Publications by authors named "Piyamitr Sritara"

103 Publications

Vitamin D epimers are associated with circulating haemoglobin levels independently of C-reactive protein.

Sci Rep 2021 Oct 20;11(1):20747. Epub 2021 Oct 20.

Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama 6th Road, Bangkok, 10400, Thailand.

Vitamin D deficiency has been shown to be associated with anaemia. Circulating 25(OH)D consists of both epimeric and nonepimeric forms. However, the relative roles of epimeric and nonepimeric vitamin D in regulating anaemia and haemoglobin levels remain unknown. Therefore, in this study, we examined the effect of vitamin D, including its epimers, on haemoglobin levels, independently of its effect on circulating high-sensitivity C-reactive protein (hsCRP). This was a cross-sectional study of 1655 subjects from a long-term follow-up cohort at the Electricity Generating Authority of Thailand. Venous blood sample were collected for determination of vitamin D [25(OH)D, 25(OH)D, 3'-epi-25(OH)D, and 3'-epi-25(OH)D], haemoglobin, and hsCRP levels. Data are presented as mean ± standard deviation. Age, sex, and body mass index (BMI) were significantly associated with circulating haemoglobin levels, while no association was found between total serum 25(OH)D and haemoglobin levels. However, when total 25(OH)D was separated into 3'-epimeric and non-3'-epimeric forms, 3'-epi-25(OH)D was significantly associated with haemoglobin levels, independently of age, sex, and BMI (P < 0.01). No association was found between non-3'-epi-25(OH)D and haemoglobin. When hsCRP was added to the model, the effect 3'-epi-25(OH)D on haemoglobin levels remained significant (P < 0.01). In conclusion, vitamin D epimers are associated with circulating haemoglobin levels, which supports the role of vitamin D in red blood cell and iron physiology.
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http://dx.doi.org/10.1038/s41598-021-00086-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528815PMC
October 2021

Economic evaluation of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation: a systematic review and meta-analysis.

BMJ Evid Based Med 2021 Oct 11. Epub 2021 Oct 11.

Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand.

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 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=59.9%), $6353.24 ($4076.03 to $8630.45; I=0%), $7664.58 ($2979.79 to $12 349.37; I=0%) and $8573.07 ($1877.05 to $15 269.09; I=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=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.
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http://dx.doi.org/10.1136/bmjebm-2020-111634DOI Listing
October 2021

Cardio-ankle vascular index as a predictor of major adverse cardiovascular events in metabolic syndrome patients.

Clin Cardiol 2021 Nov 29;44(11):1628-1635. Epub 2021 Sep 29.

Division of Cardiology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

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.
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http://dx.doi.org/10.1002/clc.23735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571554PMC
November 2021

Long-term air pollution exposure and decreased kidney function: A longitudinal cohort study in Bangkok Metropolitan Region, Thailand from 2002 to 2012.

Chemosphere 2022 Jan 1;287(Pt 1):132117. Epub 2021 Sep 1.

Air Pollution and Health Effect Research Center, Prince of Songkla University, Songkhla, Thailand; Department of Mechanical and Mechatronics Engineering, Faculty of Engineering, Prince of Songkla University, Songkhla, Thailand. Electronic address:

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), ozone (O), nitrogen dioxide (NO), sulfur dioxide (SO), 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 (-1.99%, 95% confidence interval (CI): -3.33, -0.63), SO (-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, and SO, no significant association was observed between CO and eGFR.

Conclusions: Our findings support the hypothesis that long-term exposure to high concentrations of PM and SO is associated with the progression of kidney dysfunction in subjects of the EGAT cohort study.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132117DOI Listing
January 2022

Role of MT1A Polymorphism and Environmental Mercury Exposure on the Montreal Cognitive Assessment (MoCA).

Neuropsychiatr Dis Treat 2021 22;17:2429-2439. Epub 2021 Jul 22.

Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Purpose: Many age-related structural and functional changes in the brain have important consequences. Long-term exposure to mercury and the impact of functional polymorphisms of metal-regulating proteins such as metallothioneins (MTs) can result in neurological-neurobehavioral effects in elderly individuals. Therefore, the aims of this study are to examine the associations between biomarkers of mercury exposure and cognitive impairment and to investigate the effect of the rs8052394 single nucleotide polymorphism (SNP) of the potential modifier gene MT1A on different domains of the Montreal Cognitive Assessment (MoCA).

Materials And Methods: We studied 436 participants aged ≥55 years from the Electricity Generating Authority of Thailand study. They underwent a physical examination, an extensive cognitive assessment with the MoCA (cutoff <26 points), and a biochemical analysis related to diabetes and dyslipidemia. The blood mercury level was determined by inductively coupled plasma mass spectrometry. Genotyping of the MT1A rs8052394 SNP was performed by the restriction fragmentation length polymorphism method.

Results: The mean age of the study population was 58.8±3.01 years, and most had ≥12 years of education (75.7%). The primary study finding was that the prevalence of mild cognitive impairment (MCI) in older Thai adults was 39.7%. The frequency distributions of the G allele of the rs8052394 SNP of the MT1A gene were significantly associated with the total and sub-domain MoCA scores. The prevalence of MCI was significantly associated with increased age, hypertriglyceridemia, hyperhomocysteinemia, the third tertile of blood mercury concentration, and the rs8052394 variant genotype of MT1A (P values for all odds ratios <0.05).

Conclusion: These findings suggested that neurocognitive effects associate with mercury exposure and genetic susceptibility in toxicokinetics. Public health strategies can be used to implement as a comprehensive action plan to educate vulnerable populations on how to reduce mercury exposure. Concurrently, impact of such genetic predisposition requires replication for identifying and protecting susceptible individuals from mercury toxicity.
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http://dx.doi.org/10.2147/NDT.S320374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314684PMC
July 2021

Gut microbiota-generated metabolite, trimethylamine-N-oxide, and subclinical myocardial damage: a multicenter study from Thailand.

Sci Rep 2021 07 22;11(1):14963. Epub 2021 Jul 22.

Cardiovascular Unit, Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.

Plasma Trimethylamine-N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, is mechanistically linked to cardiovascular disease (CVD) and adverse cardiovascular events. We aimed to examine the relationship between plasma TMAO levels and subclinical myocardial damage using high-sensitivity cardiac troponin-T (hs-cTnT). We studied 134 patients for whom TMAO data were available from the Cohort Of patients at a high Risk of Cardiovascular Events-Thailand (CORE-Thailand) registry, including 123 (92%) patients with established atherosclerotic disease and 11 (8%) with multiple risk factors. Plasma TMAO was measured by NMR spectroscopy. In our study cohort (mean age 64 ± 8.9 years; 61% men), median TMAO was 3.81 μM (interquartile range [IQR] 2.89-5.50 μM), and median hs-cTnT was 15.65 ng/L (IQR 10.17-26.67). Older patients and those with diabetic or hypertension were more likely to have higher TMAO levels. Plasma TMAO levels correlated with those of hs-cTnT (r = 0.54; p < 0.0001) and were significantly higher in patients with subclinical myocardial damage (hs-cTnT ≥ 14 ng/L; 4.48 μM vs 2.98 μM p < 0.0001). After adjusting for traditional risk factors, elevated TMAO levels remained independently associated with subclinical myocardial damage (adjusted odds ratio [OR]: 1.58; 95% CI 1.24-2.08; p = 0.0007). This study demonstrated that plasma TMAO was an independent predictor for subclinical myocardial damage in this study population.
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http://dx.doi.org/10.1038/s41598-021-93803-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298599PMC
July 2021

Effects of long-term air pollution exposure on ankle-brachial index and cardio-ankle vascular index: A longitudinal cohort study using data from the Electricity Generating Authority of Thailand study.

Int J Hyg Environ Health 2021 07 15;236:113790. Epub 2021 Jun 15.

Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

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), sulfur dioxide (SO), nitrogen dioxide (NO), ozone (O), 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, O, NO, SO 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 was positively associated with CAVI (6.67%, 95% CI: 0.21, 13.1). In contrast, 1-year average PM was inversely associated with CAVI although the association was not significant. Although not significantly, 1-year average NO and CO were positively associated with prevalence of high or moderate CAVI.

Conclusions: Although not statistically significant, long-term NO and CO exposure was associated with ABI and CAVI in the participants of the EGAT study.
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http://dx.doi.org/10.1016/j.ijheh.2021.113790DOI Listing
July 2021

Tropical Oil Consumption and Cardiovascular Disease: An Umbrella Review of Systematic Reviews and Meta Analyses.

Nutrients 2021 May 4;13(5). Epub 2021 May 4.

Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.

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.
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http://dx.doi.org/10.3390/nu13051549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148021PMC
May 2021

The Involvement of Selenium in Type 2 Diabetes Development Related to Obesity and Low Grade Inflammation.

Diabetes Metab Syndr Obes 2021 14;14:1669-1680. Epub 2021 Apr 14.

Graduate Program in Nutrition, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Background: Effects of the micronutrient selenium have been proposed in obesity and type 2 diabetes mellitus (T2DM) that involve impairments in glucose metabolic pathways and the insulin signaling cascade, mediated through oxidative stress and inflammation. However, the evidence collected to date through animal and epidemiologic studies has been inconclusive. Therefore, in the present study, we aimed to evaluate the relationships of selenium status and inflammation with T2DM and obesity.

Methods: Participants in the re-survey of the Electricity Generating Authority of Thailand (EGAT)2 study conducted in 2013 (N=655, age 45-60 years) were allocated to three groups based on their body mass index (World Health Organization Asia-Pacific Classification), and their serum selenium and high-sensitivity C-reactive protein (hs-CRP) concentrations and other clinical parameters were compared.

Results: Significant differences in serum selenium and hs-CRP among the groups were associated with differences in fasting blood glucose and glycated hemoglobin, as well as differences in the prevalence of prediabetes or T2DM. The adjusted odds ratios (ORs) (95% confidence intervals) for prediabetes or diabetes were 1.991 (1.318-3.009) and 3.786 (2.087-6.896) for the lowest and highest tertiles of serum selenium concentration in the entire sample and obese participants, respectively. Furthermore, the rising extent of hs-CRP increased the significantly associated with prediabetes or diabetes (adjusted ORs; 2.268 for the entire sample, 4.043 for the overweight and 1.910 for the obesity).

Conclusion: Selenium status may be linked to both obesity and T2DM through its effects on signaling pathways. Further nutrigenomic studies are required to clarify the relationship between selenium and metabolic diseases.
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http://dx.doi.org/10.2147/DMSO.S303146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055366PMC
April 2021

Metabolic syndrome and severe periodontitis were associated in Thai adults: A cross-sectional study.

J Periodontol 2021 10 6;92(10):1420-1429. Epub 2021 Mar 6.

Department of Periodontology, Center of Excellent in Periodontal Disease and Dental Implant, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.

Background: Studies support the relationship between metabolic syndrome (MetS) and periodontitis. However, age is the major confounding factor for both conditions. Therefore, this cross-sectional study was performed to investigate the relationship between MetS and severe periodontitis in different Thai adult age groups.

Methods: Data on the medical history, medical examination, and full mouth oral examination of 5,690 Electricity Generating Authority of Thailand employees aged 25 to 77 years were collected. The prevalence ratio (PR) between risk variables, MetS, and periodontitis was determined using Poisson regression analysis. Moreover, the subgroup analysis and effect modification by age on severe periodontitis were performed.

Results: Overall, MetS was significantly associated with severe periodontitis compared with non-severe periodontitis (adjusted PR, 1.11; 95% confidence interval [CI], 1.01 to 1.13). The association was modified by age, with negative effect modification observed on the multiplicative and additive scales. The subgroup analysis revealed a significant relationship between MetS and severe periodontitis only in participants aged <45 years with an adjusted PR of 1.69 (95% CI, 1.29 to 2.21). All MetS components, except hypertension, were associated with severe periodontitis in this group.

Conclusions: There is a significant relationship between MetS and severe periodontitis in adults aged <45 years. Therefore, attempts to control the risk of MetS and periodontitis should be emphasized for early adults to reduce the incidence of these conditions and related complications when they become elderly.
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http://dx.doi.org/10.1002/JPER.20-0651DOI Listing
October 2021

Periodontitis is associated with cardiovascular diseases: A 13-year study.

J Clin Periodontol 2021 03 19;48(3):348-356. Epub 2021 Jan 19.

Chulalongkorn University, Bangkok, Thailand.

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.
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http://dx.doi.org/10.1111/jcpe.13418DOI Listing
March 2021

Associations between alcohol consumption trajectory and deaths due to cancer, cardiovascular diseases and all-cause mortality: a 30-year follow-up cohort study in Thailand.

BMJ Open 2020 12 24;10(12):e038198. Epub 2020 Dec 24.

Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

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.
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http://dx.doi.org/10.1136/bmjopen-2020-038198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768972PMC
December 2020

Cognitive impairment is associated with mitochondrial dysfunction in peripheral blood mononuclear cells of elderly population.

Sci Rep 2020 12 8;10(1):21400. Epub 2020 Dec 8.

Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.

Cognitive impairment is commonly found in the elderly population. Evidence suggests that mitochondrial function in lymphocytes are potential biomarkers in the progression of neurodegeneration, as peripheral mitochondrial function is associated with mild cognitive impairment (MCI) in the elderly population. Therefore, we hypothesize that impaired mitochondrial ATP production and oxidative stress in peripheral blood mononuclear cells (PBMCs) are associated with cognitive impairment in the elderly population. Data were collected from 897 participants from the EGAT (The Electricity Generating Authority of Thailand) cohort. The participants were classified to be in the normal cognition group (n = 428) or mild cognitive impairment group (n = 469), according to their MoCA score. The association of mitochondrial function and cognitive status was analyzed by binary logistic regression analysis. MCI participants had higher age, systolic blood pressure, waist/hip ratio, and lower plasma high- and low-density lipoprotein cholesterol levels, when compared to the normal cognition group. In addition, estimated glomerular filtration rate were lower in the MCI group than those in the normal cognition group. Collectively, MCI is associated with mitochondrial dysfunction in PBMCs as indicated by decreasing mitochondrial ATP production, increasing proton leak, and oxidative stress, in the elderly population, independently of the possible confounding factors in this study.
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http://dx.doi.org/10.1038/s41598-020-78551-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723050PMC
December 2020

Optimal INR level in elderly and non-elderly patients with atrial fibrillation receiving warfarin: a report from the COOL-AF nationwide registry in Thailand.

J Geriatr Cardiol 2020 Oct;17(10):612-620

Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

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.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2020.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657951PMC
October 2020

Effect of alirocumab on major adverse cardiovascular events according to renal function in patients with a recent acute coronary syndrome: prespecified analysis from the ODYSSEY OUTCOMES randomized clinical trial.

Eur Heart J 2020 11;41(42):4114-4123

Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA.

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.
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http://dx.doi.org/10.1093/eurheartj/ehaa498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700757PMC
November 2020

Roles of kininogen-1, basement membrane specific heparan sulfate proteoglycan core protein, and roundabout homolog 4 as potential urinary protein biomarkers in diabetic nephropathy.

EXCLI J 2020 24;19:872-891. Epub 2020 Jun 24.

Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.

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.
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http://dx.doi.org/10.17179/excli2020-1396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355151PMC
June 2020

Long-term effects of socioeconomic status on the incidence of decreased glomerular filtration rate in a Southeast Asian cohort.

J Epidemiol Community Health 2020 11 7;74(11):925-932. Epub 2020 Jun 7.

Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Background: There is limited information on the role of low socioeconomic status (SES) in the development of new chronic kidney disease (CKD) in the general population, especially from developing countries. This study will test the hypothesis that low SES increases the risk of incidence of decreased glomerular filtration rate (GFR, used as an estimate for CKD) in a Thai worker cohort.

Method: In this prospective, longitudinal observational study, we evaluated the association of income and educational attainment on incident decreased GFR ( <60 mL/min/1.73 m) over a 27-year period in employees of Electricity Generating Authority of Thailand. In 1985, subjects participated in a health survey and were re-examined in 1997, 2002, 2007 and 2012. Education was classified into three categories: low, 0-8th grade; medium, 9-12th grade; and high, >12th grade. Income was categorised as follows: low <10 000 Thai Baht (THB)/month; medium, 10 000-20 000 THB/month; and high, >20 000 THB/month. HRs of <60 mL/min/1.73 m were estimated using Cox interval-censored models with high income or education as the reference groups after adjustments for clinical risk factors.

Results: Participants (n=3334) were followed for 23 (15, 27) years. When evaluated separately, both education and income were risk factors for <60 mL/min/1.73 m (adjusted HR education: medium-1.26 (95% CI 1.13 to1.42) and low-1.57 (95% CI 1.36 to 1.81) and adjusted HR income: medium-1.21 (95% CI 0.97 to 1.50) and low-1.47 (95% CI 1.18 to 1.82)). When both income and education were included together, low and medium education remained independently associated with <60 mL/min/1.73 m.

Conclusions: Low education was independently associated with increased risk of decreased GFR in a Thai worker population. Strategies to identify risk factors among low SES may be useful to prevent early CKD.
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http://dx.doi.org/10.1136/jech-2019-212718DOI Listing
November 2020

Herbal or traditional medicine consumption in a Thai worker population: pattern of use and therapeutic control in chronic diseases.

BMC Complement Altern Med 2019 Sep 18;19(1):258. Epub 2019 Sep 18.

Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.

Background: Herbal and traditional medicines (HTM) are widely used in Asian countries. Specific data on prevalent of HTM usage and association with chronic diseases in the Thai population is currently lacking. We examined the prevalence and factors associated with HTM use in a Thai worker population. In addition, we explored the relationship between HTM use and therapeutic control of cardiovascular risk factors and documented the most common types of HTM used in various chronic diseases.

Methods: Employees of EGAT (The Electric Generating Authority of Thailand) who had participated in a health examination were studied. Each participant documented their HTM consumption and self-reported chronic diseases in a questionnaire. Clinical disease and therapeutic control were also defined by concomitant laboratory tests.

Results: Of a total of 6592 subjects, 32.6% were HTM-users. Age < 50 years, female gender, self-reported history of diabetes, liver disease, cancer, dyslipidemia, and alcohol use were independently associated with HTM use. HTM consumption increased in proportion to the numbers of self-reported chronic diseases. There were no differences in the therapeutic control of cardiovascular risk factors between HTM users and non-users. Liver and kidney function were not different. The most commonly used HTM was turmeric.

Conclusions: HTM consumption is common in community-based Thai subjects, with higher use among those with chronic diseases. Although there were no differences in control of cardiovascular risk factors between HTM users and non-users, many of the commonly used herbs have relevant biological activities for chronic disease prevention or treatment.
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http://dx.doi.org/10.1186/s12906-019-2652-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749623PMC
September 2019

Pharmacokinetics and pharmacodynamics of single dose of inhaled nebulized sodium nitrite in healthy and hemoglobin E/β-thalassemia subjects.

Nitric Oxide 2019 12 9;93:6-14. Epub 2019 Sep 9.

Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand. Electronic address:

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), 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) of 1.3 l/kg and half-life (t) of 0.6 h. CL and V 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 in RBC than healthy subjects. FE 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) 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.
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http://dx.doi.org/10.1016/j.niox.2019.09.001DOI Listing
December 2019

Contribution of Four Polymorphisms in Renin-Angiotensin-Aldosterone-Related Genes to Hypertension in a Thai Population.

Int J Hypertens 2019 14;2019:4861081. Epub 2019 Aug 14.

Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.

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 , , , and 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 (=0.422), rs699 (=0.36), rs5186 (=0.49), and rs1799998 (=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.
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http://dx.doi.org/10.1155/2019/4861081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710803PMC
August 2019

Ten-year survival and factors associated with increased mortality in patients admitted for acute decompensated heart failure in Thailand.

Singapore Med J 2020 Jun 6;61(6):320-326. Epub 2019 Sep 6.

Division of Cardiology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

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.
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http://dx.doi.org/10.11622/smedj.2019108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905128PMC
June 2020

The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential : A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation.

Cardiovasc Diabetol 2019 06 4;18(1):71. Epub 2019 Jun 4.

Unidad de Prevención Cardiometabólica Cardiocob. Servicio de Cardiología Hospital el Pino Santiago de Chile, Sociedad Inter Americana de Cardiología SIAC Chairman Cardiovascular Prevention Comite, Santiago de Chile, Chile.

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.
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http://dx.doi.org/10.1186/s12933-019-0864-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549355PMC
June 2019

Periodontitis is associated with elevated serum levels of cardiac biomarkers-Soluble ST2 and C-reactive protein.

J Clin Periodontol 2019 08;46(8):809-818

Medical and Health Department, Electricity Generating Authority of Thailand, Nonthaburi, Thailand.

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.
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http://dx.doi.org/10.1111/jcpe.13149DOI Listing
August 2019

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial.

Eur Heart J 2019 09;40(33):2801-2809

Division of Cardiology, University of Colorado School of Medicine, 1700 N. Wheeling Street, Aurora, CO, USA.

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.
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http://dx.doi.org/10.1093/eurheartj/ehz299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736383PMC
September 2019

The rate of patients at high risk for cardiovascular disease with an optimal low-density cholesterol level: a multicenter study from Thailand.

J Geriatr Cardiol 2019 Apr;16(4):344-353

Division of Cardiology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

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.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2019.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503480PMC
April 2019

Carrier frequency of spinal muscular atrophy in Thailand.

Neurol Sci 2019 Aug 19;40(8):1729-1732. Epub 2019 Apr 19.

Department of Internal Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

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.
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http://dx.doi.org/10.1007/s10072-019-03885-5DOI Listing
August 2019

Periodontitis as the risk factor of chronic kidney disease: Mediation analysis.

J Clin Periodontol 2019 06;46(6):631-639

Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

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 . 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.
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http://dx.doi.org/10.1111/jcpe.13114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593715PMC
June 2019

Mediation Effect of Neutrophil Lymphocyte Ratio on Cardiometabolic Risk Factors and Cardiovascular Events.

Sci Rep 2019 02 22;9(1):2618. Epub 2019 Feb 22.

Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, is associated with cardiovascular events (CVEs), but its causal pathway is unknown. We aimed to explore the extent to which NLR is directly associated with CVEs or mediated through diabetes mellitus (DM), hypertension (HT) and creatinine (Cr). The study used data on 2,501 subjects from the Electricity Generating Authority of Thailand cohort 2002-2012. Two causal pathways A: NLR→(DM→Cr→HT)→CVEs and B: NLR→(DM → HT→Cr)→CVEs were constructed. A generalized structural equation model and 1,000-replication bootstrapping were applied. The incidence rate of CVE was 8.8/1000/year. Prevalence rates of HT, DM, and chronic kidney disease were 45.1%, 23.6%, and 16.5%, respectively. The total effect of NLR on CVEs was explained partly (44%) by a direct effect and partly (56%) by an indirect effect through DM, HT and Cr. For pathway A, the direct OR of NLR on CVE was 1.25 (95% CI: 1.13, 1.39); the ORs for the indirect effects of NLR on CVEs mediated through DM, Cr, and poor-controlled HT were 1.06 (95% CI: 1.01, 1.11), 1.01 (95% CI: 1.00, 1.02), and 1.07 (95% CI: 1.01, 1.14) respectively. Results were similar for pathway B. Our findings demonstrate that roughly half of the relationship between NLR and CVEs may be mediated through DM, HT and Cr.
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http://dx.doi.org/10.1038/s41598-019-39004-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384908PMC
February 2019

Heart failure with reduced ejection fraction: comparison of patient characteristics and clinical outcomes within Asia and between Asia, Europe and the Americas.

Eur J Heart Fail 2019 May 10;21(5):577-587. Epub 2018 Dec 10.

British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.

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.
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http://dx.doi.org/10.1002/ejhf.1347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607486PMC
May 2019
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