Vascular fingerprint and vascular damage markers associated with vascular events in testicular cancer patients during and after chemotherapy.
Metastatic testicular cancer (TC) can be cured with bleomycin, etoposide and cisplatin (BEP) chemotherapy. This comes at the price of an increased cardiovascular disease risk, not only years afterwards, but also during and shortly after chemotherapy. To prevent cardiovascular events, high-risk patients should be identified. The aim of this study was to assess BEP-chemotherapy induced vascular damage and to find risk factors for early vascular events.



A prospective cohort study was performed in (B)EP treated TC patients. Development of venous and arterial vascular events was assessed. Vascular damage markers (von Willebrand factor [vWF], coagulation factor VIII [FVIII], intima media thickness [IMT]) and cardiovascular risk factors were assessed before and until 1 year after chemotherapy. Before start of chemotherapy a vascular fingerprint was estimated. Presence of ≥3 risk factors was defined as high-risk vascular fingerprint: body mass index >25 kg/m(2), current smoking, blood pressure >140/90 mm Hg, total cholesterol >5.1 and/or low-density lipoprotein >2.5 mmol/L or glucose ≥7 mmol/L.



Seventy-three patients were included. Eight (11%) developed vascular events (four arterial events, four pulmonary embolisms). vWF and FVIII increased during chemotherapy, especially in patients with vascular events. Sixteen patients (22%) had a high-risk vascular fingerprint before start of chemotherapy. These patients had arterial events more often (3/16 [19%] versus 1/57 [2%]; p = 0.031) and higher vWF levels and IMT.



Endothelial activation and upregulation of procoagulant activity seem important mechanisms involved in early (B)EP-chemotherapy-induced vascular events. Before chemotherapy, a quarter already had cardiovascular risk factors. A vascular fingerprint could identify patients at risk for arterial events. This vascular fingerprint, when validated, can be used as a tool to select patients who may benefit from preventive strategies.
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
S
S
Lubberts
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
H
H
Boer
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
R
R
Altena
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
C
C
Meijer
Department of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
A M
AM
van Roon
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
N
N
Zwart
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
S F
SF
Oosting
Department of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
P W
PW
Kamphuisen
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
J
J
Nuver
Department of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
A J
AJ
Smit
Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
A B
AB
Mulder
Department of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
J D
JD
Lefrandt
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: j.a.gietema@umcg.nl.
J A
JA
Gietema
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D001761:Bleomycin / Q000008:administration & dosage; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000175:diagnosis*; D059168:Carotid Intima-Media Thickness; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005169:Factor VIII / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013736:Testicular Neoplasms / Q000150:complications / Q000188:drug therapy*; D055815:Young Adult; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D017127:Glycation End Products, Advanced; D014841:von Willebrand Factor; D001761:Bleomycin; D005047:Etoposide; D005169:Factor VIII; D002945:Cisplatin
Bleomycin; Cardiovascular diseases; Carotid intima media thickness; Chemotherapy, adjuvant; Cisplatin; Factor VIII; Growth differentiation factor 15; Risk factors; Testicular neoplasms; Von Willebrand factor