title: Prognostic interplay of coronary artery calcification and underlying vascular dysfunction in patients with suspected coronary artery disease.
abstract: OBJECTIVE
  This study sought to evaluate the interrelation of atherosclerotic burden, as assessed by coronary artery calcium (CAC) score and coronary vascular function, as assessed by quantitative estimates of coronary flow reserve (CFR), with respect to prediction of clinical outcomes.
  
  
  BACKGROUND
  The contribution of coronary vascular dysfunction, atherosclerotic burden, and the 2 combined to cardiac events is unknown.
  
  
  METHODS
  A total of 901 consecutive patients underwent (82)Rubidium myocardial perfusion imaging (MPI) positron emission tomography (PET) and CAC scan. All patients had normal MPI. The primary endpoint was a composite of major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, late revascularization, and admission for heart failure.
  
  
  RESULTS
  At baseline, CFR decreased (2.15 ± 0.72, 2.02 ± 0.65, and 1.88 ± 0.64, p < 0.0001) with increasing levels of CAC (0, 1 to 399, and ≥400). Over a median of 1.53 years (interquartile range: 0.77 to 2.44), there were 57 MACE. Annual risk-adjusted MACE rates were higher for patients with CFR <2.0 compared with ≥2.0 (1.9 vs. 5.5%/year, p = 0.0007) but were only borderline associated with CAC (3.1%, 3.4%, and 6.2%/year for CAC of 0, 1 to 399, and ≥400, respectively; p = 0.09). Annualized adjusted MACE was increased in the presence of impaired CFR even among patients with CAC = 0 (1.4% vs. 5.2%, p = 0.03). Cox proportional hazards analysis revealed that CFR improved model fit, risk discrimination, and risk reclassification over clinical risk, whereas CAC only modestly improved model fit without improving risk discrimination or reclassification.
  
  
  CONCLUSIONS
  In symptomatic patients with normal MPI, global CFR but not CAC provides significant incremental risk stratification over clinical risk score for prediction of major adverse cardiac events.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Non-Invasive Cardiovascular Imaging Program, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Masanao
authors.initials: M
authors.lastname: Naya
authors.forename: Venkatesh L
authors.initials: VL
authors.lastname: Murthy
authors.forename: Courtney R
authors.initials: CR
authors.lastname: Foster
authors.forename: Mariya
authors.initials: M
authors.lastname: Gaber
authors.forename: Josh
authors.initials: J
authors.lastname: Klein
authors.forename: Jon
authors.initials: J
authors.lastname: Hainer
authors.forename: Sharmila
authors.initials: S
authors.lastname: Dorbala
authors.forename: Ron
authors.initials: R
authors.lastname: Blankstein
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Di Carli
mesh_terms: D000368:Aged; D057791:Cardiac Imaging Techniques; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000150:complications* / Q000175:diagnosis* / Q000401:mortality; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy; D009204:Myocardial Revascularization; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D061205:Vascular Calcification / Q000150:complications* / Q000175:diagnosis* / Q000401:mortality