title: Effect of phosphodiesterase type 5 inhibition on microvascular coronary dysfunction in women: a Women's Ischemia Syndrome Evaluation (WISE) ancillary study.
abstract: BACKGROUND
  Microvascular coronary dysfunction (MCD) is associated with symptoms and signs of ischemia, and also adverse outcomes in women without macrovascular obstructive coronary artery disease (M-CAD). Although MCD can be quantified using coronary flow reserve (CFR), treatment is poorly defined.
  
  
  OBJECTIVE
  Phosphodiesterase type 5 (PDE-5) inhibition acutely improves MCD in these women.
  
  
  METHODS
  The subjects were 23 symptomatic women (age 54 ± 11 y) participating in an ancillary study of the Women's Ischemia Syndrome Evaluation with baseline CFR ≤3.0 (Doppler flow wire and intracoronary adenosine) and without M-CAD. Coronary flow reserve was remeasured 45 minutes after PDE-5 inhibition (100 mg oral sildenafil). The primary measure of interest was change in CFR adjusted for baseline variables.
  
  
  RESULTS
  The relationship between log(2)-transformed CFR post-PDE-5 inhibition (adjusted) and baseline was different from the line of identity (slope: 0.55 vs 1.0, P = 0.008; intercept: 0.73 vs 0.0, P = 0.01), indicating that PDE-5 inhibition improves CFR and the lower the baseline CFR, the greater the response. Among women with baseline CFR ≤2.5 (n = 11), CFR increased from 2.1 ± 0.2 to 2.7 ± 0.6 (P = 0.006). For women with baseline CFR >2.5 (n = 12), CFR did not change (3.1 ± 0.3 to 3.0 ± 0.6; P = 0.70).
  
  
  CONCLUSIONS
  For women with symptoms and signs of ischemia and no M-CAD, PDE-5 inhibition is associated with acute improvement in CFR, and the effect concentrates among those with CFR ≤2.5. If these acute effects are sustained, then PDE-5 inhibition would provide a rational strategy for management of MCD in symptomatic women without M-CAD. The longer-term effects warrant study in a randomized trial using a sustained-acting PDE-5 inhibitor.
authors.affiliation: Division of Cardiovascular Medcinie, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Denardo
authors.forename: Xuerong
authors.initials: X
authors.lastname: Wen
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Handberg
authors.forename: C Noel
authors.initials: CN
authors.lastname: Bairey Merz
authors.forename: George S
authors.initials: GS
authors.lastname: Sopko
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Cooper-Dehoff
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
mesh_terms: D000241:Adenosine; D000328:Adult; D000368:Aged; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D015150:Echocardiography, Doppler; D005260:Female; D006801:Humans; D016014:Linear Models; D008833:Microcirculation / Q000187:drug effects; D055806:Microvessels / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011687:Purines / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States; D014665:Vasodilator Agents / Q000627:therapeutic use*; D016387:Women's Health
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D000241:Adenosine