Eur J Vasc Endovasc Surg (2009) 37, 297e299

Search for Serum Biomarkers Associated

with Abdominal Aortic Aneurysm
Growth e A Pilot Study
M. Vega de Céniga a,*, M. Esteban b, J.M. Quintana c, A. Barba a,
L. Estallo a, N. de la Fuente a, B. Viviens a, J.L. Martin-Ventura d

a
Department of Angiology and Vascular Surgery, Hospital de Galdakao-Usansolo, Bizkaia, Spain
b
Biochemistry Laboratory, Hospital de Galdakao-Usansolo, Bizkaia, Spain
c
Research Unit, Hospital de Galdakao-Usansolo, CIBER Epidemiology and Public Health (CIBERESP), Spain
d
Vascular Research Laboratory, Fundación Jiménez Dı´az, Autonoma University, Madrid, Spain

Submitted 13 August 2008; accepted 11 November 2008

Available online 25 December 2008

KEYWORDS Abstract Introduction: Serological biomarkers could reflect asymptomatic infrarenal aortic
Abdominal aortic aneurysm (AAA) activity and guide patient management.
aneurysm; Report: Serum concentrations of C-reactive protein (CRP), alpha 1-antitrypsin and lipoprotei-
Serum biomarkers; n(a) were measured in blood samples from 35 AAA patients and 35 controls and correlated with
CRP; the aortic diameter and AAA growth in the previous 12 months.
Alpha 1-antitrypsin; We found a positive correlation between CRP and AAA diameter (r Z 0.46; p Z 0.007) and
Lipoprotein(a) alpha 1-antitrypsin and AAA growth (r Z 0.55; p Z 0.004).
Conclusions: Alpha 1-antitrypsin may be a promising biomarker of AAA growth.
ª 2008 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Current assessment of asymptomatic infrarenal aortic
aneurysms (AAA) is performed solely with serial imaging.
Predicting AAA expansion would greatly help in individual
patient management.
Inflammation plays an essential role in AAA complex
pathogenesis. Serum inflammatory markers might reflect
the AAA activity in asymptomatic phases and could be
prognostic indicators of AAA growth.
We designed a pilot study to discriminate the most
promising among previously reported candidates: C-reactive
protein (CRP), alpha 1-antitrypsin (a1-AT) and lipoprotein(a)
(Lp(a)).

* Corresponding author. M. Vega de Céniga, Department of

Angiology and Vascular Surgery, Hospital de Galdakao-Usansolo,
Barrio Labeaga s/n, 48960 Galdakao-Usansolo (Bizkaia), Spain.
Tel.: þ34 94 400 7000x2236; fax: þ34 94 400 7006.
E-mail address: melina.vegadeceniga@osakidetza.net (M. Vega
de Céniga).
Methods
We recruited 35 consecutive AAA patients (Octobere
December 2007). We excluded two patients for either thor-
aco-abdominal aneurysm or immunosuppressive therapy.

1078-5884/$34 ª 2008 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.ejvs.2008.11.014
298 M. Vega de Céniga et al.

The patients with 30e39-mm AAA were followed up with 200

annual ultrasound scanning and those with 40e49-mm AAA
with semi-annual CT scans. The patients with 50-mm AAA

were admitted for elective AAA repair. We measured the
maximum transverse and antero-posterior external diame-
ters of the infrarenal aorta, perpendicular to the aortic
axis. We included 35 controls randomly selected from
screened 65-year-old men with ultrasound-confirmed, non-
dilated (<30 mm) infrarenal aortas. The study was
approved by our local Research and Ethics Committees. We
obtained informed consent from the patients and controls.
We recorded clinical data, AAA size at the time of blood
sample collection and recent AAA growth (millimetre
difference in ultrasound/CT scans taken currently and 12
months previously) when available. We quantified CRP
(immunoturbidimetric method, Roche Diagnostics Ltd. West
Sussex, UK), a1-AT (immunonephelometric method, Dade
Behring, Inc. Deerfield, IL) and Lp(a) (immunoturbidimetric
method, Roche Diagnostics Ltd, West Sussex, UK): assay
coefficients of variation were <3.9%, <4.8% and <8.2%,
respectively.
Parametric and non-parametric tests, Spearman’s
correlation, linear regression and multivariate analysis
were used for statistical analysis (SPSS 15.0, p  0.05 as
level of significance).
Results
The AAA patients and controls are described in Table 1. The
median AAA size (n Z 35) was 43 (35e52) mm and median
AAA growth (n Z 25) was 3 (0e6) mm.
The median unadjusted serum levels of CRP, a1-AT and
Lp(a) were significantly higher in the AAA patients: CRP 4.1
(1.9e7.3) versus 1.9 (0.5e5) mg l1; a1-AT 147 (131e168)
versus 125.5 (114e135.5) mg dl1; Lp(a) 47 (20e117.5)
versus 27 (9e47) mg dl1. After adjustment for age, gender
and smoking, these differences were, at best, of marginal
significance, p-values for CRP, a1-AT and Lp(a) were 0.32,
0.06 and 0.05, respectively.
We observed significant positive correlations between
CRP and AAA size (r Z 0.46, p Z 0.007) and a1-AT and
alpha1-antitrypsin (mg/dL)
180
160
140
120
100
-2 0 2 4 6 8 10 12
AAA growth in previous 12 months (mm)
Figure 1 Correlation of a1-AT levels with recent AAA
expansion. The linear regression line for 25 patients is shown:
r Z 0.55, p Z 0.004.
recent AAA expansion, estimated by linear regression,
r Z 0.55, p Z 0.004 (Fig. 1): both correlations remained
significant after adjustment for age, sex and active
smoking. There were no correlations between CRP, a1-AT
or Lp(a) values and aortic diameter in the control group
(p Z 0.73, 0.71 and 0.22, respectively). Multivariate anal-
ysis showed that CRP levels were reduced by statin intake
(p Z 0.016).
Discussion
There is conflicting evidence about the association between
CRP and AAA size or expansion.1,2 In this pilot study, we
observed a correlation between CRP and AAA size, but
could not find any reliable association with recent AAA
growth. Moreover, we observed that the association
between CRP and AAA size was modulated by statins. Sta-
tins have pleiotropic effects and could participate in the
prevention and/or stabilisation of AAA.3

Table 1 Cardiovascular risk factors and co-morbidity in the AAA patients and controls
AAA patients (n Z 35) Control group (n Z 35) p-value
Age (years) 71  6.8 (54e83) 65  0.29 (64e65) <0.0001
Gender (male/female) 33 (94.3%)/2 (5.7%) 35 (100%)/0 (0%) 0.49
Active smoking 12 (34.3%) 6 (17.1%) 0.1
Arterial hypertension 20 (57.1%) 17 (48.6%) 0.47
Diabetes mellitus 5 (14.3%) 6 (17.1%) 0.74
Hypercholes terolaemia 20 (57.1%) 17 (48.6%) 0.47
Heart disease 7 (20%) 8 (22.9%) 0.77
COPD 5 (14.3%) 2 (5.7%) 0.42
Chronic renal failure 3 (8.6%) 0 (0%) 0.24
Peripheral artery disease 8 (22.9%) 1 (2.9%) 0.032
Cerebrovascular disease 7 (20%) 0 (0%) 0.017
Statin treatment 17 (48.6%) 7 (20%) 0.012
COPD, chronic obstructive pulmonary disease; Student’s t-test for continuous variables; Pearson’s chi-square or Fisher’s exact test for
categorical variables.
Serum Biomarkers and AAA
The strength of our observations is limited by the small
sample size and retrospective evaluation of AAA growth.
However, Lp(a) was not associated with either AAA size or
recent expansion in our study.
Increased serum a1-AT has been associated with the
future development of AAA and has been correlated with
AAA expansion but not size4; our pilot observations support
this. Hence, serum a1-AT concentration remains a possible
biomarker of AAA growth.
Acknowledgements
We are grateful to Susana Garcı́a and Urko Aguirre from the
Hospital de Galdakao-Usansolo Research Unit for their
assistance with the design of the study and the statistical
analysis. This work was supported by a grant from the
Hospital de Galdakao-Usansolo Research Committee.
299
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