endothelin-1 and Intracranial-Arteriosclerosis

We studied the association of endothelin (ET)-1 with carotid atherosclerosis and asymptomatic cerebrovascular lesions in patients with essential hypertension. Neurologically normal patients with essential hypertension (n=293; 138 male, 155 female; mean age, 65 years) and age-matched control subjects (n=242) were studied with B-mode ultrasonography of the common and internal carotid arteries and magnetic resonance imaging of the brain. Plasma ET-1 was measured by enzyme immunoassay. Hypertensive patients were divided into groups with carotid plaques and low ET-1 concentrations (< 0.75 pg/ml; PL group); carotid plaques and mid-range ET-1 (0.75 to 1.55 pg/ml; PM group); carotid plaques and high ET-1 (> or = 1.55 pg/ml; PH group); no plaques and low ET-1 (NPL); no plaques and mid-range ET-1 (NPM); and no plaques and high ET-1 (NPH). Overall, ET-1 concentrations were significantly higher in patients than in control subjects. Carotid plaque prevalence was significantly related to ET-1 in hypertensive patients. ET-1 showed a significant positive relationship with the number of asymptomatic lacunar infarcts of the brain in hypertensive patients with carotid plaques (rho=0.48, p<0.001). No significant relationship was seen between ET-1 and periventricular hyperintensity scores in patients with plaques. ET-1 did not show a relationship to either brain lesion type in patients without carotid plaques. Thus, ET-1 may foster asymptomatic lacunar cerebral infarcts by promoting carotid atherosclerosis in patients with essential hypertension.

Topics: Adult; Aged; Carotid Artery Diseases; Cerebral Infarction; Cerebrovascular Disorders; Endothelin-1; Female; Humans; Hypertension; Intracranial Arteriosclerosis; Magnetic Resonance Imaging; Male; Middle Aged; Osmolar Concentration; Reference Values; Ultrasonography

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.

Topics: Aged; Carotid Stenosis; Cross-Sectional Studies; Endarterectomy, Carotid; Endothelin-1; Event-Related Potentials, P300; Female; Follow-Up Studies; Humans; Intracranial Arteriosclerosis; Male; Middle Aged; Prognosis; Survival Analysis