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FOCUS ISSUE: PROVE IT-TIMI 22

Relationship Between Uncontrolled Risk Factors and C-Reactive Protein Levels in Patients Receiving Standard or Intensive Statin Therapy for Acute Coronary Syndromes in the PROVE IT-TIMI 22 Trial

Kausik K. Ray, MRCP, MD^_*, Christopher P. Cannon, MD, FACC^_*,_*, Richard Cairns, MSc, David A. Morrow, MD, MPH^_*, Nader Rifai, PhD, Ajay J. Kirtane, MD, Carolyn H. McCabe, BS^_*, Allan M. Skene, PhD, C. Michael Gibson, MS, MD, Paul M. Ridker, MD, MPH^_*, Eugene Braunwald, MD, MACC^_* for the PROVE IT-TIMI 22 Investigators

^_* Brigham and Women’s Hospital/Harvard Medical School, Boston, Massachusetts
Nottingham Clinical Research Group, Boston, Massachusetts
Children’s Hospital, Boston, Massachusetts
Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Manuscript received July 21, 2005; revised manuscript received August 3, 2005, accepted August 8, 2005.

^_* Reprint requests and correspondence: Dr. Christopher P. Cannon, The TIMI Study Group, 350 Longwood Avenue, 1st Floor, Boston, Massachusetts 02115 (Email: cpcannon{at}partners.org).

OBJECTIVES: This study sought to evaluate what set of factors correlate with higher or lower C-reactive protein (CRP) levels in patients receiving standard and intensive statin therapy.

BACKGROUND: C-reactive protein levels in blood are becoming recognized as a potential means of monitoring cardiovascular risk. Although statin therapy is known to reduce CRP levels, many patients have a high CRP level despite statin therapy.

METHODS: This study was a cross-sectional study of 2,885 patients from the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) trial, which assessed the relationship between uncontrolled cardiovascular risk factors and CRP level at four months after enrollment.

RESULTS: In a multivariate model, several risk factors were weakly but independently associated with higher CRP levels: age, gender (with or without hormone replacement therapy), body mass index >25 kg/m², smoking, low-density lipoprotein 70 mg/dl, glucose >110 mg/dl, high-density lipoprotein <50 mg/dl, triglycerides >150 mg/dl, and the intensity of statin therapy. A direct relationship between the number of uncontrolled risk factors present and CRP levels (p < 0.0001) was observed for both statin regimens. Despite the presence of each uncontrolled risk factor, prior randomization to intensive statin therapy was associated with a lower CRP level (p < 0.0001). Across all strata, defined by the number of uncontrolled risk factors present, CRP levels were lower among those receiving intensive statin therapy.

CONCLUSIONS: The use of intensive statin therapy lead to a lower CRP level independent of the presence of single or multiple cardiovascular risk factors. Even among patients receiving intensive statin therapy, a lower CRP level was observed in patients with the fewest coronary risk factors present, suggesting that control of multiple risk factors may be a means to further achieve lower CRP levels.

Abbreviations and Acronyms   ACS = acute coronary syndrome   BMI = body mass index   BP = blood pressure   CAD = coronary artery disease   CI = confidence interval   CRP = C-reactive protein   HDL = high-density lipoprotein   hs-CRP = high-sensitivity CRP   IQR = interquartile range   LDL = low-density lipoprotein   PROVE IT–TIMI 22 = Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22   TG = triglyceride

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