Triglyceride–Glucose Index and Short‐Term Functional Prognosis in Patients With Acute Ischemic Stroke: A Retrospective Study

BackgroundMatrix metalloproteinase-9 (MMP-9) and brain-derived neurotrophic factor (BDNF) have documented roles in the inflammatory injury cascade of neurovascular units following ischemic brain injury. However, their dynamic changes and predictive values after acute ischemic stroke (AIS) have not been well elucidated.ObjectiveTo investigate the temporal profiles of serum MMP-9 and BDNF concentrations and their relationship with the prognosis in patients with AIS.MethodsMMP-9 and BDNF levels were measured in 42 AIS patients in prospectively collected blood samples, which were taken on the first day (Day 1), the second day (Day 2), and the fifth day (Day 5) after admission. Healthy subjects (n = 40) were used as controls. The AIS patients were divided into groups of good functional prognosis (n = 24) and poor prognosis (n = 18) according to their modified Rankin Scale score at 3 months. Longitudinal analysis of MMP-9 and BDNF and their association with neurological prognosis was performed using repeated measurement ANOVA.ResultsAt baseline (Day 1), the levels of serum MMP-9 and BDNF were significantly higher in the AIS group than in the normal control group (P < 0.01). Repeated measurement ANOVA showed a significant main effect and interaction of MMP-9 between good prognosis and the poor group (P < 0.05). Further simple-effect analysis showed that the MMP-9 level was significantly increased in the poor prognosis group compared with the good prognosis group at T5 (P < 0.05). There were no significant time-dependent or the interaction effect (all P > 0.05), but a main effect (P < 0.05) for BDNF. Compared with the poor prognosis group, the simple-effect results indicated that the BDNF level of the good prognosis group was lower at Day 1, while the same was reversed for expression at Day 5 (P < 0.05).ConclusionMMP-9 and BDNF are closely related to the prognosis of patients with AIS in a time-dependent manner. The dynamic changes of the two biomarkers are superior to baseline levels in predicting the prognosis of AIS patients. A sustained decrease in MMP-9 and an increase in BDNF levels in AIS patients after several days of treatment implied a favourable prognosis.

Introduction: The triglyceride-glucose (TyG) index is reported to be related to poor functional outcomes and all-cause mortality post-stroke. However, the association between TyG index and recurrent stroke after acute ischemic stroke (AIS) has not been well described. We aimed to identify whether the TyG index was associated with 1-year recurrent stroke after AIS. Methods: Baseline patient information was collected at admission, and the TyG index was calculated. Recurrent stroke events were followed up at 1, 3, 6, and 12 months after diagnosis. We then examined the association between the TyG index and risk of 1-year recurrent stroke using multivariable Cox regression models and restricted cubic spline analyses. Results: Among 2,288 participants, the mean TyG index was 8.8 ± 0.7. Those in the fourth quartile (Q4) demonstrated higher recurrent stroke risk than those in Q1 (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI], 0.98–2.72; p = 0.059). Subgroup analysis revealed a sex-specific association between TyG index and recurrent stroke (p for interaction = 0.022). Additionally, restricted cubic splines analyses showed a nonlinear association between the TyG index and 1-year recurrent stroke. In females, patients in the Q4 had a 2.95-fold increased recurrent stroke risk than did patients in the Q1 (adjusted HR = 2.95; 95% CI: 1.09–7.94; p = 0.032); the risk increased when the TyG index was >8.73. However, no significant correlation was observed in males. Conclusion: A nonlinear association was found between the TyG index and 1-year recurrent stroke risk. Subsequently, a high TyG index could predict an increased 1-year recurrent stroke risk in female AIS patients.

Background: Early outcome prediction after acute ischemic stroke (AIS) is critical to guide care and rehabilitation strategies. Pre-existing chronic structural injury to cerebral white matter (WM), including ischemic WM hyperintensity (WMH) and microstructural changes within the normal-appearing WM (NAWM), is known to impede post-stroke recovery. Quantitative assessment of total pre-existing WM injury may therefore improve prognostication of functional stroke outcomes. Peak width of skeletonized mean diffusivity (PSMD) is an automated marker of cerebral small vessel disease and global WM injury. In a cohort of AIS patients, we measured PSMD in the hemisphere contralateral to the acute infarct and characterized its association with 90-day functional outcomes. Methods: Brain MRI with diffusion tensor imaging sequences was acquired within 48 hours of AIS admission. WMH volume (WMHv) was measured in a semi-automated manner. NAWM masks were constructed by subtracting the WMH and chronic infarct masks from a probabilistic WM atlas. NAWM mean diffusivity (MD) was then measured in the NAWM mask. PSMD was extracted by skeletonizing the WM tracts in the MD image using the Fractional Anisotropy image and the FSL Tract-Based Spatial Statistics pipeline with a mask for the contralesional hemisphere. Excellent outcome was defined as a modified Rankin scale score &lt; 2 at 3-6 months post-stroke. Logistic regression analysis was performed to evaluate predictors of excellent outcome. Results: In 292 AIS patients, increasing PSMD and NAWM MD, but not WMHv, were associated with decreased likelihood of excellent outcome in univariable analysis. Increasing age, admission NIHSS score, DWI volume, and female sex were also negatively associated with excellent outcome. In backward stepwise logistic regression, including all significant variables from the univariable step, increasing age (β = -0.03; P = 0.01), NIHSS (β = -0.1; P = 0.0005), DWI volume (β = -0.02; P = 0.0004), PSMD (β = -0.08; P = 0.03), and female sex (β = -0.7; P = 0.01) were associated with decreased likelihood of excellent outcome. Conclusion: In AIS patients, automated determination of contralesional PSMD, as a marker of chronic, global white matter injury, is an independent predictor of functional outcomes.

Background: Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor-ß family. Elevated GDF-15 concentrations are associated with increased risks of cardiovascular diseases, diabetes mellitus and cerebrovascular disease.Objective: This study aimed to determine the clinical significance of serum GDF-15 level after acute ischemic stroke (AIS) in a Chinese population.Methods: We compared serum GDF-15 levels between 83 AIS patients and 124 controls. At admission and on day 7, we recorded the National Institutes of Health Stroke Scale score and measured serum GDF-15 levels for AIS patients and for control patients at admission. Stroke volumes were calculated using diffusion-weighted magnetic resonance imaging performed at admission. Clinical outcomes were evaluated 90 days later using the modified Rankin Scale.Results: Serum GDF-15 level at admission was significantly higher in AIS patients than in controls (p < .01). GDF-15 level on day 7 was significantly higher in the poor outcomes group than in the good outcomes group (p < .05). Higher GDF-15 levels at admission and on day 7 were related to larger stroke volumes (p < .01). Binary logistic regression indicated that serum GDF-15 level at admission may be independently related with AIS (p < .01). Serum GDF-15 level on day 7 may independently associated with poor outcomes after AIS (p < .05).Conclusions: GDF-15 level at admission may independently related to AIS, and GDF-15 level on day 7 could independently predict outcomes at 90 days after AIS. GDF-15 may provide prognostic information after AIS in a Chinese population.

BackgroundThe triglyceride glucose (TyG) index is a noninsulin-based marker for insulin resistance (IR) in general practice. Although smoking and heavy drinking have been regarded as major risk factors for various chronic diseases, there is limited evidence regarding the combined effects of smoking and alcohol consumption on IR. This study aimed to investigate the relationship between the TyG index and smoking and alcohol consumption using two Korean population-based datasets.MethodsThis study included 10,568 adults in the Korean National Health and Nutrition Examination Survey (KNHANES) and 9586 adults in the Korean Initiatives on Coronary Artery Calcification (KOICA) registry datasets. Multivariate logistic analysis was conducted to explore the relationship between smoking and alcohol consumption and the TyG index. To assess the predictive value of smoking and alcohol consumption on high TyG index, the area under the curve (AUC) were compared and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses were derived.ResultsThe combined effect of smoking and alcohol consumption was an independent risk factor of a higher TyG index in the KNHANES (adjusted odds ratio: 4.33, P < .001) and KOICA (adjusted odds ratio: 1.94, P < .001) datasets. Adding smoking and alcohol consumption to the multivariate logistic models improved the model performance for the TyG index in the KNHANES (AUC: from 0.817 to 0.829, P < .001; NRI: 0.040, P < .001; IDI: 0.017, P < .001) and KOICA (AUC: from 0.822 to 0.826, P < .001; NRI: 0.025, P = .006; IDI: 0.005, P < .001) datasets.ConclusionsSmoking and alcohol consumption were independently associated with the TyG index. Concurrent smokers and alcohol consumers were more likely to have a TyG index that was ≥8.8 and higher than the TyG indices of non-users and those who exclusively consumed alcohol or smoking tobacco.

Correlation of the Triglyceride-Glucose Index with Clinical Prognosis of Patients with Acute Ischemic Stroke Treated with Mechanical Thrombectomy.

BackgroundThe triglyceride glucose (TyG) index has been proposed as a reliable marker of insulin resistance (IR) and an independent predictor of cardiovascular disease risk. However, its prognostic value in patients with acute decompensated heart failure (ADHF) remains unclear.MethodsA total of 932 hospitalized patients with ADHF from January 1st, 2018 to February 1st, 2021 were included in this retrospective study. The TyG index was calculated as ln [fasting triglyceride level (mg/dL) × fasting plasma glucose level (mg/dL)/2]. Patients were divided into tertiles according to TyG index values. The primary endpoints were all-cause death, cardiovascular (CV) death and major adverse cardiac and cerebral events (MACCEs) during follow-up. We used multivariate adjusted Cox proportional hazard models and restricted cubic spline analysis to investigate the associations of the TyG index with primary endpoints.ResultsDuring a median follow-up time of 478 days, all-cause death, CV death and MACCEs occurred in 140 (15.0%), 103 (11.1%) and 443 (47.9%) cases, respectively. In multivariate Cox proportional hazard models, the risk of incident primary endpoints was associated with the highest TyG tertile. After adjustment for confounding factors, hazard ratios (HRs) for the highest tertile (TyG index ≥ 9.32) versus the lowest tertile (TyG index < 8.83) were 2.09 (95% confidence interval [CI], 1.23–3.55; p = 0.006) for all-cause death, 2.31 (95% CI, 1.26–4.24; p = 0.007) for CV death and 1.83 (95% CI, 1.18–3.01; p = 0.006) for MACCEs. Restricted cubic spline analysis also showed that the cumulative risk of primary endpoints increased as TyG index increased. When the TyG index was used as a continuous variable, the hazard ratios of the three primary endpoints rapidly increased within the higher range of the TyG index (all cause death, TyG > 9.08; CV death, TyG > 9.46; MACCEs, TyG > 9.87).ConclusionsThe elevated TyG index was independently associated with poor prognosis, and thus would be useful in the risk stratification in patients with ADHF.

Triglyceride glucose (TyG) index and the progression of liver fibrosis: A cross-sectional study.

Soluble form suppression of tumorigenicity 2 (sST2) is known to have prognostic value in ST-elevation myocardial infarction (STEMI) and could impact mortality after acute ischemic stroke (AIS). However, before considering sST2 as a therapeutic target, the kinetics of release and its association with adverse clinical events in both STEMI and AIS patients have to be determined. We prospectively enrolled 251 STEMI patients, treated with primary percutaneous coronary intervention, and 152 AIS patients treated with mechanical thrombectomy. We evaluated the level of sST2 in patient sera at five time point (admission, 4, 24, 48h and 1month from admission for STEMI patients and admission, 6, 24, 48h and 3months from admission for AIS patients). Major adverse clinical events (MACE) (all-cause death, acute myocardial infarction, stroke or hospitalization for heart failure) in STEMI patients and all-cause death in AIS patients were recorded during a 12-month follow-up. Mean age of the study population was 59 ± 12 and 69 ± 15years in STEMI and AIS patients, respectively. In STEMI patients, sST2 peaked 24h after admission (25.5ng/mL interquartile range (IQR) [14.9-29.1]) whereas an earlier and lower peak was observed in AIS patients (16.8ng/mL IQR [15.2-18.3] at 6h). Twenty-five (10.0%) STEMI patients experienced a MACE and 12 (7.9%) AIS patients had all-cause death within the first 12months. A high level of sST2 at 24h was associated with MACE in STEMI patients (hazard ratio (HR) = 2.5; 95% confidence interval (CI) [1.1-5.6], p = 0.03) and all-cause death in AIS patients (HR = 11.7; 95% CI [3.8-36.2], p < 0.01) within the first 12months. The study highlights that sST2 levels at 24h are associated with an increased risk to adverse clinical events in both diseases.

IntroductionPrompt diagnosis of obstructive sleep apnea (OSA) after acute ischemic stroke (AIS) is critical for optimal clinical outcomes, but in-laboratory conventional polysomnograms (PSG) are not routinely practical. Though portable out-of-center type III cardiopulmonary sleep studies (out-of-center cardiopulmonary sleep testing [OCST]) are widely available, these studies have not been validated in patients who have recently suffered from AIS. We hypothesized that OCST in patients with AIS would yield similar results when compared to conventional PSG.MethodsPatients with AIS had simultaneous type III OCST and PSG studies performed within 72 hours from symptom onset. The accuracy of OCST was compared to PSG using: chi-square tests, receiver operatory characteristic curves, Bland–Altman plot, paired Student’s t-test/Wilcoxon signed-rank test, and calculation of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).ResultsTwenty-one out of 23 subjects with AIS (age 61±9.4 years; 52% male; 58% African-American) successfully completed both studies (9% technical failure). Nearly all (95%) had Mallampati IV posterior oropharynx; the mean neck circumference was 16.8±1.6 in. and the mean body mass index (BMI) was 30±7 kg/m2. The apnea hypopnea index (AHI) provided by OCST was similar to that provided by PSG (19.8±18.0 vs 22.0±22.7, respectively; P=0.49). On identifying subjects by OCST with an AHI ≥5 on PSG, OCST had the following parameters: sensitivity 100%, specificity 85.7%, PPV 93%, and NPV 100%. On identifying subjects with an AHI ≥15 on PSG, OCST parameters were as follows: sensitivity 100%, specificity 83.3%, PPV 81.8%, and NPV 100%. Bland–Altman plotting showed an overall diagnostic agreement between OCST and PSG modalities for an AHI cutoff >5, despite fine-grained differences in estimated AHIs.ConclusionCompared with PSG, OCST provides similar diagnostic information when run simultaneously in AIS patients. OCST is a reliable screening tool for early diagnosis of OSA in AIS patients.

BackgroundResearch into the acute kidney disease (AKD) after acute ischemic stroke (AIS) is rare, and how clinical features influence its prognosis remain unknown. We aim to employ interpretable machine learning (ML) models to study AIS and clarify its decision-making process in identifying the risk of mortality.MethodsWe conducted a retrospective cohort study involving AIS patients from January 2020 to June 2021. Patient data were randomly divided into training and test sets. Eight ML algorithms were employed to construct predictive models for mortality. The performance of the best model was evaluated using various metrics. Furthermore, we created an artificial intelligence (AI)-driven web application that leveraged the top ten most crucial features for mortality prediction.ResultsThe study cohort consisted of 1633 AIS patients, among whom 257 (15.74%) developed subacute AKD, 173 (10.59%) experienced AKI recovery, and 65 (3.98%) met criteria for both AKI and AKD. The mortality rate stood at 4.84%. The LightGBM model displayed superior performance, boasting an AUROC of 0.96 for mortality prediction. The top five features linked to mortality were ACEI/ARE, renal function trajectories, neutrophil count, diuretics, and serum creatinine. Moreover, we designed a web application using the LightGBM model to estimate mortality risk.ConclusionsComplete renal function trajectories, including AKI and AKD, are vital for fitting mortality in AIS patients. An interpretable ML model effectively clarified its decision-making process for identifying AIS patients at risk of mortality. The AI-driven web application has the potential to contribute to the development of personalized early mortality prevention.

Disrupted white matter structural networks in patients with acute ischemic stroke in the right basal ganglia

Background: Incidence of gastrointestinal (GI) bleeding after acute ischemic stroke (AIS) was reported as 1.5% during hospitalization, one-thirds of which required blood transfusion. However, it is not known about the long-term incidence and the incidence rates by period after AIS. Methods: AIS patients who were admitted to the 14 participating hospitals between 2011 and 2013 were identified using a nationwide multicenter prospective stroke registry database. GI bleeding was captured with related diagnosis codes by International Classification of Diseases-10th Revision through the linkage between the registry database and the claims data. Bleeding requiring at least 2 packs of blood transfusion was defined as major GI bleeding. Incidence rates were calculated for each period as follow; 0-30 days, 31-90 days, 91-180 days, 181-365 days, 1-2 years, 2-3years, after 3 years. Results: Of 10,818 AIS patients, 59.0% were male and mean age was 67.5 ± 12.9 years. The median follow-up duration was 3.1 (interquartile range 2.3 to 4.0) years. During 31,208 person-years, 947 patients (8.8%) had 1,224 episodes of major GI bleeding. Annual incidence rate was 3.92 per 100 person-years. The incidence rates by periods were the highest at 19.21 per 100 person-years in the first month of AIS, gradually decreased to 9.02 in one to three months, 6.18 in three to six months, and 3.48 in six to twelve months. After three years, it remained at about 2.62 events per 100 person-years. During the observation period, only one major GI bleeding occurred without recurrence in about 80% of patients, about 13% recurred twice, and about 6% of patients had three or more recurrences. In the multivariable recurrent event analysis, anemia at admission, lower eGFR below 60, and mRS at 3 months ≥4 were independently associated with higher risk of major GI bleeding during the most of the observation period above 3 years. Conclusions: Major GI bleeding, requiring transfusion, seems to occur frequently after AIS, and the risk was gradually decreased after stroke. The efforts are needed to prevent it, especially in stroke patients with anemia and decreased renal function.

To investigate the relation between obesity-related indices and mild cognitive impairment (MCI) in elderly patients with type 2 diabetes (T2D). A total of 597 eligible elderly patients with T2D were included in this retrospective study. All patients were divided into MCI group and normal cognitive group based on neuropsychological assessment. Twelve obesity-related indices were calculated, including body mass index (BMI), waist-hip ratio (WHR), waist-to-height ratio (WHtR), lipid accumulation product (LAP), body roundness index (BRI), conicity index (CI), visceral adiposity index (VAI), body adiposity index (BAI), abdominal volume index (AVI), a body shape index (ABSI), triglyceride glucose (TyG) index and cardiometabolic index (CMI). Multivariate logistic regression analysis, tests for trend and restricted cubic splines were used to assess the relationships between the tests for trend and MCI in elderly patients with T2D. Receiver operating characteristic (ROC) curves and areas under the curves (AUC) were used to assess the performance and predictive ability of the obesity-related indices for identifying MCI in elderly patients with T2D. Multivariate logistic regression showed that elevated BMI, WHR, WHtR, LAP, BRI, CI, VAI, AVI, TyG index, and CMI were associated with an increased risk of MCI in elderly T2D patients after adjusting for potential confounders (all P<0.05). In addition, TyG index, LAP, CMI, VAI, AVI, WHR, WHtR, BRI, and CI had negative correlations with Montreal Cognitive Assessment (MoCA) scores (all P<0.05). There was a significant linear trend between the levels of BMI (P for trend = 0.004, P for non-linearity = 0.637), WHR (P for trend = 0.006, P for non-linearity = 0.430), WHtR (P for trend <0.001, P for non-linearity = 0.452), BRI (P for trend <0.001, P for non-linearity = 0.252), AVI ( P for trend <0.001, P for non-linearity = 0.944), and TyG index (P for trend <0.001, P for non-linearity = 0.514) and risk of MCI in elderly patients with T2D after adjusting for potential confounders. There was a nonlinear association between LAP, VAI or CMI and risk of MCI in elderly patients with T2D (all P for non-linearity < 0.001). CMI had the greatest AUC (AUC = 0.682), followed by VAI (AUC = 0.679), TyG index (AUC = 0.673), LAP (AUC = 0.669), AVI (AUC = 0.580), WHtR and BRI (AUC = 0.575), BMI (AUC = 0.560), CI (AUC = 0.556), WHR (AUC = 0.554), BAI (AUC = 0.547), and ABSI (AUC = 0.536). Elevated obesity-related indices, particularly CMI, VAI, TyG index and LAP, which displayed the higher predictive power, were instrumental in forecasting and evaluating MCI in elderly T2D patients. These findings may provide clues for future studies exploring early diagnostic biomarkers and treatment of MCI in elderly T2D patients.

Cardiogenic stroke is associated with substantial morbidity and mortality, necessitating a better understanding of its clinical characteristics for improved patient outcomes. This study aimed to identify clinical characteristics influencing short-term functional prognosis in patients with cardiogenic stroke. The study prospectively enrolled 212 patients with cardiogenic stroke, collecting their clinical data and laboratory results. The modified Rankin Scale score at 90 days was used to define functional prognosis, with patients having a good prognosis (modified Rankin Scale ≤2; n = 164) or poor prognosis (modified Rankin Scale ≥3; n = 48). The poor prognosis group had higher rates of total anterior circulation infarcts (12.5% vs 0.0%; P < .001) and posterior circulation infarction (50.0% vs 38.4%; P < .001) compared with the good prognosis group. Lesion characteristics differed significantly, with the poor prognosis group exhibiting more large-area lesions (39.6% vs 18.9%; P < .001) and multiple confluent lesions (56.3% vs 24.4%; P < .001). Admission-based National Institute of Health Stroke Scale scores were higher in the poor prognosis group (median [IQR], 12 [8-18] vs 5 [4-7]; P <.001), correlating with worse outcomes. The admission National Institute of Health Stroke Scale score predicted patients' 90-day prognosis with good accuracy (area under the curve, 0.937 [95% CI, 0.895-0.965]; P < .001), with a threshold of 7 yielding 85.42% sensitivity and 85.37% specificity. Higher admission National Institute of Health Stroke Scale scores were significantly associated with poor functional prognosis at 90 days, highlighting the importance of early National Institute of Health Stroke Scale-based assessment for improved outcomes.