Insulin-like growth factor-1 as a prognostic marker in patients with acute ischemic stroke.
ABSTRACT: Insulin-like growth factor-1 (IGF-1) has been associated with cardiovascular risk factors and atherosclerosis. The aim of the present study was to evaluate the prognostic value of IGF-1 levels in patients with acute ischemic stroke (AIS).All patients with first-ever AIS from August 1, 2012 to August 31, 2013 were recruited to participate in the study. Clinical data were collected. The National Institutes of Health Stroke Scale (NIHSS) score was assessed on admission blinded to serum IGF-1 levels. For the assessment of functional outcome at 90 days Modified Rankin Scale (mRS) was used. On admission, serum IGF-1 levels were determined by chemiluminescence immunoassay. The influence of IGF-1 levels on functional outcome and death was assessed by multivariate logistic regression analysis.Patients with an unfavorable outcomes and non-survivors had significantly decreased serum IGF-1 levels on admission (P<0.0001 for both). IGF-1 was an independent prognostic marker of functional outcome and death [odds ratio 0.89 (0.84-0.93) and 0.90 (0.84-0.95), respectively, P<0.0001 for both, adjusted for age, NIHSS score and other predictors] in patients with ischemic stroke. Serum IGF-1 levels ?130 ng/mL was as an value indicator for unfavorable functional outcome (OR 3.31, 95% CI:1.87-5.62; P<0.0001), after adjusting for other significant confounders.We reported a significant association between low serum IGF-1 levels and unfavorable functional outcome and death.
Project description:<h4>Background</h4>This study assessed whether serum lipid levels are associated with the risk of symptomatic intracerebral hemorrhage (sICH) and functional outcomes in patients with acute ischemic stroke after receiving intravenous thrombolysis.<h4>Methods</h4>We retrospectively analyzed consecutive ischemic stroke patients who were treated with intravenous tissue plasminogen activator between January 2007 and January 2017. Lipid levels on admission, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels, as well as potential predictors of sICH were tested using univariate and multivariate analyses.<h4>Results</h4>Of the 229 enrolled patients (100 women, aged 68 ± 13 years), 14 developed sICH and 103 (45%) had favorable functional outcomes at 3 months. The patients with sICH more often had diabetes mellitus (71% vs. 26%, <i>P</i> = 0.01) and had more severe stroke (mean National Institutes of Health Stroke Scale [NIHSS] score of 16 vs. 13, <i>P</i> = 0.045). Regarding lipid subtype, total cholesterol, LDL-C, HDL-C, and triglyceride levels were not associated with sICH or functional outcomes. According to the results of multivariate analysis, the frequency of sICH was independently associated with diabetes mellitus (odds ratio [OR] = 6.04; 95% CI [1.31-27.95]; <i>P</i> = 0.02) and the NIHSS score (OR = 1.12; 95% CI [1.02-1.22]; <i>P</i> = 0.01). A higher NIHSS score was independently associated with unfavorable functional outcomes (OR = 0.86; 95% CI [0.81-0.91]; <i>P</i> < 0.001).<h4>Conclusions</h4>Serum lipid levels on admission, including total cholesterol, LDL-C, HDL-C, and triglyceride levels, were not associated with sICH or 3-month functional outcomes after intravenous thrombolysis for acute ischemic stroke.
Project description:Clinical-Diffusion mismatch (CDM; NIHSS score ?8 & DWI lesion volume ?25 mL) and Perfusion-Diffusion mismatch (PDM; difference >20% between initial DWI and MTT lesion volumes) have been proposed as surrogates for ischemic brains that are at risk of infarction. However, their utility to improve the selection of patients for thrombolytic treatment remains controversial. Our aim was to identify molecular biomarkers that can be used with neuroimaging to facilitate the selection of ischemic stroke patients for systemic thrombolysis.We prospectively studied 595 patients with ischemic stroke within 12 h of the stroke onset. A total of 184 patients received thrombolytic treatment according to the SITS-MOST criteria. DWI and MTT volumes were measured at admission. The main outcome variable was good functional outcome at 3 months (modified Rankin scale <3). Serum levels of glutamate (Glu), IL-10, TNF-?, IL-6, NSE, and active MMP-9 also were determined at admission.Patients treated with t-PA who presented with PDM had higher IL-10 levels at admission (p?<?0.0001). In contrast, patients with CDM had higher levels of IL-10 (p?<?0.0001) as well as Glu and TNF-? (all p?<?0.05) and lower levels of NSE and active MMP-9 (all p?<?0.0001). IL-10???30 pg/mL predicts good functional outcome at 3 months with a specificity of 88% and a sensitibity of 86%. IL-10 levels ?30 pg/mL independently in both patients with PDM (OR, 18.9) and CDM (OR, 7.5), after an adjustment for covariates.Serum levels of IL-10 facilitate the selection of ischemic stroke patients with CDM and PDM for systemic thrombolysis.
Project description:<h4>Background</h4>We analyzed the prognostic value of b-type natriuretic peptide (BNP) and sensitive cardiac Troponin (s-cTnI) in patients with ischemic stroke or transient ischemic attack (TIA) and their significance in predicting stroke aetiology.<h4>Methods</h4>In a prospectively enrolled cohort we measured BNP and s-cTnI levels upon admission. Primary endpoints were mortality, unfavorable functional outcome and stroke recurrence after 90 days and after 12 months. Secondary endpoint was cardioembolic aetiology.<h4>Results</h4>In 441 patients BNP but not s-cTnI remained an independent predictor for death with an adjusted HR of 1.2 (95% CI 1.1-1.4) after 90 days and 1.2 (95% CI 1.0-1.3) after one year. The comparison of the Area under Receiver Operating Characteristic (AUROC) of model A (age, NIHSS) and model B (age, NIHSS, BNP) showed an improvement in the prediction of mortality (0.85 (95% CI 0.79-0.90) vs. 0.86 (95% CI 0.81-0.92), Log Rank p?=?0.004). Furthermore the category free net reclassification improvement (cfNRI) when adding BNP to the multivariate model was 57.5%, p<0.0001. For the prediction of functional outcome or stroke recurrence both markers provided no incremental value. Adding BNP to a model including age, atrial fibrillation and heart failure lead to a higher discriminatory accuracy for identification of cardioembolic stroke than the model without BNP (AUC 0.75 (95% CI 0.70-0.80) vs. AUC 0.79, (95% CI 0.75-0.84), p?=?0.008).<h4>Conclusion</h4>BNP is an independent prognostic maker for overall mortality in patients with ischemic stroke or TIA and may improve the diagnostic accuracy to identify cardioembolic aetiology.<h4>Trial registration</h4>ClinicalTrials.gov NCT00390962.
Project description:Objective:Many stroke patients make a partial recovery in function during the first 3 months, partially through promoting insulin-like growth factor-1 (IGF-1) function. A prognostic biomarker that associates with IGF-1 function may predict clinical outcome and recovery of stroke. This study evaluated plasma concentrations of IGF-1, IGF binding protein (IGFBP)-3 and cyclic-glycine-proline (cGP) and their associations with clinical outcome in stroke patients. Methods:Thirty-four patients were recruited within 3 days of stroke. Clinical assessments included the National Institutes of Health Stroke Scale (NIHSS) within 3 days (baseline), and at days 7 and 90; the modified Rankin Scale (mRS) and Fugl-Meyer Upper-Limb Assessment Scale (FM-UL) at days 7 and 90. Plasma samples were collected from the patients at the baseline, days 7 and 90. Fifty age-matched control participants with no history of stroke were also recruited and provided plasma samples. IGF-1, IGFBP-3, and cGP concentrations were analyzed using ELISA or HPLC-MS. Results:Baseline concentrations of IGFBP-3, cGP, and cGP/IGF-1 ratio were lower in stroke patients than the control group. The neurological scores of stroke patients were improved and plasma cGP and cGP/IGF-1 ratio increased over time. Baseline cGP/IGF-1 ratio was correlated with the NIHSS scores at day 90 and the changes in NIHSS scores from the baseline to 90 days. Interpretation:Low cGP concentrations and cGP/IGF-1 ratio in stroke patients suggest an impaired IGF-1 function. The cGP/IGF-1 ratio at admission maybe further developed as a prognostic biomarker for stroke recovery.
Project description:Insulin-like growth factor I (IGF-I) has neuroprotective effects in experimental ischemic stroke (IS). However, in patients who have suffered IS, various associations between the levels of serum IGF-I (s-IGF-I) and clinical outcome have been reported, probably reflecting differences in sampling time-points and follow-up periods. Since changes in the levels of post-stroke s-IGF-I have not been extensively explored, we investigated whether decreases in the levels of s-IGF-I between the acute time-point (median, 4 days) and 3 months (?IGF-I, further transformed into ?IGF-I-quintiles, ?IGF-I-q) are associated with IS severity and outcome.In the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) conducted in Gothenburg, Sweden, patients with IS who had s-IGF-I measurements available were included (N?=?354; 65% males; mean age, 55 years). Baseline stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) and converted into NIHSS-quintiles (NIHSS-q). Outcomes were assessed using the modified Rankin Scale (mRS) at 3 months and 2 years.In general, the levels of s-IGF-I decreased (positive ?IGF-I), except for those patients with the most severe NIHSS-q. After correction for sex and age, the 3rd ?IGF-I-q showed the strongest association to mRS 0-2 [Odds Ratio (OR) 5.11, 95% confidence interval (CI) 2.18-11.9], and after 2 years, the 5th ?IGF-I-q (OR 3.63, 95% CI 1.40-9.38) showed the strongest association to mRS 0-2. The associations remained significant after multivariate correction for diabetes, smoking, hypertension, and hyperlipidemia after 3 months, but were not significant (p?=?0.057) after 2 years. The 3-month associations withstood additional correction for baseline stroke severity (p?=?0.035), whereas the 2-year associations were further attenuated (p?=?0.31).Changes in the levels of s-IGF-I are associated primarily with temporally near 3-month outcomes, while associations with long-term 2-year outcomes are weakened and attenuated by other factors. The significance of the change in post-stroke s-IGF-I is compatible with a positive role for IGF-I in IS recovery. However, the exact mechanisms are unknown and probably reflects combinations of multiple peripheral and central actions.
Project description:Hyperthermia is a predictor of poor outcome in ischemic (IS) and intracerebral hemorrhagic (ICH) stroke. Our aim was to study the plausible mechanisms involved in the poor outcome associated to hyperthermia in stroke. We conducted a case-control study including patients with IS (n = 100) and ICH (n = 100) within the first 12 hours from symptom onset. Specifically, IS and ICH patients were consecutively included into 2 subgroups, according to the highest body temperature within the first 24 hours: Tmax <37.5°C and Tmax ≥37.5°C, up to reach 50 patients per subgroup of temperature for both IS and ICH patients. Body temperature was determined at admission and every 4 hours during the first 48 hours. Main outcome variable was poor functional outcome (modified Rankin scale score >2) at 3 months. Serum levels of glutamate and active MMP-9 were measured at admission. Our results showed that Tmax ≥37.5°C within the first 24 hours was independently associated with poor outcome in both IS (OR, 12.43; 95% CI, 3.73-41.48; p<0.0001) and ICH (OR, 4.29; 95% CI, 1.32-13.91; p = 0.015) after adjusting for variables with a proven biological relevance for outcome. However, when molecular markers levels were included in the logistic regression model, we observed that glutamate (OR, 1.01; 95% CI, 1.00-1.02; p = 0.001) and infarct volume (OR, 1.06; 95% CI, 1.01-1.10; p = 0.015) were the only variables independently associated to poor outcome in IS, and active MMP-9 (OR, 1.04; 95% CI, 1.00-1.08; p = 0.002) and National Institute of Health Stroke Scale (NIHSS) at admission (OR, 1.29; 95% CI, 1.13-1.49; p<0.0001) in ICH. In conclusion, these results suggest that although the outcome associated to hyperthermia is similar in human IS and ICH, the underlying mechanisms may be different.
Project description:Purpose:We evaluated the relationship between pretreatment IL-6 and hsCRP levels, symptom severity and functional outcome of patients with acute ischemic stroke (AIS) treated with IV-thrombolysis. Patients and Methods:IL-6 and hsCRP samples were obtained from 83 consecutively treated Caucasian patients with AIS prior to initiation of IV-thrombolysis. Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS), whereas functional outcome was assessed with modified Rankin Scale (mRS). The commercially available sets of enzymatic immune tests were used to estimate the concentrations of inflammatory markers in serum. Results:Medians of IL-6 serum concentrations prior to IV-thrombolysis were lower in patients with favorable (mRS 0-2 pts) functional outcome than in those with unfavorable (mRS 3-6 pts) functional outcome, both at hospital dismission (5.92: 2.30-7.71 vs 9.46: 3.79-17.29 pg/mL; p<0.01) and on the ninetieth day from stroke onset (5.87: 2.30-10.58 vs 10.9: 5.94-17.28 pg/mL; p<0.01). There were no existing differences regarding hsCRP levels between groups (2.49: 0.11-9.82 vs 4.44: 0.32-9.87 mg/dL; p=0.30 and 2.57: 0.11-2.57 vs 2.83: 0.32-9.32 mg/dL; p=0.75, respectively). Patients with lacunar strokes were characterized by lower median of IL-6 (5.96: 2.87-13.0% vs 7.29: 2.30-17.28; p=<0.02) and hsCRP (2.25: 0.11-9.82 vs 4.84: 0.35-9.87; p=0.01) than those with nonlacunar infarctions. Multivariate analysis showed an impact of IL-6 on mRS measured on hospital dismission and after three months, regardless of their initial NIHSS, presence of hemorrhagic transformation and type 2 diabetes. No impact of hsCRP, lacunar etiology and patients' age on functional outcome existed. Conclusion:Regardless of the stroke etiology, pretreatment of IL-6, but not of hsCRP levels, may help to predict functional outcome after IV-thrombolysis independently of symptom severity and stroke complications.
Project description:BACKGROUND:Early prediction of unfavorable outcome after ischemic stroke is of great significance to the clinical and therapeutic management. A nomogram is a better visual tool than earlier models and prognostic scores to predict clinical outcomes, which incorporates different factors to develop a graphic continuous scoring system and calculates accurately the risk probability of poor outcome entirely based on individual characteristics. However, to date, no nomogram models have been found to predict the probability of 6-month poor outcome after ischemic stroke. We aimed to develop and validate a nomogram for individualized prediction of the probability of 6-month unfavorable outcome in Chinese patients with ischemic stroke. METHODS:Based on the retrospective stroke registry, a single-center study which included 499 patients from May, 2013 to May, 2018 was conducted in Nanjing First Hospital (China) for ischemic stroke within 12?h of symptoms onset. The main outcome measure was 6-month unfavorable outcome (mRS?>?2). To generate the nomogram, NIHSS score on admission, Age, previous Diabetes mellitus and crEatinine (NADE) were integrated into the model. We assessed the discriminative performance by using the area under the curve (AUC) of receiver-operating characteristic (ROC) and calibration of risk prediction model by using the Hosmer-Lemeshow test. RESULTS:A visual NADE nomogram was constructed that NIHSS score on admission (OR: 1.190, 95%CI: 1.125-1.258), age (OR: 1.068, 95%CI: 1.045-1.090), previous diabetes mellitus (OR: 1.995, 95%CI: 1.236-3.221) and creatinine (OR: 1.010, 95%CI: 1.002-1.018) were found to be significant predictors of 6-month unfavorable outcome after acute ischemic stroke in Chinese patients. The AUC-ROC of nomogram was 0.791. Calibration was good (p?=?0.4982 for the Hosmer-Lemeshow test). CONCLUSION:The NADE is the first nomogram developed and validated in Chinese ischemic stroke patients to provide an individual, visual and precise prediction of the risk probability of 6-month unfavorable outcome.
Project description:Intravenous (i.v.) tissue-type plasminogen activator (tPA) is the only approved noninvasive therapy for acute ischemic stroke (AIS). However, after tPA treatment, the outcome of patients with different subtypes of stroke according to their vascular risk factors remains to be elucidated. We aim to explore the relationship between the outcome and different risk factors in patients with different subtype of acute strokes treated with i.v. tPA. Records of patients in this cohort were reviewed. Data collected and analysed included the demographics, vascular risk factors, baseline National Institutes of Health Stroke Scale (NIHSS) scores, 90-day modified Rankin Scores (mRS), and subtypes of stroke. By using the 90-day mRS, patients were dichotomized into favorable versus unfavorable outcome in each subtype of stroke. We identified the vascular risk factors that are likely associated with the poor outcome in each subtype. Among 570 AIS patients received i.v. tPA, 217 were in the large artery atherosclerosis (LAA) group, 146 in the small vessel occlusion (SVO) group, and 140 in the cardioaortic embolism (CE) group. Lower NIHSS score on admission was related to favorable outcome in patients in all subtypes. Patients with history of dyslipidemia were likely on statin treatment before their admission and hence less likely to have elevated cholesterol level on admission. Therefore, there was a possible paradoxical effect on the outcome in patients with LAA and SVO subtypes of strokes. SVO patients with history of diabetes had higher risk of unfavorable outcome. SVO patients had favorable outcome if their time from onset to treatment was short. In conclusion, the outcome of patients treated with i.v. tPA may be related to different vascular risk factors associated with different subtypes of stroke.
Project description:Cerebral venous outflow may play a decisive role in acute ischemic stroke. Here, we assessed the relation of cerebral sinus vein characteristics with clinical and imaging surrogates of early outcome in acute ischemic stroke. We evaluated cerebral vein characteristics in 212 patients with the middle cerebral artery (MCA) occlusive stroke confirmed by CT angiography CTA within 6 h from symptom onset. Readout parameters included volume and density of the sigmoid sinus (SS) and density of the superior sagittal sinus (SupSagS). These were correlated with early clinical outcome defined as hospital death (HD), final infarct volume (FIV), and National Institute of Health Stroke Scale (NIHSS) at discharge. We found a correlation for the volume of the right SS and the FIV when the M1 segment of the MCA of either side was occluded (p = 0.002, Rho = 0.206, n = 134). A decrease in SS density was more pronounced in the subgroup with unfavorable outcome (NIHSS > 15 + HD) but only when the left hemisphere was affected (p = 0.026, n = 101). On stepwise logistic regression analysis, adjusted for on-admission NIHSS, age at presentation, and FIV, smaller SS volume was independently associated with lower odds for hospital death (n = 183, OR 0.13, 95 % CI 0.02-0.94, p = 0.043). A larger right SS and a decrease in density increase the risk of unfavorable early clinical and imaging outcome in AIS. This finding of an outflow pattern independent of the stroke site implicates an involvement of the cerebral venous drainage system in the pathophysiology of ischemic stroke.