Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA.

BACKGROUND: Comparisons between ticagrelor and clopidogrel for the secondary prevention of stroke in CYP2C19 loss-of-function carriers have not been extensively performed. METHODS: We conducted a randomized, double-blind, placebo-controlled trial at 202 centers in China involving patients with a minor ischemic stroke or transient ischemic attack (TIA) who carried CYP2C19 loss-of-function alleles. Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive ticagrelor (180 mg on day 1 followed by 90 mg twice daily on days 2 through 90) and placebo clopidogrel or to receive clopidogrel (300 mg on day 1 followed by 75 mg once daily on days 2 through 90) and placebo ticagrelor; both groups received aspirin for 21 days. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days. RESULTS: A total of 11,255 patients were screened and 6412 patients were enrolled, with 3205 assigned to the ticagrelor group and 3207 to the clopidogrel group. The median age of the patients was 64.8 years, and 33.8% were women; 98.0% belonged to the Han Chinese ethnic group. Stroke occurred within 90 days in 191 patients (6.0%) in the ticagrelor group and 243 patients (7.6%) in the clopidogrel group (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008). Secondary outcomes were generally in the same direction as the primary outcome. Severe or moderate bleeding occurred in 9 patients (0.3%) in the ticagrelor group and in 11 patients (0.3%) in the clopidogrel group; any bleeding occurred in 170 patients (5.3%) and 80 patients (2.5%), respectively. CONCLUSIONS: Among Chinese patients with minor ischemic stroke or TIA who were carriers of CYP2C19 loss-of-function alleles, the risk of stroke at 90 days was modestly lower with ticagrelor than with clopidogrel. The risk of severe or moderate bleeding did not differ between the two treatment groups, but ticagrelor was associated with more total bleeding events than clopidogrel. (Funded by the Ministry of Science and Technology of the People's Republic of China and others; CHANCE-2 ClinicalTrials.gov number, NCT04078737.).

High-density lipoprotein cholesterol and brain aging amongst rural-dwelling older adults: a population-based magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Current evidence supports the involvement of lipids in brain aging. A range of serum lipids is explored in association with brain structure and cognitive function amongst rural-dwelling older adults. METHODS: This population-based cross-sectional study included 184 rural-dwelling adults (age ≥ 65 years, 39.1% women) in Shandong, China. In 2014-2016, data on demographics, lifestyle, health conditions and serum lipids were collected. Volumes of gray matter, white matter, ventricles, hippocampus and white matter hyperintensity were automatically estimated on brain magnetic resonance imaging. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE), and mild cognitive impairment (MCI) was defined according to Petersen's criteria. Data were analyzed using the general linear regression, logistic regression and mediation models. RESULTS: Of the 184 participants, 47 were defined with MCI. Low high-density lipoprotein cholesterol (HDL-C; <1.55 vs. ≥1.55 mmol/l) was significantly associated with reduced volumes of total white matter (multi-adjusted ß = -9.77, 95% confidence interval -19.48-0.06) and hippocampus (-0.23, -0.46-0.01), a lower MMSE score (-1.49, -2.67-0.31) and a higher likelihood of MCI (multi-adjusted odds ratio 3.21, 95% confidence interval 1.42-7.29). The mediation effects of structural brain measures on the associations between a low level of HDL-C and MMSE score or MCI were not statistically significant (p > 0.05). CONCLUSIONS: This study suggests that low HDL-C may be involved in structural brain aging and cognitive dysfunction amongst rural-dwelling older adults in China, but the association of low HDL-C with cognitive aging phenotypes appears not to be mediated by brain structure.

Genetic characterization of inbred lines from Shaan A and B groups for identifying loci associated with maize grain yield.

BACKGROUND: Increasing grain yield is a primary objective of maize breeding. Dissecting the genetic architecture of grain yield furthers genetic improvements to increase yield. Presented here is an association panel composed of 126 maize inbreds (AM126), which were genotyped by the genotyping-by-sequencing (tGBS) method. We performed genetic characterization and association analysis related to grain yield in the association panel. RESULTS: In total, 46,046 SNPs with a minor allele frequency (MAF) ≥0.01 were used to assess genetic diversity and kinship in AM126. The results showed that the average MAF and polymorphism information content (PIC) were 0.164 and 0.198, respectively. The Shaan B group, with 11,284 unique SNPs, exhibited greater genetic diversity than did the Shaan A group, with 2644 SNPs. The 61.82% kinship coefficient in AM126 was equal to 0, and only 0.15% of that percentage was greater than 0.7. A total of 31,983 SNPs with MAF ≥0.05 were used to characterize population structure, LD decay and association mapping. Population structure analysis suggested that AM126 can be divided into 6 subgroups, which is consistent with breeding experience and pedigree information. The LD decay distance in AM126 was 150 kb. A total of 51 significant SNPs associated with grain yield were identified at P < 1 × 10- 3 across two environments (Yangling and Yulin). Among those SNPs, two loci displayed overlapping regions in the two environments. Finally, 30 candidate genes were found to be associated with grain yield. CONCLUSIONS: These results contribute to the genetic characterization of this breeding population, which serves as a reference for hybrid breeding and population improvement, and demonstrate the genetic architecture of maize grain yield, potentially facilitating genetic improvement.

Colchicine in patients with acute ischaemic stroke or transient ischaemic attack (CHANCE-3): multicentre, double blind, randomised, placebo controlled trial.

OBJECTIVES: To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3). DESIGN: Multicentre, double blind, randomised, placebo controlled trial. SETTING: 244 hospitals in China between 11 August 2022 and 13 April 2023. PARTICIPANTS: 8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled. INTERVENTIONS: Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days. MAIN OUTCOME MEASURES: The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat. RESULTS: 4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83). CONCLUSIONS: The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05439356.

Effect of different doses of colchicine on high sensitivity C-reactive protein in patients with acute minor stroke or transient ischemic attack: A pilot randomized controlled trial.

BACKGROUND AND PURPOSE: Patients with elevated levels of high-sensitivity C-reactive protein (hsCRP) are at increased risk of recurrent stroke. Colchicine is a unique anti-inflammatory medication that has shown promise in reducing cardiovascular event. The current study mainly tested the ability of colchicine at different doses to reduce hsCRP levels after stroke. METHODS: This was a randomized controlled and open label trial. Eligible patients with acute minor ischemic stroke or transient ischemic attack (TIA) were randomized within 24 h after symptom onset in a 1:1:1:1 ratio to four groups with different doses of colchicine. Group 1: 0.5 mg of colchicine per day for 14 days; groups 2: starting with 1 mg of colchicine on days 1 through 7, and maintaining with 0.5 mg per day on days 8 through 14; group 3 and 4: respectively, 2 mg and 3 mg of colchicine on day 1, following with 1 mg per day on days 2 through 7 and continuing with 0.5 mg per day on days 8 through 14. Blood specimens were collected at randomization, 24 h, 72 h, 7 days and 14 days after index event for hsCRP measurements. The primary outcome was the change of hsCRP levels between baseline and 14 days. RESULTS: A total of 39 patients were enrolled. Patients in group 2 had reduced level of hsCRP at 14-day compared with baseline value (p = 0.005). Time-course analyses showed that patients in groups of 1 and 2 had lower hsCRP level at 7-day than that at baseline, and patients in groups of 1, 2 and 3 had lower ratios of hsCRP levels at 72 h to those at baseline. Low dose of colchicine was well tolerated without discontinuation of drug. CONCLUSION: Early treatment with low dose of colchicine reduced hsCRP levels in the patients with acute minor ischemic stroke and TIA.

Characterizing Global and Regional Brain Structures in Amnestic Mild Cognitive Impairment Among Rural Residents: A Population-Based Study.

BACKGROUND: Structural brain magnetic resonance imaging (MRI) scans may provide reliable neuroimaging markers for defining amnestic mild cognitive impairment (aMCI). OBJECTIVE: We sought to characterize global and regional brain structures of aMCI among rural-dwelling older adults with limited education in China. METHODS: This population-based study included 180 participants (aged≥65 years, 42 with aMCI and 138 normal controls) in the Shandong Yanggu Study of Aging and Dementia during 2014-2016. We defined aMCI following the Petersen's criteria. Global and regional brain volumes were automatically segmented on MRI scans and compared using a region-of-interest approach. Data were analyzed using general linear regression models. RESULTS: Multi-adjusted ß-coefficient (95% confidence interval) of brain volumes (cm3) associated with aMCI was -12.07 (-21.49, -2.64) for global grey matter (GM), -18.31 (-28.45, -8.17) for global white matter (WM), 28.17 (12.83, 44.07) for cerebrospinal fluid (CSF), and 2.20 (0.24, 4.16) for white matter hyperintensities (WMH). Furthermore, aMCI was significantly associated with lower GM volumes in bilateral superior temporal gyri, thalamus and right cuneus, and lower WM volumes in lateral areas extending from the frontal to the parietal, temporal, and occipital lobes, as well as right hippocampus (p < 0.05). CONCLUSION: Brain structure of older adults with aMCI is characterized by reduced global GM and WM volumes, enlarged CSF volume, increased WMH burden, reduced GM volumes in bilateral superior temporal gyri, thalamus, and right cuneus, and widespread reductions of lateral WM volumes.