Stroke. 2007;38:1374-1376
Published online before print March 1, 2007,
doi: 10.1161/01.STR.0000260206.56774.aa
(Stroke. 2007;38:1374.)
© 2007 American Heart Association, Inc.
Pravastatin Decreases Wall Shear Stress and Blood Velocity in the Internal Carotid Artery Without Affecting Flow Volume
Results From the PROSPER MRI Study
Frieke M.A. Box, MS;
Jeroen van der Grond, PhD;
Anton J.M. de Craen, PhD;
Inge H. Palm-Meinders, MD;
Rob J. van der Geest, MS;
J. Wouter Jukema, MD, PhD;
Johan H.C. Reiber, PhD;
Mark A. van Buchem, MD, PhD;
Gerard J. Blauw, MD, PhD for the PROSPER Study Group
From the Division of Image Processing (F.M.A.B., R.J.v.d.G., J.H.C.R.) of the Department of Radiology (J.v.d.G., I.H.P.M. M.A.v.B.) and the Departments of Gerontology & Geriatrics (A.J.M.d.C., G.J.B.) and Cardiology (J.W.J.) Leiden University Medical Center, Leiden, the Netherlands.
Correspondence to Frieke M.A. Box, MSc, Division of Image Processing, Department of Radiology, C2S, PO Box 9600, 2300 RC Leiden, the Netherlands. E-mail F.M.A.Box{at}lumc.nl
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Abstract
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Background and Purpose Despite speculations, it is unknown
whether statins affect wall shear stress (WSS). Therefore, the
effect of pravastatin on WSS was investigated.
Methods In 355 elderly individuals participating in the PROSPER study (follow up after 3 years), the effect of 40 mg pravastatin on WSS was assessed in the internal carotid artery using magnetic resonance imaging.
Results WSS and blood velocity decreased both in the pravastatin group and in the placebo group but decreased faster in the pravastatin group (P<0.04, P<0.02). Blood volume flow did not differ between the groups.
Conclusions In elderly subjects, the WSS and blood velocity of the internal carotid artery declines significantly over time and this decline is more pronounced in subjects treated with 40 mg pravastatin compared with the placebo group.
Key Words: blood flow blood flow velocity computer-assisted image processing magnetic resonance imaging statins
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Introduction
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Arterial vessel areas with low or oscillating wall shear stress
(WSS) are most prone to develop atherosclerotic plaques.
1 Statins
have been shown to be important clinical pharmacological tools
to prevent atherosclerosis and have other favorable effects,
eg, increasing nitric oxide availability and reducing blood
viscosity.
24
To date, the possible effects of statins on WSS are unknown. An increase in WSS will decrease atherosclerotic plaques and increase nitric oxide availability, whereas a decrease in blood viscosity will reduce WSS.1,5 We examined the effect of 40 mg pravastatin per day on WSS in the internal carotid artery in subjects participating in the nested magnetic resonance imaging (MRI) study of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).6
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Methods
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The PROSPER is a double-blind, randomized, placebo-controlled
trial aimed at assessing the effect of therapy with 40 mg pravastatin
on vascular events in 5804 men and women, aged 70 to 82 years,
with vascular disease or at risk for vascular disease.
6 Three
hundred fifty-five Dutch participants of the PROSPER study had
two successive MRIs of the internal carotid artery, allowing
the assessment of WSS. The first MRI was acquired during the
lead-in period and the second MRI after an average follow up
of 33 (SD=1.4) months.
Flow measurements were performed on a 1.5 T-MR system (Philips Medical Systems) in a plane perpendicular to the internal carotid artery 4 cm distal to the bifurcation. We used a gradient echo phase-contrast technique with retrospective gating with peripheral pulse unit; repetition time/echo time 16/9 ms; flip angle 7.5°; slice thickness 5 mm, scan matrix 256x154, field of view 250x188 mm, velocity encoding 100 cm/s, and 1 number of signal averages.
For a parabolic velocity profile the flow volume (Flow), the maximum velocity in the vessel cross section (Vmax), the diameter (Diam), and WSS have the following relations5,7:
and
The viscosity (µ)
was taken as 3.39 mPa/s at baseline and 3.32 mPa/s at follow
up.
4 The cardiac cycle was divided into 16 time phases. To segment
the image, a parabolic velocity profile was fitted to the measured
data (
Figure).
7 Parameters during systole and diastole were
assessed by averaging the three consecutive phases with highest
and lowest Flow, respectively. For calculation of the probability
values, we used the linear mixed model corrected for smoking
behavior.

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An example of a (A) measured velocity profile and depicted as a (B) gray value with the (C) fitted paraboloid and the (D) segmented vessel.
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Results
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Baseline characteristics for the 355 participants are presented
in
Table 1. In the pravastatin group, low-density lipoprotein
decreased from 3.9±0.8 mmol/L to 2.5±0.5 mmol/L
and high-density lipoprotein increased from 1.2±0.3 mmol/L
to 1.3±0.4 mmol/L at follow up; cholesterol in the placebo
group remained unaltered. This was similar to the entire PROSPER
study group.
6 We found no significant differences in blood pressure
between the two groups. Errors in data conversion and positioning
of the scan plane left 328 vessels in the pravastatin group
and 334 vessels in the placebo group for analysis. WSS, Flow,
Vmax, and Diam data are presented in
Table 2. At baseline, there
were no significant differences in these parameters between
the groups. At follow up, WSS and Vmax-M showed a significant
decrease in both groups. However, in the pravastatin group,
the decrease in WSS and Vmax and the increase in Diam was larger
than in the control group (
P<0.05).
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Discussion
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Our study indicates that WSS decreases faster over time in elderly
individuals treated with pravastatin than in those treated with
placebo. This finding is surprising because it can be expected
that because of its reducing effect on atherosclerosis, pravastatin
would lead to less decrease of WSS over time.
We confirmed WSS decline with age measured by Gnasso et al in both groups.5 A decrease in Flow or Vmax, in the paraboloid model, gives a WSS decrease and a diameter increase gives a WSS decrease. The faster WSS decrease in the pravastatin group is probably caused by the fast decrease in Vmax. Because blood velocity increases in the presence of a stenosis,8 a relative decrease in Vmax might reflect a decrease of stenoses.
As a result of the limited resolution of our MRI protocol, the diameter could not be measured directly. An increase in diameter for the pravastatin group is in agreement with Stroes et al.9 However, a faster decay of Vmax compared with Flow would give a wrong impression of diameter increase (Equation 1).
Summary
In elderly subjects, the WSS and Vmax of the internal carotid artery declines significantly over time and this decline is more pronounced in subjects treated with 40 mg pravastatin compared with the placebo group.
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Appendix
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PROSPER Study Group: (Glasgow) J. Shepherd (chairman and principal
investigator), S.M. Cobbe, I. Ford, A. Gaw, P.W. Macfarlane,
C.J. Packard, and D.J. Stott; (Leiden) G.J. Blauw (principal
investigator), E.L.E.M. Bollen, A.M. Kamper, and R.G.J. Westendorp;
(Cork) M.B. Murphy (principal investigator), B.M. Buckely, M.
Hyland, and I.J. Perry.
End point Committee: S.M. Cobbe (chairman), J.W. Jukema, P.W. Macfarlane, A.E. Meinders, D.J. Stott, B.J. Sweeny, and C. Twomey.
J.W.J. is an established clinical investigator of the Netherlands Heart Foundation.
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Acknowledgments
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Sources of Funding
This work was financed by the Netherlands Heart Foundation Grant 2000.119. The PROSPER study was sponsored by Bristol Myers-Squibb, Princeton, NJ. The sponsor had no role in the design, data collection, data analyses, and data interpretation of the study or writing of the report.
Disclosures
None.
Received November 14, 2006;
accepted November 22, 2006.
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References
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