Publications by authors named "Virginia Byers Kraus"

71 Publications

Association of Sleep and Circadian Patterns and Genetic Risk with Incident Type 2 Diabetes: A Large Prospective Population-Based Cohort Study.

Eur J Endocrinol 2021 Sep 1. Epub 2021 Sep 1.

C Mao, Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, China.

Objective To examine the association of incident type 2 diabetes (T2D) risk with sleep factors, genetic risk, and their combination effects. Design Large prospective population-based cohort study. Methods This population-based prospective cohort study included 360 403 (mean [SD] age: 56.6 [8.0] years) participants without T2D at baseline from the UK Biobank. Genetic risk was categorized as high (highest quintile), intermediate (quintiles 2 to 4), and low (lowest quintile) based on a polygenic risk score for T2D. Sleep scores, including long or short sleep duration, insomnia, snoring, late chronotype, and excessive daytime sleepiness, were categorized as an unfavourable, intermediate, or favourable sleep and circadian pattern. Results During a median follow-up of 9.0 years, 13 120 incident T2D cases were recorded. Among the participants with an unfavourable sleep and circadian pattern, 6.96% (95% CI, 6.68%-7.24%) developed T2D versus 2.37% (95% CI, 2.28%-2.46%) of participants with a favourable sleep and circadian pattern (adjusted HR: 1.53, 95% CI: 1.45-1.62). Of participants with a high genetic risk, 5.53% (95% CI, 5.36%-5.69%) developed T2D versus 2.01% (95% CI, 1.91%-2.11%) of participants with a low genetic risk (adjusted HR: 2.89, 95% CI: 2.72-3.07). The association with sleep and circadian patterns was independent of genetic risk strata. Participants in the lowest quintile with an unfavourable sleep and circadian pattern were 3.97-fold more likely to develop T2D than those in the lowest quintile with a favourable sleep and circadian pattern. Conclusions Sleep and circadian patterns and genetic risk were independently associated with incident T2D. These results indicate the benefits of adhering to a healthy sleep and circadian pattern in entire populations, independent of genetic risk.
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http://dx.doi.org/10.1530/EJE-21-0314DOI Listing
September 2021

Extracellular Vesicles as Biological Indicators and Potential Sources of Autologous Therapeutics in Osteoarthritis.

Int J Mol Sci 2021 Aug 3;22(15). Epub 2021 Aug 3.

Duke Molecular Physiology Institute, Duke University School of Medicine, Duke University, Durham, NC 27701, USA.

Along with cytokines, extracellular vesicles (EVs) released by immune cells in the joint contribute to osteoarthritis (OA) pathogenesis. By high-resolution flow cytometry, we characterized 18 surface markers and 4 proinflammatory cytokines carried by EVs of various sizes in plasma and synovial fluid (SF) from individuals with knee OA, with a primary focus on immune cells that play a major role in OA pathogenesis. By multiplex immunoassay, we also measured concentrations of cytokines within (endo) and outside (exo) EVs. EVs carrying HLA-DR, -DP and -DQ were the most enriched subpopulations in SF relative to plasma (25-50-fold higher depending on size), suggesting a major contribution to the SF EV pool from infiltrating immune cells in OA joints. In contrast, the CD34 medium and small EVs, reflecting hematopoietic stem cells, progenitor cells, and endothelial cells, were the most significantly enriched subpopulations in plasma relative to SF (7.3- and 7.7-fold higher). Ratios of EVs derived from neutrophils and lymphocytes were highly correlated between SF and plasma, indicating that plasma EVs could reflect OA severity and serve as systemic biomarkers of OA joint pathogenesis. Select subsets of plasma EVs might also provide next generation autologous biological products for intra-articular therapy of OA joints.
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http://dx.doi.org/10.3390/ijms22158351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347326PMC
August 2021

A template for physical resilience research in older adults: Methods of the PRIME-KNEE study.

J Am Geriatr Soc 2021 Jul 29. Epub 2021 Jul 29.

Duke University School of Medicine, Durham, North Carolina, USA.

Background: Older adults with similar health conditions often experience widely divergent outcomes following health stressors. Variable recovery after a health stressor may be due in part to differences in biological mechanisms at the molecular, cellular, or system level, that are elicited in response to stressors. We describe the PRIME-KNEE study as an example of ongoing research to validate provocative clinical tests and biomarkers that predict resilience to specific health stressors.

Methods: PRIME-KNEE is an ongoing, prospective cohort study that will enroll 250 adults ≥60 years undergoing total knee arthroplasty. Data are collected at baseline (pre-surgery), during surgery, daily for 7 days after surgery, and at 1, 2, 4, and 6 months post-surgery. Provocative tests include a cognition-motor dual-task walking test, cerebrovascular reactivity assessed by functional near-infrared spectroscopy, peripheral blood mononuclear cell reactivity ex vivo to lipopolysaccharide toxin and influenza vaccine, and heart rate variability during surgery. Cognitive, psychological, and physical performance batteries are collected at baseline to estimate prestressor reserve. Demographics, medications, comorbidities, and stressor characteristics are abstracted from the electronic medical record and via participant interview. Blood-based biomarkers are collected at baseline and postoperative day 1. Repeated measures after surgery include items from a delirium assessment tool and pain scales administered daily by telephone for 7 days and cognitive change index (participant and informant), lower extremity activities of daily living, pain scales, and step counts assessed by Garmin actigraphy at 1, 2, 4, and 6 months after surgery. Statistical models use these measures to characterize resilience phenotypes and evaluate prestressor clinical indicators associated with poststressor resilience.

Conclusion: If PRIME-KNEE validates feasible clinical tests and biomarkers that predict recovery trajectories in older surgical patients, these tools may inform surgical decision-making, guide pre-habilitation efforts, and elucidate mechanisms underlying resilience. This study design could motivate future geriatric research on resilience.
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http://dx.doi.org/10.1111/jgs.17384DOI Listing
July 2021

A phase 2 trial of the somatostatin analog pasireotide to prevent GI toxicity and acute GVHD in allogeneic hematopoietic stem cell transplant.

PLoS One 2021 25;16(6):e0252995. Epub 2021 Jun 25.

Division of Hematologic Malignancies and Cellular Therapy, Duke University School of Medicine, Durham, NC, United States of America.

Background: Allogeneic hematopoietic stem cell transplantation (HCT) is an often curative intent treatment, however it is associated with significant gastrointestinal (GI) toxicity and treatment related mortality. Graft-versus-host disease is a significant contributor to transplant-related mortality. We performed a phase 2 trial of the somatostatin analog pasireotide to prevent gastrointestinal toxicity and GVHD after myeloablative allogeneic HCT.

Methods: Patients received 0.9mg pasireotide every 12 hours from the day prior to conditioning through day +4 after HCT (or a maximum of 14 days). The primary outcomes were grade 3-4 gastrointestinal toxicity through day 30 and acute GVHD. Secondary outcomes were chronic GVHD, overall survival and relapse free survival at one year. Stool and blood samples were collected from before and after HCT for analyses of stool microbiome, local inflammatory markers, and systemic inflammatory and metabolic markers. Results were compared with matched controls.

Results: Twenty-six patients received pasireotide and were compared to 52 matched contemporaneous controls using a 1-2 match. Grade 3-4 GI toxicity occurred in 21 (81%) patients who received pasireotide and 35 (67%) controls (p = 0.33). Acute GVHD occurred in 15 (58%) patients in the pasireotide group and 28 (54%) controls (p = 0.94). Chronic GVHD occurred in 16 patients in the pasireotide group (64%) versus 22 patients in the control group (42%) (p = 0.12). Overall survival at 1 year in the pasireotide group was 63% (95% CI: 47%,86%) versus 82% (95% CI: 72%, 93%) in controls (log-rank p = 0.006). Relapse-free survival rate at one year was 40% (95% CI: 25%, 65%) in the pasireotide group versus 78% (95% CI: 68%, 91%) in controls (log-rank p = 0.002). After controlling for the effect of relevant covariates, patients in the pasireotide group had attenuated post-HCT loss of microbial diversity. Analysis of systemic inflammatory markers and metabolomics demonstrated feasibility of such analyses in patients undergoing allogeneic HCT. Baseline level and pre-to-post transplant changes in several inflammatory markers (including MIP1a, MIP1b, TNFa, IL8Pro, and IL6) correlated with likelihood of survival.

Conclusions: Pasireotide did not prevent gastrointestinal toxicity or acute GVHD compared to contemporaneous controls. Pasireotide was associated with numerically higher chronic GVHD and significantly decreased OS and RFS compared to contemporaneous controls. Pasireotide may provide a locally protective effect in the stool microbiome and in local inflammation as measured by stool calprotectin, stool beta-defensin, and stool diversity index.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252995PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232534PMC
June 2021

Profiling and targeting connective tissue remodeling in autoimmunity - A novel paradigm for diagnosing and treating chronic diseases.

Autoimmun Rev 2021 Jan 12;20(1):102706. Epub 2020 Nov 12.

Institute of Translational Immunology and Research Center for Immune Therapy, University Medical Center, Mainz, Germany; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address:

Connective tissue (ConT) remodeling is an essential process in tissue regeneration, where a balanced replacement of old tissue by new tissue occurs. This balance is disturbed in chronic diseases, often autoimmune diseases, usually resulting in the buld up of fibrosis and a gradual loss of organ function. During progression of liver, lung, skin, heart, joint, skeletal and kidney diseasesboth ConT formation and degradation are elevated, which is tightly linked to immune cell activation and a loss of specific cell types and extracellular matrix (ECM) structures that are required for normal organ function. Here, we address the balance of key general and organ specific components of the ECM during homeostasis and in disease, with a focus on collagens, which are emerging as both structural and signaling molecules harbouring neoepitopes and autoantigens that are released during ConT remodeling. Specific collagen molecular signatures of ConT remodeling are linked to disease activity and stage, and to prognosis across different organs. These signatures accompany and further drive disease progression, and often become detectable before clinical disease manifestation (illness). Recent advances allow to quantify and define the nature of ConT remodeling via blood-based assays that measure the levels of well-defined collagen fragments, reflecting different facets of ConT formation and degradation, and associated immunological processes. These novel serum assays are becoming important tools of precision medicine, to detect various chronic and autoimmune diseases before their clinical manifestation, and to non-invasively monitor the efficacy of a broad range of pharmacological interventions.
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http://dx.doi.org/10.1016/j.autrev.2020.102706DOI Listing
January 2021

Fine Particulate Matter and Poor Cognitive Function among Chinese Older Adults: Evidence from a Community-Based, 12-Year Prospective Cohort Study.

Environ Health Perspect 2020 06 18;128(6):67013. Epub 2020 Jun 18.

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China.

Background: Research on the relationship between long-term exposure to particulate matter with aerodynamic diameter () and poor cognitive function is lacking in developing countries, especially in highly polluted areas.

Objectives: We evaluated associations of long-term exposure to with poor cognitive function in a diverse, national sample of older adults in China.

Methods: This analysis included data on 13,324 older adults (5,879 who were 65-79 years of age, 3,052 who were 80-89 years of age, 2,634 who were 90-99 years of age, and 1,759 who were of age) with normal cognitive function at baseline from March 2002 to September 2014, with 64,648 person-years of follow-up. We used a geographic information system analysis to estimate the annual average satellite-derived concentration for the geocoded location of the participants' baseline residences. Poor cognitive function was defined as a score of less than 18 on the Chinese version of the Mini-Mental State Examination (MMSE). Competing risk models were performed to explore the association of with poor cognitive function.

Results: Each increase in was associated with a 5.1% increased risk of poor cognitive function [adjusted hazard ratio (HR): 1.051; 95% confidence interval (CI): 1.023, 1.079]. Compared to the lowest quartile of (), adjusted values were 1.20 (95% CI: 1.09, 1.33), 1.27 (95% CI: 1.15, 1.41), and 1.21 (95% CI: 1.09, 1.34) for the second (), third (), and fourth () quartiles of , respectively ( for trend ). Subgroup analyses suggested stronger associations between and poor cognitive impairment in men than women. The association was positive in the 65- to 79- and age group but not significant and positive in the other two age groups with similar results.

Conclusion: was identified as a risk factor for poor cognitive function in Chinese older adults. Improving air quality may reduce the future population burden of poor cognitive function, especially in areas with high air pollution. https://doi.org/10.1289/EHP5304.
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http://dx.doi.org/10.1289/EHP5304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302441PMC
June 2020

Leisure activities and disability in activities of daily living among the oldest-old Chinese population: evidence from the Chinese Longitudinal Healthy Longevity Study.

Aging (Albany NY) 2020 06 12;12(11):10687-10703. Epub 2020 Jun 12.

Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.

Introduction: To investigate the independent and joint effects of leisure activities on disability in activities of daily living (ADL) among the oldest-old Chinese population (aged ≥ 80 years).

Results: A total of 3696 participants with ADL disability were identified during the median follow-up period of 3.1 years. Compared to the participants who "never" watched TV or listened to the radio and who "never" kept domestic animals or pets, those who engaged in these activities "almost every day" had a significantly lower ADL disability risk (adjusted hazard ratios were 0.74 and 0.66, respectively; both < 0.001). Furthermore, participants engaging in multiple leisure activities showed a reduced risk of ADL disability ( for trend < 0.001).

Conclusions: Frequently watching TV or listening to the radio and keeping domestic animals or pets was associated with a lower risk of ADL disability among the oldest-old Chinese population.

Methods: We included 12,331 participants (aged ≥ 80 years) (mean [SD] age: 89.5 [7.0] years) who managed to perform ADL independently at baseline in the Chinese Longitudinal Healthy Longevity Survey 1998-2014 waves. Cox proportional hazards models were used to examine whether leisure activities were associated with ADL disability.
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http://dx.doi.org/10.18632/aging.103287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346052PMC
June 2020

Development and Validation of a Nomogram for Predicting the 6-Year Risk of Cognitive Impairment Among Chinese Older Adults.

J Am Med Dir Assoc 2020 06 3;21(6):864-871.e6. Epub 2020 Jun 3.

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address:

Objective: Although some people with mild cognitive impairment may not suffer from dementia lifelong, about 5% of them will progress to dementia within 1 year in community settings. However, a general tool for predicting the risk of cognitive impairment was not adequately studied among older adults.

Design: Prospective cohort study.

Setting: Community-living, older adults from 22 provinces in China.

Participants: We included 10,066 older adults aged 65 years and above (mean age, 83.2 ± 11.1 years), with normal cognition at baseline in the 2002-2008 cohort and 9354 older adults (mean age, 83.5 ± 10.8 years) in the 2008-2014 cohort of the Chinese Longitudinal Healthy Longevity Survey.

Methods: We measured cognitive function using the Chinese version of the Mini-Mental State Examination. Demographic, medical, and lifestyle information was used to develop the nomogram via a Lasso selection procedure using a Cox proportional hazards regression model. We validated the nomogram internally with 2000 bootstrap resamples and externally in a later cohort. The predictive accuracy and discriminative ability of the nomogram were measured by area-under-the-curves and calibration curves, respectively.

Results: Eight factors were identified with which to construct the nomogram: age, baseline of the Mini-Mental State Examination, activities of daily living and instrumental activities of daily living score, chewing ability, visual function, history of stroke, watching TV or listening to the radio, and growing flowers or raising pets. The area-under-the-curves for internal and external validation were 0.891 and 0.867, respectively, for predicting incident cognitive impairment. The calibration curves showed good consistency between nomogram-based predictions and observations.

Conclusions And Implications: The nomogram-based prediction yielded consistent results in 2 separate large cohorts. This feasible prognostic nomogram constructed using readily ascertained information may assist public health practitioners or physicians to provide preventive interventions of cognitive impairment.
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http://dx.doi.org/10.1016/j.jamda.2020.03.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299771PMC
June 2020

Biomarkers Associated with Physical Resilience After Hip Fracture.

J Gerontol A Biol Sci Med Sci 2020 09;75(10):e166-e172

Center for the Study of Aging and Human Development, Duke University, Durham, North Carolina.

Background: Clinically similar older adults demonstrate variable responses to health stressors, heterogeneity attributable to differences in physical resilience. However, molecular mechanisms underlying physical resilience are unknown. We previously derived a measure of physical resilience after hip fracture-the expected recovery differential (ERD)-that captures the difference between actual recovery and predicted recovery. Starting with biomarkers associated with physical performance, morbidity, mortality, and hip fracture, we evaluated associations with the ERD to identify biomarkers of physical resilience after hip fracture.

Methods: In the Baltimore Hip Studies (N = 304) sera, we quantified biomarkers of inflammation (TNFR-I, TNFR-II, sVCAM-1, and IL-6), metabolic and mitochondrial function (non-esterified fatty acids, lactate, ketones, acylcarnitines, free amino acids, and IGF-1), and epigenetic dysregulation (circulating microRNAs). We used principal component analysis, canonical correlation, and least absolute shrinkage and selection operator regression (LASSO) to identify biomarker associations with better-than-expected recovery (greater ERD) after hip fracture.

Results: Participants with greater ERD were more likely to be women and less disabled at baseline. The complete biomarker set explained 37% of the variance in ERD (p < .001) by canonical correlation. LASSO regression identified a biomarker subset that accounted for 27% of the total variance in the ERD and included a metabolic factor (aspartate/asparagine, C22, C5:1, lactate, glutamate/mine), TNFR-I, miR-376a-3p, and miR-16-5p.

Conclusions: We identified a set of biomarkers that explained 27% of the variance in ERD-a measure of physical resilience after hip fracture. These ERD-associated biomarkers may be useful in predicting physical resilience in older adults facing hip fracture and other acute health stressors.
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http://dx.doi.org/10.1093/gerona/glaa119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518564PMC
September 2020

Osteoarthritis: Current Molecular Biomarkers and the Way Forward.

Calcif Tissue Int 2021 Sep 4;109(3):329-338. Epub 2020 May 4.

Rheumatology, Biomarkers and Research, Nordic Bioscience, Herlev, Denmark.

The ultimate hope of researchers and patients is a pathway to development of treatments for osteoarthritis to modify the disease process in addition to the symptoms. However, development of disease modifying drugs requires objective endpoints such as measures of joint structure, joint tissue homeostasis and/or joint survival-measures such as provided by imaging biomarkers, molecular biomarkers and joint replacement frequency, respectively. Although biomarkers supporting investigational drug use and drug approval include surrogate endpoints that may not necessarily reflect or directly correlate with the clinical outcome of interest, a formal biomarker qualification process currently exists that is a rigorous three stage process that yields biomarker approvals (or denials) for specific contexts of use. From a cost perspective, biochemical biomarkers are the 'ones to beat'; however, even well-validated biomarkers may not cross the translation gaps for eventual use in healthcare unless they offer an advantage in terms of cost per quality adjusted life year. This review summarizes the case FOR and AGAINST biomarkers in drug development and highlights the current data for a subset of biomarkers in the osteoarthritis research field informing on cartilage homeostasis, joint inflammation and altered subchondral bone remodeling.
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http://dx.doi.org/10.1007/s00223-020-00701-7DOI Listing
September 2021

Number of natural teeth, denture use and mortality in Chinese elderly: a population-based prospective cohort study.

BMC Oral Health 2020 04 10;20(1):100. Epub 2020 Apr 10.

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, #7 Panjiayuan Nanli, Chaoyang, Beijing, 100021, China.

Background: The associations between the number of natural teeth/denture use and all-cause mortality remain unclear due to lake of investigation for the potential interaction between tooth loss and denture use and for the potential changes in these exposures over time in older adults. We undertake this study to evaluate the associations of the number of natural teeth and/or denture use with mortality in Chinese elderly.

Methods: This is a prospective cohort study of 36,283 older adults (median age: 90). The number of natural teeth and denture use were collected with structured questionnaire. We evaluated hazard ratios (HRs) and confidence intervals (CIs) using a Cox proportional hazards model adjusting for demographic factors, education, income, lifestyle factors, and comorbidities.

Results: We documented 25,857 deaths during 145,947 person-years of observation. Compared to those with 20+ teeth, tooth loss was associated with a gradual increase in mortality, with an adjusted HR of 1.14 (95% CI, 1.06 to 1.23) for those with 10-19 teeth, 1.23 (95% CI, 1.15 to 1.31) for those with 1-9 teeth, and 1.35 (95% CI, 1.26 to 1.44) for those without natural teeth. Denture use was associated with lower risk of mortality (adjusted HR 0.81; 95% CI, 0.77 to 0.84). Subgroup analyses indicated that the benefit of denture use was greater in men than in women (P = 0.02) and tended to decrease with age (P < 0.001). The effects of denture use did not differ among various degrees of tooth loss (P = 0.17).

Conclusions: Tooth loss was associated with an increased risk of mortality in older adults. Denture use provided a protective effect against death for all degrees of tooth loss however, this effect appeared to be modified by sex and age.
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http://dx.doi.org/10.1186/s12903-020-01084-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147045PMC
April 2020

Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study.

Ann Rheum Dis 2020 06 6;79(6):829-836. Epub 2020 Apr 6.

Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, China

Objectives: To evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort.

Methods: This population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables.

Results: At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3-9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080).

Conclusions: Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.
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http://dx.doi.org/10.1136/annrheumdis-2020-217176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286049PMC
June 2020

Associations of habitual fish oil supplementation with cardiovascular outcomes and all cause mortality: evidence from a large population based cohort study.

BMJ 2020 03 4;368:m456. Epub 2020 Mar 4.

Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China

Objectives: To evaluate the associations of habitual fish oil supplementation with cardiovascular disease (CVD) and mortality in a large prospective cohort.

Design: Population based, prospective cohort study.

Setting: UK Biobank.

Participants: A total of 427 678 men and women aged between 40 and 69 who had no CVD or cancer at baseline were enrolled between 2006 and 2010 and followed up to the end of 2018.

Main Exposure: All participants answered questions on the habitual use of supplements, including fish oil.

Main Outcome Measures: All cause mortality, CVD mortality, and CVD events.

Results: At baseline, 133 438 (31.2%) of the 427 678 participants reported habitual use of fish oil supplements. The multivariable adjusted hazard ratios for habitual users of fish oil versus non-users were 0.87 (95% confidence interval 0.83 to 0.90) for all cause mortality, 0.84 (0.78 to 0.91) for CVD mortality, and 0.93 (0.90 to 0.96) for incident CVD events. For CVD events, the association seemed to be stronger among those with prevalent hypertension (P for interaction=0.005).

Conclusions: Habitual use of fish oil seems to be associated with a lower risk of all cause and CVD mortality and to provide a marginal benefit against CVD events among the general population.
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http://dx.doi.org/10.1136/bmj.m456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249244PMC
March 2020

Long-term exposure to ambient fine particulate matter and fasting blood glucose level in a Chinese elderly cohort.

Sci Total Environ 2020 May 8;717:137191. Epub 2020 Feb 8.

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China. Electronic address:

Fasting blood glucose level is the primary indicator for the diagnosis of diabetes. We aim to conduct a longitudinal study on the association between long-term fine particulate matter (PM) exposure and fasting blood glucose concentrations. We recruited and followed up 1449 participants older than 65 years of age in 2009, 2012, 2014, and 2017 in eight counties in China. Fasting blood glucose was repeatedly measured 3697 times in total among these participants. Data on annual ground-level PM concentrations with a 0.01° spatial resolution from 2005 to 2016 were used to assess exposures. An increase of 10 μg/m in 3-year average exposure to PM was associated with an increase of 0.146 mmol/L (95% confidence interval [CI]: 0.045, 0.248) in fasting blood glucose in all participants. The association was more pronounced among the subgroup with diabetes compared to the subgroup without diabetes (P < .05). In conclusion, Long-term PM exposure was associated with an increase in fasting blood glucose levels among elderly people. Elderly individuals with diabetes are particularly vulnerable to high level exposures of PM. SUMMARY: Long-term PM exposure was associated with an increase in fasting blood glucose levels among elderly people. Elderly individuals with diabetes are particularly vulnerable to high level exposures of PM.
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http://dx.doi.org/10.1016/j.scitotenv.2020.137191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183512PMC
May 2020

Long-term exposure to PM and incidence of disability in activities of daily living among oldest old.

Environ Pollut 2020 Apr 2;259:113910. Epub 2020 Jan 2.

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, 100021, China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address:

Currently the Chinese government has adopted World Health Organization interim target-1 values as the national ambient air quality standards values. However, the population-based evidence was insufficient, especially for the oldest old (aged 80+). We evaluated the association of fine particulate matters (PM) exposure and incidence of disability in activities of daily living (ADL) in 15 453 oldest old in 886 counties/cities in China from 2002 to 2014 using Cox model with penalized splines and competing risk models to evaluate the linear or non-linear association. After adjusting for potential confounders, a J-shaped association existed between PM exposure with a threshold concentration of 33 μg/m, and incident disability in ADL. Above this threshold, the risk magnitude significantly increased with increase of PM concentrations; compared to 33 μg/m, the hazard ratio ranged from 1.03 (1.00-1.06) at 40 μg/m to 2.25 (1.54-3.29) at 110 μg/m. The risk magnitude was not significantly changed below this threshold. Each 10 μg/m increase in PM exposure corresponded to a 7.7% increase in the risk of disability in ADL (hazard ratio 1.077, 95% CI 1.051-1.104). Men, smokers, and participants with cognitive impairment might be more vulnerable to PM exposure. The study provided limited population-based evidence for the oldest old and detected a threshold of 33 μg/m, and supported that reduction to current World Health Organization interim target-1value (35 μg/m) and Chinese national ambient air quality standards (35 μg/m) or lower may be associated with lower risk of disability in ADL.
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http://dx.doi.org/10.1016/j.envpol.2020.113910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261238PMC
April 2020

Association of cognitive impairment and elderly mortality: differences between two cohorts ascertained 6-years apart in China.

BMC Geriatr 2020 Jan 28;20(1):29. Epub 2020 Jan 28.

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, #7 Panjiayuan Nanli, Chaoyang, Beijing, 100021, China.

Background: Cognitive impairment is a major contributor to mortality among the elderly. However, the relationship between cognitive impairment evaluated by educational levels and mortality and the trend between cognitive impairment and mortality with time are unclear. We aim to evaluate the differences in associations of cognitive impairment, taking the stratification by educational levels into account, with all-cause mortality and further explore the relationship of cognitive impairment with mortality in different age and sex groups in two cohorts ascertained 6 years apart in China.

Methods: A total of 13,906 and 13,873 Chinese elderly aged 65 years and older were included in the 2002-2008 and 2008-2014 cohorts from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Mortality data was ascertained from interviews with family members or relatives of participants. Cognitive function, evaluated by the Mini-Mental State Examination (MMSE), were defined by different cut-offs taking educational background into account. Cox models were used to explore the relationship of cognitive impairment with mortality.

Results: For the 2002-2008 and 2008-2014 cohorts, 55,277 and 53,267 person-years were followed up, and the mean (SD) age were 86.5 (11.6) and 87.2 (11.3) years, respectively. Compared to normal cognition, cognitive impairment was independently associated with higher mortality risk after controlling for potential confounders, with hazard ratios (HRs) of 1.32 (95% confidence interval [CI], 1.25-1.39) in 2002-2008 cohort and 1.26 (95% CI, 1.19-1.32) in 2008-2014 cohort, stratified by educational levels. The trend of cognitive impairment with all-cause mortality risk decreased from 2002 to 2008 to 2008-2014 cohort, while no significant interaction of cognitive impairment with cohort for all-cause mortality was observed. The associations of cognitive impairment and mortality were decreased with age in the two cohorts.

Conclusions: Cognitive impairment evaluated by different cut-offs were associated with increased risk of mortality, especially among those aged 65-79 years in the two cohorts; this advocates that periodic screening for cognitive impairment among the elderly is warranted.
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http://dx.doi.org/10.1186/s12877-020-1424-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988297PMC
January 2020

Immune cell extracellular vesicles and their mitochondrial content decline with ageing.

Immun Ageing 2020 4;17. Epub 2020 Jan 4.

1Duke Molecular Physiology Institute, Duke University School of Medicine, Duke University, Durham, North Carolina 27701 USA.

Background: Although the mechanisms of action are not fully understood, extracellular vesicles (EVs) have emerged as key indicators and effectors of immune function. Characterizing circulating EVs associated with stem and immune cells across the lifespan of healthy individuals could aid an understanding of immunosenescence, a process of age-related decline of cells in both adaptive and innate immune systems.

Results: Using high resolution multicolor flow cytometry, we identified three major subsets of EVs of varying sizes in healthy control (HC) plasma. Multiple plasma EVs associated with immune cells declined with ageing in HCs. In addition, we observed age-associated declines of respiring mitochondria cargo in EVs of several types of immune cells, suggesting that these parent cells may experience a decline in mitophagy or a mitochondrial dysfunction-induced immunosenescence. By contrast, the number of CD34 hematopoietic stem cell-associated EVs were high and carried respiring mitochondria, which did not decline with age.

Conclusion: As demonstrated here, multicolor flow cytometry simultaneously measures plasma EV size, surface markers and cargo that reflect biological processes of specific cell types. The distinct surface markers and cytokine cargo of plasma EVs suggest that they may carry different bio-messages and originate by different biogenesis pathways.
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http://dx.doi.org/10.1186/s12979-019-0172-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942666PMC
January 2020

Combined associations of hs-CRP and cognitive function with all-cause mortality among oldest-old adults in Chinese longevity areas: a prospective cohort study.

Immun Ageing 2019 17;16:30. Epub 2019 Nov 17.

1National Institute of Environmental and Health, Chinese Center for Disease Control and Prevention, Bejing, 100021 People's Republic of China.

Background: Inflammatory markers, such as high sensitivity C-reactive protein (hs-CRP), and cognitive impairment (CI) are associated with mortality; CRP is related to the deterioration of CI. However, it is still unknown whether these two indices predict mortality independent of each other. Furthermore, their joint effect on all-cause mortality has not been well established, especially in oldest-old adults.

Methods: Based on data from the 2012 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), we included 1447 oldest-old adults (mean age 84.7 years and 58.7% were female, weighted) with information on hs-CRP (stratified by a cutoff value of 3.0 mg/L) and cognition (quantified by Mini-Mental Status Examination (MMSE) scored according to the personal educational level) at baseline. Mortality was assessed in followed 2014 and 2017 waves. Cox proportional hazards regression models were used, with adjustment for hs-CRP and cognition (mutually controlled) and several traditional mortality risk factors.

Results: During a median follow-up period of 32.8 months (Q1-Q3, 9.7-59.0 months), 826 participants died. Hs-CRP [HR : 1.64 (95% CI, 1.17, 2.30)] and cognition [HR : 2.30 (95% CI, 1.64, 3.21)] each was independent predictor of all-cause mortality, even after accounting for each other and other covariates. Monotonic and positive associations were observed in combined analyses, in which the highest mortality risk was obtained in elders with both high hs-CRP and CI [HR: 3.56 (95% CI, 2.35, 5.38)].The combined effects were stronger in male and younger oldest-old (aged 80-89 years).

Conclusion: High hs-CRP and CI, both individually and jointly, were associated with increased all-cause mortality risks in Chinese oldest-old. Intervention strategies for preventing inflammation and maintaining adequate cognitive function may be more important in male and younger oldest-old for reducing mortality risk.
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http://dx.doi.org/10.1186/s12979-019-0170-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859603PMC
November 2019

Associations of plasma high-sensitivity C-reactive protein concentrations with all-cause and cause-specific mortality among middle-aged and elderly individuals.

Immun Ageing 2019 5;16:28. Epub 2019 Nov 5.

1Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, 510515 Guangdong China.

Background: The association of high-sensitivity C-reactive protein (hsCRP) with mortality is controversial. We aimed to investigate the associations of hsCRP concentrations with the risks of all-cause and cause-specific mortality and identify potential modifying factors affecting these associations among middle-aged and elderly individuals.

Methods: This community-based prospective cohort study included 14,220 participants aged 50+ years (mean age: 64.9 years) from the Health and Retirement Study. Cox proportional hazard models were employed to estimate the associations between the hsCRP concentrations and the risk of all-cause and cause-specific mortality with adjustment for sociodemographic and lifestyle factors, self-reported medical history, and other potential confounders.

Results: In total, 1730 all-cause deaths were recorded, including 725 cardiovascular- and 417 cancer-related deaths, after an 80,572 person-year follow-up (median: 6.4 years; range: 3.6-8.1 years). The comparisons of the groups with the highest (quartile 4) and lowest (quartile 1) hsCRP concentrations revealed that the adjusted hazard ratios and 95% confidence intervals were 1.50 (1.31-1.72) for all-cause mortality, 1.44 (1.13-1.82) for cardiovascular mortality, and 1.67 (1.23-2.26) for cancer mortality. The associations between high hsCRP concentrations and the risks of all-cause, cardiovascular, and cancer mortality were similar in the men and women ( for interaction > 0.05).

Conclusions: Among middle-aged and older individuals, elevated hsCRP concentration could increase the risk of all-cause, cardiovascular, and cancer mortality in men and women.
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http://dx.doi.org/10.1186/s12979-019-0168-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833146PMC
November 2019

Association of Blood Chemistry Quantifications of Biological Aging With Disability and Mortality in Older Adults.

J Gerontol A Biol Sci Med Sci 2020 09;75(9):1671-1679

Department of Epidemiology, Columbia University Mailman School of Public Health, New York.

Quantification of biological aging has been proposed for population surveillance of age-related decline in system integrity and evaluation of geroprotective therapies. However, methods of quantifying biological aging have been little studied in geriatric populations. We analyzed three clinical-biomarker-algorithm methods to quantify biological aging. Klemera-Doubal method Biological Age and homeostatic dysregulation algorithms were parameterized from analysis of U.S. National Health and Nutrition Examination Surveys (NHANES) data (N = 36,207) based on published methods. Levine method Biological Age was adapted from published analysis of NHANES data. Algorithms were applied to biomarker data from the Duke Established Populations for Epidemiologic Studies of the Elderly (Duke-EPESE) cohort of older adults (N = 1,374, aged 71-102 years, 35% male, 52% African American). We tested associations of biological aging measures with participant reported Activities of daily living (ADL), instrumental activities of daily living (IADL) dependencies, and mortality. We evaluated the sensitivity of results to the demographic composition of reference samples and biomarker sets used to develop biological aging algorithms. African American and white Duke-EPESE participants with more advanced biological aging reported dependence in more ADLs and IADLs and were at increased risk of death over follow-up through 2017. Effect sizes were similar across algorithms, but were strongest for Levine method Biological Age (per-quintile increase in ADL incidence rate ratio = 1.25, 95% confidence interval [1.17-1.37], IADL incidence rate ratio = 1.23 [1.15-1.32], mortality hazard ratio = 1.12 [1.08-1.16]). Results were insensitive to demographic composition of reference samples, but modestly sensitive to the biomarker sets used to develop biological aging algorithms. Blood-chemistry-based quantifications of biological aging show promise for evaluating the effectiveness of interventions to extend healthy life span in older adults.
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http://dx.doi.org/10.1093/gerona/glz219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494046PMC
September 2020

Higher dietary diversity scores and protein-rich food consumption were associated with lower risk of all-cause mortality in the oldest old.

Clin Nutr 2020 07 25;39(7):2246-2254. Epub 2019 Oct 25.

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China. Electronic address:

Background & Aims: Dietary diversity is widely advocated in national and international recommendations although whether the beneficial effects on survival or longevity still apply in the final phase of the lifespan remains understudied. We aimed to prospectively examine the association of dietary diversity, food items with all-cause mortality among the oldest old (80+) and determine whether dietary diversity recommendations were appropriate for this population.

Methods: The study included 28,790 participants aged 80+ (9957 octogenarians, 9925 nonagenarians, and 8908 centenarians). A baseline dietary diversity score (DDS) was constructed based on nine food items of a food frequency questionnaire. Cox models with penalized splines evaluated non-linear associations of DDS as continuous variable with mortality to identify cut-offs of DDS.

Results: We documented 23,503 deaths during 96,739 person-years of follow-up. Each one unit increase in DDS was associated with a 9% lower risk of mortality (adjusted hazard ratio (HR): 0.91; 95% confidential interval (CI): 0.90-0.92). Compared to participants whose DDS less than 2 scores, those with a DDS of 2, 3, 4, 5, and higher than 6 scores had a lower mortality risk, the HRs were 0.86 (0.82-0.89), 0.78 (0.75-0.81), 0.69 (0.66-0.72), 0.65 (0.62-0.68), and 0.56 (0.53-0.58) respectively, and a significant trend emerged (p < 0.001). Protein-rich food items were associated with prominent beneficial effects on mortality including meat (HR and 95% CI for high vs low frequency: 0.70 (0.68-0.72)), fish and sea food (HR, 0.74 (0.72-0.77)), egg (HR, 0.75 (0.73-0.77)), and bean (HR, 0.80 (0.78-0.82)).

Conclusions: Even after the age of 80, the DDS tool may offer a simple and straightforward mean of identifying and screening individuals at high risk for mortality. Recommendation of dietary diversity, especially consumption of protein-rich food, may be advocated to reduce mortality risk and promote longevity in the oldest old.
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http://dx.doi.org/10.1016/j.clnu.2019.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182467PMC
July 2020

Trends in the Incidence of Activities of Daily Living Disability Among Chinese Older Adults From 2002 to 2014.

J Gerontol A Biol Sci Med Sci 2020 10;75(11):2113-2118

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China.

Background: Evidence of the trend of the incidence of activities of daily living (ADL) disability among Chinese older people is limited. We aimed to investigate the time trends and potential risk factors for the incidence of ADL disability among Chinese older people (≥65 years).

Methods: We established two consecutive and nonoverlapping cohorts (6,857 participants in the 2002 cohort and 5,589 participants in the 2008 cohort) from the Chinese Longitudinal Healthy Longevity Survey. ADL disability was defined as the need for assistance with at least one essential activity (dressing, bathing, toileting, eating, indoor activities, and continence). Cox proportional hazards models were used to identify factors associated with the trend in the incidence of ADL disability from 2002 to 2014.

Results: The incidence (per 1,000 person-years) of ADL disability decreased significantly from 64.2 in the 2002 cohort to 46.6 in the 2008 cohort (p < .001), and decreasing trends in the incidence of ADL disability were observed for all sex, age, and residence subgroups (all p < .001), even after adjusting for multiple potential confounding factors. Moreover, we found that adjustment for sociodemographic, lifestyle information, and cardiovascular risk factors (hypertension, diabetes, heart disease, and stroke) explained less of the decline in ADL disability during the period from 2002 to 2014.

Conclusion: The incidence of ADL disability among the older adults in China appears to have decreased during the study period, and this finding cannot be explained by existing sociodemographic and lifestyle information and cardiovascular risk factors.
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http://dx.doi.org/10.1093/gerona/glz221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973258PMC
October 2020

Meta-analysis of pain and function placebo responses in pharmacological osteoarthritis trials.

Arthritis Res Ther 2019 07 15;21(1):173. Epub 2019 Jul 15.

Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Duke Molecular Physiology Institute, PO Box 104775, Room 51-205, Carmichael Building, 300 N Duke St., Durham, NC, 27701-2047, USA.

Objective: To evaluate contextual effects in the form of placebo responses (PRs) for patient-reported pain and function and objectively measured function in osteoarthritis (OA) clinical trials.

Methods: Two authors independently searched major electronic databases from inception to 20 May 2019. Included studies were randomized, placebo-controlled OA trials of pharmacological agents reporting both patient-reported and objectively measured outcomes. PRs for each type of outcome measure were compared by standardized mean differences (SMDs). The placebo response ratio (PRR) assessed the placebo to treatment effect size. The effect sizes of PRs and PRRs were pooled using a random effects model.

Results: Twenty-one trials met the inclusion criteria; 20 were double-blinded with one not reporting on blinding status. Compared with patients' self-reported outcome (PRO) pain, PRs were significantly lower for PRO function (SMD - 0.16 [95% CI = - 0.28, - 0.05], p = 0.006), objectively measured muscle strength (SMD - 0.34 [95% CI - 0.58, - 0.10], p = 0.006), and range of motion (SMD = - 0.31 [95% CI = - 0.54, - 0.08], p = 0.008) function. Generally, PRs for function outcomes (patient-reported and objectively measured) were similar. The overall PRR for different measures ranged from the smallest (most favorable) for walking time/distance (0.30, 95% CI 0.16 to 0.43) to the largest for PRO pain (0.44, 95% CI 0.23 to 0.65).

Conclusion: Function measures both subjective and objective had less contextual effects than pain measures in OA trials. Our results support the OMERACT-OARSI recommendations to include measures of physical function in all clinical trials of hip and knee OA and suggest that a greater use of function measures might enhance the success rates of pharmacological OA trials. Increasing the availability of mobile health apps should facilitate the acquisition of measured function data.
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http://dx.doi.org/10.1186/s13075-019-1951-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631867PMC
July 2019

Synovial fluid biomarkers associated with osteoarthritis severity reflect macrophage and neutrophil related inflammation.

Arthritis Res Ther 2019 06 13;21(1):146. Epub 2019 Jun 13.

Duke Molecular Physiology Institute, Duke University School of Medicine, Box 104775, 300 North Duke St, Durham, NC, 27701, USA.

Background: To identify a synovial fluid (SF) biomarker profile characteristic of individuals with an inflammatory osteoarthritis (OA) endotype.

Methods: A total of 48 knees (of 25 participants) were characterized for an extensive array of SF biomarkers quantified by Rules Based Medicine using the high-sensitivity multiplex immunoassay, Myriad Human InflammationMAP® 1.0, which included 47 different cytokines, chemokines, and growth factors related to inflammation. Multivariable regression with generalized estimating equations (GEE) and false discovery rate (FDR) correction was used to assess associations of SF RBM biomarkers with etarfolatide imaging scores reflecting synovial inflammation; radiographic knee OA severity (based on Kellgren-Lawrence (KL) grade, joint space narrowing, and osteophyte scores); knee joint symptoms; and SF biomarkers associated with activated macrophages and knee OA progression including CD14 and CD163 (shed by activated macrophages) and elastase (shed by activated neutrophils).

Results: Significant associations of SF biomarkers meeting FDR < 0.05 included soluble (s)VCAM-1 and MMP-3 with synovial inflammation (FDR-adjusted p = 0.025 and 1.06 × 10); sVCAM-1, sICAM-1, TIMP-1, and VEGF with radiographic OA severity (p = 1.85 × 10 to 3.97 × 10); and VEGF, MMP-3, TIMP-1, sICAM-1, sVCAM-1, and MCP-1 with OA symptoms (p = 2.72 × 10 to 0.050). All these SF biomarkers were highly correlated with macrophage markers CD163 and CD14 in SF (r = 0.43 to 0.90, FDR < 0.05); all but MCP-1 were also highly correlated with neutrophil elastase in SF (r = 0.62 to 0.89, FDR < 0.05).

Conclusions: A subset of six SF biomarkers was related to synovial inflammation in OA, as well as radiographic and symptom severity. These six OA-related SF biomarkers were specifically linked to indicators of activated macrophages and neutrophils. These results attest to an inflammatory OA endotype that may serve as the basis for therapeutic targeting of a subset of individuals at high risk for knee OA progression.

Trial Registration: Written informed consent was received from participants prior to inclusion in the study; the study was registered at ClinicalTrials.gov ( NCT01237405 ) on November 9, 2010, prior to enrollment of the first participant.
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http://dx.doi.org/10.1186/s13075-019-1923-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567574PMC
June 2019

Associations between superoxide dismutase, malondialdehyde and all-cause mortality in older adults: a community-based cohort study.

BMC Geriatr 2019 04 15;19(1):104. Epub 2019 Apr 15.

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, #7 Panjiayuan Nanli, Chaoyang, Beijing, 100021, China.

Background: Oxidative stress is an important theory of aging but population-based evidence has been lacking. This study aimed to evaluate the associations between biomarkers of oxidative stress, including plasma superoxide dismutase (SOD) activity and malondialdehyde (MDA), with all-cause mortality in older adults.

Methods: This is a community-based cohort study of 2224 participants (women:1227, median age: 86 years). We included individuals aged 65 or above and with plasma SOD activity and/or MDA tests at baseline. We evaluated the hazard ratios (HRs) and 95% confidence intervals (CIs) by multivariable Cox models.

Results: We documented 858 deaths during six years of follow-up. There was a significant interaction effect of sex with the association between SOD activity and mortality (P < 0.001). Compared with the lowest quintile, the risk of all-cause mortality was inversely associated with increasing quintiles of plasma SOD activity in women(P-trend< 0.001), with adjusted HRs for the second through fifth quintiles of 0.73 (95% CI 0.53-1.02), 0.52(95% CI 0.38-0.72), 0.53(95% CI 0.39-0.73), and 0.48(95% CI 0.35-0.66). There were no significant associations between SOD activity and mortality in men (P-trend = 0.64), and between MDA and mortality in all participants (P-trend = 0.79).

Conclusions: Increased activity of SOD was independently associated with lower all-cause mortality in older women but not in men. This epidemiological study lent support for the free radical/oxidative stress theory of aging.
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http://dx.doi.org/10.1186/s12877-019-1109-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466801PMC
April 2019

Plasma 25-Hydroxyvitamin D Concentrations Are Inversely Associated with All-Cause Mortality among a Prospective Cohort of Chinese Adults Aged ≥80 Years.

J Nutr 2019 06;149(6):1056-1064

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China.

Background: High concentrations of plasma 25-hydroxyvitamin D [25(OH)D], a marker of circulating vitamin D, have been associated with a lower risk of mortality in epidemiologic studies of multiple populations, but the association for Chinese adults aged ≥80 y (oldest old) remains unclear.

Objective: We investigated the association between plasma [25(OH)D] concentration and all-cause mortality among Chinese adults aged ≥80 y.

Design: The present study is a prospective cohort study of 2185 Chinese older adults (median age: 93 y). Prospective all-cause mortality data were analyzed for survival in relation to plasma 25(OH)D using Cox proportional hazards regression models, with adjustments for potential sociodemographic and lifestyle confounders and biomarkers. The associations were measured with HR and 95% CIs.

Results: The median plasma 25(OH)D concentration was 34.4 nmol/L at baseline. Over the 5466 person-year follow-up period, 1100 deaths were identified. Men and women were analyzed together as no effect modification by sex was found. After adjusting for multiple potential confounders, the risk of all-cause mortality decreased as the plasma 25(OH)D concentration increased (P-trend <0.01). Compared with the lowest age-specific quartile of plasma 25(OH)D, the adjusted HRs for mortality for the second, third, and fourth age-specific quartiles were 0.72 (95% CI: 0.57, 0.90), 0.73 (95% CI: 0.58, 0.93), and 0.61 (95% CI: 0.47, 0.81), respectively. The observed associations were broadly consistent across age and other subgroups. Sensitivity analyses generated similar results after excluding participants who died within 2 y of follow-up or after further adjustment for ethnicity and chronic diseases.

Conclusions: A higher plasma 25-hydroxyvitamin D concentration was associated with a reduced risk of all-cause mortality among Chinese adults aged ≥80 y. This observed inverse association warrants further investigation in randomized controlled trials testing vitamin D supplementation in this age group.
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http://dx.doi.org/10.1093/jn/nxz041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543202PMC
June 2019

Specific Leisure Activities and Cognitive Functions Among the Oldest-Old: The Chinese Longitudinal Healthy Longevity Survey.

J Gerontol A Biol Sci Med Sci 2020 03;75(4):739-746

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China.

Background: Little is known about the role of specific leisure activities in affecting cognitive functions. We aim to examine the associations of specific leisure activities with the risk of cognitive impairment among oldest-old people in China.

Methods: This community-based prospective cohort study included 10,741 cognitively normal Chinese individuals aged 80 years or older (median age 88 years) from the Chinese Longitudinal Healthy Longevity Survey. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Cox proportional hazards models were utilized to estimate the effects of specific leisure activities on cognitive impairment outcome.

Results: During a median follow-up time of 3.4 years (41,760 person-years), 2,894 participants developed cognitive impairment. Compared to those who "never" engaged in watching TV or listening to radio, reading books or newspapers, and playing cards or mah-jong, those who engaged in such activities "almost every day" reduced their risk of cognitive impairment, the fully-adjusted hazard ratios were 0.56 (0.51-0.61), 0.64 (0.53-0.78), and 0.70 (0.56-0.86), respectively. The association between the risk of cognitive impairment and watching TV and listening to the radio, playing cards or mah-jong, and reading books or newspapers were stronger among those who had two or more years of education. Moreover, the association between risk of cognitive impairment and watching TV and listening to radio was stronger in men than in women.

Conclusions: In conclusion, a greater frequency of TV watching or radio listening, reading books or newspapers, and playing cards or mah-jong may decrease the risk of cognitive impairment among the oldest-old.
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http://dx.doi.org/10.1093/gerona/glz086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776703PMC
March 2020

Glycated Hemoglobin and All-Cause and Cause-Specific Mortality Among Adults With and Without Diabetes.

J Clin Endocrinol Metab 2019 08;104(8):3345-3354

Department of Epidemiology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), Guangzhou, China.

Context: The patterns of associations between glycated Hb (HbA1c) and mortality are still unclear.

Objective: To explore the extent to which ranges of HbA1c levels are associated with the risk of mortality among participants with and without diabetes.

Design, Setting, And Patients: This was a nationwide, community-based prospective cohort study. Included were 15,869 participants (median age 64 years) of the Health and Retirement Study, with available HbA1c data and without a history of cancer. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for mortality.

Results: A total of 2133 participants died during a median follow-up of 5.8 years. In participants with diabetes, those with an HbA1c level of 6.5% were at the lowest risk of all-cause mortality. When HbA1c level was <5.6% or >7.4%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 6.5%. As for participants without diabetes, those with an HbA1c level of 5.4% were at the lowest risk of all-cause mortality. When the HbA1c level was <5.0%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 5.4%. However, we did not observe a statistically significant elevated risk of all-cause mortality above an HbA1c level of 5.4%.

Conclusions: A U-shaped and reverse J-shaped association for all-cause mortality was found among participants with and without diabetes. The corresponding optimal ranges for overall survival are predicted to be 5.6% and 7.4% and 5.0% and 6.5%, respectively.
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http://dx.doi.org/10.1210/jc.2018-02536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328059PMC
August 2019

High-Density Lipoprotein Cholesterol and All-Cause and Cause-Specific Mortality Among the Elderly.

J Clin Endocrinol Metab 2019 08;104(8):3370-3378

Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.

Context: The patterns of the association between high-density lipoprotein cholesterol (HDL-C) concentrations and mortality among the elderly are still unclear.

Objective: To examine the association of HDL-C concentrations with mortality and to identify the optimal HDL-C concentration range that predicts the lowest risk of all-cause mortality among the elderly.

Design: This was a nationwide, community-based, prospective cohort study.

Participants: This study included 7766 elderly individuals (aged ≥65 years; mean age: 74.4 years) from the Health and Retirement Study. Cox proportional hazards models and Cox models with penalized smoothing splines were used to estimate hazard ratios (HRs) with 95% CI for all-cause and cause-specific mortality.

Results: During a median follow-up of 5.9 years, 1921 deaths occurred. After a full adjustment for covariates, a nonlinear (P < 0.001 for nonlinearity) association was found between HDL-C and all-cause mortality [minimum mortality risk at 71 mg/dL (1.84 mM)]; the risk for all-cause mortality was significantly higher in the groups with HDL-C concentration <61 mg/dL (1.58 mM; HR: 1.18; 95% CI: 1.05 to 1.33) and with HDL-C concentration >87 mg/dL (2.25 mM; HR: 1.56; 95% CI: 1.17 to 2.07) than in the group with HDL-C concentrations ranging from 61 to 87 mg/dL (1.58 to 2.25 mM). Nonlinear associations of HDL-C concentrations with both cardiovascular and noncardiovascular mortality were also observed (both P < 0.001 for nonlinearity).

Conclusions: Among the elderly, nonlinear associations were found between HDL-C and all-cause and cardiovascular mortality. The single optimal HDL-C concentration and range were 71 mg/dL and 61 to 87 mg/dL, respectively.
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http://dx.doi.org/10.1210/jc.2018-02511DOI Listing
August 2019

Association of Body Mass Index With Disability in Activities of Daily Living Among Chinese Adults 80 Years of Age or Older.

JAMA Netw Open 2018 09 7;1(5):e181915. Epub 2018 Sep 7.

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China.

Importance: Body mass index (BMI) shows a U-shaped association with impaired physical functioning among adults; the association is reduced or eliminated with aging.

Objective: To examine whether BMI is associated with subsequent disability in activities of daily living (ADL) in Chinese adults age 80 years or older.

Design, Setting, And Participants: Data were obtained on 16 022 adults age 80 years or older who were able to perform ADL independently at baseline from the Chinese Longitudinal Healthy Longevity Study, a community-based prospective cohort study conducted in 23 provinces of China. The study was initiated in 1998, with follow-up and recruitment of new participants in 2000, 2002, 2005, 2008, 2011, and 2014.

Main Outcomes And Measures: Disability in ADL was defined as dependence in eating, toileting, bathing, dressing, indoor activities, and/or continence.

Results: Among the 16 022 participants, 45.2% were men and 54.8% were women, with a mean (SD) age of 92.2 (7.2) years and a mean (SD) BMI (calculated as weight in kilograms divided by height in meters squared) of 19.3 (3.8). During 70 606 person-years of follow-up, 8113 participants with disability in ADL were identified. Cox proportional hazards regression models with penalized splines showed that BMI was linearly associated with disability in ADL: each 1-kg/m2 increase in BMI corresponded to a 4.5% decrease in the risk of disability in ADL. In comparison with individuals in the fourth quintile for BMI, the adjusted hazard ratio for disability in ADL was 1.38 (95% CI, 1.29-1.48) in the first quintile, 1.37 (95% CI, 1.28-1.47) in the second quintile, 1.11 (95% CI, 1.04-1.19) in the third quintile, and 0.85 (95% CI, 0.79-0.91) in the fifth quintile (P < .001 for trend). When BMI was categorized by Chinese guidelines, the underweight group (BMI <18.5) showed significantly increased risk of disability in ADL (hazard ratio, 1.34; 95% CI, 1.28-1.41) and the overweight or obese group (BMI ≥24.0) showed significantly decreased risk of disability in ADL (hazard ratio, 0.84; 95% CI, 0.78-0.91) compared with the normal weight group (BMI 18.5 to <24.0) (P < .001 for trend).

Conclusions And Relevance: Higher BMI was associated with a lower risk of disability in ADL among Chinese adults age 80 years or older, which suggests that current recommendations for BMI may need to be revisited. More attention should be paid on underweight, rather than overweight or obesity, for the prevention of disability in ADL after age 80 years.
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http://dx.doi.org/10.1001/jamanetworkopen.2018.1915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324469PMC
September 2018
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