Yongjun Wang

BACKGROUND: The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial showed that the combined treatment of clopidogrel and aspirin decreases the 90-day risk of stroke without increasing hemorrhage in comparison with aspirin alone, but provided insufficient data to establish whether the benefit persisted over a longer period of time beyond the trial termination. We report the 1-year follow-up outcomes of this trial. METHODS AND RESULTS: The trial was a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China. We randomly assigned 5170 patients within 24 hours after onset of minor stroke or high-risk transient ischemic attack to clopidogrel-aspirin therapy (loading dose of 300 mg of clopidogrel on day 1, followed by 75 mg of clopidogrel per day for 90 days, plus 75 mg of aspirin per day for the first 21 days) or to the aspirin-alone group (75 mg/d for 90 days). The primary outcome was stroke event (ischemic or hemorrhagic) during 1-year follow-up. Differences in outcomes between groups were assessed by using the Cox proportional hazards model. Stroke occurred in 275 (10.6%) patients in the clopidogrel-aspirin group, in comparison with 362 (14.0%) patients in the aspirin group (hazard ratio, 0.78; 95% confidence interval, 0.65-0.93; P=0.006). Moderate or severe hemorrhage occurred in 7 (0.3%) patients in the clopidogrel-aspirin group and in 9 (0.4%) patients in the aspirin group (P=0.44). CONCLUSIONS: The early benefit of clopidogrel-aspirin treatment in reducing the risk of subsequent stroke persisted for the duration of 1-year of follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.

The osteogenic differentiation of human aortic valve interstitial cells (hVICs) is the key cellular mechanism of calcified aortic valve disease (CAVD). This study aimed to explore how curcumin (CCM) inhibits the osteogenic differentiation of hVICs and elucidate the molecular mechanisms involved. In this study, CCM inhibited the osteogenic differentiation of hVICs under osteogenic medium (OM) conditions by reversing the OM-induced increase in calcified nodule formation and osteogenesis-specific markers (ALP and Runx2). RNA sequencing identified 475 common differentially expressed genes with Venn diagrams of the different groups. Kyoto Encyclopedia of Genes and Genomes enrichment revealed that the CCM inhibition of hVIC osteogenic differentiation was enriched in the NF-κB, PI3K-AKT, TNF, Jak-STAT, and MAPK signaling pathways. In addition, CCM suppressed the phosphorylation of ERK, IκBα, AKT, and interfered with the translocation of P65 into the cell nucleus in hVICs under OM culture conditions. In conclusion, CCM inhibited the osteogenic differentiation of hVICs via interfering with the activation of NF-κB/AKT/ERK signaling pathways. Our findings provide novel insights into a critical role for CCM in CAVD progression and shed new light on CCM-directed therapeutics for CAVD.

The association between blood pressure variability (BPV) and the risk of all-cause mortality and cardiovascular diseases (CVD) is not well understood. The Kailuan study is a prospective longitudinal cohort study on cerebrovascular events and cardiovascular factors. In this study, resting blood pressure was measured at baseline and every 2 years from 2006 to 2007. BPV is mainly defined as the coefficient of variation (CV). Hazard ratio (HR), with 95% confidence intervals (CI) was calculated using Cox regression model. Among 52 387 participants, we identified 1817 who ended up with all-cause death and 1198 with CVD. Each 4.68% increase in BPV was associated with a 13% increase in the risk of mortality (HR = 1.13, 95% CI = 1.09-1.18) and a 7% increase in CVD (HR = 1.07, 95% CI = 1.02-1.13), respectively. After adjustment of confounding factors, the HR of comparing participants in the highest versus lowest quartile of CV of systolic blood pressure (SBP) was 1.37 (1.19, 1.57) for all-cause death, 1.18 (1.01, 1.39) for CVD. Similar results were also observed when BPV was measured by different parameters. We concluded that visit-to-visit BPV was associated with all-cause death and cardiovascular and cerebrovascular events in Chinese general population.