment stenosis score (HR 1.11 per segment, 95% CI 1.05-1.18, p < 0.001) were associated with increased risk of MACE. Beyond age, gender and CACS (C-index 0.64), CCTA improved discrimination by maximal stenosis, number of obstructive vessels and segment stenosis score (C-index 0.77, 0.77 and 0.78, respectively). Similarly, CCTA findings improved risk reclassification by per-patient maximal stenosis [integrated discrimination improvement (IDI) index 0.03, p = 0.03] and number of obstructive vessels (IDI index 0.06, p = 0.002), and by trend for segment stenosis score (IDI 0.03, p = 0.06).


CONCLUSIONS
For asymptomatic diabetic individuals, CCTA measures of CAD severity confer incremental risk prediction, discrimination and reclassification on a per-patient, per-vessel and per-segment basis.
Department of Radiology, Weill Cornell Medical College and The NewYork-Presbyterian Hospital, New York, NY, USA. Electronic address: james.min@cshs.org.
James K
JK
Min
Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Troy M
TM
Labounty
Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Millie J
MJ
Gomez
Department of Medicine, University of Erlangen, Erlangen, Germany.
Stephan
S
Achenbach
Department of Medicine, Wayne State University, Henry Ford Hospital, Detroit, MI, USA.
Mouaz
M
Al-Mallah
Department of Medicine, Harbor UCLA Medical Center, Los Angeles, CA, USA.
Matthew J
MJ
Budoff
Department of Radiology, Giovanni XXIII Hospital, Monastier, Treviso, Italy; Department of Radiology, Erasmus Medical Center, Rotterdam, Netherlands.
Filippo
F
Cademartiri
Tennessee Heart and Vascular Institute, Hendersonville, TN, USA.
Tracy Q
TQ
Callister
Division of Cardiology, Severance Cardiovascular Hospital, Seoul, South Korea.
Hyuk-Jae
HJ
Chang
Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Victor
V
Cheng
William Beaumont Hospital, Royal Oak, MI, USA.
Kavitha M
KM
Chinnaiyan
Department of Medicine and Radiology, University of Ottawa, Ontario, Canada.
Benjamin
B
Chow
Baptist Cardiac and Vascular Institute, Miami, FL, USA.
Ricardo
R
Cury
Capitol Cardiology Associates, Albany, NY, USA.
Augustin
A
Delago
Department of Public Health, Weill Cornell Medical College, New York, NY, USA.
Allison
A
Dunning
Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria.
Gudrun
G
Feuchtner
University of Munich, Munich, Germany.
Martin
M
Hadamitzky
Cardiovascular Medical Group, Los Angeles, CA, USA.
Jorg
J
Hausleiter
University Hospital, Zurich, Switzerland.
Philipp
P
Kaufmann
Seoul National University Hospital, Seoul, South Korea.
Yong-Jin
YJ
Kim
Department of Medicine and Radiology, University of British Columbia, Vancouver, BC, Canada.
Jonathon
J
Leipsic
Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Fay Y
FY
Lin
Department of Radiology, Giovanni XXIII Hospital, Monastier, Treviso, Italy; Department of Radiology, Erasmus Medical Center, Rotterdam, Netherlands.
Erica
E
Maffei
William Beaumont Hospital, Royal Oak, MI, USA.
Gilbert
G
Raff
Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Leslee J
LJ
Shaw
Walter Reed Medical Center, Bethesda, MD, USA.
Todd C
TC
Villines
Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Daniel S
DS
Berman
D000368:Aged; D002118:Calcium / Q000378:metabolism*; D003251:Constriction, Pathologic; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000473:pathology*; D048909:Diabetes Complications / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000473:pathology; D009204:Myocardial Revascularization; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014057:Tomography, X-Ray Computed
D002118:Calcium
Coronary CT angiography; Coronary artery calcium score; Coronary artery disease; Major adverse cardiac events