Moderate-dose atorvastatin improves arterial endothelial function in patients with angina pectoris and normal coronary angiogram: a pilot study

Abstract

IntroductionEndothelial dysfunction could contribute to the pathophysiology of angina pectoris (AP) in patients with normal coronary angiograms. Besides lipid-lowering effects, statins exert pleiotropic effects including improving endothelial function.Material and methodsOur double-blind study included 58 patients with AP, noninvasively confirmed myocardial ischemia and a normal coronary angiogram. The effect of once-daily 20 mg atorvastatin (A) was compared with placebo (P) for 6 months. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery, and microcirculation by peripheral arterial tonometry (EndoPAT) measuring the reactive hyperemia index (RHI), indicating microcirculatory endothelial function, and the augmentation index (AI), an indicator of arterial stiffness. The impact of AP on the quality of life was monitored using the Seattle Angina Questionnaire (SAQ).ResultsBrachial artery endothelial dysfunction was found in 91.4% of patients at study entry, and subnormal RHI in 41%. Group A showed an improvement of FMD compared with group P, both at 3 and 6 months (+120.8% vs. –21.2%, and +70.8% vs. –1.9%, respectively, p < 0.001). No difference was detected in the RHI. Rate-normalized AI showed an improvement (−114.49% group A vs. –30.77% group P, p = 0.077), although the differences between the groups were not significant. According to the SAQ, an improvement was found in almost all observed variables with the exception of the issue of quality of life (QoL), where patients in both groups assessed their QoL at the control study visits as poorer compared with baseline.ConclusionsModerate-dose atorvastatin therapy improves endothelial function of large conduit arteries in patients with AP and a normal coronary angiogram, which probably reflects positive effects on coronary artery endothelial function. No effect was found with vascular effects at the level of the peripheral microcirculation.

Statin-Induced Nitric Oxide Signaling: Mechanisms and Therapeutic Implications

“…Inactive Rho inhibits the Rho/Rho-kinase (ROCK) pathway, which leads to an increase in the half-life of eNOS mRNA and increased production of NO [13,14,20]. tissue regeneration [3][4][5][6][7][8][9]. Several of these effects are mediated through the actions of statins on endothelial nitric oxide (NO) signaling pathways.…”

“…Pleiotropic effects of statins make this drug class distinct from other lipid-modifying agents [1,2] those effects independent of cholesterol-lowering. Numerous putative therapeutic benefits have been ascribed to statins including suppression of apoptosis, antioxidant and anti-inflammatory effects, immunomodulation, neuroprotection and promotion of tissue regeneration [3][4][5][6][7][8][9]. Several of these effects are mediated through the actions of statins on endothelial nitric oxide (NO) signaling pathways.…”

Effects of Statin Treatment on Patients with Angina and Normal or Nearly Normal Angiograms

“…A number of studies exploring the effects of statin treatment on soft endpoints actually had pathophysiological endpoints that have helped us understand the causes of ischaemia in patients with non-obstructive CAD. 19,20,[24][25][26][27][28][29][30][31] It is currently recognised that myocardial ischaemia in these individuals is often the consequence of reduced coronary microvascular dilatory responses and increased coronary resistance due to endothelial dysfunction and/or vasomotor disorder (involving the microvascular and/or epicardial bed). 34 Studies in patients with angina and non-obstructive CAD show that statins increase myocardial perfusion and improve symptoms in subjects with mild coronary atherosclerosis and even in those with normal angiograms.…”

“…34 Studies in patients with angina and non-obstructive CAD show that statins increase myocardial perfusion and improve symptoms in subjects with mild coronary atherosclerosis and even in those with normal angiograms. 19,24,26,29 Current international guidelines suggest statin treatment for all patients with chronic coronary syndrome, including those with microvascular angina. 34 Finally, preliminary data have shown that statin treatment improves survival in patients with mild coronary atherosclerosis (1-49% lumen stenosis) but not in those with normal angiograms (0% lumen stenosis).…”

“…26 In summary, several small observational and randomised trials have shown that statin treatment has beneficial effects in patients with angina and non-obstructive coronary angiograms (with or without hypercholesterolaemia). 19,20,[24][25][26][27][28][29][30][31] These effects include improvements in endothelial and microvascular function, exercise capacity and myocardial perfusion, as well as a reduction in or regression of angina symptoms. 19,20,[24][25][26][27][28][29][30][31]…”