C-reactive protein and severity of coronary allograft vasculopathy

Arising from: Sarno G et al. (2008) Multicenter assessment of coronary allograft vasculopathy by intravascular ultrasound-derived analysis of plaque composition. Nat Clin Pract Cardiovasc Med 6: 61–69 [doi:10.1038/ncpcardio1410]

Authors' response: Sarno G and Vanderheyden M (2009) Assessment of coronary allograft vasculopathy in humans by intravascular ultrasound-derived analysis of plaque composition: a multicenter experience. Nat Clin Pract Cardiovasc Med 6 [doi:10.1038/ncpcardio1474]

We read with interest the manuscript by Sarno et al.,¹ in which the authors show that the change in plaque burden and composition over time in coronary allograft vasculopathy (CAV) seemed to affect clinical outcome. They suggest that risk factors, such as inflammation and oxidative stress, are associated with plaque composition after heart transplantation. However, the authors fail to demonstrate a significant correlation between necrotic core content and C-reactive protein (CRP) concentrations, and they report no differences in CRP levels between patients who did and did not undergo revascularization.

In their discussion, the authors mentioned that substantially raised concentrations of CRP have been identified in previous studies of patients at high risk of CAV, but no association has been found with severity of angiographic CAV. We would like to note that the authors have overlooked a manuscript published by our group, which clearly showed a strong association between high CRP concentrations and development of angiographic CAV.² Our data showed that early elevations of CRP concentrations during the first 3 months after heart transplantation were associated with subsequent development, progression, and severity of CAV. Furthermore, our data established a significant association between elevated CRP levels and development of ischemic events, including revascularization procedures. The authors referenced the article by Hognestad et al.³ regarding the association between systemic inflammation and incidence of CAV, but seemed to have overlooked that the data from that group also showed a significant association between CRP levels and severity of CAV. Both Hognestad et al.³ and our own data² have established a very important point regarding early biomarkers of CAV. Both groups showed that high CRP levels within the first 6 months after heart transplantation are strong predictors of CAV onset and progression. Hognestad et al.³ have also demonstrated that the use of statins in their patients significantly reduced CRP levels, supporting the conclusion that therapies, such as statins, could explain the lack of association in their data between CRP levels with necrotic core content or need for revascularization.

We would like also to comment on some additional points taken from Sarno et al.'s discussion. First, efforts need to be directed towards evaluation of the status of allograft microvasculature, since CAV is not limited only to the epicardial arteries, but also compromises the small intramyocardial arteries and arterioles. Our data have shown, for example, that heart transplant recipients with high CRP levels have a significantly upregulated expression of adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), in the arterial and arteriolar endothelium within the heart, as well as elevated soluble ICAM-1 in circulation.² These findings indicate that microvessel compromise within the heart is mirrored systemically. Second, Sarno et al. also mentioned the need for a longitudinal study to better establish the association between risk factors and subsequent change in plaque composition. It would be extremely interesting to know, as shown by Hognestad et al.³ and ourselves,² if the authors could establish an association between early high levels of proinflammatory molecules, such as CRP, and change in plaque burden and composition over time in heart transplant patients.