Determinants of arterial wall remodeling during lipid-lowering therapy: Serial intravascular ultrasound observations from the reversal of atherosclerosis with aggressive lipid Lowering therapy (REVERSAL) trial

Abstract

Conclusion: Plaque stabilization therapy with statin medications results in constrictive remodeling of the arterial wall and appears related to the anti-inflammatory effects of statin medications. Summary: The authors sought to study remodeling of coronary arteries during plaque-stabilizing therapy and to relate this remodeling to markers of lipid metabolism and inflammation. The Reversal of Atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) trial examined reversal of coronary artery atherosclerosis during 18 months of intensive vs moderate lipid-lowering therapy. The authors identified 210 patients with mild luminal narrowing coronary lesions. External elastic membrane (EEM) area, lumen area, and plaque area were determined at the site of the coronary lesions and at a reference site proximal to the lesions. Measurements were taken at baseline and during follow-up. The remodeling ratio (RR) was calculated by dividing EEM area of the lesion by EEM reference area. Changes in remodeling and changes in plaque area were correlated with lipid profile and inflammatory markers. The lesions examined showed a progression in plaque area (8.9% ± 25.7%) and a decrease in RR (−3.0% ± 11.2%) during follow-up. Direct effects with RR were correlated with percentage change in plaque area (P < .0001), baseline RR (P < .0001), and baseline lesion lumen area (P = .019) as well as change in high sensitivity C-reactive protein levels (P = .027) and baseline hypertension (P = .014). Age (P = .037) and percentage change in triglyceride levels (P = .049) demonstrated significant inverse relationships with RR during follow-up. There were no associations between changes in treatment group (moderate vs high-intensity statin therapy) levels of low-density (LDL) or high-density lipoprotein (HDL) cholesterol. Comment: Plaque regression and stabilization appears to be accompanied by a reduction in vessel size. Correlation of these effects with C-reactive protein, but not serum levels of HDL or LDL cholesterol, suggest drugs targeting arterial inflammation may be more effective than those targeting simple measures of lipid metabolism. The anti-inflammatory effects of statins may turn out to be more important than their cholesterol-lowering effects.