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Plasma Fibroblast Growth Factor 23 Concentration Is Associated with Intracranial Cerebral Atherosclerosis in Acute Ischemic Stroke Patients.

ABSTRACT: BACKGROUND AND PURPOSE:Fibroblast growth factor 23 (FGF23) is associated with atherosclerosis via nitric-oxide-associated endothelial dysfunction and calcium-phosphate-related bone mineralization. This study aimed to determine the association of the plasma FGF23 concentration with intracranial cerebral atherosclerosis (ICAS) and extracranial cerebral atherosclerosis (ECAS). METHODS:We prospectively enrolled 262 first-ever ischemic stroke patients in whom brain magnetic resonance was performed and a blood sample acquired within 24 h after admission. Plasma FGF23 concentrations were measured using an enzyme-linked immunosorbent assay. The presence of ICAS or ECAS was defined as a ?50% decrease in arterial diameter in magnetic resonance angiography. The burden of cerebral atherosclerosis was calculated by adding the total number of vessels defined as ICAS or ECAS. RESULTS:Our study population included 152 (58.0%) males. The mean age was 64.7 years, and the plasma FGF23 concentration was 347.5±549.6 pg/mL (mean±SD). ICAS only, ECAS only, and both ICAS and ECAS were present in 31.2% (n=82), 4.9% (n=13), and 6.8% (n=18) of the subjects, respectively. In multivariate binary and ordinal logistic analyses, after adjusting for sex, age, and variables for which p<0.1 in the univariate analysis, the plasma FGF23 concentration (per 100 pg/mL) was positively correlated with the presence of ICAS [odds ratio (OR)=1.07, 95% CI=1.00-1.15, p=0.039], burden of ICAS (OR=1.09, 95% CI=1.04-1.15, p=0.001), and burden of ECAS (OR=1.06, 95% CI=1.00-1.12, p=0.038), but it was not significantly related to the presence of ECAS (OR=1.05, 95% CI=0.99-1.12, p=0.073). CONCLUSIONS:The plasma FGF23 may be a potential biomarker for cerebral atherosclerosis, particularly the presence and burden of ICAS in stroke patients.

SUBMITTER: Chang Y

PROVIDER: S-EPMC6974828 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Plasma Fibroblast Growth Factor 23 Concentration Is Associated with Intracranial Cerebral Atherosclerosis in Acute Ischemic Stroke Patients.

Chang Yoonkyung Y Kim Jinkwon J Woo Ho Geol HG Ryu Dong Ryeol DR Oh Hyung Jung HJ Song Tae Jin TJ

Journal of clinical neurology (Seoul, Korea) 20200101 1

<h4>Background and purpose</h4>Fibroblast growth factor 23 (FGF23) is associated with atherosclerosis via nitric-oxide-associated endothelial dysfunction and calcium-phosphate-related bone mineralization. This study aimed to determine the association of the plasma FGF23 concentration with intracranial cerebral atherosclerosis (ICAS) and extracranial cerebral atherosclerosis (ECAS).<h4>Methods</h4>We prospectively enrolled 262 first-ever ischemic stroke patients in whom brain magnetic resonance w ...[more]

PMID: 31942755

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Project description:High plasma fibroblast growth factor-23 (FGF23) concentration predicts the risk of death and poor outcomes in patients with chronic kidney disease or chronic heart failure. We checked if FGF23 concentration could be modified in patients with end stage liver disease (ESLD) and predict mortality. We measured plasma FGF23 in 200 patients with ESLD registered on a liver transplant waiting list between January 2005 and October 2008. We found that median plasma FGF23 concentration was above normal values in 63% of the patients. Increased FGF23 concentration was not explained by its classical determinants: hyperphosphataemia, increased calcitriol concentration or decreased renal function. FGF23 concentration correlated with the MELD score, serum sodium concentration, and GFR. Forty-six patients died before being transplanted and 135 underwent liver transplantation. We analyzed the prognostic value of FGF23 levels. Mortality was significantly associated with FGF23 levels, the MELD score, serum sodium concentration and glomerular filtration rate. On multivariate analyses only FGF23 concentration was associated with mortality. FGF23 levels were independent of the cause of the liver disease. To determine if the damaged liver can produce FGF23 we measured plasma FGF23 concentration and liver FGF23 mRNA expression in control and diethyl-nitrosamine (DEN)-treated mice. FGF23 plasma levels increased with the apparition of liver lesions in DEN-treated mice and that FGF23 mRNA expression, which was undetectable in the liver of control mice, markedly increased with the development of liver lesions. The correlation between FGF23 plasma concentration and FGF23 mRNA expression in DEN-treated mice suggests that FGF23 production by the liver accounts for the increased plasma FGF23 concentration. In conclusion chronic liver lesions can induce expression of FGF23 mRNA leading to increased FGF23 concentration, which is associated with a higher mortality in patients on a liver-transplant waiting list. In these patients FGF23 concentration was the best predictor of mortality.

Project description:Background Studies suggest the presence of sex differences in hypertension prevalence and its associated outcomes in atherosclerosis and stroke. We hypothesized a higher intracranial atherosclerosis burden among men with hypertension and acute ischemic stroke compared with women. Methods and Results A multicenter retrospective study was performed from a prospective database identifying patients with hypertension presenting with intracranial atherosclerosis-related acute ischemic stroke and imaged with intracranial vessel wall magnetic resonance imaging. Proximal and distal plaques on vessel wall magnetic resonance imaging were scored. Negative binomial models assessed the associations between plaque-count and sex and the interaction between sex and treatment. Covariates were selected by a least absolute shrinkage and selection operator procedure. Sixty-one patients (n=42 men) were included. There were no significant differences in demographic or cardiovascular risk factors except for smoking history (P=0.002). Adjusted total and proximal plaque counts for men were 1.6 (95% CI, 1.2-2.1; P<0.01) and 1.4 (95% CI, 1.0-1.9; P=0.03) times as high as women, respectively. Female sex was more protective for proximal plaque if treated for hypertension. The risk ratio of men versus women was 1.5 (95% CI, 1.0-2.1) for treated patients. The risk ratio of men versus women was 0.7 (95% CI, 0.4-1.3) for untreated patients. The relative difference between these 2 risk ratios was 2.0 (95% CI, 1.1-3.9), which was statistically significant from the interaction test, P=0.04. Conclusions Men with hypertension with acute ischemic stroke have significantly higher total and proximal plaque burdens than women. Women with hypertension on anti-hypertensive medication showed a greater reduction in proximal plaque burden than men. Further confirmation with a longitudinal cohort study is needed and may help evaluate whether different treatment guidelines for managing hypertension by sex can help reduce intracranial atherosclerosis burden and ultimately acute ischemic stroke risk.

Dataset Information

Plasma Fibroblast Growth Factor 23 Concentration Is Associated with Intracranial Cerebral Atherosclerosis in Acute Ischemic Stroke Patients.

Publications

Plasma Fibroblast Growth Factor 23 Concentration Is Associated with Intracranial Cerebral Atherosclerosis in Acute Ischemic Stroke Patients.

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