Effect of Intensive Atorvastatin Therapy on Microvascular Function
Background. There is a discrepancy between the marked reduction in adverse events with statins and their modest effect on atheroma regression. We hypothesized that, in a Western population, high-dose atorvastatin will result in alterations in coronary atheroma composition, phenotype, and microvascular function.
Methods. Serial coronary radiofrequency intravascular ultrasound (VH-IVUS), coronary flow reserve (CFR), and hyperemic microvascular resistance (HMR) were performed at baseline and after 6 months of treatment with 80 mg atorvastatin in 20 patients with moderate coronary artery disease (CAD). For each VH-IVUS frame (n = 2249), changes in total plaque atheroma, composition, and phenotype (pathological intimal thickening, fibrotic plaque, fibroatheroma), and serial remodeling were assessed.
Results. Total serum cholesterol decreased from 186.0 mg/dL (interquartile range [IQR], 168.0 to 212.5 mg/dL) to 139.0 mg/dL (IQR, 124.3 to 151.3 mg/dL). Percent atheroma volume did not change significantly (-0.5% [IQR, -2.8% to 3.7%]; P=.90) and serial remodeling analysis demonstrated 40% constrictive, 24% incomplete, and 36% expansive patterns. There was a trend toward lower percent fibrous tissue (-3.47 ± 1.78%; P=.07) and percent fibro-fatty tissue (-2.52 ± 1.24%; P=.06) and increase in percent necrotic core (+2.74 ± 1.65%; P=.11) and percent dense calcium (+1.99 ± 0.81; P=.02), which translated into significantly less pathological intimal thickening (4% vs 12%; P<.0001) and more fibroatheromas (67% vs 57%; P<.0001) at follow-up compared to baseline. There were modest non-significant improvements in CFR (+0.26 [IQR, -0.37 to 0.76]; P=.23) and HMR (-0.22 [IQR, -0.56 to 0.28]; P=.12).
Conclusions. In this pilot study of Western patients with moderate CAD, high-dose atorvastatin resulted in alterations in coronary atheroma composition with corresponding changes in plaque phenotype and modest improvement in coronary microvascular function.
Contemporary therapy of atherosclerosis includes risk-factor modification and pharmacologic therapy aimed at stabilizing or regressing disease. The cornerstone of anti-atherosclerotic therapy, 5-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are thought to exert their protective effect through a number of mechanisms including low density lipoprotein (LDL) lowering, halting progression of atherosclerosis, anti-inflammatory effects, and other pleiotropic effects. Several prospective trials have shown a correlation between the degree of LDL lowering by statins and their effects on reducing progression and/or inducing regression of atheroma in patients with coronary artery disease (CAD).
Nevertheless, there remains a discrepancy between the significant relative-risk reduction in clinical events with statins and their relatively modest effect on atheroma regression. It has therefore been proposed that the protective effects of statins are mediated through alterations in coronary atheroma composition and improvement in endothelial function, serum viscosity, and microvascular function. Existing studies evaluating the effect of statins on atheroma composition have been limited to Asian populations, in which the more fibrotic and calcified atherosclerotic phenotype differs from that observed in Western populations.
Accordingly, the aim of this pilot study was to assess the change in coronary atheroma size, composition, and phenotype, and serial remodeling using radiofrequency intravascular ultrasound (virtual histology intravascular ultrasound [VH-IVUS]), and coronary microvascular function in a Western population treated with high-dose atorvastatin (80 mg) for 6 months. We hypothesized that in a Western cohort with moderate CAD, high-dose atorvastatin will result in significant alterations in atheroma composition, plaque phenotype, and coronary microvascular function.
Abstract and Introduction
Abstract
Background. There is a discrepancy between the marked reduction in adverse events with statins and their modest effect on atheroma regression. We hypothesized that, in a Western population, high-dose atorvastatin will result in alterations in coronary atheroma composition, phenotype, and microvascular function.
Methods. Serial coronary radiofrequency intravascular ultrasound (VH-IVUS), coronary flow reserve (CFR), and hyperemic microvascular resistance (HMR) were performed at baseline and after 6 months of treatment with 80 mg atorvastatin in 20 patients with moderate coronary artery disease (CAD). For each VH-IVUS frame (n = 2249), changes in total plaque atheroma, composition, and phenotype (pathological intimal thickening, fibrotic plaque, fibroatheroma), and serial remodeling were assessed.
Results. Total serum cholesterol decreased from 186.0 mg/dL (interquartile range [IQR], 168.0 to 212.5 mg/dL) to 139.0 mg/dL (IQR, 124.3 to 151.3 mg/dL). Percent atheroma volume did not change significantly (-0.5% [IQR, -2.8% to 3.7%]; P=.90) and serial remodeling analysis demonstrated 40% constrictive, 24% incomplete, and 36% expansive patterns. There was a trend toward lower percent fibrous tissue (-3.47 ± 1.78%; P=.07) and percent fibro-fatty tissue (-2.52 ± 1.24%; P=.06) and increase in percent necrotic core (+2.74 ± 1.65%; P=.11) and percent dense calcium (+1.99 ± 0.81; P=.02), which translated into significantly less pathological intimal thickening (4% vs 12%; P<.0001) and more fibroatheromas (67% vs 57%; P<.0001) at follow-up compared to baseline. There were modest non-significant improvements in CFR (+0.26 [IQR, -0.37 to 0.76]; P=.23) and HMR (-0.22 [IQR, -0.56 to 0.28]; P=.12).
Conclusions. In this pilot study of Western patients with moderate CAD, high-dose atorvastatin resulted in alterations in coronary atheroma composition with corresponding changes in plaque phenotype and modest improvement in coronary microvascular function.
Introduction
Contemporary therapy of atherosclerosis includes risk-factor modification and pharmacologic therapy aimed at stabilizing or regressing disease. The cornerstone of anti-atherosclerotic therapy, 5-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are thought to exert their protective effect through a number of mechanisms including low density lipoprotein (LDL) lowering, halting progression of atherosclerosis, anti-inflammatory effects, and other pleiotropic effects. Several prospective trials have shown a correlation between the degree of LDL lowering by statins and their effects on reducing progression and/or inducing regression of atheroma in patients with coronary artery disease (CAD).
Nevertheless, there remains a discrepancy between the significant relative-risk reduction in clinical events with statins and their relatively modest effect on atheroma regression. It has therefore been proposed that the protective effects of statins are mediated through alterations in coronary atheroma composition and improvement in endothelial function, serum viscosity, and microvascular function. Existing studies evaluating the effect of statins on atheroma composition have been limited to Asian populations, in which the more fibrotic and calcified atherosclerotic phenotype differs from that observed in Western populations.
Accordingly, the aim of this pilot study was to assess the change in coronary atheroma size, composition, and phenotype, and serial remodeling using radiofrequency intravascular ultrasound (virtual histology intravascular ultrasound [VH-IVUS]), and coronary microvascular function in a Western population treated with high-dose atorvastatin (80 mg) for 6 months. We hypothesized that in a Western cohort with moderate CAD, high-dose atorvastatin will result in significant alterations in atheroma composition, plaque phenotype, and coronary microvascular function.
SHARE
