Changes in the estimated glucose disposal rate and incident cardiovascular disease: two large prospective cohorts in Europe and Asia.

Background And Aims: Previous study found that estimated glucose disposal rate (eGDR) was significantly associated with cardiovascular disease (CVD). However, little is known about the change in eGDR over time and its association with the development of CVD. The aim of this study was to investigate the association of change in eGDR with CVD risk.

Plasma Phenylacetylglutamine Levels and Prognosis of Ischemic Stroke: A Multicenter Prospective Study Based on the CATIS Trial.

Background: Phenylacetylglutamine is implicated in platelet clotting and thrombosis, but its prognostic value in ischemic stroke remains unclear. We aimed to explore the associations of plasma phenylacetylglutamine levels with adverse outcomes after ischemic stroke in a multicenter prognostic cohort study.

Methods: Our multicenter prognostic cohort study included 3564 Chinese patients with ischemic stroke from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke).

Antiphospholipid Antibodies Modify the Prognostic Value of Baseline Platelet Count for Clinical Outcomes After Ischemic Stroke.

Background: Antiphospholipid antibodies (aPLs) have been reported to be involved in platelet-mediated thrombosis and inflammation, but the impact on the prognosis of ischemic stroke remains unclear. We aimed to examine whether the association between baseline platelet count (PLT) and long-term clinical outcomes within 2 years after ischemic stroke onset is modulated by aPLs.

Methods And Results: A total of 2938 patients with ischemic stroke were included in this prospective cohort study.

Plasma Polyamines and Short-Term Adverse Outcomes Among Patients With Ischemic Stroke: A Prospective Cohort Study.

Background: Polyamines have been reported to be associated with neurological function, but the associations between polyamines and the prognosis of ischemic stroke remain unclear. We aimed to prospectively investigate whether elevated plasma polyamine levels are associated with adverse outcomes in patients with ischemic stroke.

Methods And Results: Plasma polyamine levels were measured at admission in 3570 patients with acute ischemic stroke, and clinical outcomes were assessed at 3 months after stroke onset.

Association of Crohn's disease and ulcerative colitis with the risk of neurological diseases: a large-scale Mendelian randomization study.

Observational studies suggested increased risks of Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS) in patients with Crohn's disease (CD) and ulcerative colitis (UC). We aimed to assess the causality for the associations of CD and UC with the risks of AD, PD, and MS through a two-sample Mendelian randomization (MR) study. Independent single nucleotide polymorphisms associated with CD (17,897 cases and 33,977 controls) and UC (13,768 cases and 33,977 controls) were identified as genetic instruments based on a European-descent genome-wide association study (GWAS) released by the International Inflammatory Bowel Disease Genetics Consortium.

Alcohol drinking modified the effect of plasma YKL-40 levels on stroke-specific mortality of acute ischemic stroke.

Objectives: Our study aimed to evaluate the association between plasma human cartilage glycoprotein-39 (YKL-40) and stroke-specific mortality at two years in acute ischemic stroke patients according to the drinking status and amount of alcohol consumption. We further investigated the effect of the interaction between these conditions and YKL-40 levels on the outcome.

Methods: We measured plasma YKL-40 levels in 3267 participants from the China Antihypertensive Trial in Acute Ischemic Stroke.

Associations of computer gaming with incident dementia, cognitive functions, and brain structure: a prospective cohort study and Mendelian randomization analysis.

Background: Computer gaming has recently been suggested to be associated with benefits for cognition, but its impact on incident dementia remains uncertain. We aimed to investigate the observational associations of playing computer games with incident dementia, cognitive functions, and brain structural measures, and further explore the genetic associations between computer gaming and dementia.

Methods: We included 471,346 White British participants without dementia at baseline based on the UK Biobank, and followed them until November 2022.

Physical Activity, Sleep, and Risk of Late-Onset Severe Mental Illness: A Prospective Cohort Study From UK Biobank.

Background And Hypothesis: Previous studies have found that both physical inactivity and poor sleep are deleteriously associated with severe mental illness (SMI). The aim of current study was to investigate the joint association of physical activity (PA) and sleep with late-onset SMI (schizophrenia and bipolar disorder) risk.

Study Design: A total of 340 187 (for schizophrenia)/340 239 (for bipolar disorder) participants without schizophrenia or bipolar disorder from the UK Biobank were included.

Genetically Determined Plasma Hepatocyte Growth Factor Levels Are Associated With the Risk and Prognosis of Ischemic Stroke.

Background: Observational studies suggest that hepatocyte growth factor (HGF) is associated with the risk and prognosis of ischemic stroke, but the causality of these associations remains unclear. Therefore, we conducted Mendelian randomization (MR) analyses to explore the associations of genetically determined plasma HGF levels with the risk and prognosis of ischemic stroke.

Methods: A total of 13 single-nucleotide polymorphisms associated with plasma HGF were selected as genetic instruments based on the data from a genome-wide association study with 21 758 European participants.

Association of Cardiac Biomarkers in Combination With Cognitive Impairment After Acute Ischemic Stroke.

Background: Poststroke cognitive impairment is a severe and common clinical complication that constitutes a substantial global health burden. We aimed to evaluate the association of 3 cardiac biomarkers in combination with poststroke cognitive impairment and their prognostic significance.

Methods And Results: This prospective study included 566 patients with ischemic stroke.

The bidirectional association between frailty index and cardiovascular disease: A Mendelian randomization study.

Background And Aim: Observational studies have suggested a relationship between frailty and cardiovascular disease (CVD), but the causality is still uncertain. We used bidirectional Mendelian randomization (MR) design to investigate the potential causal associations between frailty and four main CVDs, including hypertension, myocardial infarction (MI), heart failure (HF), and atrial fibrillation (AF).

Methods And Results: Independent single-nucleotide polymorphisms for frailty index (FI) and CVDs (hypertension, MI, HF, and AF) were selected as genetic instruments based on European-descent genome-wide association studies (GWASs).

Blood pressure control and antihypertensive medication use after discharge and prognosis of ischemic stroke.

Objective: To investigate the effect of consistently blood pressure (BP) control status after discharge on adverse clinical outcomes among ischemic stroke (IS) patients.

Methods: Three thousand, four hundred and six acute IS patients were included and followed up at 3 months, 12 months, and 24 months after stroke. Study outcomes were defined as death, vascular events and composite of death or vascular events.

Plasma Amino Acid Neurotransmitters and Ischemic Stroke Prognosis: A Multicenter Prospective Study.

Background: Plasma amino acid neurotransmitter dysregulation is suggested to be implicated in the development of ischemic stroke, but its prognostic value for ischemic stroke remains controversial.

Objective: We aimed to prospectively investigate the associations between plasma amino acid neurotransmitters levels and adverse outcomes after ischemic stroke in a large-scale multicenter cohort study.

Methods: We measured 4 plasma amino acid neurotransmitters (glutamic acid, aspartic acid, gamma-aminobutyric acid, and glycine) among 3486 patients with ischemic stroke from 26 hospitals across China.

Causal Effects of YKL-40 on Ischemic Stroke and Its Subtypes: A 2-Sample Mendelian Randomization Study.

Background Chitinase-3 like protein 1 (CHI3L1, YKL-40) was reported to be implicated in the development of ischemic stroke, but whether the association between them was causal remained unclear. We conducted a 2-sample Mendelian randomization study to explore the associations of genetically determined plasma YKL-40 with ischemic stroke and its subtypes (large artery stroke, small vessel stroke, and cardioembolic stroke). Methods and Results Based on genome-wide association study data of 3394 European-descent individuals, we selected 13 single-nucleotide polymorphisms associated with plasma YKL-40 as genetic instruments.

Association Between Prekallikrein and Stroke: A Mendelian Randomization Study.

Background High plasma prekallikrein was reported to be associated with increased risks of stroke, but the causality for these associations remains unclear. We aimed to investigate the associations of genetically predicted plasma prekallikrein concentrations with all-cause stroke, ischemic stroke, 3 ischemic stroke subtypes, and intracerebral hemorrhage (ICH) using a 2-sample Mendelian randomization approach. Methods and Results Seven independent prekallikrein-related single-nucleotide polymorphisms were identified as genetic instruments for prekallikrein based on a genome-wide association study with 1000 European individuals.

HS-CRP Modifies the Prognostic Value of Platelet Count for Clinical Outcomes After Ischemic Stroke.

Background We examined whether the relationship between baseline platelet count and clinical outcomes is modulated by HS-CRP (high-sensitivity C-reactive protein) in patients with ischemic stroke. Methods and Results A total of 3267 patients with ischemic stroke were included in the analysis. The primary outcome was a combination of death and major disability at 1 year after ischemic stroke.

Plasma homeostatic chemokines CCL19 and CCL21 and the prognosis of ischemic stroke in two Chinese prospective cohorts.

Background: The homeostatic chemokines CCL19 and CCL21 are involved in carotid plaque vulnerability and post-ischemic neuroinflammatory responses. This study aimed to examine the prognostic values of CCL19 and CCL21 in ischemic stroke.

Methods: Plasma CCL19 and CCL21 were measured in 4483 ischemic stroke patients from two independent cohorts of CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) and IIPAIS (Infectious Factors, Inflammatory Markers, and Prognosis of Acute Ischemic Stroke), and participants were followed up at 3 months after stroke.

High Serum Brain-Derived Neurotrophic Factor Is Associated With Decreased Risks of Poor Prognosis After Ischemic Stroke.

Background: BDNF (brain-derived neurotrophic factor) has been implicated in cardiovascular homeostasis and ischemic stroke pathogenesis. We aimed to prospectively investigate the associations between serum BDNF levels and the prognosis of ischemic stroke in a multicenter cohort study.

Methods: This prospective study follows the STROBE reporting guideline.

Associations of Rheumatoid Factor, Rheumatoid Arthritis, and Interleukin-6 Inhibitor with the Prognosis of Ischemic Stroke: a Prospective Multicenter Cohort Study and Mendelian Randomization Analysis.

Rheumatoid factor (RF), an established diagnostic biomarker for rheumatoid arthritis (RA), is associated with cardiovascular diseases, but its impact on clinical outcomes of ischemic stroke remains unclear. We aimed to investigate the observational associations between serum RF and prognosis of ischemic stroke, and further examined the genetic associations of RA and its therapeutic strategy, interleukin-6 (IL-6) inhibitor, with prognosis of ischemic stroke. We measured serum RF levels in 3474 Chinese ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke.

Intercellular adhesion molecule 4 and ischemic stroke: a two-sample Mendelian randomization study.

Background: Experimental studies suggested that intercellular adhesion molecule 4 (ICAM-4) might be implicated in ischemic stroke, but the population-based evidence on the relationship between ICAM-4 and ischemic stroke were limited. Herein, we performed a two-sample Mendelian randomization (MR) analysis to investigate the associations of genetically determined plasma ICAM-4 with the risks of ischemic stroke and its subtypes.

Methods: A total of 11 single-nucleotide polymorphisms associated with ICAM-4 were selected as instrumental variables based on the genome-wide association studies (GWAS) with 3,301 European individuals.

Association between human blood metabolome and the risk of breast cancer.

Background: Breast cancer is the most common cancer among women with limited treatment options. To identify promising drug targets for breast cancer, we conducted a systematical Mendelian randomization (MR) study to screen blood metabolome for potential causal mediators of breast cancer and further predict target-mediated side effects.

Methods: We selected 112 unique blood metabolites from 3 large-scale European ancestry-based genome-wide association studies (GWASs) with a total of 147,827 participants.