Journal of Thrombosis and Thrombolysis

, Volume 22, Issue 1, pp 71–76 | Cite as

Cholesterol, C-reactive protein, and cerebrovascular events following intensive and moderate statin therapy

  • Jessica L. Mega
  • David A. Morrow
  • Christopher P. Cannon
  • Sabina Murphy
  • Richard Cairns
  • Paul M. Ridker
  • Eugene Braunwald
Thrombosis and Neurologic Science


Background: While statins have been shown to reduce cerebrovascular events (CVE), the relationship between cholesterol, C-reactive protein (CRP), and CVE in patients treated with different statin strategies is still being explored.

Methods: PROVE IT-TIMI 22 was a randomized trial of intensive (atorvastatin 80 mg/day) and moderate (pravastatin 40 mg/day) statin therapy in 4,162 patients with acute coronary syndromes followed for an average of 24 months; serial biomarkers allowed for an assessment of the lipid and non-lipid effects of statins as they relate to CVE.

Results: In this study, 45 patients on intensive statin therapy and 40 patients on moderate statin therapy had a CVE during the study period (2.1% v. 1.9%, P = 0.62). While the lipid profiles of patients with and without CVE were similar, those with CVE had higher CRP levels at 30 days and 4 months (2.7 v. 1.9, 2.4 v. 1.7 mg/L; P = 0.012, P = 0.005). Day 30 CRP remained an independent predictor of CVE after adjusting for age, development of atrial fibrillation, diabetes, and prior CVE. Patients with low density lipoprotein (LDL) levels < 70 mg/dL and ≥ 70 mg/dL had similar rates of CVE, while patients with CRP < 2 mg/L tended to have lower event rates when compared to those with higher levels. The lowest rates of CVE were seen in patients who had LDL < 70 mg/dL and CRP < 2 mg/L.

Conclusion: In PROVE IT - TIMI 22, achieved LDL levels did not appear to independently impact the rate of CVE. In contrast, patients with elevated CRP levels were at higher risk of stroke or transient ischemic attack, reinforcing the link between inflammation and CVE.

Condensed abstract

The goal of this PROVE IT-TIMI 22 sub-study was to examine the relationship between cholesterol, CRP, and CVE in patients on intensive and moderate statin therapy. The achieved lipid levels were similar in patients with and without a CVE; however, the achieved levels of CRP were higher in patients who subsequently developed a stroke or TIA. These findings further support the relationship between inflammation and CVE.


C-reactive protein Cerebrovascular event Cholesterol Hydroxymethylglutaryl-CoA reductase inhibitors 



cerebrovascular event


C-reactive protein


transient ischemic attack


acute coronary syndrome


3-hydroxy-3-methylglutaryl coenzyme


Pravastatin or Atorvastatin Evaluation and Infection Therapy


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Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Jessica L. Mega
    • 1
    • 2
    • 5
  • David A. Morrow
    • 1
    • 3
  • Christopher P. Cannon
    • 1
    • 3
  • Sabina Murphy
    • 1
  • Richard Cairns
    • 4
  • Paul M. Ridker
    • 3
  • Eugene Braunwald
    • 1
    • 3
  1. 1.TIMI (Thrombolysis in Myocardial Infarction) Study GroupBoston
  2. 2.Cardiovascular Division, Department of MedicineMassachusetts General Hospital and Harvard Medical SchoolBoston
  3. 3.Cardiovascular Division, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBoston
  4. 4.Nottingham Clinical Research GroupNottinghamEngland
  5. 5.MGH Cardiovascular DivisionBoston

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