Search

Abstract Background Although red meat consumption has been associated with risk of atherosclerotic coronary artery disease and stroke, no prospective study has examined this with the risk of chronic limb-threatening ischemia (CLTI). Methods In a prospective study of 63,257 Chinese in Singapore, who were aged 45–74 years old at recruitment, diet was assessed via a validated semi-quantitative food frequency questionnaire. Incident CLTI cases were ascertained via linkage with nationwide hospital records for lower extremity amputation or angioplasty for peripheral arterial disease. Multivariable Cox models were used to examine associations between quartiles of meat intake and CLTI risk. Results After a mean follow-up of 18.8 years, there were 1069 cases of CLTI. Higher intake of red meat intake was associated with increased risk of CLTI in a stepwise manner. Comparing extreme quartiles of red meat intake, the hazard ratio (HR) for the association with CLTI risk was 1.24 [95% confidence interval (CI) = 1.03–1.49; P-trend = 0.02]. In stratified analysis, red meat intake had a stronger association with CLTI risk among those without diabetes [HR (95% CI) comparing extreme quartiles = 1.41 (1.10–1.80); P-trend = 0.03] than among those with diabetes at baseline [HR (95% CI) comparing extreme quartiles = 1.04 (0.79–1.38); P-trend = 0.05] (P-interaction = 0.03). Otherwise, the associations were not different by sex, BMI, smoking status, hypertension, alcohol consumption, or history of cardiovascular diseases. Using a theoretical model in substitution analysis that substituted three servings per week of red meat with poultry or fish/shellfish, the relative risk of CLTI was reduced by 13–14%. Conclusions Consumption of red meat was associated with higher CLTI risk in this Asian cohort. Substituting red meat with poultry or fish/shellfish may reduce this risk.

Abstract While rapid demographic changes in Asia are driving the incidence of chronic aging-related diseases, the limited availability of high-quality in vivo data hampers our ability to understand complex multi-factorial contributions, including gut microbial, to healthy aging. Leveraging a well-phenotyped cohort of community-living octogenarians in Singapore, we used deep shotgun-metagenomic sequencing for high-resolution taxonomic and functional characterization of their gut microbiomes (n = 234). Joint species-level analysis with other Asian cohorts identified distinct age-associated shifts characterized by reduction in microbial richness, and specific Alistipes and Bacteroides species enrichment (e.g., Alistipes shahii and Bacteroides xylanisolvens). Functional analysis confirmed these changes correspond to metabolic potential expansion in aging towards alternate pathways synthesizing and utilizing amino-acid precursors, vis-à-vis dominant microbial guilds producing butyrate in gut from pyruvate (e.g., Faecalibacterium prausnitzii, Roseburia inulinivorans). Extending these observations to key clinical markers helped identify >10 robust microbial associations to inflammation, cardiometabolic and liver health, including potential probiotic species (e.g., Parabacteroides goldsteinii) and pathobionts (e.g., Klebsiella pneumoniae), highlighting the microbiome’s role as biomarkers and potential targets for promoting healthy aging.

Abstract Background It is unclear if improving diet quality after midlife could reduce the risk of physical frailty at late life. We aimed to associate changes in diet quality after midlife with physical frailty at late life. Methods Diet quality in 12,580 participants from the Singapore Chinese Health Study was assessed with the Dietary Approaches to Stop Hypertension (DASH) scores at baseline (1993–1998; mean age 53 years) and follow-up 3 (2014–2016; mean age 73 years). Physical frailty was assessed using the modified Cardiovascular Health Study phenotype at follow-up 3. Multivariable logistic regressions examined associations between DASH scores and physical frailty. Results Comparing participants in extreme quartiles of DASH scores, the odds ratios (OR) [95% confidence interval (CI)] for physical frailty were 0.85 (0.73,0.99) at baseline and 0.49 (0.41, 0.58) at follow-up 3. Compared to participants with consistently low DASH scores, participants with consistently high scores (OR 0.74, 95% CI: 0.59, 0.94) and those with > 10% increase in scores (OR 0.78, 95% CI: 0.64, 0.95) had lower odds of frailty. Compared to those in the lowest DASH tertiles at both time-points, significantly lower odds of physical frailty were observed in those who were in the highest DASH tertiles at both time points [0.59 (0.48, 0.73)], and in those who improved their scores from the lowest [0.68 (0.51, 0.91)] or second tertile at baseline [0.61 (0.48, 0.76)] to the highest tertile at follow-up 3. Conclusions Maintaining a high diet quality or a substantial improvement in diet quality after midlife could lower the risk of physical frailty at late life.

Background The prospective association between sleep duration and the development of late-life depressive symptomology is unclear. Aims To investigate sleep duration from midlife to late life in relation to risk of depressive symptoms in late life. Method A total of 14 361 participants from the Singapore Chinese Health Study were included in the present study. Daily sleep duration was self-reported at baseline (mean age of 52.4 years; 1993–98), follow-up 2 (mean age of 65.2 years; 2006–10) and follow-up 3 (mean age of 72.5 years; 2014–16) interviews. Depressive symptoms were evaluated using the Geriatric Depression Scale at follow-up 3 interviews. Modified Poisson regression models were performed to estimate relative risks and 95% confidence intervals of late-life depressive symptoms in relation to sleep duration at baseline and the two follow-up interviews. Results Compared with sleeping 7 h per day, a short sleep duration of ≤5 h per day at baseline (i.e. midlife) was related to a higher risk of depressive symptoms (relative risk 1.10, 95% CI 1.06–1.15), and this risk was not affected by subsequent prolongation of sleep. Conversely, a long sleep duration of ≥9 h per day at baseline was not related to risk of depressive symptoms. At follow-up 3 (i.e. late life), both short sleep (relative risk 1.20, 95% CI 1.16–1.25) and long sleep (relative risk 1.12, 95% CI 1.07–1.18) duration were cross-sectionally associated with depressive symptoms. Conclusion Short sleep duration in midlife, regardless of subsequent prolongation, is associated with an increased risk of depression in late life. Contrariwise, both short and long sleep duration in late life co-occur with depressive symptoms.

Objectives: Our study evaluated the independent and overall associations of vegetable and fruit consumption at midlife with the likelihood of physical frailty in later life. We also investigated whether specific nutrients in these foods could have accounted for these associations, if present. Design: Prospective cohort study. Setting: A population-based cohort of Chinese adults followed over a period of 20 years in Singapore. Participants: We used data from 11,959 subjects who participated in the baseline (1993–1998) and follow-up 3 (2014–2017) interviews of the Singapore Chinese Health Study. Measurements: At baseline, dietary intake was evaluated using a validated food frequency questionnaire. During the follow-up 3 visits, physical frailty was assessed using a modified Cardiovascular Health Study phenotype that included weakness, slowness, exhaustion and weight loss. Multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations with physical frailty. Results: Participants had mean ages of 52 years at baseline, and 72 years at follow-up 3. Baseline intake of vegetables, but not of fruits, showed a dose-dependent inverse relationship with physical frailty at follow-up 3 (Ptrend = 0.001). Compared to participants in the lowest quintile of vegetable intake, those in the highest quintile had reduced odds of frailty [OR (95% CI): 0.73 (0.60−0.89)]. Among the components of physical frailty, vegetable intake had the strongest inverse association with weakness defined by handgrip strength [OR (95% CI) between extreme quintiles: 0.62 (0.52−0.73); Ptrend < 0.001]. In models that were individually adjusted for nutrients, the vegetable-frailty association was attenuated and no longer statistically significant after adjusting for the intake of β-carotene, lutein, folate, α-carotene, and isothiocyanates. Conclusion: : Increased midlife intake of vegetables was associated with reduced odds of physical frailty in later life, and the intake of β-carotene, lutein, folate, α-carotene, and isothiocyanates could have accounted for this association.

Background: Cognitive impairment (CI) raises risks for unplanned healthcare utilisation and expenditures and for premature mortality. It may also reduce risks for planned expenditures. Therefore, the net cost implications for those with CI remain unknown. Method: We examined differences in healthcare utilisation and cost between those with and without CI. Using administrative healthcare utilisation and cost data linked to the Singapore Chinese Health Study cohort, we estimated regression-adjusted differences in annual healthcare utilisation and costs by CI status determined by modified Mini-Mental State Exam. Estimates were stratified by ex ante mortality risk constructed from out-of-sample Cox model predictions applied to the full sample, with a separate analysis restricted to decedents. These estimates were used to project differential healthcare costs by CI status over 5 years. Results: Patients with CI had 17% higher annual cost compared to those without CI (SGD4870 versus SGD4177, P

Setting: Although age at menopause has been linked to higher risk of physical frailty in later life, little is known about other reproductive factors. Objectives: Our study aimed to investigate the associations between 1) age at menarche, 2) age at natural menopause, 3) duration of reproductive period, 4) number of children, 5) use of oral contraceptives (OCP), and 6) use of hormone replacement therapy (HRT) with the risk of physical frailty in late life. Design: We used data from 5934 women of the Singapore Chinese Health Study who experienced natural menopause, and participated in the third follow-up interviews when physical frailty was assessed. Logistic regression was used to evaluate association of reproductive factors evaluated during baseline and prior follow-up interviews with physical frailty at follow-up 3. Participants: Community-dwelling Chinese women living in Singapore. Participants had a mean age of 52.6 years at baseline (1993–1998), and a mean age of 72.8 years during the third follow-up (2014–2017). Measurements: Sociodemographic characteristics, level of education, smoking history, physical activity, and history of physician-diagnosed comorbidities were collected. Participants’ weight and height were self-reported. We used a modified Cardiovascular Health Study phenotype to assess physical frailty. Results: Age at menarche was inversely associated with the likelihood of physical frailty (Ptrend = 0.001); each one-year decrease in age at menarche was associated with a 9% increase (95% CI: 4%–14%) in odds of physical frailty. Age at menopause was also inversely associated with the likelihood of physical frailty (Ptrend = 0.009); every one-year decrease in age at menopause was associated with 2% (0%–4%) increased odds. In the assessment of frailty, younger ages at menarche and menopause were associated with greater likelihood of being in the slowest quintile for timed up-and-go and weakest quintile for handgrip strength. Conversely, duration of reproductive period, parity, and use of oral contraceptives or hormone replacement therapy were not significantly associated with the likelihood of physical frailty. Conclusions: In our population-based cohort of Chinese women, younger ages at menarche and menopause were associated with higher likelihood of physical frailty in later life.

Objectives: Epidemiological evidence of how midlife intake of fruits and vegetables affects the likelihood of depressive symptoms in late life remains limited and controversial. We examined this association in an Asian cohort. Design: Prospective population-based cohort study. Setting: Chinese living in Singapore. Participants: A total of 13,738 adults from the Singapore Chinese Health Study. Measurements: The consumption of 14 fruits and 25 vegetables were assessed using a validated 165-item food-frequency questionnaire at baseline (1993–1998), when participants were aged 45–74 years (mean age 52.4 years). Depressive symptoms were evaluated using the Geriatric Depression Scale during the third follow-up interviews (2014–2016), when participants were aged 61–96 years (mean age 72.5 years), and depression was defined by ≥5 out of 15 scores. Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: After a mean follow-up of 19.6 years, depressive symptoms were identified among 3,180 participants. Consumption of fruits was inversely associated with the odds of depressive symptoms in a dose-response manner: comparing extreme quartiles, the OR (95% CI) of depressive symptoms was 0.71 (0.63−0.81; P-trend

Preclinical and limited epidemiological studies suggest that oxidative stress may be implicated in geriatric depression. Our study investigated the association between midlife dietary total antioxidant capacity (TAC) and depressive symptoms in late life among 13,712 participants in a population-based cohort of Chinese in Singapore. At baseline (1993–1998), intake of antioxidants from diet and supplements at a mean age of 52.4 years was estimated using a validated food frequency questionnaire to derive two dietary TAC indices from vitamins C and E, carotenoids and flavonoids: the Comprehensive Dietary Antioxidant Index (CDAI) and Vitamin C Equivalent Antioxidant Capacity (VCEAC). At follow-up 3 (2014–2016), when participants were at a mean age of 72.5 years, depressive symptoms were assessed using the Geriatric Depression Scale, and depression, defined as having ≥5 symptoms, was presented in 3173 (23.1%) participants. Both CDAI and VCEAC indices were inversely associated with odds of depressive symptoms in a stepwise manner: the OR (95% CI) comparing the extreme quartiles was 0.73 (0.64–0.83; Ptrend < 0.01) for the CDAI and 0.77 (0.68–0.87; Ptrend < 0.01) for the VCEAC. Specifically, higher intakes of vitamin C, carotenoids, and flavonoids were associated with a lower likelihood of depressive symptoms. Our findings support the recommendation of an antioxidant-rich diet for the prevention of depression.

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes.Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10−8) and suggestive (p < 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals).Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue.Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

ObjectivesA short measure of quality of life in old age is essential. The present study examined the factor structure and validity of the 13-item WHOQOL-AGE among the oldest-old.MethodsData came from 1,000 Chinese aged ≥85 years in Singapore. Exploratory and confirmatory factor analyzes were conducted on the WHOQOL-AGE. Regression examined the demographic, social and health correlates of the identified factors.ResultsFactor analyzes suggested a bifactor model of the WHOQOL-AGE, which comprised three specific factors, namely “health,” “environment” and “mastery,” in addition to the general factor (“overall”). Partial scalar invariance (concerning only one item) and scalar invariance were established across gender and education level respectively, generally supporting the measurement invariance of this model. Regression results demonstrated known-groups validity. Health correlates were more predictive of “health” than “environment” and “mastery,” with more basic and instrumental activities of daily living, lower depressive symptomatology and fewer falls positively relating to “health.” Strength of social network and social engagement (social correlates) positively related to “environment” and “mastery” but not “health.”ConclusionThe WHOQOL-AGE exhibits a bifactor structure and known-groups validity among the oldest-old Chinese in Singapore. It seems useful to capture different facets of quality of life in the concerned population.

Abstract Circulating concentrations of metabolites (collectively called kynurenines) in the kynurenine pathway of tryptophan metabolism increase during inflammation, particularly in response to interferon-gamma (IFN-γ). Neopterin and the kynurenine/tryptophan ratio (KTR) are IFN-γ induced inflammatory markers, and together with C-reactive protein (CRP) and kynurenines they are associated with various diseases, but comprehensive data on the strength of associations of inflammatory markers with circulating concentrations of kynurenines are lacking. We measured circulating concentrations of neopterin, CRP, tryptophan and seven kynurenines in 5314 controls from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). The associations of neopterin, KTR and CRP with kynurenines were investigated using regression models. In mixed models, one standard deviation (SD) higher KTR was associated with a 0.46 SD higher quinolinic acid (QA), and 0.31 SD higher 3-hydroxykynurenine (HK). One SD higher neopterin was associated with 0.48, 0.44, 0.36 and 0.28 SD higher KTR, QA, kynurenine and HK, respectively. KTR and neopterin respectively explained 24.1% and 16.7% of the variation in QA, and 11.4% and 7.5% of HK. CRP was only weakly associated with kynurenines in regression models. In summary, QA was the metabolite that was most strongly associated with the inflammatory markers. In general, the inflammatory markers were most strongly related to metabolites located along the tryptophan–NAD axis, which may support suggestions of increased production of NAD from tryptophan during inflammation.

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Abstract It is difficult to identify people with nonalcoholic fatty liver disease (NAFLD) who are at high risk for developing hepatocellular carcinoma (HCC). A polygenic risk score (PRS) for hepatic fat (HFC‐PRS) derived from non‐Asians has been reported to be associated with HCC risk in European populations. However, population‐level data of this risk in Asian populations are lacking. Utilizing resources from 24,333 participants of the Singapore Chinese Health Study (SCHS), we examined the relationship between the HFC‐PRS and HCC risk. In addition, we constructed and evaluated a NAFLD‐related PRS (NAFLD‐PRS) with HCC risk in the SCHS. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of HCC incidence with both HFC‐PRS and NAFLD‐PRS. The HFC‐PRS and NAFLD‐PRS were highly correlated (Spearman r = 0.79, p

Summary: Background: To evaluate whether circulating proteins are associated with survival after lung cancer diagnosis, and whether they can improve prediction of prognosis. Methods: We measured up to 1159 proteins in blood samples from 708 participants in 6 cohorts. Samples were collected within 3 years prior to lung cancer diagnosis. We used Cox proportional hazards models to identify proteins associated with overall mortality after lung cancer diagnosis. To evaluate model performance, we used a round-robin approach in which models were fit in 5 cohorts and evaluated in the 6th cohort. Specifically, we fit a model including 5 proteins and clinical parameters and compared its performance with clinical parameters only. Findings: There were 86 proteins nominally associated with mortality (p

Summary: Genomic researchers increasingly utilize commercial cloud service providers (CSPs) to manage data and analytics needs. CSPs allow researchers to grow Information Technology (IT) infrastructure on demand to overcome bottlenecks when combining large datasets. However, without adequate security controls, the risk of unauthorized access may be higher for data stored on the cloud. Additionally, regulators are mandating data access patterns and specific security protocols for the storage and use of genomic data. While CSP provides tools for security and regulatory compliance, building the necessary controls required for cloud solutions is not trivial. Research Assets Provisioning and Tracking Online Repository (RAPTOR) by the Genome Institute of Singapore is a cloud-native genomics data repository and analytics platform that implements a “five-safes” framework to provide security and governance controls to data contributors and users, leveraging CSP for sharing and analysis of genomic datasets without the risk of security breaches or running afoul of regulations.

Background: To evaluate the utility of polygenic risk scores (PRSs) in identifying high-risk individuals, different publicly available PRSs for breast (n=85), prostate (n=37), colorectal (n=22), and lung cancers (n=11) were examined in a prospective study of 21,694 Chinese adults. Methods: We constructed PRS using weights curated in the online PGS Catalog. PRS performance was evaluated by distribution, discrimination, predictive ability, and calibration. Hazard ratios (HR) and corresponding confidence intervals (CI) of the common cancers after 20 years of follow-up were estimated using Cox proportional hazard models for different levels of PRS. Results: A total of 495 breast, 308 prostate, 332 female-colorectal, 409 male-colorectal, 181 female-lung, and 381 male-lung incident cancers were identified. The area under receiver operating characteristic curve for the best-performing site-specific PRS were 0.61 (PGS000873, breast), 0.70 (PGS00662, prostate), 0.65 (PGS000055, female-colorectal), 0.60 (PGS000734, male-colorectal), 0.56 (PGS000721, female-lung), and 0.58 (PGS000070, male-lung), respectively. Compared to the middle quintile, individuals in the highest cancer-specific PRS quintile were 64% more likely to develop cancers of the breast, prostate, and colorectal. For lung cancer, the lowest cancer-specific PRS quintile was associated with 28–34% decreased risk compared to the middle quintile. In contrast, the HR observed for quintiles 4 (female-lung: 0.95 [0.61–1.47]; male-lung: 1.14 [0.82–1.57]) and 5 (female-lung: 0.95 [0.61–1.47]) were not significantly different from that for the middle quintile. Conclusions: Site-specific PRSs can stratify the risk of developing breast, prostate, and colorectal cancers in this East Asian population. Appropriate correction factors may be required to improve calibration. Funding: This work is supported by the National Research Foundation Singapore (NRF-NRFF2017-02), PRECISION Health Research, Singapore (PRECISE) and the Agency for Science, Technology and Research (A*STAR). WP Koh was supported by National Medical Research Council, Singapore (NMRC/CSA/0055/2013). CC Khor was supported by National Research Foundation Singapore (NRF-NRFI2018-01). Rajkumar Dorajoo received a grant from the Agency for Science, Technology and Research Career Development Award (A*STAR CDA - 202D8090), and from Ministry of Health Healthy Longevity Catalyst Award (HLCA20Jan-0022).

Abstract Background Family history, and genetic and non-genetic risk factors can stratify women according to their individual risk of developing breast cancer. The extent of overlap between these risk predictors is not clear. Methods In this case-only analysis involving 7600 Asian breast cancer patients diagnosed between age 30 and 75 years, we examined identification of high-risk patients based on positive family history, the Gail model 5-year absolute risk [5yAR] above 1.3%, breast cancer predisposition genes (protein-truncating variants [PTV] in ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, or TP53), and polygenic risk score (PRS) 5yAR above 1.3%. Results Correlation between 5yAR (at age of diagnosis) predicted by PRS and the Gail model was low (r=0.27). Fifty-three percent of breast cancer patients (n=4041) were considered high risk by one or more classification criteria. Positive family history, PTV carriership, PRS, or the Gail model identified 1247 (16%), 385 (5%), 2774 (36%), and 1592 (21%) patients who were considered at high risk, respectively. In a subset of 3227 women aged below 50 years, the four models studied identified 470 (15%), 213 (7%), 769 (24%), and 325 (10%) unique patients who were considered at high risk, respectively. For younger women, PRS and PTVs together identified 745 (59% of 1276) high-risk individuals who were not identified by the Gail model or family history. Conclusions Family history and genetic and non-genetic risk stratification tools have the potential to complement one another to identify women at high risk.

Asia is home to the most rapidly aging populations in the world. This study focuses on two countries in Asia that are advanced in terms of their demographic transition: the Republic of Korea and Singapore. We developed a demographic and economic state-transition microsimulation model based on the Korean Longitudinal Study of Aging and the Singapore Chinese Health Study. The model was employed to compare projections of functional status and disability among future cohorts of older adults, including disparities in disability prevalence by educational attainment. The model also projects increasing disparities in the prevalence of activities-of-daily-living disability and other chronic diseases between those with low and high educational attainment. Despite overall increases in educational attainment, all elderly, including those with a college degree, experience an increased burden of functional disability and chronic diseases because of survival to older ages. These increases have significant economic and social implications, including increased medical and long-term care expenditures, and an increased caregiver burden.

Abstract Background Patients with diabetes are at increased risk of developing chronic limb-threatening ischemia (CLTI) due to peripheral arterial disease, and this often results in lower extremity amputation (LEA). Little is known of the interaction between diabetes and other vascular risk factors in affecting the risk of CLTI. Methods We investigated the association of diabetes, and its interaction with hypertension, body mass index (BMI) and smoking, with the risk of LEA due to CLTI in the population-based Singapore Chinese Health Study. Participants were interviewed at recruitment (1993–1998) and 656 incident LEA cases were identified via linkage with nationwide hospital database through 2017. Multivariate-adjusted Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% CIs for the associations. Results The HR (95% CI) for LEA risk was 13.41 (11.38–15.79) in participants with diabetes compared to their counterparts without diabetes, and the risk increased in a stepwise manner with duration of diabetes (P for trend

Abstract Background and Aim Chronic hepatitis C virus (HCV) infection, long‐term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene–environment interactions in HCC. To address genetic susceptibility to HCC, we conducted a genome‐wide association study (GWAS). Methods Two case‐control studies on HCC were conducted in the United States. DNA samples were genotyped using the Illumian microarray chip with over 710 000 single nucleotide polymorphisms (SNPs). We compared these SNPs between 705 HCC cases and 1455 population controls for their associations with HCC and verified our findings in additional studies. Results In this GWAS, we found that two SNPs were associated with HCC at P

Abstract Background Among older adults, living alone is often associated with higher risk of Emergency Department (ED) admissions. However, older adults living alone are very heterogeneous in terms of health. As more older adults choose to live independently, it remains unclear if the association between living alone and ED admissions is moderated by health status. We studied the association between living alone and ED admission outcomes (number of admissions, inpatient days and inpatient costs) among older adults with and without multimorbidity. Methods We used data from 16,785 individuals of the third follow-up of the Singapore Chinese Health Study, a population-based cohort of older Singapore Chinese (mean age: 73(61-96) years). Participants were interviewed face-to-face from 2014 to 2016 for sociodemographic/health factors and followed-up for one year on ED admission outcomes using Singapore Ministry of Health’s Mediclaim Database. We first applied multivariable logistic regression and two-part models to test if living alone is a risk factor for ED admission outcomes. We then ran stratified and joint effect analysis to examine if the associations between living alone and ED admission outcomes were moderated by multimorbidity. Results Compared to living with others, living alone was associated with higher odds of ED admission [Odds Ratio (OR) 1.28, 95 % Confidence Interval(CI) 1.08-1.51)], longer inpatient days (+0.61, 95 %CI 0.25-0.97) and higher inpatient costs (+322 USD, 95 %CI 54-591). The interaction effects of living arrangement and multimorbidity on ED admissions and inpatient costs were not statistically different, whereas the interaction between living arrangements and multimorbidity on inpatient days was borderline significant (p-value for interaction=0.050). Compared to those living with others and without multimorbidity, the relative mean increase was 1.13 inpatient days (95 %CI 0.39-1.86) for those living alone without multimorbidity, and 0.73 inpatient days ( 95 %CI 0.29-1.17) for those living alone with multimorbidity. Conclusions Older adults living alone were at higher risk of ED admission and higher inpatient costs regardless of multimorbidity, while those living alone without multimorbidity had the longest average inpatient days. To enable aging in place while avoiding ED admissions, interventions could provide instrumental support and regular health monitoring to older adults living alone, regardless of their health status.

Background: Previous analysis showed that the incidence rates of skin cancer in Singapore increased from 1968 to 2006, especially among older Chinese, and particularly for basal cell carcinoma (BCC). Objective: We updated the skin cancer incidence rates and time trends among the Chinese, Malays, and Indians in Singapore. Methods: We analyzed the skin cancer incidence from the nationwide Singapore Cancer Registry from 1968 to 2016. Results: Among 12,692 cases diagnosed from 1968 to 2016, there were 8367 (65.9%) cases of BCC, 3598 (28.3%) of squamous cell carcinoma (SCC), and 727 (5.8%) of melanoma. The mean ages at skin cancer diagnosis were 72.7 years for SCC, 66.9 years for BCC, and 59.8 years for melanoma. Sun-exposed areas accounted for 81.3% of BCCs, 61.6% of SCCs, and 26.7% of melanomas. The age-standardized incidence rate of cutaneous BCC was highest in the Chinese and increased by 2.5 fold over the study period, followed by a lower rate and slower increase in the Malays, and the lowest rate among the Indians. The SCC and melanoma incidences remained low in all 3 ethnicities during this study period. The Chinese had the highest relative risk for developing any skin cancer (P

Abstract Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40–80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was − 0.91 standard-deviations lower in women than men (95%CI − 0.98; − 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m2 increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p

Abstract Background Blood type has been associated with the risk of gastric cancer, but few studies have examined the association with esophageal squamous cell carcinoma (ESCC). Methods We conducted a case-control study using genotyping data of Chinese individuals, including cases of 2022 ESCC, 1189 gastric cardia adenocarcinoma, 1161 gastric noncardia adenocarcinoma, and 2696 controls. Genetic blood type was imputed using three single nucleotide polymorphisms. We used logistic regression to examine the association between blood type and the risk of each cancer. Results Compared to blood type O, the risk of ESCC was significantly elevated for blood type B and AB, with the highest risk for type AB (OR, 95%CI: 1.34, 1.07–1.67). Analysis of genotype suggested that the association of ESCC was from carrying the B allele. Similarly, blood type was significantly associated with gastric noncardia adenocarcinoma (P

Xuling Chang et al. study whether low frequency variants are associated with leukocyte telomere length and whether these variants predispose to incident cancers and mortalities among East Asians. They find that three East Asian specific variants at POT1, TERF1 and STN1 loci are associated with leukocyte telomere length and report a mechanistic pathway linking TERF1, leukocyte telomere length and incident colon cancer.

Abstract Background Although obesity can be clinically defined by body mass index (BMI), waist circumference, percent body fat, or visceral fat area, it is unclear which specific measure is best associated with mobility disability in oldest-old adults. Methods Among 589 Chinese participants aged 85 years and older in a population-based cohort in Singapore, we measured waist circumference, computed BMI, estimated appendicular skeletal muscle mass, percent body fat, and visceral fat area using bioelectrical impedance analysis, and evaluated mobility disability using the Loco-Check questionnaire. We computed areas under the receiver operating characteristic curves (AUCROC) to compare how well these measures discriminated between those with and without mobility disability. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the associations between obesity defined by these measures and mobility disability. Results Compared to BMI, which had an AUCROC (95% CI) of 0.68 (0.64–0.72) for the discrimination of mobility disability, only visceral fat area had a significantly higher discriminative performance [AUCROC (95% CI) of 0.71 (0.67–0.75) (Padjusted = 0.002)]. The optimal cut-offs of visceral fat area for the discrimination of mobility disability were ≥ 104 cm2 in men and ≥ 137 cm2 in women. In fully adjusted models, only obesity defined by visceral fat area was significantly associated with mobility disability [OR (95% CI) of 2.04 (1.10–3.77)]; obesity defined by the other measures were not associated with mobility disability after adjusting for visceral fat. Conclusion In oldest-old adults, visceral fat area was the best discriminator for obesity associated with mobility disability.

Introduction: Body mass index (BMI), despite being widely used as a marker of obesity, fails to fully capture cardiovascular risks as it is an insufficient biomarker of abdominal adiposity, unlike waist circumference (WC). We aim to characterize associations between BMI and WC with cardiovascular structure and function in older adults. Methods: Among an observational cohort study of community older adults, transthoracic echocardiography determined cardiovascular structure and function, while aerobic capacity was determined by peak oxygen uptake (VO2) metrics. The cut-offs for obesity were 27.5kg/m2 for BMI, and >90cm for males and >80cm for females for WC. Results: 970 older adults without cardiovascular disease [mean age 73±4 years, 432 (44%) males], 124 (12.8%) were obese by BMI definition while 347 (35.7%) were obese by WC definition. Inter-definitional agreement was fair (Cohen’s κ=0.345). Unlike BMI definition, participants defined as obese by WC were more likely to be women (65% vs 50%, p

Polygenic risk scores predict the likelihood that an individual will develop a certain cancer, however these are often specific for a given population. Here, the authors show that a risk score developed to assess the risk of breast cancer in European women can also predict risk in Asian populations.

BackgroundMultiple biomarkers have performed well in predicting type 2 diabetes mellitus (T2DM) risk in Western populations. However, evidence is scarce among Asian populations.MethodsPlasma triglyceride-to-high density lipoprotein (TG-to-HDL) ratio, alanine transaminase (ALT), high-sensitivity C-reactive protein (hs-CRP), ferritin, adiponectin, fetuin-A, and retinol-binding protein 4 were measured in 485 T2DM cases and 485 age-and-sex matched controls nested within the prospective Singapore Chinese Health Study cohort. Participants were free of T2DM at blood collection (1999 to 2004), and T2DM cases were identified at the subsequent follow-up interviews (2006 to 2010). A weighted biomarker score was created based on the strengths of associations between these biomarkers and T2DM risks. The predictive utility of the biomarker score was assessed by the area under receiver operating characteristics curve (AUC).ResultsThe biomarker score that comprised of four biomarkers (TG-to-HDL ratio, ALT, ferritin, and adiponectin) was positively associated with T2DM risk (P trend

Objectives We aimed to evaluate the association between fibre intake and its food sources, and the risk of total knee replacement (TKR) due to severe knee osteoarthritis (KOA).Methods We used data from the Singapore Chinese Health Study, a prospective cohort study that recruited 63 257 participants aged 45–74 years from 1993 to 1998. At baseline, we assessed diet using a validated 165-item semiquantitative food frequency questionnaire, together with body mass index (BMI) and lifestyle factors. Incident TKR cases were identified via record linkage with nationwide hospital discharge database through 2017.Results There were 2816 cases of incident TKR due to severe KOA. The total fibre intake at baseline was not associated with the risk of TKR after adjustment for confounders. Among the food sources of fibre, higher intake of legumes was associated with a lower risk of TKR in a dose-dependent manner; compared with those having the lowest quartile intake, HR (95% CI) was 0.86 (0.76, 0.96) for those having the highest quartile intake (p for trend=0.004). This association was consistent after including BMI in the model and homogeneous across BMI categories. The consumption of other fibre sources, namely grain products, nuts and seeds, soy food, fruits and vegetables, was not associated with the risk of TKR.Conclusion Intake of legumes, but not total fibre, was associated with a reduced risk of TKR. Further research is needed to replicate our findings and to evaluate possible biological mechanisms that could explain the effect of dietary legumes on pathogenesis or progression of KOA.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Abstract Aims Galectin‐3 (Gal‐3) is implicated in the pathogenesis of heart failure and is also influenced by ageing. This study aims to determine the extent to which Gal‐3 levels estimate odds of myocardial dysfunction in ageing cohorts, ‘upstream’ prior to clinical disease. Methods and results Four hundred seventy‐five asymptomatic subjects underwent simultaneous assessments of cardiovascular structure and function, with measurements of circulating Gal‐3. Myocardial dysfunction was defined as impaired myocardial relaxation (ratio of peak velocity flow in early diastole E (m/s) to peak velocity flow in late diastole by atrial contraction A (m/s)

BackgroundFetuin-A is a hepatokine that involved in the pathogenesis of insulin resistance. Previous epidemiological studies have found a positive association between blood fetuin-A and type 2 diabetes mellitus (T2DM) risk among Caucasians and African Americans. We aimed to investigate the prospective relationship between fetuin-A and T2DM in an Asian population for the first time.MethodsA nested case-control study was established within a prospective cohort of Chinese living in Singapore. At blood collection (1999 to 2004), all participants were free of diagnosed T2DM and aged 50 to 79 years. At subsequent follow-up (2006 to 2010), 558 people reported to have T2DM and were classified as incident cases, and 558 controls were randomly chosen from the participants who did not develop T2DM to match with cases on age, sex, dialect group, and date of blood collection. Plasma fetuin-A levels were measured retrospectively in cases and controls using samples collected at baseline. Conditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval (CI). Restricted cubic spline analysis was used to examine a potential non-linear association between fetuin-A levels and T2DM risk.ResultsCompared with those in the lowest fetuin-A quintile, participants in the highest quintile had a two-fold increased risk of developing T2DM (OR, 2.06; 95% CI, 1.21 to 3.51). A non-linear association was observed (P nonlinearity=0.005), where the association between fetuin-A levels and T2DM risk plateaued at plasma concentrations around 830 µg/mL.ConclusionThere is a positive association between plasma fetuin-A levels and risk of developing T2DM in this Chinese population.

Shortening of leukocyte telomere length (LTL) is associated with age and increased risk for various chronic diseases. Here, the authors report genome-wide association studies for LTL in Singaporean Chinese populations and find that longer LTL associates with less severe outcomes of respiratory disease phenotypes.

Abstract Background Telomeres and telomerase play key roles in the chromosomal maintenance and stability. Recent epidemiological studies have shown that longer telomeres are associated with increased risk of several cancer types. However, epidemiological data for telomere length and risk of breast cancer are sparse. Methods We prospectively studied the association between telomere length and risk of breast cancer in 14,305 middle-aged or older Chinese women of the Singapore Chinese Health Study including 442 incident breast cancer cases after 12.3 years of follow-up. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiple quantitative polymerase chain reaction method. The Cox proportional hazard regression method was used to estimate hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for breast cancer associated with longer telomeres after adjustment for potential confounders. Results Longer telomeres were significantly associated with higher risk of breast cancer in a dose-dependent manner (P trend = 0.006); the highest quartile of telomere length was associated with a statistically significant 47% higher risk of breast cancer compared with the lowest quartile of telomere length after the adjustment for age and other known risk factors for breast cancer (HRQ4 vs Q1 = 1.47, 95% CI = 1.11, 1.94). Conclusions The findings of the present study support the hypothesis that longer telomeres may be a risk factor for breast cancer. Telomere length in peripheral blood leukocytes may be developed as a biomarker for breast cancer risk prediction.

GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

Abstract Background Although retinol binding protein 4 (RBP4) has been implicated in insulin resistance in experimental studies, the association between RBP4 and risk of type 2 diabetes remains unclear. We assessed this association in a Chinese population, and pooled our results with those from two prior studies. Methods Plasma RBP4 levels were measured among 571 incident type 2 diabetes cases and 571 controls nested within the Singapore Chinese Health Study. All participants were free of diabetes, cancer and cardiovascular disease at blood collection (1999–2004). Incident cases of physician-diagnosed diabetes were self-reported at subsequent interviews (2006–2010). Results Plasma RBP4 levels were significantly higher in men than women, and the respective median values were 30 (interquartile range: 24–35) μg/mL and 25 (interquartile range: 21–31) μg/mL, respectively. With adjustment for diabetes risk factors, compared to the lowest quartile, the odds ratio (OR) and confidence interval (CI) for risk of type 2 diabetes associated with the highest quartile of RBP4 levels were 1.23 (0.73–2.07; P-trend = 0.14) in all subjects, 0.63 (0.27–1.45; P-trend = 0.65) in men, and 2.29 (1.05–5.00; P-trend = 0.018) in women. The difference in the risk estimates between men and women was statistically significant (P-interaction = 0.032). When we pooled our results with two prior studies, ORs (95% CIs) comparing high versus low category of RBP4 was 1.01 (0.70–1.46; I 2 = 8.2%; P-heterogeneity = 0.34) in men, and 1.73 (1.28–2.33; I 2 = 0%; P-heterogeneity = 0.80) in women. Conclusions Increased plasma RBP4 levels were associated with higher risk of type 2 diabetes in women but not in men.

Abstract Background Experimental studies have shown that exposure to incense burning may have deleterious effects on kidney function and architecture. However, the association between chronic exposure to incense smoke and risk of end-stage renal disease (ESRD) has not been reported in epidemiologic studies. Methods We investigated this association in the Singapore Chinese Health Study, a prospective population-based cohort of 63,257 Chinese men and women of 45–74 years of age in Singapore during recruitment from 1993 to 1998. Information on the practice of incense burning at home, diet, lifestyle and medical history was collected at baseline interviews. ESRD cases were identified through linkage with the nationwide Singapore Renal Registry through 2015. We used Cox proportional hazards regression analysis to estimate hazard ratio (HR) and 95% confidence interval (CI) of ESRD associated with domestic incense burning. Results Among cohort participants, 76.9% were current incense users. After an average 17.5 years of follow-up, there were 1217 incident ESRD cases. Compared to never users, the multivariable-adjusted HR for ESRD risk was 1.05 (95% CI, 0.80 to 1.38) for former users and 1.26 (95% CI, 1.02 to1.57) for current users of incense. In analysis by daily or non-daily use and duration, the increased ESRD risk was observed in daily users who had used incense for > 20 years; HR was 1.25 (95% CI, 1.07 to 1.46). Conversely, the risk was not increased in those who did not use incense daily or who had used daily but for ≤20 years. Conclusions Our findings demonstrate that long-term daily exposure to domestic incense burning could be associated with a higher risk of ESRD in the general population.

Abstract Background Haptoglobin (Hp) is a plasma protein with strong anti‐inflammation and antioxidant activities. Its plasma level is known to be inversely associated with many inflammatory diseases, including cardiovascular diseases. However, the association of HP genetic variants with coronary artery disease (CAD) severity/mortality, and how they interact with common CAD risk factors are largely unknown. Methods We conducted the analysis in a Singaporean Chinese CAD population with Gensini severity scores (N = 582) and subsequently evaluated the significant findings in an independent cohort with cardiovascular mortality (excluding stroke) as outcome (917 cases and 19,093 controls). CAD risk factors were ascertained from questionnaires, and stenosis information from medical records. Mortality was identified through linkage with the nationwide registry of births and deaths in Singapore. Linear regression analysis between HP genetic variant (rs217181) and disease outcome were performed. Interaction analyses were performed by introducing an interaction term in the same regression models. Results Although rs217181 was not significantly associated with CAD severity and cardiovascular mortality (excluding stroke) in all subjects, when stratified by hypertension status, hypertensive individuals with the minor T allele have more severe CAD (β = 0.073, SE = 0.030, p = 0.015) and non‐hypertensive individuals with the T allele have lower risk for mortality (odds ratio = 0.771 (0.607–0.980), p = 0.033). Conclusion HP genetic variant is not associated with CAD severity and mortality in the general population. However, hypertensive individuals with the rs217181 T allele associated with higher Hp levels had more severe CAD while non‐hypertensive individuals with the same allele had lower risk for mortality in the Chinese population.

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, the authors perform discovery GWAS for BP in East Asians and meta-analysis in East Asians and Europeans and report ancestry-specific BP SNPs and selection signals.

Background Although hypertension is an established risk factor for chronic kidney disease, less is known about the relationship of pulse pressure (PP), a measure of arterial stiffness, with chronic kidney disease. We investigated the association of systolic blood pressure (BP), diastolic BP, PP, and mean arterial pressure with the risk of end‐stage renal disease (ESRD) in the prospective population‐based Singapore Chinese Health Study. Methods and Results We used data from 30 636 participants who had BP measured at ages 46 to 85 years during follow‐up I interviews between 1999 and 2004. Information on lifestyle factors was collected at recruitment from 1993 to 1998, and selected factors were updated at follow‐up I. We identified 463 ESRD cases over an average 11.3 years of follow‐up I by linkage with the nationwide Singapore Renal Registry. Cox proportional hazards regression models were used to assess the relations between different BP indexes and ESRD risk. Each BP index was positively associated with ESRD when studied individually. However, when PP was included as a covariate, systolic and diastolic BP and mean arterial pressure were no longer associated with ESRD. Conversely, PP remained significantly associated with ESRD risk in a dose‐dependent manner (Ptrend

The chromosome 15q25.1 locus is a leading susceptibility region for lung cancer. Here, the authors interrogate three GWAS cohorts with 42,901 individuals to investigate potential pathological pathways such as gated channel activity and neuroactive ligand receptor interaction in lung cancer etiology.

Abstract Background Recent genome-wide association studies (GWAS) have identified 97 body-mass index (BMI) associated loci. We aimed to evaluate if dietary intake modifies BMI associations at these loci in the Singapore Chinese population. Methods We utilized GWAS information from six data subsets from two adult Chinese population (N = 7817). Seventy-eight genotyped or imputed index BMI single nucleotide polymorphisms (SNPs) that passed quality control procedures were available in all datasets. Alternative Healthy Eating Index (AHEI)-2010 score and ten nutrient variables were evaluated. Linear regression analyses between z score transformed BMI (Z-BMI) and dietary factors were performed. Interaction analyses were performed by introducing the interaction term (diet x SNP) in the same regression model. Analysis was carried out in each cohort individually and subsequently meta-analyzed using the inverse-variance weighted method. Analyses were also evaluated with a weighted gene-risk score (wGRS) contructed by BMI index SNPs from recent large-scale GWAS studies. Results Nominal associations between Z-BMI and AHEI-2010 and some dietary factors were identified (P = 0.047-0.010). The BMI wGRS was robustly associated with Z-BMI (P = 1.55 × 10− 15) but not with any dietary variables. Dietary variables did not significantly interact with the wGRS to modify BMI associations. When interaction analyses were repeated using individual SNPs, a significant association between cholesterol intake and rs4740619 (CCDC171) was identified (β = 0.077, adjPinteraction = 0.043). Conclusions The CCDC171 gene locus may interact with cholesterol intake to increase BMI in the Singaporean Chinese population, however most known obesity risk loci were not associated with dietary intake and did not interact with diet to modify BMI levels.

Abstract Recent genome-wide association studies (GWAS) have identified multiple loci associated with coronary artery disease (CAD) among predominantly Europeans. However, their relevance to multi-ethnic populations from Southeast Asia is largely unknown. We performed a meta-analysis of four GWAS comprising three Chinese studies and one Malay study (Total N = 2,169 CAD cases and 7,376 controls). Top hits (P T, G185C) in APOA5 for CAD that reached robust genome-wide significance (Meta P = 7.09 × 10−10, OR = 1.636). Conditional probability analysis indicated that the association at rs2075291 was independent of previously reported index SNP rs964184 in APOA5. We further replicated 10 loci previously identified among predominantly Europeans (P: 1.33 × 10−7–0.047). Seven pathways (P: 1.10 × 10−5–0.019) were identified. We identified a missense SNP, rs2075291, in APOA5 associated with CAD at a genome-wide significance level and provided new insights into pathways contributing to the susceptibility to CAD in the multi-ethnic populations from Southeast Asia.

Abstract Background SuPAR is a biomarker that reflects the level of immune activation. As inflammation plays an important role in the ageing process of the cardiovascular system, we hypothesized that suPAR might be a useful predictive biomarker of the ageing heart. Methods We performed conventional and tissue Doppler echocardiography and measured plasma suPAR levels. Results We studied community adults (n=120, 37.5% female) (mean age: 70.3±9.3 years) without known cardiovascular disease (CVD). Participants with impaired myocardial relaxation were older (84% vs 59% were aged ≥71 years, p=0.002), with more diabetes mellitus (27% vs 11%, p=0.034). SuPAR levels were higher among participants with impaired myocardial relaxation (3.9 ng/ml vs 3.0 ng/ml, p=0.015). At the univariate level, older age (OR 3.6; 95%CI 1.6, 8.5; p=0.003), diabetes mellitus (OR 3.04; 95%CI 1.1, 8.8; p=0.04), systolic blood pressure (OR 1.03; 95%CI 1.001, 1.1; p=0.041) and suPAR levels ≥3.00ng/ml (OR 3.4; 95%CI 1.16, 7.4; p=0.002) were associated with impaired myocardial relaxation. In multivariable regression analysis, only older age (OR 2.8; 95%CI 1.1, 6.7; p=0.026) and suPAR (OR 2.7; 95%CI 1.2, 6.1; p=0.018) remained independently associated with impaired myocardial relaxation. Receiver operating characteristics (ROC) curve analysis revealed an area under the curve (AUC) value of 0.63 (95% CI 0.54, 0.71) for model that included age alone. Addition of suPAR significantly increased AUC value to 0.70 (95%CI 0.60, 0.79), which was significantly larger than the model with age alone (p=0.016). Conclusion We demonstrate additional ability of suPAR, over age, to predict impaired myocardial relaxation. Trial registration ClinicalTrials.gov Identifier: NCT02791139 (Registered May 31, 2016).

Abstract Background Fibroblast growth factor 21 (FGF-21) is mainly secreted by liver and has been reported to be involved in the pathogenesis of type 2 diabetes. Some prospective studies have shown a positive association between FGF-21 and diabetes risk. However, no study has examined whether the association differed by sex, which has been reported between FGF-21 and atherosclerosis. Therefore, we prospectively evaluated the sex-specific association between FGF-21 and diabetes in a Chinese population. Methods Serum FGF-21 concentration was measured in a case-control study comprising of 251 incident diabetes cases and 251 age-sex-matched controls nested within a prospective population-based cohort, the Singapore Chinese Health Study. At blood collection between 1999 and 2004, participants were free of diagnosed diabetes, cardiovascular disease, and cancer. Incident self-reported diabetes cases were identified at follow-up II interview (2006–2010). Odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariable logistic regression models. Results After adjustment for risk biomarkers of diabetes including lipids, liver enzymes and inflammatory marker, the OR of type 2 diabetes with per one unit increment in log FGF-21 concentration was 1.16 (95% CI 0.90–1.50). Significant interaction was found with sex (P-interaction = 0.029): the OR (95% CI) was 1.50 (1.00-2.25) in women and 0.89 (0.52–1.53) in men. Conclusions Higher serum FGF-21 level was associated with an increased risk of diabetes in Chinese women but not in men. The sex difference in the association between FGF-21 and diabetes risk deserves further investigation and replication in other populations.

Objective To study the association of educational level and risk of death from all causes, cardiovascular disease (CVD) and cancer among Asian populations.Design A pooled analysis of 15 population-based cohort studies.Setting and participants 694 434 Asian individuals from 15 prospective cohorts within the Asia Cohort Consortium.Interventions None.Main outcome measures HRs and 95% CIs for all-cause mortality, as well as for CVD-specific mortality and cancer-specific mortality.Results A total of 694 434 participants (mean age at baseline=53.2 years) were included in the analysis. During a mean follow-up period of 12.5 years, 103 023 deaths were observed, among which 33 939 were due to cancer and 34 645 were due to CVD. Higher educational levels were significantly associated with lower risk of death from all causes compared with a low educational level (≤primary education); HRs and 95% CIs for secondary education, trade/technical education and ≥university education were 0.88 (0.85 to 0.92), 0.81 (0.73 to 0.90) and 0.71 (0.63 to 0.80), respectively (ptrend=0.002). Similarly, HRs (95% CIs) were 0.93 (0.89 to 0.97), 0.86 (0.78 to 0.94) and 0.81 (0.73 to 0.89) for cancer death, and 0.88 (0.83 to 0.93), 0.77 (0.66 to 0.91) and 0.67 (0.58 to 0.77) for CVD death with increasing levels of education (both ptrend

Background The association of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern with stroke and coronary artery disease (CAD) mortality has not been evaluated in Asian populations, and the role of mineral intakes as potential mediators is not clear. Methods and Results We used data from 57 078 participants of the Singapore Chinese Health Study aged 45 to 74 years at baseline (1993–1998). Information on usual diet was collected by a validated 165‐item food frequency questionnaire at recruitment, and mortality information was obtained via registry linkage up to December 31, 2014. We constructed DASH scores based on quintiles of intake of 7 predefined food items and sodium. Cox proportional hazard models were used to calculate hazard ratios and corresponding 95% CIs. Greater adherence to the DASH dietary pattern was significantly associated with a lower risk of CAD (hazard ratio between extreme quintiles, 0.76; 95% CI, 0.65–0.90; P trend