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Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease
Steven E Nissen1, E Murat Tuzcu, Paul Schoenhagen
1Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. nissens@ccf.org
Insights
Intensive statin therapy significantly slows atherosclerosis progression by lowering low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) levels. Greater reductions in both LDL cholesterol and CRP correlate with slower disease progression in coronary artery disease patients.
Area of Science:
- Cardiology
- Biochemistry
- Medical Research
Background:
- Recent trials indicate superior outcomes with intensive statin therapy compared to moderate treatment.
- Intensive statin regimens achieve greater reductions in low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP).
- These biomarker reductions suggest a link to the progression of cardiovascular disease.
Purpose of the Study:
- To investigate the relationship between intensive statin treatment, biomarker levels, and atherosclerosis progression.
- To compare the effects of moderate versus intensive statin therapy on coronary atherosclerosis.
- To determine if reductions in LDL cholesterol and CRP independently correlate with reduced atherosclerosis progression.
Main Methods:
- Intravascular ultrasonography was used in 502 patients with coronary artery disease.
- Patients were randomized to moderate (pravastatin 40 mg) or intensive (atorvastatin 80 mg) statin treatment.
- Atherosclerosis progression was assessed via ultrasonography after 18 months, with lipoprotein and CRP levels measured at baseline and follow-up.
Main Results:
- Overall, LDL cholesterol decreased from 150.2 to 94.5 mg/dL, and CRP decreased from 2.9 to 2.3 mg/L (P<0.001).
- Reductions in LDL cholesterol, CRP, apolipoprotein B-100, and non-HDL cholesterol were related to atherosclerosis progression.
- After adjusting for lipid reductions, decreased CRP levels independently correlated with slower atherosclerosis progression.
Conclusions:
- Intensive statin treatment reduces the progression of atherosclerosis in coronary artery disease patients compared to moderate treatment.
- This reduced progression is significantly linked to greater reductions in both atherogenic lipoproteins and CRP levels.
- Optimizing statin therapy to achieve greater reductions in LDL cholesterol and CRP may be crucial for managing atherosclerosis.
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 documented coronary disease. Patients were randomly assigned to receive moderate treatment (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 progression 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 atherosclerosis 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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