Endothelial Dysfunction, Increased Arterial Stiffness, and Cardiovascular Risk Prediction in Patients With Coronary Artery Disease: FMD-J (Flow-Mediated Dilation Japan) Study A

J Am Heart Assoc. 2018 Jul 12;7(14):e008588. doi: 10.1161/JAHA.118.008588.


Background: The usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known.

Methods and results: We measured flow-mediated vasodilation (FMD) and brachial-ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow-up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver-operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06-0.74; P=0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09-0.79; P=0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01-3.44; P=0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23-3.90; P=0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed.

Conclusions: In patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification.

Clinical trial registration: URL: www.umin.ac.jp. Unique identifier: UMIN000012950.

Keywords: arterial stiffness; coronary artery disease; endothelial function; flow‐induced dilation; pulse wave velocity.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brachial Artery / diagnostic imaging
  • Cardiovascular Diseases
  • Coronary Artery Disease / epidemiology
  • Coronary Artery Disease / physiopathology*
  • Death, Sudden, Cardiac / epidemiology*
  • Endothelium, Vascular / physiopathology
  • Female
  • Heart Failure / epidemiology*
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Pulse Wave Analysis
  • Risk Assessment
  • Stroke / epidemiology*
  • Vascular Stiffness / physiology*
  • Vasodilation