Association of arterial stiffness with coronary flow reserve in revascularized coronary artery disease patients.

AIM: To investigate the association of arterial wave reflection with coronary flow reserve (CFR) in coronary artery disease (CAD) patients after successful revascularization. METHODS: We assessed 70 patients with angiographically documented CAD who had undergone recent successful revascularization. We measured (1) reactive hyperemia index (RHI) using fingertip peripheral arterial tonometry (RH-PAT Endo-PAT); (2) carotid to femoral pulse wave velocity (PWVc-Complior); (3) augmentation index (AIx), the diastolic area (DAI%) and diastolic reflection area (DRA) of the central aortic pulse wave (Arteriograph); (4) CFR using Doppler echocardiography; and (5) blood levels of lipoprotein-phospholipase A2 (Lp-PLA2). RESULTS: After adjustment for age, sex, blood pressure parameter, lipidemic, diabetic and smoking status, we found that coronary flow reserve was independently related to AIx (b = -0.38, r = 0.009), DAI (b = 0.36, P = 0.014), DRA (b = 0.39, P = 0.005) and RT (b = -0.29, P = 0.026). Additionally, patients with CFR < 2.5 had higher PWVc (11.6 ± 2.3 vs 10.2 ± 1.4 m/s, P = 0.019), SBPc (139.1 ± 17.8 vs 125.2 ± 19.1 mmHg, P = 0.026), AIx (38.2% ± 14.8% vs 29.4% ± 15.1%, P = 0.011) and lower RHI (1.26 ± 0.28 vs 1.50 ± 0.46, P = 0.012), DAI (44.3% ± 7.9% vs 53.9% ± 6.7%, P = 0.008), DRA (42.2 ± 9.6 vs 51.6 ± 11.4, P = 0.012) and LpPLA2 (268.1 ± 91.9 vs 199.5 ± 78.4 ng/mL, P = 0.002) compared with those with CFR ≥ 2.5. Elevated LpPLA2 was related with reduced CFR (r = -0.33, P = 0.001), RHI (r = -0.37, P < 0.001) and DRA (r = -0.35, P = 0.001) as well as increased PWVc (r = 0.34, P = 0.012) and AIx (r = 0.34, P = 0.001). CONCLUSION: Abnormal arterial wave reflections are related with impaired coronary flow reserve despite successful revascularization in CAD patients. There is a common inflammatory link between impaired aortic wall properties, endothelial dysfunction and coronary flow impairment in CAD.

Effects of ranolazine on left ventricular diastolic and systolic function in patients with chronic coronary disease and stable angina.

INTRODUCTION: The present study examined the effect of ranolazine, which acts via the mechanism of selective inhibition of late INa+, on parameters of left ventricular systolic and diastolic function in patients suffering from angiographically confirmed chronic coronary artery disease, presenting with chronic stable angina. METHODS: We studied 40 patients (age 67 ± 9 years; 30 men, 10 women) with chronic coronary artery disease who reported angina symptoms on optimal medication and who were not suitable for invasive treatment. Patients were randomized to the ranolazine group (group A, 20 patients taking oral ranolazine 500 mg bid for 3 months) and the control group (group B, 20 patients who did not receive the drug). Left ventricular systolic and diastolic function was assessed echocardiographically at baseline and after the end of the three-month treatment period. Left ventricular ejection fraction by the modified Simpson's method, E and A left ventricular filling velocities, E/A ratio, deceleration time (DT) of E, isovolumic relaxation time (IVRT), E and A waves, and the E/E ratio were measured using 2-dimensional echocardiography, Doppler and tissue Doppler imaging (TDI). RESULTS: Group A patients demonstrated a clear improvement of their initial angina symptoms. There were no adverse effects from ranolazine requiring withdrawal from the study. There was no statistically significant change in left ventricular systolic function in either group. A statistically significant change was seen in indexes of diastolic function measured using both conventional Doppler and TDI in Group A patients compared with Group B patients after three months' ranolazine treatment period. The changes in left ventricular diastolic function indexes in Group A patients were as follows: E 0.58 ± 0.11 vs. 0.76 ± 0.12 m/s, p<0.001; A 0.71 ± 0.22 vs. 0.83 ± 0.19 m/s, p<0.001; E/A 0.81 ± 0.14 vs. 0.97 ± 0.17, p<0.005; 5.4 ± 0.7 vs. 6.8 ± 0.9 cm/s, p<0.005; 7.2 ± 0.8 vs. 8.3 ± 1.1 cm/s, p<0.005; E/ 10.7 ± 1.1 vs. 11.1 ± 0.8, p=ns; DT 251 ± 14 vs. 226 ± 17 ms, p<0.004; IVRT 95 ± 11 vs. 74 ± 9 ms, p<0.001. Systolic function did not change: EF 46.3 ± 3.4 vs. 46.7 ± 2.7%, p: ns. CONCLUSIONS: The use of ranolazine in patients suffering from chronic coronary artery disease has a favorable impact on diastolic function parameters. Accordingly, a clinical benefit could be observed due to an improvement in patients' symptoms.

Association of Lp-PLA2 with digital reactive hyperemia, coronary flow reserve, carotid atherosclerosis and arterial stiffness in coronary artery disease.

BACKGROUND: Lipoprotein-associated Phospholipase A2 (Lp-PLA2), has a powerful inflammatory and atherogenic action in the vascular wall and is an independent marker of poor prognosis in coronary artery disease (CAD). We investigate the association of Lp-PLA2 with markers of vascular dysfunction and atherosclerosis with proven prognostic value in CAD. METHODS: In 111 patients with angiographically documented chronic CAD, we measured 1) carotid intima-media thickness (CIMT), 2) reactive hyperemia using fingertip peripheral arterial tonometry (RH-PAT), 3) coronary flow reserve (CFR), by Doppler echocardiography 4) pulse wave velocity (PWV) and 5) blood levels of Lp-PLA2. RESULTS: Patients with Lp-PLA2 concentration >234.5 ng/ml (50th percentile) had higher CIMT (1.44 ± 0.07 vs. 1.06 ± 0.06 mm), PWV (11.0 ± 2.36 vs. 9.7 ± 2.38 m/s) and lower RH-PAT(1.24 ± 0.25 vs. 1.51 ± 0.53) and CFR (2.39 ± 0.75 vs. 2.9 ± 0.86) compared to those with lower Lp-PLA (p < 0.05 for all comparisons). Lp-PLA2 was positively associated with CIMT (regression coefficient b: 0.30 per unit of Lp-PLA2, p = 0.02), PWV (b:0.201, p = 0.04) and inversely with RHI-PAT (b: -0.371, p < 0.001) and CFR (b:-0.32, p = 0.002). In multivariate analysis, Lp-PLA2 was an independent determinant of RHI-PAT, CFR, CIMT and PWV in a model including age, sex, smoking, diabetes, dyslipidemia and hypertension (p < 0.05 for all vascular markers). Lp-PLA2, RHI-PAT and CFR were independent predictors of cardiac events during a 3-year follow-up. CONCLUSIONS: Elevated Lp-PLA2 concentration is related with endothelial dysfunction, carotid atherosclerosis, impaired coronary flow reserve and increased arterial stiffness and adverse outcome in CAD patients. These findings suggest that the prognostic role of Lp-PLA2 in chronic CAD may be explained by a generalized detrimental effect of this lipase on endothelial function and arterial wall properties.