Publications by authors named "Hung-Fat Tse"

561 Publications

Concomitant Hepatorenal Dysfunction and Malnutrition in Valvular Heart Surgery: Long-Term Prognostic Implications for Death and Heart Failure.

J Am Heart Assoc 2022 May 16;11(10):e024060. Epub 2022 May 16.

Division of Cardiology Department of Medicine The University of Hong Kong Shenzhen Hospital Shenzhen China.

Background Strategies to improve long-term prediction of heart failure and death in valvular surgery are urgently needed because of an increasing number of procedures globally. This study sought to report the prevalence, changes, and prognostic implications of concomitant hepatorenal dysfunction and malnutrition in valvular surgery. Methods and Results In 909 patients undergoing valvular surgery, 3 groups were defined based on hepatorenal function (the modified model for end-stage liver disease excluding international normalized ratio score) and nutritional status (Controlling Nutritional Status score): normal hepatorenal function and nutrition (normal), hepatorenal dysfunction or malnutrition alone (mild), and concomitant hepatorenal dysfunction and malnutrition (severe). Overall, 32%, 46%, and 19% of patients were classified into normal, mild, and severe groups, respectively. Over a 4.1-year median follow-up, mild and severe groups incurred a higher risk of mortality (hazard ratio [HR], 3.17 [95% CI, 1.40-7.17] and HR, 9.30 [95% CI, 4.09-21.16], respectively), cardiovascular death (subdistribution HR, 3.29 [95% CI, 1.14-9.52] and subdistribution HR, 9.29 [95% CI, 3.09-27.99]), heart failure hospitalization (subdistribution HR, 2.11 [95% CI, 1.25-3.55] and subdistribution HR, 3.55 [95% CI, 2.04-6.16]), and adverse outcomes (HR, 2.11 [95% CI, 1.25-3.55] and HR, 3.55 [95% CI, 2.04-6.16]). Modified model for end-stage liver disease excluding international normalized ratio and controlling nutritional status scores improved the predictive ability of European System for Cardiac Operative Risk Evaluation (area under the curve: 0.80 versus 0.73, <0.001) and Society of Thoracic Surgeons score (area under the curve: 0.79 versus 0.72, =0.004) for all-cause mortality. One year following surgery (n=707), patients with persistent concomitant hepatorenal dysfunction and malnutrition (severe) experienced worse outcomes than those without. Conclusions Concomitant hepatorenal dysfunction and malnutrition was frequent and strongly linked to heart failure and mortality in valvular surgery.
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http://dx.doi.org/10.1161/JAHA.121.024060DOI Listing
May 2022

Generation of a human iPSC line CIBi010-A with a reporter for ASGR1 using CRISPR/Cas9.

Stem Cell Res 2022 May 5;62:102800. Epub 2022 May 5.

Cell Inspire Therapeutics Co., Ltd., Shenzhen 518101, China. Electronic address:

ASGR1 is a liver-specific surface marker that has been used to purify human pluripotent stem cell (PSC)-derived hepatocytes (iHeps). Furthermore, ASGR1 iHeps represents a more mature subpopulation of iHeps. To utilize this marker for optimizing iHep differentiation and purification, we substituted the stop coden of ASGR1 with a fluorescent reporter protein mCherry in a human iPSC line iPSN0052 via CRISPR/Cas9-mediated homologus recombination. The generated CIBi010-A enableds us to monitor ASGR1 expression during hepatic differentiation and thus can be used to optimize our hepatic differentiation procedures.
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http://dx.doi.org/10.1016/j.scr.2022.102800DOI Listing
May 2022

Regression of IgG4-related coronary arteritis and aortitis with immunosuppressive therapy.

Eur Heart J Case Rep 2022 May 8;6(5):ytac156. Epub 2022 Apr 8.

Department of Medicine, The University of Hong Kong, Hong Kong, China.

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http://dx.doi.org/10.1093/ehjcr/ytac156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071294PMC
May 2022

Generation of Human Liver Chimeric Mice and Harvesting of Human Hepatocytes from Mouse Livers.

Methods Mol Biol 2022 ;2429:379-390

The Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, SAR, China.

Primary human hepatocytes (PHHs) are widely used as an in vitro model to evaluate various aspects of human hepatic physiology and pathology. However, PHHs isolated from the human liver have very limited ability for ex vivo expansion in culture. Fah/Rag2/Il2rg (FRG) mice are proven to be an ideal bioincubator for repopulation of PHHs. The human liver chimeric FRG mouse is not only a humanized animal model for disease study and drug screening in vivo, but also a potential source of PHHs for cellular therapy. This chapter describes experimental protocols to generate chimeric FRG mice with humanized liver and to isolate PHHs from human liver chimeric FRG mice. Using these methods, PHHs can be expanded to more than 100-fold for harvesting.
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http://dx.doi.org/10.1007/978-1-0716-1979-7_25DOI Listing
May 2022

Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model.

Nat Commun 2022 Apr 19;13(1):2028. Epub 2022 Apr 19.

AIDS Institute and Department of Microbiology, State Key Laboratory of Emergent Infectious Disease, The University of Hong Kong, Hong Kong, China.

Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19), with macrophages as one of the main cell types involved. It is urgent to understand the interactions among permissive cells, macrophages, and the SARS-CoV-2 virus, thereby offering important insights into effective therapeutic strategies. Here, we establish a lung and macrophage co-culture system derived from human pluripotent stem cells (hPSCs), modeling the host-pathogen interaction in SARS-CoV-2 infection. We find that both classically polarized macrophages (M1) and alternatively polarized macrophages (M2) have inhibitory effects on SARS-CoV-2 infection. However, M1 and non-activated (M0) macrophages, but not M2 macrophages, significantly up-regulate inflammatory factors upon viral infection. Moreover, M1 macrophages suppress the growth and enhance apoptosis of lung cells. Inhibition of viral entry using an ACE2 blocking antibody substantially enhances the activity of M2 macrophages. Our studies indicate differential immune response patterns in distinct macrophage phenotypes, which could lead to a range of COVID-19 disease severity.
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http://dx.doi.org/10.1038/s41467-022-29731-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018716PMC
April 2022

Multi-Omics Signatures Link to Ticagrelor Effects on Vascular Function in Patients With Acute Coronary Syndrome.

Arterioscler Thromb Vasc Biol 2022 Apr 7:101161ATVBAHA121317513. Epub 2022 Apr 7.

Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, China (C.-C.F.T., Y.-H.C., Y.-K.W., H.-F.T.).

Background: Long-term antiplatelet agents including the potent P2Y12 antagonist ticagrelor are indicated in patients with a previous history of acute coronary syndrome. We sought to compare the effect of ticagrelor with that of aspirin monotherapy on vascular endothelial function in patients with prior acute coronary syndrome.

Methods: This was a prospective, single center, parallel group, investigator-blinded randomized controlled trial. We randomized 200 patients on long-term aspirin monotherapy with prior acute coronary syndrome in a 1:1 fashion to receive ticagrelor 60 mg BD (n=100) or aspirin 100 mg OD (n=100). The primary end point was change from baseline in brachial artery flow-mediated dilation at 12 weeks. Secondary end points were changes to platelet activation marker (CD41_62p) and endothelial progenitor cell (CD34/133) count measured by flow cytometry, plasma level of adenosine, IL-6 (interleukin-6) and EGF (epidermal growth factor), and multi-omics profiling at 12 weeks.

Results: After 12 weeks, brachial flow-mediated dilation was significantly increased in the ticagrelor group compared with the aspirin group (ticagrelor: 3.48±3.48% versus aspirin: -1.26±2.85%, treatment effect 4.73 [95% CI, 3.85-5.62], <0.001). Nevertheless ticagrelor treatment for 12 weeks had no significant effect on platelet activation markers, circulating endothelial progenitor cell count or plasma level of adenosine, IL-6, and EGF (all >0.05). Multi-omics pathway assessment revealed that changes in the metabolism and biosynthesis of amino acids (cysteine and methionine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis) and phospholipids (glycerophosphoethanolamines and glycerophosphoserines) were associated with improved brachial artery flow-mediated dilation in the ticagrelor group.

Conclusions: In patients with prior acute coronary syndrome, ticagrelor 60 mg BD monotherapy significantly improved brachial flow-mediated dilation compared with aspirin monotherapy and was associated with significant changes in metabolomic and lipidomic signatures.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT03881943.
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http://dx.doi.org/10.1161/ATVBAHA.121.317513DOI Listing
April 2022

Challenges in management of ST elevation myocardial infarction during COVID-19 pandemic.

Cardiol Plus 2021 Oct 30;6(4):218-230. Epub 2021 Dec 30.

Department of Medicine, Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong.

The coronavirus disease-2019 (COVID-19) pandemic has brought unprecedented changes to our world and health-care system. Its high virulence and infectiousness directly infect people's respiratory system and indirectly disrupt our health-care infrastructure. In particular, ST elevation myocardial infarction (STEMI) is a clinical emergency emphasizes on the establishment of care system to minimize delay to reperfusion. As such, the impact of COVID-19 on STEMI care, ranging from disease severity, patient delay, diagnostic difficulty, triage to selection of reperfusion strategy and postoperative care, is immense. Importantly, not only we have to save our patients, but we must also need to protect all health-care workers and prevent environmental contamination. Otherwise, in-hospital transmission can quickly evolve into nosocomial outbreak with staff infection and quarantine which lead to health-care system collapse. In this article, we will discuss the challenges in various aspects of STEMI management during COVID-19, as well as the mitigation measures we can take to optimize outcome and our future.
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http://dx.doi.org/10.4103/2470-7511.334400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951676PMC
October 2021

Assessment and mitigation of bleeding risk in atrial fibrillation and venous thromboembolism: A Position Paper from the ESC Working Group on Thrombosis, in collaboration with the European Heart Rhythm Association, the Association for Acute CardioVascular Care and the Asia-Pacific Heart Rhythm Society.

Europace 2022 Mar 22. Epub 2022 Mar 22.

Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool Heart & Chest Hospital, Liverpool, UK.

Whilst there is a clear clinical benefit of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and venous thromboembolism (VTE) in reducing the risks of thromboembolism, major bleeding events (especially intracranial bleeds) may still occur and be devastating. The decision to initiate and continue anticoagulation is often based on a careful assessment of both the thromboembolism and bleeding risk. The more common and validated bleeding risk factors have been used to formulate bleeding risk stratification scores, but thromboembolism and bleeding risk factors often overlap. Also, many factors that increase bleeding risk are transient and modifiable, such as variable international normalized ratio values, surgical procedures, vascular procedures, or drug-drug and food-drug interactions. Bleeding risk is also not a static 'one off' assessment based on baseline factors but is dynamic, being influenced by ageing, incident comorbidities, and drug therapies. In this Consensus Document, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in patients with AF and VTE, with the view to summarizing 'best practice' when approaching antithrombotic therapy in these patients. We address the epidemiology and size of the problem of bleeding risk in AF and VTE, review established bleeding risk factors, and summarize definitions of bleeding. Patient values and preferences, balancing the risk of bleeding against thromboembolism are reviewed, and the prognostic implications of bleeding are discussed. We propose consensus statements that may help to define evidence gaps and assist in everyday clinical practice.
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http://dx.doi.org/10.1093/europace/euac020DOI Listing
March 2022

Osteogenic Circulating Endothelial Progenitor Cells are Associated with Vascular Aging of the Large Arteries in Rheumatoid Arthritis.

Clin Interv Aging 2022 17;17:287-294. Epub 2022 Mar 17.

Cardiology Division, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Regions, People's Republic of China.

Background And Aim: Rheumatoid arthritis is associated with both abnormal bone metabolism and accelerated vascular aging but a mechanistic link was lacking. This study aims to investigate the role of osteocalcin (OCN)-expressing circulating endothelial progenitor cells (EPCs) in vascular aging, as determined by arterial calcifications in rheumatoid arthritis.

Methods: We performed flow cytometry studies in 145 consecutive patients with rheumatoid arthritis to determine osteogenic circulating levels of OCN-positive (OCN+) CD34+KDR+ and OCN+CD34+ versus conventional early EPC CD34+CD133+KDR+. Total calcium load of the thoracic aorta (ascending plus descending) and the carotid arteries were assessed by non-contrast computed tomography (CT) and contrast CT angiography.

Results: Osteogenic EPCs OCN+CD34+KDR+ ( = 0.002) and OCN+CD34+ ( = 0.001), together with clinical parameters of age, history of hypertension, systolic blood pressure, serum levels of triglycerides, HbA1c and creatinine, use of leflunomide and brachial-ankle pulse-wave velocity (all < 0.05), were associated with the clustered presence of aortic and carotid calcification. Multivariable analyses revealed that circulating OCN+CD34+KDR+ (B = 14.4 [95% CI 4.0 to 24.8], = 0.007) and OCN+CD34+ (B = 9.6 [95% CI 4.9 to 14.3], < 0.001) remained independently associated with increased aortic calcium load. OCN+CD34+ EPC (B = 0.8 [95% CI 0.1 to 1.5], = 0.023), but not OCN+CD34+KDR+ EPC (B = 1.2 [95% CI -0.2 to 2.6], P = 0.09), was further independently associated with carotid calcium load. In comparison, conventional early EPC CD34+CD133+KDR+ had no significant association with aortic or carotid calcium load (P = 0.46 and 0.88, respectively).

Conclusion: Circulating level of osteogenic EPC is associated with increased vascular aging in terms of calcification of the large arteries in patients with rheumatoid arthritis. The findings may suggest a role of the bone-vascular axis underlying vascular aging in rheumatic diseases. Further research is needed to characterize the mechanistic links and basis of these observations.
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http://dx.doi.org/10.2147/CIA.S337118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8937309PMC
March 2022

Opportunistic screening for asymptomatic left ventricular dysfunction in type 2 diabetes mellitus.

Postgrad Med J 2022 Mar 8. Epub 2022 Mar 8.

Cardiology Division, Department of Medicine, University of Hong Kong, Hong Kong, Hong Kong

Background: International guidelines recommend natriuretic peptide biomarker-based screening for patients at high heart failure (HF) risk to allow early detection. There have been few reports about the incorporation of screening procedure to existing clinical practice.

Objective: To implement screening of left ventricular dysfunction in patients with type 2 diabetes mellitus (DM).

Method: A prospective screening study at the DM complication screening centre was performed.

Results: Between 2018 and 2019, 1043 patients (age: 63.7±12.4 years; male: 56.3%) with mean glycated haemoglobin of 7.25%±1.34% were recruited. 81.8% patients had concomitant hypertension, 31.1% had coronary artery disease, 8.0% had previous stroke, 5.5% had peripheral artery disease and 30.7% had chronic kidney disease (CKD) stages 3-5. 43 patients (4.1%) had an elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration above the age-specific diagnostic thresholds for HF, and 43 patients (4.1%) had newly detected atrial fibrillation (AF). The prevalence of elevated NT-proBNP increased with age from 0.85% in patients aged <50 years to 7.14% in those aged 70-79 years and worsening kidney function from 0.43% in patients with CKD stage 1 to 42.86% in CKD stage 5. In multivariate logistic regression, male gender (OR: 3.67 (1.47-9.16), p=0.005*), prior stroke (OR: 3.26 (1.38-7.69), p0.007*), CKD (p<0.001*) and newly detected AF (OR: 7.02 (2.65-18.57), p<0.001*) were significantly associated with elevated NT-proBNP. Among patients with elevated NT-proBNP, their mean left ventricular ejection fraction (LVEF) was 51.4%±14.7%, and 45% patients had an LVEF <50%.

Conclusion: NT-proBNP and ECG screening could be implemented with relative ease to facilitate early detection of cardiovascular complication and improve long-term outcomes.
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http://dx.doi.org/10.1136/postgradmedj-2022-141548DOI Listing
March 2022

Temporal trends and patterns of infective endocarditis in a Chinese population: A territory-wide study in Hong Kong (2002-2019).

Lancet Reg Health West Pac 2022 May 4;22:100417. Epub 2022 Mar 4.

Division of Cardiology, Department of Medicine, The University of Hong Kong, Hong Kong, China.

Background: The characteristics of infective endocarditis (IE) in Asians are poorly understood. Therefore, we aim to describe the epidemiological trends and clinical features of IE in Hong Kong.

Methods: All patients with incident IE from 2002-2019 in a territory-wide clinical database in Hong Kong were identified. We studied the age- and sex-adjusted and one-year mortality of IE between 2002 and 2019 and identified significant contributors to 1-year all-cause death using the attributable fraction. We used propensity score and inverse propensity of treatment weighting to study the association of surgery with mortality.

Findings: A total of 5139 patients (60.4 ± 18.2years, 37% women) were included. The overall incidence of IE was 4.9 per 100,000 person-year, which did not change over time ( = 0.17). Patients in 2019 were older and more comorbid than those in 2002. The one-year crude mortality rate was 30% in 2002, which did not change significantly over time ( = 0.10). Between 2002 and 2019, the rate of surgery increased and was associated with a 51% risk reduction in 1-year all-cause mortality (Hazard Ratio 0.49 [0.28-0.87],  = 0.015). Advanced age (attributable fraction 19%) and comorbidities (attributable fraction 15%) were significant contributors to death.

Interpretation: The incidence of IE in Hong Kong did not change between 2002 and 2019. Patients with IE in 2019 were older and had more comorbidities than those in 2002. Mortality of IE remains persistently high in Hong Kong. Together, these data can guide public health strategies to improve the outcomes of patients with IE.

Funding: This work was supported by Sanming Project of Medicine in Shenzhen, China [No. SZSM201911020] and HKU-SZH Fund for Shenzhen Key Medical Discipline [No. SZXK2020081].
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http://dx.doi.org/10.1016/j.lanwpc.2022.100417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897627PMC
May 2022

A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study.

Eur Heart J 2022 May;43(18):1702-1711

Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Aims: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations.

Methods And Results: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS.

Conclusion: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.
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http://dx.doi.org/10.1093/eurheartj/ehac093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9076396PMC
May 2022

Prevalence and Prognostic Importance of Massive Tricuspid Regurgitation in Patients Undergoing Tricuspid Annuloplasty With Concomitant Left-Sided Valve Surgery: A Study on Rheumatic Valvular Heart Disease.

Front Cardiovasc Med 2022 27;9:686208. Epub 2022 Jan 27.

Division of Cardiology, Department of Medicine, The University of Hong Kong Shen Zhen Hospital, Shenzhen, China.

Background: The presence of tricuspid regurgitation (TR) is very common in patients with concomitant left-sided valve disease. Recent studies have advocated an additional grading of massive TR that is beyond severe. The present study sought to characterize the spectrum of TR in patients undergoing tricuspid annuloplasty (TA) and to evaluate the prognostic value of TR severity for post-operative outcome following TA.

Methods: A total of 176 patients who underwent TA with combined left-sided valve surgery, secondary to rheumatic valvular heart disease, were prospectively evaluated. The severity of TR was quantified by effective regurgitant orifice area (EROA) using the proximal isovelocity surface area method. Patients were categorized as having non-massive TR (EROA < 0.6 cm) or massive TR (EROA ≥ 0.6 cm). Adverse outcome was defined as all-cause mortality or heart failure requiring hospital admission following TA.

Results: A total of 55 (31%) patients were considered to have massive TR. Patients with massive TR had a greater right ventricular dimension but a smaller left ventricular dimension compared with those with non-massive TR. After a median follow-up of 39 months, 35 adverse events occurred. Cox-regression analysis showed that both continuous EROA and dichotomized EROA (massive vs. non-massive TR) were independently associated with adverse events even after multivariable adjustment. Further, Harrell C index demonstrated that the addition of massive TR provided better discrimination ability of a prediction model to known prognosticators following TA.

Conclusions: Massive TR is common and up to 31% of study population had massive TR. Massive TR was associated with adverse outcome in patients undergoing TA. Classification of the severity of TR by quantitative measures and identification of massive TR in patients with concomitant left-sided valve disease are essential when considering the optimal timing of corrective surgery.
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http://dx.doi.org/10.3389/fcvm.2022.686208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829045PMC
January 2022

Mendelian randomization analysis of vitamin D in the secondary prevention of hypertensive-diabetic subjects: role of facilitating blood pressure control.

Genes Nutr 2022 Jan 29;17(1). Epub 2022 Jan 29.

Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.

Background: Vitamin D (Vit-D) promotes vascular repair and its deficiency is closely linked to the development of type 2 diabetes mellitus (T2DM) and hypertension. Whether genetially predicted vitamin D status (serological 25-hydroxyvitamin D [25(OH)D]) confers secondary protection against cardiovascular diseases (CVD) among high-risk hypertensive-diabetic subjects was unknown.

Methods: This is a prospective, individual-data, two-sample Mendelian randomization study. We interrogated 12 prior GWAS-detected SNPs of comprehensive Vit-D mechanistic pathways using high-throughput exome chip analyses in a derivation subcohort (n = 1460) and constructed a genetic risk score (GRS) (rs2060793, rs4588, rs7041; F-statistic = 32, P < 0.001) for causal inference of comprehensive CVD hard clinical endpoints in an independent sample of hypertensive subjects (n = 3746) with prevailing co-morbid T2DM (79%) and serological 25(OH)D deficiency [< 20 ng/mL] 45%.

Results: After 55.6 ± 28.9 months, 561 (15%) combined CVD events including myocardial infarction, unstable angina, ischemic stroke, congestive heart failure, peripheral vascular disease, and cardiovascular death had occurred. Kaplan-Meier analysis showed that genetically predicted reduced vitamin D status was associated with reduced event-free survival from combined CVD events (log-rank = 13.5, P = 0.001). Multivariate-adjusted per-allele increase in GRS predicted reduced combined CVD events (HR = 0.90 [0.84 to 0.96], P = 0.002). Mendelian randomization indicates that increased Vit-D exposure, leveraged through each 1 ng/mL genetically instrumented rise of serum Vit-D, protects against combined CVD events (Wald's estimate: OR = 0.86 [95%CI 0.75 to 0.95]), and myocardial infarction (OR = 0.76 [95%CI 0.60 to 0.90]). Furthermore, genetically predicted increase in Vit-D status ameliorates risk of deviation from achieving guideline-directed hypertension control (JNC-8: systolic target < 150 mmHg) (OR = 0.89 [95%CI 0.80 to 0.96]).

Conclusions: Genetically predicted increase in Vit-D status [25(OH)D] may confer secondary protection against incident combined CVD events and myocardial infarction in a hypertensive-diabetic population where serological 25(OH)D deficiency is common, through facilitating blood pressure control.
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http://dx.doi.org/10.1186/s12263-022-00704-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903706PMC
January 2022

Reply: High-sensitive cardiac troponin after CPAP in obstructive sleep apnoea.

Eur Respir J 2022 02 17;59(2). Epub 2022 Feb 17.

Dept of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.

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http://dx.doi.org/10.1183/13993003.03176-2021DOI Listing
February 2022

Prognosis and treatment of atrial fibrillation in Asian cities: 1-year review of the Asia-Pacific Heart Rhythm Society Atrial Fibrillation Registry.

Europace 2022 Jan 13. Epub 2022 Jan 13.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK.

Aims: The aim of this study is to describe the implementation of the current guidance for stroke prevention and treatment option in atrial fibrillation (AF) and to evaluate mortality and morbidity in relation to therapeutic decisions, including persistence with treatment at 1 year in Asia-Pacific regions.

Methods And Results: We recruited 4664 patients consecutive in- and outpatients with AF who presented to cardiologists in five countries under the Asia-Pacific Heart Rhythm Society (APHRS) in whom 1-year follow-up was completed for 4003 (65.5% male; mean age 68.5 years). Oral anticoagulant (OAC) use remained high, 77% at follow-up, including 17% prescribed a vitamin K antagonist (VKA) and 60% a non-VKA oral anticoagulant (NOAC). At 1-year follow-up, 93% and 88% remained on a VKA or NOAC, respectively. With good adherence to OAC therapy, 1-year mortality was only 2.7%. Most deaths were non-cardiovascular (72.3%) and the 1-year incidence of stroke/transient ischaemic events (TIA) was low (<1%). Hospital readmissions were common for non-cardiovascular cases and atrial tachyarrhythmias. On multivariate analysis, independent baseline predictors of mortality and/or stroke/TIA/peripheral embolism were age, previous heart failure for >12 months, and malignancy. Independent predictors of mortality were age, chronic obstructive pulmonary disease, malignancy, and diuretic use. AF as a primary presentation was predictive of lower mortality and/or stroke/TIA/peripheral embolism as well as mortality.

Conclusion: In this 1-year analysis of the APHRS-AF registry, overall OAC use and persistence were high and were associated with low 1-year cardiovascular mortality and morbidity, but mortality and morbidity related to non-cardiovascular causes were high in AF patients, particularly from malignancy and pneumonia.
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http://dx.doi.org/10.1093/europace/euab327DOI Listing
January 2022

Low-dose aspirin and incidence of lung carcinoma in patients with chronic obstructive pulmonary disease in Hong Kong: A cohort study.

PLoS Med 2022 01 13;19(1):e1003880. Epub 2022 Jan 13.

Cardiology Division, Department of Medicine, The University of Hong Kong-Shen Zhen Hospital, Shenzhen City, Guangdong Province, China.

Background: Evidence suggests that chronic obstructive pulmonary disease (COPD) is associated with a higher risk of lung carcinoma. Using a territory-wide clinical electronic medical records system, we investigated the association between low-dose aspirin use (≤160 mg) among patients with COPD and incidence of lung carcinoma and the corresponding risk of bleeding.

Methods And Findings: This is a retrospective cohort study conducted utilizing Clinical Data Analysis Reporting System (CDARS), a territory-wide database developed by the Hong Kong Hospital Authority. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between aspirin nonusers (35,049 patients) with new aspirin users (7,679 patients) among all eligible COPD patients from 2005 to 2018 attending any public hospitals. The median age of the cohort was 75.7 years (SD = 11.5), and 80.3% were male. Competing risk regression with Cox proportional hazards model were performed to estimate the subdistribution hazard ratio (SHR) of lung carcinoma with low-dose aspirin and the associated bleeding events. Of all eligible patients, 1,779 (4.2%, 1,526 and 253 among nonusers and users) were diagnosed with lung carcinoma over a median follow-up period of 2.6 years (interquartile range [IQR]: 1.4 to 4.8). Aspirin use was associated with a 25% lower risk of lung carcinoma (SHR = 0.75, 95% confidence interval [CI] 0.65 to 0.87, p = <0.001) and 26% decrease in lung carcinoma-related mortality (SHR = 0.74, 95% CI 0.64 to 0.86, p = <0.001). Subgroup analysis revealed that aspirin was beneficial for patients aged above or below 75 years, but was also beneficial among populations who were male, nondiabetic, and nonhypertensive. Aspirin use was not associated with an increased risk of upper gastrointestinal bleeding (UGIB) (SHR = 1.19, 95% CI 0.94 to 1.53, p = 0.16), but was associated with an increased risk of hemoptysis (SHR = 1.96, 95% CI 1.73 to 2.23, p < 0.001). The main limitations of the study were (i) that one group of patients may be more likely to seek additional medical attention, although this was partially mitigated by the use of propensity score analysis; and (ii) the observational nature of the study renders it unable to establish causality between aspirin use and lung carcinoma incidence.

Conclusions: In this study, we observed that low-dose aspirin use was associated with a lower risk of lung carcinoma and lung carcinoma-related mortality among COPD patients. While aspirin was not associated with an increased risk of UGIB, the risk of hemoptysis was elevated.
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http://dx.doi.org/10.1371/journal.pmed.1003880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757901PMC
January 2022

Asian Pacific Society of Cardiology Consensus Recommendations on Dyslipidaemia.

Eur Cardiol 2021 Feb 9;16:e54. Epub 2021 Dec 9.

National Heart Centre Singapore Singapore.

The prevalence of dyslipidaemia has been increasing in the Asia-Pacific region and this is attributed to dietary changes and decreasing physical activity. While there has been substantial progress in dyslipidaemia therapy, its management in the region is hindered by limitations in awareness, adherence and healthcare costs. The Asian Pacific Society of Cardiology (APSC) developed these consensus recommendations to address the need for a unified approach to managing dyslipidaemia. These recommendations are intended to guide general cardiologists and internists in the assessment and treatment of dyslipidaemia and are hoped to pave the way for improving screening, early diagnosis and treatment. The APSC expert panel reviewed and appraised the evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed, which were then put to an online vote. The resulting consensus recommendations tackle contemporary issues in the management of dyslipidaemia, familial hypercholesterolaemia and lipoprotein(a) in the Asia-Pacific region.
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http://dx.doi.org/10.15420/ecr.2021.36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728885PMC
February 2021

Different layers of disease substrates for ventricular tachyarrhythmias in arrhythmogenic right ventricular cardiomyopathy?

Heart Rhythm 2022 Apr 6;19(4):546-547. Epub 2022 Jan 6.

Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Hong Kong-Guangdong Stem Cell and Regenerative Medicine Research Centre, The University of Hong Kong and Guangzhou Institutes of Biomedicine and Health, Hong Kong SAR, China; Cardiac and Vascular Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2021.12.033DOI Listing
April 2022

COVID-19 and Acute Coronary Syndrome: Lessons for Everyone.

Lancet Reg Health West Pac 2022 Feb 22;19:100346. Epub 2021 Dec 22.

Cardiology Division, Department of Medicine, Queen Mary Hospital, the University of Hong Kong, Hong Kong SAR, China.

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http://dx.doi.org/10.1016/j.lanwpc.2021.100346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692128PMC
February 2022

CRISPR-targeted genome editing of human induced pluripotent stem cell-derived hepatocytes for the treatment of Wilson's disease.

JHEP Rep 2022 Jan 30;4(1):100389. Epub 2021 Oct 30.

The Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Background & Aims: Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by loss-of-function mutations in , which encodes a copper-transporting protein. It is characterized by excessive copper deposition in tissues, predominantly in the liver and brain. We sought to investigate whether gene-corrected patient-specific induced pluripotent stem cell (iPSC)-derived hepatocytes (iHeps) could serve as an autologous cell source for cellular transplantation therapy in WD.

Methods: We first compared the phenotype and cellular function of ATP7B before and after gene correction using CRISPR/Cas9 and single-stranded oligodeoxynucleotides (ssODNs) in iHeps (derived from patients with WD) which were homozygous for the ATP7B R778L mutation (ATP7B). Next, we evaluated the therapeutic potential of cellular transplantation of WD gene-corrected iHeps in an immunodeficient WD mouse model ( ; ARG).

Results: We successfully created iPSCs with heterozygous gene correction carrying 1 allele of the wild-type gene (ATP7B) using CRISPR/Cas9 and ssODNs. Compared with ATP7B iHeps, gene-corrected ATP7B iHeps restored ATP7B subcellular localization, its subcellular trafficking in response to copper overload and its copper exportation function. Moreover, cellular transplantation of ATP7B iHeps into ARG mice via intra-splenic injection significantly attenuated the hepatic manifestations of WD. Liver function improved and liver fibrosis decreased due to reductions in hepatic copper accumulation and consequently copper-induced hepatocyte toxicity.

Conclusions: Our findings demonstrate that gene-corrected patient-specific iPSC-derived iHeps can rescue the and disease phenotypes of WD. These proof-of-principle data suggest that iHeps derived from gene-corrected WD iPSCs have potential use as an autologous cell source for therapy of WD as well as other inherited liver disorders.

Lay Summary: Gene correction restored ATP7B function in hepatocytes derived from induced pluripotent stem cells that originated from a patient with Wilson's disease. These gene-corrected hepatocytes are potential cell sources for autologous cell therapy in patients with Wilson's disease.
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http://dx.doi.org/10.1016/j.jhepr.2021.100389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633686PMC
January 2022

Inappropriate rate response in a leadless pacemaker due to automatic rate profile optimization.

Pacing Clin Electrophysiol 2022 Jan 17;45(1):141-144. Epub 2021 Nov 17.

Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.

A three-axis accelerometer sensor is incorporated in a leadless pacemaker (Micra , Medtronic ) for rate adaptation. Three sensor setpoints at lower rate (LR), activity of daily living rate (ADLR), and upper rate (UR) are used to convert detected acceleration to a desired rate response. We describe inappropriate rate acceleration at rest and during chest physiotherapy in a sedentary elderly patient with leadless pacemaker. The underlying mechanism and various programming options are discussed.
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http://dx.doi.org/10.1111/pace.14393DOI Listing
January 2022

Circulating Biomarkers for Cardiovascular Disease Risk Prediction in Patients With Cardiovascular Disease.

Front Cardiovasc Med 2021 1;8:713191. Epub 2021 Oct 1.

Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.

Cardiovascular disease (CVD) is the leading cause of death globally. Risk assessment is crucial for identifying at-risk individuals who require immediate attention as well as to guide the intensity of medical therapy to reduce subsequent risk of CVD. In the past decade, many risk prediction models have been proposed to estimate the risk of developing CVD. However, in patients with a history of CVD, the current models that based on traditional risk factors provide limited power in predicting recurrent cardiovascular events. Several biomarkers from different pathophysiological pathways have been identified to predict cardiovascular events, and the incorporation of biomarkers into risk assessment may contribute to enhance risk stratification in secondary prevention. This review focuses on biomarkers related to cardiovascular and metabolic diseases, including B-type natriuretic peptide, high-sensitivity cardiac troponin I, adiponectin, adipocyte fatty acid-binding protein, heart-type fatty acid-binding protein, lipocalin-2, fibroblast growth factor 19 and 21, retinol-binding protein 4, plasminogen activator inhibitor-1, 25-hydroxyvitamin D, and proprotein convertase subtilisin/kexin type 9, and discusses the potential utility of these biomarkers in cardiovascular risk prediction among patients with CVD. Many of these biomarkers have shown promise in improving risk prediction of CVD. Further research is needed to assess the validity of biomarker and whether the strategy for incorporating biomarker into clinical practice may help to optimize decision-making and therapeutic management.
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http://dx.doi.org/10.3389/fcvm.2021.713191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517145PMC
October 2021

Mendelian Randomization Focused Analysis of Vitamin D on the Secondary Prevention of Ischemic Stroke.

Stroke 2021 12 27;52(12):3926-3937. Epub 2021 Sep 27.

Division of Cardiology, Queen Mary Hospital (Y.-H.C., J.J.H., Y.-K.W., K.-W.A., H.-F.T.), The University of Hong Kong, Hong Kong SAR, China.

Background And Purpose: Experimental studies showed vitamin D (Vit-D) could promote vascular regeneration and repair. Prior randomized studies had focused mainly on primary prevention. Whether Vit-D protects against ischemic stroke and myocardial infarction recurrence among subjects with prior ischemic insults was unknown. Here, we dissected through Mendelian randomization any effect of Vit-D on the secondary prevention of recurrent ischemic stroke and myocardial infarction.

Methods: Based on a genetic risk score for Vit-D constructed from a derivation cohort sample (n=5331, 45% Vit-D deficient, 89% genotyped) via high-throughput exome-chip screening of 12 prior genome-wide association study-identified genetic variants of Vit-D mechanistic pathways (, , and ; F statistic, 73; <0.001), we performed a focused analysis on prospective recurrence of myocardial infarction (MI) and ischemic stroke in an independent subsample with established ischemic disease (n=441, all with prior first ischemic event; follow-up duration, 41.6±14.3 years) under a 2-sample, individual-data, prospective Mendelian randomization approach.

Results: In the ischemic disease subsample, 11.1% (n=49/441) had developed recurrent ischemic stroke or MI and 13.3% (n=58/441) had developed recurrent or de novo ischemic stroke/MI. Kaplan-Meier analyses showed that genetic risk score predicted improved event-free survival from recurrent ischemic stroke or MI (log-rank, 13.0; =0.001). Cox regression revealed that genetic risk score independently predicted reduced risk of recurrent ischemic stroke or MI combined (hazards ratio, 0.62 [95% CI, 0.48-0.81]; <0.001), after adjusted for potential confounders. Mendelian randomization supported that Vit-D is causally protective against the primary end points of recurrent ischemic stroke or MI (Wald estimate: odds ratio, 0.55 [95% CI, 0.35-0.81]) and any recurrent or de novo ischemic stroke/MI (odds ratio, 0.64 [95% CI, 0.42-0.91]) and recurrent MI alone (odds ratio, 0.52 [95% CI, 0.30-0.81]).

Conclusions: Genetically predicted lowering in Vit-D level is causal for the recurrence of ischemic vascular events in persons with prior ischemic stroke or MI.
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http://dx.doi.org/10.1161/STROKEAHA.120.032634DOI Listing
December 2021

Management of adrenoleukodystrophy: From pre-clinical studies to the development of new therapies.

Biomed Pharmacother 2021 Nov 21;143:112214. Epub 2021 Sep 21.

HKUMed Laboratory of Cellular Therapeutics, the University of Hong Kong, Hong Kong; State Key Laboratory of Pharmaceutical Biotechnology, the University of Hong Kong, Hong Kong; Prenatal Diagnostic Centre and Cord Blood Bank, China. Electronic address:

X-linked adrenoleukodystrophy (X-ALD) is an inherited neurodegenerative disorder associated with mutations of the ABCD1 gene that encodes a peroxisomal transmembrane protein. It results in accumulation of very long chain fatty acids in tissues and body fluid. Along with other factors such as epigenetic and environmental involvement, ABCD1 mutation-provoked disorders can present different phenotypes including cerebral adrenoleukodystrophy (cALD), adrenomyeloneuropathy (AMN), and peripheral neuropathy. cALD is the most severe form that causes death in young childhood. Bone marrow transplantation and hematopoietic stem cell gene therapy are only effective when performed at an early stage of onsets in cALD. Nonetheless, current research and development of novel therapies are hampered by a lack of in-depth understanding disease pathophysiology and a lack of reliable cALD models. The Abcd1 and Abcd1/Abcd2 knock-out mouse models as well as the deficiency of Abcd1 rabbit models created in our lab, do not develop cALD phenotypes observed in human beings. In this review, we summarize the clinical and biochemical features of X-ALD, the progress of pre-clinical and clinical studies. Challenges and perspectives for future X-ALD studies are also discussed.
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http://dx.doi.org/10.1016/j.biopha.2021.112214DOI Listing
November 2021

Correction to: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and cardiac arrhythmias: a systematic review and meta‑analysis.

Cardiovasc Diabetol 2021 Sep 4;20(1):177. Epub 2021 Sep 4.

Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Room 1929B/K1931, Block K, Hong Kong, China.

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http://dx.doi.org/10.1186/s12933-021-01371-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418742PMC
September 2021

Association of serum uric acid with biventricular myocardial dysfunction in patients with type 2 diabetes mellitus.

Nutr Metab Cardiovasc Dis 2021 09 29;31(10):2912-2920. Epub 2021 Jun 29.

Division of Cardiology, Department of Medicine, The University of Hong Kong Shenzhen Hospital, Shenzhen, China; Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China. Electronic address:

Background And Aims: Increased serum uric acid (SUA) is common in type 2 diabetes mellitus (T2DM) and is associated with left ventricular (LV) myocardial dysfunction. Nonetheless the association of SUA with right ventricular (RV) function in T2DM has not been studied. This study aimed to investigate the association of SUA with biventricular myocardial function in patients with T2DM.

Methods And Results: A total of 560 patients with T2DM were enrolled and divided into four groups according to sex-specific quartiles of SUA. Transthoracic echocardiography was performed and two-dimensional speckle tracking was used to measure biventricular myocardial strain, including LV global longitudinal strain (GLS), circumferential strain (CS), radial strain (RS), and RV free wall longitudinal strain (RV-FWLS). The absolute value of all biventricular strain parameters showed a stepwise decrease across SUA quartiles (all P < 0.01). In particular, LV assessment by GLS, CS and RS demonstrated that those in the 4th quartile were impaired compared with the other quartiles (all P < 0.05). Similarly, RV-FWLS of the 4th quartile was significantly impaired compared with the 1st and 2nd quartiles (all P < 0.05). The same reduction in biventricular strain across SUA quartiles was observed in patients with estimated glomerular filtration rate < or ≥60 ml/min/1.73 m, and glycated hemoglobin < or ≥7.0% (all P < 0.05). Multivariable linear regression analysis demonstrated that higher quartile of SUA was independently associated with impaired biventricular myocardial strain (all P < 0.05).

Conclusions: SUA was independently associated with biventricular myocardial dysfunction in asymptomatic T2DM patients, regardless of renal function or diabetic control.
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http://dx.doi.org/10.1016/j.numecd.2021.06.012DOI Listing
September 2021

Effect of Berberine on Cardiovascular Disease Risk Factors: A Mechanistic Randomized Controlled Trial.

Nutrients 2021 Jul 26;13(8). Epub 2021 Jul 26.

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Cardiovascular disease (CVD) is a major contributor to the global burden of disease. Berberine, a long-standing, widely used, traditional Chinese medicine, is thought to have beneficial effects on CVD risk factors and in women with polycystic ovary syndrome. The mechanisms and effects, specifically in men, possibly via testosterone, have not been examined previously. To assess the effect of berberine on CVD risk factors and any potential pathway via testosterone in men, we conducted a randomized, double-blind, placebo-controlled, parallel trial in Hong Kong. In total, 84 eligible Chinese men with hyperlipidemia were randomized to berberine (500 mg orally, twice a day) or placebo for 12 weeks. CVD risk factors (lipids, thromboxane A2, blood pressure, body mass index and waist-hip ratio) and testosterone were assessed at baseline, and 8 and 12 weeks after intervention. We compared changes in CVD risk factors and testosterone after 12 weeks of intervention using analysis of variance, and after 8 and 12 weeks using generalized estimating equations (GEE). Of the 84 men randomized, 80 men completed the trial. Men randomized to berberine had larger reductions in total cholesterol (-0.39 mmol/L, 95% confidence interval (CI) -0.70 to -0.08) and high-density lipoprotein cholesterol (-0.07 mmol/L, 95% CI -0.13 to -0.01) after 12 weeks. Considering changes after 8 and 12 weeks together, berberine lowered total cholesterol and possibly low-density lipoprotein-cholesterol (LDL-c), and possibly increased testosterone. Changes in triglycerides, thromboxane A2, blood pressure, body mass index and waist-hip ratio after the intervention did not differ between the berberine and placebo groups. No serious adverse event was reported. Berberine is a promising treatment for lowering cholesterol. Berberine did not lower testosterone but instead may increase testosterone in men, suggesting sex-specific effects of berberine. Exploring other pathways and assessing sex differences would be worthwhile, with relevance to drug repositioning and healthcare.
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http://dx.doi.org/10.3390/nu13082550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401658PMC
July 2021

Importance of attributes and willingness to pay for oral anticoagulant therapy in patients with atrial fibrillation in China: A discrete choice experiment.

PLoS Med 2021 08 26;18(8):e1003730. Epub 2021 Aug 26.

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Background: Adherence to oral anticoagulant therapy in patients with atrial fibrillation (AF) in China is low. Patient preference, one of the main reasons for discontinuation of oral anticoagulant therapy, is an unfamiliar concept in China.

Methods And Findings: A discrete choice experiment (DCE) was conducted to quantify patient preference on 7 attributes of oral anticoagulant therapy: antidote (yes/no), food-drug interaction (yes/no), frequency of blood monitoring (no need, every 6/3/1 month[s]), risk of nonfatal major bleeding (0.7/3.1/5.5/7.8[%]), risk of nonfatal stroke (ischemic/hemorrhagic) or systemic embolism (0.6/3.2/5.8/8.4[%]), risk of nonfatal acute myocardial infarction (AMI) (0.2/1.0/1.8/2.5[%]), and monthly out-of-pocket cost (0/120/240/360 RMB) (0 to 56 USD). A total of 16 scenarios were generated by using D-Efficient design and were randomly divided into 2 blocks. Eligible patients were recruited and interviewed from outpatient and inpatient settings of 2 public hospitals in Beijing and Shenzhen, respectively. Patients were presented with 8 scenarios and asked to select 1 of 3 options: 2 unlabeled hypothetical treatments and 1 opt-out option. Mixed logit regression model was used for estimating patients' preferences of attributes of oral anticoagulants and willingness to pay (WTP) with adjustments for age, sex, education level, income level, city, self-evaluated health score, histories of cardiovascular disease/other vascular disease/any stroke/any bleeding, and use of anticoagulant/antiplatelet therapy. A total of 506 patients were recruited between May 2018 and December 2019 (mean age 70.3 years, 42.1% women). Patients were mainly concerned about the risks of AMI (β: -1.03; 95% CI: -1.31, -0.75; p < 0.001), stroke or systemic embolism (β: -0.81; 95% CI: -0.90, -0.73; p < 0.001), and major bleeding (β: -0.69; 95% CI: -0.78, -0.60; p < 0.001) and were willing to pay more, from up to 798 RMB to 536 RMB (124 to 83 USD) monthly. The least concerning attribute was frequency of blood monitoring (β: -0.31; 95% CI: -0.39, -0.24; p < 0.001). Patients had more concerns about food-drug interactions even exceeding preferences on the 3 risks, if they had a history of stroke or bleeding (β: -2.47; 95% CI: -3.92, -1.02; p < 0.001), recruited from Beijing (β: -1.82; 95% CI: -2.56, -1.07; p < 0.001), or men (β: -0.96; 95% CI: -1.36, -0.56; p < 0.001). Patients with lower educational attainment or lower income weighted all attributes lower, and their WTP for incremental efficacy and safety was minimal. Since the patients were recruited from 2 major hospitals from developed cities in China, further studies with better representative samples would be needed.

Conclusions: Patients with AF in China were mainly concerned about the safety and effectiveness of oral anticoagulant therapy. The preference weighting on food-drug interaction varied widely. Patients with lower educational attainment or income levels and less experience of bleeding or stroke had more reservations about paying for oral anticoagulant therapies with superior efficacy, safety, and convenience of use.
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http://dx.doi.org/10.1371/journal.pmed.1003730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432810PMC
August 2021

Application of Patient-Specific iPSCs for Modelling and Treatment of X-Linked Cardiomyopathies.

Int J Mol Sci 2021 Jul 29;22(15). Epub 2021 Jul 29.

Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Inherited cardiomyopathies are among the major causes of heart failure and associated with significant mortality and morbidity. Currently, over 70 genes have been linked to the etiology of various forms of cardiomyopathy, some of which are X-linked. Due to the lack of appropriate cell and animal models, it has been difficult to model these X-linked cardiomyopathies. With the advancement of induced pluripotent stem cell (iPSC) technology, the ability to generate iPSC lines from patients with X-linked cardiomyopathy has facilitated in vitro modelling and drug testing for the condition. Nonetheless, due to the mosaicism of the X-chromosome inactivation, disease phenotypes of X-linked cardiomyopathy in heterozygous females are also usually more heterogeneous, with a broad spectrum of presentation. Recent advancements in iPSC procedures have enabled the isolation of cells with different lyonisation to generate isogenic disease and control cell lines. In this review, we will summarise the current strategies and examples of using an iPSC-based model to study different types of X-linked cardiomyopathy. The potential application of isogenic iPSC lines derived from a female patient with heterozygous Danon disease and drug screening will be demonstrated by our preliminary data. The limitations of an iPSC-derived cardiomyocyte-based platform will also be addressed.
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http://dx.doi.org/10.3390/ijms22158132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347533PMC
July 2021
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