Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease

N Engl J Med. 2005 Jan 6;352(1):29-38. doi: 10.1056/NEJMoa042000.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / therapeutic use
  • Atorvastatin
  • Biomarkers / blood
  • C-Reactive Protein / drug effects
  • C-Reactive Protein / metabolism*
  • Cholesterol, LDL / blood*
  • Cholesterol, LDL / drug effects
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / drug therapy*
  • Coronary Vessels / diagnostic imaging
  • Disease Progression
  • Female
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Lipids / blood
  • Male
  • Middle Aged
  • Myocardial Infarction / prevention & control
  • Pravastatin / administration & dosage
  • Pravastatin / therapeutic use*
  • Pyrroles / administration & dosage
  • Pyrroles / therapeutic use*
  • Regression Analysis
  • Risk Factors
  • Secondary Prevention
  • Ultrasonography, Interventional


  • Anticholesteremic Agents
  • Biomarkers
  • Cholesterol, LDL
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Pyrroles
  • C-Reactive Protein
  • Atorvastatin
  • Pravastatin