Danish Medical Bulletin - No. 1. February 2004. Vol. 51 Page 137.

Influence of simvastatin on coronary artery remodelling

Evaluation by three-dimensional IVUS

Lisette Okkels Jensen

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This PhD dissertation was accepted by the Faculty of Health Sciences of the University of Southern Denmark, Odense, and defended on December 3, 2003.

Official opponents: Steven E. Nissen, USA, Erling Falk and Peter Bie.

Tutors: Per Thayssen, Knud Erik Pedersen, Steen Stender, Keld Sørensen and Torben Haghfelt.

Correspondence: Lisette Okkels Jensen, Dept. of Cardiology, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense C.

Dan Med Bull 2004;51:137.

ABSTRACT

Prevention studies have shown that the effect of statin therapy on the occurrence of cardiac events is greater than might immediately be supposed from angiographically demonstrated atherosclerotic regression. In coronary angiography (CAG), it is exclusively vascular lumen that is represented, and this is used as a surrogate marker for the atherosclerotic changes that take place purely in the vessel wall. Intravascular ultrasound (IVUS) reveals both vessel wall and lumen, and by using a third dimension together with conventional two-dimensional IVUS both a cross-sectional image and a longitudinal image are obtained, and volume measurements of the coronary atherosclerotic segment can be performed.

The object was to investigate whether simvastatin therapy for 12 months could cause a morphological change in the form of remodelling that could be measured as plaque regression by ECG-triggered three dimensional IVUS and a functional change measured as changes in coronary flow reserve and peripheral endothelial function in patients with hypercholesterolaemia and atherosclerotic coronary arteries.

In 46 male patients CAG, EKG-triggered 3D IVUS, intracoronary Doppler and ultrasonic scan of the brachial artery were performed at baseline, after three months diet and after another 12 months on simvastatin therapy.

Besides an LDL cholesterol reduction of 42%, 12 months' simvastatin therapy resulted in a significant reduction in plaque volume of 6.8% and a reduction in vessel volume of 3.6%, while there were no changes in lumen dimensions. In all, plaque regression was demonstrated in 80% of the patients, and in these patients there was a significant reduction in plaque volume of 10.4% and a reduction in vessel volume of 5.4% without changes in lumen size. There was a significant correlation between the changes in plaque volume and vessel volume, while there was no correlation between changes in plaque volume and lumen volume.

Endothelial function in the brachial artery was improved with a significant increase in endothelium-dependent flow-mediated response of 36.9%, whereas coronary flow reserve measured with an intracoronary Doppler wire was unchanged after 12 months' simvastatin therapy.

Simvastatin therapy for 12 months causes remodelling in atherosclerotic coronary arteries with a reduction in plaque and vessel volume, while lumen dimensions are not changed. This illustrates the fact that the compensatory mechanism with positive remodelling is reversible. Endothelial dysfunction in a peripheral artery is partly reversible without this correlating with morphological or functional changes in atherosclerotic coronary arteries.

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