Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia.

Abstract

BACKGROUND This study aimed to determine if cholesterol-lowering therapy improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. METHODS AND RESULTS Nine patients with hypercholesterolemia were studied before and after cholesterol-lowering therapy with pravastatin (an inhibitor of HMG-CoA reductase) for 6 +/- 3 months, which lowered serum cholesterol from 272 +/- 8 to 187 +/- 16 mg/dL (P < .01). Control patients with serum cholesterol of 218 +/- 23 mg/dL also were studied twice in a similar interval (8 +/- 2 months) with no cholesterol-lowering drugs. Acetylcholine (the endothelium-dependent vasodilator) and papaverine and nitrate (endothelium-independent vasodilators) were infused into the study coronary artery. Changes in the diameter of the epicardial coronary artery and coronary blood flow were assessed by quantitative coronary arteriography and an intracoronary Doppler catheter. In patients with hypercholesterolemia, acetylcholine-induced vasoconstriction of the epicardial artery was less (P < .05) and the acetylcholine-induced increases in coronary blood flow were greater (P < .001) after than before pravastatin. In control patients, responses of the epicardial coronary artery and coronary blood flow to acetylcholine did not change over the follow-up period. The vasomotor responses to papaverine or nitrate were similar between the two groups, and no interval changes in their responses were noted in either group. CONCLUSIONS These results suggest that cholesterol-lowering therapy with pravastatin may improve endothelium-dependent coronary vasomotion, which may possibly contribute to the improvement of myocardial perfusion as well as the regression of coronary atherosclerosis.

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

“…[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.…”

“…[4][5][6][7] Subsequently, lipid-lowering agents may have various consequences on arterial stiffness. First, statins are known to have a beneficial effect on endothelial function, thereby restoring nitric oxide (NO) bio-activity in atherosclerotic populations 8,9 and thus producing an NO-induced large artery dilatation and reduction of stiffness. 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.…”

The effects of atorvastatin on coronary endothelial function in patients with recent myocardial infarction

“…Thus, statin therapy may support one of the fundamental survival responses to maintain tissue viability in the face of acute or chronic myocardial ischemia in patients with obstructive coronary artery disease. [22][23][24] We have shown that an improvement in lipid profile could be considered to be another factor for the improvement of endothelial function in the coronary artery. Recently, Sakabe et al 25 reported that atorvastatin therapy has some beneficial effects within 2 weeks, including effects on LDL subfraction distribution and remnant-like particle-cholesterol (RLP-C), antioxidant effects, and alterations in endothelial function of the brachial artery, which may be important in the treatment of cardiovascular diseases.…”

LDL-cholesterol lowering and atherosclerosis - clinical benefit and possible mechanisms: an update

“…In humans, coronary atherosclerosis and hypercholesterolaemia have also been associated with dysfunction of endothelium-mediated vasomotion, which impairs coronary or myocardial blood flow and forearm blood flow [123][124][125][126]. Lipid-lowering therapy has shown to improve the endothelium medi ated vasomotion after relative short periods of time [127][128][129]. For example, Egashira et al [127] demonstrated a significant improvement in coronary blood flow in response to acetylcholine infusion in patients with hypercholesterolaemia and pravastatin therapy.…”

“…Lipid-lowering therapy has shown to improve the endothelium medi ated vasomotion after relative short periods of time [127][128][129]. For example, Egashira et al [127] demonstrated a significant improvement in coronary blood flow in response to acetylcholine infusion in patients with hypercholesterolaemia and pravastatin therapy. Anderson et al [130] showed recently that the addition of antioxidant therapy with probucol to cholesterol-lowering treatment with lovastatin im proved acetylcholine-induced, endothelium-depen dent vasodilation significantly more than cholesterol lowering alone.…”