title: The CHADS2 and CHA2DS2-VASc scores predict adverse vascular function, ischemic stroke and cardiovascular death in high-risk patients without atrial fibrillation: role of incorporating PR prolongation.
abstract: OBJECTIVE
  To investigate whether the CHADS2 and CHA2DS2-VASc scores have clinical utility for prediction of adverse vascular function and vascular dysfunction-mediated incident cardiovascular (CV) events among high-risk patients without atrial fibrillation (AF), and the additional value of incorporating PR prolongation to the scores.
  
  
  METHODS
  We analyzed 579 high-risk CV outpatients without clinical AF in a prospective cohort for new-onset ischemic stroke, myocardial infarction (MI), congestive heart failure (CHF), and CV death. Brachial flow-mediated dilation (FMD) and nitroglycerin-mediated dilatation (NMD), carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were determined.
  
  
  RESULTS
  Baseline CHADS2 score was associated with lower FMD (Pearson r = -0.16, P < 0.001) and NMD (r = -0.17, P < 0.001), higher carotid IMT (r = 0.30, P < 0.001) and PWV (r = 0.35, P < 0.001; similar for CHA2DS2-VASc score: All P < 0.05). After follow-up of 63 ± 11 months, 82 patients (14.2%) developed combined CV endpoint. ROC curve analysis showed that both CHADS2 and CHA2DS2-VASc scores were predictors for ischemic stroke (C-Statistic: CHADS2 0.70, P = 0.004; CHA2DS2-VASc 0.68, P = 0.010), MI (CHADS2 0.63, P = 0.030; CHA2DS2-VASc 0.70, P = 0.001), and CV death (CHADS2 0.63, P = 0.022; CHA2DS2-VASc 0.65, P = 0.011). Higher CHADS2 score was associated with reduced event-free survival from combined CV endpoints (log-rank = 16.7, P < 0.001) with differences potentiated if stratified by CHA2DS2-VASc score (log-rank = 29.2, P < 0.001). Incorporating PR prolongation, the CHA2DS2-VASc-PR score achieved the highest C-Statistic for CV death prediction (0.70, P < 0.001) superior to the CHADS2 score (chi-square: 12.1, P = 0.0005).
  
  
  CONCLUSIONS
  The CHADS2 and CHA2DS2-VASc predict vascular dysfunction and cardiovascular events in high-risk CV patients without clinical AF, with further improved performance incorporating PR prolongation.
authors.affiliation: Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, China; School of Public Health, The University of Hong Kong, China.
authors.forename: Yap-Hang
authors.initials: YH
authors.lastname: Chan
authors.affiliation: Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, China.
authors.forename: Kai-Hang
authors.initials: KH
authors.lastname: Yiu
authors.affiliation: Division of Neurology, Queen Mary Hospital, The University of Hong Kong, China.
authors.forename: Kui-Kai
authors.initials: KK
authors.lastname: Lau
authors.affiliation: Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, China.
authors.forename: Yuen-Fung
authors.initials: YF
authors.lastname: Yiu
authors.affiliation: Department of Medicine, Tung Wah Hospital, China.
authors.forename: Sheung-Wai
authors.initials: SW
authors.lastname: Li
authors.affiliation: School of Public Health, The University of Hong Kong, China.
authors.forename: Tai-Hing
authors.initials: TH
authors.lastname: Lam
authors.affiliation: Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, China.
authors.forename: Chu-Pak
authors.initials: CP
authors.lastname: Lau
authors.affiliation: Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, China; Research Center of Heart, Brain, Hormone and Healthy Ageing, University of Hong Kong, China.
authors.forename: Chung-Wah
authors.initials: CW
authors.lastname: Siu
authors.affiliation: Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, China; Research Center of Heart, Brain, Hormone and Healthy Ageing, University of Hong Kong, China. Electronic address: hftse@hkucc.hku.hk.
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000503:physiopathology*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D004106:Dilatation; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006305:Health Status Indicators; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000473:pathology; D005996:Nitroglycerin / Q000737:chemistry; D016016:Proportional Hazards Models; D011446:Prospective Studies; D063177:Pulse Wave Analysis; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D005996:Nitroglycerin
keywords: Adverse cardiovascular events; CHADS(2) and CHA(2)DS(2)-VASc scores; Cardiovascular continuum; PR prolongation; Risk prediction; Vascular dysfunction