title: Insulin resistance is a major determinant of myocardial blood flow impairment in anginal patients.
abstract: OBJECTIVE
  In patients with chest pain, stress-induced myocardial perfusion abnormalities are often the result of depressed myocardial blood flow (MBF) reserve. We investigated the relative contribution of cardiovascular risk factors and coronary atherosclerosis to MBF abnormalities in anginal patients.
  
  
  METHODS
  We studied 167 patients with typical (n = 100) or atypical (n = 67) chest pain who underwent quantitative evaluation of MBF by PET at rest and after dipyridamole infusion, and quantitative coronary angiography (invasive or by 64-slice CT). Patients with left ventricular (LV) dysfunction (ejection fraction <45 %) were excluded. Coronary atherosclerosis of ≥50 % was defined as obstructive.
  
  
  RESULTS
  At rest median MBF was 0.60 ml min-1g-1, and after dipyridamole infusion median MBF was 1.22 ml min-1g-1. MBF reserve was <2 in 77 of 167 patients (46 %). Coronary atherosclerosis was present in 67 patients (40 %), 26 with obstructive disease. In a univariate analysis several variables were associated with reduced MBF at rest, including male gender, coronary atherosclerosis and elevated LV end-diastolic diameter, and during hyperaemia, including male gender, insulin resistance (IR), smoking habit, LV ejection fraction and end-diastolic diameter. In a multivariate analysis, after adjustment for LV function and for pharmacological treatments, male gender was the only independent predictor of reduced MBF at rest (P < 0.001), while male gender (P = 0.003), IR (P = 0.033) and coronary atherosclerosis (P < 0.001) remained the only independent predictors of reduced hyperaemic MBF. IR (P = 0.043) and coronary atherosclerosis (P = 0.005) were the only predictors of depressed MBF reserve. Coronary atherosclerosis, male gender and IR showed additive effects on hyperaemic MBF.
  
  
  CONCLUSIONS
  In patients with chest pain and normal LV systolic function, IR, male gender and coronary atherosclerosis are independent and additive determinants of impaired hyperaemic MBF.
authors.affiliation: Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Liga
authors.forename: Daniele
authors.initials: D
authors.lastname: Rovai
authors.forename: Tiziana
authors.initials: T
authors.lastname: Sampietro
authors.forename: Cecilia
authors.initials: C
authors.lastname: Vecoli
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Todiere
authors.forename: Chiara
authors.initials: C
authors.lastname: Caselli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.forename: Antonio
authors.initials: A
authors.lastname: L'abbate
authors.forename: Danilo
authors.initials: D
authors.lastname: Neglia
references.citation: Diabetes Care. 2000 Jan;23(1):57-63
references.pmid: 10857969
references.citation: J Am Coll Cardiol. 2009 Sep 1;54(10):877-85
references.pmid: 19712795
references.citation: Circulation. 2006 Apr 18;113(15):1888-904
references.pmid: 16618833
references.citation: Circulation. 2002 Jan 15;105(2):186-93
references.pmid: 11790699
references.citation: Eur Heart J. 2007 Jan;28(1):88-136
references.pmid: 17220161
references.citation: BMC Med Genet. 2012 Oct 02;13:92
references.pmid: 23031426
references.citation: Eur Heart J. 2006 Jun;27(11):1341-81
references.pmid: 16735367
references.citation: Circulation. 1999 Apr 13;99(14):1795-801
references.pmid: 10199874
references.citation: Am J Physiol Heart Circ Physiol. 2011 Dec;301(6):H2279-84
references.pmid: 21984541
references.citation: Eur J Nucl Med. 1998 Sep;25(9):1313-21
references.pmid: 9724382
references.citation: J Nucl Med. 2011 Sep;52(9):1369-77
references.pmid: 21849399
references.citation: J Nucl Cardiol. 2012 Dec;19(6):1182-9
references.pmid: 22879076
references.citation: J Nucl Cardiol. 2006 Nov;13(6):761-7
references.pmid: 17174807
references.citation: J Am Coll Cardiol. 2008 Jan 29;51(4):466-72
references.pmid: 18222358
references.citation: Circ Heart Fail. 2013 Mar;6(2):184-92
references.pmid: 23258572
references.citation: J Nucl Med. 2009 Feb;50(2):214-9
references.pmid: 19164219
references.citation: Circulation. 2005 May 10;111(18):2291-8
references.pmid: 15851590
references.citation: Am J Cardiol. 2005 Dec 15;96(12):1718-20
references.pmid: 16360363
references.citation: Eur J Nucl Med Mol Imaging. 2012 Jan;39(1):102-12
references.pmid: 22005845
references.citation: Cardiovasc Res. 2001 Apr;50(1):151-61
references.pmid: 11282088
references.citation: J Am Coll Cardiol. 2003 Apr 16;41(8):1387-93
references.pmid: 12706936
references.citation: Circulation. 1995 Aug 15;92(4):796-804
references.pmid: 7641359
references.citation: J Am Coll Cardiol. 2008 Aug 19;52(8):636-43
references.pmid: 18702967
references.citation: N Engl J Med. 2007 Feb 22;356(8):830-40
references.pmid: 17314342
references.citation: J Nucl Med. 2011 Nov;52(11):1704-12
references.pmid: 21930670
references.citation: Circulation. 2000 Sep 12;102(11):1233-8
references.pmid: 10982536
references.citation: J Am Coll Cardiol. 1999 Feb;33(2):463-70
references.pmid: 9973027