An Increase in Vascular Stiffness is Positively Associated with Mitochondrial Bioenergetics Impairment of Peripheral Blood Mononuclear Cells in the Elderly Population.

The cardio-ankle vascular index (CAVI) is a non-invasive parameter reflecting vascular stiffness. CAVI correlates with the burden of atherosclerosis and future cardiovascular events. Mitochondria of peripheral blood mononuclear cells (PBMCs) have been identified as a non-invasive source for assessing systemic mitochondrial bioenergetics. This study aimed to investigate the relationship between CAVI values and mitochondrial bioenergetics of PBMCs in the elderly population. This cross-sectional study enrolled participants from the Electricity Generating Authority of Thailand (EGAT) between 2017 and 2018. 1640 participants with an ankle-brachial index greater than 0.9 were included in this study. All participants were stratified into three groups based on their CAVI values as high (CAVI ≥9), moderate (9 >CAVI ≥8), and low (CAVI <8), in which each group comprised 702, 507 and 431 participants, respectively. The extracellular flux analyzer was used to measure mitochondrial respiration of isolated PBMCs. The mean age of the participants was 67.9 years, and 69.6% of them were male. After adjusted with potential confounders including age, sex, smoking status, body mass index, diabetes, dyslipidemia, hypertension, and creatinine clearance, participants with high CAVI values were independently associated with impaired mitochondrial bioenergetics, including decreased basal respiration, maximal respiration, and spare respiratory capacity, as well as increased mitochondrial reactive oxygen species. This study demonstrated that CAVI measurement reflects the underlying impairment of cellular mitochondrial bioenergetics in PBMCs. Further longitudinal studies are necessary to establish both a causal relationship between CAVI measurement and underlying cellular dysfunction.

Genetic Polymorphisms of Endothelial Nitric Oxide Synthase Associated with Hypertension and Blood Homocysteine Levels.

Purpose: Endothelial dysfunction is a key mechanism in the development of hypertension and is closely linked to impairment of endothelial nitric oxide synthase (eNOS) and hyperhomocysteinemia. Genetic polymorphisms of eNOS (rs1799983 and rs2070744) are strongly associated with the risk of hypertension in individuals of Asian ethnicities. This study aimed to investigate the relationship between these polymorphisms and the risk of hypertension associated with homocysteine levels. Participants and Methods: For this cross-sectional study, we enrolled 370 Thai men aged 40-60 years from the Electricity Generating Authority of Thailand cohort study for both variants genotyping by TaqMan allelic discrimination analysis. Clinical, anthropometric, and biochemical parameters were also analyzed. Results: In the high blood pressure group (n = 267), systolic and diastolic blood pressure and triglyceride levels were higher in those with homocysteine levels ≥ 15 µmol/L than in those with homocysteine levels < 15 µmol/L (p < 0.05). Significant risk of hypertension was found in GG and GT of rs1799983 (G894T), and in TT and TC of rs2070744 (T-786C), with higher ORs in heterozygous genotypes (all p values < 0.05). Further evaluation of the interactions between SNPs and HCY revealed that individuals with the GT or TC genotype, together with hyperhomocysteinemia, had an increased risk of hypertension (all p<0.05). Conclusion: eNOS variants rs1799983 and rs2070744 may be risk factors for hypertension linked to hyperhomocysteinemia. These findings provide potentially useful healthcare strategies for the management of hypertension.

Role of Dietary Factors on DNA Methylation Levels of TNF-Alpha Gene and Proteome Profiles in Obese Men.

Integrated omics-based platforms from epigenomics and proteomics technologies are used to identify several important mechanisms in obesity etiology, food components, dietary intake, regulation of biological pathways, and potential new intervention targets. Therefore, this study aimed to analyze whether dietary factors involved in the methylation of tumor necrosis factor (TNF)-α are implicated in differential protein expression in people with normal weight and obesity. METHODS: The participants were classified into the non-obese (N = 100) and obese (N = 133) groups. DNA methylation levels of the TNF-alpha gene and proteomics were analyzed using the pyrosequencing method and LC-MS-MS, respectively. RESULTS: Comparison between geometric means of DNA methylation of TNF-α showed lower levels in subjects with obesity than in those without obesity (p < 0.05). There were associations between dietary factors and some metabolic syndrome components and TNF-α DNA methylation levels. Proteomic analysis showed important signaling pathways related to obesity, with 95 significantly downregulated proteins and 181 upregulated proteins in the non-obese group compared with the obese group. CONCLUSION: This study shows an association between the dietary factors involved in the methylation of TNF-α and differential protein expression related to obesity. However, a large sample size in future studies is required to confirm our results.

Biological age as estimated by baseline circulating metabolites is associated with incident diabetes and mortality.

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.

Longitudinal study of vitamin D status among Thai individuals in a sun-abundant country.

Background: Vitamin D deficiency is a major public health problem worldwide, even in countries with abundant sunshine. Understanding the risk factors for vitamin D deficiency is important to inform public health recommendations. We conducted a longitudinal analysis of vitamin D status in Thai individuals to assess changes in vitamin D status over time and identify potential determinants. Study design: This study is a long term prospective cohort study. Methods: Of the 1239 participants who were employees of the Electricity Generating Authority of Thailand, serum 25-hydroxyvitamin D (25(OH)D) levels were measured by liquid chromatography/tandem mass spectrometry from samples collected in 2009 and 2019. Results: There was a significant 14.8% increase in serum total 25(OH)D (P < 0.001) from 2009 to 2019, which resulted from significant increases in both 25(OH)D3 and 25(OH)D2. The epimeric form of 25(OH)D2 also increased significantly, while there was no increase in the epimeric form of 25(OH)D3. A univariate analysis showed significant associations between increased total 25(OH)D and increasing age, male sex, and lower body mass index. After controlling for baseline vitamin D status, multivariate regression analyses found that the direction of association and significance from univariate analyses persisted for total 25(OH)D and 25(OH)D3. However, a univariate association found between female sex and an increase in 25(OH)D2 was not significant in multivariate regression analysis. Conclusions: A long-term trend of improved vitamin D status was found among Thai adult individuals over a 10-year period; however, improvements were less noticeable in women.

Associations between residential greenness and air pollution and the incident metabolic syndrome in a Thai worker cohort.

Increasing air pollution and decreasing exposure to greenness may contribute to the metabolic syndrome (MetS). We examined associations between long-term exposure to residential greenness and air pollution and MetS incidence in the Bangkok Metropolitan Region, Thailand. Data from 1369 employees (aged 52-71 years) from the Electricity Generating Authority of Thailand cohort from 2002 to 2017 were analyzed. The greenness level within 500 m of each participant's residence was measured using the satellite-derived Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI). The kriging approach was used to generate the average concentration of each air pollutant (PM10, CO, SO2, NO2, and O3) at the sub-district level. The average long-term exposure to air pollution and greenness for each participant was calculated over the same period of person-time. Cox proportional hazards models were used to analyze the greenness-air pollution-MetS associations. The adjusted hazard ratio of MetS was 1.42 (95% confidence interval (CI): 1.32, 1.53), 1.22 (95% CI: 1.15, 1.30), and 2.0 (95% CI: 1.82, 2.20), per interquartile range increase in PM10 (9.5 µg/m3), SO2 (0.9 ppb), and CO (0.3 ppm), respectively. We found no clear association between NDVI or EVI and the incidence of MetS. On the contrary, the incident MetS was positively associated with NDVI and EVI for participants exposed to PM10 at concentrations more than 50 µg/m3. In summary, the incidence of MetS was positively associated with long-term exposure to air pollution. In areas with high levels of air pollution, green spaces may not benefit health outcomes.

Residential greenness and kidney function: A cohort study of Thai employees.

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 (PM10, O3, NO2, SO2, 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 PM10 and SO2 were included in the models, the associations between NDVI and eGFR became weaker. The additions of O3, NO2, 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.

Association of body mass index and dietary intake with mild cognitive impairment and dementia: a retrospective cohort study.

BACKGROUND: The prevalence of cognitive impairment in older adults is gradually increasing, and this is leading to many adverse outcomes. Common causes of cognitive impairment in advancing age are mild cognitive impairment (MCI) and dementia. However, how the nutritional status and nutrient intake are related to MCI and dementia is controversial. Therefore, we aimed to evaluate the association of body mass index (BMI) and dietary intake with the risk of MCI and dementia. METHODS: This retrospective cohort study involved 821 participants aged ≥ 50 years from a previous population-based cohort study: the Electricity Generating Authority of Thailand (EGAT) study in 2013-2014 (baseline) and 2018-2019 (follow-up). Dietary intake was recorded using a 12-month self-reported food frequency questionnaire. MCI and dementia were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria using the Montreal Cognitive Assessment with ADL and the Kessler Psychological Distress Scale (K10) at study entry and at the 5-year follow-up. RESULTS: Among the 821 participants, the mean age was 60.0 ± 4.3 years, and the incidence rate of MCI and dementia was 42.5 and 11.2 per 1,000 person-years, respectively. The rate of MCI and dementia was higher in participants aged ≥ 60 years and with an education level of < 7 years. The rate of MCI was also higher in those with a BMI of ≥ 25 kg/m2 and type 2 diabetes. Compared to BMI 18.5-22.9 kg/m2, BMI of ≥ 25 kg/m2 (odds ratio 1.91 [95% confidence interval, 1.12-3.26], p < 0.001) was associated with an increased risk of MCI after adjusted for age, education level, and type 2 diabetes. Regarding dietary intake, fresh red meat consumption was inversely associated with the risk of MCI (p = 0.037) and dementia (p = 0.011) after adjusting for age, education level, type 2 diabetes, and BMI. CONCLUSION: Obesity was associated with a greater risk of MCI. Moreover, low consumption of fresh red meat could be a risk factor for MCI and dementia. Further studies are required to confirm and explain these findings.

Association between Dietary Zinc Intake, Serum Zinc Level and Multiple Comorbidities in Older Adults.

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.

Pharmacological Activities of Fingerroot Extract and Its Phytoconstituents Against SARS-CoV-2 Infection in Golden Syrian Hamsters.

Background: The outbreak of COVID-19 has led to the suffering of people around the world, with an inaccessibility of specific and effective medication. Fingerroot extract, which showed in vitro anti-SARS-CoV-2 activity, could alleviate the deficiency of antivirals and reduce the burden of health systems. Aim of Study: In this study, we conducted an experiment in SARS-CoV-2-infected hamsters to determine the efficacy of fingerroot extract in vivo. Materials and Methods: The infected hamsters were orally administered with vehicle control, fingerroot extract 300 or 1000 mg/kg, or favipiravir 1000 mg/kg at 48 h post-infection for 7 consecutive days. The hamsters (n = 12 each group) were sacrificed at day 2, 4 and 8 post-infection to collect the plasma and lung tissues for analyses of viral output, lung histology and lung concentration of panduratin A. Results: All animals in treatment groups reported no death, while one hamster in the control group died on day 3 post-infection. All treatments significantly reduced lung pathophysiology and inflammatory mediators, PGE2 and IL-6, compared to the control group. High levels of panduratin A were found in both the plasma and lung of infected animals. Conclusion: Fingerroot extract was shown to be a potential of reducing lung inflammation and cytokines in hamsters. Further studies of the full pharmacokinetics and toxicity are required before entering into clinical development.

Increased Efficiency of Mitochondrial Coupling With a Reduction in Other Mitochondrial Respiratory Parameters in Peripheral Blood Mononuclear Cells Is Observed in Older Adults.

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.

Effects of AGT and AGTR1 Genetic Polymorphisms and Changes in Blood Pressure Over a Five-Year Follow-Up.

Purpose: The renin-angiotensin system plays an important role in the central regulation of blood pressure (BP). Genetic variations of angiotensinogen (AGT) and angiotensin II type 1 receptor (AGTR1) may increase susceptibility to elevated BP and hypertension. This study investigated the effects of AGT rs699 and AGTR1 rs5186 single nucleotide polymorphisms (SNPs) on BP at baseline and at a 5-year follow-up. Paticipants and Methods: The study population consisted of participants from the Electricity Generating Authority of Thailand cohort study (n=354); data were collected at baseline (2013) and 5 years later (2018). Genotyping of the two SNPs was performed using TaqMan® assay and statistical analyses were performed with SNPStats software. Results: The frequencies of the two SNPs were within the Hardy-Weinberg equilibrium (p=0.22 for AGT rs699 and p=0.06 for AGTR1 rs5186). For each SNP, mutant genotypes were significantly associated with increased systolic BP and/or diastolic BP in the codominant and recessive models. Risk alleles of AGT rs699 and AGTR1 rs5186 were associated with increased odds of hypertension and hypertension with metabolic syndrome at follow-up. Conclusion: Overall, our results suggest that polymorphisms of genes in the renin-angiotensin system increase susceptibility to the development and progression of hypertension and the development of the metabolic syndrome.

The hidden financial catastrophe of chronic kidney disease under universal coverage and Thai "Peritoneal Dialysis First Policy".

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.

Patient Characteristics, Procedural Details, and Outcomes of Contemporary Percutaneous Coronary Intervention in Real-World Practice: Insights from Nationwide Thai PCI Registry.

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.

Association between ApoA1 Gene, Plasma Lipid Profile, hsCRP Level, and Risk of Arterial Stiffness in Thai Elderly.

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.

Using real world evidence to generate cost-effectiveness analysis of fibrinolytic therapy in patients with ST-segment elevation myocardial infarction in Thailand.

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.

Targeted metabolomics suggests a probable role of the FTO gene in the kynurenine pathway in prediabetes.

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.

Causal association pathways between fetuin-A and kidney function: a mediation analysis.

OBJECTIVE: Body mass index (BMI), uric acid, diabetes mellitus, and hypertension are risk factors for reduced kidney function and are associated with fetuin-A levels, but their causal pathways remain unclear. The objective of this study was to investigate this knowledge gap. METHODS: A repeated cross-sectional design was used to assess causal pathway effects of fetuin-A on the estimated glomerular filtration rate (eGFR), which is mediated through BMI, uric acid, diabetes mellitus, and hypertension. RESULTS: Among 2305 participants, the mean eGFR at baseline decreased from 98.7 ± 23.6 mL/minute/1.73 m2 in 2009 to 92.4 ± 22.9 mL/minute/1.73 m2 in 2014. Fetuin-A was significantly associated with eGFR , suggesting that increasing fetuin-A levels predict a decrease in eGFR. Additionally, the indirect effect of fetuin-A on eGFR, as assessed through BMI, was also significant. The effects of fetuin-A on eGFR through other mediation pathways showed variable results. CONCLUSIONS: Our study revealed a possible role of fetuin-A in the etiology of declining renal function through mediating body mass index, uric acid, diabetes mellitus, and hypertension via complex causal pathways. Further studies to clarify these mediated effects are recommended.

Bone Mineral Density and Trabecular Bone Score in Predicting Vertebral Fractures in Male Employees of the Electricity Generating Authority of Thailand.

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.

Causal relationship of excess body weight on cardiovascular events through risk factors.

Excess body weight is associated with cardiovascular events (CVEs) and premature death. This study aimed to find the causal pathways between excess body weight and CVEs through risk factors in a general adult population. A total of 7921 employees of the Electricity Generating Authority of Thailand were enrolled during 1997-2009. Baseline characteristics and blood test results were collected. A body mass index (BMI) ≥ 23 kg/m2, using WHO criteria for Asians was defined as excess body weight. A mediation analysis was applied to assess potential causal pathways. BMI ≥ 23 kg/m2 was considered as an independent variable, whereas diabetes mellitus (DM), hypertension (HT), and chronic kidney disease (CKD) were considered as mediators, and CVEs (i.e., fatal and non-fatal coronary artery disease or stroke) were considered as the outcomes. The prevalence of BMI ≥ 23 kg/m2, DM, HT, and CKD were 62.7%, 7.8%, 28.1% and 11.8% respectively. During an average of 17.2 ± 5.5 years follow-up, subjects with BMI ≥ 23 kg/m2 compared with those with lower BMIs more frequently developed CVEs (9.4 vs 6.2%, P < 0.001). The effects of BMI ≥ 23 kg/m2 on CVEs were mediated indirectly through DM and HT with significant ORs of 1.61 (1.34, 2.09) and 1.57 (1.39, 1.80), respectively. The indirect effect of CKD on CVEs was significantly increased if mediated through DM → HT or HT [ORs of 1.17 (1.09, 1.32) and 1.20 (1.10, 1.32), respectively]. Subjects with excess body weight were prone to develop CVEs which were mediated indirectly through DM and HT. The effect of CKD on CVEs was small but enhanced if it occurred as a complication of DM or HT.