Study Of Men Research Articles

Oxylipins Associated with D3-Creatine Muscle Mass/Weight and Physical Performance among Community-Dwelling Older Men.

Poor physical function is highly prevalent with aging, and strongly associated with D3-creatine muscle mass/weight. Using metabolomics, we previously identified several triglycerides consisting mostly of polyunsaturated fatty acids that were higher in older adults with good mobility. Here, we sought to further investigate polyunsaturated fatty-acid-related metabolites, i.e., oxylipins, and their associations with D3-creatine muscle mass/weight, gait speed, grip strength, and the Short Physical Performance Battery among 463 older men from the Osteoporotic Fractures in Men Study (MrOS). Oxylipins were measured in fasting serum using liquid chromatography-mass spectrometry. Muscle mass was estimated using D3-creatine dilution and adjusted for body size. We used linear regression to determine oxylipins associated with D3-creatine muscle mass/weight and physical performance, while adjusting for age, education, physical activity, Western dietary pattern, fish oil supplementation, and multiple comparisons. Among 42 oxylipins, none were associated with grip strength and 3 were associated with the Short Physical Performance Battery. In contrast, 18 and 17 oxylipins were associated with D3-creatine muscle mass/weight and gait speed, respectively. A subset of associations between oxylipins and gait speed were partially attenuated by D3-creatine muscle mass/weight. Higher levels of fatty acid alcohol and ketone oxylipins tended to be most strongly associated with gait speed and D3-creatine muscle mass/weight, potentially reflecting anti-inflammatory activity from these select oxylipins in MrOS older men.

Long-term exposure to low air pollutant concentrations and hospitalisation for respiratory diseases in older men: A prospective cohort study in Perth, Australia

BackgroundAcute exposure to ambient air pollution even at low concentrations has been associated with increased hospitalisation for respiratory diseases but the effects of long-term exposure are less certain. In this study, we investigated the associations between long-term exposures to PM2.5, PM2.5 absorbance and NO2 and hospitalisation for asthma, chronic obstructive pulmonary disease and pneumonia in a cohort of older men living in Perth, Western Australia, a city where the levels of air pollutants are well below the world standards. Materials and methodsThe study population of 11,156 men with no prior hospitalisation for respiratory disease was drawn from the Health in Men Study (HIMS) cohort of men aged >65 years living in Perth, Western Australia between 1996-1999. PM2.5, PM2.5 absorbance (PM2.5a) and NO2 were measured across the Perth metropolitan area over three seasons in 2012. Land use regression (LUR) models were used to estimate annual concentrations of PM2.5, PM2.5 absorbance and NO2 at the residential address of each participant from inception (1996) to 2015. Hospitalisation for respiratory disease between inception and 2015 was ascertained using the Western Australian Data Linkage System. The association between exposure to air pollution with hospitalisation for respiratory disease was examined using Cox regression analysis. ResultsNo statistically significant associations were observed in the fully adjusted models. However, positive associations were observed with first hospitalisation for pneumonia (HR 1.08, 95% CI: 1.01–1.16) when adjusted for age, year of enrolment, smoking status, education, BMI and physical activity. ConclusionsIn this longitudinal study of older men we found no evidence of associations between increased long-term exposure to low-level air pollution with increased risk of hospitalisation for respiratory diseases in Perth, Australia. More studies on respiratory morbidity associated with exposure to low levels of air pollution are needed for more comprehensive understanding of the overall risk.

Distressing dreams, cognitive decline, and risk of dementia: A prospective study of three population-based cohorts.

SummaryBackgroundDistressing dreams are associated with faster cognitive decline and increased dementia risk in people with Parkinson's disease (PD). Whether distressing dreams might be associated with cognitive decline and dementia in people without PD is unknown. This study investigated the association between self-reported distressing dream frequency and the risk of cognitive decline and incident dementia in community-dwelling men and women without cognitive impairment or PD.MethodsRisk of cognitive decline was evaluated in 605 middle-aged adults (mean age = 50 years [IQR 44–57]; 55·7% female) from the Midlife in the United States (MIDUS) study, who were cognitively normal at baseline, and were followed-up for a maximum of 13 years (IQR 9–10). Cognitive decline was defined as having an annual rate of decline in global cognitive function (measured using five cognitive tests) ≥ 1 standard deviation faster than the mean decline rate from baseline to follow-up. Risk of incident all-cause dementia was evaluated in 2600 older adults (mean age = 83 years [IQR 81–84]; 56·7% female) pooled from the Osteoporotic Fractures in Men Study (MrOS) and the Study of Osteoporotic Fractures (SOF), who were dementia-free at baseline, and were followed-up for up a maximum of 7 years (IQR 4–5). Incident dementia was based on doctor-diagnosis. Frequency of distressing dreams was assessed in all cohorts at baseline (January 2002 – March 2012) using item 5h of the Pittsburgh Sleep Quality Index. The association between self-reported distressing dream frequency (“never”, “less than weekly”, “weekly”) and later cognitive outcomes, was evaluated using multivariable logistic regression in both the middle-aged and pooled older adult cohorts.FindingsAfter adjustment for all covariates, a higher frequency of distressing dreams was linearly and statistically significantly associated with higher risk of cognitive decline amongst middle-aged adults (P for trend = 0·016), and higher risk of incident all-cause dementia amongst older adults (P for trend <0·001). Compared with middle-aged adults who reported having no distressing dreams at baseline, those who reported having weekly distressing dreams had a 4-fold risk of experiencing cognitive decline (adjusted odds ratio [aOR] = 3·99; 95% CI: 1·07, 14·85). Amongst older adults, the difference in dementia risk was 2·2-fold (aOR = 2·21; 95% CI: 1·35, 3·62). In sex-stratified analyses, the associations between distressing dreams and both cognitive outcomes were only statistically significant amongst men.InterpretationDistressing dreams predict cognitive decline and all-cause dementia in middle-aged and older adults without cognitive impairment or PD - especially amongst men. These findings may help to identify individuals at risk of dementia and could facilitate early prevention strategies.FundingThe study received no external funding.

Mediation analysis of multiple mediators with incomplete omics data.

There is an increasing interest in using multiple types of omics features (e.g., DNA sequences, RNA expressions, methylation, protein expressions, and metabolic profiles) to study how the relationships between phenotypes and genotypes may be mediated by other omics markers. Genotypes and phenotypes are typically available for all subjects in genetic studies, but typically, some omics data will be missing for some subjects, due to limitations such as cost and sample quality. In this article, we propose a powerful approach for mediation analysis that accommodates missing data among multiple mediators and allows for various interaction effects. We formulate the relationships among genetic variants, other omics measurements, and phenotypes through linear regression models. We derive the joint likelihood for models with two mediators, accounting for arbitrary patterns of missing values. Utilizing computationally efficient and stable algorithms, we conduct maximum likelihood estimation. Our methods produce unbiased and statistically efficient estimators. We demonstrate the usefulness of our methods through simulation studies and an application to the Metabolic Syndrome in Men study.

Ambient air pollution and risk of incident dementia in older men living in a region with relatively low concentrations of pollutants: The Health in Men Study

BackgroundIn areas with moderate to severe air pollution, pollutant concentrations are associated with dementia risk. It is unclear whether the same relationship is present in regions with lower ambient air pollution. ObjectiveTo determine whether exposure to air pollution is associated with risk of incident dementia in general, and Alzheimer's disease and vascular dementia in particular, in older men living in a relatively low ambient air pollution region. MethodsThe cohort comprised 11,243 men residing in Perth, Australia. Participants were aged ≥65 years and free of a dementia diagnosis at time of recruitment in 1996–1999. Incident dementia was identified from recruitment to 2018 via ICD diagnosis codes and subsequent study waves. Concentrations for three air pollutants, nitrogen dioxide (NO2), fine particulate matter less than 2.5 μm in diameter (PM2.5), and black carbon (BC) were estimated at participants’ home addresses using land-use regression models. We used Cox proportional hazards regression models adjusting for smoking status, physical activity, BMI, education, and socio-economic status. ResultsOf 3053 (27.2%) incident cases of dementia, 1670 (54.7%) and 355 (11.6%) had documented Alzheimer's disease and vascular dementia. The average concentration of NO2 was 13.5 (SD 4.4) μg/m3, of PM2.5 was 4.54 (SD 1.6) μg/m3 and of BC was 0.97 (SD 0.29) ×10−5 m−1. None of the air pollutants were associated with incident dementia or Alzheimer's disease. In the unadjusted model, increased exposure to PM2.5 was associated with an increased risk of vascular dementia (for a 5 μg/m3 increase: HR 1.62, 95% CI 1.13, 2.31). However, this association was attenuated following adjustment for confounders (HR 1.39, 95% CI 0.93, 2.08). NO2 and BC were not associated with vascular dementia incidence. DiscussionExposure to air pollution is not associated with increased risk of incident dementia in older men living in a region with relatively low ambient air pollution.

Do Self-Assessments for Informed Study Decisions Actually Inform Study Decisions? A Model for Evaluating the Consequential Validity Aspect

Pre-enrolment self-assessments are a promising way to address student commitment and retention in an early stage. Such assessments aim to inform study decisions by evoking reflection and providing advice for further preparation. Though these assessments require a solid validation process, so far the consequential validity aspect tends to be ignored. To address this gap, the current study investigates self-assessment impact on study choice certainty and enrolment as well as self-assessment fairness. Prospective students (N = 662) orienting towards studying in higher online education took a self-assessment consisting of six subtests. The impact appeared in line with the assessment's purpose for 68.9% of the prospective students: their study choice certainty was adapted or remained unchanged in accordance with their obtained scores. Study choice certainty after the self-assessment related positively to enrolment probability. Additionally, the impact appeared fair (similar across subgroups), though men's study choice certainty appeared relatively robust against unfavourable scores.

Association of sleep abnormalities in older adults with risk of developing Parkinson's disease.

Parkinson's disease (PD) is associated with abnormalities of sleep macro- and microstructure as measured using polysomnography (PSG). Whether these abnormalities precede the development of PD is unknown. This study investigated the association between PSG measured sleep abnormalities in older adults and the risk of incident PD. A total of 2,770 men from the ancillary sleep study of the Osteoporotic Fractures in Men Study (MrOS), a population-based cohort from the United States, who were free from PD baseline and underwent overnight PSG, were included in this longitudinal analysis. Incident PD was based on a clinical diagnosis from a medical professional. Multivariable logistic regression was used to estimate odds ratios (OR) for incident PD by quartiles of PSG measures, with adjustment for sociodemographic characteristics, medical comorbidities, and lifestyle factors. During a median follow-up of 9.8 years, 70 (2.5%) cases of incident PD were identified. Longer total sleep time, lower rapid eye movement sleep (REM) percentage, a lower α/θ ratio during non-REM sleep and higher minimum oxygen saturations during REM sleep, were each associated with an increased risk of developing PD. Conversely, a higher awakening index was associated with a decreased risk of developing PD. The OR for the highest risk quartiles compared to the lowest risk quartiles, ranged from 2.1 to 3.7 (p's < .05). The associations remained significant when cases occurring within the first two years of follow-up were excluded from the analyses. Macro- and micro-structural sleep abnormalities precede the development of PD by several years and can identify individuals at high risk of developing PD in the future.

The Hospital Frailty Risk Score Identifies Fewer Cases of Frailty in a Community-Based Cohort of Older Men Than the FRAIL Scale and Frailty Index.

The recently developed Hospital Frailty Risk Score (HFRS) allows ascertainment of frailty from administrative data. We aimed to compare the HFRS against the widely used FRAIL Scale and Frailty Index. Population-based cohort study linked to Western Australian Hospital Morbidity Data Collection and Death Registrations. The Health in Men Study with frailty determined at Wave 2 (2001/2004), mortality in the 1-year period following Wave 2, and disability at Wave 3 (2008). Participants were 4228 community-based men aged ≥75years, followed untilWave 3. We used multivariable regression to determine the association between each frailty measure and outcomes of length of stay (LOS), death, and disability. We also determined if the additional cases of frailty identified by one measure over the other was associated with these outcomes. Of 4228 men studied, the HFRS (n= 689) identified fewer men as frail than the FRAIL Scale (n=1648) and Frailty Index (n= 1820). In the fully adjusted models, all 3 frailty measures were associated with longer LOS and mortality, whereas only the FRAIL Scale and Frailty Index were significantly associated with disability. The additional cases of frailty identified by the FRAIL Scale and Frailty Index had longer LOS and greater risks of death and disability. The fully adjusted hazard ratio for death among the additional cases of frailty identified by the FRAIL Scale (compared to being not frail on both HFRS and FRAIL Scale) was 2.14 (95% CI 1.48-3.08). The HFRS is associated with adverse outcomes. However, it identified approximately 60% fewer men who were frail than the FRAIL Scale and Frailty Index, and the additional cases identified were also at high risks of adverse outcomes. Users of the HFRS should be aware of the differences with other frailty measures.

Isoflavone and soy food intake and risk of lung cancer in never smokers: report from prospective studies in Japan and China.

Evidence from several cohorts has suggested that a higher intake of isoflavone is associated with lower risk of lung cancer in never smokers, but the association has not been investigated by histologic type of lung cancer. Adenocarcinoma is a common histologic type found in never smokers. We hypothesized that a higher intake of isoflavone is associated with a lower risk of lung adenocarcinoma among never smokers. Here, we examined the associations of isoflavone and soy food intake with lung cancer and its histologic types in never smokers. We performed a pooled analysis using data from the Japan Public Health Center-based Prospective Study, Shanghai Women's Health Study and Shanghai Men's Study with 147,296 never smokers aged 40-74years with no history of cancer. During 1,990,040 person-years of follow-up, 1247 lung cancer cases were documented. Dietary isoflavone and soy food intake were assessed using a food-frequency questionnaire. Multivariable Cox proportional hazards models assessed the associations between isoflavone and soy intake with incidence of lung cancer by histologic type. A higher intake of dietary isoflavone and soy food were associated with reduced risk of lung adenocarcinoma. The multivariable hazard ratios (HRs) (95% CI) of risk of lung adenocarcinoma for the highest versus lowest intakes of isoflavone and soy food were 0.74 (0.60-0.92) and 0.78 (0.63-0.96), respectively. The multivariable HRs of risk of lung adenocarcinoma associated with each 10mg/day increase in isoflavone and each 50g/day increase in soy food intake were 0.81 (0.70-0.94) and 0.84 (0.73-0.96), respectively. Higher intake of isoflavone and soy food was associated with lower risk of lung adenocarcinoma in never smokers.

Anemia is associated with increased risk of non-vertebral osteoporotic fractures in elderly men: the MrOS Sweden cohort

SummaryThis study includes 1005 men from the Gothenburg part of the Osteoporotic Fracture in Men Study (MrOS). Included are 66 men with anemia (hemoglobin < 130 g/L). The follow-up time was up to 16 years, and the main results are that anemia is associated with all fractures and non-vertebral osteoporotic fractures.IntroductionAnemia and osteoporotic fractures are conditions that are associated with increased morbidity and mortality. Clinical studies have suggested that anemia can be used as a predictor of future osteoporotic fractures.MethodMen from the Osteoporotic Fractures in Men Study (MrOS) Sweden, Gothenburg, with available hemoglobin (Hb) values (n = 1005, median age 75.3 years (SD 3.2)), were included in the current analyses. Of these, 66 suffered from anemia, defined as Hb < 130 g/L. Median follow-up time for fracture was 10.1 years and the longest follow-up time was 16.1 years.ResultsMen with anemia had, at baseline, experienced more falls and had a higher prevalence of diabetes, cancer, prostate cancer, hypertension, and stroke. Anemia was not statistically significantly associated with bone mineral density (BMD). Men with anemia had higher serum levels of fibroblast growth factor 23 (iFGF23) (p < 0.001) and phosphate (p = 0.001) and lower serum levels of testosterone (p < 0.001) and estradiol (p < 0.001). Moreover, men with anemia had an increased risk of any fracture (hazard ratio (HR) 1.97, 95% CI 1.28–3.02) and non-vertebral osteoporotic fracture (HR 2.15, 95% CI 1.18–3.93), after adjustment for age and total hip BMD, in 10 years. The risk for any fracture was increased in 10 and 16 years independently of falls, comorbidities, inflammation, and sex hormones. The age-adjusted risk of hip fracture was increased in men with anemia (HR 2.32, 95% CI 1.06–5.12), in 10 years, although this was no longer statistically significant after further adjustment for total hip BMD.ConclusionsAnemia is associated with an increased risk for any fracture and non-vertebral osteoporotic fracture in elderly men with a long follow-up time. The cause is probably multifactorial and our results support that anemia can be used as a predictor for future fracture.

Within-night repeatability and long-term consistency of sleep apnea endotypes: the Multi-Ethnic Study of Atherosclerosis and Osteoporotic Fractures in Men Study.

Obstructive sleep apnea (OSA) is characterized by multiple "endotypic traits," including pharyngeal collapsibility, muscle compensation, loop gain, and arousal threshold. Here, we examined (1) within-night repeatability, (2) long-term consistency, and (3) influences of body position and sleep state, of endotypic traits estimated from in-home polysomnography in mild-to-severe OSA (apnea-hypopnea index, AHI > 5 events/h). Within-night repeatability was assessed using Multi-Ethnic Study of Atherosclerosis (MESA): Traits derived separately from "odd" and "even" 30-min periods were correlated and regression (error vs. N windows available) provided a recommended amount of data for acceptable repeatability (Rthreshold = 0.7). Long-term consistency was assessed using the Osteoporotic Fractures in Men Study (MrOS) at two time points 6.5 ± 0.7 years apart, before and after accounting for across-year body position and sleep state differences. Within-night dependence of traits on position and state (MESA plus MrOS data) was estimated using bootstrapping. Within-night repeatability for traits ranged from R = 0.62-0.79 and improved to R = 0.69-0.83 when recommended amounts of data were available (20-35 7-min windows, available in 94%-98% of participants); repeatability was similar for collapsibility, loop gain, and arousal threshold (R = 0.79-0.83), but lower for compensation (R = 0.69). Long-term consistency was modest (R = 0.30-0.61) and improved (R = 0.36-0.63) after accounting for position and state differences. Position/state analysis revealed reduced loop gain in REM and reduced collapsibility in N3. Endotypic traits can be obtained with acceptable repeatability. Long-term consistency was modest but improved after accounting for position and state changes. These data support the use of endotypic assessments in large-scale epidemiological studies. The data used in the manuscript are from observational cohort studies and are not a part of the clinical trial.

Control of Epstein-Barr Virus (EBV) in the Oral Cavity Is Associated With Persistence of Oral Human Papillomavirus (HPV)16/18 Among Men From the HPV Infection in Men Study.

Human papillomavirus (HPV)-related oropharyngeal cancer (OPC) incidence is increasing among men. Biomarkers that can identify oral HPV16/18 infections likely to persist, the obligate precursor for HPV-OPC, are needed. We assessed the association between oral Epstein-Barr virus (EBV) and oral HPV16/18 persistence among 63 men in the HPV Infection in Men Study who tested positive for HPV16/18 at the baseline visit. Control of oral coinfections, including EBV, could serve as a biomarker of immune competence and the ability to control oral HPV. Detection of oral EBV was significantly associated with oral HPV16/18 ≥12-month persistence. Detection of oral EBV deserves evaluation as a biomarker for oral HPV persistence and HPV-related OPC.

Lower Leg Power and Grip Strength Are Associated With Increased Fall Injury Risk in Older Men: The Osteoporotic Fractures in Men Study.

Past research has not investigated both lower-extremity power and upper-extremity strength in the same fall injury study, particularly nonfracture fall injuries. In the Osteoporotic Fractures in Men Study (baseline: N = 5 994; age 73.7 ± 5.9 years; 10.2% non-White), fall injuries (yes/no) were assessed prospectively with questionnaires approximately every 3 years over 9 years. Maximum leg power (Watts) from Nottingham single leg press and maximum grip strength (kg) from handheld dynamometry were assessed at baseline and standardized to kg body weight. Physical performance included gait speed (6-m usual; narrow walk) and chair stands speed. Of men with ≥1/4 follow-ups (N = 5 178; age 73.4 ± 5.7 years), 40.4% (N = 2 090) had ≥1 fall injury. In fully adjusted repeated-measures logistic regressions, lower power/kg and grip strength/kg had higher fall injury risk (trend across quartiles: both p < .0001), with lower quartiles at significantly increased risk versus highest Q4 except for grip strength Q3 versus Q4. Fall injury risk was 19% higher per 1 standard deviation (SD) lower power/kg (95% confidence interval [CI]: 1.12-1.26) and 16% higher per SD lower grip strength/kg (95% CI: 1.10-1.23). In models including both leg power/kg and grip strength/kg, odds ratios (ORs) were similar and independent of each other and physical performance (leg power/kg OR per SD = 1.13, 95% CI: 1.06-1.20; grip strength/kg OR per SD = 1.11, 95% CI: 1.05-1.17). Lower leg power/kg and grip strength/kg predicted future fall injury risk in older men independent of physical performance. Leg power potentially identifies fall injury risk better than grip strength at higher muscle function, though grip strength may be more suitable in clinical/practice settings.

The Association between Smoking and Anal Human Papillomavirus in the HPV Infection in Men Study.

Previous studies show an association between smoking and anal cancer. The objective of this study was to assess the association between smoking and anal HPV (human papillomavirus) prevalence, incidence, and persistence in men. The HPV Infection in Men (HIM) Study is a multinational study that enrolled HIV-negative men. At baseline and follow-up visits, anal specimens were collected. HPV genotyping was assessed by linear array. Prevalence ratios (PR) were used to assess the association between smoking and anal HPV prevalence. Odds ratios (OR) were used to assess the association between smoking and anal HPV incidence and ≥12-months persistence. Current smokers have a higher prevalence [adjusted PR (aPR), 1.36; 95% confidence interval (CI), 1.06-1.73) and incidence [adjusted OR (aOR), 1.74; 95% CI, 1.26-2.39] and ≥12-months persistence (aOR, 1.67; 95% CI, 1.19-2.33) of any anal HPV compared with never smokers. There were no differences in the prevalence, incidence, or persistence of anal HPV between former and never smokers. Smoking status was not associated with the prevalence or persistence of anal HPV among men who have sex with men but was associated with higher incidence of HR-HPV. Among men that have sex with women (MSW), current smokers had an increased prevalence and incidence of LR-HPV compared with never smokers. Current smokers had a higher prevalence, persistence, and incidence of HPV compared with never smokers. Further research is needed to assess the role smoking in anal HPV persistence and progression to disease. Prevention initiatives should raise awareness about smoking and the risk factor of anal HPV infection and anal cancer.

Distressing dreams and risk of Parkinson's disease: A population-based cohort study

SummaryBackgroundParkinson's disease (PD) is associated with alterations to the phenomenology of dreaming - including an increased frequency of distressing dreams. Whether distressing dreams may precede the development of PD is unknown. This study investigated the association between frequent distressing dreams and the risk of incident PD.Methods3818 men aged 67 years or older from the Osteoporotic Fractures in Men Study (MrOS), a population-based cohort from the USA, who were free from PD at baseline (December 2003 – April 2011) and completed item 5h of the Pittsburgh Sleep Quality Index - which probes the frequency of distressing dreams in the past month, were included in this analysis. Incident PD was based on doctor diagnosis. Multivariable logistic regression was used to estimate odds ratios (OR) for incident PD according to distressing dream frequency, with adjustment for potential confounders.FindingsDuring a mean follow-up of 7·3 years, 91 (2·4%) cases of incident PD were identified. Participants with frequent distressing dreams at baseline had a 2-fold risk for incident PD (OR, 2·01; 95% CI, 1·1-3·6, P = 0.02). When stratified by follow-up time, frequent distressing dreams were associated with a greater than 3-fold risk for incident PD during the first 5 years after baseline (OR, 3·38; 95% CI, 1·3-8·7; P = 0·01), however no effect was found during the subsequent 7 years (OR, 1·55; 95% CI, 0·7-3·3; P = 0·26).InterpretationIn this prospective cohort, frequent distressing dreams were associated with an increased risk for incident PD. The association was only significant within the 5 years prior to diagnosis, which suggests that frequent distressing dreams may be a prodromal symptom of PD.FundingThe study received no external funding.

Recent fall and high imminent risk of fracture in older men and women.

despite fall history being a well-known risk factor for falls and fractures, the association between very recent falls and imminent fracture risk is not clearly elucidated. to study the very recent (<4months) fall-related absolute risk of fractures in the following year. two large prospective cohort studies of women (Study of Osteoporotic Fractures [SOF]) and men (Osteoporotic Fractures in Men Study [MrOS]) aged 65years or older were included. Data on falls were collected every 4months, and the primary outcomes were any non-spine and hip fractures in the next 12months. a total of 9,704 women contributed 419,149, and 5,994 men contributed 223,885 four-monthly periods of observations during the 14.8-year SOF and 12.6-year MrOS follow-up. Falls within 4months indicated a high risk of non-spine and hip fractures in the following year for both sexes; in women, a recent fall indicated an 8.1% absolute risk of a non-spine fracture within 1year, a 2.5-fold higher risk than that in women without falls, a 2.5% absolute risk of hip fracture, and a 3.1-fold increased risk. Falls increased the risk of fractures regardless of whether a fracture occurred or not. Men had similar risk patterns, albeit with a lower absolute risk of fracture. in older people, a fall within 4months indicates a high risk of fracture in the next year, regardless of fracture occurrence. A recent fall warrants urgent evaluation and consideration of treatments to reduce the imminent risk of fractures.

0316 Actigraphy-Derived Sleep Health Profiles and Mortality in Older Men and Women

Abstract Introduction To identify actigraphy sleep health profiles in older men (Osteoporotic Fractures in Men Study; N=2,640) and women (Study of Osteoporotic Fractures; N=2.430), and to determine whether the identified profiles predict mortality. Methods We applied a novel and flexible clustering approach (Multiple Coalesced Generalized Hyperbolic mixture modeling) to identify sleep health profiles based on actigraphy midpoint timing, midpoint variability, sleep interval length, continuity, and napping/inactivity. Adjusted Cox models were used to determine whether profile membership predicts time to all-cause mortality. Results We identified similar profiles with different prevalences in men and women: High Sleep Propensity [HSP] (20% of women; 39% of men; high napping and high continuity); Adequate Sleep [AS] (74% of women; 31% of men; average actigraphy levels); and Abnormal Continuity/Timing [ACT] (6% of women; 30% of men; low continuity and late/variable midpoint). In women, ACT was associated with increased mortality risk (Hazard Ratio [HR]=1.59 for ACT vs. AS; 1.75 for IS vs. HSP). In men, ACT and AS were associated with increased mortality risk relative to HSP (1.19 for IS vs. HSP; 1.22 for AS vs. HSP). Conclusion These findings suggest several considerations for sleep-related interventions in older adults. For instance, interventions may be developed to target the combination of low continuity with late/variable midpoint. Findings also indicate that high napping/inactivity co-occurs with high sleep continuity in some older adults. Although high napping/inactivity is typically considered a risk factor for deleterious health outcomes, our findings suggest that it may not be inherently problematic when occurring in combination with high sleep continuity. Support (If Any) The Osteoporotic Fractures in Men (MrOS) Study is supported by NIH grants U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, UL1 TR000128, R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839. The Study of Osteoporotic Fractures (SOF) is supported by NIH grants R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576, and R01 AG026720. This study is also supported by NIH grants R01AG056331 and RF1AG056331 (PI: Wallace), R56AG065251 (PI: Lee), K01MH112683 (PI: Smagula), and R35HL135815 (PI: Redline).

Transethnic meta-analysis of exome-wide variants identifies new loci associated with male-specific metabolic syndrome.

Metabolic syndrome (MetS) is a group of very common human conditions promoting strong understand the impact of rare variants, beyond exome-wide association studies, to potentially discover causative variants, across different ethnic populations. We performed transethnic, exome-wide MetS association studies on MetS in men. We analyzed genotype data of 5302 European subjects (2658 cases and 2644 controls), in the discovery stage of the European METabolic Syndrome In Men study, generated from exome chips, and 2481 subjects (714 cases and 1767 controls), in the replication stage, across 6 independent cohorts of 5 ancestries (T2D-GENES consortium), using whole-exome sequencing. We therefore evaluated gene-level and variant-level associations, of rare variants for MetS, using logistic regression (LR) and multivariate analyses (MulA). Gene-based association found the gene for the cholesteryl ester transfer protein (CETP) (from MulA, p value = 4.67×10-9; from LR, p value = 0.009) to well associate with MetS. At two missense variants, from 8 rare variants in CETP, Ala390Pro (rs5880) (from MulA, p value = 1.28×10-7; from LR, p value = 1.34×10-4) and Arg468Gln (rs1800777) (from MulA, p value = 2.40×10-5; from LR, p value = 1.49×10-3) significantly associated with MetS across five ancestries. Our findings highlight novel rare variants of genes that confer MetS susceptibility, in Europeans, that are shared with diverse populations, emphasizing an opportunity to further understand the biological target or genes that underlie MetS, across populations.

Changes in Objectively Measured Physical Activity Are Associated With Perceived Physical and Mental Fatigability in Older Men.

Lower physical activity (PA) is associated with greater perceived fatigability, a person-centered outcome. The association between change in PA and fatigability with advanced age has yet to be established. Community-dwelling older men (N = 1 113, age = 84.1 ± 3.9 years at Year 14) had free-living PA assessed using SenseWear Armband prospectively at Year 7 (2007-2009) and Year 14 (2014-2016) of Osteoporotic Fractures in Men Study, a longitudinal cohort established in 2000 (baseline). We categorized percent changes in PA into groups (large decline → large increase) for 4 metrics: step count, light intensity PA (LIPA, metabolic equivalents [METs] >1.5 to <3.0), moderate-to-vigorous PA (MVPA, METs ≥ 3.0), and sedentary behavior (SB, METs ≤ 1.5, excluding sleep). Perceived physical and mental fatigability were measured (Year 14) with the Pittsburgh Fatigability Scale (PFS, higher score = greater fatigability; range = 0-50). Associations between each metric of percent changes in PA and fatigability were examined using linear regression, adjusted for demographics, change in health conditions, and Year 7 step count or total PA (METs > 1.5). Men declined 2 336 ± 2 546 (34%) steps/d, 24 ± 31 (25%) LIPA min/d, 33 ± 58 (19%) MVPA min/d, and increased 40 ± 107 (6%) SB min/d over 7.2 ± 0.7 years. Compared to large decline (% change less than -50%), those that maintained or increased step count had 3-8 points lower PFS Physical scores; those who maintained or increased LIPA and MVPA had 2-3 and 2-4 points lower PFS Physical scores, respectively (all p ≤ .01). Associations were similar, but smaller, for PFS Mental scores. Older men who maintained or increased PA had lower fatigability, independent of initial PA. Our findings inform the types and doses of PA that should be targeted to reduce fatigability in older adults.

Associations of components of sarcopenia with risk of fracture in the Osteoporotic Fractures in Men (MrOS) study.

The association between the components of sarcopenia and fractures has not been clearly elucidated and has hindered the development of appropriate therapeutic interventions. Our aim was to evaluate the associations between the individual components of sarcopenia, specifically lean mass, strength, and physical performance and fracture (any fracture, hip fracture, major osteoporotic fracture) in the Osteoporotic Fractures in Men (MrOS) study. The Osteoporotic Fractures in Men study (MrOS) recruited 5995 men ≥ 65 years of age. We measured appendicular lean mass (ALM) by dual-energy X-ray absorptiometry (low as residual value < 20th percentile for the cohort), walking speed (fastest trial of usual pace, values < 0.8 m/s were low), and grip strength (max score of 2 trials, values < 30 kg were low). Information on fractures was assessed tri-annually over an average follow-up of 12 years and centrally adjudicated. Cox proportional hazard models estimated the hazard ratio (HR) (95% confidence intervals) for slow walking speed, low grip strength, and low lean mass. Overall, 1413 men had a fracture during follow-up. Slow walking speed was associated with an increased risk for any HR = 1.39, 1.05-1.84; hip HR = 2.37, 1.54-3.63; and major osteoporotic, HR = 1.89, 1.34-2.67 in multi-variate-adjusted models. Low lean mass and low grip strength were not significantly associated with fracture. In this cohort of older adult men, the risk of experiencing any, hip, or major osteoporotic fracture is greater in men with slow walking speed in comparison to men with normal walking speed, but low grip strength and low lean mass were not associated with fracture.