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  • Oxford University Press (OUP)  (5)
  • Yang, Jie  (5)
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  • Oxford University Press (OUP)  (5)
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  • 1
    In: Age and Ageing, Oxford University Press (OUP), Vol. 51, No. 11 ( 2022-11-01)
    Abstract: The evidence for the comparative effectiveness and safety of ticagrelor versus clopidogrel in older patients with acute coronary syndrome (ACS) is limited, especially in the acute phase of ACS. This study aimed to compare the in-hospital outcomes of ticagrelor versus clopidogrel in older patients with ACS. Methods Hospitalised ACS patients aged ≥75 years who were recruited to the Improving Care for Cardiovascular Disease in China-ACS project between November 2014 and December 2019 and received aspirin and P2Y12 receptor inhibitors within 24 h after first medical contact were included. The primary outcomes were in-hospital major adverse cardiovascular events (MACE) and major bleeding. Multivariable Cox regression was performed to evaluate the comparative effectiveness and safety of ticagrelor and clopidogrel. Inverse probability of treatment weighting (IPTW) and propensity score matching analyses were performed to evaluate the robustness of the results. Results Of 18,244 ACS patients, 18.5% received ticagrelor. Multivariable-adjusted analysis revealed comparable risks of in-hospital MACE between patients receiving ticagrelor and clopidogrel (hazard ratio [HR] 1.12, 95% confidence interval [CI] 0.92–1.35). However, ticagrelor use was associated with 45% higher risk of in-hospital major bleeding compared with clopidogrel use (HR 1.45, 95% CI 1.09–1.91). Similar results were found in the IPTW analysis. Conclusions ACS patients aged ≥75 years receiving ticagrelor during the acute phase had similar risk of in-hospital MACE, but higher risk of in-hospital major bleeding compared with those receiving clopidogrel. More evidence is needed to guide the use of P2Y12 receptor inhibitors during hospitalisation in older patients with ACS. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02306616.
    Type of Medium: Online Resource
    ISSN: 0002-0729 , 1468-2834
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2065766-3
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  • 2
    In: International Journal of Epidemiology, Oxford University Press (OUP), Vol. 51, No. 2 ( 2022-05-09), p. 567-578
    Abstract: The relative importance of healthy lifestyle factors and cardiovascular health metrics for the risk of heart failure is uncertain in Chinese populations. We aimed to compare the strength of associations between healthy lifestyle factors and ideal cardiovascular health metrics in the risk of heart failure in middle-aged Chinese adults. Methods A healthy lifestyle score (HLS) was constructed using smoking, drinking, physical activity, diet, body mass index and waist circumference, and compared with a more comprehensive set of metrics that included cardiovascular-disease risk biomarkers (blood pressure, blood glucose and blood lipids) in addition to the HLS. This broader set of factors [called ‘ideal cardiovascular health metrics’ (ICVHMs)] was evaluated in 487 197 participants in the China Kadoorie Biobank. Results A total of 4208 incident cases of heart failure were recorded during a median follow-up of 10 years. Both HLS [hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.85, 0.91] and ICVHMs (0.87: 0.84, 0.89) were inversely associated with risk of heart failure (P  & lt; 0.001 for linear trend). Compared with participants with 0–1 HLS, the multivariable-adjusted HR of those with 4–5 HLS was 0.68 (0.59, 0.77). Compared with participants with 0–2 ICVHMs, the adjusted HR (95% CIs) of those who had 7–8 ICVHMs was 0.47 (0.36, 0.60). ICVHMs were more strongly predictive of risk of heart failure (area under curve, 0.61 vs 0.58, P  & lt; 0.001) than healthy lifestyle factors alone. Conclusions Higher levels of healthy lifestyle factors and ICVHMs were each inversely associated with heart failure, and lifestyle factors combined with cardiometabolic factors improved the prediction of heart failure compared with healthy lifestyle factors alone.
    Type of Medium: Online Resource
    ISSN: 0300-5771 , 1464-3685
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1494592-7
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  • 3
    In: European Journal of Preventive Cardiology, Oxford University Press (OUP), ( 2024-01-10)
    Abstract: Lowering low-density lipoprotein cholesterol (LDL-C) through PCSK9 inhibition represents a new therapeutic approach to preventing and treating cardiovascular disease (CVD). Phenome-wide analyses of PCSK9 genetic variants in large biobanks can help to identify unexpected effects of PCSK9 inhibition. Methods and results In the prospective China Kadoorie Biobank, we constructed a genetic score using three variants at the PCSK9 locus associated with directly measured LDL-C [PCSK9 genetic score (PCSK9-GS)]. Logistic regression gave estimated odds ratios (ORs) for PCSK9-GS associations with CVD and non-CVD outcomes, scaled to 1 SD lower LDL-C. PCSK9-GS was associated with lower risks of carotid plaque [n = 8340 cases; OR = 0.61 (95% confidence interval: 0.45–0.83); P = 0.0015] , major occlusive vascular events [n = 15 752; 0.80 (0.67–0.95); P = 0.011], and ischaemic stroke [n = 11 467; 0.80 (0.66–0.98); P = 0.029] . However, PCSK9-GS was also associated with higher risk of hospitalization with chronic obstructive pulmonary disease [COPD: n = 6836; 1.38 (1.08–1.76); P = 0.0089] and with even higher risk of fatal exacerbations amongst individuals with pre-existing COPD [n = 730; 3.61 (1.71–7.60); P = 7.3 × 10−4] . We also replicated associations for a PCSK9 variant, reported in UK Biobank, with increased risks of acute upper respiratory tract infection (URTI) [pooled OR after meta-analysis of 1.87 (1.38–2.54); P = 5.4 × 10−5] and self-reported asthma [pooled OR of 1.17 (1.04–1.30); P = 0.0071] . There was no association of a polygenic LDL-C score with COPD hospitalization, COPD exacerbation, or URTI. Conclusion The LDL-C-lowering PCSK9 genetic variants are associated with lower risk of subclinical and clinical atherosclerotic vascular disease but higher risks of respiratory diseases. Pharmacovigilance studies may be required to monitor patients treated with therapeutic PCSK9 inhibitors for exacerbations of respiratory diseases or respiratory tract infections. Lay summary Genetic analyses of over 100 000 participants of the China Kadoorie Biobank, mimicking the effect of new drugs intended to reduce cholesterol by targeting the PCSK9 protein, have identified potential severe effects of lower PCSK9 activity in patients with existing respiratory disease.
    Type of Medium: Online Resource
    ISSN: 2047-4873 , 2047-4881
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2646239-4
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  • 4
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2023
    In:  Nucleic Acids Research Vol. 51, No. 21 ( 2023-11-27), p. 11668-11687
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 51, No. 21 ( 2023-11-27), p. 11668-11687
    Abstract: Unscheduled R-loops are a major source of replication stress and DNA damage. R-loop-induced replication defects are sensed and suppressed by ATR kinase, whereas it is not known whether R-loop itself is actively involved in ATR activation and, if so, how this is achieved. Here, we report that the nuclear form of RNA-editing enzyme ADAR1 promotes ATR activation and resolves genome-wide R-loops, a process that requires its double-stranded RNA-binding domains. Mechanistically, ADAR1 interacts with TOPBP1 and facilitates its loading on perturbed replication forks by enhancing the association of TOPBP1 with RAD9 of the 9–1-1 complex. When replication is inhibited, DNA–RNA hybrid competes with TOPBP1 for ADAR1 binding to promote the translocation of ADAR1 from damaged fork to accumulate at R-loop region. There, ADAR1 recruits RNA helicases DHX9 and DDX21 to unwind R-loops, simultaneously allowing TOPBP1 to stimulate ATR more efficiently. Collectively, we propose that the tempo-spatially regulated assembly of ADAR1-nucleated protein complexes link R-loop clearance and ATR activation, while R-loops crosstalk with blocked replication forks by transposing ADAR1 to finetune ATR activity and safeguard the genome.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2013
    In:  Modern Rheumatology Vol. 23, No. 4 ( 2013-07), p. 686-693
    In: Modern Rheumatology, Oxford University Press (OUP), Vol. 23, No. 4 ( 2013-07), p. 686-693
    Type of Medium: Online Resource
    ISSN: 1439-7595 , 1439-7609
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2013
    detail.hit.zdb_id: 2023498-3
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