The relationship between endothelin-1, event-related P300 potentials, and prognosis in cerebral arteriosclerosis.

Abstract

To search for a potential role of endothelin-1 (ET-1), a potent vasoconstrictor and presumably neurotoxic 21-amino acid peptide, for dysfunction of brain signal processing and cerebrovascular morbidity in nondemented patients with cerebral arteriosclerosis. Cross-sectional study with longitudinal follow-up. University-affiliated teaching hospital. A total of 106 nondemented patients with significant stenosis of either the internal carotid (cAD, cases; n = 63, mean age +/- SD, 62 +/- 7 years) or peripheral arteries (pAD, disease controls; n = 43, 60 +/- 11 years) were investigated before carotid endarterectomy and bypass surgery, respectively. After a mean follow-up of about 19 months, cerebrovascular morbidity of the cAD and pAD patients was evaluated by phone. Brain signal processing functions by event-related visual P300 potentials; cerebrovascular events by a structured telephone interview; the extent of arteriosclerosis by venous ET-1 concentration. Venous ET-1 levels were elevated in both cAD and pAD patient groups, but to the same degree. In these patients, ET-1 concentration was correlated slightly with diastolic blood pressure (r = .334, P = .0326, stepwise regression). Only in cAD patients with ET-1 levels above the 75th percentile were P300 latencies markedly prolonged compared with their lower ET-1 level counterparts. Furthermore, the P300 latencies of the cAD patients, but not of the pAD patients, correlated positively with venous ET-1 concentration and inversely with pack years of smoking (r = .728, P = .0002; stepwise regression). In contrast to base-line P300 abnormalities and classical risk factors (e.g., hypertension), high ET-1 levels predicted an increased cerebrovascular morbidity of cAD, but not of pAD, patients (P = .0044; Mantel Cox test). In nondemented patients with cerebral arteriosclerosis, endothelin-1 is associated with P300 abnormalities reflecting subclinical dysfunction of brain signal processing. In the long-term, high venous ET-1 levels also appear to predict a higher cerebrovascular morbidity of cAD patients even after carotid endarterectomy.