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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: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.

Project description:Background: The contribution of metabolic profile to the cerebral collateral circulation in acute ischemic stroke (AIS) has not been fully outlined. In this study, we conducted a metabolomic study to assess the relationship between the metabolic biomarkers and the collateral status of AIS. Methods: A two-stage study was conducted from September 2019 to June 2021 in our hospital. There were 96 subjects including 66 patients with AIS and 30 healthy controls in the discovery stage and 80 subjects including 53 patients with AIS and 27 healthy controls in the validation stage. Collateral circulation was assessed by the Tan score based on computed tomographic angiography (CTA). Liquid chromatography-tandem mass spectrometry was used to identify differential metabolic markers. Then, an ELISA was employed to detect the plasma levels of sphingosine-1-phosphate (S1P). Results:There were 114 differential metabolites between patients with AIS and control groups and 37 differential metabolites between good collateral circulation (GCC) and poor collateral circulation (PCC) groups. The pathway enrichment analysis revealed that arginine biosynthesis was the only statistically significant pathway between AIS and control groups and sphingolipid metabolism was the only statistically significant pathway between GCC and PCC groups. The differential metabolites sphinganine-1-phosphate (SA1P) and S1P belong to the sphingolipid metabolism. In the discovery stage, when the GCC group was compared with the PCC group, the receiver operating characteristic (ROC) analysis showed that plasma SA1P relative levels demonstrated an area under the curve (AUC) of 0.719 (95% CI: 0.582-0.834), and S1P levels demonstrated an AUC of 0.701 (95% CI: 0.567-0.819). In addition, both plasma SA1P and S1P relative levels showed significant negative correlations with the 90-day modified Rankin Scale (mRS) score. In the validation sample, higher plasma S1P levels were independent predictors of GCC (p = 0.014), and plasma S1P levels demonstrated an AUC of 0.738 (95% CI: 0.599-0.849) to differentiate patients with GCC from patients with PCC. In addition, plasma S1P levels also showed significant negative correlations with the 90-day mRS score. Conclusion: We first illustrated the association between plasma metabolic profiles and cerebral collateral circulation in patients with AIS. Plasma S1P levels might be a potential diagnostic biomarker for predicting collateral circulation status in patients with AIS.

Project description:BackgroundFibroblast activation protein α (FAP), a membrane glycoprotein with dipeptidyl-peptidase and collagenase properties, is expressed in atherosclerotic plaques and remodeling of the extracellular matrix based on fibrosis. Fibrosis is a main contributor of atrial cardiomyopathies. In acute MI, circulating FAP is associated with outcome. Here, we investigated the correlation of circulating FAP to echocardiographic parameters of atrial remodeling and neurological impairment in acute ischemic stroke.MethodsCirculating FAP plasma concentrations were determined by ELISA in 47 patients with acute stroke and 22 control patients without stroke. Echocardiography was performed in all participants. Laboratory analysis, National Institutes of Health Stroke Scale (NIHSS) scoring and prolonged Holter-ECG-monitoring were performed in all stroke patients.ResultsPatients with acute stroke had lower circulating FAP concentrations than the control cohort (92 ± 24 vs. 106 ± 22 ng/mL, P < 0.001). There was no difference between the circulating FAP concentration comparing stroke due to atrial fibrillation, embolic stroke of undetermined source (ESUS) or atherosclerotic origin. Septal atrial conduction time (sPA-TDI) and left atrial (LA) volume index to tissue Doppler velocity (LAVI/a') representing echocardiographic parameters of LA remodeling did not correlate with FAP concentrations (sPA-TDI: r = 0.123, p = 0.31; LAVI/a': r = 0.183, p = 0.132). Stroke severity as assessed by NIHSS inversely correlated with circulating FAP (r = -0.318, p = 0.04). FAP concentration had a fair accuracy for identifying stroke in the receiver operating characteristic (ROC) analysis (AUC = 0.710, 95% CI: 0.577-0.843). A FAP concentration of 101 ng/mL discriminated between presence and absence of stroke with a sensitivity of 72% and a specificity of 77%. Lower circulating FAP concentration was associated with cardio-cerebro-vascular events within 12 months after admission.ConclusionsOur study is the first to associate FAP with echocardiographic parameters of LA-remodeling and function. FAP did not correlate with sPA-TDI and LAVI/a'. However, FAP was associated with stroke, neurological impairment, and cardio-cerebral events within 12 months. Therefore, FAP might enable individualized risk stratification in ischemic stroke.

Dataset Information

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

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

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