title: Coronary endothelial function testing provides superior discrimination compared with standard clinical risk scoring in prediction of cardiovascular events.
abstract: BACKGROUND
  Endothelial dysfunction is regarded as the early stage of atherosclerosis and is associated with cardiovascular (CV) events. This study was designed to determine whether assessment of coronary endothelial function (CEF) is safe and can reclassify risk in patients with early coronary artery disease beyond the Framingham risk score (FRS).
  
  
  RESULTS
  CEF was evaluated using intracoronary acetylcholine in 470 patients who presented with chest pain and nonobstructive coronary artery disease. CV events were assessed after a median follow-up of 9.7 years. The association between CEF and CV events was examined, and the net reclassification improvement index (NRI) was used to compare the incremental contribution of CEF when added to FRS.The mean age was 53 years, and 68% of the patients were women with a median FRS of 8. Complications (coronary dissection) occurred in three (0.6%) and CV events in 61 (13%) patients. In univariate analysis, microvascular CEF [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.72-0.97, P=0.032] and epicardial CEF (HR 0.73, 95% CI 0.59-0.90, P=0.01) were found to be significant predictors of CV events, whereas FRS was not (HR 1.05, 95% CI 0.85-1.26, P=0.61). When added to FRS, microvascular CEF correctly reclassified 11.3% of patients [NRI 0.11 (95% CI 0.019-0.21)], epicardial CEF correctly reclassified 12.1% of patients [NRI 0.12 (95% CI -0.02 to 0.26)], and the combined microvascular and epicardial CEF correctly reclassified 22.8% of patients [NRI 0.23 (95% CI 0.08-0.37)].
  
  
  CONCLUSIONS
  CEF testing is safe and adds value to the FRS, with superior discrimination and risk stratification compared with FRS alone in patients presenting with chest pain or suspected ischemia.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic Rochester, Rochester, Minnesota, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Reriani
authors.forename: Jaskanwal D
authors.initials: JD
authors.lastname: Sara
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Flammer
authors.forename: Rajiv
authors.initials: R
authors.lastname: Gulati
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Charanjit
authors.initials: C
authors.lastname: Rihal
authors.forename: Ryan
authors.initials: R
authors.lastname: Lennon
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000503:physiopathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D042241:Early Diagnosis; D015150:Echocardiography, Doppler; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006334:Heart Function Tests; D006801:Humans; D007261:Infusions, Intra-Arterial; D053208:Kaplan-Meier Estimate; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D008910:Minnesota; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000109:Acetylcholine