Role of N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and inteleukin-6 in predicting a poor outcome after a stroke.

OBJECTIVE: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6) concentrations can be important biomarkers in the acute stroke setting. In acute ischemic and hemorrhagic stroke patients, we investigated the association of NT-proBNP, hsCRP, and IL-6 serum concentrations with stroke severity and functional and cognitive outcomes at discharge. METHODS: Seventy-eight patients (53 men; median age 72 years) admitted with ischemic or hemorrhagic stroke within 48 h of symptom onset were evaluated for clinical stroke severity (Scandinavian stroke scale; SSS), functional status before the stroke (modified Rankin scale; mRS), and cerebrovascular disease risk factors. Cognitive (Mini Mental State Examination) and functional (mRS) outcomes were evaluated at hospital discharge. Blood samples were drawn for the assessment of NT-proBNP, hsCRP, and IL-6 concentrations within 24 h of admission. RESULTS: Greater NT-proBNP and hsCRP serum concentrations were associated with greater clinical stroke severity, adjusting for the patients' gender, age, stroke type, mRS score on admission, and presence of heart failure (ß = -0.292, p = 0.012; ß = -0.303, p = 0.009). In multivariate adjusted regression models with IL-6, hsCRP, and NT-proBNP considered together, IL-6 and hsCRP remained associated with worse functional (ß = 0.210, p = 0.022) and cognitive (ß = -0.269, p = 0.014) outcomes at discharge, respectively. In receiver operating characteristic analyses, the investigated blood biomarkers produced a minimal increase in predictive values for outcomes at discharge above the SSS score, age, and gender. CONCLUSIONS: In acute stroke patients, greater NT-proBNP and hsCRP serum concentrations are independently associated with greater clinical stroke severity. Elevated concentrations of IL-6 and hsCRP are associated with worse functional and cognitive outcomes at discharge, respectively.

Early senescence in heterozygous ABCA1 mutation skin fibroblasts: a gene dosage effect beyond HDL deficiency?

PURPOSE: Homozygous ABCA1 gene mutation causes Tangier disease (TD). The effects reported in heterozygous state regard plasma HDL, cell cholesterol efflux and coronary artery disease. We investigated whether in vitro replicative skin fibroblast senescence shown in TD proband (Hom), his father (Het), and in a healthy control might be induced in a "gene-dosage way". METHODS: Senescence was evaluated by staining test for ß-Galactosidase and telomere length (TL) on fibroblast DNA at different replicative stages. ABCG1 and LDLR (low density lipoprotein receptor) gene expression was also evaluated. RESULTS: Hom cells showed early senescent morphology and reduced growth at all passages in vitro. The cell positive percentage for ß-Galactosidase test was highly increased in Hom compared to Het cells at late replicative status (66.1% vs 41.3% respectively). TL was significantly shorter at high stage either in Hom (p<0.0001) or in Het (p<0.005). At early replication cycles ABCG1 gene expression was about 3-fold higher in Hom compared to Het cells (0.44 vs 0.14 arbitrary unit). CONCLUSIONS: ABCA1 gene mutation may have "gene-dosage way" effect on in vitro fibroblast senescence. Furthermore, increased ABCG1 and LDLR gene expression could highlight a role of ABCA1 on cytoskeleton regulation associated to cell cholesterol metabolism.