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Background: Adipose tissue (AT) distribution, which differs by race/ethnicity, can differentially impact risk for cardiometabolic disease. Traditional analyses using AT volumes tend to place all ATs in a regression model, estimating an increase in one AT volume while “holding other volumes constant”; however, the compositional nature of the data suggests the other ATs cannot remain constant. Compositional data analysis (CODA) methods eliminate this concern by comparing logratios of components. CODA was designed for analyses of data like those of body composition , but has yet to be used in this field. We demonstrate the use of CODA for the comparison of visceral AT (VAT) and subcutaneous AT of the abdomen (ASAT) and thigh (TSAT) with prevalence of cardiometabolic diseases. Methods: This cross-sectional analysis used 615 African Caribbean men from Tobago aged 50-91 years (mean age 63.6 years, mean BMI 27.7 kg/m 2 ). AT volumes were obtained from CT scans of the abdomen (VAT and ASAT) and of the mid-thigh (TSAT). An additive log2 ratio transformation was applied to the ATs to generate the VAT, ASAT, and TSAT component effects relative to the other tissues captured in the respective CT scan. Ordinal logistic regression analyses were performed for increasing hypertension or glucose impairment categories (defined in Table) after adjustment for age, disease status, and lifestyle factors. Results: After full adjustment (Table), a 2-fold higher ASAT volume (relative to other abdominal tissues) was associated with higher odds, and a 2-fold higher TSAT volume (relative to other thigh tissues) was associated with lower odds, of being in a higher hypertension category. After BMI adjustment, no AT was associated with glucose impairment category. VAT was not a significant predictor for either outcome in African Ancestry men. Conclusion: CODA methods, which avoid problematic assumptions made in traditional analyses, found significant and opposing associations of TSAT and ASAT with hypertension categories in African Ancestry men.

Background: While overall obesity remains a major risk factor for cardiometabolic diseases, the location of stored fat is also thought to play a role. In addition to fat storage in ectopic sites, the density of fat, a marker of fat quality, is emerging as a novel risk factor for cardiometabolic diseases. Previous studies have focused primarily on visceral (VAT) and abdominal subcutaneous (SAT) adipose tissue density and in predominantly white cohorts; however, studies in populations of African ancestry who are at higher risk of cardiometabolic diseases are lacking. Additionally, information is lacking on associations of density of other relevant ectopic fat depots, such as intermuscular adipose tissue (IMAT), with cardiometabolic risk factors. Methods: We investigated whether VAT, SAT, or thigh IMAT densities were associated with cardiometabolic measures in 648 black men aged 50-91 years (mean age 63.6 years, mean BMI 27.7 kg/m 2 ). Adipose tissue volume (cm 3 ) and density (Hounsfield units, HU) was measured in the abdomen (between L4 and L5) and mid-thigh from computed tomography scans. Cardiometabolic measures, including blood pressure, fasting serum glucose and insulin homeostasis, and serum lipids (N=476), were transformed as needed and used as outcomes in multiple linear regression models adjusting for age, lifestyle factors, medication use (antihypertensive, antidiabetic, or lipid-lowering), and corresponding fat depot volume. Results: After adjustment (Table), VAT, SAT, and IMAT densities were significantly associated with fasting insulin, insulin resistance, and lipids. Results remain similar after adjustment for BMI instead of fat volume and in a sensitivity analysis excluding those taking relevant medications. Conclusion: As reported in other studies, in our study among African ancestry individuals VAT and SAT were associated with several cardio-metabolic risk factors. Importantly, our findings suggest that thigh IMAT density may be a novel predictor of cardiometabolic risk in African ancestry men.

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.

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.

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.