Angiotensin converting enzyme inhibition for arterial hypertension reduces the risk of recurrence in patients with chronic subdural hematoma possibly by an antiangiogenic mechanism.
OBJECTIVE
Chronic subdural hematoma (CSH) is characterized by pathological vascularization of the parietal membrane. Plasma leakage from immature vessels may be involved in hematoma enlargement and recurrence. We tested the hypothesis that the antiangiogenic side-effect of angiotensin converting enzyme (ACE)-inhibitor treatment for the control of arterial hypertension reduces the risk of recurrence in CSH.


METHODS
We analyzed the data of 438 patients with CSH treated by a standard surgical procedure for hematoma evacuation in our department between 1995 and 2003. Patients with coagulopathies, malignancies, and independent neurological disorders were excluded from this study. Patient records were screened for age, sex, pre- and postoperative Markwalder score, arterial hypertension, medication with ACE-inhibitors, and recurrence of CSH. The rate of ACE-inhibitor treatment in our CSH patients was compared with an age-matched control group treated for herniated lumbar disc at the same time. The concentration of vascular endothelial growth factor was analyzed in hematoma samples and corresponding venous blood in 40 consecutive patients.


RESULTS
A total of 310 patients were included in this study. The demographic data of Group A (with ACE-inhibition) and Group B (without ACE-inhibition) were comparable. In Group A, 5% (four out of 81) of the patients experienced recurrence as opposed to 18% (42 out of 229) in Group B (P = 0.00345). A negative correlation was found between the yearly rates of medication with ACE-inhibitors and recurrence (r = -0.8488; P = 0.0044). The rate of ACE-inhibitor treatment was lower in the CSH patients (25%) than in the control group (40%). The VEGF content was significantly lower in the hematoma in patients with ACE-inhibition (mean, 8891 pg/ml; range, 4300-18,300 pg/ml) than in patients without (mean, 22,565 pg/ml; range, 4200-89,650 pg/ml; P = 0.0116).


CONCLUSIONS
Our data suggest that ACE-inhibitor treatment for the control of arterial hypertension lowers the risk of recurrence in patients undergoing operation for CSH and possibly even the development of CSH. This effect might be the result of an antiangiogenic mechanism of ACE-inhibitors.
Weigel
Ralf
R
Department of Neurosurgery, Division of Neurosurgical Research, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Hohenstein
Axel
A
Schlickum
Linda
L
Weiss
Christel
C
Schilling
Lothar
L
D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D020200:Hematoma, Subdural, Chronic / Q000139:chemically induced / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D055502:Secondary Prevention
D020533:Angiogenesis Inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors