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CLINICAL RESEARCH: ATHEROSCLEROSIS

Does shear stress modulate both plaque progression and regression in the thoracic aorta?

Human study using serial magnetic resonance imaging

Jolanda J. Wentzel, PhD^*,||, Roberto Corti, MD^*,, Zahi A. Fayad, PhD, Paul Wisdom, Bsc, Frank Macaluso, Bsc, Mark O. Winkelman, Msc, Valentin Fuster, MD, PhD and Juan J. Badimon, PhD^,*

^* Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York
Imaging Science Laboratory, Mount Sinai School of Medicine, New York, New York
Cardiovascular Biology Research Laboratory, Mount Sinai School of Medicine, New York, New York
Damen Dredging Equipment, Research Department, Nijkerk, the Netherlands
^|| Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands

Manuscript received August 6, 2004; revised manuscript received November 12, 2004, accepted December 14, 2004.

^* Reprint requests and correspondence: Dr. Juan J. Badimon, Professor of Medicine, Cardiovascular Biology Research Laboratory, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1030, New York, New York 10029-6574 (Email: juan.badimon{at}mssm.edu).

OBJECTIVES: The purpose of this study was to investigate the role of shear stress (SS) in plaque regression.

BACKGROUND: A condition favorable to the development of atherosclerotic lesions is low oscillating SS. In the descending thoracic aorta, the relationship between plaque distribution and SS has never been characterized. The regression of plaque as the result of lipid-lowering therapy is associated with reverse atherogenic mechanisms. Therefore, we investigated the role of SS in plaque regression. Magnetic resonance imaging (MRI) provides a unique opportunity to noninvasively study morphology and hemodynamics.

METHODS: Cross-sectional images of atherosclerotic plaques in the descending thoracic aorta of 10 asymptomatic, hypercholesteremic patients were acquired at baseline and 24 months after starting lipid-lowering therapy by using a black-blood sequence on a 1.5-T clinical MRI system (5 mm x 780 µm x 780 µm). Average wall thickness (WT) was derived per quadrant. The aorta was subdivided in segments 2 cm in length starting 1 cm from the aortic arch.

RESULTS: Average WT decreased with increasing distance from the arch (3.0 ± 0.7 mm vs. 2.5 ± 0.3 mm; p < 0.05) and showed a helical pattern from the proximal to distal segments. Phase-contrast MRI was performed in the thoracic aorta of eight healthy volunteers to derive typical average SS distribution. Shear stress predicted the location of WT (r² = 0.29, p < 0.05) but did not predict plaque regression. The best predictor of plaque regression was baseline WT.

CONCLUSIONS: Our data showing an association between WT and average low SS locations support the role of local hemodynamics in the development of atherosclerotic lesions in descending thoracic aorta. Furthermore, SS does not seem to be the major predictor for plaque regression by lipid-lowering interventions. Therefore, our data suggest that other mechanisms are involved in the lipid-reversal mechanism.

Abbreviations and Acronyms   ANOVA = analysis of variance   LDL = low-density lipoprotein   MRI = magnetic resonance imaging   NWT = normalized wall thickness   SS = shear stress   WT = wall thickness   WTbaseline = wall thickness at baseline

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