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.
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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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