Plasma C-reactive protein as a marker of cardiac allograft vasculopathy in heart transplant recipients.
OBJECTIVE
This study was initiated to determine whether heart transplant recipients (HTRs) with cardiac allograft vasculopathy (CAV) have increased levels of high-sensitivity C-reactive protein (hsCRP) and to examine whether an increase in hsCRP after heart transplantation predicts the development of CAV. Furthermore, the effect of pravastatin on plasma levels of hsCRP in HTRs was investigated.


BACKGROUND
The relationship between CAV and hsCRP, as well as the effect of statins on hsCRP in HTRs, has not been well established.


METHODS
On referral for their annual angiographic control study, 150 consecutive HTRs (mean 6.5 years since transplantation) were included. Plasma levels of hsCRP were measured before angiography and compared with patients with (n = 52) and without (n = 98) CAV. In 49 of these patients, we additionally analyzed hsCRP in blood samples stored from their six-month visit after the transplantation procedure. Furthermore, in a randomized, crossover study, hsCRP was analyzed in 17 male HTRs before and after six weeks of treatment with 20 mg pravastatin.


RESULTS
Median levels of CRP were elevated among patients with CAV compared with those with normal angiograms [3.86 (1.78 to 7.00) vs. 1.08 (0.72 to 2.13) mg/l, p < 0.001]. Prospectively evaluated hsCRP levels from six months to follow-up were significantly higher among those who developed CAV compared with those with normal angiograms [+2.76 (1.56 to 5.00) vs. +0.07 (-0.57 to 0.41) mg/l, p < 0.001]. On multivariate analysis, the increase in hsCRP was the only significant predictor of CAV. Six weeks of treatment with pravastatin significantly reduced hsCRP levels by 25%, without any relation to changes in lipid values.


CONCLUSIONS
Elevated plasma levels of CRP are associated with angiographic evidence of CAV, and the increase in hsCRP is a strong predictor of development of CAV. Statin treatment reduces levels of hsCRP and should be used in HTRs, regardless of their lipid levels.
Hognestad
Aina
A
Department of Cardiology, Rikshospitalet, Oslo, Norway. aina.hognestad@klinmed.uio.no
Endresen
Knut
K
Wergeland
Ragnhild
R
Stokke
Oddvar
O
Geiran
Odd
O
Holm
Torbjorn
T
Simonsen
Svein
S
Kjekshus
John K
JK
Andreassen
Arne K
AK
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis / Q000276:immunology*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D018592:Cross-Over Studies; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D014184:Transplantation, Homologous / Q000473:pathology
D000924:Anticholesteremic Agents; D015415:Biomarkers; D002097:C-Reactive Protein; D017035:Pravastatin