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Leukocyte activation: relation to cardiovascular mortality after cerebrovascular ischemia
P Falke1, A M Elneihoum, K Ohlsson
1Department of Medicine, University of Lund, University Hospital, Malmö, Sweden.
Insights
Markers of systemic leukocyte activation, including soluble tumor necrosis factor receptor protein-1 (sTNFR-1) and neutrophil gelatinase-associated lipocalin (NGAL), predict cardiovascular mortality in patients with acute cerebral ischemia.
Area of Science:
- Cardiovascular Research
- Immunology
- Neurology
Background:
- Activated leukocytes play a role in atherosclerotic vascular disease.
- Systemic leukocyte activation may influence cardiovascular mortality after cerebrovascular events.
Purpose of the Study:
- To investigate the relationship between markers of systemic leukocyte activation and cardiovascular mortality following cerebrovascular ischemia.
- To assess plasma levels of sTNFR-1, NGAL, and NP4 as predictors of long-term cardiovascular death.
Main Methods:
- Observational follow-up study of 144 patients (90 stroke, 54 TIA) within 1-3 days of cerebral ischemia.
- Plasma levels of sTNFR-1, NGAL, and NP4 measured using enzyme-linked immunosorbent assays.
- 4-year follow-up to determine cardiovascular mortality, analyzed with logistic regression.
Main Results:
- 42 patients (29%) died within 4 years, 38 from cardiovascular causes.
- Higher leukocyte activation was associated with significantly increased 4-year cardiovascular mortality (p < 0.005).
- Elevated sTNFR-1 (OR 2.0, p < 0.01) and NGAL (OR 3.6, p = 0.02) were independent predictors of cardiovascular mortality.
Conclusions:
- Plasma markers of leukocyte activation are significant predictors of long-term cardiovascular mortality in patients with acute cerebral ischemia.
- Activated leukocytes may contribute to the progression of atherosclerotic vascular disease and its cardiovascular consequences.
- sTNFR-1 and NGAL show potential as biomarkers for risk stratification in post-ischemic patients.
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.