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Novel Screening Tool
for Abdominal Aortic Aneurysms
based on Plasma D-Dimer and Myeloperoxidase
Wolf Eilenberg, Medical University Vienna
Wolf Eilenberg
Department of Surgery, Division of Vascular SurgeryMedical University of ViennaGeneral Hospital, Vienna, Austria
SPECIAL RESEARCH PROGRAMME SFB-54: “INTHRO”Cellular Mediators Linking Inflammation and Thrombosis
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Disclosure
Wolf Eilenberg, Medical University Vienna 2
Speaker name: Wolf Eilenberg
I have the following potential conflicts of interest to report:
NONE
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Neutrophil depletion inhibits AAA formation in mouse models• Eliason et al. Circulation 2005
Neutrophil-released proteases and ROS contribute to media destruction• Houard et al. FASEB J 2009
Neutrophil myeloperoxidase (MPO) is elevated in blood of AAA patients• Vega de Ceniga et al. Ann Vasc Surg 2014
Neutrophil involvement in AAA
3Wolf Eilenberg, Medical University Vienna
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Diagnostic marker potential of MPO for AAA compared to the established marker D-dimer
4Wolf Eilenberg, Medical University Vienna
p<0.001p<0.001
D-DimerAUC=0.830p<0.001
1 – Specificity
Sen
siti
vity
MPOAUC=0.829p<0.001
1 – Specificity
Sen
siti
vity
Exploration set:Plasma measurements of MPO and D-dimer in AAA patients (N=41) andhealthy controls (N=38) matched for age, sex, BMI and smoker status
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Development of a diagnostic scorebased on combined D-Dimer and MPO values
5Wolf Eilenberg, Medical University Vienna
Plot of cross-validated predicted probabilities vs. true outcome status:
Calibration plot (observed event rates vs. predicted probabilities in quartiles):
- Logistic regression model by stepwise backward elimination of clinical and laboratory parameters
- Only D-dimer and MPO show significant independent importance for AAA diagnosis - D-dimer: odds ratio 3.96 and 95% confidence interval 1.65-12.81 - MPO: odds ratio 1.23 and 95% confidence interval 1.08-1.43
Plot of cross-validatedpredicted probabilitiesversus true outcome status
ROC curve:
The area under the ROC curve and the discrimination slopes was 0.85 and 0.415 respectively.
Model 3: model with marker and demographic variables
## ORs 2.5 % 97.5 % pvals ## (Intercept) 0.000 0.000 0.014 0.001 ## Smoker2 19.711 1.608 492.095 0.040 ## DDimer 3.130 1.269 10.755 0.034 ## Monos_Sys 1.001 0.999 1.003 0.120 ## CD16monos_per 1.087 0.985 1.219 0.115 ## MPO 1.318 1.132 1.614 0.002
AUC=0.834Coefficient ofdiscrimination(R2)=0.404
Diagnostic linear score
derived from the logistic model
according to the estimated regression coefficients
SCORE = -3.442 + 1.375 * D-dimer + 0.205 * MPO
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Validation of the diagnostic scorebased on combined D-Dimer and MPO values
6Wolf Eilenberg, Medical University Vienna
AUC=0.934Coefficient of discrimination=0.489
Validation set:
Plasma samples from AAA patients (N=30) [median aneurysm diameter 54.6 mm (IQR=10.3)]
and unmatched healthy controls (N=29)
DICH- positive predictive value of 95.7% (78.1%-99.9%) - negative predicted value of 77.8% (60.9%-89.9%)
SCORE Sensitivity: 73.3% (54.1%-87.7%)Specificity: 96.6% (82.2%-99.9%)
SCORE predicts probability as PROB=1/(1+exp(-SCORE)
A simplified classifier: dichotomized SCORE (DICH)SCORE < 0 ... DICH=0SCORE >= 0 .... DICH=1
DICH * Disease Crosstabulation
Disease
Totalhealthy AAA
DICH 0 Count 28 8 36
% within DICH 77,8% 22,2% 100,0%
1 Count 1 22 23
% within DICH 4,3% 95,7% 100,0%
Total Count 29 30 59
% within DICH 49,2% 50,8% 100,0%
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Acknowledgement
7Wolf Eilenberg, Medical University Vienna
Laboratory work
Christine Brostjan
Branislav Zagrapan
Sarah Hetzer
Katharina Münch
Suriya Prausmüller
Paimann Nawrozi
Felix Juster
Patrick Kirchweger
Johannes Klopf
Marie-Therese Grasl
Hubert Hayden
Katharina Seif
Luca Martelanz
Renata Rajic
Alexandra R Szewcik
Alexandros Potolidos
Katharina Dosch
Clinical work
Christoph Neumayer
Ihor Huk
Biomedical Statistics
Georg Heinze
Alexandra Kaider