Sex Differences In Association Research Articles

The traction requirements of female and male basketball players

Despite basketball being a popular sport among both genders, basketball footwear is designed primarily based on men. This may be problematic for women as the footwear they utilize may not be optimized for female performance and excessive traction may increase the risk of lower extremity non-contact injuries. While there are known sex-associated differences in the execution of basketball-related movements, the traction requirements of women have yet to be determined. Therefore, the purpose of this study was to compare the traction requirements of women and men performing basketball-related movements. Twenty collegiate-level basketball players (10 women and 10 men) participated in this study performing five basketball-related movements (Cross Cut, Lateral Cut, Quick Start, Jump Stop and Side Shuffle). Women and men were found to have similar traction requirements across many of movements, but significant differences were found during phases of the Quick Stop, Lateral Cut and Cross Cut. Overall, while the traction requirements of women and men appear similar, subtle differences exist at specific time points, which may be utilized to optimize gender-specific outsole design.

Disparities in the treatment of cardiogenic shock: does sex matter?

The use of extracorporeal life support for cardiogenic shock has significantly increased over the past decade. However, there are insufficient data for the presence of sex-associated outcomes differences. Our study assesses differences between male and female patients placed on venoarterial extracorporeal life support (VA-ECLS) for cardiogenic shock from an international database. This is a multicentre, retrospective study on 9888 adult patients on VA-ECLS for cardiogenic shock from the Extracorporeal Life Support Organization registry from 2011 to 2019. The 1:1 nearest neighbour propensity score matching was performed. The primary end point was in-hospital mortality. Secondary end points include bleeding, infection and other complications. There were 6747 (68%) male patients and 3141 (32%) female patients. Male patients were more likely to have history of myocardial infarction, coronary artery disease, diabetes, chronic kidney disease and congestive heart failure. Female patients were more likely to be centrally cannulated. After propensity score matching, there was no difference seen in in-hospital mortality. In regards to complications, female patients were more likely to experience limb ischaemia, whereas males were more likely to receive renal replacement therapy and have longer hospital stays. Multivariable logistic regression confirmed sex was not independently associated with mortality. There was no difference in-hospital mortality between male and female patients receiving VA-ECLS for cardiogenic shock. Female patients were more likely to have limb ischaemia as a complication. Varying cannulation approaches for female patients should be further investigated.

Comprehensive analysis of ESR1-related ceRNA axis as a novel prognostic biomarker in hepatocellular carcinoma.

Aims: To further understand, detect and treat hepatocellular carcinoma (HCC), it is urgent to conduct more in-depth research on the mechanism of sex-associated differences. Materials & methods: We established a ceRNA triple regulatory axis associated with ESR1 in HCC and performed expression, survival and nuclear-cytoplasmic localization analyses. In addition to this, we performed methylation analysis and immune infiltration analysis of the ceRNA axis. Results: We constructed the LINC01018/hsa-miR-197-3p/GNA14 (lncRNA/miRNA/mRNA) ceRNA axis to further explain the mechanism of sex-related prognosis in the development of HCC and to provide new insights into candidate biomarkers for targeted therapies. Conclusion: Our study is an innovative attempt at demonstrating the mechanism underlying the prognosis associated with sex differences in HCC by constructing a ceRNA axis (LINC01018/hsa-miR-197-3p/GNA14).

Sex-Related Differences in Short-Term Outcomes after Mobile VA-ECMO Implantation: Five-Year Experience of an ECMO Retrieval Program.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) represents an increasingly used method for circulatory support. Despite the ongoing research, survival following VA-ECMO therapy remains low. Sex-related differences might impact the outcome of therapeutic measures. We aimed to compare all-cause mortality among female and male patients who underwent VA-ECMO as a bridge to recovery investigating sex-related differences. From January 2015 until August 2020, 87 patients were supported by VA-ECMO as a part of our out-of-center mobile ECMO program. In order to analyze sex-associated differences in early clinical outcomes, patients were divided into two sex categories: men (n = 62) and women (n = 25). All relevant data (in-hospital mortality, ICU and hospital stay, renal failure requiring dialysis, lung failure, bleeding, stroke and septic shock) were analyzed retrospectively after the extraction from our institutional database. Mean age of the study population was 53 ± 14 years. Mean EuroSCORE II predicted mortality was 6.5 ± 3.7. In-hospital mortality rate was not significantly lower in the female group (58.3%) vs. the male group (71.2%), p = 0.190. The mean length of ICU and hospital stay was 9 ± 11 in the male group vs. 10 ± 13 in the female group, p = 0.901, and 10 ± 12 (male group) vs. 11 ± 13 (female group), p = 0.909, respectively. Renal failure requiring hemodialysis (36.2% (males) vs. 28.6% (females), p = 0.187) was comparable between both groups. Respiratory failure was diagnosed in 31 (56.4%) male vs. 8 (34.8%) female patients, p = 0.068, while 16 (28.6%) male vs. 3 (13.0%) female patients (p = 0.118) suffered from septic shock. Based on our data, there were no sex-specific outcome discrepancies in patients treated with mobile VA-ECMO implantation.

Hypoxia-induced pulmonary hypertension upregulates eNOS and TGF-β contributing to sex-linked differences in BMPR2 +/R899X mutant mice.

Dysfunctional bone morphogenetic protein receptor 2 (BMPR2) and endothelial nitric oxide synthase (eNOS) have been largely implicated in the pathogenesis of pulmonary arterial hypertension (PAH); a life-threatening cardiopulmonary disease. Although the incident of PAH is about three times higher in females, males with PAH usually have a worse prognosis, which seems to be dependent on estrogen-associated cardiac and vascular protection. Here, we evaluated whether hypoxia-induced pulmonary hypertension (PH) in humanized BMPR2+/R899X loss-of-function mutant mice contributes to sex-associated differences observed in PAH by altering eNOS expression and inducing expansion of hyperactivated TGF-β-producing pulmonary myofibroblasts. To test this hypothesis, male and female wild-type (WT) and BMPR2+/R899X mutant mice were kept under hypoxic or normoxic conditions for 4 weeks, and then right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) were measured. Chronic hypoxia exposure elevated RVSP, inducing RVH in both groups, with a greater effect in BMPR2+/R899X female mice. Lung histology revealed no differences in vessel thickness/area between sexes, suggesting RVSP differences in this model are unlikely to be in response to sex-dependent vascular narrowing. On the other hand, hypoxia exposure increased vascular collagen deposition, the number of TGF-β-associated α-SMA-positive microvessels, and eNOS expression, whereas it also reduced caveolin-1 expression in the lungs of BMPR2+/R899X females compared to males. Taken together, this brief report reveals elevated myofibroblast-derived TGF-β and eNOS-derived oxidants contribute to pulmonary microvascular muscularization and sex-linked differences in incidence, severity, and outcome of PAH.

Sex differences in the associations between psychological symptoms and tumor necrosis factor-alpha levels among obese and nonobese children aged 6–13 in Taiwan

BackgroundEvidence of associations between psychological symptoms and tumor necrosis factor (TNF)-α level is scant, as is evidence on sex differences in associations for children and adolescents with obesity. This study examined sex differences in associations between psychological symptoms (self-concept, anxiety, depression, anger, and disruptive behavior) and TNF-α level in Taiwanese children and adolescents with healthy weight, overweight, or obesity. MethodsIn 2010, 564 first, fourth, and seventh graders—comprising 250 children with overweight or obesity (44.3 %), 330 adolescents (58.5 %), and 303 males (53.7 %)—underwent a health examination and blood sampling and completed a questionnaire. ResultsA significantly higher TNF-α level was found in children and adolescents with healthy weight than in those with overweight or obesity (median: 14.5 vs. 4.1 (pg/mL); p < 0.001). In multiple linear regression models, anxiety was significantly positively associated with TNF-α level in female participants with healthy weight (β = 0.11 per 10 increments in anxiety, 95 % confidence interval = 0.01–0.22). LimitationsGiven the cross-sectional nature of the study, no inferences of causal relationships among TNF-α level, obesity, and psychological symptoms could be made. ConclusionsThe findings enrich the literature on the TNF-α–psychological symptom association. Sex differences were found in children and adolescents without obesity rather than in those without obesity, and a higher TNF-α level was associated with increased anxiety in girls without obesity. The role of sex differences in the complex associations among psychological symptoms, TNF-α level, and overweight or obesity requires further investigation.

Sex-specific associations between metabolic hormones, severe mental disorders and antipsychotic treatment

BackgroundMetabolic dysregulation has been associated with severe mental disorders (SMD) and with antipsychotic (AP) treatment, but the role of sex is unknown. To identify possible sex-related processes linked to SMD and AP treatment, we investigated sex differences in associations between hormones involved in metabolic regulation in patients with SMD compared to healthy controls (HC) and AP treatment. MethodsWe included patients with SMD (N = 1753) and HC (N = 1194) and measured hormones involved in metabolic regulation (insulin, cortisol, thyroid-stimulating hormone (TSH), thyroxine, leptin, adiponectin, testosterone, sex hormone-binding globulin (SHBG), prolactin). Patients were grouped according to use of first-generation AP (N = 163), second-generation AP (N = 1087) or no use of AP (N = 503). Hormones were used one by one as dependent variables in multiple regression analyses with interactions between sex and SMD patients versus HC, and between sex and AP treatment, followed by analyses in males and females separately. ResultsWe found significant interactions between sex and SMD patients versus HC for testosterone, SHBG and adiponectin, with significantly higher testosterone and lower adiponectin levels in females. Furthermore, we found significant interaction between sex and AP groups for TSH, testosterone and insulin, with significantly lower TSH levels in AP-treated females, and lower testosterone and higher insulin levels in AP-treated males. ConclusionsOur findings suggest sex differences in metabolic hormones related to both SMD and AP treatment, indicating sex-dependent mechanisms. Clinicians should be aware of potential sex-specific metabolic changes during AP treatment and experimental studies are warranted to clarify the underlying mechanisms.

Sex differences in associations between alcohol use and sleep in mid-to-late life

ObjectivesTo examine associations between alcohol use and sleep in middled-aged/older adults and to test sex as a moderator of this relationship. MethodsParticipants were 183 adults (46% female) ages 50 and above who consumed alcohol in the past year. Linear regressions tested sex as a moderator of associations between alcohol use and sleep parameters. Alcohol use was measured using the Alcohol Use Disorders Identification Test (AUDIT). Overall sleep health and sleep quality were assessed using the Pittsburgh Sleep Quality Index (PSQI), and pre-sleep arousal was assessed using the Pre-Sleep Arousal Scale. ResultsOverall, 11% of participants screened positive for hazardous drinking (AUDIT scores of 7+/8+ for women/men), and 59% reported poor overall sleep health (scores >5 on the PSQI). Alcohol use was not associated with overall sleep health (B = −0.25, p = .08) or pre-sleep arousal (B = 0.15, p = .64). However, contrary to hypotheses, more hazardous drinking was associated with better subjective sleep quality, only among women (B = −0.08, p = .009). Alcohol use was not associated with sleep quality among men (B = 0.01, p = .58). Associations remained significant when controlling for age, symptoms of anxiety and depression, body mass index, use of sleep medication, number of medical conditions, and chronic pain. ConclusionsAmong middle-aged and older adults, alcohol use is more strongly associated with sleep patterns among women than men, when assessed concurrently (i.e., at the same time point). Findings support the need for further consideration of sex differences in associations between alcohol use and sleep.

Sex-associated differences in patellotrochlear morphology in small-breed dogs

Sex-associated differences in patellotrochlear morphology in small-breed dogs

Unmet Healthcare Needs among College Students during the COVID-19 Pandemic: Implications for System-Wide and Structural Changes for Service Delivery.

Background: During the COVID-19 pandemic, college students faced health disparities in addition to a negative burden on academic performance; however, little is reported in the literature regarding healthcare utilization. Methods: A cross-sectional survey was conducted among consenting college student participants aged 18 or older from a Hispanic-serving institution. Descriptive and bivariate statistics were used to analyze demographic characteristics and the types of healthcare services needed by such characteristics. Logistic regression was used to adjust for noted sex differences in associations between reporting limited healthcare services and types of healthcare services. Results: The study population of 223 participants was mostly Hispanic/Latino (65%) and female (73%). Of the population, 11% reported they could not obtain needed healthcare services, with time being reported as the most common reason. Significant associations were found between seeking general healthcare services/routine screening, seeking mental health services, and seeking sexual health services with reporting limited healthcare services, with sex-adjusted odds ratios and 95% confidence intervals of 1.90 (95% CI: 1.08, 3.36), 3.21 (95% CI: 1.44, 4.15), and 2.58 (95% CI: 1.05, 6.35), respectively. Conclusions: Availability and inability to obtain health services may exacerbate college student health disparities. Targeted interventions are needed in the population to mitigate the potential burdens of unmet healthcare needs, particularly among minority college students.

LB885 Sex-associated differences in genomic profiles of melanoma

Sex differences in melanoma incidence and survival are well-documented with females having a decreased risk of metastasis and overall better survival outcomes than males, even after adjusting for tumor stage. There are numerous factors that could contribute to these disparities, including differences in behavior, host immunity, and tumoral factors. Here, we seek to examine sex-based tumor mutational differences, which may impact both melanoma prognosis and treatment outcomes. We assessed the genomic profiles of 2468 melanoma patients in the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (v10.0).

Sex differences in association between Internet addiction and aggression among adolescents aged 12 to 18 in mainland of China

BackgroundPrevious studies have reported that Internet addiction (IA) is an important predictor of aggression. However, little is known whether aggression is a risk factor of IA. This study aims to explore whether IA can predict total and sub-types of aggression, whether aggression also can predict IA, and the potential sex difference. MethodA total of 15,977 adolescents aged 12 to 18 were recruited though a stratified cluster sampling across five representative provinces in mainland of China. Young's Internet Addiction Test (IAT) and Buss and Warren's Aggression Questionnaire (BWAQ) were used to measure IA and aggression, respectively. ResultsThe prevalence of IA and total aggression was 16.8 % and 25.0 %, respectively. Binary logistic regression analysis indicated that IAT score was significantly associated with total and five sub-types of aggression (P < 0.001). However, scores of physical aggression, hostility, and indirect aggression were positively associated with IA (P < 0.001), while verbal aggression and anger were not significant (P > 0.05). Moreover, the interaction of sex and IA was significant for aggression. Specifically, females with IA had higher risks of anger and indirect aggression but had lower risks of physical and verbal aggression compared to males with IA. LimitationsCross-sectional design, self-reported information, and only Chinese rural adolescents. ConclusionsIA is a strong risk factor of total and five sub-types of aggression, while not all sub-types of aggression are predictors of IA. Prevention programs for adolescents' IA and aggression should consider different aggression sub-types and sex.

Contribution of Sex Differences to HIV Immunology, Pathogenesis, and Cure Approaches.

Approximately 38 million people were living with human immunodeficiency virus (HIV) in 2020 and 53% of those infected were female. A variety of virological and immunological sex-associated differences (sexual dimorphism) in HIV infection have been recognized in males versus females. Social, behavioral, and societal influences play an important role in how the HIV pandemic has affected men and women differently. However, biological factors including anatomical, physiologic, hormonal, and genetic differences in sex chromosomes can each contribute to the distinct characteristics of HIV infection observed in males versus females. One striking example of this is the tendency for women to have lower HIV plasma viral loads than their male counterparts early in infection, though both progress to AIDS at similar rates. Sex differences in acquisition of HIV, innate and adaptive anti-HIV immune responses, efficacy/suitability of specific antiretroviral drugs, and viral pathogenesis have all been identified. Sex differences also have the potential to affect viral persistence, latency, and cure approaches. In this brief review, we summarize the major biological male/female sex differences in HIV infection and their importance to viral acquisition, pathogenesis, treatment, and cure efforts.

An investigation into possible sex differences in Association of Haemoglobin with survival among Haemodialysis patients in the J-DOPPS cohort.

Lower haemoglobin levels are common among females without kidney diseases. However, little is known about the sex-specific management of anaemia in haemodialysis patients. This prospective cohort study investigated the role of sex differences in the association between categorical baseline or time-varying haemoglobin levels and all-cause mortality via cox regression using data from 6890 patients in the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS, 2005-2015). Likelihood ratio tests were used to evaluate the effect modification of sex on the relationship between haemoglobin and mortality. A total of 781 patients died during the median follow-up of 31 months. Mortality risk, adjusted for case mix, varied between five haemoglobin categories, with the highest category (≥12 g/dL) having a hazard ratio of 0.73 (0.41-1.29) for females and 2.02 (1.03-3.95) for males versus 10-10.9g/dL. Despite this difference, the p-value comparing the overall among males versus females was.35. Similar associations were observed in models stratified by patient age (<75 years), time on dialysis (≤1year), and models lagging the haemoglobin exposure. The results based on this sample of Japanese haemodialysis patients did not support the hypothesis that the association between haemoglobin and survival differed by sex. We also could not conclude that the association was identical, as the parameter estimates are consistent with male patients having a relatively greater mortality risk than female patients at higher haemoglobin levels. More detailed investigations into the effects of higher haemoglobin levels by sex might help better understand strategies for anaemia management.

Abstract 259: BMPR2 +/r899x Mutation Contributes To Sex-linked Disparity In Hypoxia-induced Pulmonary Hypertension

Introduction: Dysfunctional bone morphogenetic protein receptor 2 (BMPR2) and endothelial nitric oxide synthase (eNOS) have been implicated in the pathogenesis of pulmonary arterial hypertension (PAH), a life-threatening disease characterized by pulmonary vascular remodeling, elevated right ventricular systolic pressure (RVSP), and right ventricular hypertrophy (RVH). Although the incidence of this disease is three times higher in females, males with PAH usually have a worse prognosis. The mechanism behind this sex-associated difference remains undetermined. Objective: Determine whether BMPR2 +/R899X loss-of-function mutation contributes to sex-associated differences in PAH, including the degree of vascular remodeling, RVSP, and RVH. Methods: Wild-type (WT) and BMPR2 +/R899X mice (male/female) were exposed to hypoxia (Hx) or normoxia (Nx) for 4 weeks, when the RVSP and RVH were measured. Lung tissue was used for western blot and histological analysis. Results/Discussion: Hx exposure elevated RVSP, inducing RVH in both groups, with a greater effect in BMPR2 +/R899X mice compared to WT (RVSP: 45.0+/- 2.2 and 34.9 +/- 1.3 mmHg, respectively). A higher RVSP was observed in BMPR2 +/R899X female mice, with males exhibiting more pronounced RVH, suggesting females might have a protective mechanism against severe RVH. Lung histology revealed no differences in vessel thickness/area between sexes, which may indicate that the RVSP differences are unlikely a response to vascular remodeling. Hx exposure increased the amount of α-SMA+ microvessels and eNOS expression in BMPR2 +/R899X females compared to males, but further experiments are required to determine whether elevated eNOS reflects higher function or an oxidative stress-driven endothelial cell phenotype. Conclusion: This work is uncovering the translational relevance of BMPR2 +/R899X mutation in the sex-linked differences in PAH incidence, severity, and outcome.

Sex- and age-specific associations between cardiometabolic risk and white matter brain age in the UK Biobank cohort.

Cardiometabolic risk (CMR) factors are associated with accelerated brain aging and increased risk for sex‐dimorphic illnesses such as Alzheimer's disease (AD). Yet, it is unknown how CMRs interact with sex and apolipoprotein E‐ϵ4 (APOE4), a known genetic risk factor for AD, to influence brain age across different life stages. Using age prediction based on multi‐shell diffusion‐weighted imaging data in 21,308 UK Biobank participants, we investigated whether associations between white matter Brain Age Gap (BAG) and body mass index (BMI), waist‐to‐hip ratio (WHR), body fat percentage (BF%), and APOE4 status varied (i) between males and females, (ii) according to age at menopause in females, and (iii) across different age groups in males and females. We report sex differences in associations between BAG and all three CMRs, with stronger positive associations among males compared to females. Independent of APOE4 status, higher BAG (older brain age relative to chronological age) was associated with greater BMI, WHR, and BF% in males, whereas in females, higher BAG was associated with greater WHR, but not BMI and BF%. These divergent associations were most prominent within the oldest group of females (66–81 years), where greater BF% was linked to lower BAG. Earlier menopause transition was associated with higher BAG, but no interactions were found with CMRs. In conclusion, the findings point to sex‐ and age‐specific associations between CMRs and brain age. Incorporating sex as a factor of interest in studies addressing CMR may promote sex‐specific precision medicine, consequently improving health care for both males and females.

Sex-Associated Differences in Neurovascular Dysfunction During Ischemic Stroke.

Neurovascular units (NVUs) are basic functional units in the central nervous system and include neurons, astrocytes and vascular compartments. Ischemic stroke triggers not only neuronal damage, but also dissonance of intercellular crosstalk within the NVU. Stroke is sexually dimorphic, but the sex-associated differences involved in stroke-induced neurovascular dysfunction are studied in a limited extend. Preclinical studies have found that in rodent models of stroke, females have less neuronal loss, stronger repairing potential of astrocytes and more stable vascular conjunction; these properties are highly related to the cerebroprotective effects of female hormones. However, in humans, these research findings may be applicable only to premenopausal stroke patients. Women who have had a stroke usually have poorer outcomes compared to men, and because stoke is age-related, hormone replacement therapy for postmenopausal women may exacerbate stroke symptoms, which contradicts the findings of most preclinical studies. This stark contrast between clinical and laboratory findings suggests that understanding of neurovascular differences between the sexes is limited. Actually, apart from gonadal hormones, differences in neuroinflammation as well as genetics and epigenetics promote the sexual dimorphism of NVU functions. In this review, we summarize the confirmed sex-associated differences in NVUs during ischemic stroke and the possible contributing mechanisms. We also describe the gap between clinical and preclinical studies in terms of sexual dimorphism.

Sex Differences and Similarities in Risk Factors of Physical Aggression in Adolescence

Considerable research has documented risk factors of physical aggression in adolescence. However, less is known of sex differences in these associations. The current study addressed this important area by examining sex differences in concurrent associations of physical aggression with mental health concerns, trauma exposure, and substance use. The study sample consisted of 3686 boys (mean age 15.9 years) and 3881 girls (mean age 16.0 years) from Young-HUNT3, a population-based study of adolescents in Norway. Logistic regression was used to analyze the association of physical aggression, measured as involvement in physical fighting, with possible risk factors: attention problems, anxiety and depression, loneliness, self-esteem problems, trauma exposure, PTSD symptoms, and substance use. Twenty-one percent (n = 773) of boys and three percent (n = 133) of girls reported participating in physical fights. The results indicated that all risk factors were associated with physical aggression in the total sample as well as in boys and girls separately. Interaction effects with sex emerged for attention problems, anxiety and depression, loneliness, traumatic events, alcohol intoxication, and narcotics use, with larger odds ratios for girls than for boys. Attention problems, traumatic events, and alcohol intoxication showed unique associations with physical aggression for both boys and girls, in addition to PTSD symptoms for boys. In sum, boys’ and girls’ engagement in physical aggression was associated mainly with the same risk factors, but several of the factors increased the relative risk more for girls than for boys. The findings can inform interventions targeting physical aggression in adolescence.

Corpus Callosum Volumes in Children with Autism Spectrum Disorders: Sex-Associated Differences.

This study aimed to analyze the relationship between sex and corpus callosum (CC) volume in children with autism spectrum disorders (ASD) aged 2-4years. This prospective study included 50 children with ASD and 50 typically developing (TD) children aged 2-4years. Midsagittal slices of the CCs of the participants were divided into five subregions using FreeSurfer software. The PMCC, AMCC and TCC volumes were significantly higher in ASD participants than in TD participants, and results were significant in females with ASD rather than in males with ASD (all P < 0.05). In toddlers with ASD, the CC volumes were increased and more pronounced in females than in males. This could be due to overgrowth of axons or/and axonal pruning disorders.

Sex differences in the association of vital exhaustion with regional fat deposition and subclinical cardiovascular disease risk

ObjectiveVital exhaustion (VE) is more strongly associated with cardiovascular disease (CVD) risk for women than men. This study examined whether sex differences in associations of VE with CVD risk markers are accounted for by unique associations of VE with regional adiposity. MethodsThe study enrolled 143 persons (18–55 years) without diagnosed conditions. VE was assessed by the Maastricht questionnaire. CVD indices were measured using the euglycemic-hyperinsulinemia clamp, resting blood pressure, and blood draws. Regional adiposity was measured using computed tomography and 2-D echocardiography. This cross-sectional study employed a path analysis approach, including relevant covariates. ResultsOf the cohort, aged 38.7 ± 8.4 years, 65% were men, and 41% were obese. The final model had excellent fit (χ2(36) = 36.5, p = .45; RMSEA = 0.009, CFI = 0.999). For women, but not men, the model indicated paths from VE to: 1) lower insulin sensitivity (B = −0.10, p = .04), and higher total cholesterol to HDL ratio (B = 0.12, p = .09), triglycerides (B = 0.10, p = .08), and C-reactive protein (B = 0.08, p = .09) through visceral adiposity; 2) higher mean arterial pressure (B = 0.14, p = .04), lower insulin sensitivity (B = −0.09, p = .08), and higher C-reactive protein (B = 0.12, p = .07) through subcutaneous adiposity; 3) lower insulin sensitivity (B = −0.07, p = .08) and higher total cholesterol to HDL ratio (B = 0.16, p = .03) through liver adiposity; and 4) higher C-reactive protein (B = 0.08, p = .09) through epicardial adiposity. ConclusionResults extend prior evidence by showing that the association of VE with CVD risk in women is linked with specific regional adiposity elevation. Further study of adiposity-related mechanisms in women who experience early decline in vitality may inform clinical targets for CVD prevention.