Combination of Flow-Mediated Vasodilation and Nitroglycerine-Induced Vasodilation Is More Effective for Prediction of Cardiovascular Events

Hypertension. 2016 May;67(5):1045-52. doi: 10.1161/HYPERTENSIONAHA.115.06839. Epub 2016 Mar 14.


Measurement of nitroglycerine-induced vasodilation has been performed to differentiate endothelium-dependent vasodilation from endothelium-independent vasodilation as a control test for flow-mediated vasodilation (FMD). Recently, nitroglycerine-induced vasodilation per se has been reported to be a useful marker of the grade of atherosclerosis. The present study aimed to evaluate the prognostic value of FMD combined with nitroglycerine-induced vasodilation for future cardiovascular events. We measured FMD and nitroglycerine-induced vasodilation in 402 subjects, including patients with cardiovascular diseases. During a median follow-up period of 32.3 months, 38 first major cardiovascular events (death from cardiovascular causes, acute myocardial infarction, stroke, and coronary revascularization) occurred. Receiver-operator characteristic curve analysis revealed that FMD alone and nitroglycerine-induced vasodilation alone can predict cardiovascular events with areas under the curve of 0.671 (cutoff 3.3%) and 0.692 (cutoff 11.6%), respectively. FMD combined with nitroglycerine-induced vasodilation predicts cardiovascular events with an area under the curve of 0.701. After adjustment for age, sex, and cardiovascular risk factors, above cutoff FMD (≥3.3%) and below cutoff nitroglycerine-induced vasodilation (<11.6%; hazard ratio, 5.55; 95% confidence interval, 1.61-25.46;P=0.006) and below cutoff FMD (<3.3%) and below cutoff nitroglycerine-induced vasodilation (<11.6%; hazard ratio, 7.20; 95% confidence interval, 2.37-31.36;P<0.001) remained strong independent indicator of cardiovascular events. These findings suggest that the combination of FMD and nitroglycerine-induced vasodilation measurements can more accurately predict cardiovascular events compared with FMD alone.

Clinical trial registration: URL: Unique identifier: UMIN000001167.

Keywords: atherosclerosis; biomarkers; cardiovascular diseases; endothelium; myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Atherosclerosis / diagnosis*
  • Atherosclerosis / drug therapy
  • Blood Flow Velocity / drug effects
  • Brachial Artery / drug effects*
  • Brachial Artery / physiology
  • Cardiovascular Diseases / physiopathology*
  • Cohort Studies
  • Endothelium, Vascular / drug effects*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitroglycerin / administration & dosage*
  • Predictive Value of Tests
  • Proportional Hazards Models
  • ROC Curve
  • Retrospective Studies
  • Risk Factors
  • Vasodilation / drug effects*


  • Nitroglycerin

Associated data

  • JPRN/UMIN000001167