Pravastatin Treatment Increases Collagen Content and Decreases Lipid Content, Inflammation, Metalloproteinases, and Cell Death in Human Carotid Plaques

Abstract

Background-The clinical benefits of lipid lowering with statins are attributed to changes in plaque composition leading to lesion stability, but supporting clinical data from human studies are lacking. Therefore, we investigated the effect of 3 months of pravastatin treatment on composition of human carotid plaques removed during carotid endarterectomy. Methods and Results-Consecutive patients with symptomatic carotid artery stenosis received 40 mg/d pravastatin (nϭ11) or no lipid-lowering therapy (nϭ13; control subjects) for 3 months before scheduled carotid endarterectomy.

Effects of atorvastatin on aortic pulse wave velocity in patients with hypertension and hypercholesterolaemia: a preliminary study

“…After this early phase, the increase in PWV tends to disappear and is even reversed as a consequence of the remodelling of the vascular wall. [10][11][12]28 Such experimental findings agree with the slight increase in PWV that we observed in the present study after the 12-week treatment.…”

“…[8][9][10][11][12]28 Furthermore, in patients with hypercholesterolaemia, radial artery compliance was found to increase to a larger extent after a two-year treatment than after a six-month treatment of simvastatin. 15,29 Finally, all these findings taken together agree with the clinical observations that, although favourable changes in lesion composition were observed within three months of statin treatment, clinical trials suggest that event reduction takes six-twelve months after initiation of treatment.…”

“…3 Secondly, statins cause, at an early phase, a rapid reduction of lipid vascular content, and thereby may be responsible for an absolute or relative increase in collagen, a process causing an increase of arterial stiffness. [10][11][12] Finally, in subjects with hypercholesterolaemia, statin treatments are associated with either decreased or unchanged alterations of arterial stiffness. 13,14 In subjects with hypertension, the situation may be even more complex to evaluate since increased stiffness may be the consequence of both high blood pressure and intrinsic modifications of the arterial wall.…”

The HMG-CoA reductase inhibitor rosuvastatin and the angiotensin receptor antagonist candesartan attenuate atherosclerosis in an apolipoprotein E-deficient mouse model of diabetes via effects on advanced glycation, oxidative stress and inflammation

“…Whereas candesartan was effective at reducing inflammation as evidenced by a decrease in macrophage infiltration and MCP-1 levels in the plaque, rosuvastatin did not have such a marked effect on these parameters. Previous studies have shown reduced inflammation in plaques from people with and without type 2 diabetes in response to various statins [17,43].…”

“…While a reduction in LDL-cholesterol was observed in many of these studies, it is now considered that statins also mediate pleiotropic antiatherogenic effects that are independent of their effects on lipoproteins, and that this action may contribute to their efficacy in reducing cardiovascular events. Indeed, HMGCoA reductase inhibitors have been shown to attenuate, although not in the context of diabetes, many of the stages critical to atherosclerotic plaque development including monocyte chemotaxis [13], neutrophil-endothelial cell interaction [13], smooth muscle cell apoptosis [14], migration [15] and proliferation [16], as well as plaque stability [17].…”