title: Peripheral endothelial function and cardiovascular events in high-risk patients.
abstract: BACKGROUND
  Endothelial dysfunction is a key component of vascular vulnerability. Reactive hyperemia index (RHI), as assessed by the peripheral arterial tonometry, can noninvasively evaluate endothelial function. This study was designed to determine the additional prognostic value of endothelial function to the Synergy Between PCI With Taxus and Cardiac Surgery Score (SYNTAXsc) and the Framingham Risk Score (FRS) in predicting cardiovascular events in high-risk patients.
  
  
  RESULTS
  We undertook a two-center prospective study in 528 stable patients at high-risk for cardiovascular events from the years 2006-2011. The RHI was measured before coronary angiography and coronary complexity was assessed by SYNTAXsc. After optimal therapies including coronary revascularization, there was follow-up with patients until August 2012. Cardiovascular events consist of cardiovascular death, myocardial infarction, unstable angina, ischemic stroke, coronary revascularization, heart failure-induced hospitalization, aortic disease, and peripheral arterial disease. During 1468 person-years of follow-up, 105 patients developed cardiovascular events. Multivariate Cox proportional hazards analysis identified B-type natriuretic peptide (BNP), SYNTAXsc, and RHI as independent cardiovascular event predictors (hazard ratio [95% confidence interval]: natural logarithm of BNP per 0.1: 1.019 [1.002 to 1.037]; P=0.023, SYNTAXsc per tertile: 2.426 [1.825 to 3.225]; P<0.0001, RHI per 0.1: 0.761 [0.673 to 0.859]; P<0.0001). When RHI was added to the FRS, BNP, and SYNTAXsc, net reclassification index was significantly improved (27.5%; P<0.0001), with a significant increase in the C-statistic (from 0.728 [0.679 to 0.778] to 0.766 [0.726 to 0.806]; P=0.031).
  
  
  CONCLUSIONS
  Advanced endothelial dysfunction significantly correlated with near future cardiovascular events in high-risk patients. This physiological vascular measurement improved risk discrimination when added to the FRS, BNP, and SYNTAXsc.
  
  
  BACKGROUND
  clinicaltrials.gov (http://www.clinicaltrials.gov). Unique identifier: NCT00737945.
authors.affiliation: Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Seigo
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sumida
authors.forename: Koichi
authors.initials: K
authors.lastname: Sugamura
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Nozaki
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ohba
authors.forename: Junichi
authors.initials: J
authors.lastname: Matsubara
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kurokawa
authors.forename: Koichiro
authors.initials: K
authors.lastname: Fujisue
authors.forename: Masaaki
authors.initials: M
authors.lastname: Konishi
authors.forename: Eiichi
authors.initials: E
authors.lastname: Akiyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nagayoshi
authors.forename: Megumi
authors.initials: M
authors.lastname: Yamamuro
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Satomi
authors.initials: S
authors.lastname: Iwashita
authors.forename: Hideaki
authors.initials: H
authors.lastname: Jinnouchi
authors.forename: Masataka
authors.initials: M
authors.lastname: Taguri
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Matsui
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000401:mortality; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D054855:Drug-Eluting Stents; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D007564:Japan; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008365:Manometry; D008875:Middle Aged; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects* / Q000295:instrumentation / Q000401:mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D020097:Natriuretic Peptide, Brain
keywords: cardiovascular events; endothelial dysfunction; follow‐up study