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CLINICAL STUDY

Plasma C-reactive protein as a marker of cardiac allograft vasculopathy in heart transplant recipients

Aina Hognestad, MD^*,*, Knut Endresen, MD, PhD^*, Ragnhild Wergeland, MS, Oddvar Stokke, MD, PhD, Odd Geiran, MD, PhD, Torbjorn Holm, MD, PhD^*, Svein Simonsen, MD, PhD^*, John K. Kjekshus, MD, PhD^* and Arne K. Andreassen, MD, PhD^*

^* Department of Cardiology, Rikshospitalet, Oslo, Norway
Department of Clinical Chemistry, Rikshospitalet, Oslo, Norway
Department of Thoracic Surgery, Rikshospitalet, Oslo, Norway

Manuscript received November 15, 2002; revised manuscript received March 17, 2003, accepted March 27, 2003.

^* Reprint requests and correspondence: Dr. Aina Hognestad, Department of Cardiology, Rikshospitalet, Sognsvannsveien 20, N-0027 Oslo, Norway.
aina.hognestad{at}klinmed.uio.no

OBJECTIVES: 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.

Abbreviations and Acronyms   BMI   body mass index   CAV   cardiac allograft vasculopathy   HLA   human leukocyte antigen   hsCRP   high-sensitivity C-reactive protein   HTR   heart transplant recipient   ROC   receiver-operating characteristics

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