ORCID Profile
0000-0003-4665-7887
Current Organisation
Aix-Marseille Université
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Publisher: Springer Science and Business Media LLC
Date: 30-10-2017
DOI: 10.1038/NG.3978
Publisher: Massachusetts Medical Society
Date: 05-2014
Publisher: Springer Science and Business Media LLC
Date: 21-02-2014
Abstract: Previous studies suggested that high dietary carbohydrate intake is associated with increased cardiovascular risk through raised triglyceride and decreased high-density lipoprotein-cholesterol levels. However, the relation between carbohydrate intake and arterial stiffness has not been established. The purpose of this study was to examine this relation among high-risk cardiovascular patients. We studied the relation between dietary macronutrient intake and arterial stiffness in 364 patients with documented cardiovascular diseases or risk equivalent (coronary artery diseases 62%, ischemic stroke 13%, diabetes mellitus 55%) and in 93 age-and-sex matched control subjects. Dietary macronutrient intake was assessed using a validated food-frequency questionnaire (FFQ) for Chinese. Heart-ankle pulse wave velocity (PWV) was measured non-invasively with a Vascular Profiling System (VP2000, Colin Corp. USA). A dietary pattern with ≥60% total energy intake derived from carbohydrates was defined as a high-carbohydrate diet according to the Dietary Reference Intakes (DRI) for Chinese. Subjects who consumed a high-carbohydrate diet had significantly higher mean PWV than those who did not consume a high-carbohydrate diet ( P = 0.039 ). After adjustment for potential confounders, high-carbohydrate diet was associated with significantly increased PWV [B = 73.50 (10.81 to 136.19), P = 0.022 ]. However, there was no significant association between high-carbohydrate diet and PWV in controls (P = 0.634). High-carbohydrate diet is associated with increased arterial stiffness in patients with established cardiovascular disease or risk equivalent.
Publisher: Springer Science and Business Media LLC
Date: 22-12-2015
DOI: 10.1038/NCOMMS10206
Abstract: Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance ( P .69 × 10 −7 ), including three Asian-specific coding variants in known genes ( CETP p.Asp459Gly, PCSK9 p.Arg93Cys and LDLR p.Arg257Trp). Furthermore, missense variants at two novel loci— PNPLA3 p.Ile148Met and PKD1L3 p.Thr429Ser — also influence levels of triglycerides and low-density lipoprotein cholesterol, respectively. Another novel gene, TEAD2 , is found to be associated with high-density lipoprotein cholesterol through gene-based association analysis. Most of these newly identified coding variants show suggestive association ( P .05) with CAD. These findings demonstrate that exome-wide genotyping on s les of non-European ancestry can identify additional population-specific possible causal variants, shedding light on novel lipid biology and CAD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2018
DOI: 10.1161/ATVBAHA.118.311726
Abstract: In patients with stable coronary artery disease, conventional risk factors provide limited incremental predictive value for cardiovascular events. We sought to investigate whether a panel of cardiometabolic biomarkers alone or combined with conventional risk factors would exhibit incremental value in the prediction of cardiovascular events. In the discovery cohort, we measured serum adiponectin, A-FABP (adipocyte fatty acid–binding protein), lipocalin-2, FGF (fibroblast growth factor)-19 and 21, plasminogen activator inhibitor-1, and retinol-binding protein-4 in 1166 Chinese coronary artery disease patients. After a median follow-up of 35 months, 170 patients developed new-onset major adverse cardiovascular events (MACE). In the model with age ≥65 years and conventional risk factors, area under the curve for predicting MACE was 0.68. Addition of lipocalin-2 to the age-clinical risk factor model improved predictive accuracy (area under the curve=0.73). Area under the curve further increased to 0.75 when a combination of lipocalin-2, A-FABP, and FGF-19 was added to yield age-biomarkers-clinical risk factor model. The adjusted hazard ratio on MACEs for lipocalin-2, A-FABP, and FGF-19 levels above optimal cutoffs were 2.23 (95% CI, 1.62–3.08), 1.99 (95% CI, 1.43–2.76), and 1.65 (95% CI, 1.15–2.35), respectively. In the validation cohort of 1262 coronary artery disease patients with type 2 diabetes mellitus, the age-biomarkers-clinical risk factor model was confirmed to provide good discrimination and calibration over the conventional risk factor alone for prediction of MACE. A combination of the 3 biomarkers, lipocalin-2, A-FABP, and FGF-19, with clinical risk factors to yield the age-biomarkers-clinical risk factor model provides an optimal and validated prediction of new-onset MACE in patients with stable coronary artery disease.
Publisher: Springer Science and Business Media LLC
Date: 18-07-2018
DOI: 10.1038/S41598-018-29263-3
Abstract: Targeted next generation sequencing of gene panels has become a popular tool for the genetic diagnosis of hypertrophic (HCM) and dilated cardiomyopathy (DCM). However, it is uncertain whether the use of Whole Exome Sequencing (WES) represents a more effective approach for diagnosis of cases with HCM and DCM. In this study, we performed indirect comparisons of the coverage and diagnostic yield of WES on genes and variants related to HCM and DCM versus 4 different commercial gene panels using 40 HCM and DCM patients, assuming perfect coverage in those panels. We identified 6 pathogenic or likely pathogenic among 14 HCM patients (diagnostic yield 43%). 3 pathogenic or likely pathogenic were found among the 26 DCM patients (diagnostic yield 12%). The coverage was similar to that of four existing commercial gene panels due to the clustering of mutation within MYH7, MYBPC3, TPM1, TNT2, and TTN. Moreover, the coverage of WES appeared inadequate for TNNI3 and PLN. We conclude that most of the pathogenic variants for HCM and DCM can be found within a small number of genes which were covered by all the commercial gene panels, and the application of WES did not increase diagnostic yield.
Publisher: Wiley
Date: 25-04-2023
DOI: 10.1111/GCB.16722
Abstract: Warm drylands represent 19% of land surfaces worldwide and host ca. 1100 tree species. The risk of decline due to climate aridification of this neglected bio ersity has been overlooked despite its ecological and societal importance. To fill this gap, we assessed the risk of decline due to climate aridification of tree species in warm drylands based on spatialized occurrence data and climate models. We considered both species vulnerability and exposure, compared the risk of tree species decline across five bioregions and searched for phylogenetic correlates. Depending on the future climate model, from 44% to 88% of warm drylands' tree species will undergo climate aridification with a high risk of decline even under the most optimistic conditions. On a regional scale, the rate of species that will undergo climate aridification in the future varies from 21% in the Old World North, to 90% in Australia, with a risk of decline confirming the high level of risk predicted at the global scale. Using generalized linear mixed models, we found that, species more exposed to climate aridification will be more at risk, but also that species vulnerability is a key driver of their risk of decline. Indeed, the warm drylands specialist species will be less at risk due to climate aridification than species being marginal in warm drylands. We also found that the risk of decline is widespread across the main clades of the phylogeny and involves several evolutionary distinct species. Estimating a high risk of decline for numerous tree species in all warm drylands, including emblematic dryland endemics, our work warns that future increase in aridity could result in an extensive erosion of tree bio ersity in these ecosystems.
Publisher: Oxford University Press (OUP)
Date: 18-10-2015
Abstract: At least 30 million people worldwide carry a diagnosis of atrial fibrillation (AF), and many more suffer from undiagnosed, subclinical, or 'silent' AF. Atrial fibrillation-related cardiovascular mortality and morbidity, including cardiovascular deaths, heart failure, stroke, and hospitalizations, remain unacceptably high, even when evidence-based therapies such as anticoagulation and rate control are used. Furthermore, it is still necessary to define how best to prevent AF, largely due to a lack of clinical measures that would allow identification of treatable causes of AF in any given patient. Hence, there are important unmet clinical and research needs in the evaluation and management of AF patients. The ensuing needs and opportunities for improving the quality of AF care were discussed during the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference in Nice, France, on 22 and 23 January 2015. Here, we report the outcome of this conference, with a focus on (i) learning from our 'neighbours' to improve AF care, (ii) patient-centred approaches to AF management, (iii) structured care of AF patients, (iv) improving the quality of AF treatment, and (v) personalization of AF management. This report ends with a list of priorities for research in AF patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-06-2016
Abstract: We evaluated lipoprotein‐associated phospholipase A 2 (Lp‐ PLA 2 ) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp‐ PLA 2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial. Plasma Lp‐ PLA 2 activity was determined at baseline (n=14 500) at 1 month (n=13 709) serially (n=100) at 3, 6, and 18 months and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp‐ PLA 2 activity levels and outcomes. At baseline, the median Lp‐ PLA 2 level was 172.4 μmol/min per liter (interquartile range 143.1–204.2 μmol/min per liter). Comparing the highest and lowest Lp‐ PLA 2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) for hospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ≈65% persistent reduction in median Lp‐ PLA 2 activity. There were no associations between on‐treatment Lp‐ PLA 2 activity or changes of Lp‐ PLA 2 activity and outcomes, and there were no significant interactions between baseline and on‐treatment Lp‐ PLA 2 activity or changes in Lp‐ PLA 2 activity levels and the effects of darapladib on outcomes. Although high Lp‐ PLA 2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp‐ PLA 2 activity by ≈65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp‐ PLA 2 activity. URL : www.clinicaltrials.gov . Unique identifier: NCT 00799903.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.HLC.2017.05.120
Abstract: The epidemic of atrial fibrillation (AF) is increasingly recognised as a growing health problem worldwide. Although epidemiological studies on AF in the Asia-Pacific region are scarce, given the increasing age and size of populations in this region, the burden of AF is expected to be far greater than in North America and Europe. This is not only due to the growing, ageing population but also an increased incidence of risk factors for AF, such as hypertension, obesity, metabolic syndrome and diabetes, in the Asia-Pacific region. While further, high quality data on such aspects as risk factors, racial disparities and clinical implications is urgently required, there is an immediate need for increased focus on appropriate stroke prophylaxis and risk factor management to minimise the clinical complications and societal burden of AF.
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.HRTHM.2014.12.014
Abstract: Preclinical studies suggest that neuromodulation with thoracic spinal cord stimulation (SCS) improves left ventricular (LV) function and remodeling in systolic heart failure (HF). The purpose of this study was to evaluate the safety and efficacy of a SCS system for the treatment of systolic HF. We performed a prospective, multicenter pilot trial in patients with New York Heart Association (NYHA) class III HF, left ventricular ejection fraction (LVEF) 20%-35%, and implanted defibrillator device who were prescribed stable optimal medical therapy. Dual thoracic SCS leads were used at the T1-T3 level. The device was programmed to provide SCS for 24 hours per day (50 Hz at pulse width 200 μs). We enrolled 22 patients from 5 centers:17 patients underwent implantation of a SCS device and 4 patients who did not fulfill the study criteria served as nontreated controls. No deaths or device-device interactions were noted during the 6-month period in the 17 SCS-treated patients. Fifteen of 17 completed the efficacy endpoint assessments: composite score improved by 4.2 ± 1.3, and 11 patients (73%) showed improvement in ≥4 of 6 efficacy parameters. There was significant improvement in NYHA class (3.0 vs 2.1, P = .002 13/17 improved) Minnesota Living with Heart Failure Questionnaire (42 ± 26 vs 27 ± 22, P = .026 12/17 improved) peak maximum oxygen consumption (14.6 ± 3.3 vs 16.5 ± 3.9 mL/kg/min, P = .013 10/15 improved) LVEF (25% ± 6% vs 37% ± 8%, P<.001 14/16 improved) and LV end-systolic volume (174 ± 57 vs 137 ± 37 mL, P = .002 11/16 improved) but not in N-terminal prohormone brain natriuretic peptide. No such improvements were observed in the 4 nontreated patients. The results of this first-in-human trial suggest that high thoracic SCS is safe and feasible and potentially can improve symptoms, functional status, and LV function and remodeling in patients with severe, symptomatic systolic HF.
Publisher: Oxford University Press (OUP)
Date: 06-08-2015
DOI: 10.1002/STEM.2094
Abstract: Adult mesenchymal stem cells (MSCs) are immunoprivileged cells due to the low expression of major histocompatibility complex (MHC) II molecules. However, the expression of MHC molecules in human-induced pluripotent stem cells (iPSCs)-derived MSCs has not been investigated. Here, we examined the expression of human leukocyte antigen (HLA) in human MSCs derived from iPSCs, fetuses, and adult bone marrow (BM) after stimulation with interferon-γ (IFN-γ), compared their repair efficacy, cell retention, inflammation, and HLA II expression in immune humanized NOD Scid gamma (NSG) mice of hind limb ischemia. In the absence of IFN-γ stimulation, HLA-II was expressed only in BM-MSCs after 7 days. Two and seven days after stimulation, high levels of HLA-II were observed in BM-MSCs, intermediate levels were found in fetal-MSCs, and very low levels in iPSC-MSCs. The levels of p-STAT1, interferon regulatory factor 1, and class II transactivator exhibited similar phenomena. Moreover, p-STAT1 antagonist significantly reversed the high expression of HLA-II in BM-MSCs. Compared to adult BM-MSCs, transplanting iPSC-MSCs into hu-PBMNC NSG mice revealed markedly more survival iPSC-MSCs, less inflammatory cell accumulations, and better recovery of hind limb ischemia. The expression of HLA-II in MSCs in the ischemia limbs was detected in BM-MSCs group but not in iPSC-MSCs group at 7 and 21 days after transplantation. Our results demonstrate that, compared to adult MSCs, human iPSC-MSCs are insensitive to proinflammatory IFN-γ-induced HLA-II expression and iPSC-MSCs have a stronger immune privilege after transplantation. It may attribute to a better therapeutic efficacy in allogeneic transplantation. Stem Cells 2015 :3452–3467
Publisher: American Diabetes Association
Date: 06-04-2017
DOI: 10.2337/DB16-1384
Abstract: Fibroblast growth factor 21 (FGF21) is increasingly recognized as an important metabolic regulator of glucose homeostasis. Here, we conducted an exome-chip association analysis by genotyping 5,169 Chinese in iduals from a community-based cohort and two clinic-based cohorts. A custom Asian exome-chip was used to detect genetic determinants influencing circulating FGF21 levels. Single-variant association analysis interrogating 70,444 single nucleotide polymorphisms identified a novel locus, GCKR, significantly associated with circulating FGF21 levels at genome-wide significance. In the combined analysis, the common missense variant of GCKR, rs1260326 (p.Pro446Leu), showed an association with FGF21 levels after adjustment for age and sex (P = 1.61 × 10−12 β [SE] = 0.14 [0.02]), which remained significant on further adjustment for BMI (P = 3.01 × 10−14 β [SE] = 0.15 [0.02]). GCKR Leu446 may influence FGF21 expression via its ability to increase glucokinase (GCK) activity. This can lead to enhanced FGF21 expression via elevated fatty acid synthesis, consequent to the inhibition of carnitine almitoyl-transferase by malonyl-CoA, and via increased glucose-6-phosphate–mediated activation of the carbohydrate response element binding protein, known to regulate FGF21 gene expression. Our findings shed new light on the genetic regulation of FGF21 levels. Further investigations to dissect the relationship between GCKR and FGF21, with respect to the risk of metabolic diseases, are warranted.
Publisher: Springer Science and Business Media LLC
Date: 15-10-2016
DOI: 10.1007/S00125-016-4132-Z
Abstract: Genome-wide association studies (GWASs) have identified many common type 2 diabetes-associated variants, mostly at the intronic or intergenic regions. Recent advancements of exome-array genotyping platforms have opened up a novel means for detecting the associations of low-frequency or rare coding variants with type 2 diabetes. We conducted an exomechip association analysis to identify additional type 2 diabetes susceptibility variants in the Chinese population. An exome-chip association study was conducted by genotyping 5640 Chinese in iduals from Hong Kong, using a custom designed exome array, the Asian Exomechip. Single variant association analysis was conducted on 77,468 single nucleotide polymorphisms (SNPs). Fifteen SNPs were subsequently genotyped for replication analysis in an independent Chinese cohort comprising 12,362 in iduals from Guangzhou. A combined analysis involving 7189 cases and 10,813 controls was performed. In the discovery stage, an Asian-specific coding variant rs2233580 (p.Arg192His) in PAX4, and two variants at the known loci, CDKN2B-AS1 and KCNQ1, were significantly associated with type 2 diabetes with exome-wide significance (p We identified the association of a PAX4 Asian-specific missense variant rs2233580 with type 2 diabetes in an exome-chip association analysis, supporting the involvement of PAX4 in the pathogenesis of type 2 diabetes. Our findings suggest PAX4 is a possible effector gene of the 7q32 locus, previously identified from GWAS in Asians.
Publisher: Springer Science and Business Media LLC
Date: 31-03-2016
DOI: 10.1038/NRDP.2016.16
Abstract: Atrial fibrillation (AF) is the most common sustained cardiac rhythm disorder, and increases in prevalence with increasing age and the number of cardiovascular comorbidities. AF is characterized by a rapid and irregular heartbeat that can be asymptomatic or lead to symptoms such as palpitations, dyspnoea and dizziness. The condition can also be associated with serious complications, including an increased risk of stroke. Important recent developments in the clinical epidemiology and management of AF have informed our approach to this arrhythmia. This Primer provides a comprehensive overview of AF, including its epidemiology, mechanisms and pathophysiology, diagnosis, screening, prevention and management. Management strategies, including stroke prevention, rate control and rhythm control, are considered. We also address quality of life issues and provide an outlook on future developments and ongoing clinical trials in managing this common arrhythmia.
Publisher: European Respiratory Society (ERS)
Date: 2018
DOI: 10.1183/23120541.00135-2017
Abstract: Current guideline-recommended screening for pulmonary hypertension in patients with systemic sclerosis has not been evaluated in systemic lupus erythematosus (SLE), which is disproportionately prevalent in Asians. This multicentre, cross-sectional screening study aims to study the prevalence of pulmonary hypertension among SLE patients using these guidelines, and identify independent predictors and develop a prediction model for pulmonary hypertension in SLE patients. SLE patients from participating centres will undergo an echocardiography- and biomarker-based pulmonary hypertension screening procedure as in the DETECT study. Standard right heart catheterisation will be provided to patients with intermediate or high echocardiographic probability of pulmonary hypertension. Those with low echocardiographic probability will rescreen within 1 year. The primary measure will be the diagnosis and types of pulmonary hypertension and prevalence of pulmonary hypertension in SLE patients. The secondary measures will be the predictors and prediction models for pulmonary hypertension in SLE patients. The estimated s le size is approximately 895 participants. The results of the SOPHIE study will be an important contribution to the literature of SLE-related pulmonary hypertension and may be immediately translatable to real clinical practice. Ultimately, this study will provide the necessary evidence for establishing universal guidelines for screening of pulmonary hypertension in SLE patients.
No related grants have been discovered for Hung Fat Tse.