Association between clonal hematopoiesis-related gene mutations and unfavorable functional outcome in patients with large-artery atherosclerotic stroke.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is a phenomenon that characterizes individuals with somatic mutations that are related to hematologic malignancy but without hematologic abnormalities. Presence of CHIP is associated with the atherosclerotic cardiovascular disease through the activation of the interleukin 6 (IL-6) pathway; however, its role on unfavorable functional outcomes in different etiologies of ischemic stroke remains unclear. We aimed to investigate the association between CHIP-related gene mutations and unfavorable functional outcomes of ischemic stroke with different etiologies. METHODS: We prospectively studied a cohort of 3396 stroke patients with identified etiologies, and identified CHIP and the presence of the IL6R variant (IL6R p.Asp358Ala) by whole-genome sequencing. The IL6R p.Asp358Ala coding mutation was used as a genetic inhibition for IL-6 signaling. The primary outcome was unfavorable functional outcome [(Modified Rankin Scale), mRS 2-6] at 3 months. RESULTS: Of the 3396 patients, 110 (3.2%) were CHIP carriers and the median age was 62 years (IQR, 54.0-69.0). The CHIP increased the risk of unfavorable functional outcome among patients with hyper-inflammation status of high-sensitivity C-reactive protein (hsCRP) > median levels in patients with large-artery atherosclerosis (LAA) (OR 2.45, 95% CI 1.00-5.98, p = 0.049, pinteraction = 0.01). Presence of IL6R variant (IL6R p.Asp358Ala) could attenuate the risk of unfavorable functional outcome only in patients with CHIP (OR 0.30, 95%CI 0.12-0.76, p = 0.01, pinteraction = 0.02), and especially in LAA patients with CHIP (OR 0.1, 95%CI 0.02-0.42, p = 0.002; pinteraction = 0.001). CONCLUSION: CHIP is associated with unfavorable functional outcomes in patients with LAA stroke and hyper-inflammation. Genetic IL-6 signaling inhibition might attenuate the risk of unfavorable functional outcomes in CHIP carriers, especially in LAA stroke patients.

Somatic mutation contributing to clonal haematopoiesis is a risk factor of recurrent stroke in first-ever acute ischaemic stroke: a prospective cohort study.

BACKGROUND: Somatic mutation contributes to clonal haematopoiesis of indeterminate potential (CHIP) is related to age and associated with a higher risk of stroke and atherosclerotic cardiovascular disease. Here, we investigated the prognostic significance of CHIP in a large first-ever acute ischaemic stroke (AIS) cohort and explored the underlying mechanisms. METHODS: We studied a prospective cohort of 6016 patients who had a first-ever AIS in China. Whole-genome sequencing was performed to identify CHIP. High-sensitivity C reactive protein (hs-CRP) levels above 3 mg/L at baseline were defined as hyperinflammation. Recurrent stroke during the 3-month follow-up was the primary outcome. RESULTS: Among the 6016 patients who had a first-ever AIS, with a median age was 62 years (IQR, 54.0‒70.0), 3.70% were identified as CHIP carriers. The most common mutations occurred in the DNMT3A (30.0%) and TET2 (11.4%) genes. During a follow-up of 3 months, the presence of CHIP was associated with recurrent stroke (HR 1.62, 95% CI 1.04 to 2.51, p=0.03), recurrent ischaemic stroke (HR 1.64, 95% CI 1.04 to 2.58, p=0.03) and combined vascular events (HR 1.58, 95% CI 1.02 to 2.44, p=0.04) after adjusting for hsCRP levels at baseline in patients who had a first-ever AIS. Subgroup analysis demonstrated that CHIP was only associated with recurrent stroke when patients under hyperinflammation (OR 3.10, 95% CI 1.92 to 5.00, p<0.001) but not in those without hyperinflammation (OR 0.18, 95% CI 0.03 to 1.04, p=0.06, Pinteraction=0.002). CONCLUSION: Our results suggest that somatic mutations contributing to CHIP increase the risk of short-term recurrent stroke in patients who had a first-ever AIS. Hyperinflammation may be important in the relationship between CHIP and recurrent stroke.

External validation of ABCD series scores for predicting early stroke events following transient ischemic attack in a large nationwide registry.

Introduction: In the context of modern guideline-based strategies, new validations of prognostic scores for predicting early stroke risk are needed. We aimed to compare the validity of the ABCD series scores and assess the incremental values of risk components for predicting in-hospital stroke events in patients with transient ischemic attack (TIA). Patients and methods: We abstracted data from the Chinese Stroke Center Alliance (CSCA), a nationwide registry with 68,433 TIA patients admitted within 7 days of symptom onset from 1476 hospitals. TIA was defined by time-based criteria according to the World Health Organization (WHO). The discrimination of ABCD, ABCD2, ABCD2-I, and ABCD3 scores for predicting in-hospital stroke events was assessed by the area under the receiver-operating characteristics curves (AUC). The incremental predictive values of added risk predictor were determined by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results: A total of 29,286 TIA patients were included, of whom 1466 (5.0%) had in-hospital stroke events. Compared with ABCD2-I score (AUC 0.79, 95% confidence interval [CI] 0.77-0.80), ABCD (AUC 0.58, 95% CI 0.57-0.60), ABCD2 (AUC 0.58, 95% CI 0.56-0.59), and ABCD3 (AUC 0.58, 95% CI 0.56-0.60) had lower predictive utility. An incremental value was observed when adding infarction on DWI (IDI = 0.0597, NRI = 1.1036) into ABCD2 score to be ABCD2-I. Conclusion: The traditional scales utilizing medical history (ABCD, ABCD2, and ABCD3 scores) show fair ability for predicting in-hospital stroke events after TIA, but the ABCD2-I score, which adds infarction on DWI, improves the predictive ability.

Systematic estimation of BMI: A novel insight into predicting overweight/obesity in undergraduates.

The prevalence of overweight-obesity has increased sharply among undergraduates worldwide. In 2016, approximately 52% of adults were overweight-obese. This cross-sectional study aimed to investigate the prevalence of overweight-obesity and explore in depth the connection between eating habits and overweight-obesity among Chinese undergraduates.The study population included 536 undergraduates recruited in Shijiazhuang, China, in 2017. They were administered questionnaires for assessing demographic and daily lifestyle characteristics, including sex, region, eating speed, number of meals per day, and sweetmeat habit. Anthropometric status was assessed by calculating the body mass index (BMI). The determinants of overweight-obesity were investigated by the Pearson χ test, Spearman rho test, multivariable linear regression, univariate/multivariate logistic regression, and receiver operating characteristic curve analysis.The prevalence of undergraduate overweight-obesity was 13.6%. Sex [male vs female, odds ratio (OR): 1.903; 95% confidence interval (95% CI): 1.147-3.156], region (urban vs rural, OR: 1.953; 95% CI: 1.178-3.240), number of meals per day (3 vs 2, OR: 0.290; 95% CI: 0.137-0.612), and sweetmeat habit (every day vs never, OR: 4.167; 95% CI: 1.090-15.933) were significantly associated with overweight-obesity. Eating very fast was positively associated with overweight-obesity and showed the highest OR (vs very slow/slow, OR: 5.486; 95% CI: 1.622-18.553). However, the results of multivariate logistic regression analysis indicated that only higher eating speed is a significant independent risk factor for overweight/obesity (OR: 17.392; 95% CI, 1.614-187.363; P = .019).Scoremeng = 1.402 × scoresex + 1.269 × scoreregion + 19.004 × scoreeatin speed + 2.546 × scorenumber of meals per day + 1.626 × scoresweetmeat habit and BMI = 0.253 × Scoremeng + 18.592. These 2 formulas can help estimate the weight status of undergraduates and predict whether they will be overweight or obese.