Dear Editor,
In their systematic review and meta-analysis, Wang et al. concluded that high-sensitivity C-reactive protein (hsCRP) plasma levels may be a diagnostic biomarker for abdominal aortic aneurysms (AAAs) when their diameter is <50 mm, but not when it is largerCitation1. AAA patients with medium or small AAAs had higher hsCRP values compared with controls (difference in means: 1.391; 95% confidence interval [CI]: 0.821–1.781; p < .001)Citation1. However, in patients with large AAAs there was no difference in hsCRP levels between AAA patients and controls (difference in means: 1.769; 95% CI: −1.387 to 4.925; p = .272)Citation1. These results must be interpreted within the context of the reviewed evidence (heterogeneous observational studies) and bearing in mind the significant publication bias apparent from the analysis. Some additional comments may be of interest.
A recent case–control study from China (not included in the meta-analysis by Wang et al.Citation1 as it was only recently published) aimed to identify risk factors for AAAsCitation2. This study identified dyslipidemia (odds ratio [OR]: 2.61; 95% CI: 1.45–4.70; p < .01) serum hsCRP (OR: 2.43; 95% CI: 1.37–4.31; p < .01) and homocysteine (OR: 2.73; 95% CI: 1.61–4.65; p < .01) as predictors of AAAsCitation2.
Another study from China (which was not included in the meta-analysisCitation1 as it was very recently published) similarly investigated the association among hsCRP and CRP genetic polymorphisms with AAAsCitation3. This study also demonstrated that elevated serum hsCRP was an independent risk factor for AAA (OR: 3.91; 95% CI: 2.45–6.23; p < .001). It also suggested that genetic polymorphisms in the CRP gene could influence the concentration of serum hsCRP and the likelihood of an AAACitation3.
Besides hsCRP, other inflammatory markers may better predictors of AAAs. A recent study on rats showed that serum calprotectin may be a more promising biomarker for AAAs than hsCRPCitation4.
A limitation of using hsCRP as a prognostic marker is that its values fluctuate substantially in response to any inflammatory stimulusCitation5. Although high hsCRP levels are associated with AAAs in the meta-analysis by Wang et al.Citation1, an increase in hsCRP levels should not be viewed as proof of the presence of an AAA.
In addition, the authors supported that the lack of association between hsCRP levels with larger AAAs suggested that hsCRP levels may be inversely associated with AAA expansionCitation1. What mechanism would explain this lack of association given the fact that larger AAAs demonstrate increased inflammation compared with smaller AAAsCitation6?
Elevated levels of hsCRP may well be associated with AAAs, but the available evidence is still inconclusive. Furthermore, assuming the association is real, the mechanisms through which AAAs lead to elevated hsCRP levels must be elucidated. Finally, even if a true association between AAA and hsCRP is demonstrated, hsCRP is unlikely to have high specificity (as its levels can be affected by any inflammatory condition). It is hence unclear how hsCRP could be used as a diagnostic marker for AAAs in current practice.
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The contents of this letter and the opinions expressed within are those of the authors, and it was the decision of the authors to submit the letter for publication.
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K.I.P. and F.T. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.
References
- Wang Y, Shen G, Wang H, et al. Association of high sensitivity C-reactive protein and abdominal aortic aneurysm: a meta-analysis and systematic review. Curr Med Res Opin 2017:1-8. doi: 10.1080/03007995.2017.1354825
- Yuan H, Han X, Jiao D, Zhou P. A case–control study of risk factors of abdominal aortic aneurysm. Heart Surg Forum 2016;19:E224-8
- Shangwei Z, Yingqi W, Jiang Z, et al. Serum high-sensitive C-reactive protein level and CRP genetic polymorphisms are associated with abdominal aortic aneurysm. Ann Vasc Surg. 2017 May 24. pii: S0890-5096(17)30700-8. doi: 10.1016/j.avsg.2017.05.024. [Epub ahead of print]
- Morris D, Theoharis S, Davakis S, et al. Serum calprotectin as a novel biomarker in abdominal aortic aneurysm pathogenesis and progression: preliminary data from experimental model in rats. Curr Vasc Pharmacol. 2017 Feb 2. doi: 10.2174/1570161115666170202155724. [Epub ahead of print]
- Paraskevas KI, Mikhailidis DP. C-reactive protein (CRP): more than just an innocent bystander? Curr Med Res Opin 2008;24:75-8
- Freestone T, Turner RJ, Coady A, et al. Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol 1995;15:1145-51