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Background: Elevated homocysteine levels are associated with increased blood coagulation and platelet activity and may modulate the response to antiplatelet therapies. We aimed to investigate the effects of homocysteine levels on the efficacy and safety of ticagrelor–acetylsalicylic acid (ASA) versus clopidogrel–ASA among patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles. Methods: We conducted a post hoc analysis of the CHANCE-2 (The Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events–II) trial. Participants were randomly assigned to treatment with ticagrelor–ASA or clopidogrel–ASA. We categorized participants into groups with elevated and non-elevated homocysteine levels, based on the median level. The primary efficacy outcome was recurrent stroke within 90-day follow-up. The primary safety outcome was severe or moderate bleeding within 90 days. Results: A total of 2740 participants were randomly assigned to receive ticagrelor–ASA and 2700 to receive clopidogrel–ASA. Use of ticagrelor–ASA was associated with a reduced risk of recurrent stroke among participants with elevated homocysteine levels (74 [5.3%] v. 119 [8.5%]; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.45–0.81), but not among those with non-elevated levels (86 [6.4%] v. 87 [6.7%]; HR 0.97, 95% CI 0.71–1.32; p = 0.04 for interaction). When analyzed as a continuous variable, the benefits of ticagrelor–ASA with regard to recurrent stroke increased as homocysteine levels increased (p = 0.04 for interaction). No significant interaction between homocysteine levels and treatment with regard to severe or moderate bleeding was observed (p = 0.7 for interaction). We found a significant interaction between homocysteine levels and therapy with regard to recurrent stroke in females (p = 0.04 for interaction) but not males. Interpretation: In comparison with clopidogrel–ASA, ticagrelor–ASA conferred more benefit to patients with elevated homocysteine levels, particularly to female patients, in this secondary analysis of a randomized controlled trial involving patients with minor ischemic stroke or TIA. Trial registration: ClinicalTrials.gov, no. NCT04078737 [ABSTRACT FROM AUTHOR]

Background: Body mass index (BMI) may affect the response to platelet P2Y12 receptor inhibitors. We aimed to explore whether BMI influenced the efficacy and safety of ticagrelor and clopidogrel for secondary prevention of minor ischemic stroke or transient ischemic attack (TIA) among patients enrolled in the CHANCE-2 (Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial. Methods: In a multicentre, randomized, double-blind, placebo-controlled trial, conducted in China, we randomized patients with minor stroke or TIA who carried the CYP2C19 loss-of-function allele to receive either ticagrelor–acetylsalicylic acid (ASA) or clopidogrel–ASA. We classified patients into obese (BMI ≥ 28) or nonobese (BMI < 28) groups. The primary efficacy outcome was stroke within 90 days, and the primary safety outcome was severe or moderate bleeding within 90 days. Results: Among 6412 patients, 876 were classified as obese and 5536 were classified as nonobese. Compared with clopidogrel–ASA, ticagrelor–ASA was associated with a significantly lower rate of stroke within 90 days among patients with obesity (25 [5.4%] v. 47 [11.3%]; hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30–0.87), but not among those in the nonobese group (166 [6.0%] v. 196 [7.0%]; HR 0.84, 95% CI 0.69–1.04) The interaction of treatment and BMI group was significant (p for interaction = 0.04). We did not observe any difference by BMI group in rates of severe or moderate bleeding (9 [0.3%] v. 10 [0.4%] in the nonobese group; 0 [0.0%] v. 1 [0.2%] in the obese group; p for interaction = 0.99). Interpretation: In this secondary analysis of a randomized controlled trial involving patients with minor ischemic stroke or TIA, compared with clopidogrel–ASA, patients with obesity received more clinical benefit from ticagrelor–ASA therapy than those without obesity. Trial registration: Clinicaltrials.gov, no. NCT04078737. [ABSTRACT FROM AUTHOR]

Aims: The monocyte to high‐density lipoprotein cholesterol ratio (MHR) has emerged as a novel inflammatory biomarker of atherosclerotic cardiovascular disease. However, it has not yet been identified whether MHR can predict the long‐term prognosis of ischemic stroke. We aimed to investigate the associations of MHR levels with clinical outcomes in patients with ischemic stroke or transient ischemic attack (TIA) at 3 months and 1 year. Methods: We derived data from the Third China National Stroke Registry (CNSR‐III). Enrolled patients were divided into four groups by quartiles of MHR. Multivariable Cox regression for all‐cause death and stroke recurrence and logistic regression for the poor functional outcome (modified Rankin Scale score 3–6) were used. Results: Among 13,865 enrolled patients, the median MHR was 0.39 (interquartile range, 0.27–0.53). After adjustment for conventional confounding factors, the MHR level in quartile 4 was associated with an increased risk of all‐cause death (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.10–1.90), and poor functional outcome (odd ratio [OR], 1.47; 95% CI, 1.22–1.76), but not with stroke recurrence (HR, 1.02; 95% CI, 0.85–1.21) at 1 year follow‐up, compared with MHR level in quartile 1. Similar results were observed for outcomes at 3 months. The addition of MHR to a basic model including conventional factors improved predictive ability for all‐cause death and poor functional outcome validated by the C‐statistic and net reclassification index (all p < 0.05). Conclusions: Elevated MHR can independently predict all‐cause death and poor functional outcome in patients with ischemic stroke or TIA. [ABSTRACT FROM AUTHOR]

Aim: The association between magnesium and outcomes after stroke is uncertain. We aimed to investigate the association of serum magnesium with all‐cause mortality and poor functional outcome. Methods: We included patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) from the China National Stroke Registry III. We used Cox proportional hazards model for all‐cause mortality and logistic regression model for poor functional outcome (modified Rankin Scale [mRS] 2–6/3–6) to examine the relationships. Results: Among the 6483 patients, the median (interquartile range) magnesium was 0.87 (0.80–0.93) mmol/L. Patients in the first quartile had a higher risk of mRS score 3–6/2–6 at 3 months (adjusted odds ratio [OR]: 1.30; 95% confidence interval [CI]: 1.02, 1.64; adjusted OR: 1.29; 95% CI: 1.04–1.59) compared with those in the fourth quartile. Similar results were found for mRS score 26 at 1 year. The age‐ and sex‐adjusted hazard ratio (HR) with 95% CI in first quartile magnesium was 1.40 (1.02–1.93) for all‐cause mortality within 1 year, but became insignificant (HR: 1.03; 95% CI: 0.71–1.50) after adjusting for potential variables. Conclusions: Low serum magnesium was associated with a high risk of poor functional outcome in patients with AIS or TIA. [ABSTRACT FROM AUTHOR]

Main problem: The prognostic value of soluble lectin‐like oxidized low‐density lipoproteinreceptor‐1 (sLOX‐1) for stroke was unclearly. This study aimed to investigate the association between sLOX‐1 and recurrent stroke in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). Methods: Data were obtained from the Third China National Stroke Registry. Eligible cases consisted of 400 patients who developed recurrent stroke within 1‐year follow‐up, 800 controls were selected using age‐ and sex‐matched with a 1:2 case–control ratio. Conditional logistic regressions were used to evaluate the association between sLOX‐1 and recurrent stroke. Results: Among 1200 patients included in this study, the median (interquartile range) of sLOX‐1 was 247.12 (132.81–413.58) ng/L. After adjustment for conventional confounding factors, the odds ratio with 95% confidence interval in the highest tertile versus the lowest tertile was 2.23 (1.61–3.08) for recurrent stroke, 2.31 (1.64–3.24) for ischemic stroke, 2.30 (1.66–3.19) for combined vascular events within 1‐year follow‐up. Furthermore, the addition of sLOX‐1 to a conventional risk model had an incremental effect on predictive value for recurrent stroke (C‐statistics 0.76, p < 0.0001; integrated discrimination improvement 13.38%, p < 0.0001; net reclassification improvement 55.39%, p < 0.0001). Similar results were observed when the timepoint was set up as 3 months. Subgroup analysis showed the association between higher sLOX‐1 and recurrent stroke was more pronounced in patients with a history of stroke (p for interaction = 0.0062). Conclusions: sLOX‐1 was positively associated with the risk of recurrent stroke, which may be a candidate biomarker to improve risk stratification of recurrent stroke. [ABSTRACT FROM AUTHOR]

Background: Evidence on the risk-benefit ratio of dual antiplatelet therapies among patients with stroke and impaired renal function is limited and inconsistent.Objective: To investigate the effect of renal function on the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin treatment.Design: Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT04078737).Setting: 202 centers in China.Patients: CYP2C19 loss-of-function allele carriers with minor stroke or transient ischemic attack.Intervention: Ticagrelor-aspirin and clopidogrel-aspirin.Measurements: Renal function was evaluated by estimated glomerular filtration rate (eGFR) levels. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days, respectively.Results: Among 6378 patients, 4050 (63.5%) had normal (eGFR ≥90 mL/min/1.73 m2), 2010 (31.5%) had mildly decreased (eGFR 60 to 89 mL/min/1.73 m2), and 318 (5.0%) had moderately to severely decreased (eGFR <60 mL/min/1.73 m2) renal function. The corresponding differences in recurrent stroke between ticagrelor-aspirin and clopidogrel-aspirin for normal, mildly decreased, and moderately to severely decreased renal function was -2.8 percentage points (95% CI, -4.4 to -1.3 percentage points) (hazard ratio [HR], 0.63 [CI, 0.49 to 0.81]), -0.2 percentage point (CI, -2.4 to 2.0 percentage points) (HR, 0.98 [CI, 0.69 to 1.39]), and 3.7 percentage points (CI, -2.3 to 10.1 percentage points) (HR, 1.31 [CI, 0.48 to 3.55]), respectively. Rates of severe or moderate bleeding did not substantially differ by treatment assignments across eGFR categories.Limitation: Renal function was only evaluated by using eGFR, and the proportion of patients with severely decreased renal function was low.Conclusion: Patients with normal, rather than impaired, renal function received greater benefit from ticagrelor-aspirin versus clopidogrel-aspirin.Primary Funding Source: Ministry of Science and Technology of the People's Republic of China. [ABSTRACT FROM AUTHOR]

Aims: Gamma‐glutamyl transferase (GGT) is considered a marker of oxidative stress in vivo. In this study, we aimed to examine the association of serum GGT levels with 3‐month and 1‐year stroke recurrence in patients with acute ischemic stroke or transient ischemic attack (TIA). Methods: We conducted a large and multicenter cohort study. Participants with ischemic stroke or TIA who had a baseline GGT measurement were enrolled in the China National Stroke Registry‐3 study from August 2015 to March 2018. They were divided into four groups according to sex‐specific quartiles of GGT levels. The effect of GGT on stroke recurrence and other vascular events was examined during the 1‐year follow‐up period. Multivariate Cox regression models were performed to evaluate the association. Discrimination tests were used to examine the degree to which incorporating GGT into the conventional model predicted stroke adverse outcomes. Results: A total of 12,504 patients were enrolled. At both the 3‐month and 1‐year follow‐ups, patients in the highest quartile group of GGT levels exhibited a higher risk of stroke recurrence [HR 1.32 (95% CI 1.07–1.63), HR 1.34 (95% CI 1.13–1.60)], ischemic stroke [HR 1.37 (95% CI 1.10–1.71), HR 1.37 (95% CI 1.14–1.64)], and combined vascular events [HR 1.34 (95% CI 1.09–1.65), HR 1.34 (95% CI 1.13–1.59)] than those in the lowest quartile group. Moreover, the Kaplan–Meier curves revealed that the incidence rates of stroke adverse outcomes were quite different in the four groups. The highest quartile group showed the highest cumulative incidence, while the lowest quartile group showed the lowest cumulative incidence. After applying discrimination tests, adding GGT into the conventional model resulted in slight improvements in predicting stroke adverse outcomes (NRI: 10%–14%). Conclusion: This study demonstrated that elevated GGT levels were positively associated with an increased risk of stroke adverse outcomes, namely, recurrence, ischemic stroke, and combined vascular events. [ABSTRACT FROM AUTHOR]

Introduction: Serum potassium abnormality is a risk factor of incident stroke, but whether it is associated with recurrent stroke in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) remains unknown. This study aimed to investigate the association of serum potassium with the risk of recurrent stroke in patients with AIS or TIA. Methods: We included 12,425 patients from the China National Stroke Registry III. Patients were classified into 3 groups according to tertiles of potassium. The outcomes were recurrence of stroke and combined vascular events at 1 year. Cox proportional hazards regression was adopted to explore the associations by calculating hazard ratios (HRs) and their 95% confidence intervals (CIs). Results: Among 12,425 enrolled patients, the median (interquartile range) of potassium was 3.92 (3.68–4.19) mmol/L. Compared with the highest tertile, after adjusted for confounding factors, the lowest tertile potassium was associated with increased risk of recurrent stroke at 1 year. The adjusted HR with 95% CI was 1.21 (1.04–1.41). There was an independent, linear association between serum potassium and stroke recurrence. Per 1 mmol/L decrease of potassium was associated with 19% higher risk of recurrent stroke (HR, 1.19; 95% CI, 1.04–1.37). Similar trends were found in ischemic stroke and combined vascular events. Conclusions: Lower serum potassium level was independently associated with elevated risk of recurrent stroke in patients with AIS or TIA. The finding suggested that monitoring serum potassium may help physicians to identify patients at high risk of recurrent stroke and to stratify risk for optimal management. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to identify the risk of bleeding events and potential risk factors within 90 days in patients who carried CYP2C19 loss‐of‐function alleles and received dual antiplatelet therapy after minor stroke or transient ischemic attack. Methods: A total of 6,412 patients were enrolled from the CHANCE‐2 (Clopidogrel with Aspirin in High‐Risk Patients with Acute Non‐disabling Cerebrovascular Events II) trial. The main outcome was any bleeding within 90 days defined by the criteria from GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries). Results: A total of 250 (3.9%) bleeding events were reported, which occurred mainly within the 21 days of dual antiplatelet therapy (200 cases, 3.1%). Minor bleeding of the skin bruises, epistaxis, and gum bleeding were most frequent. Multivariate analysis showed that treatment with ticagrelor‐aspirin compared with clopidogrel‐aspirin was associated with increased bleeding (hazard ratio [HR] = 2.21, 95% confidence interval [CI] = 1.68–2.89, p < 0.001). Current smoking was associated with a lower risk of bleeding (HR = 0.70, 95% CI = 0.52–0.95, p = 0.02). Additionally, ticagrelor‐aspirin compared with clopidogrel‐aspirin was associated with higher risk of bleeding in patients aged <65 years (HR = 2.87, 95% CI = 1.95–4.22) and those without diabetes mellitus (HR = 2.65, 95% CI = 1.88–3.73; p for interaction = 0.04 and 0.03, respectively). Interpretation: Bleeding events mostly occurred within the 21‐day dual antiplatelet therapy stage and were generally mild. The risk of bleeding was greater in nonsmoking patients, and was associated with treatment with ticagrelor‐aspirin compared with clopidogrel‐aspirin, particularly in patients aged <65 years and nondiabetic patients. ANN NEUROL 2022;91:380–388 [ABSTRACT FROM AUTHOR]