Relation of markers of inflammation (C-reactive protein, fibrinogen, von Willebrand factor, and leukocyte count) and statin therapy to long-term mortality in patients with angiographically proven coronary artery disease.
We evaluated a possible interaction between statins and inflammation in 1,246 patients with angiographically diagnosed coronary artery disease. Four different inflammatory markers were determined: high, sensitive C-reactive protein (hs-CRP) (p = 0.001), fibrinogen (p = 0.006), von Willebrand factor (p = 0.006), and leukocyte count (p = 0.03); these levels were significantly higher among the 88 patients who died of cardiac causes during follow-up (median 2.9 years) than among survivors. In a multivariate backward stepwise Cox regression mode, only hs-CRP was evaluated to be a significant predictor of death from coronary artery disease. This prediction was lost in statin-treated patients. Compared with patients receiving statin medication, patients without statins did not have increased cardiac mortality (even when low-density lipoprotein [LDL] levels were >125 mg/dl) when hs-CRP levels were not elevated. In contrast, patients without statins and elevated hs-CRP (top quartile) had a 2.3-fold increase in risk for fatal coronary events, independent of LDL levels. In conclusion, only elevated hs-CRP was selected as an independent predictor of death. Statin therapy is associated with elevated hs-CRP, with a risk reduction for fatal coronary events, independent of LDL levels; this, in part, may be explained by the anti-inflammatory effects on atherosclerosis.
Bickel
Christoph
C
Department of Medicine II, Johannes Gutenberg University Mainz, Germany. cbickel@t-online.de
Rupprecht
Hans J
HJ
Blankenberg
Stefan
S
Espiniola-Klein
Christine
C
Schlitt
Axel
A
Rippin
Gerd
G
Hafner
Gerd
G
Treude
Rainer
R
Othman
Hisham
H
Hofmann
Klaus-Peter
KP
Meyer
Jürgen
J
D000209:Acute-Phase Proteins / Q000032:analysis*; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000401:mortality*; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D014841:von Willebrand Factor / Q000032:analysis
D000209:Acute-Phase Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014841:von Willebrand Factor; D005340:Fibrinogen; D002097:C-Reactive Protein