Steven E. Nissen, M.D., E. Murat Tuzcu, M.D., Paul Schoenhagen, M.D., Tim Crowe, B.S., William J. Sasiela, Ph.D., John Tsai, M.D., John Orazem, Ph.D., Raymond D. Magorien, M.D., Charles O’Shaughnessy, M.D.,and Peter Ganz, M.D., for the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) Investigators*

ABSTRACT

background

Recent trials have demonstrated better outcomes with intensive than with moderate
statin treatment. Intensive treatment produced greater reductions in both low-density
lipoprotein (LDL) cholesterol and C-reactive protein (CRP), suggesting a relationship
between these two biomarkers and disease progression.

methods

We performed intravascular ultrasonography in 502 patients with angiographically doc-
umented coronary disease. Patients were randomly assigned to receive moderate treat-
ment (40 mg of pravastatin orally per day) or intensive treatment (80 mg of atorvastatin
orally per day). Ultrasonography was repeated after 18 months to measure the pro-
gression of atherosclerosis. Lipoprotein and CRP levels were measured at baseline and
follow-up.

results

In the group as a whole, the mean LDL cholesterol level was reduced from 150.2 mg per
deciliter (3.88 mmol per liter) at baseline to 94.5 mg per deciliter (2.44 mmol per liter) at
18 months (P<0.001), and the geometric mean CRP level decreased from 2.9 to 2.3 mg
per liter (P<0.001). The correlation between the reduction in LDL cholesterol levels and
that in CRP levels was weak but significant in the group as a whole (r=0.13, P=0.005),
but not in either treatment group alone. In univariate analyses, the percent change in the
levels of LDL cholesterol, CRP, apolipoprotein B-100, and non–high-density lipoprotein
cholesterol were related to the rate of progression of atherosclerosis. After adjustment
for the reduction in these lipid levels, the decrease in CRP levels was independently and
significantly correlated with the rate of progression. Patients with reductions in both
LDL cholesterol and CRP that were greater than the median had significantly slower rates
of progression than patients with reductions in both biomarkers that were less than the
median (P=0.001).

conclusions

For patients with coronary artery disease, the reduced rate of progression of athero-
sclerosis associated with intensive statin treatment, as compared with moderate statin
treatment, is significantly related to greater reductions in the levels of both atherogenic
lipoproteins and CRP.

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