Measures Of Adiposity Research Articles

Associations between adiposity and white matter hyperintensities: Cross-sectional and longitudinal analyses of 34,653 participants.

White matter hyperintensities (WMH) increase the risk of stroke and cognitive impairment. This study aims to determine the cross-sectional and longitudinal associations between adiposity and WMH. Participants were enrolled from the UK Biobank cohort. Associations of concurrent, past, and changes in overall and central adiposity with WMH were investigated by linear and nonlinear regression models. The association of longitudinal adiposity and WMH volume changes was determined by a linear mixed model. Mediation analysis investigated the potential mediating effect of blood pressure. In 34,653 participants with available adiposity measures and imaging data, the concurrent obese group had a 25.3% (β [95% CI] = 0.253 [0.222-0.284]) higher WMH volume than the ideal weight group. Increment in all adiposity measures was associated with a higher WMH volume. Among them, waist circumference demonstrated the strongest effect (β [95% CI] = 0.113 [0.101-0.125]). Past adiposity also demonstrated similar effects. Among the subset of 2664 participants with available WMH follow-up data, adiposity measures were predictive of WMH change. Regarding changes of adiposity, compared with ideal weight stable group, those who turned from ideal weight to overweight/obese had a 8.1% higher WMH volume (β [95% CI] = 0.081 [0.039-0.123]), while participants who turned from overweight/obese to ideal weight demonstrated no significant WMH volume change. Blood pressure partly meditates the associations between adiposity and WMH. Both concurrent and past adiposity were associated with a higher WMH volume. The detrimental effects of adiposity on WMH occurred throughout midlife and in the elderly and may still exist after changes in obesity status.

Oral curcumin phytosome supplementation improves anthropometric measures of adiposity and enhances endothelial function in rats on a high-fat-diet regimen

Objectives: Curcumin has a protective role in endothelial function and nitric oxide (NO) production in animal models of different diseases; however, the role of curcumin on aortic reactivity in rats placed on a high-fat diet (HFD) remains unclear. This study aims to determine whether oral curcumin phytosome supplementation can reduce adiposity and enhance endothelial function. Materials and Methods: Rats were assigned to one of three groups: normal diet (ND), HFD for 20 weeks, and HFD supplemented with curcumin phytosome (HFD + Curcumin). Anthropometric measures were recorded weekly for the three groups, until the end of the feeding regimen. After 20 weeks of feeding on HFD, myographic investigations were conducted on thoracic aortic rings dissected from HFD and HFD + Curcumin rats. The response to high potassium chloride (KCl), incremental doses of phenylephrine (Phe) before and after L-NAME treatment, acetylcholine (ACh), or sodium nitroprusside (SNP), was evaluated. ACh-induced relaxation was also assessed in HFD + Curcumin rats, after preincubation with chromium III-mesoporhyrin. Results: HFD rats exhibited increased adiposity measures, some of which were negatively correlated with vasorelaxation response to ACh. HFD + Curcumin rats had reduced anthropometric measures, compared to HFD rats. Aortic rings from HFD and HFD + Curcumin rats exhibited comparable contractile responses to KCl and Phe. The difference in contractile response to Phe before and after L-NAME incubation was greater for HFD + Curcumin rats. ACh induced greater vasorelaxant responses in HFD + Curcumin rats. There was no group difference in the relaxant response to SNP. In HD + Curcumin rats, chromium III mesoporphyrin significantly reduced ACh-induced relaxations. Conclusion: Oral curcumin phytosome supplementation could reduce adiposity in rats placed on an HFD and may have enhanced basal and stimulated NO release from the endothelium, and heme oxygenase-1 may partly mediate this curcumin protective role. This study provides evidence that this curcumin formulation, taken as a daily supplement, may be effective in providing some protection against adiposity-associated adverse cardiovascular disorders.

Gender differences in midlife to later-life cumulative burden and variability of obesity measures and risk of all-cause and cause-specific mortality.

Previous studies have reported the gender-specific association between general and central obesity measures, using snapshot assessments, and mortality events. This study seeks to further explore this link by examining how the longitudinal cumulative burden and variability of obesity measures from midlife to later-life impact mortality events in the Atherosclerosis Risk in Communities (ARIC) study population, specifically in relation to gender differences. Using data from the ARIC study, a total of 7615 (4360 women) participants free of cardiovascular disease, cancer, and early mortality events were included in the data analysis. Longitudinal cumulative burden (estimated by the area under the curve (AUC) using a quadratic mixed-effects method) and variability (calculated according to average successive variability (ASV)) were considered as exposures, separately and all together. Cox proportional hazard regression models were used to estimate multivariable-adjusted standardized hazard ratios. The mean age was 62.4 and the median follow-up was 16.9 years. In men, AUCs of waist-related obesity measures, and also ASVs of all obesity measures were associated with increased all-cause mortality risk. In women, waist circumference and waist-to-height ratio AUCs were associated with increased all-cause mortality risk. Regarding cardiovascular mortality, all adiposity measures ASVs in both genders and waist-related obesity measures AUCs in men were associated with increased risk. Significant gender differences were found for the associations between cumulative and variability of waist-to-hip ratio for all-cause mortality and all adiposity measures ASVs for cardiovascular mortality risk with higher impact among men. Cumulative burden and variability in general and central obesity measures were associated with higher all-cause and cardiovascular mortalities among men. In women, general obesity measures variability, as well as cumulative and variability of central adiposity measure, increased all-cause mortality risk.

Leptin and adiposity measures from birth to later childhood: Findings from the Hyperglycemia and Adverse Pregnancy Outcomes Follow-Up Study.

Cord blood (CB) leptin is positively associated with adiposity at birth, but the association with child adiposity is unclear. We hypothesized that CB leptin is positively associated with adiposity in peripubertal children and with childhood leptin. Leptin was measured in 986 CB and 931 childhood stored samples from a prospective birth cohort. Adiposity measures were collected at birth and mean age 11.5 years. Linear and logistic regression analyses were used to evaluate associations between log-transformed CB leptin and neonatal and childhood adiposity measures as continuous and categorical variables, respectively. CB leptin was positively associated with neonatal and childhood adiposity. Childhood associations were attenuated when adjusted for maternal body mass index (BMI) and glucose, but remained statistically significant for childhood body fat percentage (β = 1.15%, confidence interval [CI] = 0.46-1.84), body fat mass (β = 0.69 kg, 95% CI = 0.16-1.23), sum of skin-folds (β = 1.77 mm, 95% CI = 0.31-3.24), log-transformed child serum leptin (β = 0.13, 95% CI = 0.06-0.20), overweight/obesity (OR = 1.21, 95% CI = 1.03-1.42), obesity (OR = 1.31, 95% CI = 1.04-1.66) and body fat percentage >85th percentile (OR = 1.38, 95% CI = 1.12-1.73). Positive associations between newborn adiposity measures and CB leptin confirmed previous reports. CB leptin is positively associated with neonatal and childhood adiposity and child leptin levels, independent of maternal BMI and maternal hyperglycemia. CB leptin may be a biomarker of future adiposity risk.

Associations of Plastic Bottle Exposure with Infant Growth, Fecal Microbiota, and Short-Chain Fatty Acids.

Murine models show that plastics, via their chemical constituents (e.g., phthalates), influence microbiota, metabolism, and growth. However, research on plastics in humans is lacking. Here, we examine how the frequency of plastic bottle exposure is associated with fecal microbiota, short-chain fatty acids (SCFAs), and anthropometry in the first year of life. In 442 infants from the prospective Nurture birth cohort, we examined the association of frequency of plastic bottle feeding at 3 months with anthropometric outcomes (skinfolds, length-for-age, and weight-for-length) at 12 months of age and growth trajectories between 3 and 12 months. Furthermore, in a subset of infants (n = 70) that contributed fecal samples at 3 months and 12 months of age, we examined plastic bottle frequency in relation to fecal microbiota composition and diversity (measured by 16S rRNA gene sequencing of V4 region), and fecal SCFA concentrations (quantified using gas chromatography mass spectrometry). At 3 months, 67.6% of infants were plastic bottle fed at every feeding, 15.4% were exclusively breast milk fed, and 48.9% were exclusively formula fed. After adjustment for potential confounders, infants who were plastic bottle fed less than every feeding compared to those who were plastic bottle fed at every feeding at 3 months did not show differences in anthropometry over the first 12 months of life, save for lower length-for-age z-score at 12 months (adjusted β = -0.45, 95% CI: -0.76, -0.13). Infants who were plastic bottle fed less than every feeding versus every feeding had lower fecal microbiota alpha diversity at 3 months (mean difference for Shannon index: -0.59, 95% CI: -0.99, -0.20) and lower isovaleric acid concentration at 3 months (mean difference: -2.12 μmol/g, 95% CI: -3.64, -0.60), but these results were attenuated following adjustment for infant diet. Plastic bottle frequency was not strongly associated with microbiota diversity or SCFAs at 12 months after multivariable adjustment. Frequency of plastic bottle use was associated with differential abundance of some bacterial taxa, however, significance was not consistent between statistical approaches. Plastic bottle frequency at 3 months was not strongly associated with measures of adiposity or growth (save for length-for-age) over the first year of life, and while plastic bottle use was associated with some features of fecal microbiota and SCFAs in the first year, these findings were attenuated in multivariable models with infant diet. Future research is needed to assess health effects of exposure to other plastic-based products and objective measures of microplastics and plastic constituents like phthalates.

Abstract B098: Adiposity measures and obesity-related cancer: A report from the Oklahoma Strong Heart Study and Strong Heart Family Study

Abstract Background: Obesity, defined as a body mass index (BMI) ≥30 kg/m2, disproportionately affects American Indian (AI) people and is increasingly implicated in the incidence of certain cancers. Indeed, while obesity-related cancers account for 43% of incident cancers among all Americans, they account for 51% of incident cancers among AI people. Emerging evidence indicates that body fat distribution (e.g., central vs. peripheral) is associated with cancer independent of BMI. AI adults have a higher prevalence of central adiposity than other populations, yet prospective measures of adiposity associated with increased risk of obesity-related cancer over time in AI people remain limited. Methods: We partnered with the Strong Heart Study/Strong Heart Family Study (SHS/SHFS) and the Oklahoma Central Cancer Registry to link study cohort records with cancer surveillance records from 1997-2019 to systematically classify cancer incidence among cohort participants. We evaluated baseline measures of adiposity, including waist circumference (females cutpoint at 88 cm, males cutpoint at 102 cm) waist-to-hip ratio (females cutpoint at 0.85, males cutpoint at 0.90), and percent body fat (females cutpoint at 35%, males cutpoint at 25%), by the presence of incident obesity-related cancer. We classified survival time as time from the baseline exam date to cancer diagnosis, death, or the end of the study period, whichever occurred first. Participants without a cancer event were censored. To compare survival time by each adiposity measure, we used the log-rank test and generated Kaplan-Meier curves. Results: We identified 140 participants with an obesity-related cancer that linked with a cancer registry record (n=1956 without cancer). The average age at the baseline SHS/SHFS exam was 54 years for those with cancer and 48 years for those without cancer. The average age at cancer diagnosis was 69 years. The most common forms of obesity-related cancer were colorectal (n=40, 29%) and post-menopausal female breast cancer (n=35, 25%). We observed a higher incidence of obesity-related cancer among those with high waist circumference (7.8% v. 4.3%), high waist-to-hip ratio (7.5% vs. 4.2%), and high percent body fat (7.4% v. 4.6%) compared with lower levels of these adiposity measures. We observed differences in time to cancer by waist circumference (p=0.004), waist-to-hip ratio (p=0.03), and percent body fat (p=0.03). Discussion: We observed significant differences in time to cancer diagnosis by multiple adiposity measures within the SHS/SHFS in Oklahoma. As a next step, we plan to link with the other SHS/SHFS sites in the Dakotas and Arizona. This study will provide a solid foundation upon which to base interventions to ameliorate risk factors for obesity-related factors in this underserved population. Citation Format: Amanda E. Janitz, Jessica A. Reese, Jean A. Leidner, Janis E. Campbell, Amanda M. Fretts, Dorothy A. Rhoades. Adiposity measures and obesity-related cancer: A report from the Oklahoma Strong Heart Study and Strong Heart Family Study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B098.

Prenatal exposure to Per- and polyfluoroalkyl substances and adiposity measures of children at 4 and 6 years: A prospective birth cohort in China

There is growing evidence that prenatal exposure to Per- and polyfluoroalkyl substances (PFAS) was associated with childhood obesity, but evidence on multiple adiposity measures including arm circumference (AC), and waist circumference (WC) among Chinese children is limited. We investigated the associations of prenatal exposure to PFAS with adiposity measures of children at 4 and 6 years of age in the Shanghai-Minhang Birth Cohort Study. A total of 573 mother-child pairs with maternal PFAS concentrations and at least one measurement of adiposity measures of children were included in the present study. Eleven PFAS were assessed in maternal fasting blood samples. Information on children's weight, height, AC, and WC was collected at follow-ups. Weight for age Z score (WAZ), body mass index for age Z score (BMIz), and children overweight were calculated based on the World Health Organization Child Growth Standards. Multivariate linear regression, Poisson regression with robust error variance, and Bayesian Kernel Machine Regression (BKMR) models were used to examine the associations of prenatal exposure to PFAS with children's adiposity measures. Eight PFAS with detection rates above 85 % were included in the analyses. In the multivariate linear regression models, maternal PFNA concentrations were associated with a greater AC (β = 0.29, 95 % Confidence Interval (CI): 0.04–0.55) in 4-year-old children and with an increase in WAZ (β = 0.26, 95 % CI: 0.06–0.46), BMIz (β = 0.31, 95 % CI: 0.09–0.53), AC (β = 0.49, 95 % CI: 0.08–0.90), and WC (β = 1.47, 95 % CI: 0.41–2.52) in 6-year-old children. We also observed the associations of maternal concentrations of PFOS, PFNA, PFUdA, and PFTrDA with the increased risk of children overweight in 6-year-old children. BKMR models further supported the findings from multivariate linear regression and Poisson regression models, and identified PFNA as the most important contributor. Moreover, the associations described above were generally more pronounced in girls. In conclusion, prenatal exposure to PFAS was associated with an increased risk of children's adiposity with a sex-specific manner, and PFNA contributed most to the associations after controlling for the effect of co-exposure to other PFAS compounds, especially among girls at 6 years of age.

Associations of general and central adiposity with hypertension and cardiovascular disease among South Asian populations: a systematic review and meta-analysis

BackgroundThe relevance of measures of general and central adiposity for cardiovascular disease (CVD) risks in populations of European descent is well established. However, it is less well characterised in South...

Differential sex associations of regional adiposity with cognition and brain pathology in Israeli older adults with Type II Diabetes

AbstractBackgroundAdiposity and Type II diabetes (T2D) are consistently associated with cognitive impairment and dementia. Body mass index (BMI) is the most common measure of global adiposity, but its associations with cognition in old age are inconsistent. BMI does not represent regional fat distribution, which might differ between the sexes. In this study, we examined sex differences in the relationships of regional adiposity with cognition and AD‐related brain volumes in older adults participating in the Israel Diabetes and Cognitive Decline study.MethodsRegional adiposity was measured by abdominal MRI in 89 participants (32.6% women), including hepatic and pancreatic fat, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Participants were assessed for global cognition, episodic memory (EP), working memory (WM), executive function (EF), and language. A subsample (N = 50) underwent brain MRI assessing total gray matter [GM], hippocampus, inferior, middle, and superior frontal gyrus [IFG, MFG, and SFG, respectively]. Linear regressions examined associations of regional adiposity with cognition and AD‐related brain volumes adjusting for age, sex, education, and BMI (and intracranial volume for MRI measures).ResultsIn the whole sample, higher pancreatic fat was associated with lower EF (r = ‐0.369, p = 0.024). In men, high pancreatic fat was associated with lower global cognition (Men: r = ‐0.311; p = 0.048; Women: r = ‐0.122; p = 0.706), EF (Men: r = ‐0.384; p = 0.033; Women: r = ‐0.508; p = 0.661) and language (Men: r = ‐0.309; p = 0.049; Women: r = 0.082; p = 0.798). In the whole sample, no associations were found between pancreatic fat % and AD‐related brain volumes. Surprisingly, in men, higher pancreatic fat was associated with greater GM volume (Men: r = 0.411; p = 0.046; Women: r = ‐0.231; p = 0.521). In women, higher pancreatic fat was associated with smaller IFG (Men: r = ‐0.185, p = 0.386; Women: r = ‐0.642, p = 0.045). Hepatic fat %, VAT, and SAT did not associate with AD‐related brain volumes or cognitive measures.ConclusionIn Israeli older adults with T2D, different regional fat depots are linked to different cognitive and brain outcomes in men and women. Specifically, more pancreatic fat, but not other fat depots, is associated with poorer cognition. These findings highlight the value of examining distinct fat depots rather than global obesity concerning brain and cognition, and the need to account for sex differences in these associations.

Bone Marrow Stromal Stem Cell Fate Decision: A Potential Mechanism For Bone Marrow Adipose Increase with Aging-related Osteoporosis.

Osteoporosis is a systemic bone disease that seriously threatens the health and quality of life in middle-aged and older adults. In this review, we describe the relationship between bone marrow adipose tissue and aging osteoporosis and mainly focus on bone marrow mesenchymal stem cell osteogenic-adipose differentiation fate with aging along with the relevant mechanisms responsible for these changes. We summarized recent advances in regulating the bone marrow mesenchymal stem cell differentiation due to aging in this review. Aging-related bone mass loss is accompanied by expanding bone marrow adipose because of an imbalance of bone marrow mesenchymal stem cell differentiation, resulting in adipogenesis. Ectopic adipocytes in the bone marrow increase with age and are a key factor responsible for the aging-related bone mass decrease. Transcription factors and classical regulating pathways are involved in this process during aging. As the global aging population increases, not only older women but also older men face a great fracture risk. Therefore, finding molecular mechanisms controlling the stimulating adipogenesis in BMSC during aging is important for providing the new cue for prevention and therapeutics for aging-related bone loss. Furthermore, upon physical examination of older people, except for the bone mineral density and bone turnover biochemical marker, the bone marrow adipose measurement should be taken into account when assessing the fracture risk and treatment plan that will be beneficial in clinical practice.

Body mass index and cancer risk among adults with and without cardiometabolic diseases: evidence from the EPIC and UK Biobank prospective cohort studies

BackgroundWhether cancer risk associated with a higher body mass index (BMI), a surrogate measure of adiposity, differs among adults with and without cardiovascular diseases (CVD) and/or type 2 diabetes (T2D) is unclear. The primary aim of this study was to evaluate separate and joint associations of BMI and CVD/T2D with the risk of cancer.MethodsThis is an individual participant data meta-analysis of two prospective cohort studies, the UK Biobank (UKB) and the European Prospective Investigation into Cancer and nutrition (EPIC), with a total of 577,343 adults, free of cancer, T2D, and CVD at recruitment. We used Cox proportional hazard regressions to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between BMI and incidence of obesity-related cancer and in turn overall cancer with a multiplicative interaction between BMI and the two cardiometabolic diseases (CMD). HRs and 95% CIs for separate and joint associations for categories of overweight/obesity and CMD status were estimated, and additive interaction was quantified through relative excess risk due to interaction (RERI).ResultsIn the meta-analysis of both cohorts, BMI (per ~ 5 kg/m2) was positively associated with the risk of obesity-related cancer among participants without a CMD (HR: 1.11, 95%CI: 1.07,1.16), among participants with T2D (HR: 1.11, 95% CI: 1.05,1.18), among participants with CVD (HR: 1.17, 95% CI: 1.11,1.24), and suggestively positive among those with both T2D and CVD (HR: 1.09, 95% CI: 0.94,1.25). An additive interaction between obesity (BMI ≥ 30 kg/m2) and CVD with the risk of overall cancer translated into a meta-analytical RERI of 0.28 (95% CI: 0.09–0.47).ConclusionsIrrespective of CMD status, higher BMI increased the risk of obesity-related cancer among European adults. The additive interaction between obesity and CVD suggests that obesity prevention would translate into a greater cancer risk reduction among population groups with CVD than among the general population.

Associations of cord plasma per- and polyfluoroakyl substances (PFAS) with neonatal and child body composition and adiposity: The GUSTO study

BackgroundThe influence of prenatal exposure to per- and poly- fluoroalkyl substances (PFAS) on birth size and offspring adiposity is unclear, especially for the newer, shorter-chained replacement PFAS. MethodsIn the GUSTO multi-ethnic Singaporean mother-offspring cohort, 12 PFAS were measured in 783 cord plasma samples using ultra-performance-liquid chromatography-tandem-mass-spectrometer (UPLC-MS/MS). Outcomes included offspring anthropometry, other indicators of body composition/metabolic health, and MRI-derived abdominal adiposity (subset) at birth and 6 years of age. PFAS were modeled individually, in categories of long-chain and short-chain PFAS, and as scores of three principal components (PC) derived using PC analysis (PC1, PC2, and PC3 reflect predominant exposure patterns to “very-long-PFAS”, “long-PFAS”, and “short-PFAS”, respectively). Associations with outcomes were assessed using multivariable linear regressions, adjusted for important covariates such as maternal sociodemographic and lifestyle factors. ResultsOverall, cord PFAS levels showed either no or positive associations (mostly for long-chain PFAS) with birth weight, length and head circumference. In general, PFAS were associated with higher neonatal abdominal adiposity, driven by shorter-chain PFAS. Perfluoroheptanoic acid (PFHpA) was associated with higher volumes of superficial subcutaneous adipose tissue (sSAT) (3.75 [1.13, 6.37] mL per SD increase in PFAS) and internal adipose tissue (IAT) (1.39 [0.41, 2.38] mL). Higher levels of perfluorobutanesulfonic acid (PFBS), short-chain PFAS, and PC3 were associated with higher IAT volume (β range 1.22–1.41 mL/SD, all P < 0.02), especially in girls. Higher PC3 score was additionally associated with higher sSAT (3.12 [0.45, 5.80] mL) volume. At age 6 years, most observed associations did not persist. No consistent associations were observed between PFAS and whole-body adiposity measures. ConclusionsFetal exposure to emerging short-chain PFAS was associated with higher abdominal adiposity at birth but not at age 6 years. Further research is needed to replicate the findings and to determine if these effects may reappear beyond early childhood. Population exposure to newer PFAS and consequent health impact must be monitored.

Genetic causal association of adiposity, body fat distribution with incident heart failure in a European cohort: A linear and non-linear Mendelian randomisation analysis

Abstract Background Excess adiposity has been associated with higher risk of heart failure in observational studies. However, these observational studies are prone to residual confounding and the shape and strength of the independent associations of adiposity measures with heart failure is uncertain. Purpose This study aimed to compare the associations of usual and genetically determined general and central adiposity measures on incident heart failure in a European population cohort. Methods The MR analysis was performed in a cohort of 326,300 adults (mean age 55.9 years, 56% women) of European ancestry with complete genetic data and no prior cardiac and vascular disease recruited from UK general population in 2006-2010. Resurvey on a subset of 20,346 participants was conducted in 2012-13. Regression dilution ratios (RDR) of the different adiposity measures were calculated using Pearson’s correlation method to obtain usual levels of each adiposity measure. Participants were followed up by linkage to electronic health records for incident heart failure events. Externally weighted genetic risk scores (GRS) for body mass index (BMI) and waist circumference (WC) adjusted for BMI (WCadjBMI) were constructed using single nucleotide polymorphisms (SNPs) that were genome-wide significant for BMI and WC as reported by the Genetic Investigation of ANthropometric Traits (GIANT) consortium. Associations of usual measured adiposity measures and genetically predicted usual adiposity (76-SNP BMI-GRS [pleiotropic for other adiposity measures], 36-SNP BMI-GRS [non-pleiotropic for other adiposity measures] and 68-SNP WCadjBMI-GRS) with incident HF subtypes were determined using Cox proportional hazards regression models. The shapes of the associations of genetically predicted adiposity with heart failure at different levels of adiposity measures were examined using localized average causal effects within strata of residual adiposity measures after adjustment for GRS and correction for regression dilution. Hazard ratios (HRs) are presented as per equivalent 5 usual BMI units higher adiposity measure. Results Over a median follow-up of 12.8 years, there were 6,570 first-ever incident HF events. A positive non-linear association (J-shape) was observed between genetically predicted BMI and heart failure with while positive log-linear association was observed for genetically predicted WCadjBMI. Consistent with the observational analyses, the hazard ratio per 5 BMI units equivalent higher genetically predicted WCadjBMI were notably stronger (68-SNP WCadjBMI GRS: HR 2.03, 95% CI1.04-3.97) than for genetically predicted BMI (36-SNP GRS-BMI: HR 1.78, 95% CI 1.12-2.81 and 76-SNP GRS-BMI: HR 1.99, 95% CI 1.62-2.45). Conclusion The findings provide evidence for increased heart failure risk at extremes of BMI and also confirm the stronger causal role of central adiposity over general adiposity in heart failure across the whole range of waist circumference.Figure 1Figure 2

Androgen deprivation therapy for prostate cancer, measures of adiposity and strength, and adverse cardiovascular outcomes: observations from 3000 men in 5 countries in the RADICAL PC study

Abstract Background Androgen deprivation therapy (ADT) is prescribed to nearly half of patients with prostate cancer (PC). ADT is associated with weight gain, reduced muscle strength and increased cardiovascular (CV) risk. However, no PC study has examined the relationship between these physical characteristics, their change with ADT and cardiovascular outcomes. Purpose In men with PC: To compare 1-year changes in physical measures in those receiving versus not receiving ADT To evaluate the relationship between physical measures and adverse CV outcomes Methods We prospectively studied 3080 men with PC from 37 sites in 5 countries (mean age 68 years), 41% on ADT. Inclusion criteria were one of: PC diagnosed in the past 12 months; started ADT within the past 6 months; or plan to start ADT in the next month. Weight, waist and hip circumference, handgrip strength and get-up-and-go time were recorded at baseline and 1 year. Change in measurements were adjusted for age, education, race, tobacco and alcohol use, baseline cardiovascular disease and renal function. Participants were followed for a median 3 years from enrolment to document adverse CV outcomes associated with adiposity: myocardial infarction, angina, stroke, cerebrovascular disease, peripheral arterial disease, arterial revascularization, heart failure, venous thromboembolism and atrial fibrillation. The relationship between baseline physical measures and outcomes was evaluated by Cox proportional hazards models adjusted for age, diabetes, hypertension, total cholesterol, tobacco use and physical activity levels. Results Changes in physical measures are displayed in Table. ADT recipients gained 5x more weight than non-recipients. Weight gain was distributed evenly between waist and hips, resulting in no difference in waist:hip ratio. Muscle strength decreased in both groups but with 43% larger decrease among ADT recipients. The ratio of strength to body weight fell twice as much in ADT recipients as non-recipients. Gait speed slowed by 13% after 12 months’ ADT. We observed 144 adverse CV events. There was a continuous relationship between handgrip strength and CV events. Each quartile reduction in strength was associated with adjusted hazard ratio (95% CI) 1.24 (1.01-1.52). There was no detectable association between other physical measures and CV events. Conclusion ADT use is associated with increased adiposity and reduced muscle strength. Low muscle strength, reflected by low handgrip strength is a better predictor of adverse CV outcomes than increased adiposity. These findings may explain help the association between ADT use and adverse CV outcomes.Table

Abstract 14613: Sex Differences in Protein Biomarkers and Measures of Fat Distribution

Background: Sex differences in obesity and fat distribution have been well described and may explain differences in subsequent cardiovascular risk in men vs women. Underlying mechanisms are not fully elucidated and warrant further investigation. Objective: This study aims to examine sex differences in the associations of obesity and fat distribution measures with cardiovascular disease (CVD) protein biomarkers reflecting key pathways including inflammation, adiposity, fibrosis, and neurohormonal regulation. Methods: We measured 71 circulating protein biomarkers in 3,143 participants with available computed tomography measures of adiposity in the Framingham Heart Study. We examined whether sex modified the association of obesity (body mass index [BMI] and waist circumference [WC]) and fat distribution measures (visceral adipose tissue [VAT]) with protein biomarkers using multiplicative interaction terms in multivariable linear regression models. Sex-stratified analyses were performed as appropriate. Results: Among 3,143 participants (mean age 50 years, 48.7% women), we found that sex modified the association of BMI with 8 protein biomarkers including AGP-1, adipsin, IGFBP-1, IGFBP-2, ADM, KLKB1, MCP-1, and ucMGP (FDR-q int &lt; 0.05 for all, Figure 1 ). For example, BMI was associated with higher MCP-1 levels in women, but not in men (ß 0.132, SE 0.025, p &lt; 0.0001 in women vs ß 0.036, SE 0.028, p = 0.20 in men, FDR-q int 0.03). We found that sex also modified the association of WC and VAT with key CVD protein biomarkers including AGP-1 and A1M. Conclusions: We found that sex modified the association of obesity and adipose traits with cardiovascular risk as ascertained using biomarkers of CVD. These findings highlight potential biological pathways that may contribute to obesity-related cardiometabolic disease uniquely in men versus women.

Independent relevance of adiposity measures to coronary heart disease risk among 0.5 million adults in UK Biobank.

Evidence on body fat distribution shows opposing effects of waist circumference (WC) and hip circumference (HC) for coronary heart disease (CHD). We aimed to investigate the causality and the shape of such associations. UK Biobank is a prospective cohort study of 0.5million adults aged 40-69years recruited between 2006 and 2010. Adjusted hazard ratios (HRs) for the associations of measured and genetically predicted body mass index (BMI), WC, HC and waist-to-hip ratio with incident CHD were obtained from Cox models. Mendelian randomization (MR) was used to assess causality. The analysis included 456 495 participants (26 225 first-ever CHD events) without prior CHD. All measures of adiposity demonstrated strong, positive and approximately log-linear associations with CHD risk over a median follow-up of 12.7 years. For HC, however, the association became inverse given the BMI and WC (HR per usual SD 0.95, 95% CI 0.93-0.97). Associations for BMI and WC remained independently positive after adjustment for other adiposity measures and were similar (1.14, 1.13-1.16 and 1.18, 1.15-1.20, respectively), with WC displaying stronger associations among women. Blood pressure, plasma lipids and dysglycaemia accounted for much of the observed excess risk. MR results were generally consistent with the observational, implying causality. Body fat distribution measures displayed similar associations with CHD risk as BMI except for HC, which was inversely associated with CHD risk (given WC and BMI). These findings suggest that different measures of body fat distribution likely influence CHD risk through both overlapping and independent mechanisms.

Increased body weight and central adiposity markers are positively associated with the 20-year incidence of cardiovascular disease: The ATTICA epidemiological study (2002–2022)

Increased adiposity predisposes to cardiovascular disease (CVD). We hypothesized that the presence of obesity would be positively associated with CVD risk, and that the co-presence of central obesity would modify/enhance this association. This was a prospective study (2002–2022) among 1845 Greek adults (mean age, 44.8 ± 13.5 years; men, 49.8%). At baseline, the presence of overweight/obesity was assessed via body mass index (BMI), whereas central obesity was defined as waist circumference ≥102/88 cm, waist-to-hip-ratio ≥0.95/0.80, or waist-to-height-ratio ≥0.50 in men/women. BMI was reevaluated at 10 years and longitudinal BMI trajectories (2002–2012) were identified. CVD incidence was recorded at 20 years (ratio of new cases to the number of participants assessed). Compared with participants with normal weight at baseline, those with obesity exhibited a 27% higher 20-year CVD risk after adjustment for age, sex, lifestyle habits, and medical status (hazard ratio, 1.271; 95% confidence interval, 1.012–1.597). In similar multiadjusted models, compared with participants who were always non-overweight/obese, those who were always overweight/obese exhibited a 40% higher 20-year CVD risk (hazard ratio, 1.403; 95% confidence interval, 1.018–1.936). Additional control for high-sensitivity C-reactive protein attenuated the associations. In the combined baseline body weight classification analysis, CVD incidence was the lowest in participants with normal weight without central obesity, moderate in those with overweight/obesity without central obesity, and highest in those with normal weight and central obesity and overweight/obesity and central obesity (P < .001). Obesity leads to increased CVD risk, partly mediated by inflammation. The combination of BMI with simple measures of abdominal adiposity is superior for CVD risk screening.

Association of vitamin D levels with anthropometric and adiposity indicators across all age groups: a systematic review of epidemiologic studies.

It has not been established whether vitamin D deficiency is associated with anthropometric state; therefore, this systematic review examined the relationship between serum vitamin D levels with anthropometrics and adiposity across different ages. Studies that examined vitamin D deficiency with adiposity measures in different age groups were searched in the PubMed, Scopus, Embase, and Google Scholar databases until November 2023. Two investigators independently reviewed titles and abstracts, examined full-text articles, extracted data, and rated the quality in accordance with the Newcastle-Ottawa criteria. Seventy-two studies, with a total of 59,430 subjects, were included. Of these studies, 27 cross-sectional studies and one longitudinal study (with 25,615 participants) evaluated the possible link between 25(OH)D serum concentrations and anthropometric/adiposity indices in the pediatric population. Forty-two cross-sectional studies and two cohort investigations (with 33,815 participants) investigated the relationship between serum 25(OH)D levels and adiposity measures in adults and/or the elderly population. There is evidence supporting links between vitamin D deficiency and obesity, and revealed an inverse association between vitamin D and adiposity indicators, specifically in female subjects. However, the effects of several confounding factors should also be considered. Most published studies, most of which were cross-sectional, reported a negative association between vitamin D and female adiposity indicators. Therefore, serum vitamin D levels should be monitored in overweight/obese individuals.

Adiposity, Weight Change, and Urinary Melatonin Levels among Men in the Multiethnic Cohort.

Low levels of 6-sulfatoxymelatonin, the primary urinary metabolite of melatonin, have been linked to cancer and cardiometabolic outcomes in White and female populations. We examined the association between adulthood adiposity and 6-sulfatoxymelatonin levels in a racially and ethnically diverse population. Our study included 4,078 men in the Multiethnic Cohort with adiposity measurements at enrollment (1993-1996) and biomarkers measured in urines collected in 1995 and 2005. Multivariable linear regression models were used to estimate the percent change in 6-sulfatoxymelatonin levels and 95% confidence intervals (CI). Associations were examined separately by racial/ethnic group. The prevalence of obesity varied by race and ethnicity, from 10% for Japanese American men to 34% for Native Hawaiian men. Compared with men with normal body mass index (BMI), men who were overweight (-7.8%; 95% CI, -11.9 to -3.5%) and obese (-18.1%; 95% CI, -23.2 to -12.6%) had significantly lower 6-sulfatoxymelatonin levels adjusting for potential confounding factors. Increasing weight gain in adulthood was also associated with lower 6-sulfatoxymelatonin (Ptrend < 0.0001). The inverse associations for BMI and weight change were qualitatively similar across racial and ethnic groups. Obesity is inversely associated with melatonin in a racially diverse population. This finding is relevant given higher rates of obesity among Black, Native Hawaiian, and Latino men, as well as potential racial and ethnic differences in circadian function. Melatonin may be a relevant biomarker among obesity-associated malignancies and could shed light on a potential mechanism of cancer disparities.

Physiological gradient in lumbar spine fat fraction and R2* and its impact on osteoporosis diagnosis

BACKGROUNDBone marrow adiposity and R2* have been explored as an imaging biomarker for osteoporosis. Chemical shift-encoded MRI (CSE-MRI) is a method that allows for relatively accurate measurement of adiposity and R2* in bone marrow in a simple manner. Additionally, there are reports of a physiological gradient of fat distribution in the lumbar spine. This physiological gradient of fat distribution can potentially impact the prediction of osteoporosis. Furthermore, the distribution of R2* is not well understood. PURPOSEThis study examined how lumbar spine fat fraction (FF) and R2* change with different levels of the lumbar spine, how they influence osteoporosis prediction, and how they change according to measurement methods. STUDY DESIGN/SETTINGCross-sectional study using retrospectively collected data. PATIENT SAMPLEThe study included patients who underwent dual-energy X-ray absorptiometry and lumbar spine CSE-MRI within one-month intervals between 2017 and 2022. OUTCOME MEASURESReproducibility of FF and R2* based on measurement techniques, changes in FF and R2* according to vertebral level and osteoporosis status, and diagnostic power of osteoporosis based on vertebral level. METHODSPatients were categorized into the normal bone density, osteopenia, and osteoporosis groups based on bone mineral density. The relationship between groups and spine level before and after BMD adjustment was investigated using generalized estimating equations. Comparisons between the three groups and various measures of reliability were conducted using intraclass correlation coefficient. The diagnostic performance for predicting osteoporosis was evaluated with a receiver operating characteristic curve. RESULTSComparing the three groups, FF increased with osteoporosis severity, while R2* decreased (p<.001). The intra/inter-rater agreement for FF and R2* was excellent. A physiological gradient within individuals was observed, where FF increased towards the lower lumbar spine (p=.002). R2* tended to decrease, but it was not statistically significant (p=.218). There was no statistically significant difference in the diagnosis of osteoporosis based on FF or R2* across different lumbar spine levels. CONCLUSIONSThere was an increase in FF and a decrease in R2* from T12 to L5. However, the predictive power of osteoporosis did not significantly differ between each level.