title: Quantitative relationship between coronary artery calcium score and hyperemic myocardial blood flow as assessed by hybrid 15O-water PET/CT imaging in patients evaluated for coronary artery disease.
abstract: BACKGROUND
  The incremental value of CAC over traditional risk factors to predict coronary vasodilator dysfunction and inherent myocardial blood flow (MBF) impairment is only scarcely documented (MBF). The aim of this study was therefore to evaluate the relationship between CAC content, hyperemic MBF, and coronary flow reserve (CFR) in patients undergoing hybrid (15)O-water PET/CT imaging.
  
  
  METHODS
  We evaluated 173 (mean age 56 ± 10, 78 men) patients with a low to intermediate likelihood for coronary artery disease (CAD), without a documented history of CAD, undergoing vasodilator stress (15)O-water PET/CT and CAC scoring. Obstructive coronary artery disease was excluded by means of invasive (n = 44) or CT-based coronary angiography (n = 129).
  
  
  RESULTS
  91 of 173 patients (52%) had a CAC score of zero. Of those with CAC, the CAC score was 0.1-99.9, 100-399.9, and ≥400 in 31%, 12%, and 5% of patients, respectively. Global CAC score showed significant inverse correlation with hyperemic MBF (r = -0.32, P < .001). With increasing CAC score, there was a decline in hyperemic MBF on a per-patient basis [3.70, 3.30, 2.68, and 2.53 mL · min(-1) · g(-1), with total CAC score of 0, 0.1-99.9, 100-399.9, and ≥400, respectively (P < .001)]. CFR showed a stepwise decline with increasing levels of CAC (3.70, 3.32, 2.94, and 2.93, P < .05). Multivariate analysis, including age, BMI, and CAD risk factors, revealed that only age, male gender, BMI, and hypercholesterolemia were associated with reduced stress perfusion. Furthermore, only diabetes and age were independently associated with CFR.
  
  
  CONCLUSIONS
  In patients without significant obstructive CAD, a greater CAC burden is associated with a decreased hyperemic MBF and CFR. However, this association disappeared after adjustment for traditional CAD risk factors. These results suggest that CAC does not add incremental value regarding hyperemic MBF and CFR over established CAD risk factors in patients without obstructive CAD.
authors.affiliation: Department of Cardiology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Danad
authors.forename: Pieter G
authors.initials: PG
authors.lastname: Raijmakers
authors.forename: Yolande E
authors.initials: YE
authors.lastname: Appelman
authors.forename: Hendrik J
authors.initials: HJ
authors.lastname: Harms
authors.forename: Stefan
authors.initials: S
authors.lastname: de Haan
authors.forename: Koen M
authors.initials: KM
authors.lastname: Marques
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Kuijk
authors.forename: Cornelis P
authors.initials: CP
authors.lastname: Allaart
authors.forename: Otto S
authors.initials: OS
authors.lastname: Hoekstra
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: Albert C
authors.initials: AC
authors.lastname: van Rossum
authors.forename: Paul
authors.initials: P
authors.lastname: Knaapen
mesh_terms: D002114:Calcinosis / Q000175:diagnosis* / Q000453:epidemiology*; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000175:diagnosis* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging / Q000706:statistics & numerical data*; D009426:Netherlands / Q000453:epidemiology; D010104:Oxygen Radioisotopes; D049268:Positron-Emission Tomography / Q000706:statistics & numerical data*; D015995:Prevalence; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013382:Subtraction Technique; D014057:Tomography, X-Ray Computed / Q000706:statistics & numerical data*; D014867:Water
chemical_list: D010104:Oxygen Radioisotopes; D014867:Water
references.citation: Eur J Nucl Med Mol Imaging. 2009 Oct;36(10):1603-10
references.pmid: 19387640
references.citation: Circulation. 2000 Apr 25;101(16):1931-9
references.pmid: 10779459
references.citation: Am J Cardiol. 1994 Jun 15;73(16):1169-73
references.pmid: 8203333
references.citation: N Engl J Med. 1994 Jun 23;330(25):1782-8
references.pmid: 8190154
references.citation: J Am Coll Cardiol. 1990 Mar 15;15(4):827-32
references.pmid: 2407762
references.citation: Circulation. 2001 Jul 31;104(5):527-32
references.pmid: 11479248
references.citation: J Nucl Med. 2010 Mar;51(3):477-83
references.pmid: 20150272
references.citation: Circulation. 2002 Jan 29;105(4):539-42
references.pmid: 11815441
references.citation: Circulation. 2010 Aug 10;122(6):603-13
references.pmid: 20660808
references.citation: Eur J Nucl Med Mol Imaging. 2011 May;38(5):930-9
references.pmid: 21271246
references.citation: JACC Cardiovasc Imaging. 2010 Jun;3(6):623-40
references.pmid: 20541718
references.citation: J Am Coll Cardiol. 1999 Sep;34(3):777-86
references.pmid: 10483960
references.citation: J Am Coll Cardiol. 2001 Feb;37(2):451-7
references.pmid: 11216962
references.citation: J Nucl Med. 2010 Apr;51(4):575-80
references.pmid: 20237035
references.citation: J Am Coll Cardiol. 1997 Jun;29(7):1542-8
references.pmid: 9180117
references.citation: Circulation. 1996 Sep 1;94(5):1175-92
references.pmid: 8790070
references.citation: J Am Coll Cardiol. 1998 Sep;32(3):673-9
references.pmid: 9741510
references.citation: Cardiovasc Res. 2003 Feb;57(2):312-9
references.pmid: 12566104
references.citation: Circulation. 1995 Apr 1;91(7):1944-51
references.pmid: 7895351
references.citation: J Am Coll Cardiol. 2006 Sep 5;48(5):1018-26
references.pmid: 16949496
references.citation: Eur J Nucl Med Mol Imaging. 2009 Feb;36(2):219-29
references.pmid: 18704406
references.citation: Eur J Nucl Med Mol Imaging. 2004 May;31(5):663-70
references.pmid: 14740179
references.citation: Circulation. 1975 Apr;51(4 Suppl):5-40
references.pmid: 1116248
references.citation: Basic Res Cardiol. 2009 Sep;104(5):485-98
references.pmid: 19468781
references.citation: Am Heart J. 2001 Oct;142(4):691-7
references.pmid: 11579361
references.citation: Eur Heart J. 2008 Aug;29(16):2006-13
references.pmid: 18573865
references.citation: Am J Cardiol. 2008 May 15;101(10):1444-7
references.pmid: 18471456
references.citation: Circulation. 2001 Nov 13;104(20):2401-6
references.pmid: 11705815
references.citation: N Engl J Med. 1979 Jun 14;300(24):1350-8
references.pmid: 440357
references.citation: J Nucl Med. 2005 Jan;46(1):75-88
references.pmid: 15632037
references.citation: J Am Coll Cardiol. 1998 Jan;31(1):126-33
references.pmid: 9426030