Imaging-Guided Evaluation Of High-Dose Atorvastatin On Atherosclerotic Vascular Remodeling: A Multimodal Radiological, Physiological, And Histopathological Study

Abstract

Background and aim

Atherosclerosis is a complex disease characterized by lipids accumulation, inflammatory cells and fibrotic material formation in the arteries which leads to plaques growth and vascular remodeling. "Vascular alteration" represents the geometry change of artery as a consequence of plaques growth and can be investigated using modeling and imaging. In the current study we aimed to evaluate the role of atorvastatin on atherosclerosis at a radiological, histological and physiological level by studying vascular remodeling.

Method

Prospective interventional study: Eligible patients were 40–75 years of age, had coronary or carotid atherosclerotic disease and angiographic stenosis >30%, and were divided into 3 arms (low-dose atorvastatin 10 mg/d; high-dose atorvastatin 80 mg/d; control) for a period of 12 months. Serial examinations were conducted at 0, 3, 6, and 12 months of follow-up. Radiological examinations included IVUS assessment of plaque burden (percent atheroma volume [PAV]; total atheroma volume [TAV]; remodeling index). Coronary physiological examination included fractional flow reserve (FFR); coronary flow reserve (CFR); and index of microcirculatory resistance (IMR). Laboratory examination included lipid profile and inflammatory parameters (hs-CRP).

Results

Atorvastatin High Dose showed superior results across the lipid, inflammatory, physiological, and imaging markers when compared with the Low Dose and Placebo groups. After 12 months LDL-C decreased by 54% in the High Dose versus 37% in the Low Dose and HDL-C rose by 30% and 17%, respectively. High Dose therapy showed superior reduction of hs-CRP (64%), PAV (36%) and TAV (33%) signifying significant plaque regression and decreased vascular remodeling. Coronary physiology also increased by 50% and IMR decreased by 46% respectively in High Dose therapy. The strongest predictors of plaque regression were multivariate regression analysis LDL-C reduction ( = 0.42, p <0.001) and reduction in macrophages ( =0.41, p<0.001).

Conclusion

In the present study the effect of atorvastatin on atherosclerosis has been evaluated using different methods, combining advanced cardiovascular imaging techniques to characterize both the plaques burden and the vascular response. Atorvastatin improve multiple heath parameter, in particularly lipid profile and inflammation markers, at higher dosage (80mg/daily) compared to lower ones (10mg/daily).