Sándor Imre

Early-Onset Carotid Atherosclerosis Is Associated With Increased Intima-Media Thickness and Elevated Serum Levels of Inflammatory Markers

Background and Purpose— Several factors have been held responsible for the development of atherosclerosis. To avoid the masking effect of age, we evaluated correlates of carotid atherosclerosis in patients <55 years of age. Methods— Plasma lipids, oxidative resistance of low-density lipoprotein, homocysteine, inflammatory markers, plasma viscosity, and red cell deformability were measured in fasting blood samples of 100 subjects: 45 patients with >30% stenosis of the internal carotid artery, 20 patients with carotid occlusion, and 35 control subjects. Stenosis and intima-media thickness (IMT) of the carotid artery were evaluated by duplex ultrasound. Results— White blood cell (WBC) count, plasma fibrinogen, C-reactive protein (CRP), and lipoprotein(a) levels were significantly higher in patients than in control subjects, and patients had increased IMT (P <0.01 for all comparisons). There was a tendency for higher homocysteine levels in patients. Smokers had higher WBC, fibrinogen, and CRP levels. After the effect of smoking was controlled for, WBC count, natural logarithmic transform of homocysteine, and online-measured IMT remained significantly higher in patients than in control subjects. WBC, fibrinogen, and CRP levels were highest in the highest IMT quartile (P =0.012, P =0.007, and P =0.036, respectively). Conclusions— Inflammatory markers and homocysteine have a more important role than lipid factors in early-onset carotid atherosclerosis. We cannot recommend the measurement of low-density lipoprotein peroxidation as a routine screening test to identify high-risk patients for early-onset carotid atherosclerosis. The confounding effect of smoking on inflammatory markers should be considered in studies on atherosclerosis.

Increased proportion of docosahexanoic acid and high lipid peroxidation capacity in erythrocytes of stroke patients.

Intracellular accumulation of lipid peroxides that derive from the autoxidation of membrane polyunsaturated fatty acids reduces the deformability of erythrocytes contributing to the hemorheological disturbances observed in acute cerebral ischemia. The present study deals with the biochemical background of increased lipid peroxidation capacity in the erythrocytes of stroke patients. Methods A complete clinical and laboratory assessment was made of 24 men and 18 women (aged 50 to 78 years; 64.5+13.9 years, mean+SD) who had an ischemic hemispheric lesion of the brain. Lipid peroxide content, lipid peroxidation capacity, superoxide dismutase activity, and fatty acid composition of erythrocytes were compared in stroke patients and 22 healthy subjects matched for age. The lipid peroxide content of the erythrocytes was estimated before and after the autoxidative test; the results were expressed as nanomoles of malondialdehyde per gram of hemoglobin. The increase of the lipid peroxide content in the erythrocytes during the autoxidative test measures the lipid peroxidation capacity. Results In comparison with healthy subjects (1.45+0.30 nmol MDA/g Hb per 24 hours), the lipid peroxidation capacity was found to be significantly higher (4.18+0.41 nmol MDA/g Hb per 24 hours) (P<.01) in the erythrocytes of stroke patients. The stroke patients could be divided into two groups on the basis of lipid peroxidation capacity of their erythrocytes. Twenty patients had erythrocytes with high lipid peroxidation (<4 nmol MDA/g Hb per 24 hours), and 22 patients had very high lipid peroxidation capacity (>4 nmol MDA/g Hb per 24 hours). There was no significant difference in superoxide dismutase activity in the erythrocytes of patients compared with healthy subjects. Before the autoxidative test was conducted, the fatty acid composition in the erythrocytes of stroke patients with very high lipid peroxidation capacity was measured and found to be generally normal; only the proportion of docosahexanoic acid (22:6 n-3) was markedly (P<.01) increased. Conclusions The results suggest that the erythrocytes of ischemic stroke patients with very high lipid peroxidation capacity displaying an abnormal fatty acid composition are much more vulnerable to lipid peroxidation. The increased proportion of docosahexanoic acid and the high lipid peroxidation capacity of erythrocytes play a pathogenetic role and explain the hemorheological disturbances observed in the microcirculation of stroke patients.