title: Peripheral microvascular dysfunction predicts residual risk in coronary artery disease patients on statin therapy.
abstract: OBJECTIVE
  Although lowering of low-density lipoprotein cholesterol (LDL-C) by statins is essential in treatment of coronary artery disease (CAD) patients, there is considerable residual risk of secondary coronary artery events (CAE). We examined whether microvascular dysfunction (MiD), measured by peripheral artery tonometry (PAT), can predict prognosis of CAD patients previously treated with statins.
  
  
  METHODS
  We measured log-transformed reactive hyperemia index (L_RHI) in 213 CAD patients who had already achieved LDL-C <100 by statin therapy. Patients were followed-up for secondary CAE for a median of 2.7 years. Patients were divided into two groups: L_RHI ≥ 0.54 (n = 99) and L_RHI < 0.54 (n = 114).
  
  
  RESULTS
  During follow-up, CAE occurred in 4 (4.0%) patients in the L_RHI ≥ 0.54 group and 18 (15.8%) patients in the L_RHI < 0.54 group (P = 0.006). Cox regression analysis indicated that L_RHI was an independent predictor for CAE even after adjustment by Framingham traditional risk factors (FRF; age, T-C/HDL-C ratio, systolic blood pressure, diabetes, current smoker, and gender) and estimated glomerular filtration rate (eGFR) for secondary CAE (HR 0.79, 95% CI: 0.66-0.95). ROC analysis for CAE prediction showed that the AUC for models including FRF only, FRF + eGFR, and FRF + eGFR + L_RHI were 0.60, 0.71, and 0.77, respectively. Moreover, adding eGFR to FRF only (0.63, P = 0.003) and adding L_RHI to the FRF + eGFR model were associated with significant improvement of net reclassification improvement (0.79, P = 0.007).
  
  
  CONCLUSIONS
  MiD measured by non-invasive PAT adds incremental predictive ability to traditional risk factors for prognosis of CAD patients successfully treated with statins.
authors.affiliation: Department of Cardiology, Kameda Medical Center, Chiba, Japan; Life Science and Bioethics Research Center, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: yuya8950@gmail.com.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Matsue
authors.affiliation: Department of Rheumatology, Kameda Medical Center, Chiba, Japan; Harvard School of Public Health, Boston, MA, USA.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Cardiology, Kameda Medical Center, Chiba, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Nagahori
authors.affiliation: Department of Cardiology, Kameda Medical Center, Chiba, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ohno
authors.affiliation: Department of Cardiology, Kameda Medical Center, Chiba, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Cardiology, Kameda Medical Center, Chiba, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Matsumura
authors.affiliation: Department of Cardiology, Kameda Medical Center, Chiba, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Life Science and Bioethics Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000368:Aged; D019540:Area Under Curve; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006940:Hyperemia / Q000150:complications / Q000175:diagnosis*; D008297:Male; D008365:Manometry; D008833:Microcirculation; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Coronary artery disease; Microvascular dysfunction; Noninvasive; Optimal medical therapy; Statin