Abstract 11013: Endothelial Dysfunction Highly Predicts Future Diabetic Evolution and Development of Adverse Cardiovascular or Fatal Events
Background:Although diabetes mellitus (DM) and endothelial dysfunction (ED) are thought to affect atherogenic processes, we know little about the clinical impact of ED on evolutional mechanisms of DM. This study assessed hypothesis that ED accelerates diabetic evolution (DME) and adverse clinical events.
Methods: ED was graded by reactive changes in lumen diameter of right brachial artery following transient forearm occlusion (FMD; flow-mediated endothelium-dependent vasodilation) in consecutive 518 patients with stable coronary artery disease using high-resolution ultrasonography.The enrolled patients were categorized into 3 groups according to the values of FMD, and their glucose tolerance and adverse clinical events were followed-up for 36 months or more. We prospectively followed up DME, which was defined as newly diagnosed DM by 75g-OGTT or new administration of an antidiabetic agent.
Results:For a mean follow-up period of 60 months with 100% follow-up, the patients with severe ED (FMD<4%; Group-L, n=174), more frequently manifested DME [Group-L versus Group-M with mild ED (4%≤FMD<8%, n=171) plus Group-H with preserved endothelial function (FMD 8% or more, n=173): 25 (14.4%) versus 12 (7.0%) plus 7(4.0%), p<0.001, by Kaplan-Meier analysis]. The patients in Group-L more frequently developed cardiovascular events (CVE)[Group-L versus Group-M plus Group-H: 48 (28%) versus 13 (7.6%) plus 3(1.7%), p<0.001, by Kaplan-Meier analyses] and resulted in fatal events [Group-L versus Group-M plus Group-H: 15(8.6%) versus 4(2.3%) plus 2(1.2%), p<0.001]. HbA1c significantly elevated in Group-L (5.9±0.6 to 6.2±0.9, p=0.009) but not in Group-M or Group-H. Cox proportional hazard model analysis including clinical variables showed that severe ED was a significant predictor for future DME (hazard ratio=2.69, p=0.011), CVE (hazard ratio=3.75, p<0.001), and all-causal death (hazard ratio=5.87, p=0.009).
Conclusion:This is the first clinical ultrasonic vascular investigation demonstrating that endothelial dysfunction accelerates diabetic evolution and causes excess of adverse cardiovascular events or fatal events and strategies based on practical status of endothelial function are required for metabolic and vascular management.
- © 2012 by American Heart Association, Inc.