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Objectives: It is unclear how metabolomic assessment of biological aging performs in non-White populations and whether such an approach can predict future mortality. We aimed to evaluate the application of serum metabolomics combined with machine learning methodologies to predict incident diabetes and mortality in a Thai population., Design, Setting and Participants: We analyzed serum samples and mortality data over 11 years from among 454 participants with no previous history of diabetes and with a fasting plasma glucose ≥85th percentile (5.4 mmol/L) but <7 mmol/L., Measurements: Untargeted serum metabolomics were assessed using liquid chromatography/mass spectrometry. A deep artificial neural network was used to predict biological age based on serum metabolite profiles and chronological age., Results: The mean age of participants was 40.5 ± 6.4 years, and 70.8% were men. We found a significant positive correlation between metabolomic age and chronological age (r = 0.71, P < 0.001). After 5 years, 61 of 404 participants with available glycated hemoglobin status (15.1%) progressed to diabetes. Chronological age was associated with incident diabetes but was not significant (P = 0.08), after adjusting for BMI and sex. Metabolomic age was significantly related to incident diabetes after controlling for BMI and sex (P < 0.05). Over the 11-year follow-up, 10 participants died owing to non-accidental causes. When metabolomic age and chronological age were included together in the model, metabolomic age (but not chronological age) was associated with mortality, independent of age, sex, and BMI. Among all identifiable metabolites, beta-D-mannosylphosphodecaprenyl and phosphatidylserines were the five leading metabolites associated with mortality., Conclusion: We concluded that serum metabolomic profile was associated with incident diabetes as well as mortality over our 11-year study period, which may render it potentially useful in assessing biological aging in humans., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Mitochondrial dysfunction is a factor potentially contributing to the Aging process. However, evidence surrounding changes in mitochondrial function and aging is still limited; therefore, this study aimed to investigate further the association between them. Possible confounding factors were included in the statistical analysis to explore the possibility of any independent associations. One thousand seven hundred and sixty-nine participants (619 middle-aged adults [age < 65] and 1,150 older adults [age ≥ 65]) from the Electricity Generating Authority of Thailand were enrolled in the study. The clinical characteristics and medical history were collected. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood and used for analysis of mitochondrial function. Several parameters pertinent to mitochondrial respiration including non-mitochondrial respiration, basal respiration, maximal respiration, proton leak, and spare respiratory capacity were found to be two to three times lower in the mitochondria isolated from the cells of older adults. Interestingly, the mitochondrial ATP production was only slightly reduced, and the percentage of coupling efficiency of PBMC mitochondria was significantly higher in the older adult group. The mitochondrial mass and oxidative stress were significantly reduced in older adult participants; however, the ratio of oxidative stress to mass was significantly increased. The association of these parameters with age was still shown to be the same from the outcome of the multivariate analyses. The mitochondrial functions and mitochondrial mass in PBMCs were shown to decline in association with age. However, the upregulation of mitochondrial oxidative stress production and mitochondrial coupling efficiency might indicate a compensatory response in mitochondria during aging., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Higher residential greenness is associated with a lower risk of chronic kidney disease, but evidence on the association between greenness exposure and kidney function has not been conducted. Using cohort data from Electricity Generating Authority of Thailand (EGAT) employees, we investigated the association between long-term exposure to greenness and kidney function using estimated glomerular filtration rate (eGFR) in Bangkok Metropolitan Region (BMR), Thailand. We analyzed data from 2022 EGAT workers (aged 25-55 years at baseline) from 2009 to 2019. The level of greenness was calculated using the satellite-derived Enhanced Vegetation Index (EVI) and Normalized Difference Vegetation Index (NDVI). From 2008 to 2019, the average concentration of each air pollutant (PM 10 , O 3 , NO 2 , SO 2 , and CO) at the sub-district level in BMR was generated using the Kriging method. Long-term exposure for each participant was defined as the 1-year average concentrations before the date of the physical examination in 2009, 2014, and 2019. We employed linear mixed effects models to evaluate associations of NDVI and EVI with eGFR. The robustness of the results was also tested by including air pollutants in the models. After relevant confounders were controlled, the interquartile range increase in NDVI was associated with higher eGFR [1.03% (95%CI: 0.33, 1.74)]. After PM 10 and SO 2 were included in the models, the associations between NDVI and eGFR became weaker. The additions of O 3 , NO 2 , and CO strengthened the associations between them. In contrast, we did not find any association between EVI and eGFR. In conclusion, there was a positive association between NDVI and eGFR, but not for EVI. Air pollutants had a significant impact on the relationship between NDVI and eGFR. Additional research is needed to duplicate this result in various settings and populations to confirm our findings., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Zinc is one of the essential micronutrients in the geriatric population, but the importance of zinc status and dietary zinc intake has been poorly characterized. We aimed to explore the relationships among dietary zinc intake, serum zinc concentrations and multimorbidity in a cross-sectional study of 300 employees of Electric Generating Authority of Thailand aged ≥ 60 years. Comprehensive questionnaires were completed, and clinical and laboratory assessments were performed. Factors associated with low serum zinc concentrations were identified using multivariate multinomial logistic regression analyses. The mean serum zinc level was 80.5 (12.8) µg/dL. After adjustment for baseline characteristics, being female and having been in education for ≤12 years were independent risk factors for the lowest tertile (T1) of serum zinc. After additional adjustment for clinical and biochemical parameters, there was a significant association between depression (Thai Geriatric Depression Scale-15 score > 5) and low serum zinc levels (T1 vs. T3, odds ratio (OR): 2.24; 95% confidence interval (CI): 1.06−4.77). Furthermore, as serum albumin increased, serum zinc concentration substantially increased (T1 vs. T3, OR: 0.01; 95% CI: 0.002−0.070). Therefore, the early detection of risk factors and the further management of depression and low serum albumin may assist physicians in preventing low serum concentrations.

Objective: Universal health coverage can decrease the magnitude of the individual patient's financial burden of chronic kidney disease (CKD), but the residual financial hardship from the patients' perspective has not been well-studied in low and middle-income countries (LMICs). This study aimed to evaluate the residual financial burden in patients with CKD stage 3 to dialysis in the "PD First Policy" under Universal Coverage Scheme (UCS) in Thailand., Methods: This multicenter nationwide cross-sectional study in Thailand enrolled 1,224 patients with pre-dialysis CKD, hemodialysis (HD), and peritoneal dialysis (PD) covered by UCS and other health schemes for employees and civil servants. We interviewed patients to estimate the proportion with catastrophic health expenditure (CHE) and medical impoverishment. The risk factors associated with CHE were analyzed by multivariable logistic regression., Results: Under UCS, the total out-of-pocket expenditure in HD was over two times higher than PD and nearly six times higher than CKD stages 3-4. HD suffered significantly more CHE and medical impoverishment than PD and pre-dialysis CKD [CHE: 8.5, 9.3, 19.5, 50.0% ( p < 0.001) and medical impoverishment: 8.0, 3.1, 11.5, 31.6% ( p < 0.001) for CKD Stages 3-4, Stage 5, PD, and HD, respectively]. In the poorest quintile of UCS, medical impoverishment was present in all HD and two-thirds of PD patients. Travel cost was the main driver of CHE in HD. In UCS, the adjusted risk of CHE increased in PD and HD (OR: 3.5 and 16.3, respectively) compared to CKD stage 3., Conclusions: Despite universal coverage, the residual financial burden remained high in patients with kidney failure. CHE was considerably lower in PD than HD, although the rates remained alarmingly high in the poor. The "PD First' program" could serve as a model for other LMICs. However, strategies to minimize financial distress should be further developed, especially for the poor., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sangthawan, Klyprayong, Geater, Tanvejsilp, Anutrakulchai, Boongird, Gojaseni, Kuhiran, Lorvinitnun, Noppakun, Parapiboon, Sirilak, Tankee, Taruangsri, Sangsupawanich, Sritara, Chaiyakunapruk and Kitiyakara.)

Objectives: To assess cost-effectiveness of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) by pooling incremental net benefits (INBs)., Design: Systematic review and meta-analysis., Setting: We searched PubMed, Scopus and Centre for Evaluation of Value and Risks in Health Registry from inception to December 2019., Participants: Patients with AF., Main Outcome Measures: The INB was defined as a difference of incremental effectiveness multiplied by willing to pay threshold minus the incremental cost; a positive INB indicated favour treatment. These INBs were pooled (stratified by level of country income, perspective, time-horizon, model types) with a random-effects model if heterogeneity existed, otherwise a fixed effects model was applied. Heterogeneity was assessed using Q test and I 2 statistic. Risk of bias was assessed using the economic evaluations bias (ECOBIAS) checklist., Results: A total of 100 eligible economic evaluation studies (224 comparisons) were included. For high-income countries (HICs) from a third-party payer (TPP) perspective, the pooled INBs for DOAC versus VKA pairs were significantly cost-effective with INBs (95% CI) of $6632 ($2961.67 to $10 303.72; I 2 =59.9%), $6353.24 ($4076.03 to $8630.45; I 2 =0%), $7664.58 ($2979.79 to $12 349.37; I 2 =0%) and $8573.07 ($1877.05 to $15 269.09; I 2 =0%) for dabigatran, apixaban, rivaroxaban and edoxaban relative to VKA, respectively but only dabigatran was significantly cost-effective from societal perspective (SP) with an INB of $11 746.96 ($2429.34 to $21 064.59; I 2 =52.4%). The pooled INBs of all comparisons for upper-middle income countries (UMICs) were not significantly cost-effective. The ECOBIAS checklist indicated that risk of bias was mostly low for most items with the exception of five items which should be less influenced on pooling INBs., Conclusions: Our meta-analysis provides comprehensive economic evidence that allows policy makers to generalise cost-effectiveness data to their local context. All DOACs may be cost-effective compared with VKA in HICs with TPP perspective. The pooling results produced moderate to high heterogeneity particularly in UMICs. Further studies are required to inform UMICs with SP., Prospero Registeration Number: CRD 42019146610., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Apolipoprotein A1 (ApoA1) gene polymorphism is linked to high-density lipoprotein cholesterol (HDL-C) levels. Variations in this gene, along with dyslipidemia and inflammation, may increase the risk of vascular stiffness. This study aimed to investigate the link between ApoA1 rs670 genetic variations, various biochemical parameters, and the risk of arterial stiffness in older people., Methods: This population-based cross-sectional study included 355 participants (≥60 years) who completed a demographic and lifestyle information questionnaire. Clinical and anthropometric examination, biochemical analysis, and ApoA1 rs670 genotyping by real-time PCR were performed. The cardio-ankle vascular index (CAVI) was used to assess arterial stiffness., Results: Age, BMI, waist circumference, SBP, LDL-C, and high-sensitivity C-reactive protein (hs-CRP) were associated with high CAVI (≥9) among older people. The mean CAVI (8.19 ± 2.78) for the ApoA1 rs670 AA genotype was lower than that of the GG genotypes (8.94 ± 1.00, p < 0.05). These results are supported by HDL-C (OR = 0.47, 95% CI: 0.24-0.93; p =0.030) and high hs-CRP (OR = 0.30, 95% CI: 0.16-0.57; p =0.006) levels together with adjusted ORs of both variables., Conclusion: ApoA1 rs670 genetic variations involved in the synthesis, transport, and processing of HDLs, hypertension, and inflammation are linked to arterial stiffness. Further studies are required to clarify these mechanisms., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Pruttaya Supajaree et al.)

Background: Percutaneous coronary intervention (PCI) practice and outcomes vary substantially in different parts of the world. The contemporary data of PCI in Asia are limited and only available from developed Asian countries., Objectives: To explore the pattern of practice and results of PCI procedures in Thailand as well as a temporal change of PCI practice over time compared with the registry from other countries., Methods: Thai PCI Registry is a prospective nationwide registry that was an initiative of the Cardiac Intervention Association of Thailand (CIAT). All cardiac catheterization laboratories in Thailand were invited to participate during 2018-2019, and consecutive PCI patients were enrolled and followed up for 1 year. Patient baseline characteristics, procedural details, equipment and medication use, outcomes, and complications were recorded., Results: Among the 39 hospitals participated, there were 22,741 patients included in this registry. Their mean age (standard deviation) was 64.2 (11.7) years and about 70% were males. The most common presentation was acute coronary syndrome (57%) with a high proportion of ST-elevation myocardial infarction (28%). Nearly two-thirds of patients had multivessel disease and significant left main stenosis was reported in 11%. The transradial approach was used in 44.2%. The procedural success rate was very high (95.2%) despite the high complexity of the lesions (56.9% type C lesion). The incidence of procedural complications was 5.3% and in-hospital mortality was 2.8%., Conclusion: Thai PCI Registry provides further insights into the current practice and outcomes of PCI in Southeast Asia. The success rate was very high, and the complications were very low despite the high complexity of the treated lesions., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Nakarin Sansanayudh et al.)

Background: Due to limited access to primary percutaneous coronary intervention for the management of ST-segment elevation myocardial infarction (STEMI) in low-to-middle-income countries (LMICs), fibrinolysis serves as a vital alternative reperfusion therapy. Among fibrinolytic agents, the cost-effectiveness of tenecteplase (TNK) in LMICs as compared to streptokinase (SK) for STEMI management remains unknown., Methods: Cost-effectiveness was analyzed using a hybrid model consisting of short-term analysis (30-days decision tree model) and long-term analysis (Markov model). Both health care provider and societal perspectives over a lifetime horizon with 3% discount rate were considered. Input parameters were obtained from Thailand's national health database, a network meta-analysis and literature review. Outcome measure was an incremental cost-effectiveness ratio (ICER) determined by an incremental cost per quality-adjusted life years (QALY) gain. An ICER of less than $5,590 per QALY gain is considered cost-effective. Series of sensitivity analyses were also performed., Findings: From the societal perspective, TNK increases cost by $827 and increases QALY by 0·173. Thus, the ICER is $4,777 per QALY gained. Similarly, the ICER from health care provider perspective is $4,664 per QALY gained. In the probabilistic sensitivity analysis, using 5,590 USD per QALY as threshold, the probability of TNK being cost-effective was 83% from both perspectives. The most influential parameters were risk ratio of death for treatment with TNK compared to SK and drug cost of TNK., Interpretation: In a resource-limited country like Thailand, tenecteplase is a cost-effective fibrinolytic drug for treatment of STEMI compared to streptokinase., Funding: None., Competing Interests: The authors declare no conflict of interests., (© 2022 The Authors.)

Background: Genome-wide association studies have identified the alpha-ketoglutarate dependent dioxygenase gene (FTO) as the first susceptibility gene of obesity. In the present study, we utilized targeted metabolomics in an attempt to further elucidate mechanisms underlying the action of the FTO gene., Methods: This study was part of a health survey of employees of the Electricity Generating Authority of Thailand ( n = 79, 10 female and 69 male). Targeted metabolomics was performed by liquid chromatography-mass spectrometry using Biocrates AbsoluteIDQ-p180 kit. Genotyping of FTO rs9939609 was performed by real-time PCR (TaqMan™ MGB probes)., Results: Using OPLS-DA variable importance in projection (VIP), tryptophan was found to be among the metabolites with the 10 highest VIP scores. Pearson's correlation analysis showed that kynurenine and tryptophan were positively correlated only in subjects with the rs9939609 A allele ( n  = 32, r  = 0.56, p  < 0.001) and the correlation coefficients were significantly higher in subjects having the A allele than in those without the A allele ( p  < 0.05). Moreover, the kynurenine/tryptophan ratio was significantly associated with the presence of the A allele, independently of body mass index and sex., Conclusions: The FTO gene is likely to influences the conversion of tryptophan to kynurenine., Competing Interests: The authors declare there are no competing interests., (©2022 Chailurkit et al.)

Purpose: Osteoporotic VF is frequently asymptomatic and affects not only women but also men. Identifying patients at risk is essential for early management and prevention. BMD and the TBS are measurements of bone strength and trabecular microarchitecture, respectively. Their role in VF prediction in men is less well-studied. We determined the BMD and TBS predictive ability for osteoporotic VF in men., Methods: A total of 115 male participants of the Electricity Generating Authority of Thailand (EGAT) cohorts without a history of VF who completed the baseline BMD and TBS measurements in 2012 and a thoracolumbar spine radiograph in 2017 were recruited. The VF was assessed using the Genant semiquantitative method. Logistic regression analysis was performed to identify factors associated with the fracture. The area under the receiving operator curve (AUC) was analyzed to define VF predictive ability., Results: Forty subjects (34.78%) had VFs. The unadjusted relative risks (95% confidence interval) for VF for one standard deviation decrease in the TBS and low TBS were 1.319 (1.157-1.506) and 2.347 (1.496-3.682), respectively, and remained significant after BMD and age adjustment. For VF prediction, combined models had a greater AUC than models predicted from a single variable. The use of low TBS, femoral neck BMD, and age provided the best AUC (0.693)., Conclusion: BMD and the TBS could predict osteoporotic VF in male EGAT employees. The use of both BMD and the TBS in the VF prediction process improved predictive ability., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2022 Chaninart Sakulpisuti et al.)

Background: Kidney dysfunction is considered a cardiovascular risk factor. However, few longitudinal studies have examined the effects of air pollution on kidney function. We evaluated associations between long-term air pollution exposure and estimated glomerular filtration rate (eGFR) using data from a cohort of the Electricity Generating Authority of Thailand (EGAT) study in Bangkok Metropolitan Region, Thailand., Methods: This longitudinal study included 1839 subjects (aged 52-71 years in 2002) from the EGAT1 cohort study during 2002-2012. eGFR, based on creatinine, was measured in 2002, 2007, and 2012. Annual mean concentrations of air pollutants (i.e., particulate matter with an aerodynamic diameter ≤10 μm (PM 10 ), ozone (O 3 ), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), and carbon monoxide (CO)) prior to a measurement of creatinine were assessed with the ordinary kriging method. Mixed-effect linear regression models were used to assess associations between air pollutants and eGFR, while controlling for potential covariates. eGFR values are expressed as percent change per interquartile range (IQR) increments of each pollutant., Results: Lower eGFR was associated with higher concentrations of PM 10 (-1.99%, 95% confidence interval (CI): -3.33, -0.63), SO 2 (-4.89%, 95%CI: -6.69, -3.07), and CO (-0.97%, 95%CI: -1.96, 0.03). However, after adjusting for temperature, relative humidity, PM 10 , and SO 2 , no significant association was observed between CO and eGFR., Conclusions: Our findings support the hypothesis that long-term exposure to high concentrations of PM 10 and SO 2 is associated with the progression of kidney dysfunction in subjects of the EGAT cohort study., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: This study compares glycoproteomes in Thai Alzheimer's disease (AD) patients with those of cognitively normal individuals., Methods: Study participants included outpatients with clinically diagnosed AD ( N = 136) and healthy controls without cognitive impairment ( N = 183). Blood samples were collected from all participants for biochemical analysis and for Apolipoprotein E ( APOE ) genotyping by real-time TaqMan PCR assays. Comparative serum glycoproteomic profiling by liquid chromatography-tandem mass spectrometry was then performed to identify differentially abundant proteins with functional relevance., Results: Statistical differences in age, educational level, and APOE ɛ3/ɛ4 and ɛ4/ɛ4 haplotype frequencies were found between the AD and control groups. The frequency of the APOE ɛ4 allele was significantly higher in the AD group than in the control group. In total, 871 glycoproteins were identified, including 266 and 259 unique proteins in control and AD groups, respectively. There were 49 and 297 upregulated and downregulated glycoproteins, respectively, in AD samples compared with the controls. Unique AD glycoproteins were associated with numerous pathways, including Alzheimer's disease-presenilin pathway (16.6%), inflammation pathway mediated by chemokine and cytokine signaling (9.2%), Wnt signaling pathway (8.2%), and apoptosis signaling pathway (6.7%)., Conclusion: Functions and pathways associated with protein-protein interactions were identified in AD. Significant changes in these proteins can indicate the molecular mechanisms involved in the pathogenesis of AD, and they have the potential to serve as AD biomarkers. Such findings could allow us to better understand AD pathology., Competing Interests: The authors report no conflicts of interest associated with this work., (Copyright © 2021 Naphatthakarn Kerdsaeng et al.)

Background: Arterial stiffness, as reflected in the cardio-ankle vascular index (CAVI), is a risk factor for major adverse cardiovascular events (MACEs)., Hypothesis: Combining CAVI and metabolic syndrome (MetS) may enhance prediction of MACEs in a general adult population., Methods: A total of 3807 employees of the Electricity Generating Authority of Thailand were enrolled in a longitudinal health study during 2007-2008. Baseline characteristics were collected and CAVI determined. Subjects with previous coronary artery disease or stroke were excluded from analysis. MetS was defined using the modified NCEP-ATP III for Asians. The primary study endpoint was occurrence of a MACE (myocardial infarction, stroke, or cardiovascular death)., Results: MetS was present in 39.2% at study baseline. The prevalence of CAVI > 9 was higher in subjects with MetS compared to those without (33.7% vs. 28.5%, P = 0.001). During the 12.4 ± 0.6 years follow-up, 227 participants developed MACEs and 350 died. MetS was more common in patients who developed a MACE (8.2% vs. 5.0%, p < 0.001) than was non-MetS, but it was not a significant risk after adjusting covariables. Participants with CAVI > 9 had greater risk for MACEs 1.34 (95% CI: 1.01, 1.79) relative to those with CAVI < 9. Participants with both MetS and CAVI > 9 had the worst outcomes, with the highest frequency of MACEs, among the four groups., Conclusion: Arterial stiffness assessed by CAVI may enhance prediction of future MACEs, adding to the null predictive power of MetS. This index can be used to motivate MetS patients to modify their life-styles for prevention., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Ankle-brachial index (ABI) and cardio-ankle vascular index (CAVI) are surrogate measures of atherosclerosis based on the functional performance of vessels, and are highly related to cardiovascular events. However, only a few longitudinal studies have been conducted on their associations with long-term air pollution exposure., Objective: This study aimed to examine whether long-term air pollution exposure is associated with ABI and CAVI in workers of the Electricity Generating Authority of Thailand (EGAT) in the Bangkok Metropolitan Region (BMR)., Methods: This longitudinal study included 1261 participants (age range, 57-76 years as of 2007) of the EGAT study (2007-2017). ABI and CAVI were measured in 2007, 2012, and 2017. Annual mean concentrations of particulate matter ≤10 μm in diameter (PM 10 ), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), ozone (O 3 ), and carbon monoxide (CO) were estimated by ordinary kriging using data from 22 background and 7 traffic monitoring stations in BMR between 2002 and 2017. Linear mixed-effects models were used to assess associations between air pollution (expressed as 1-year, 3-year, and 5-year average concentration) and ABI and CAVI (expressed as percent changes per interquartile range (IQR) increase in PM 10 , O 3 , NO 2 , SO 2, and CO). We also applied the mixed-effect ordinal logistic models to calculate odds ratios (ORs) of having high or moderate CAVI per an IQR increase in air pollution., Results: After controlling for potential confounders, 1-year average CO was negatively associated with ABI, but not significantly (-0.48%, 95% CI: -1.03, 0.07). Three-year average NO 2 was positively associated with CAVI (6.67%, 95% CI: 0.21, 13.1). In contrast, 1-year average PM 10 was inversely associated with CAVI although the association was not significant. Although not significantly, 1-year average NO 2 and CO were positively associated with prevalence of high or moderate CAVI., Conclusions: Although not statistically significant, long-term NO 2 and CO exposure was associated with ABI and CAVI in the participants of the EGAT study., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

The health effects of saturated fat, particularly tropical oil, on cardiovascular disease are unclear. We investigated the effect of tropical oil (palm and coconut oils), lard, and other common vegetable oils (soybean and rice bran oils) that are widely used in tropical and Asian countries on lipid profiles. We performed an umbrella review of meta-analyses and systematic reviews. Electronic databases (Medline, Scopus, Embase, and Cochrane) were searched up to December 2018 without language restriction. We identified nine meta-analyses that investigated the effect of dietary oils on lipid levels. Replacement of polyunsaturated fatty-acid-rich oils (PUFAs) and monounsaturated FA-rich oils (MUFAs) with palm oil significantly increased low-density lipoprotein cholesterol (LDL-c), by 3.43 (0.44-6.41) mg/dL and 9.18 (6.90-11.45) mg/dL, respectively, and high-density lipoprotein cholesterol (HDL-c), by 1.89 (1.23-2.55) mg/dL and 0.94 (-0.07-1.97) mg/dL, respectively. Replacement of PUFAs with coconut oil significantly increased HDL-c and total cholesterol -by 2.27 (0.93-3.6) mg/dL and 5.88 (0.21-11.55) mg/dL, respectively-but not LDL-c. Substituting lard for MUFAs and PUFAs increased LDL-c-by 8.39 (2.83-13.95) mg/dL and 9.85 (6.06-13.65) mg/dL, respectively-but not HDL-c. Soybean oil substituted for other PUFAs had no effect on lipid levels, while rice bran oil substitution decreased LDL-c. Our findings show the deleterious effect of saturated fats from animal sources on lipid profiles. Replacement of unsaturated plant-derived fats with plant-derived saturated fats slightly increases LDL-c but also increases HDL-c, which in turn may exert a neutral effect on cardiovascular health.

Aim: To prospectively evaluate the association between periodontitis and the incidence of cardiovascular diseases (CVDs) in Thai adults., Materials and Methods: Medical data from the questionnaires and physical examinations of 1850 participants aged 47-73 years from EGAT study were gathered. Random half-mouth periodontal examination of each participant was performed by calibrated periodontists, and periodontal status was defined. The incidence of new CVD events, including coronary heart disease (CHD) and stroke, was verified by cardiologists. The Cox proportional hazard regression model was used to estimate hazard ratios (HRs)., Results: The prevalence of no/mild, moderate and severe periodontitis in the study participants was 11.7%, 52.7% and 35.6%, respectively. During the 13-year follow-up, CVD events occurred in 110 (5.9%) participants, with 82 (4.4%) from CHD and 28 (1.5%) from stroke. After adjusting for cardiovascular risk factors, a significant association between severe periodontitis and the incidence of CHD was found compared with the no/mild periodontitis group with an HR of 4.53 (95% confidence intervals: 1.08-19.02). However, no significant association was seen when considering total CVD events and stroke outcome., Conclusions: This study demonstrates that severe periodontitis is associated with an increased incidence of CHD, independent of established cardiovascular risk factors., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare. Provenance and peer review: Commissioned; externally peer reviewed. This article is part of a series produced in conjunction with WHO and the Alliance for Health Policy Systems and Research with funding from the Doris Duke Charitable Foundation. The BMJ peer reviewed, edited, and made the decision to publish.

Objectives: This study examined the association between alcohol consumption trajectory and deaths due to cancer, cardiovascular diseases (CVDs) and all-cause mortality in Thailand., Design: Data were obtained from a Thai prospective cohort study with more than 30 years of follow-up (n=1961)., Setting: All participants resided in Bangkok and its vicinity., Participants: Employees from the Electricity Generating Authority of Thailand aged between 35 and 54 years old were randomly selected., Main Outcome Measures: Exposure was alcohol consumption trajectory over the study period from 1985 to 2012. The main outcomes were all-cause mortality, and deaths due to cancer and CVDs recorded in national vital registries between 2002 and 2015. Cox's proportional hazard regression was used to determine the associations between alcohol consumption trajectory and each outcome adjusting for sample characteristics, health behaviours and health conditions., Results: From a total of 59 312 person years, 276 deaths were observed. Compared with drinkers who drank occasionally or most occasional over their lifetime, consistent regular or mostly consistent-regular drinkers had higher rates of all-cause mortality (HR: 1.53; 95% CI 1.09 to 2.16) and cancer mortality (HR: 2.05; 95% CI 1.13 to 3.74). The study did not find a significant association between trajectory of alcohol consumption and deaths due to CVDs., Conclusions: Regular drinking of alcohol increased risk for all-cause and cancer mortality. Effective interventions should be implemented to reduce number of regular drinkers in order to saves life of individuals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Statins reduce cardiovascular risk in patients with acute coronary syndrome (ACS) and normal-to-moderately impaired renal function. It is not known whether proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide similar benefit across a range of renal function. We determined whether effects of the PCSK9 inhibitor alirocumab to reduce cardiovascular events and death after ACS are influenced by renal function., Methods and Results: ODYSSEY OUTCOMES compared alirocumab with placebo in patients with recent ACS and dyslipidaemia despite intensive statin treatment. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 was exclusionary. In 18 918 patients, baseline eGFR was 82.8 ± 17.6 mL/min/1.73 m2, and low-density lipoprotein cholesterol (LDL-C) was 92 ± 31 mg/dL. At 36 months, alirocumab decreased LDL-C by 48.5% vs. placebo but did not affect eGFR (P = 0.65). Overall, alirocumab reduced risk of the primary outcome (coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina requiring hospitalization) with fewer deaths. There was no interaction between continuous eGFR and treatment on the primary outcome or death (P = 0.14 and 0.59, respectively). Alirocumab reduced primary outcomes in patients with eGFR ≥90 mL/min/1.73 m2 (n = 7470; hazard ratio 0.784, 95% confidence interval 0.670-0.919; P = 0.003) and 60 to <90 (n = 9326; 0.833, 0.731-0.949; P = 0.006), but not in those with eGFR < 60 (n = 2122; 0.974, 0.805-1.178; P = 0.784). Adverse events other than local injection-site reactions were similar in both groups across all categories of eGFR., Conclusions: In patients with recent ACS, alirocumab was associated with fewer cardiovascular events and deaths across the range of renal function studied, with larger relative risk reductions in those with eGFR > 60 mL/min/1.73 m2., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Asian population are at increased risk of bleeding during the warfarin treatment, so the recommended optimal international normalized ratio (INR) level may be lower in Asians than in Westerners. The aim of this prospective multicenter study was to determine the optimal INR level in Thai patients with non-valvular atrial fibrillation (NVAF)., Methods: Patients with NVAF who were on warfarin for stroke prevention were recruited from 27 hospitals in the nationwide COOL-AF registry in Thailand. We collected demographic data, medical history, risk factors for stroke and bleeding, concomitant disease, electrocardiogram and laboratory data including INR and antithrombotic medications. Outcome measurements included ischemic stroke/transient ischemic attack (TIA) and major bleeding. Optimal INR level was assessed by the calculation of incidence density for six INR ranges (< 1.5, 1.5-1.99, 2-2.49, 2.5-2.99, 3-3.49, and ≥ 3.5)., Results: A total of 2, 232 patients were included. The mean age of patients was 68.5 ± 10.6 years. The mean follow-up duration was 25.7 ± 10.6 months. There were 63 ischemic stroke/TIA and 112 major bleeding events. The lowest prevalence of ischemic stroke/TIA and major bleeding events occurred within the INR range of 2.0-2.99 for patients < 70 years and 1.5-2.99 for patients ≥ 70 years., Conclusions: The INR range associated with the lowest risk of ischemic stroke/TIA and bleeding in the Thai population was 2.0-2.99 for patients < 70 years and 1.5-2.99 for patients ≥ 70 years. The rates of major bleeding and ischemic stroke/TIA were both higher than the rates reported in Western population., (Copyright and License information: Journal of Geriatric Cardiology 2020.)

Diabetic nephropathy, a major complication of diabetes mellitus (DM), is increasing worldwide and the large majority of patients have type 2 DM. Microalbuminuria has been used as a diagnostic marker of diabetic nephropathy. But owing to its insufficient sensitivity and specificity, other biomarkers are being sought. In addition, the pathophysiology of diabetic nephropathy is not fully understood and declines in renal function occur even without microalbuminuria. In this study, we investigated urinary proteins from three study groups (controls, and type 2 diabetic subjects with or without microalbuminuria). Non-targeted label-free Nano-LC QTOF analysis was conducted to discover underlying mechanisms and protein networks, and targeted label-free Nano-LC QTOF with SWATH was performed to qualify discovered protein candidates. Twenty-eight proteins were identified as candidates and functionally analyzed via String DB, gene ontology and pathway analysis. Four predictive mechanisms were analyzed: i) response to stimulus, ii) platelet activation, signaling and aggregation, iii) ECM-receptor interaction, and iv) angiogenesis. These mechanisms can provoke kidney dysfunction in type 2 diabetic patients via endothelial cell damage and glomerulus structural alteration. Based on these analyses, three proteins (kininogen-1, basement membrane-specific heparan sulfate proteoglycan core protein, and roundabout homolog 4) were proposed for further study as potential biomarkers. Our findings provide insights that may improve methods for both prevention and diagnosis of diabetic nephropathy., (Copyright © 2020 Na Nakorn et al.)

Introduction: Data on the long-term outcomes of Asian patients admitted for acute decompensated heart failure is scarce. The objectives of this study were to determine short-term, intermediate-term and long-term survival among patients admitted for acute decompensated heart failure in Thailand, and to identify factors independently associated with increased mortality., Methods: Patients who were admitted with a primary diagnosis of heart failure were enrolled in the Thai Acute Decompensated Heart Failure Registry (ADHERE) from 18 hospitals located across Thailand during 2006. Medical record data was collected according to ADHERE protocol. Mortality data was collected from death certificates on file at the Thailand Bureau of Registration Administration., Results: A total of 1,451 patients were included. The mean age of the patients was 63.7 ± 14.4 years, and 49.7% were male. One-year, five-year and ten-year mortality rates in Thai patients admitted for acute decompensated heart failure were 28.0%, 58.2% and 73.3%, respectively. Independent predictors of increased mortality were identified. There were more cardiovascular-related deaths than non-cardiovascular-related deaths (54.6% vs. 45.4%, respectively)., Conclusions: The ten-year mortality rate in Thai patients admitted for acute decompensated heart failure was 73.3%. Many factors were found to be independently associated with increased mortality, including left ventricular ejection fraction., (Copyright: © Singapore Medical Association.)

Branched-chain amino acids (BCAAs) and lysophosphatidylcholines (LPCs) have been reported to be associated with diabetes. The purpose of the present study was to investigate the relative contributions of BCAAs and LPCs to the progression of prediabetes to diabetes using a targeted metabolomic approach. This study was part of a health survey of employees of the Electricity Generating Authority of Thailand ( n = 79; nine females and 70 males). A targeted metabolomics analysis was performed using an AbsoluteIDQ ® p180 kit, flow injection analysis, and liquid chromatography-tandem mass spectrometry. The highest variable importance in projection (VIP) scores for the progression to diabetes of the amino acids and phospholipids were associated with isoleucine and LPC acyl C28:1, respectively. Using logistic regression analysis, we found that high baseline isoleucine concentration was associated with a higher incidence of diabetes, while high LPC acyl 28:1 was associated with a lower incidence. Isoleucine and LPC acyl 28:1 were independently associated with incident diabetes in a model that also included conventional risk factors for diabetes (baseline fasting plasma glucose (FPG), age, sex, and body mass index (BMI)). In addition, isoleucine and LPC acyl 28:1 were independently associated with serum HbA1c 5 years later in a robust regression model that also included baseline FPG, age, sex, and BMI. Isoleucine, LPC acyl 28:1, age, and FPG were significantly associated with HbA1c at this time. In conclusion, these results provide evidence that isoleucine and LPC acyl C28:1 have respective positive and negative independent associations with incident diabetes.

Inhaled sodium nitrite has been reported to decrease pulmonary artery pressure in hemoglobin E/β-thalassemia (HbE/β-thal) patients with pulmonary hypertension. This study investigated the pharmacokinetics and pharmacodynamics of inhaled nebulized sodium nitrite in 10 healthy subjects and 8 HbE/β-thal patients with high estimated pulmonary artery pressure. Nitrite pharmacokinetics, fraction exhaled nitric oxide (FE NO ), estimated right ventricular systolic pressure (eRVSP) measured by echocardiography, and platelet activation were determined. Nebulized sodium nitrite at doses used in this study (37.5 and 75 mg for healthy subjects and 15 mg for HbE/β-thal patients) was well tolerated and did not cause changes in methemoglobin levels and systemic blood pressure. Absorption of inhaled nitrite was rapid with the absolute bioavailability of 18%. In whole blood, nitrite exhibited the dose-independent pharmacokinetics with clearance (CL) of 1.5 l/h/kg, volume of distribution (V d ) of 1.3 l/kg and half-life (t 1/2 ) of 0.6 h. CL and V d of nitrite was higher in red blood cells (RBC) than whole blood and plasma. HbE/β-thal patients had lower nitrite CL and longer t 1/2 in RBC than healthy subjects. FE NO increased immediately after inhalation. Following nitrite inhalation, eRVSP remained unchanged but platelet activation was suppressed as evidenced by inhibition of adenosine diphosphate (ADP)-induced P-selectin expression and increase in phosphorylated vasodilator-stimulated phosphoprotein (P-VASP Ser239 ) in platelets. There were no changes in markers of oxidative and nitrosative stress after inhalation. Our results support further development of inhaled nebulized sodium nitrite for treatment of pulmonary hypertension in β-thalassemia., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin-kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI., Methods and Results: Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77-0.99; P = 0.032) and Type 2 (0.77, 0.61-0.97; P = 0.025), but not Type 4 MI., Conclusion: After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: The roles of genes in the renin-angiotensin-aldosterone system (RAAS) in hypertension, including angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II receptor type 1 (AGTR1), and aldosterone synthase (CYP11B2), have been widely studied across different ethnicities, but there has been no such investigation in Thai population., Materials and Methods: Using 4,150 Thais recorded in the Electricity Generating Authority of Thailand (EGAT) study, we examined the association of rs1799752, rs699, rs5186, and rs1799998 located in or near ACE , AGT , AGTR1 , and CYP11B2 genes in hypertension. We investigated their roles in hypertension using multivariate logistic regression and further examined their roles in blood pressure (BP) using quantile regression. Sex, age, and BMI were adjusted as potential confounders., Results: We did not observe associations between hypertension and rs1799752 ( P =0.422), rs699 ( P =0.36), rs5186 ( P =0.49), and rs1799998 ( P =0.71). No evidence of association between these SNPs and BP was found across an entire distribution. A nonlinear relationship between age and BP was observed., Conclusion: In Thai population, our study showed no evidence of association between RAAS-related genes and hypertension. While our study is the first and largest study to investigate the role of RAAS-related genes in hypertension in Thai population, restricted statistical power due to limited sample size is a limitation., Competing Interests: All authors declare no conflicts of interest.

Spinal muscular atrophy (SMA) is one of the leading causes of death in infants and young children from heritable diseases. Patients diagnosed with SMA develop symmetrical progressive muscle weakness and atrophy from degeneration of alpha motor neurons. Approximately 95% of patients have a homozygous deletion of survival motor neuron 1 (SMN1) gene in exon 7 and inherited in autosomal recessive pattern. Considering the high prevalence of SMA carrier in many population, it is possible that SMA is one of the most common autosomal recessive disorders in Thailand and Southeast Asia. In this study, we analyzed DNA from peripheral blood of 505 healthy Thai adults using quantitative PCR-based for SMN1 gene exon 7 copy number analysis. Individual samples with heterozygous deletion of SMN1 gene were confirmed with MLPA. The result identified 9 samples (1.78%) with heterozygous deletion and 39 samples as more than 2 copies of SMN1. No homozygous deletion was detected in the samples. In conclusion, we established carrier frequency of SMA in selected Thai population at 1.8% from 505 participants. The prevalence coincides with prevalence in East Asia and Caucasian population. The result could be implemented for SMA carrier screening in couples at risk in the region.

Aim: This cross-sectional study examined the associations between periodontitis and the serum cardiac biomarkers-soluble ST2 (sST2) and C-reactive protein (CRP)-in systemically healthy adults., Materials and Methods: Periodontitis severity was determined using mean probing depth (PD) or clinical attachment level (CAL) and a categorical variable (no/mild, moderate, or severe). Oral hygiene was evaluated using plaque scores. Regression analyses assessed the associations between periodontal variables and sST2 or CRP levels, adjusting for age, sex, smoking, body mass index, systolic blood pressure, fasting plasma glucose, and high-density or low-density lipoprotein cholesterol., Results: The study population comprised 799 individuals, aged 50-73 years. After multivariable adjustment, greater mean PD/CAL, severe periodontitis, and poor oral hygiene were associated with elevated sST2 and CRP levels (p < 0.05). Greater mean PD or CAL was associated with increased odds of having sST2 in the top quintile (>22.7 μg/L) (odds ratio [OR] [95% confidence interval (CI)]: 1.7 [1.1-2.4] and 1.3 [1.1-1.7], respectively) and CRP > 3 mg/L (OR: 1.5 [1.1-2.1] and 1.3 [1.0-1.5], respectively). Individuals with poor oral hygiene were more likely to have sST2 > 22.7 μg/L (OR: 2.0 [1.0-4.0]) and CRP > 3 mg/L (OR: 2.0 [1.1-3.5]), compared to those with good oral hygiene., Conclusions: Periodontitis and poor oral hygiene were associated with elevated serum sST2 and CRP levels., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: To determine sequences and magnitude of causality among periodontitis, diabetes and chronic kidney disease (CKD) by mediation analysis., Methods: Ten-year-data were retrieved from the Electric Generation Authority of Thailand (EGAT) study. A cohort of 2,635 subjects was identified with no CKD at baseline. The interested outcome was CKD incidence defined as glomerular filtration rate <60 ml/min/1.73 m 2 . The percentage of proximal sites with clinical attachment loss ≥5 mm was used to represent periodontitis. Mediation analysis with 1,000-replication bootstrapping was applied to two causal diagrams, diagram A (Periodontitis → Diabetes → CKD) and diagram B (Diabetes → Periodontitis → CKD)., Results: The cumulative incidence of CKD was 10.3 cases per 100 persons during 10-year period. In diagram A, each increasing percentage of proximal sites with severe periodontitis increased the adjusted odds ratio of CKD 1.010 (95% CI: 1.005, 1.015) and 1.007 (95% CI: 1.004, 1.013), by direct and indirect effect through diabetes, respectively. In diagram B, diabetes increased the odds of CKD twofold, with 6.5% of this effect mediated via periodontitis., Conclusions: Periodontitis had significant direct effect, and indirect effect through diabetes, on the incidence of CKD. Awareness about systemic morbidities from periodontitis should be emphasized., (© 2019 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.)

Aims: Nearly 60% of the world's population lives in Asia but little is known about the characteristics and outcomes of Asian patients with heart failure with reduced ejection fraction (HFrEF) compared to other areas of the world., Methods and Results: We pooled two, large, global trials, with similar design, in 13 174 patients with HFrEF (patient distribution: China 833, India 1390, Japan 209, Korea 223, Philippines 223, Taiwan 199 and Thailand 95, Western Europe 3521, Eastern Europe 4758, North America 613, and Latin America 1110). Asian patients were younger (55.0-63.9 years) than in Western Europe (67.9 years) and North America (66.6 years). Diuretics and devices were used less, and digoxin used more, in Asia. Mineralocorticoid receptor antagonist use was higher in China (66.3%), the Philippines (64.1%) and Latin America (62.8%) compared to Europe and North America (range 32.8% to 49.6%). The rate of cardiovascular death/heart failure hospitalization was higher in Asia (e.g. Taiwan 17.2, China 14.9 per 100 patient-years) than in Western Europe (10.4) and North America (12.8). However, the adjusted risk of cardiovascular death was higher in many Asian countries than in Western Europe (except Japan) and the risk of heart failure hospitalization was lower in India and in the Philippines than in Western Europe, but significantly higher in China, Japan, and Taiwan., Conclusion: Patient characteristics and outcomes vary between Asia and other regions and between Asian countries. These variations may reflect several factors, including geography, climate and environment, diet and lifestyle, health care systems, genetics and socioeconomic influences., (© 2018 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Hypercholesterolemia is a major risk factor for cardiovascular events in patients with established atherosclerotic disease (EAD) and in those with multiple risk factors (MRFs). This study aimed to investigate the rate of optimal low-density lipoprotein (LDL) cholesterol level in a multicenter registry of patients at high risk for cardiovascular events., Methods: A multicenter registry of EAD and MRF patients was conducted. Demographic data, medical history, cardiovascular risk factors, anthropometric data, laboratory data, and medications were recorded and analyzed. We classified patients according to target LDL levels based on recommendation by the European Society of Cardiology (ESC) 2011 into Group 1 which is EAD and diabetes or chronic kidney disease (CKD)-target LDL below 70 mg/dL, and Group 2 which is MRF without diabetes or CKD-target LDL below 100 mg/dL. The rate of optimal LDL level in patients with Group 1 and Group 2 was analyzed and stratified according to the treatment pattern of lipid-lowering medications., Results: A total of 3100 patients were included. Of those, 51.7% were male. Average age was 65.8 ± 9.7 years. Average LDL level was 96.3 ± 32.6 mg/dL. A vast majority (92.7%) received statin and 9.3% received ezetimibe. Optimal LDL level was achieved in 20.3% of patients in Group 1 (LDL < 70 mg/dL), and in 46.6% in Group 2 (LDL < 100 mg/dL). The overall rate of optimal LDL control was 23% since 89.6% of study population belongs to Group 1. The rate of optimal LDL was not different between high and low potency statin. Factors that were associated with optimal LDL control were older age, the presence of coronary artery disease or peripheral artery disease., Conclusions: The rates of optimal LDL level were unacceptably low in this study population. As such, a strategy to improve LDL control in high-risk population should be implemented.

Background Anticoagulation in patients with malignancy and atrial fibrillation is challenging because of enhanced risks for thrombosis and bleeding and the frequent need for invasive procedures. Data on direct oral antagonists in such patients are sparse. Methods and Results The ENGAGE AF - TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction Study 48) trial randomized 21 105 patients with atrial fibrillation to edoxaban or warfarin. Patients with malignancy, defined as a postrandomization new diagnosis or recurrence of remote cancer, were followed up over a median of 2.8 years. Adjusted Cox proportional hazard models were used to evaluate the safety and efficacy of edoxaban versus warfarin. Over a median of 495 days (interquartile range, 230-771 days), 1153 patients (5.5%) were diagnosed with new or recurrent malignancy, most commonly involving the gastrointestinal tract (20.6%), prostate (13.6%), and lung (11.1%). Malignancy was associated with increased risk of death (adjusted hazard ratio [HR], 3.12; 95% confidence interval [CI], 2.78-3.50) and major bleeding (adjusted HR, 2.45; 95% CI, 2.07-2.89), but not stroke/systemic embolism (adjusted HR, 1.08; 95% CI, 0.83-1.42). Relative outcomes with higher-dose edoxaban versus warfarin were consistent regardless of malignancy status for stroke/systemic embolism ( HR , 0.60 [95% CI, 0.31-1.15] for malignancy versus HR , 0.89 [95% CI, 0.76-1.05] for no malignancy; interaction P=0.25) and major bleeding ( HR , 0.98 [95% CI, 0.69-1.40] for malignancy versus HR , 0.79 [95% CI, 0.69-1.05] for no malignancy; interaction P=0.31). There was, however, a significant treatment interaction for the composite ischemic end point (ischemic stroke/systemic embolism/myocardial infarction), with greater efficacy of higher-dose edoxaban versus warfarin in patients with malignancy ( HR , 0.54; 95% CI, 0.31-0.93) compared with no malignancy ( HR , 1.02; 95% CI, 0.88-1.18; interaction P=0.026). Conclusions In patients with atrial fibrillation who develop malignancy, the efficacy and safety profile of edoxaban relative to warfarin is preserved, and it may represent a more practical alternative.

Pulmonary hypertension is a life-threatening complication in β-thalassemia. Inhaled sodium nitrite has vasodilatory effect on pulmonary vasculature. However, its effect on pulmonary artery pressure (PAP) in β-thalassemia subjects with pulmonary hypertension has never been reported. In this study, we investigated the change in PAP during inhalation of sodium nitrite in 5 β-thalassemia patients. We demonstrated that sodium nitrite administered by nebulization rapidly decreased PAP as measured by echocardiography and right heart catheterization. The effect of nitrite was short as PAP returned to baseline at end of inhalation. Our findings support acute pulmonary vasodilation effect of nitrite in β-thalassemia with pulmonary hypertension., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Atherosclerotic cardiovascular disease is a global health burden. However, there are heterogeneities among countries or regions in the risk factors and clinical manifestations of atherosclerotic diseases as well as management patterns., Methods: We collected data from 25 centres in Thailand. Patients with documented coronary artery disease, cerebrovascular disease or peripheral arterial disease, or with at least three atherosclerosis risk factors were enrolled between April 2011 and March 2014. Data on demographics, atherosclerosis risk factors and the management pattern of risk factors, including laboratory findings, were recorded., Results: In total, 9,390 patients, including 4,861 patients with established atherosclerotic disease and 4,529 patients with multiple risk factors, were enrolled. The modifiable risk factors, other than current smoking habit (5.3%), were common: hypertension (83.8%), dyslipidaemia (85.9%) and diabetes mellitus (57.4%). A majority of patients with hypertension (96.3%), dyslipidaemia (93.8%) and diabetes mellitus (78.5%) received medications for their conditions. Antiplatelet agents were given to 73.9% of patients. The undertreatment rate of cardiovascular risk factors, such as blood pressure, low-density lipoprotein cholesterol, haemoglobin A1c and smoking status, was 35.8%, 59.0%, 45.3% and 5.3%, respectively., Conclusion: Conventional atherosclerosis risk factors were common among Thai patients with established atherosclerotic disease. Even though most of the patients received recommended treatments according to established guidelines, a significant proportion of them were undertreated for atherosclerosis risk factors., (Copyright: © Singapore Medical Association)

Background: Asians have among the highest prevalence of chronic kidney disease (CKD) or end-stage renal disease in the world. A risk score capable of identifying high risk individuals at the primary care level could allow targeted therapy to prevent future development of CKD. Risk scores for new CKD have been developed in US general populations, but the impact of various risks factors for development of CKD may differ in Asian subjects. In this study, we aimed to develop risk models and simplified risk scores to predict the development of decreased glomerular filtration rate (GFR) at 10 years in an Asian general population using readily obtainable clinical and laboratory parameters., Methods: Employees of EGAT (The Electric Generating Authority of Thailand) were studied prospectively. Multivariable logistic regression models were used to assess risk factors and used to derive risk models and risk scores for developing decreased GFR at 10 years: Model 1 (Clinical only), Model 2 (Clinical + Limited laboratory tests), and Model 3 (Clinical + Full laboratory tests). The performance of the risk models or risk scores to predict incident cases with decreased GFR were evaluated by tests of calibration and discrimination., Results: Of 3186 subjects with preserved GFR (eGFR ≥60) at baseline, 271 (8.5%) developed decreased GFR (eGFR < 60) at 10 years. Model 1 (Age, sex, systolic blood pressure, history of diabetes, and waist circumference) had good performance (χ 2  = 9.02; AUC = 0.72). Model 2 (Age, Sex, systolic blood pressure, diabetes, glomerular filtration rate) had better discrimination (χ 2  = 10.87, AUC = 0.79) than Model 1. Model 3 (Model 2+ Uric acid, Hemoglobin) did not provide significant improvement over Model 2. Based on these findings, simplified categorical risk scores were developed for Models 1 and 2., Conclusions: Clinical or combined clinical and laboratory risk models or risk scores using tests readily available in a resource-limited setting had good accuracy and discrimination power to estimate the 10-year probability of developing decreased GFR in a Thai general population. The benefits of the risk scores in identifying high risk individuals in the Thai or other Asian communities for special intervention requires further studies.

Objective: Although several guidelines emphasized the importance of atherosclerotic risk factor management in peripheral arterial disease (PAD) in diabetic patients to reduce the cardiovascular mortality, authors do not know to what extent physicians follow these guidelines., Material and Method: Between May 2014 and August 2014, consecutive eligible outpatients, aged ≥45 years with established DM, were invited to be involved in this study. History, physical exam and laboratory test were reviewed. Ankle brachial index ≤0.9 was considered PAD. Then patients were evaluated the percentage of risk factor control according to American Heart Association (AHA) criteria. The good control was defined that patients have adequate risk factor control between 3-5 factors., Results: 2,247 diabetic patients were recruited for the study. 286 patients out of 2,247 were diagnosed PAD (12.7%). 236 PAD patients (82.5%) did not have any symptom of intermittent claudication, rest pain, gangrene or ulcer. According to AHA criteria, the percentage of adequate control in low density lipoprotein, HbA1C and systolic blood pressure in PAD patients was 18.9, 30.1 and 33.2% respectively. 49.8% in PAD patients had met our good risk factor control criteria., Conclusion: Most PAD in diabetic patients was asymptomatic. The atherosclerotic risk factor control was poor in this group.

Background: Coronary artery disease (CAD) is a leading cause of death in elderly because aging is the important non-modifiable risk factors of atherosclerosis and also a predictor of poor outcomes. Underuse of guideline directed therapy may contribute to suboptimal risk factor control and worse outcomes in the elderly. We aimed to explore the management of CAD, risk factors control as well as goal attainment in elderly compared to nonelderly CAD patients., Methods: The CORE-Thailand is an ongoing multicenter, prospective, observational registry of patients with high atherosclerotic risk in Thailand. The data of 4120 CAD patients enrolled in this cohort was analyzed comparing between the elderly (age ≥ 65 years) vs. nonelderly (age < 65 years)., Results: There were 2172 elderly and 1948 nonelderly patients. The elderly CAD patients had higher prevalence of hypertension, dyslipidemia, atrial fibrillation and chronic kidney disease. The proportion of patients who received coronary revascularization was not different between the elderly and nonelderly CAD patients. Antiplatelets were prescribed less in the elderly while statin was prescribed in the similar proportion. Goal attainments of risk factor control of glycemic control, low density lipoprotein cholesterol, and smoking cessation except the blood pressure goal were higher in the elderly CAD patients., Conclusions: The CORE-Thailand registry showed the equity in the treatment of CAD between elderly and non-elderly. Elderly CAD patients had higher rate of goal attainment in risk factor control except blood pressure goal. The effects of goal attainment on cardiovascular outcomes will be demonstrated from ongoing cohort.

Aim: There are limited data on the risks of chronic kidney disease (CKD) in Southeast Asian populations. Several GFR estimating equations have been developed in diverse Asian populations, but they produce markedly discrepant results. We investigated the impact of Asian equations on the mortality risk of CKD in a Thai cohort during long term follow-up, and explored the differences between equations grouped according to the reference GFR methods used to develop them., Methods: Employees of the Electricity Generating Authority of Thailand (n = 3430) were enrolled in a health survey and followed up for 22 years. The risks for all-cause mortality for each GFR stage classified by CKD-EPI or different Asian equations were assessed by using Cox proportional hazard models., Results: Equations derived from DTPA clearance (Chinese MDRD, Thai GFR, Singapore CKD-EPI) produced higher GFR, whereas equations from inulin clearance (Japanese CKD-EPI, Taiwan MDRD or Taiwan CKD-EPI) produced lower GFR compared to CKD-EPI. (Average ΔGFR: inulin, -14.9 vs. DTPA +5.80 mL/min per 1.73 m(2) , P < 0.001). CKD prevalence varied widely (0.7 to 24 %) with inulin-based equations being higher than DTPA-based. GFR stage concordance was over 80% for equations using similar reference method compared to less than 40% between inulin and DTPA-based equations. Low GFR (<45) was an independent mortality risk factor when DTPA-based equations were used, but not when inulin-based equations were used., Conclusion: Chronic kidney disease prevalence and prognosis in Thais varied widely depending on the equation used. Differences in the reference GFR methods could be an important cause for the discrepancies between Asian equations., (© 2015 Asian Pacific Society of Nephrology.)

Background: Mean platelet volume (MPV) correlates with platelet activation and has recently emerged as a potential marker of cardiovascular diseases. Previous publications also suggest possible association between MPV and some cardiovascular risk factors but the evidences are still conflicting and inconclusive., Objective: To study the association between MPV and cardiovascular risk factors., Methods: This is a cross-sectional study using data from the second survey of the Electricity Generating Authority of Thailand (EGAT) cohort. All participants of the survey who had results of MPV were included. Exclusion criteria included subjects with known hematologic disease or subjects with hematocrit <30% or platelet count <140,000/mm(3). The details of cardiovascular risk factors were documented and the association between MPV and risk factors was analyzed using fractional polynomial regression analysis., Results: There were 2727 subjects with MPV results. After excluding those who had hematologic disease, 2642 subjects were included for analysis. Univariate analysis revealed that gender, diabetes, serum triglyceride, hypertension, and prehypertension were associated with MPV. Hematocrit, platelet count and fasting plasma glucose were inversely correlated with MPV. After adjusting with other variables, the risk factors that remained significantly associated with MPV included female gender, diabetes, metabolic syndrome, serum triglyceride, hypertension, and prehypertension. Platelet count and hematocrit were found to have significant inverse correlation with MPV., Conclusion: After adjusting for other cardiovascular risk factors, the independent factors remain associated with MPV included female gender, diabetes, metabolic syndrome, serum triglyceride, hypertension and prehypertension. MPV has significant, but inverse association with platelet count and hematocrit., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Vitamin D deficiency, a major public-health worldwide, is associated with hyperuricemia but casual association is questioned. The study was conducted to determine potential causal associations between 25-hydroxy vitamin D (25(OH)D) and uric acid (UA). A cross-sectional study of the Electricity Generating Authority of Thailand (EGAT3) cohort was conducted. Subjects (n = 2,288) were used to genotype the group-specific component (GC) at rs2282679 and ATP-binding cassette subfamily G member 2 (ABCG2) at rs2231142. Mediation analysis with 1000-replication bootstrap was applied to construct causal pathways i.e., rs2282679 → 25(OH)D → UA and rs2231142 → UA → 25(OH)D: The mediator (i.e., 25(OH)D and UA) was firstly regressed on the studied gene (i.e., rs2282679 and rs2231142). A potential causal effect of C allele on UA through 25(OH)D was -0.0236 (95% CI: -0.0411, -0.0058), indicating every minor C allele resulted in decreasing the 25(OH)D and then significantly decreased the UA by 0.0236 unit. For the second pathway, the mediation effect was 0.0806 (95% CI: 0.0107, 0.1628); every T allele copy for rs2231142 increased UA and thus increased 25(OH)D by 0.0806 unit. Our study suggested potential causal associations between the GC gene and UA through the 25(OH)D mediator, and the ABCG2 and the 25(OH)D through the UA mediator but the absolute effects are very clinically small.

Hypertension incurs a significant healthcare burden in Asia-Pacific countries, which have suboptimal rates of blood pressure (BP) treatment and control. A consensus meeting of hypertension experts from the Asia-Pacific region convened in Hanoi, Vietnam, in April 2013. The principal objectives were to discuss the growing problem of hypertension in the Asia-Pacific region, and to develop consensus recommendations to promote standards of care across the region. A particular focus was recommendations for combination therapy, since it is known that most patients with hypertension will require two or more antihypertensive drugs to achieve BP control, and also that combinations of drugs with complementary mechanisms of action achieve BP targets more effectively than monotherapy. The expert panel reviewed guidelines for hypertension management from the USA and Europe, as well as individual Asia-Pacific countries, and devised a treatment matrix/guide, in which they propose the preferred combination therapy regimens for patients with hypertension, both with and without compelling indications. This report summarizes key recommendations from the group, including recommended antihypertensive combinations for specific patient populations. These strategies generally entail initiating therapy with free drug combinations, starting with the lowest available dosage, followed by treatment with single-pill combinations once the BP target has been achieved. A single reference for the whole Asia-Pacific region may contribute to increased consistency of treatment and greater proportions of patients achieving BP control, and hence reducing hypertension-related morbidity and mortality.

Objective: The outcome of patients hospitalized for atrial fibrillation (AF) is relatively poor. We sought to determine the mortality rate and predictors of mortality following hospitalization for AF and to evaluate whether the CHA2DS2-VASc score was a predictor of mortality., Methods: We examined the national database of Thailand residents who registered for government provided health insurance in 2005 and reviewed patient records from 2005 to 2010 to determine all-cause mortality. A total of 8981 patients (mean age, 65 years; 42% male) were admitted to the hospital with a diagnosis of AF. Data on demographics and comorbidities were retrieved from the database. The CHA2DS2-VASc score was calculated for each patient., Results: The hospitalization rate for AF was 15.5 per 100,000 person-years. The two most common comorbidities were hypertension (N=1638, 18.2%) and diabetes (N=1349, 15.0%). The average CHA2DS2-VASc score for all patients was 1.8. By the 72-month follow-up (average 46 months), 3948 patients (44.0%) had died. The CHA2DS2-VASc score was directly related to the mortality rate (P log-rank <0.0001). Multivariate analysis showed that a CHA2DS2-VASc score ≥ 6 (hazard ratio [HR] 2.2, 95% confidence interval [CI], 1.4-3.7, P=0.002) and the presence of chronic kidney disease (HR 2.0, 95% CI 1.7-2.4, P<0.0001) were the strongest predictors of death., Conclusion: The outcome after hospitalization for AF is relatively poor. The CHA2DS2-VASc score is an independent prognostic marker of poor outcomes following hospitalization for AF., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

ST2 is a member of the interleukin (IL)-1 receptor family biomarker, and circulating soluble ST2 concentrations are believed to reflect cardiovascular stress. Recent studies have demonstrated soluble ST2 to be a strong predictor of cardiovascular outcomes in community-based populations free of cardiovascular disease. This report reviews the role of soluble ST2 in relation to cardiovascular risk factors and clinical outcomes in the general population. Furthermore, the recommendations regarding the role of soluble ST2 in general population-based testing, as formulated by the International ST2 Consensus Panel, are presented. There may be a role for soluble ST2 in improving current risk-stratification strategies for the prediction of cardiovascular outcomes, potentially in combination with other biomarkers in a multimarker strategy. However, the role of soluble ST2 testing in the general population has not yet been conclusively established. Future studies investigating the clinical utility of soluble ST2 screening in the general population are warranted., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Vitamin D-binding protein (DBP) may alter the biological activity of total 25-hydroxyvitamin D [25(OH)D]; this could influence on the effects of vitamin D in relation to bone mineral density (BMD) and fractures. Emerging data suggest that fetuin-A may be involved in bone metabolism. We aimed to investigate the influence of DBP gene polymorphism on the relationship of vitamin D status and fetuin-A levels to BMD and bone markers., Methods: This cross-sectional study was part of a health survey of employees of the Electricity Generating Authority of Thailand (1,734 healthy subjects, 72% male). Fasting blood samples were assayed for 25(OH)D, fetuin-A, N-terminal propeptides of type 1 procollagen (P1NP), C-terminal cross-linking telopeptides of type I collagen (CTx-I), and DBP rs2282679 genotypes. L1-L4 lumbar spine and femoral BMD were measured using dual-energy X-ray absorptiometry., Results: The DBP rs2282679 genotype distribution conformed to the Hardy-Weinberg equilibrium. There were no correlations between 25(OH)D levels and BMD and bone markers. But a trend of positive correlation was observed for the DBP genotypes with total hip BMD, and for the interaction between 25(OH)D and DBP genotypes with BMD at all femoral sites. We further analyzed data according to DBP genotypes. Only in subjects with the AA (common) genotype, 25(OH)D levels were positively related to BMD and bone markers, while fetuin-A was negatively related to total hip BMD, independently of age, gender and BMI., Conclusions: The interaction between vitamin D status, as measured by circulating 25(OH)D and DBP rs2282679 genotypes, modified the association between 25(OH)D and BMD and bone markers. Differences in DBP genotypes additionally influenced the correlation of fetuin-A levels with femoral BMD.

Objective: Vitamin D deficiency is related to increased risks for a number of diseases. To date, at least 3 candidate genes, vitamin D binding protein (VDBP) gene (GC), 25-hydroxylase (CYP2R1), and 7-dehydrocholesterol reductase/NAD synthetase 1 (DHCR7/NADSYN1), have been associated with serum 25-hydroxyvitamin D (25[OH]D) levels, but their influences on the prevalence of vitamin D deficiency in relation to other known risk factors have not been clearly defined., Methods: The study assessed 4,476 individuals aged 14 to 93 years from the Thailand 4th National Health Examination Survey (2008-2009) and the Electricity Generating Authority of Thailand (EGAT) (2008) cohorts. The GC rs2282679 polymorphism on chromosome 4q12-q13 was genotyped by real-time polymerase chain reaction (PCR). Serum 25(OH)D was measured by liquid chromatography/tandem mass spectrometry. Vitamin D deficiency was defined as a 25(OH)D concentration <20 ng/mL., Results: Data were expressed as mean ± SD. There were 2,747 (61.4%) males and 1,729 (38.6%) females in the study, with an average body mass index (BMI) of 23.7 ± 4.2 kg/m2 and a mean total 25(OH)D of 28.9 ± 9.0 ng/mL. Serum 25(OH)D levels decreased progressively with the presence of the C allele. Using multiple logistic regression analysis, vitamin D deficiency was significantly associated with the GC rs2282679 genotype (odds ratio [OR] per C allele 1.80, 95% confidence interval CI 1.57-2.01), independent of established risk factors for vitamin D deficiency including age, sex, and BMI., Conclusion: A specific GC gene polymorphism is associated with lower 25(OH)D levels independent of age, sex, and adiposity in Thai subjects.

Background: Hypertension is one of the world's most common health conditions and is a leading risk factor for mortality. Although blood pressure can be modified, there is a large proportion of patients whose blood pressure remains uncontrolled. The aim of this study, termed Edvantage 360°, was to gain a deeper understanding of hypertension management in Asia from the perspective of patients and doctors, and to propose strategies to improve blood pressure control., Methods: Conducted in Hong Kong, Indonesia, Malaysia, the Philippines, South Korea, Taiwan, and Thailand, Edvantage 360° was a mixed-methods observational study that used both qualitative and quantitative elements: qualitative interviews and focus groups with patients (N = 110), quantitative interviews with patients (N = 709), and qualitative interviews with doctors (N = 85)., Results: This study found that, although there is good understanding of the causes and consequences of hypertension among Asian patients, there is a lack of urgency to control blood pressure. Doctors and patients have different expectations of each other and a divergent view on what constitutes successful hypertension management. We also identified a fundamental gap between the beliefs of doctors and patients as to who should be most responsible for the patients' hypertension management. In addition, because patients find it difficult to comply with lifestyle modifications (often because of a decreased understanding of the changes required), adherence to medication regimens may be less of a limiting factor than doctors believe., Conclusions: Doctors may provide better care by aligning with their patients on a common understanding of successful hypertension management. Doctors may also find it helpful to provide a more personalized explanation of any needed lifestyle modifications. The willingness of the doctor to adjust their patient interaction style to form a 'doctor-patient team' is important. In addition, we recommend that doctors should not attribute ineffectiveness of the treatment plan to patient non-adherence to medications, but rather adjust the medication regimen as needed.

Lead has been linked to the development of hypertension via oxidative stress. Catalase plays an important role in the disposal of hydrogen peroxide in erythrocyte and its activity was determined by CAT gene. The aims of this study were to investigate (1) the association between blood levels of antioxidant markers such as catalase, superoxide dismutase, glutathione, glutathione peroxidase, oxidative stress-marker (malondialdehyde), and blood lead level and (2) the influence of genetic polymorphism of CAT gene (rs769217) on change in blood pressure in general population of EGAT study project. This is a cross-sectional study of 332 normotensive, 432 prehypertensive, and 222 hypertensive male subjects. Hypertensive subjects had significantly higher blood lead level (5.28 μg/dL) compared to normotensive (4.41 μg/dL) and prehypertensive (4.55 μg/dL) subjects (P < 0.05). These significant findings are also found in MDA levels. Moreover, individuals with TT genotype in hypertensive group had significantly higher blood lead and MDA levels (6.06 μg/dL and 9.67 μmol/L) than those with CC genotype (5.32 μg/dL and 8.31 μmol/L, P < 0.05). Our findings suggested that decreased blood catalase activity in this polymorphism together with low level lead exposure induced lipid peroxidation may be responsible for hypertension.