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During the aging process, the vasculature undergoes pathologic changes which are strongly associated with hypertension and future cardiovascular disease (CVD) risk. Previous work to identify protein biomarkers of these subclinical vascular changes, which have largely focused on single proteins, has observed many associations in different populations. However, research in African-ancestry populations, who are at high risk for hypertensive CVD, is limited and may be biased by the existing research in Whites. Therefore, we used a proteomic approach to identify biomarkers of vascular aging as assessed by pulse-wave velocity (PWV) and abdominal aortic calcification (AAC). We included 346 African-ancestry men from the Tobago Health Study, a prospective cohort study of community-dwelling men aged ≥40 years residing on the Caribbean island of Tobago. These men were aged from 53-89 years old (mean ± SD = 63.4 ± 8.1 years) and were overweight on average (mean ± SD BMI = 27.7 ± 4.3kg/m2). 79.2% of men had hypertension, 24.6% had diabetes, and 5.9% were current smokers. We quantified protein expression using the Olink® Target 96 Cardiovascular III proteomics panel which includes 92 proteins with known association to human cardiovascular processes (CVDIII; Olink®, Waltham, MA). Brachial-ankle PWV (cm/s) was measured using an automated waveform analyzer. AAC was measured in the aorta at the iliac bifurcation via CT and scored using the Agatston method. Partial Spearman correlations were calculated to assess the relationship between each protein biomarker and both vascular aging outcomes adjusting for age, Olink® assay batch, height, weight, diabetes status, hypertension status, and current smoking. There were 13 and 5 proteins correlated with PWV and AAC, respectively (at P

Introduction: Sleep efficiency (or sleep continuity, i.e., a ratio of time spent sleeping to time spent in bed), is inversely associated with hypertension, impaired glucose metabolism, CVD risk, and mortality risk. Prolonged sedentary behavior and physical activity are independently associated with sleep efficiency. However, it is not well documented how substituting time in sedentary behavior with physical activity affects sleep efficiency, especially among African-ancestry populations, who are at high risk for CVD. Aim: To determine if displacement of sedentary time with activity was cross-sectionally associated with higher sleep efficiency among African Caribbean men (n=231) and women (n=668) from the Tobago Health Study. Methods: Sleep efficiency, sedentary behavior (SB), light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were collected using a SenseWear Pro Armband. Participants wore the armband at all times, except in water, for 4-7 days. We used the Isotemporal Substitution Framework paired with linear regression to examine associations of SB, LPA and MVPA with sleep efficiency adjusting for age, education, BMI, hypertension, diabetes, smoking, alcohol consumption, caffeine intake, and sleep medication. Results: Men (mean age ± Standard deviation: 63.2 ± 8.2 years; mean BMI 28.2 ± 4.8 kg/m 2 ) spent on average less time in SB (12.4 ± 2.9 hours/day) and more time in LPA (4.7 ± 2.1 hours /day) and MVPA (0.92 ± 0.88 hours/day) than women (mean age 55.6 ± 8.7 years; mean BMI 31.8 ± 6.4 kg/m 2 ) (all p-vales Conclusions: In this population with short sleep duration, reallocating 1 hour of SB with LPA was associated with higher sleep efficiency in both genders. In contrast, among men only, reallocating 1 hour of SB to MVPA and 1 hour of LPA to MVPA were unexpectedly associated with lower sleep efficiency. Further research is warranted to understand these relationships longitudinally to determine how truly replacing SB for activities of different intensities impacts sleep health, which could then potentially inform lifestyle guidelines in older Caribbeans. In this highly sedentary population, interventions aimed at increasing LPA may be easier to implement and maintain and provide greater sleep and overall health benefit.

Objective Skeletal muscle adiposity (SMA) increases with aging and is recognized as a major risk factor for cardiometabolic diseases, disability, and mortality among older adults. Obesity is related to dementia and cognitive decline yet the relationship between SMA and cognition remains ill defined. The objective of this study was to assess SMA and cognitive function among African Caribbean women.Design and Methods Cross-sectional analysis of 448 African Caribbean women in the Tobago Health Study (mean age, 55 years; range, 39-84 years). Cognition was assessed by the Digit Symbol Substitution Test (DSST), a test of information processing speed with a range of 0-90; higher scores suggest better cognitive function (faster information processing speed). Calf SMA (muscle density) was assessed with computed tomography (Stratec XCT-2000). Linear regression was used to assess the association of SMA with DSST adjusted for age, education, muscle area, waist circumference, alcohol intake, smoking, physical activity, diabetes, and hypertension. Results Participants had a BMI of 30.7 kg/m2. Mean (SD) DSST scores and SMA were 39.2 (13.1) and 71.7 (5.3) mg/cm3, respectively. After full adjustment, we found that one SD greater skeletal muscle adiposity was associated with a 1.40 lower DSST score (p-value=0.025). Conclusions Our findings suggest that in African Caribbean women, greater SMA is associated with slower information processing speed, an early indicator of future dementia risk. Future studies using an expanded battery of cognitive tests and longitudinal follow-up should further advance our understanding of the role of SMA and dementia risk among African ancestry populations.

Although measures of physical function such as walking speed and time to complete chair-rises are highly heritable, the genetic architecture underlying these phenotypes remains poorly defined. To identify potentially novel genes and pathways underlying physical performance in older adults, we conducted a genome-wide association meta-analysis of the short physical performance battery (SPPB) (Score 0-12) and one of its components, chair-rise time (seconds) in 24,033 Caucasian adults aged 60+ from 13 cohorts (mean cohort age 66.2 ± 5.3 to 84.3 ± 4.1 years; 56.5% women). Cohorts had a genome wide scan imputed to either the Haplotype Reference Consortium or Trans-Omics for Precision Medicine imputation panels. Single nucleotide polymorphism (SNPs) with a minor allele frequency ≥0.1% and imputation quality score ≥0.7 were included (range 7.5-10.5 million per cohort). Analyses were adjusted for age, sex, height, and population substructure. Meta-analysis was performed using a fixed-effects model. Although no genome-wide significant loci were identified, 67 and 60 suggestive loci (p< 5*10-5) were detected for SPPB score and chair-rises time, respectively. Pathway-based analyses indicated significant enrichment of genes affecting negative regulation of calcium channel activity (Bonferroni corrected p-value < 0.05). Sex-stratified gene-based analyses identified clathrin vesicle-associated sec14 protein 1 (CLVS1), significantly associated with chair-rise time in women (p= -1.5*10-7). CLVS1 is highly expressed in the cerebellum, which is involved in postural and motor function control. A larger sample size is needed to confirm and extend our findings, but our results potentially implicate a novel pathway and locus for physical performance in older women.

The epidemiology of prediabetes and its metabolomic features remain poorly characterized in the oldest old. Therefore, we characterized the serum lipidome in 635 nonagenarians and centenarians without type 2 diabetes (T2D) from the Long Life Family Study, a multicenter study of 583 families with a clustering of exceptional longevity. Despite a low T2D prevalence and incidence in the LLFS cohort, 361 (56.9%) of participants aged 90+ years had prediabetes at study entry based on either glycated hemoglobin or fasting serum glucose levels. We used LC/MS to initially assess 193 lipid metabolites in fasting serum in those with and without prediabetes. We tested the association of log transformed lipid metabolites with prediabetes using logistic regression with the Benjamini-Hochberg false-discovery rate method (FDR Disclosure I. Miljkovic: None. R. Cvejkus: None. P. An: None. B. Thyagarajan: n/a. J. Mengel-from: None. M. Feitosa: None. A. N. Benbourenane: None. J. M. Zmuda: None. Funding National Institute of Health (U01AG023746)

Introduction: Skeletal muscle adipose tissue infiltration (i.e. myosteatosis) increases with aging, and is recognized as a major risk factor for cardio-metabolic diseases. While it is known that visceral adiposity is related to dementia and cognitive decline, the relationship between myosteatosis and cognition is not well understood. Such studies are particularly needed among African ancestry women, who have greater myosteatosis and higher burden of Alzheimer’s Disease and Related Dementias compared with White women. Aim: The objective of this study was to assess if, among African Caribbean middle-aged and older women (aged 40-79), myosteatosis is associated with cognitive function. Methods: Data were collected on women (n=481) from the Tobago Health Study. Cognition was assessed by the Digit Symbol Substitution Test (DSST), a test of information processing speed; DSST is a fast, reliable and sensitive test that predicts onset of dementia. DSST was administered to participants by trained interviewers; scores ranged from 0 to 81 (lower score indicating cognitive decline). Peripheral Quantitative Computed Tomography (Stratec XCT-2000) was used to measure calf skeletal muscle density (MD), which was used as a proxy measure for the myosteatosis (lower MD reflects more adiposity). Linear regression was used to assess the association of muscle density with cognition and was adjusted for age, education, muscle area, waist circumference, alcohol intake, smoking, walking hours, diabetes and hypertension. Results for the primary predictor of interest (MD) were standardized with effects shown per standard deviation (SD). Results: Mean (SD) DSST scores were 38.8 (13.2). Overall, participants were aged 55.2 years and had a BMI of 30.7 kg/m 2 . Mean (SD) MD was 71.7((5.3) (mg/cm 3 ). As expected, in unadjusted analyses, the strongest predictors of lower DSST scores in these women were older age and lower education, higher waist circumference, diabetes and hypertension. After full adjustment, we found that a one SD increase in MD was associated with a 1.48 increase in DSST score (p-value=0.015). Conclusions: Our findings suggest that in African Caribbean women, greater myosteatosis is associated with slower information processing speed, an early indicator of future dementia risk. Future studies using expanded battery of cognitive tests and longitudinal follow-up are warranted to further advance our understanding of the novel role of myosteatosis in dementia risk among African ancestry women.

Gait speed is a heritable, robust predictor of longevity in older adults. Using genome-wide linkage analysis in 2379 individuals from 509 families (64±12 years; 45% men), we identified a locus on chromosome 16p linked to gait speed change over 7±1 years (logarithm of the odds score [LOD]=4.2). Gait speed change was calculated using a two-stage growth curve mixed-model. DNA sequencing was completed to identify single nucleotide variants (SNVs) in the linkage region. Association analyses between the 24039 SNVs in the ~1.6mBP region (3.7-5.3mBP) and gait speed change were performed adjusting for age, age2, sex, height, field center, familial relatedness and population substructure. Eleven families (188 individuals) accounted for most of the linkage signal (LOD=6.06). Associations between SNVs flanking the Mesothelin (MSLN) gene and gait speed change were identified (lead SNV rs56850119: β = -0.5±0.1, p = 6.4*10-7). Thus, MSLN is a potential positional candidate gene for mobility decline with aging.

Mitochondrial energy production decreases while fatigability increases with age. Genes associated with energy metabolism may contribute to fatigability. Using Long Life Family Study (LLFS), we initially assessed variants (SNPs) in 272 candidate autosomal genes involved in energy metabolism (previously associated with mitochondrial dysfunction disease) with perceived physical fatigability. Two generations of LLFS enrollees (N=2342, mean age=73.7, range 60-108 years) completed the Pittsburgh Fatigability Scale (PFS, 0-50, higher=greater fatigability) at Visit 2 (2014-2017). Physical fatigability prevalence was 42.1% (PFS≥15). Generalized linear mixed models assessed the association of each SNP with continuous PFS (GENESIS R package) adjusted for age, sex, field center, and family relatedness. We found no associations with perceived physical fatigability, all p>2.5E-7 (Bonferroni multiple comparison corrected p-value). Next steps will examine variants in the mitochondrial genome and BTBD3, another promising candidate gene recently discovered. Genetic biomarker(s) may identify individuals susceptible to greater fatigability to target for early intervention.

Gait speed is a predictor of overall health and mortality in older adults. Metabolomics may provide insights into biological mechanisms underlying gait speed. Herein, we examined the association between 193 lipid metabolites with gait speed in 1,717 adults (52.1% women) aged 82.0 ± 14.5. Lipidomic analysis was performed using liquid chromatography-mass spectrometry. Gait speed was measured over 4-meters and slowness was defined as

OBJECTIVE: African ancestry individuals are at high risk for hypertensive cardiovascular disease (CVD) and could benefit from early detection of arterial stiffening. We tested the association between the 2017 ACC/AHA hypertension categorizations, which include new blood pressure (BP) cutoffs and a definition for elevated BP, and arterial stiffness in 772 Afro-Caribbean men aged 50+ years (mean 64 years). METHODS: Arterial stiffness was assessed by brachial-ankle pulse-wave velocity (PWV) using a waveform analyzer. Hypertension groups were based on the 2017 ACC/AHA guidelines and by pharmacologic control status. Multiple linear/logistic regression was used to determine the association of PWV with BP and hypertension. RESULTS: Mean(SD) PWV was 1609(298) cm/s and was independently correlated with age, systolic BP, pulse, diabetes, height, and alcohol intake (all P

Emerging evidence indicates that ectopic skeletal muscle adiposity may be a risk factor for type 2 diabetes (T2D), especially in persons of African ancestry. In vitro studies suggest that a Wnt pathway inhibitor, Dickkopf-related protein 1 (DKK1), plays a role in adiposity regulation and could be a biomarker for adiposity in humans. The objective of this study was to test whether serum DKK1 levels relate to adiposity measures in a cohort from an African ancestry population at high risk for T2D. Fasting serum DKK1 was measured in a sample of 159 men of African ancestry aged ≥40 years (mean age ± SD, 63.5 ± 8.2 years; mean body mass index, 27.8 ± 4.5 kg/m2). Anthropometrics included total-body and trunk adiposity measured by dual-energy x-ray absorptiometry and lower-leg skeletal muscle density measured by CT [which reflects the intramuscular adiposity content (mg/cm3)]. Serum DKK1 was positively correlated with BMI (r = 0.20; P = 0.01), waist circumference (r = 0.15; P = 0.046), DXA total-body adiposity (r = 0.24; P = 0.003), and DXA trunk adiposity (r = 0.21; P = 0.009), independent of age and height. In addition, serum DKK1 was inversely correlated with skeletal muscle density (r = −0.25; P = 0.002), independent of age, BMI, and calf muscle area. No significant correlation was found between serum DKK1 and fasting serum glucose or insulin levels or insulin resistance estimated by homeostasis model assessment. These findings suggest that higher levels of serum DKK1 may be associated with greater overall, central, and ectopic skeletal muscle adiposity. Further studies are needed to unravel the potential role of DKK1 in the regulation of adiposity in humans.

Background Gait speed is a powerful indicator of health with aging. Potential genetic contributions to gait speed and its decline with aging are not well defined. We determined the heritability of and potential genetic regions underlying change in gait speed using longitudinal data from 2379 individuals belonging to 509 families in the Long Life Family Study (mean age 64 ± 12, range 30–110 years; 45% men). Methods Gait speed was measured over 4 m at baseline and follow-up (7 ± 1 years). Quantitative trait linkage analyses were completed using pedigree-based maximum likelihood methods with logarithm of the odds (LOD) scores greater than 3.0, indicating genome-wide significance. We also performed linkage analysis in the top 10% of families contributing to LOD scores to allow for heterogeneity among families (HLOD). Data were adjusted for age, sex, height, and field center. Results At baseline, 26.9% of individuals had “slow” gait speed less than 1.0 m/s (mean: 1.1 ± 0.2 m/s) and gait speed declined at a rate of −0.02 ± 0.03 m/s per year (p < .0001). Baseline and change in gait speed were significantly heritable (h2 = 0.24–0.32, p < .05). We did not find significant evidence for linkage for baseline gait speed; however, we identified a significant locus for change in gait speed on chromosome 16p (LOD = 4.2). A subset of 21 families contributed to this linkage peak (HLOD = 6.83). Association analyses on chromosome 16 showed that the strongest variant resides within the ADCY9 gene. Conclusion Further analysis of the chromosome 16 region, and ADCY9 gene, may yield new insight on the biology of mobility decline with aging.

Introduction: Skeletal muscle is the largest organ in the human body and vital to maintaining metabolic homeostasis. Increased skeletal muscle fat infiltration (i.e. myosteatosis) is now recognized as a major risk factor for cardio-metabolic diseases, independent of general obesity. Modifications in lifestyle, such as sleep, to reduce myosteatosis would be of great public health importance. However, studies of this relationship often use subjective data and are lacking in minority populations. The aim of this study was to examine the relation between objectively measured sleep duration and myosteatosis at the calf among African Caribbeans. Methods: Data were collected on men (n=393) and women (n=438) from the Tobago Health Study. Sleep duration and physical activity was collected using a SenseWear Pro Armband (BodyMedia, Inc.). Participants were instructed to wear the armband at all times, except in water, for 4-7 days. Measures of muscle density, intermuscular adipose tissue (IMAT), and area were obtained by peripheral QCT scans of the calf (Stratec XCT-2000). Model covariates included age, sex, BMI, diabetes, alcohol intake, smoking, and moderate to vigorous physical activity (MVPA). Linear regression was used to assess the relationship of sleep duration on skeletal muscle. Results: Mean sleep duration was 5.5 hours/day (Min 2.2, Max 11.6). Overall, participants were aged 58.7 years, had a BMI of 30.2 kg/m 2 , spent an average of 42 min/day in MVPA, and 18% were diabetic. In fully adjusted models, longer sleep duration was associated with smaller muscle area, but greater muscle density and less IMAT (all P Conclusions: In African Caribbean men and women, longer sleep duration was associated with less myosteatosis, as well as, less muscle area at the calf. Further research is warranted to understand this relationship longitudinally in order to determine how it may inform lifestyle guidelines in the Caribbean.

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10−17), arthritis (GDF5 p = 4 × 10−13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing., Muscle weakness has been associated with morbidity and mortality in older people. Here, the authors have investigated this trait further by performing a genome-wide meta-analysis of grip strength and Mendelian randomization to discover causal relationships between muscle weakness and other diseases.

Little is known about the time course of muscle–bone effects and whether a reciprocal clinical effect of bone on muscle is present. We hypothesized that lean mass (LM) measures at the arms and legs have a stronger relationship with BMD measured within the same region than the reciprocal effect. The Tobago Bone Health Study was used to address this hypothesis, examining body composition data from total body DXA scans obtained at 0, 48‐, and 120‐month visits. A longitudinal analysis of LM, LM/height2 (LMI), and LM/BMI was conducted at the upper and lower extremities separately, in relation to BMD within the corresponding region. A cross‐lagged panel model was used to study pathways from 0 to 120 months for muscle–bone and bone–muscle effects within the same visit, and across each lagged period. Models accounted for age, height, weight, race, arthritis, prior nontraumatic fracture after age 40, number of units of alcohol consumed per week, current smoking, diagnosis of diabetes mellitus, amount of walking in the last week, grip strength, and hospitalizations. Significant models demonstrating parsimony, and meeting absolute and relative fit criteria were retained. Among 1286 Afro‐Caribbean men (mean age: 53 ± 9 years, BMI: 27.43 ± 4.23 kg/m2) with data available for all visits, LM, LMI, and LM/BMI had modest contemporaneous relationships with BMD, which dissipated with lagged time. The size of these effects was stronger at the legs than at the arms. These lagged effects were primarily mediated through indirect same time‐point muscle–bone relations rather than a true directly lagged effect. Bone density showed only a small effect on LM arm measures across lagged time, but this was impossible to tease‐out from same time‐point relations. These results suggest muscle–bone relationships are not long‐lasting at least beyond 48 months. Efforts to maintain muscle and bone strength should focus on shorter‐term interventions. More studies are needed with serial bone–muscle imaging over shorter periods. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Background: Adipose tissue (AT) around and within non-AT organs (i.e., ectopic adiposity) is emerging as a strong risk factor for type 2 diabetes (T2D). Not known is whether major ectopic adiposity depots, such as hepatic, skeletal muscle, and pericardial adiposity (PAT), are associated with T2D independent of visceral adiposity (VAT). More data are particularly needed among high-risk nonobese minority populations, as the race/ethnic gap in T2D risk is greatest among nonobese. Methods: Thus, we measured several ectopic adiposity depots by computed tomography in 718 (mean age = 64 years) African-Caribbean men on the Island of Tobago overall, and stratified by obesity (obese N = 187 and nonobese N = 532). Results: In age, lifestyle risk factors, health status, lipid-lowering medication intake, body mass index and all other adiposity-adjusted regression analyses, and hepatic and skeletal muscle adiposity were associated with T2D among nonobese men only (all P

Background Circulating levels of procollagen type III N-terminal peptide (P3NP) may reflect increased fibrosis of skeletal muscle and other tissues with aging. Herein, we tested if P3NP was associated with baseline and 7-year change in physical function. Method Participants (n = 400) were from the Long Life Family Study, a study of exceptional familial longevity. Plasma P3NP concentration was measured using a sandwich enzyme-linked immunosorbent assay (inter-assay coefficient of variation Results Participants were aged 73.1 ± 15.2 years (range: 39–104), 54% female, had body mass index of 26.6 ± 4.3 kg/m2, and gait speeds of 1.0 ± 0.3 m/s. One standard deviation higher log-transformed P3NP was related to worse baseline SPPB score (β = −0.9points), gait speed (β = −0.05m/s), chair-rises per-second (β = −0.46chair-rises/10 seconds), and grip strength (β = −2.0kg; all p < .001). Higher P3NP was also associated with greater declines in gait speed (β = −1.41, p < .001) and transitioning to being unable to perform chair-rises (β = 0.41, p < .001) after 7 years. Conclusion Plasma P3NP may be a strong, novel biomarker of current and future physical function. Future research is needed to extend our findings to other cohorts and determine mechanisms underlying these associations.

Increased skeletal muscle fat infiltration (i.e. myosteatosis) is now recognized as a major risk factor for cardio-metabolic diseases. Therefore, a lifestyle modification that reduces myosteatosis would be of great public health importance. However, studies examining the association of relevant lifestyle factors with this ectopic fat depot are lacking, particularly in African ancestry populations who have a very high burden of cardio-metabolic diseases. The aim of this study was to examine the relation between objectively measured physical activity and sedentary behavior with computed tomography measured calf muscle attenuation among middle-aged and elderly African-Caribbeans from the population-based Tobago Health Study. Preliminary analyses were conducted among 134 women (mean age 59 yrs, mean BMI 31.6 kg/m 2 ) and 355 men (mean age 62 yrs, mean BMI 28 kg/m 2 ). Physical activity was measured using the SenseWear Pro armband worn for 4-7 days. We calculated the mean duration of waking time engaged in light physical activity (LPA), moderate to vigorous activity (MVPA), and sedentary behavior (SB) per day. Skeletal muscle attenuation (mg/cm 3 ) reflects the fat content of the muscle such that greater skeletal muscle fat infiltration is reflected by lower attenuation. Women spent less time in LPA (146 vs. 270 min/day) and MVPA (15 vs. 41 min/day), but more time in SB (789 vs. 647 min/day) than men (all p Our preliminary findings suggest that there is significant association between MVPA and myosteatosis among middle-aged and elderly African Caribbeans. However, SB may only be relevant for myosteatosis among women. Future analyses will be conducted in a larger sample from this cohort to confirm our findings and to test for independence from other potential confounding factors, such as diet, sleep patterns, adiposity distribution, and diabetes.

Background Animal and in vitro experiments implicate the Wnt pathway in cardiac development, fibrosis, vascular calcification, and atherosclerosis, but research in humans is lacking. We examined peripheral blood Wnt pathway gene expression and arterial stiffness in 369 healthy African ancestry men (mean age, 64 years). Methods and Results Gene expression was assessed using a custom Nanostring nC ounter gene expression panel (N=43 genes) and normalized to housekeeping genes and background signal. Arterial stiffness was assessed via brachial‐ankle pulse‐wave velocity. Fourteen Wnt genes showed detectable expression and were tested individually as predictors of pulse‐wave velocity using linear regression, adjusting for age, height, weight, blood pressure, medication use, resting heart rate, current smoking, alcohol intake, and sedentary lifestyle. Adenomatous polyposis coli regulator of Wnt signaling pathway ( APC ), glycogen synthase kinase 3β ( GSK 3B ), and transcription factor 4 ( TCF 4 ) were significantly associated with arterial stiffness ( P APC and TCF 4 expression remained independently associated with arterial stiffness ( P =0.04 and 0.003, respectively), and each explained ≈3% of the variance in pulse‐wave velocity. Conclusions The current study establishes a novel association between in vivo expression of the Wnt pathway genes, APC and TCF 4 , with arterial stiffness in African ancestry men, a population at high risk of hypertensive vascular disease.

Circulating levels of procollagen type III N-terminal peptide (P3NP) may reflect increased fibrosis of skeletal muscle and other tissues with aging. In the current study, we tested if P3NP levels were associated with baseline and 7-year change in physical function among adults aged 39-104. Participants (n=400) were from the Long Life Family Study, a study of exceptional familial longevity. Plasma P3NP concentration was measured using a sandwich enzyme-linked immunosorbent assay (inter-assay CVs

Diabetes has been linked to accelerated muscle strength decline with aging. However, the association between glucose metabolism and muscle strength decline among individuals without diabetes is less clear. We tested whether fasting plasma markers of glucose and insulin metabolism (glucose, insulin, hemoglobin A1c, and soluble receptor for advanced glycation end products (sRAGE)) are associated with grip strength decline among 1415 non-diabetic offspring of exceptionally long-lived individuals who have a low diabetes risk (age range 36-88; mean age ± SD = 60 ± 8 years; mean BMI ± SD = 27 ± 4.7 kg/m2; 57% women). Grip strength was assessed using a hand-held dynamometer at two clinic visits over an average of 7.9 years. Multiple linear mixed models were adjusted for age, sex, field center, lifestyle, comorbidities, body weight, height, weight change, and family relatedness. Each standard deviation higher fasting insulin (7.3 mIU/L) was related to greater grip strength decline (-0.38 ± 0.16 kg; p=0.016), while each standard deviation higher fasting sRAGE (430 pg/mL) was related to slower grip strength decline (0.36 ± 0.18 kg; p=0.04). Our findings suggest that even among non-diabetic individuals from families with a clustering of “healthier” metabolic profiles - insulin metabolism and advanced glycation end products may be important biomarkers of muscle strength decline with aging. Potential mechanisms, including genetic and metabolic mediators underlying the observed associations, warrant further investigation.

Skeletal muscle adipose tissue infiltration is hypothesized to lead to poorer muscle quality and function with aging. Indeed, skeletal muscle adiposity has emerged as a consistent, independent predictor of skeletal muscle strength, mobility, metabolic disorders, and survival among older adults. However, phenotypic features of skeletal muscle among the oldest-old remain poorly characterized. Herein, we evaluated the skeletal muscle characteristics of 54 nonagenarians and centenarians (mean age 98 years, range 90-110 years; 63% women) and 25 middle-aged individuals (mean age 54 years, range 40-59 years; 36% women) belonging to the Long Life Family Study (LLFS), an international, multicenter cohort of families with a clustering of longevity. Ultrasonography was used to measure echo intensity of the sternocleidomastoid muscle, which has a similar fiber type distribution to the rectus femoris. Greater echo intensity is indicative of lower muscle quality (greater adipose and fibrotic tissue). Current smoking, alcohol intake, and BMI were similar between the age groups. Nonagenarians and centenarians had lower grip strength (16.3 vs. 39 kg) and were less physically active (22.2% vs 66.7% exercised 1+ times per week) compared to younger individuals (P

Background Sarcopenia varies by ethnicity, and has a major impact on health in older adults. However, little is known about sarcopenia characteristics in African ancestry populations outside the United States. We examined sarcopenia characteristics in 2,142 African Caribbean men aged 59.0 ± 10.4 years (range: 40–92 years) in Tobago, and their association with incident mobility limitations in those aged 55+ (n = 738). Methods Body mass index (BMI), grip strength, dual-x-ray absorptiometry (DXA) appendicular lean mass (ALM), and self-reported mobility limitations were measured at baseline, and 6 years later. Change in sarcopenia characteristics, including grip strength, grip strength/BMI, ALMBMI, and ALM/ht2, were determined. Foundations for the National Institutes of Health Sarcopenia Project (FNIH) and European Working Group for Sarcopenia in Older People 2 (EWGSOP2) cut-points were also examined. Odds ratios (OR) and 95% confidence intervals (CI) for mobility limitation were calculated using multivariable linear regression models adjusted for covariates. Results Overall, sarcopenia prevalence was quite low using the FNIH (0.3%) and EWGSOP2 (0.6%) operational cut-points, but was higher in those aged 75+ (2.1% [FNIH] and 3.7% [EWGSOP2]). Prevalence was also higher when based on “weakness”, versus “low ALM.” When sarcopenia markers were examined separately, baseline levels, but not changes, were associated with incident mobility limitations. Baseline grip strength/BMI was a particularly strong risk factor for incident mobility limitations (OR per SD: 0.50; 95% CI: 0.37–0.68). Conclusions Our findings suggest that grip strength normalized to body mass, measured at one time point, may be a particularly useful phenotype for identifying African Caribbean men at risk for future mobility limitations.

Centenarians and their offspring appear to have a reduced risk of type 2 diabetes (T2D) compared to similarly aged controls. We determined the incidence of and potential risk factors for T2D among the offspring of probands and their spouses (mean age =60 years; SD=8 years), in the Long Life Family Study (LLFS), a multicenter cohort study of two-generation families with a clustering of healthy aging and exceptional survival. Incident T2D was defined as fasting serum glucose ≥126 mg/dl, or HbA1c of ≥6.5%, or self-reported with doctor diagnosis of T2D, or the use of antidiabetic medication during a mean follow-up 7.9 ± 1.1 years. Among nondiabetic offspring (n=1585) and spouses (n=495) at study entry, 58 (3.7%) and 19 (3.8%) developed incident T2D, respectively. By comparison, 5.1% of comparable aged nondiabetics developed T2D in the Framingham Offspring Study. At Visit 1, BMI, waist circumference, and fasting serum triglycerides were positively, whereas HDL-C and adiponectin were inversely associated with incident T2D among offspring in LLFS (all P Disclosure I. Miljkovic: None. R. Cvejkus: None. P. An: None. B. Thyagarajan: None. R. Boudreau: None. J.M. Zmuda: None. Funding National Institute on Aging

Background: The Wnt pathway is known to influence body composition during early human development by regulating bone formation, myogenesis and adipogenesis. We have recently shown that DKK1 is related to measures of adiposity in nondiabetic African ancestry males. Whether these relationships are true across sexes and/or in other human populations remains unknown. In this study we evaluated the relationship of DKK1 with adiposity in a sample of male and female, mixed race, nondiabetic North American individuals. Methods: Fasting serum DKK1 levels were measured using ELISAs in 201 nondiabetic subjects (age range 30.7-60 years, BMI range 19.9-64.0 kg/m2) recruited from the general population via television advertisement and mass mailing. The subjects were predominantly female (85%) and Caucasian (63%). Anthropometrics were obtained and markers of inflammation and glucose metabolism were measured from fasting serum samples. Spearman and partial Spearman correlation analysis was used to determine the association of DKK1 with measures of adiposity and insulin resistance. Results: Circulating DKK1 was positively associated with BMI (r=0.30, p Conclusion: This is the first study looking at correlation of DKK1 with adiposity in North American nondiabetic individuals. Our findings suggest that the link between DKK1 and insulin resistance maybe mediated indirectly through total and regional adiposity and that DKK1 could be a potential early biomarker for diabetes in high risk individuals. These findings support our findings in African ancestry males and add to the evidence favoring potential role of Wnt modulators in adiposity regulation in humans. Disclosure H. Ali: None. E. Oczypok: None. I. Miljkovic: None. R. Cvejkus: None. J.M. Zmuda: None. J. DeLany: None. E.E. Kershaw: Research Support; Self; Regeneron Pharmaceuticals. Funding National Institutes of Health (T32DK007252); Endocrine Fellows Foundation

Background NT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we estimated the heritability of and examined genetic associations of SNPs in the BNP gene region with circulating NT-proBNP and prevalent CVD in 4,331 participants from the Long Life Family Study (LLFS). Methods and results Genotypes of 10 SNPs from the NPPB and NPPA regions that encode BNP and A-type natriuretic peptide, respectively, were tested for association with NT-proBNP and prevalent cardiovascular disease and risk factors. We performed analyses using the Sequential Oligogenic Linkage Analysis (SOLAR) program to account for family relatedness, and adjusted all models for age, sex, and field center. The mean age of the LLFS was 69.8 years (range 24–110) with 55.4% females. NT-proBNP was significantly heritable (h2 = 0.21; P = 4x10-14), and the minor alleles of rs632793 (p Conclusion In this family-based study of subjects with exceptional longevity, we identified several allelic variants in the BNP gene region associated with NT-pro-BNP levels and prevalent CVD.

Grip strength declines with aging, is an indicator of overall health, and predicts mortality among older adults. Herein, we quantified the genetic contributions to grip strength among 4534 individuals, belonging to 574 families in the Long Life Family Study (age 70.3 ± 15.7, range 24–110 years; 56% women). Grip strength was measured using a handheld dynamometer, and the maximum value of two trials in the stronger hand was used. Quantitative trait linkage analysis was completed using pedigree-based maximum-likelihood methods with logarithm of the odds (LOD) scores >3.0 indicating genome-wide significance. Linkage analysis in the top 10% of families contributing to LOD scores was also performed to allow for heterogeneity among families (HLOD). All analyses were adjusted for age, sex, height and field center. Grip strength was lower per one year of older age (β: -0.34 ± 0.01kg, p

Background: African ancestry populations are at the epicenter of the obesity and diabetes epidemic. Secreted frizzled-related protein 5 (SFRP5) is a novel adipokine and Wnt pathway modulator which is thought to be inversely related with adiposity and diabetes risk, however data in humans is conflicting. Therefore, we examined the association of SFRP5 with parameters of obesity and insulin resistance among an African ancestry population. Methods: We measured fasting serum SFRP5 in a pilot study of 139 elderly Afro-Caribbean men (mean age 71.7years, mean BMI 27.6 kg/m2). These men represented a random subset of a population-based study comprising ∼3000 African ancestry men with anthropometrics, DXA measured adiposity, and fasting morning blood collections for biomarker analysis. SFRP5 was measured in duplicate in previously unthawed serum with ELISA. Results: Using Pearson correlations, we found SFRP5 level to be positively associated with age (R = 0.18, p = 0.03) and negatively associated with BMI (R = - 0.14, p = 0.09), waist circumference (R = - 0.18, p = 0.02) and DXA trunk fat (R = - 0.24, p = 0.003), independent of age. Among nondiabetics (N=87), SFRP5 was inversely associated with fasting insulin levels (R = - 0.21, p= 0.04) and to some extent with HOMA-IR (R = -0.20, p = 0.06), independent of age and BMI. However, after adjustment for age and waist circumference, the associations between SFRP5 and fasting serum insulin and HOMA-IR were no longer significant. Conclusion: Our findings suggest that among African ancestry men, SFRP5 might have a beneficial role against general and central obesity. Our findings also suggest that the link between SFRP5 and diabetes risk in African Ancestry men may be explained by its correlation with central adiposity. Additional larger studies among African ancestry populations are needed to explore this novel biomarker along with its temporal relationship with clinically relevant metabolic outcomes. Disclosure H. Ali: None. J.M. Zmuda: None. R. Cvejkus: None. E.E. Kershaw: Consultant; Self; Regeneron Pharmaceuticals, Inc.. A.L. Kuipers: None. C.H. Bunker: None. I. Miljkovic: None.

The wingless (Wnt) pathway is known to regulate many human systems, including embryonic development, bone mineralization, and cancer. There is emerging basic research evidence that the Wnt pathway is also involved in angiogenesis, atherosclerosis, and vascular damage repair. However, there have been no studies of the Wnt pathway and cardiovascular disease (CVD) in human populations. In a cohort of Afro-Caribbean men (the Tobago Health Study (THS)), we previously identified a potentially functional coding mutation (Ala64Thr) in the Frizzled-1 ( FZD1 ) gene, which acts as a co-receptor with the low-density lipoprotein receptor protein (LRP) to initiate the Wnt signaling cascade. This mutation has a carrier frequency of ~4% in the THS and additional studies reported in the 1000 genomes project have found similar frequencies in other predominantly West African populations. In order to investigate the phenotypic consequences of this Wnt pathway mutation on subclinical CVD, we measured carotid artery wall traits using B-mode ultrasonography in 64 Ala64Thr mutation carriers and 395 controls from the THS. For this analysis, carotid artery measures of interest included carotid plaque prevalence, and common carotid mean intima-media thickness (IMT), inter-adventitial diameter (IAD), and lumen diameter (LD). We assessed differences in carotid traits by Ala64Thr status using multiple linear regression adjusting for CVD risk factors, including age, BMI, smoking, hypertension, diabetes, alcohol intake, physical activity, and sedentary behavior. Men were aged 64 years and were overweight (BMI: 27.5kg/m 2 ), on average. Prevalence of hypertension and type 2 diabetes is high in this sample (66% and 24%, respectively). Men with Ala64Thr tended to be older and had higher prevalence of hypertension than non-carriers (P1/3 of a SD greater LD than non-carriers (P=0.01). The effect magnitude of this mutation was similar for IAD, though not statistically significant (P=0.08). There was no significant difference in carotid IMT or plaque prevalence. While this mutation is not expected to be severely deleterious using in silico prediction software, Ala64 is highly conserved and located in a putative signaling peptide sequence. Carriers of a low frequency FZD1 coding mutation show greater remodeling of the carotid artery compared to non-carriers, suggesting that the Wnt pathway may be involved in vascular changes that occur early in the atherosclerotic disease process.

Gait speed is an indicator of health and function with aging. The potential genetic contributions to gait speed and its decline with aging are not well characterized. We sought to better quantify the genetic contributions to and identify potential genes and genetic variants underlying change in gait speed among older adults. To accomplish these aims, we used data from 2379 individuals belonging to 509 families in the Long Life Family Study (mean age 64 ± 12, range 30–110 years; 45% men). Gait-speed was measured over 4 meters at baseline and after an average of 7±1.1 years. Quantitative trait linkage analyses were completed using pedigree-based maximum-likelihood methods with logarithm of the odds (LOD) scores > 3.3 indicating genome-wide significance. We also performed linkage analysis in the top 10% of families contributing to LOD scores to allow for heterogeneity among families (HLOD). Data were adjusted for age, sex, height and field center. At baseline, 26.9% of individuals had “low” gait-speed

Objective Skeletal muscle fat infiltration (known as myosteatosis) is greater in African compared with European ancestry men and may play an important role in the development of type 2 diabetes (T2D). However, prospective studies examining the magnitude of changes in myosteatosis with aging and their metabolic consequences are sparse. Methods Longitudinal changes in peripheral quantitative computed tomography measured calf myosteatosis [intermuscular fat (mm2) and skeletal muscle density as a measure of intramuscular fat (mg/cm3)] were examined in 1515 Afro-Caribbean men aged 40+ years recruited without regard to their health status. Results During an average of 6.2 years of follow-up, an age-related increase in intermuscular fat and a decrease in skeletal muscle density were observed (all P

Low trabecular (Tb) and cortical (Ct) volumetric BMD (vBMD) are related to increased fracture risk, but little is known about the patterns and correlates of Tb and Ct vBMD loss with aging. We examined the rates of change in total, Tb.vBMD, and Ct.vBMD at the radius and tibia, and identified factors associated with vBMD loss among 1569 men of African descent aged 40 years and older. Quantitative computed tomography was used to measure vBMD 6 years apart. The annualized rate of loss in Tb.vBMD was significant at the radius (–0.047%/yr, p = 0.016) but not at the tibia. At the radius, a significant loss of Tb.vBMD was observed in men aged 40 to 49 years that appeared to be attenuated and not statistically significant among older age men. In contrast, the decline in Ct.vBMD was similar at both skeletal sites (–0.254 to –0.264%/yr, p

There is strong evidence that fat accumulating in non-adipose sites, "ectopic fat", is associated with cardiovascular disease (CVD), including vascular calcification. Most previous studies of this association have assessed only a single ectopic fat depot. Therefore, our aim was to assess the association of total, regional, and ectopic fat with abdominal aorto-illiac calcification (AAC) and coronary artery calcification (CAC) in 798 African ancestry men.Participants (mean age 62) were from the Tobago Bone Health Study cohort. Adiposity was assessed via clinical examination, dual x-ray absorptiometry, and computed tomography (CT). Ectopic fat depots included: abdominal visceral adipose tissue (VAT), liver attenuation, and calf intermuscular adipose tissue (IMAT). Vascular calcification was assessed by CT and quantified as present versus absent. Associations were tested using multiple logistic regression adjusted for traditional cardiovascular risk factors. Models of ectopic fat were additionally adjusted for total body fat and standing height.All adiposity measures, except VAT, were associated with AAC. Lower liver attenuation or greater calf IMAT was associated with 1.2-1.3-fold increased odds of AAC (p 0.03 for both), though calf IMAT was a stronger predictor than liver attenuation (p 0.001) when entered in a single model. No ectopic fat measure was associated with CAC.Greater adiposity in the skeletal muscle and liver, but not in the visceral compartment, was associated with increased odds of AAC in African ancestry men. These results highlight the potential importance of both quantity and location of adiposity accumulation throughout the body.

Although obesity is a major driver of type 2 diabetes (T2D), many obese individuals do not develop T2D. Indeed, fat around and within non-adipose tissue organs (i.e., ectopic fat) is emerging as a strong risk factor for diabetes. The potential differential contribution of ectopic fat depots throughout the body on T2D risk is unclear because studies have mainly focused on visceral and/or liver fat. No study, to our knowledge, has addressed the potential independent association of visceral, liver, and skeletal muscle adiposity with T2D. Such studies are particularly needed among African ancestry populations, as generalized obesity and other risk factors do not appear to explain the high T2D burden in this population segment. To address this knowledge gap, we measured total body fat by DXA, and visceral, liver, and calf skeletal muscle adiposity by computed tomography in 490 Afro-Caribbean men, aged 50-91 years (mean age=64 years, mean BMI=27.5 kg/m 2 ). The prevalence of T2D in this population was 22.3%. We employed multiple logistic regression using total body fat percent and ectopic fat depots as predictors (Table). We found that each 7.9 HU decrease in liver attenuation (indicative of greater liver adiposity) was associated with a 33% increased odds of T2D (p=0.011). Similarly, each 4.2 mg/cm 3 decrease in muscle attenuation (indicative of greater intra-muscular adiposity) was associated with a 31% increased odds of T2D (p=0.04). These associations were independent of total and visceral adiposity. Our results support the “ectopic fat syndrome” theory, as opposed to the “portal theory”, in the pathogenesis of diabetes among African ancestry men. Longitudinal studies are needed to clarify the exact role of specific ectopic fat depots in T2D, particularly in high-risk African ancestry populations.

Objective: While ectopic adiposity is considered a risk factor for many chronic diseases, including cardiovascular disease, the extent to which this association is independent of total adiposity is yet to be established. Vascular calcification, which is associated with greater adiposity, is a subclinical marker of cardiovascular disease that may have varying etiology and clinical implications in different vascular beds. Therefore, our objective was to assess the potential independent associations of total, regional and ectopic adiposity measures with abdominal aorto-iliac calcification (AAC) and coronary artery calcification (CAC). Methods: Detailed health history, clinical exam, dual x-ray absorptiometry and computed tomography (CT) scans were obtained in 798 African ancestry men aged ≥40 years (mean(SD): 62.0(8.6)years) recruited without regard to health status from the Tobago Heart Health Study. Vascular calcification was measured by CT in the abdomen (AAC) and chest (CAC). Calcification was scored using the Agatston method and a score ≥10 was considered to be a prevalent calcification. Severity of calcification was modeled using continuous Agatston score in those with any calcification. Multivariable logistic and linear regression models were used to assess the cross-sectional association of adiposity measures with vascular calcification prevalence and severity. All models were adjusted for age, hypertension, diabetes, dyslipidemia, smoking, alcohol intake and sedentary lifestyle. In addition, models of ectopic adiposity (abdominal visceral adipose tissue, liver attenuation and calf skeletal muscle fat) were adjusted for total body fat. Results: AAC was present in 63% and CAC was present in 29% of men. After adjustment for traditional cardiovascular risk factors, 1SD greater total, trunk, or abdominal subcutaneous adiposity was associated with 1.3-1.5-fold increased odds of AAC (all p Conclusions: Independent of total adiposity, measures of ectopic adiposity were associated with greater AAC, but not CAC, prevalence in African ancestry men. These results highlight potential differences in the adiposity-vascular disease relationship that may vary by ectopic fat depot and vascular bed location. Future vascular disease research should explore potential underlying biologic mechanisms for these findings.

Body composition changes vary by age and ethnicity and have a major impact on health and physical function. However, little is known about the magnitude, tempo and patterns of these changes in African-ancestry populations, particularly outside the U.S. Thus, we examined age-specific rates-of-change in lean and fat mass in a unique population-based, longitudinal cohort study of 2621 African-ancestry men on the Caribbean island of Tobago (age: 62.0±11.8 years, range: 32-99 years). Body composition was measured with DXA at study entry and after an average of 4 and 9 years. Annualized rates of change and 95% confidence intervals were calculated using all 3 time-points with Generalized Estimating Equations stratified by 5-year baseline age-groups. Lean mass declined at a fairly constant rate in age-strata up through age ≤64 years (-0.72; -0.76, -0.67%/yr), but accelerated to -0.92 %/yr (-1.02, -0.82 %/yr) among those aged 65-69, and to -1.16 %/yr (-1.30, -1.03 %/yr) among those aged 70-74 years – plateauing in those aged 75+. This pattern of age acceleration was observed in arm but not leg lean mass. The age-specific rates of decline in lean mass in this cohort of African Caribbean men appear to be lower than those reported in older African American men. In contrast to lean mas, fat mass increased by 2.93 %/yr (2.72, 3.15 %/yr) and this rate of increase was fairly uniform across the lifespan. Additional research is needed to better define the lifestyle, medical and biological factors contributing to body composition changes across the lifespan in African-ancestry populations.

Background: Emerging evidence indicates that ectopic fat, such as that in the visceral depot or muscle fat infiltration, may be associated with diabetes, independent of general obesity.Very little is known about the health effects of fat density, an emerging novel indicator of fat quality. Existing studies have focused on visceral or pericardial fat density. There is currently no information on muscle fat density and its associations with diabetes or other cardio-metabolic disorders. Methods: The aim of this preliminary study was to investigate whether visceral (VAT) or intermuscular (IMAT) adipose tissue density was associated with measures of glucose and insulin homeostasis independent of fat depot volume. We hypothesized that adipose tissue characterized by higher density would be associated with lower glucose and insulin fasting serum levels, and lower homeostasis model assessment of insulin resistance (HOMA-IR). Adipose tissue volume (cm3) and density (Hounsfield units) were measured in the abdomen and thigh from computed tomography scans in 193 non-diabetic black men aged 50 to 87 years (mean age 61 years, mean BMI 27 kg/m2). All measures were transformed to normal distribution and partial Pearson correlation coefficients were calculated. Results: In models adjusted for age and corresponding fat volume, thigh IMAT density and abdominal paraspinal IMAT density were inversely associated with fasting insulin (=-0.15 and r=-0.16, respectively; both p Conclusion: We found a novel correlation between lower intermuscular fat density and hyperinsulinemia and insulin resistance among non-diabetic black men. These results suggest that muscle fat quality may be a novel predictor of diabetic risk even independent of overall and ectopic fat volume.

Introduction: Cardiovascular disease (CVD) is the leading cause of death throughout the world and age-adjusted rates of CVD mortality in Trinidad and Tobago are estimated to be ~2x those of the US. Given the drastic differences in culture and urbanization between Tobago and the US, we started the Tobago Heart Health Study to evaluate several aspects of subclinical CVD within a sample of men from an existing longitudinal study on the island. Hypothesis: We assessed the hypothesis that subclinical CVD burden in adult Afro-Caribbean men would be low overall, but that the burden would be substantially greater in the oldest men. Methods: We have preliminary data on subclinical CVD measures from 140 men, including carotid plaque from B-mode ultrasound, coronary artery calcification (CAC) and pericardial fat from computed tomography, and ankle-brachial index (ABI) and brachial-ankle pulse-wave velocity (baPWV) from automated waveform analysis. To assess the burden of multiple adverse measures, we calculated a subclinical CVD score (range 0-5) by summing the prevalence of the following: any carotid plaque, any CAC, highest quintile of pericardial fat, lowest quintile of ABI, or highest quintile of baPWV. For all subclinical variables of interest, we calculated means(SD) or frequencies, as appropriate, and identified age trends by testing for linear trends with age grouped as Results: The men were aged 53-88 years (mean(SD): 64(9) years) and the prevalence of hypertension, diabetes, smoking, moderate alcohol intake, and sedentary behavior were 64%, 26%, 5%, 18% and 52%, respectively. Sixteen percent of men had any carotid plaque and 25% had any CAC. Mean ABI was 1.1(0.1), mean baPWV was 1696(388)cm/s and mean pericardial fat was 41.4(27.6)cm3. Only 56% had ≥1 adverse subclinical CVD measure (23% with 1, 21% with 2, 10% with 3, 2% with 4, 0 with 5). Men in the oldest age group had significantly more carotid plaque, more CAC, lower ABI, higher baPWV and more pericardial fat compared to the younger age groups (all p Conclusions: Subclinical CVD burden was low in this sample of 140 Afro-Caribbean men from Tobago. However, prevalence of adverse subclinical CVD measures greatly increased over the age of 70. It will be important to assess the impact of this aging-related subclinical burden on clinical CVD and cardiovascular mortality risks in adult Afro-Caribbean men in future studies.

Skeletal muscle fat infiltration (known as myosteatosis) is greater in African compared with European ancestry men and may play an important role in the development of type 2 diabetes (T2D). However, prospective studies examining the magnitude of changes in myosteatosis with aging and their metabolic consequences are sparse.Longitudinal changes in peripheral quantitative computed tomography measured calf myosteatosis [intermuscular fat (mm(2) ) and skeletal muscle density as a measure of intramuscular fat (mg/cm(3) )] were examined in 1515 Afro-Caribbean men aged 40+ years recruited without regard to their health status.During an average of 6.2 years of follow-up, an age-related increase in intermuscular fat and a decrease in skeletal muscle density were observed (all P0.0001), which remained significant in those who lost weight, gained weight, or remained weight stable (all P0.0001). In addition, muscle density loss accelerated with increasing age (P0.0001). Increased intermuscular fat during follow-up was associated with an increased incident risk of T2D independent of factors known to be associated with T2D (odds ratios per 1-SD increase in intermuscular fat = 1.29; 95% CI = 1.08-1.53).Our findings suggest that both inter- and intramuscular fat increase with advancing age and that intermuscular fat contributes to development of T2D among African ancestry men.