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

Disclosure

Wolf Eilenberg, Medical University Vienna 2

Speaker name: Wolf Eilenberg

I have the following potential conflicts of interest to report:

NONE

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

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

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

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%

Acknowledgement

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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