Association of cytokines with endothelium dependent flow mediated vasodilation (FMD) of systemic arteries in patients with non-ischemic cardiomyopathy.

BACKGROUND: Aim of this study was to elucidate the relation between localised inflammatory heart disease and endothelial dysfunction in the peripheral circulation, considering circulating cytokines as a potential link. METHODS: In 38 patients with non-ischemic heart disease, myocardial biopsies were examined for myocardial inflammation (immunohistology) and virus persistence (PCR). Cytokines (sIL-4, IFN-g, IFN-b, IFN-a, sIL-12p7, TNF-a) were measured by ELISA in venous serum. Endothelial function of the radial artery was examined by ultrasound, measuring diameter changes in response to reactive hyperemia (FMD), compared to glyceroltrinitrate (GTN-MD). Patients with EF < 35% were excluded. RESULTS: Age 44 +/- 14 years, 19 male, 19 female, EF 63.5[16]%. FMD 4.38 [4.82]%. 30 patients had myocardial inflammation (8 not), 23 virus persistence (15 not). FMD correlated significantly with sIL-12p7 (p = 0.024, r = -0.365), but not with other cytokines. sIL-12p7 levels were significantly higher in patients with severely impaired FMD (n = 17), compared with normal FMD (n = 21): 10.70 [10.72] vs. 4.33 [7.81] pg/ml (p = 0.002). Endothelium independent vasodilation (GTN-MD 23.67 [8.21]%) was not impaired. CONCLUSION: Endothelial dysfunction of peripheral arteries in patients with non-ischemic cardiomyopathy is associated with elevated serum concentrations of sIL-12p7, but not of other cytokines. Circulating sIL-12p7 may partly explain, that endothelial dysfunction is not restricted to the coronary circulation, but involves systemic arteries.

Correlation of epicardial and systemic flow-mediated vasodilation in patients with atypical angina but no evidence of atherosclerotic disease.

BACKGROUND: Atypical angina represents a diagnostic challenge and can be observed in the absence of significant coronary atherosclerosis. Endothelial dysfunction is a relevant marker of prognosis, considering cardiovascular events. The aim of the present study was to compare flow-mediated vasodilation (FMD) in systemic peripheral and epicardial coronary arteries. If noninvasive measurements of FMD in systemic arteries correlated with invasive measurements of coronary FMD, this may facilitate diagnostic approaches and determination of prognosis in patients with atypical angina in the future. Patients with atherosclerosis were excluded, because structural changes of coronary vessels may impair adequate comparison. METHODS: Endothelial function (ENF) of epicardial and systemic arteries was examined in 61 consecutive patients with atypical angina in whom significant atherosclerosis was excluded by coronary angiography. ENF of the epicardial arteries was examined during heart catheterization, measuring diameter changes of the proximal left anterior descending coronary artery (LAD) in response to reactive hyperemia, induced by locally administered adenosine via infusion catheter to the mid-segment of the LAD (coronary FMD [FMDc]). ENF of the radial artery was examined with high-resolution ultrasound, measuring peripheral FMD (FMDp) in response to reactive hyperemia induced by distal cuff occlusion. Endothelium-independent vasoreactivity to glycerol trinitrate was assessed. RESULTS: In patients with atypical angina in the absence of atherosclerosis, there was a significant correlation in ENF between coronary and systemic arteries (r=0.437; P=0.001). The underlying disease was myocardial inflammation (Inf) in 48 patients, in whom the mean (+/- SD) ENF of epicardial (FMDc-Inf 3.40+/-5.55%) and systemic (FMDp-Inf 3.69+/-2.93%) arteries was significantly impaired (P<0.001), compared with 13 control (Co) patients who had normal myocardial biopsies (FMDc-Co 14.51+/-8.62%; FMDp-Co 7.69+/-3.42%). FMD of coronary (r=-0.353; P=0.005) and systemic (r=-0.542; P<0.001) arteries correlated significantly with myocardial inflammation and endothelial activation. CONCLUSIONS: There was a significant correlation in FMD between coronary and systemic arteries in patients with atypical angina but without significant atherosclerosis. Inflammatory processes are associated with endothelial dysfunction of both vascular regions.