title: Prognostic value of an abnormal response to acetylcholine in patients with angina and non-obstructive coronary artery disease: Long-term follow-up of the Heart Quest cohort.
abstract: BACKGROUND
  This study aims to determine whether small vessel disease (SVD) or vasospastic disease (VSD) has an impact on prognosis.
  
  
  METHODS
  The prospective cohort embraced 718 patients with angina equivalent symptoms and no coronary stenosis ≥50% recruited between 1997 and 2008. At baseline, patients were classified as having SVD, VSD, other cardiac disease or non-cardiac problem based on intracoronary acetylcholine application and fast atrial pacing during coronary angiography. Patients underwent follow-up between 2007 and 2015. Prognostic significance of the diagnosis on cardiovascular events (cardiovascular death or non-fatal myocardial infarction) was evaluated using Cox proportional hazards models adjusted for age and sex.
  
  
  RESULTS
  The mean follow-up duration was 11.3±2.7years. Only 11 patients (1.5%) were lost to follow-up, resulting in an analyzed population of 707 patients. Patients with SVD (HR: 4.9, 95% CI: 1.1-22.4, P=0.040) and VSD (HR: 4.8, 95% CI: 1.0-23.4, P=0.050) had an increased risk of suffering cardiovascular events compared to patients with non-cardiac problems. Among SVD patients, those with the presence of endothelial dysfunction had a particularly high risk (HR: 7.3, 95% CI: 1.5-35.5, P=0.015). Among patients with SVD or VSD, those having persisting or worsening angina during follow-up had a higher risk than patients in whom angina improved (HR: 4.8, 95% CI: 1.9-12.3, P=0.001).
  
  
  CONCLUSIONS
  Our study shows that patients with SVD or VSD have an increased risk of cardiovascular events. This particularly applies to SVD patients with endothelial dysfunction. Symptoms should be taken seriously in SVD and VSD patients.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT01318629.
authors.affiliation: Department of Geriatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address: Andreas.Schoenenberger@insel.ch.
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Schoenenberger
authors.affiliation: Department of Geriatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Adler
authors.affiliation: Department of Cardiology, Luzerner Kantonsspital, Luzern, Switzerland.
authors.forename: Samuel
authors.initials: S
authors.lastname: Gujer
authors.affiliation: Department of Cardiology, Luzerner Kantonsspital, Luzern, Switzerland.
authors.forename: Peiman
authors.initials: P
authors.lastname: Jamshidi
authors.affiliation: Department of Cardiology, Luzerner Kantonsspital, Luzern, Switzerland.
authors.forename: Richard
authors.initials: R
authors.lastname: Kobza
authors.affiliation: Department of Geriatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Stuck
authors.affiliation: Department of Biomedicine, University Hospital Basel and University of Basel, Switzerland.
authors.forename: Therese J
authors.initials: TJ
authors.lastname: Resink
authors.affiliation: Department of Biomedicine, University Hospital Basel and University of Basel, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Erne
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000503:physiopathology; D017023:Coronary Angiography / Q000379:methods*; D003324:Coronary Artery Disease / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D003329:Coronary Vasospasm / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods; D013557:Switzerland / Q000453:epidemiology; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D014665:Vasodilator Agents; D000109:Acetylcholine
keywords: Angina pectoris; Coronary artery disease; Microvascular angina; Variant