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We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases and 5,019 controls followed by replication studies in 15,460 cases and 11,472 controls, all of Chinese Han ancestry. We identify four new loci for coronary artery disease that reached the threshold of genome-wide significance (P < 5 × 10?8). These loci mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (in or near PHACTR1, TCF21, CDKN2A-CDKN2B and C12orf51). These findings provide new insights into pathways contributing to the susceptibility for coronary artery disease in the Chinese Han population. [ABSTRACT FROM AUTHOR]

Objective: To investigate the activated clotting time (ACT) level after administration of guideline-recommended dose of unfractionated heparin (UFH) and to confirm the importance of ACT monitoring in percutaneous coronary intervention (PCI)., Methods: We performed a retrospective study on 1 062 patients undergoing elective PCI in Peking Union Medical College Hospital from May 1, 2011 to December 31, 2012. All patients were administrated weight-adjusted UFH (70-100 U/kg) based on PCI guideline of ACCF/AHA/SCAI. Patients were divided into 3 groups: ACT < 300 s (598 cases), ACT 300-350 s (183 cases) and ACT > 350 s (281 cases). ACT level and factors that may affect UFH anticoagulation were analyzed., Results: (1) The mean age was (63.0 ± 10.6) years and 751 (70.7%) patients were men. The mean weight was (70.5 ± 11.7) kg, and the mean UFH dose used was (100.7 ± 9.1) U/kg. (2) The median ACT was 285 (240-352) s after the UFH use. Pre-defined ACT target (300-350 s) was achieved only in 17.2% (183/1 062) patients. (3) Age, gender, height, weight, UFH/weight and the risk factors of coronary heart disease were similar among 3 groups (all P > 0.05). Multifactor linear correlation analysis showed that UFH/weight was related to ACT level (r = 0.07, P < 0.01), but other factors were not related to ACT level (all P > 0.05). (4) Among 598 patients with ACT < 300 s, 444 (74.2%) patients received additional UFH. No major bleeding events were observed in 1 062 patients. The incidence of minor bleeding and ischemic complications within 48 h after procedure were similar among 4 groups of ACT < 300 s with additional UFH, ACT < 300 s without additional UFH, ACT 300-350 s and ACT > 350 s (all P > 0.05)., Conclusions: In this single-center study, only a small proportion of patients reached the ACT target after administration of weight-adjusted UFH. Our results supported the recommendation of ACT monitoring in current PCI guideline to improve efficacy and safety of UFH anticoagulation therapy.

Objective: To investigate the impact of gender on early outcomes of patients with acute ST-segment elevation myocardial infarction (STEMI) who were treated with primary percutaneous coronary intervention (PCI) as their reperfusion strategy., Methods: The present study included consecutive patients with STEMI treated with primary PCI in our hospital from November 2003 to December 2012. Gender difference and predictors of 30 day all-cause death were examined among 957 patients, 197 of whom were women (20.6%). The impact of gender on 30 all-cause death was further evaluated by a propensity-matched analysis to adjust the differences in baseline characteristics between men and women., Results: Compared with men, women were older ((69.4±10.2) years old vs. (60.6±12.6) years old, P<0.001), more likely to have hypertension (72.1% (142/197) vs. 54.6% (415/760), P<0.001) and diabetes (45.2% (89/197) vs. 32.4% (246/760), P = 0.001), but less likely to be treated with β-blockers (85.3% (168/197) vs. 92.0% (699/760), P = 0.006) and angiotensin converting-enzyme inhibitors/angiotensin-receptor blockers (82.2% (162/197) vs. 88.4% (672/760), P = 0.024). Symptom-to-balloon time was longer in women than in men (330 (240, 600) minutes vs. 270 (180, 450) minutes, P < 0.001). Multivariate linear regression analysis of log-transformed symptom-to-balloon time revealed that female gender was an independent predictor of longer symptom-to-balloon time (β = 0.141, 95% confidence interval (CI) 0.053-0.228, P = 0.002). Women with STEMI had higher unadjusted 30 day all-cause death (12.6% vs. 4.2%, P < 0.001) than men. Female gender independently predicted 30 day all-cause mortality both with (hazard ratio (HR) = 3.497, 95% CI 1.485-8.234, P = 0.004) and without (HR = 2.495, 95% CI 1.170-5.323, P = 0.018) the adjustment for baseline characteristics by propensity-matched analysis., Conclusions: Even with primary PCI as their reperfusion strategy, women with STEMI had higher 30 day all-cause death than men. Aggressive control of cardiovascular risk factors, adequate medical treatment and shortening of delay in reperfusion therapy might further improve the outcomes of female STEMI patients undergoing primary PCI.

Recent epidemiological studies have suggested a link between exposure to ambient air-pollution and susceptibility to metabolic disorders such as Type II diabetes mellitus. Previously, we provided evidence that both short- and long-term exposure to concentrated ambient particulate matter with aerodynamic diameter <2.5 μm (PM2.5) induces multiple abnormalities associated with the pathogenesis of Type II diabetes mellitus, including insulin resistance, visceral adipose inflammation, brown adipose mitochondrial adipose changes, and hepatic endoplasmic reticulum (ER) stress. In this report, we show that chronic inhalation exposure to PM2.5 (10 months exposure) induces macrophage infiltration and Unfolded Protein Response (UPR), an intracellular stress signaling that regulates cell metabolism and survival, in mouse white adipose tissue in vivo. Gene expression studies suggested that PM2.5 exposure induces two distinct UPR signaling pathways mediated through the UPR transducer inositol-requiring 1α (IRE1α): 1) ER-associated Degradation (ERAD) of unfolded or misfolded proteins, and 2) Regulated IRE1-dependent Decay (RIDD) of mRNAs. Along with the induction of the UPR pathways and macrophage infiltration, expression of genes involved in lipogenesis, adipocyte differentiation, and lipid droplet formation was increased in the adipose tissue of the mice exposed to PM2.5. In vitro study confirmed that PM2.5 can trigger phosphorylation of the UPR transducer IRE1α and activation of macrophages. These results provide novel insights into PM2.5-triggered cell stress response in adipose tissue and increase our understanding of pathophysiological effects of particulate air pollution on the development of metabolic disorders.