Abstract 3354: Persistent Impairment of Endothelial Function is a Predictor of Adverse Outcomes in Patients with Coronary Artery Disease
Although endothelial dysfunction is a predictor of cardiovascular events, it remains unclear whether reversibility of endothelial dysfunction in response to risk-factor reduction provides prognostic information. Thus, this study assessed the hypothesis that changes in endothelial vasomotor function in response to optimized therapies for atherosclerotic coronary artery disease (CAD) may predict future cardiovascular events.
Methods: This study included 154 consecutive patients with newly diagnosed CAD who had an impairment of flow-mediated dilation of the brachial artery (FMD) at enrollment. Measurement of FMD (expressed as percent dilation from baseline brachial arterial diameter) during reactive hyperemia was performed by high-resolution ultrasound at entry and after 6 months. All patients had individualized, optimized therapies including medications and recommended life style changes to reduce risk factors for CAD according to AHA guidelines. Patients were prospectively followed up until the occurrence of one of the following events: cardiovascular death, nonfatal myocardial infarction, recurrent or refractory angina pectoris, and ischemic stroke. The impairment of FMD was defined as < 5.5% (mean minus 1 SD of FMD in 100 age- and sex-matched normal subjects in our hospital).
Results: FMD was persistently impaired (<5.5%) in 66 (43%) patients after 6 months of the optimized therapy, while it was improved (FMD ≥ 5.5%) in the remaining 88 (57%) patients. FMD at entry was comparable between the 2 groups of the patients (3.2 ± 0.2 vs. 3.4 ± 0.2%, respectively, p = ns). During a follow-up period of 24 ± 2.7 months, events occurred in 22 (33%) of the 66 patients with persistently impaired FMD and in 6 (7%) of the 88 patients with improved FMD (p < 0.01 by chi-squire test). Using multivariate Cox hazards analysis, persistent impairment of FMD was a predictor of future cardiovascular events, independently of FMD at entry, use of medications, age, and traditional CAD risk factors (odds ratio 3.9, 95%CI 1.4 - 11.5, p < 0.01).
Conclusions: Persistent impairment of endothelial function despite optimized therapies to reduce CAD risk factors represents an adverse outcome in CAD patients. Periodic measurement of FMD may be useful for risk stratification in CAD.