title: Leukocyte activation: relation to cardiovascular mortality after cerebrovascular ischemia.
abstract: Activated leukocytes are believed to be involved in the pathogenesis and progression of atherosclerotic vascular disease and its consequences. In a 4-year observational follow-up study, we investigated whether markers for systemic leukocyte activation (leukocyte-derived inflammatory mediators) were related to cardiovascular mortality after cerebrovascular ischemia. Using enzyme-linked immunosorbent assays, we measured the plasma levels of soluble tumor necrosis factor receptor protein-1 (sTNFR-1), neutrophil gelatinase-associated lipocalin (NGAL) and neutrophil protease-4 (NP4) in 144 patients (90 stroke, 54 transient ischemic attack) 1-3 days after cerebral ischemia. During the 4 years of follow-up, 42 (29%) of the 144 patients died; 38 of cardiovascular causes and 4 of other causes. Patients with evidence of higher leukocyte activation (n = 47) had a higher 4-year cardiovascular mortality rate than those without evidence of leukocyte activation (n = 97; p < 0.005). Logistic regression analysis with age, sex and other significant predictors as covariates showed higher plasma levels of sTNFR1 and NGAL both to be significant independent predictors of cardiovascular mortality, the respective odds ratio, 95% confidence intervals, and p values being 2.0, 1.2-3.4, p < 0.01, and 3.6, 1.2-10.5, p = 0.02, respectively. We concluded that in patients with acute cerebral ischemia, plasma markers of leukocyte activation were significant predictors of long-term cardiovascular mortality. This may indicate an important role of activated leukocytes in the progression of these diseases.
authors.affiliation: Department of Medicine, University of Lund, University Hospital, Malmö, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Falke
authors.forename: A M
authors.initials: AM
authors.lastname: Elneihoum
authors.forename: K
authors.initials: K
authors.lastname: Ohlsson
mesh_terms: D000209:Acute-Phase Proteins; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D002545:Brain Ischemia / Q000097:blood / Q000401:mortality / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000401:mortality*; D002352:Carrier Proteins / Q000097:blood; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D002546:Ischemic Attack, Transient / Q000097:blood / Q000401:mortality / Q000503:physiopathology; D000071068:Lipocalin-2; D054834:Lipocalins; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin; D018375:Neutrophil Activation; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000097:blood; D020521:Stroke / Q000097:blood / Q000401:mortality / Q000503:physiopathology*; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D015703:Antigens, CD; D015415:Biomarkers; D002352:Carrier Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D012697:Serine Endopeptidases; D053146:Myeloblastin