Variability of C-reactive protein levels among patients with stable coronary artery disease and on statin therapy.
BACKGROUND
High sensitivity C-reactive protein, a marker of inflammation, has been proposed to stratify coronary artery disease risk and is lowered by HMG-CoA reductase (statin) therapy. However, the reproducibility of persistently elevated hs-CRP levels and association with other markers of inflammation in patients with stable CAD on aggressive statin therapy is unknown.


OBJECTIVE
To determine the reproducibility of hs-CRP levels measured within 2 weeks in patients with documented CAD with stable symptoms and to identify associations with other markers of inflammation.


METHODS
Levels of hs-CRP were measured twice within 14 days (7 +/- 4) in 23 patients (22 males and 1 female, average age 66 +/- 10 years) with stable CAD and hs-CRP > or = 2.0 mg/L but < or = 10 mg/L at visit 1. All patients had received statins for cholesterol management (low density lipoprotein-cholesterol 84 +/- 25 mg/dl) with no dose change for > 3 months. None had a history or evidence of malignancy, chronic infection or inflammation, or recent trauma. There was no change in medications between visits 1 and 2, and no patient reported a change in symptoms or general health during this interval. White blood cell count and pro- and anti-inflammatory cytokines were measured at both visits.


RESULTS
hs-CRP levels tended to be lower at visit 2 (median 2.4 mg/L, range 0.8-11 mg/L) than at visit 1 (median 3.3 mg/L, range 2.0-9.7; P = 0.1793). However, between the two visits hs-CRP levels decreased by more than 1.0 mg/L in 10 patients and increased by more than 1.0 mg/L in 4 patients. Changes in hs-CRP levels were unrelated to changes in levels of white blood cells (P = 0.4353). Of the cytokines tested, only the antiinflammatory cytokine interleukin-1 receptor antagonist and the pro-inflammatory cytokine interleukin-8 were above lower limits of detection, but there were no correlations between changes in these values and changes in hs-CRP (both P > 0.5).


CONCLUSIONS
In stable CAD patients on aggressive statin therapy, hs-CRP levels may fluctuate over brief periods in the absence of changes in health, cardiac symptom status and medications, and without corroboration with other measures of inflammation. Accordingly, elevated hs-CRP levels should be interpreted with caution in this setting.
Blum
Arnon
A
Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. navablum@hotmail.com
Costello
Rene
R
Samsel
Leigh
L
Zalos
Gloria
G
McCoy
Phil
P
Csako
Gyorgy
G
Waclawiw
Myron A
MA
Cannon
Richard O
RO
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy*; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D015203:Reproducibility of Results; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000097:blood
D015415:Biomarkers; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein