Addressing causal relationship between drinking behavior and metabolic syndrome: one-sample Mendelian randomization analysis.

AIMS: Alcohol drinking is associated with central obesity, hypertension, and hyperlipidemia, which further causes metabolic syndrome (MetS). However, prior epidemiological studies on such associations lack experimental evidence for a causal relationship. This study aims to explore the causal relationship between drinking behavior and MetS in Taiwan population by using Mendelian randomization (MR) analysis. METHODS: A cross-sectional study was conducted using the Taiwan Biobank database, which comprised 50 640 Han Chinese who were 30-70 years old without cancer from 2008 to 2020. In MR analysis, we constructed weighted and unweighted genetic risk scores by calculating SNP alleles significantly associated with alcohol drinking. We calculated odds ratios and 95% confidence interval (CI) by using a two-stage regression model. RESULTS: A total of 50 640 participants were included with a mean age of 49.5 years (SD: 1.67 years), 36.6% were men. The adjusted odds ratio (aOR) of MetS per 5% increase in the likelihood of genetic predisposition to drink based on weighted genetic risk score with adjustment was 1.11 (95% CI: 1.10, 1.12, P < .001). Analysis was also conducted by grouping the likelihood of genetic predisposition to drink based on quartiles with multivariate adjustment. Using Q1 as the reference group, the aORs of MetS for Q2, Q3, and Q4 were 1.19 (1.12, 1.27, p < .001), 1.31 (1.23, 1.40, p < .001), and 1.87 (1.75, 2.00, p < .001), respectively, for the weighted genetic risk score. CONCLUSIONS: This study shows a modest relationship between drinking behavior and MetS by using MR analysis.

Cognitive function and its transitions in predicting all-cause mortality among urban community-dwelling older adults.

BACKGROUND: Cognitive impairment is accompanied with high rates of comorbid conditions, leading ultimately to death. Few studies examine the relation between cognitive transition and mortality, especially in Asian population. This study evaluated baseline cognition and cognitive transition in relation to all-cause mortality among community-dwelling older adults. METHODS: We conducted a community-based prospective cohort study among 921 participants of Taichung Community Health Study for Elders in 2009. Cognitive function was evaluated by the Mini-Mental State Examination. Cognitive impairment was considered if the total score is less than 27, 24, and 21 for a participant's educational level of more than 6 years, equal or less than 6 years, and illiteracy, respectively. One-year transition in cognitive function was obtained among 517 individuals who were assessed in both 2009 and 2010. Mortality was followed up until 2016. Cox proportional hazards models were applied to estimate the adjusted hazard ratios of mortality for baseline cognitive impairment and one-year transition in cognitive status. RESULTS: After a follow-up of 6.62 years, 160 deaths were recorded. The multivariate adjusted hazard ratio (95% confidence interval) for baseline cognitive impairment was 2.08 (1.43, 3.01). Significantly increased mortality risk was observed for cognitively impaired-normal and impaired-impaired subgroups over 1 year as compared with those who remained normal [2.87 (1.25, 6.56) and 3.79 (1.64, 8.73), respectively]. The area under the receiver operating characteristic curves demonstrated that baseline cognition and one-year cognitive transition had no differential predictive ability for mortality. Besides, there was an interaction of cognitive impairment and frailty, with an additive mortality risk [5.41 (3.14, 9.35)] for the elders who presented with both. CONCLUSION: Baseline cognitive impairment rather than one-year progression is associated with mortality in a six-year follow-up on older adults.

Independent associations of urinary albumin-to-creatinine ratio and serum cystatin C with carotid intima-media thickness in community-living Taiwanese adults.

BACKGROUND: Renal function is a key factor of cardiovascular disease. Carotid intima-media thickness (IMT) has been widely used as a marker of early subclinical atherosclerosis. The determinants of cystatin C, a novel marker of renal function, have not been extensively studied in the Asian population. This study aimed to assess the determinants of cystatin C and explore whether carotid thickening was associated with urinary albumin-creatinine ratio and cystatin C in community-living Taiwanese adults. METHODS: A cross-sectional study was conducted on participants from Taichung City, Taiwan. All the participants underwent carotid ultrasonography. Carotid IMT-mean and IMT-maximum were derived. Kidney biomarkers were measured on the basis of urinary albumin-to-creatinine ratio (ACR) and cystatin C. Multiple linear regression analysis was used. RESULTS: A total of 1032 individuals were recruited, and 469 (45.44%) of them were men. An increased cystatin C level was significantly associated with older age, male gender, lack of physical activity, low HDL cholesterol, abdominal obesity, high hs-CRP, and high ACR. The multivariate-adjusted mean carotid IMT-mean and IMT-maximum values significantly increased by 80.49 and 195.23 µm for every one unit of increase in cystatin C level and by 0.07 and 0.14 µm for every one unit of increase in ACR, respectively (all p < 0.001 except ACR on IMT-maximum with p < 0.01). Lack of physical activity, low HDL, abdominal obesity, high hs-CRP, and high ACR were the determinants of cystatin C. CONCLUSION: Cystatin C and ACR were strongly and linearly associated with carotid thickening, a marker of subclinical atherosclerosis.

Frailty, transition in frailty status and all-cause mortality in older adults of a Taichung community-based population.

BACKGROUND: Previous studies have reported the associations of frailty phenotype or its components with mortality. However, studies that explored the effects of transition in frailty status on mortality were far less in Asian or Chinese. The aim of this study was to evaluate baseline frailty status and one-year change of frailty status in relation to all-cause mortality in Taiwanese community-dwelling older adults who participated in the Taichung Community Health Study for Elders. METHODS: We conducted a community-based prospective cohort study. A total of 921 community-dwelling elderly men and women aged 65-99 years in Taichung City were enrolled in 2009-2010 and were followed up through 2016. We adopted the definition of frailty proposed by Fried et al., including five components: shrinking, weakness, poor endurance and energy, slowness, and low physical activity. Cox proportional hazards models were used to determine adjusted hazard ratios (HRs) of mortality with 95% confidence intervals (CIs) for frailty at baseline and one-year change in frailty status. RESULTS: There were 160 deaths during the follow-up period. The mortality rates in groups of robust and frail were 20.26 and 84.66 per 1000 person-years respectively. After multivariate adjustment, the HR (CIs) for baseline frailty was 2.67 (1.73-4.12). Poor endurance and energy [1.88 (1.03-3.42)], slowness [2.60 (1.76-3.83)] and weakness [1.65 (1.16-2.33)] were found to be predictors of mortality. Increased risks in mortality for subgroups of robust-to-frail [2.76 (1.22-6.27)], frail-to-robust [3.87 (1.63, 9.19)], and frail-to-frail [4.08 (1.92-8.66)] over one-year period were observed compared with those remaining robust. CONCLUSION: Baseline frailty status and one-year change in frailty status are associated with 6-year all-cause mortality among Taiwanese elderly adults. Frailty may be useful for identifying older adults at high risks for mortality prevention.

Associations of TNF-α and IL-6 polymorphisms with osteoporosis through joint effects and interactions with LEPR gene in Taiwan: Taichung Community Health Study for Elders (TCHS-E).

Osteoporosis (OST) is a complex multifactorial disease considered to result from interactions of multiple gene and environmental factors. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 are pleiotropic cytokines essential for bone remodeling; and hormone leptin has immunomodulatory effects that stimulate the synthesis of IL-6 and TNF-α. Leptin is involved in the modulation of bone growth and turnover; and its actions are bound by leptin receptor (LEPR). Prior studies evaluated the effects of TNF-α, IL-6, and LEPR gene polymorphisms separately on bone mineral densities (BMD) or OST. In this study, we assessed the roles of TNF-α and IL-6 gene polymorphisms in OST through joint effects and interactions with LEPR gene. We also evaluated possible joint effects and interactions between these polymorphisms and physical activity. Ten tag-SNPs (rs1799964, rs1800629, rs3093662 in TNF-α; rs1880243, rs1800796, rs1554606 in IL-6; and rs1751492, rs8179183, rs1805096, rs1892534 in LEPR) were used to genotype 103 OST cases and 369 controls. BMD of lumbar spine (LS), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry. Our data showed that TNF-α and IL-6 polymorphisms were associated with overall and site-specific OST in both sexes, and that these associations were dependent on rs1805096 and rs1892534 genotypes of LEPR. In men, LEPR A-G-G-G haplotype was associated with FN OST (OR 4.65, 95 % CI 1.61-13.40, p = 0.004). Genotype AA/AG of LEPR rs1751492 was associated with overall and FN OST in women without physical activity, but not in women with physical activity (p < 0.05 for interaction between physical activity and LEPR rs1751492). In men, we detected significant interactions of IL-6 rs1800796 with LEPR rs1805096 and rs1892534 for FN and TH OST (all p < 0.05). Our data indicate that LEPR gene may play joint and interactive roles with TNF-α and IL-6 genes and physical inactivity in development of OST. Haplotype analyses revealed that the correlations tended to be prominent in men with FN OST.

Mitochondrial DNA haplogroup D and brain microstructure regulate cognitive function among community-dwelling older adults.

INTRODUCTION: Maintaining physical and cognitive function among older adults is important. These functional states are affected by mitochondria through various mechanisms, such as cellular energy production and oxidative stress control. Owing to its involvement in the relations among the brain, cognition, and physical function, mitochondrial function may be affected by mitochondrial DNA (mtDNA) haplogroups. This study explored the effect of mtDNA haplogroups and brain microstructure on physical and cognitive functions among community-dwelling older adults. METHODS: This study was a community-based cross-sectional research. A total of 128 subjects aged 65 years and older without dementia completed several assessments, including mtDNA sequencing, physical and cognitive function tests, and magnetic resonance imaging (MRI) scans. Cognitive function and impairment were assessed by the MMSE and AD8 questionnaires. mtDNA haplogroups were classified by HaploGrep 2 software, and white matter microstructural integrity was scanned by 3T MRI. RESULTS: The mean age of the subjects was 77.3 years. After the adjustment for covariates, the mtDNA haplogroup D carriers showed significantly lower mini-mental state examination (MMSE) scores than other carriers (p = 0.047). Further considering the brain microstructure, the mtDNA haplogroup D (p = 0.002) and white matter volumes in the left precuneus corrected for total intracranial volumes (p = 0.014) were found to be independently influencing factors of the MMSE scores. CONCLUSIONS: The mtDNA haplogroup D and white matter microstructure regulated the cognitive function among community-dwelling older adults. The findings provide new insights into the research gap. Scientists must further venture into this field.

The joint effect of cigarette smoking and polymorphisms on LRP5, LEPR, near MC4R and SH2B1 genes on metabolic syndrome susceptibility in Taiwan.

Metabolic syndrome (MetS) is a combination of medical disorders, consisting of multiple, interrelated risk factors of metabolic origin. To investigate the associations of MetS with appetite-related genes (LEPR, near MC4R and SH2B1) and cholesterol metabolism-related gene (LRP5) polymorphism variants and the joint effect of cigarette smoking and these polymorphism variants on MetS in a community-based case-control study. Metabolic syndrome was defined according to the American Heart Association and National Heart Lung Blood Institute (AHA/NHLBI) criteria. A total of 237 MetS cases and 202 subjects without MetS aged 40 or over in Taiwan were analyzed. The genotypes of LRP5-rs3736228, LEPR-rs1137100, near MC4R-rs17782313 and SH2B1-rs4788102 were analyzed by the PCR-restriction fragment length polymorphism method. A strong association of the SNP rs17782313 near MC4R gene with MetS susceptibility was found. The data indicated that the C allele of near MC4R-rs17782313 is an obvious risk factor for MetS susceptibility. The joint effects of cigarette smoking and susceptible genotypes of LRP5, LEPR, near MC4R or SH2B1 genes led to a relatively higher risk of having MetS. Using subjects with the wild-type of LRP5, LEPR, near MC4R or SH2B1 genes and without a smoking habit as a reference group, those with cigarette smoking (current and former) and more than one variant type had a 4.1-fold (95 % CI = 1.6-10.2) risk of having MetS. The genotypes of the appetite-related genes (LEPR, near MC4R and SH2B1) and cholesterol metabolism-related gene (LRP5), together with a cigarette smoking habit, are important risk factors for MetS.

Association of high-sensitivity C-reactive protein and diabetic nephropathy in patients with type 2 diabetes: a Mendelian randomization study.

INTRODUCTION: Observational studies support the relationship between C-reactive protein (CRP) level and diabetic nephropathy (DN) in patients with diabetes. The research question regarding whether the relationship between serum high-sensitivity C-reactive protein (hsCRP) level and DN is causal lacks experimental evidence. Therefore, this study aimed to evaluate the causality between hsCRP and DN based on Mendelian randomization (MR) analysis. RESEARCH DESIGN AND METHODS: A total of 2332 participants with type 2 diabetes from the Taiwan Biobank database was analyzed. Genetic risk scores (GRSs), which comprise four validated CRP loci as two instrumental variables, were calculated as unweighted and weighted scores to evaluate the causal relationship of hsCRP with DN risk. The two-stage regression model was used to estimate OR and 95% CI. RESULTS: The analyses of the observational study showed that the hsCRP level was significantly associated with DN after multivariate adjustment (adjusted OR 1.15; 95% CI 1.01 to 1.32). Unweighted/weighted GRSs for log-transformed hsCRP satisfied MR assumptions 1 and 3, respectively; that is, a significant association with hsCRP was observed but that with DN was absent (adjusted OR 1.00, 95% CI 0.92 to 1.09; 1.00, 0.72 to 1.39, respectively). The MR analyses demonstrated that a 1-unit increase in the log-transformed genetically predicted hsCRP by unweighted and weighted GRSs was associated with DN, demonstrating ORs of 1.80 (95% CI 1.51 to 2.14) and 1.67 (95% CI 1.40 to 1.98), respectively. CONCLUSIONS: The current study provided experimental evidence that hsCRP level was causally related to DN. These findings suggest that the elevated hsCRP may be a causal risk factor for DN in patients with type 2 diabetes.

Risk prediction of nephropathy by integrating clinical and genetic information among adult patients with type 2 diabetes.

AIMS: Diabetic nephropathy (DN) is a major healthcare challenge. We developed and internally and externally validated a risk prediction model of DN by integrating clinical factors and SNPs from genes of multiple CKD-related pathways in the Han Chinese population. MATERIALS AND METHODS: A total of 1526 patients with type 2 diabetes were randomly allocated into derivation (n = 1019) or validation (n = 507) sets. External validation was performed with 3899 participants from the Taiwan Biobank. We selected 66 SNPs identified from literature review for building our weighted genetic risk score (wGRS). The steps for prediction model development integrating clinical and genetic information were based on the Framingham Heart Study. RESULTS: The AUROC (95% CI) for this DN prediction model with combined clinical factors and wGRS was 0.81 (0.78, 0.84) in the derivation set. Furthermore, by directly using the information of these 66 SNPs, our final prediction model had AUROC values of 0.85 (0.82, 0.87), 0.89 (0.86, 0.91), and 0.77 (0.74, 0.80) in the derivation, internal validation, and external validation sets, respectively. Under the combined model, the results with a cutoff point of 30% showed 70.91% sensitivity, 67.84% specificity, 51.54% positive predictive value, and 82.86% negative predictive value. CONCLUSIONS: We developed and internally and externally validated a model with clinical factors and SNPs from genes of multiple CKD-related pathways to predict DN in Taiwan. This model can be used in clinical risk management practice as a screening tool to identify persons who are genetically predisposed to DN for early intervention and prevention.

Influence of adiponectin gene polymorphisms on adiponectin serum level and insulin resistance index in taiwanese metabolic syndrome patients.

Although mounting evidences have revealed an association between the gene coding for adiponectin and serum adiponectin levels, much controversy still surrounds the association of the adiponectin gene with metabolic traits such as insulin resistance in obesity and type 2 diabetes (T2DM). On the other hand, very few studies have looked into the relations between adiponectin genetic variants and risks of metabolic syndromes (Mets). The present study assessed the influence of two common adiponectin single-nucleotide polymorphisms (SNPs), rs266729 (C-11377G) and rs1501299 (G276T) in the risk of Mets. A community-based population of 137/110 case/control was genotyped by PCR-RFLP, and the levels of serum adiponectin, fasting serum glucose, fasting serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), uric acid and C-reactive protein of each subject were measured. The distribution of genotypic and allelic frequencies of C-11377G or G276T was not statistically different between the Mets and control groups. However, among the patients with Mets, those carrying GG at C-11377G had a lower level of serum adiponectin (P < 0.001), higher levels of fasting serum glucose (P = 0.0142), fasting serum insulin (P < 0.001) and HOMA-IR (P < 0.001) compared with those carrying the CC or CG genotype. Our data suggest that subjects who carry the homologous GG genotype at C-11377G of the adiponectin gene may be of higher risk of Mets and should be monitored more closely with other serum biochemical indexes.

Mitochondrial DNA haplogroups affect physical performances in Han older adults: an 8-year follow-up prospective cohort study.

AIM: The objective of this study was to explore the association between mitochondrial DNA (mtDNA) haplogroups and physical performances in Han older adults. METHODS: This study was an 8-year follow-up prospective cohort study. A total of 104 Han older adults completed the measurements of the 6-min walk test, grip strength and mitochondrial DNA sequencing. The mtDNA haplogroups were classified by using HaploGrep2 software. We used the mixed model to analyze the longitudinal effect of mtDNA haplogroups on physical performance tests among three waves of data. RESULTS: The mean age at wave 3 among men and women were 78.3 and 77.2 years, respectively. The overall proportions of mtDNA haplogroups in this study population was 26.9% F, 21.2% M, 15.4% R, 14.4% D, 8.7% B and others. After adjusted for age, sex, ethnicity, body mass index and exercise, the interaction of mtDNA haplogroup M and waves significantly affected the 6-min walk distance. Notably, the adjusted mean of the 6-min walk distance among the group of mtDNA haplogroup M was significantly lower than other haplogroups at wave 3. The adjusted mean of grip strength among the group of mtDNA haplogroup R was significantly higher than other haplogroups at wave 3. CONCLUSIONS: This finding suggests that mtDNA haplogroups might have effects on the 6-min walk test and grip strength in Han older adults, although studies of the physical performance of older adults with larger sample sizes are necessary to further substantiate these findings. Geriatr Gerontol Int 2021; 21: 166-171.

The relationship of high sensitivity C-reactive protein to percent body fat mass, body mass index, waist-to-hip ratio, and waist circumference in a Taiwanese population.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is an easily measured inflammatory biomarker. This study compared the association of percent body fat mass (%FM), body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with hs-CRP in a Taiwanese population. METHODS: A total of 1669 subjects aged 40-88 years were recruited in 2004 in a metropolitan city in Taiwan. The relationships between obesity indicators and a high level of hs-CRP were examined using multivariate logistic regression analysis. The upper quartile of the hs-CRP distributions was defined as the high category group. The areas under the curve (AUCs) of the receiver operating characteristic curves were calculated for all obesity indicators to compare their relative ability to correctly classify subjects with a high level of hs-CRP. RESULTS: After multivariate adjustment, the odds ratio for %FM was the only significant indicator that was associated with a high level of hs-CRP in men (1.55, 95% CI: 1.07-2.25). All indicators were associated with a high level of hs-CRP in women. In men, the AUCs for %FM were significantly higher than those for BMI, WHR, and WC, when demographic and lifestyle behaviors were considered (p < 0.001 for all comparisons), but they were not significantly different in females. CONCLUSIONS: Our study demonstrates that %FM is the only obesity indicator that is strongly associated with a high level of hs-CRP after adjusting for sociodemographic factors, lifestyle behaviors and components of metabolic syndrome in both genders in a Taiwanese population aged forty years and over. In men, %FM had the greatest ability to classify subjects with a high level of hs-CRP when only demographic and lifestyle behaviors were considered. Our study finding has important implications for the screening of obesity in community settings.

2-Chloro-1-(4,5,6,7-tetrahydro-thieno[3,2-c]pyridin-5-yl)ethanone.

In the title compound, C(9)H(10)ClNOS, the dihedral angle between the planar thio-phene ring and 2-chloro-ethane moiety (r.m.s deviations of 0.003 and 0.015 Å, respectively) is 45.79 (6)°. The tetra-hydro-pyridine ring adopts a half-chair conformation. The crystal packing reveals inter-molecular C-H⋯O inter-actions.

Interactions among IGF-1, AKT2, FOXO1, and FOXO3 variations and between genes and physical activities on physical performance in community-dwelling elders.

This study assessed the interactions among IGF-1, AKT2, FOXO1, and FOXO3 variations and the interactions of gene and physical activity on handgrip strength, arm muscle mass-adjusted handgrip (armGrip), gait speed (GS), timed up and go (TUG), and leg press strength (LPS). Nine single nucleotide polymorphisms (SNPs) containing three IGF-1 SNPs (rs6214, rs5742692, and rs35767), two AKT2 SNPs (rs892119 and rs35817154), two FOXO1 SNPs (rs17446593 and rs10507486), and two FOXO3 SNPs (rs9480865 and rs2153960) were genotyped in 472 unrelated elders with a mean age of 73.8 years. We observed significant interactions of IGF-1 SNP rs6214 and rs35767 with regular physical activity on TUG and GS; and AKT2 SNP rs892119 and FOXO3 SNP rs9480865 with regular physical activity on armGrip. Genotype GG of IGF-1 rs6214 and rs35767 in individuals without regular physical activity had poor performance in TUG and GS, as well as GG of AKT2 rs892119 decreased armGrip in individuals without regular physical activity. After FDR adjustment, no significant gene-gene interactions were found. A sedentary lifestyle may increase the risk of impairing physical performance and regular physical activity is a remedy for sarcopenia, even a little regular physical activity can overcome carrying some risk alleles in this pathway.

Effects of concurrent aerobic and resistance exercise in frail and pre-frail older adults: A randomized trial of supervised versus home-based programs.

BACKGROUND: This study aimed to investigate the effects of supervised and home-based exercise programs on older people with frailty or pre-frailty. METHODS: A total of 146 community-dwelling participants aged 65 and older who were prefrail or frail were randomly allocated into supervised exercise (N = 74) and home exercise (N = 72) groups. The 3-month supervised exercise training consisted of 3 exercise sessions per week, was performed at a hospital and supervised by a physical therapist. Home exercise participants took instructions on exercise and illustrated exercise handouts. The baseline and 3-month follow-up measurements included body composition, strength of selected upper and lower limb muscle groups, grip and leg press strengths, and five physical performance tests. Mixed-model repeated-measures analysis was applied to determine whether two groups differ in terms of changes before and after the intervention and to compare within-group improvements. RESULTS: After 3 months of supervised or home-based exercise, the average number of frailty criteria met and fat percentage decreased significantly. Strength of knee extensors, knee flexors and leg press improved significantly in supervised exercise group. In home-based exercise group, the strength of all muscle groups tested improved significantly, except for leg press strength. Walking speed improved in both groups, and timed-up-and-go and timed chair rise tests improved significantly only in supervised exercise group. CONCLUSIONS: Three-month supervised or home-based exercise improved walking speed and strength of the limb muscles. Supervised group showed more improvements in the physical performance tests compared with home-based exercise group.

Evaluation of single nucleotide polymorphisms in 6 candidate genes and carotid intima-media thickness in community-dwelling residents.

Evidence suggests the existence of association between a large panel of modifiable biomarkers representing inflammation, coagulation, paraoxonase, and endothelial activation pathways and carotid atherosclerosis. Thus, this study investigated whether CRP, FGA, FGB, FGG, PON1, and EDNRA gene variants affected plasma hs-CRP, fibrinogen levels, and thickness of carotid intima media thickness (IMT). Nineteen single-nucleotide polymorphisms of CRP, FGA, FGB, FGG, PON1, and EDNRA genes were examined in 480 participants from 160 families. Carotid IMT was measured by ultrasound. Generalized linear models with generalized estimating equation were utilized to consider the dependence of subjects within families. In the recessive model, homozygotes for the minor alleles of rs1800789, rs1800790 and rs4220 SNPs in FGB gene indicated a reduced risk of IMT (Exp. ß = 0.89, 0.89, 0.88), which remained significant after adjustment for confounding factors. Significant interaction effects between CRP SNP rs1130864 and rs3093059 and gender for IMT were observed with a significant association in men only. Men carrying minor-minor genotype of CRP SNP rs1130864 and rs3093059 had 0.70- and 0.78-fold lower IMT than men carrying minor-major/major-major genotype. We also observed that the interaction of CRP SNP rs1130864 and rs3093059 with obesity on IMT, hs-CRP and fibrinogen levels. These results support the hypothesis that inflammatory genes are involved in atherosclerosis, most likely via complex gene-gender and gene-obesity interactions.

Subclinical Atherosclerosis Markers of Carotid Intima-Media Thickness, Carotid Plaques, Carotid Stenosis, and Mortality in Community-Dwelling Adults.

Carotid intima-media thickness (IMT), plaque, and stenosis are widely used as early surrogate markers of subclinical atherosclerosis and strong predictors of future deaths and cardiovascular events. Albuminuria is an indicator of generalized endothelial dysfunction that speeds up atherosclerosis. However, previous studies reporting these associations cannot rule out the confounding effect of albuminuria. We aimed to examine the independent and joint relationships between IMT markers and 10-year mortality in community-dwelling Taiwanese adults. This work was a community-based prospective cohort study consisting of 2956 adults aged at least 30 years recruited in 2007 and followed up through 2019. Cox proportional hazard regression models were used to examine associations of these subclinical atherosclerosis markers with mortality. During an average of 9.41 years of follow up, 242 deaths occurred. The mortality rate was 8.70 per 1000 person-years. Compared with those with carotid IMT less than 1.0 mm, persons with severely increased carotid IMT (≥2.0 mm) had an increased risk for death (hazard ratio (HR): 1.79; 95% confidence interval (CI): 1.07, 3.00). Compared with those without carotid plaque, persons with carotid plaque were more likely to have an increased risk for death (1.65; 1.21-2.32). Compared with those with carotid stenosis less than 25%, persons with carotid stenosis of 25-36% had a significant increased risk for death (1.57; 1.12-2.22). Considering these three IMT markers along with the traditional risk factors (c-statistic: 0.85) significantly increased their predictive ability of mortality compared with any individual variable's predictive ability (all p-values < 0.001 for comparisons of c-statistic values). Carotid IMT measures, including IMT thickness, carotid plaque, and carotid stenosis were significant independent predictors of mortality. Our study supports evidence of blood pressure-related media thickening markers to assess future mortality risks in Chinese adults of general population.

The relation of metabolic syndrome according to five definitions to cardiovascular risk factors--a population-based study.

BACKGROUND: Although National Cholesterol Education Program (NCEP), International Diabetes Federation (IDF), American Heart Association and National Heart, Lung and Blood Institute (AHA/NHLBI), World Health Organization (WHO), and the European Group for the Study of Insulin Resistance (EGIR) definitions of metabolic syndrome (MetS) have been commonly used by studies, little is known about agreement among these five definitions. We examined the agreement among these five definitions and explored their relationship with risk factors of cardiovascular disease in a Taiwan population. METHODS: A total of 1305 subjects aged 40 years and over in Taiwan were analyzed. Biomedical markers and anthropometric indices were measured. Agreement among definitions was determined by the kappa statistic. Logistic regression models were fit to estimate the odds of a high cardiovascular risk group for five definitions of MetS. RESULTS: The agreement among the NCEP, IDF, and AHA/NHLBI definitions was from substantial to very good, and agreement between the WHO and EGIR definitions was also substantial. All MetS definitions were significantly associated prevalence of microalbuminuria, elevated highly sensitive CRP (hs-CRP), and arterial stiffness only in women. In men, MetS by NCEP and AHA/NHLBI was associated with elevated level of hs-CRP and arterial stiffness. MetS by WHO and EGIR were significantly associated with microalbuminuria. And MetS by WHO was the only MetS definition that significantly associated with prevalence of arterial stiffness (OR: 2.75, 95% CI: 1.22-6.19). CONCLUSIONS: The associations of these five definitions with cardiovascular risk factors were similar in women, and it was evident that the five definitions performed better in women than in men, with higher ORs observed in relation to arterial stiffness, elevated hs-CRP, and higher Framingham risk scores.

Important gene-gene interaction of TNF-α and VDR on osteoporosis in community-dwelling elders.

Gene effects on osteoporosis have been studied separately and may have been masked by gene-gene and gene-environment interactions. We evaluated gene-gene and gene-physical activity interactions of the variants of tumor necrosis factor-α (TNF-α) and vitamin D receptor (VDR) genes on osteoporosis. A total of 472 elders were included. Seven variants (TNF-α: rs1799964, rs1800629, rs3093662; VDR: rs7975232, rs1544410, rs2239185, rs3782905) were genotyped. Bone mineral densities of the lumbar spine, femoral neck, and total hip were measured by dual-energy X-ray absorptiometry. Predictive models' ability to discriminate osteoporosis status was evaluated by areas under the receiver operating characteristics (AUROC) curve. After multivariable adjustment, significant interactions of TNF-α rs1800629 and VDR rs3782905 were observed on overall and lumbar spine osteoporosis. In elderly women, we found that those carrying the CG/CC genotype of VDR rs3782905 were significantly associated with increased odds of overall osteoporosis compared with those carrying the GG genotype of VDR rs3782905 among those carrying TNF-α rs1800629 GG genotype. The adjusted odds ratios (ORs) for VDR rs3782905 CG/CC genotype in elderly women carrying TNF-α rs1800629 AG/AA and GG genotypes were 0.1 (0.01, 0.98) and 3.54 (1.51, 8.30), respectively. We observed significant differences in AUROCs between the model with traditional covariates plus variants and their interaction term and the model with traditional covariates only (AUROCs: 0.77 and 0.81; p = 0.028). Although the sample size of this study may have been relatively small, our results suggest that the interaction of the CG/CC genotype of VDR rs3782905 with TNF-α rs1800629 GG genotype was associated with increased odds of overall and lumbar spine osteoporosis in elderly women.

Relationship among urinary advanced glycation-end products, skeletal muscle mass and physical performance in community-dwelling older adults.

AIM: Advanced glycation end-products are important factors in muscle function and physical performance among older adults. However, the association between sarcopenia and urinary carboxymethyl-lysine (uCML) levels remains unclear. The present study aimed to investigate the relationship among uCML levels, skeletal muscle mass, physical performance and sarcopenia among community-dwelling older adults. METHODS: This work was a community-based cross-sectional study. The participants were recruited from the Taichung Community Health Study-Elderly and were followed up until 2017. A total of 104 participants underwent dual-energy X-ray absorptiometry examination, physical performance tests and measurement of uCML levels. After the natural log transformation of the uCML levels, Pearson's correlation coefficient and a general linear model were used for statistical analysis. RESULTS: The mean uCML levels of older men and women were 1.34 µg/mg and 1.63 µg/mg creatinine, respectively. After multivariate adjustment, grip strength among older women significantly decreased as uCML levels increased. Participants with uCML levels and Timed Up and Go test values higher than the median had a 13.76-fold risk of acquiring sarcopenia compared with those whose corresponding variables were lower than the median after adjusting for age, sex, body fat percentage, and serum creatinine and blood urea nitrogen levels. CONCLUSIONS: uCML levels were negatively associated with grip strength among older women. The joint association of uCML and Timed Up and Go test values was correlated with the risk of acquiring sarcopenia among older adults. This finding suggests that uCML levels can be used as a biomarker for screening sarcopenia and as a strategy for treating sarcopenia. Geriatr Gerontol Int 2019; 19: 1017-1022.