Sex-stratified Models Research Articles

Abstract 4141457: Forms of Childhood Maltreatment and Subclinical Cardiovascular Disease Risk in Black men and women

Background: Exposure to specific forms of childhood maltreatment have been associated with cardiovascular disease (CVD) risk factors and CVD events in adulthood. Heterogenous experiences of childhood maltreatment across race and sex exist, yet there is little evidence regarding these relationships and CVD risk in Black populations. Aims: To investigate the association between various forms of childhood maltreatment (emotional, general, physical, and sexual abuse) and surrogate markers of vascular dysfunction and test whether sex modify these associations. Methods: Forms of childhood maltreatment and indices of vascular function were assessed in a cohort of healthy Black adults without known CVD (n=404) from a large metropolitan southeastern city. Childhood maltreatment was assessed using the Early Trauma Inventory short form (ETISR-SF) consisting of physical, sexual, emotional, and general domains. A trauma severity index score was calculated by summing the indexes for each of the four domains. Higher scores are indicative of higher traumatic life events before age 18 years. Outcomes of central augmentation index (cAIx) corrected for a heart rate of 75 bpm and carotid femoral pulse wave velocity (CfPWV) were measured as indices of wave reflections and arterial stiffness using applanation tonometry (Sphygmocor Inc.), and central pulse pressure (CPP) was calculated as the difference between the aortic systolic and diastolic blood pressures. Associations between each domain and outcomes were assessed using multivariate-adjusted and sex-stratified linear regression models. Results: Mean age of the cohort was 53 + 10.3 years, 61% women. Exposure to emotional [ b = -1.5%, 95%CI: -2.7,-0.3] and physical abuse [ b = -1.3%, 95%CI: -2.5,-0.2] was associated with cAIx overall but not CPP or CfPWV after adjusting for sociodemographic, clinical factors, health behaviors, and depressive symptoms. Significant emotional abuseXsex ( P= 0.014) and physical abuseXsex ( P=< 0.001) interactions were identified for cAIx. Among women, physical abuse was associated with higher cAIx [ b =1.5%, 95%CI: 0.6, 2.4] and among men emotional [ b =-1.6%, 95%CI: -3.2, -0.0] and physical [ b =-1.7%, 95%CI: -3.1, -0.3] abuse was associated with lower cAIx. Conclusions: Exposure to emotional and physical abuse as children was associated with vascular dysfunction; moreover, exposure to physical abuse among women and not men have adverse clinical implications for CVD risk and prospects for enhanced preventive care.

Abstract 4125263: Influence of sexual orientation-related nondiscrimination laws on 30-year CVD risk among sexual minority and heterosexual adults

Introduction: Discriminatory policies are associated with worse mental health and substance use outcomes among sexual minority adults. Despite a higher risk of cardiovascular disease (CVD) than heterosexual adults, there is limited evidence on structural determinants of cardiovascular health among sexual minority adults. Therefore, we examined whether changes in sexual orientation-related nondiscrimination laws were associated with 30-year CVD risk among sexual minority and heterosexual adults. Hypothesis: We hypothesized that changes in sexual orientation-related nondiscrimination laws would be more strongly associated with 30-year CVD risk among sexual minority adults relative to exclusively heterosexual adults. Methods: We used longitudinal data from Waves III (2001-2002), IV (2008-2009), and V (2016-2018) of the National Longitudinal Study of Adolescent to Adult Health. We assessed changes in four state-level sexual orientation-related nondiscrimination laws (i.e., employment discrimination, same-sex marriage, hate crime statutes, and same-sex adoption) between Waves III and IV. Changes in sexual orientation-related nondiscrimination laws were categorized as unchanged (reference), improved, or worsened. We assessed 30-year CVD risk using the Framingham Risk Score at Wave V. We ran sex-stratified linear regression models adjusted for demographic factors to examine whether the association between change in nondiscrimination laws with 30-year CVD risk was moderated by sexual orientation (i.e., exclusively heterosexual, mostly heterosexual, homosexual/bisexual). Results: The sample included 3,827 participants with a mean age of 28.7 (±1.75) years, of whom 83.1% identified as exclusively heterosexual, 51% as female, and 15% as Black. Compared to heterosexual participants of the same sex, an improvement in nondiscrimination laws was associated with lower 30-year CVD risk among mostly heterosexual women (B -4.57, 95% CI = -8.06, -1.08) and homosexual/bisexual men (B -10.91, 95% CI = -19.33, -2.49). In contrast, compared to exclusively heterosexual women, a worsening of nondiscrimination laws was associated with higher 30-year CVD risk among homosexual/bisexual women (B 5.26, 95% CI = 0.30, 10.21). No differences were found between mostly heterosexual and exclusively heterosexual men. Conclusions: Findings suggest that efforts to enhance policies prohibiting sexual orientation-related discrimination may significantly reduce CVD risk among sexual minority adults.

Estimation of individual lifetime cardiovascular disease risk and treatment benefit in patients with established atherosclerotic cardiovascular disease: the updated SMART-REACH2 model

Abstract Background The 2021 ESC Guidelines on Cardiovascular Disease (CVD) Prevention in Clinical Practice recommend using (lifetime) risk to guide preventive treatment intensification. Purpose Updating and systematically recalibrating the SMART-REACH lifetime prediction model for the estimation of lifetime risk of recurrent CVD in patients with established atherosclerotic CVD (ASCVD) to various European and international risk regions. Methods The updated SMART-REACH (i.e., SMART-REACH2) model was derived using data from 9,477 individuals between 40-90 years with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms included in the UCC-SMART cohort in whom 2,090 ASCVD events were observed during a median follow-up of 8.9 years (interquartile range 4.5–14.1). Coefficients for type of CVD, estimated glomerular filtration rate, non-high density lipoprotein cholesterol, systolic blood pressure, duration of CVD, C-reactive protein, current smoking, and presence of diabetes were derived using sex-stratified cause-specific Cox models with age as the time axis, adjusted for the competing risk of non-CVD mortality. Lifetables were used to estimate 10-year and lifetime CVD-risk and CVD-free life expectancy. The SMART-REACH2 model was externally validated in 121,701 patients from the NOR-COR, Nor-COAST, HUNT3, SWEDEHEART, Bialystok PLUS/Polaspire, REACH-EU, and REACH non-EU (Asia, Japan, Latin America, North America) covering 43 countries. The model was recalibrated to specific risk regions based on the expected-observed ratios from representative cohorts. Performance was assessed by calibration of predicted and observed risk and Harrel’s C-statistic for discrimination. Results 16,689ASCVD events were observed in the external validation cohorts. The model was visually well calibrated for the various risk regions. The pooled C-statistic across risk regions was 0.665 [95% confidence interval 0.640-0.691], with adequate performance in the separate regions (Figure 1). Using SMART-REACH2 to estimate potential gain in CVD-free life expectancy upon treatment initiation showed varying projections. For example, two comparable 55-year-old males from the low-risk region and very high-risk region would gain an estimated 2.2 and 3.9 CVD-free life years as a result of smoking cessation (Figure 2). Conclusion(s) By using larger and more contemporary data sources, considering geographical differences, and extending the age range, the updated SMART-REACH2 model provides an improved algorithm for the estimation of lifetime risk and CVD-free life expectancy for individuals with established ASCVD, facilitating shared decision-making for cardiovascular prevention as recommended by the 2021 ESC Prevention of CVD guidelines.C-statistics across global risk regionsCase vignette

Patterns of Alcohol, Cannabis, and E-Cigarette Use/Co-Use and Mental Health Among U.S. College Students

Background Substance use and mental health are highly correlated, though few studies assess the risk for depression and anxiety associated with dual and polysubstance use among college students. The purpose of this study was to characterize the relationship between alcohol, cannabis, and e-cigarette exclusive, dual, and polysubstance use and depression and anxiety among U.S. college students by racial and ethnic subgroup and stratified by sex. Methods Data from 83,467 undergraduate students participating in the 2020–2021 Health Minds Survey, a multi-campus, web-based survey, were used. Sex-stratified logistic regression models examined the effects of exclusive (past 30-day cannabis use, past 30-day e-cigarette use, past 2-week heavy alcohol use), dual (two among cannabis, e-cigarette, or alcohol use), and polysubstance (all three substances) use on anxiety (≥10 GAD-7 score) and depression (≥15 PHQ-9 score). Results The study included 60,746 females and 22,721 males. Among females, compared to those who exclusively used alcohol, dual users of cannabis and e-cigarette had the largest odds for depression (adjusted odds ratio (aOR) = 1.92) and anxiety (aOR = 1.69) followed by polysubstance users (aORs = 1.85 and 1.53, respectively). Among males, compared to those who exclusively used alcohol, dual users of cannabis and e-cigarette had the largest odds for depression (aOR = 2.72) and anxiety (aOR = 2.23) followed by polysubstance users (aOR = 1.71 and 1.85, respectively). African American female and male students had lower odds of anxiety and depression compared to White students. Conclusions The results suggest that single, dual, and polysubstance use are associated with anxiety and depression among U.S. college students, though not necessarily in additive ways.

Major depression recurrence is associated with differences in obesity-related traits in women, but not in men.

Obesity-related cardiometabolic comorbidity is common in major depressive disorder (MDD). However, sex differences and MDD recurrence may modify the MDD-obesity-link. Sex-specific associations of MDD recurrence (single [MDDS] or recurrent episodes [MDDR]) and obesity-related traits were analyzed in 4.100 adults (51.6% women) from a cross-sectional population-based cohort in Germany (SHIP-Trend-0). DSM-IV-based lifetime MDD diagnoses and MDD recurrence status were obtained through diagnostic interviews. Obesity-related outcomes included anthropometrics (weight, body mass index, waist- and hip-circumference, waist-to-hip ratio, waist-to-height ratio), bioelectrical impedance analysis of body fat mass and fat-free mass, and subcutaneous (SAT) and visceral adipose tissue (VAT) from abdominal magnetic resonance imaging. Sex-stratified linear regression models predicting obesity-related traits from MDD recurrence status were adjusted for age, education, and current depressive symptoms. 790 participants (19.3%) fulfilled lifetime MDD criteria (23.8% women vs. 14.5% men, p<0.001). In women, MDDS was inversely associated with anthropometric indicators of general and central obesity, while MDDR was positively associated with all obesity-related traits, except waist-to-hip ratio and fat-free mass. In women, MDDR versus MDDS was associated with higher levels of obesity across all outcomes except fat-free mass. In men, MDD was positively associated with SAT regardless of MDD recurrence. Additionally, lifetime MDD was positively associated with VAT in men. Results remained significant in sensitivity analyses after exclusion of participants with current use of antidepressants. The MDD-obesity association is modified by MDD recurrence and sex independent of current depressive symptoms. Accounting for sex and MDD recurrence may identify individuals with MDD at increased cardiometabolic risk.

Myocardial Infarction Quality of Care and Outcomes in Asian Ethnic Groups in the United States.

National-level differences in myocardial infarction (MI) quality of care among Asian patients in the United States are unclear. We assessed the quality of MI care in the 6 largest US Asian ethnic groups. Patients aged ≥18 years with ST-segment-elevation MI or non-ST-segment-elevation MI in the Get With The Guidelines-Coronary Artery Disease registry (711 US hospitals, 2015-2021) were assessed. The odds of MI-related quality of care and process outcomes were evaluated in Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, and other Asian adults compared with non-Hispanic White adults. Sex-stratified logistic regression models were adjusted for age and clinical characteristics. There were 5691 Asian patients (1520 Asian Indian, 422 Chinese, 430 Filipino, 114 Japanese, 283 Korean, 553 Vietnamese, and 2369 other Asian) and 141 271 non-Hispanic White patients, overall 30% female, and mean age of 66.5 years. Relative to non-Hispanic White adults, among patients with ST-segment-elevation MI, door-to-ECG time ≤10 minutes was less likely in Asian Indian (adjusted odds ratio [aOR], 0.64 [95% CI, 0.50-0.82]), Chinese (aOR, 0.65 [95% CI, 0.46-0.93]), and Korean (aOR, 0.57 [95% CI, 0.33-0.97]) men and in other Asian women (aOR, 0.61 [95% CI, 0.41-0.90]). Door-to-balloon time ≤90 minutes was less likely in Asian Indian men (aOR, 0.71 [95% CI, 0.56-0.90]) and Filipina women (aOR, 0.48 [95% CI, 0.24-0.98]). In patients with ST-segment-elevation MI or non-ST-segment-elevation MI, optimal medical therapy for MI was less likely in Korean men (aOR, 0.65 [95% CI, 0.47-0.90]) and more likely in Asian Indian men (aOR, 1.22 [95% CI, 1.06-1.40]) and women (aOR, 1.32 [95% CI, 1.04-1.67]) and Filipina women (aOR, 1.84 [95% CI, 1.27-2.67]). MI quality of care varies among US Asian patients with ST-segment-elevation MI and non-ST-segment-elevation MI. Quality improvement programs must identify and address the factors that result in suboptimal MI quality of care among US Asian patients.

Parental perceptions of neighborhood safety and preschool children's outdoor play: An exploration of sex and safety type differences

Despite the growing evidence on the influence of neighborhood safety on physical activity, few studies have specifically focused on preschool-aged children and differentiated the various domains of neighborhood safety. This study investigates the relationship between parental perceptions of neighborhood safety and preschool children's time spent outdoors and explores potential sex differences in this relationship. This study analyzed nationally representative data from 1656 Korean children (848 boys and 808 girls) aged 3, 5, 6 years collected over the course of three waves of the Panel Study on Korean Children (PSKC). Outdoor playtime was measured by maternal reports of the time their children spent playing outdoors on a typical weekday. Parental perceptions of neighborhood safety were assessed using two items that inquired about neighborhood safety in terms of crime and accidents, respectively. Fixed effects estimates revealed that parental perceptions of social safety were associated with an increase in children's outdoor physical activity (b = 3.778, p < 0.05), whereas perceptions of physical safety were not. Sex-stratified models showed that the association between parental perceptions of social safety and children's outdoor play was driven largely by boys (b = 8.498, p < 0.001), with no association observed for girls. The findings of this study underscore the importance of addressing the social safety of neighborhood environments to promote outdoor play in preschool children. Moreover, sex differences should be considered when developing interventions aimed at increasing physical activity among young children.

Serial gait speed measurements over time and dynamic survival prediction in older adults

BackgroundA one-time gait speed measurement predicts mortality risk. A framework for updating a clinician’s mortality risk perception with new information from each clinic visit is needed. We used joint modeling of longitudinal and survival data for dynamic prediction of mortality risk. MethodsWe fit sex-stratified joint models to 20-meter (bi)annual longitudinal gait speed measured every 6 months and 14-year survival data from the Health, Aging and Body Composition Study allowing for non-linear fluctuations of gait speed and controlling for important covariates such as age, recent hospitalization, blood pressure, obesity, and comorbidities. ResultsParticipants (N = 3048) were 74 years old with gait speed 1.18 m/s. They were 42% Black, and 52% died over 14 years. Higher gait speed of 0.1 m/s was associated with 23% (95% confidence interval or CI = 20–25%) and 25% (CI = 21–28%) reductions in mortality risk in men and women; and a 0.05 m/s annualized slowing (slope) with 31% (CI = 13–51%) increase in men (all p < 0.05), with findings persisting after covariate adjustment. Distant gait speed history over a year prior contributed little for mortality risk prediction with mean change of only 1–2% in 5-year risk. ConclusionThe two most recent gait speeds appear sufficient to consider for mortality risk in the present initial analysis. More frequent gait speeds need to be considered in mortality risk prediction before definitive conclusions supporting real-world application.

Exposure to multiple ambient air pollutants changes white matter microstructure during early adolescence with sex-specific differences

BackgroundAir pollution is ubiquitous, yet questions remain regarding its impact on the developing brain. Large changes occur in white matter microstructure across adolescence, with notable differences by sex.MethodsWe investigate sex-stratified effects of annual exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) at ages 9–10 years on longitudinal patterns of white matter microstructure over a 2-year period. Diffusion-weighted imaging was collected on 3T MRI scanners for 8182 participants (1–2 scans per subject; 45% with two scans) from the Adolescent Brain Cognitive Development (ABCD) Study®. Restriction spectrum imaging was performed to quantify intracellular isotropic (RNI) and directional (RND) diffusion. Ensemble-based air pollution concentrations were assigned to each child’s primary residential address. Multi-pollutant, sex-stratified linear mixed-effect models assessed associations between pollutants and RNI/RND with age over time, adjusting for sociodemographic factors.ResultsHere we show higher PM2.5 exposure is associated with higher RND at age 9 in both sexes, with no significant effects of PM2.5 on RNI/RND change over time. Higher NO2 exposure is associated with higher RNI at age 9 in both sexes, as well as attenuating RNI over time in females. Higher O3 exposure is associated with differences in RND and RNI at age 9, as well as changes in RND and RNI over time in both sexes.ConclusionsCriteria air pollutants influence patterns of white matter maturation between 9–13 years old, with some sex-specific differences in the magnitude and anatomical locations of affected tracts. This occurs at concentrations that are below current U.S. standards, suggesting exposure to low-level pollution during adolescence may have long-term consequences.

DNA methylation near MAD1L1, KDM2B, and SOCS3 mediates the effect of socioeconomic status on elevated body mass index in African American adults.

Obesity and poverty disproportionally affect African American persons. Epigenetic mechanisms could partially explain the association between socioeconomic disadvantage and body mass index (BMI). We examined the extent to which epigenetic mechanisms mediate the effect of socioeconomic status (SES) on BMI. Using data from African American adults from the Atherosclerosis Risk in Communities (ARIC) Study (n = 2664, mean age = 57years), education, income, and occupation were used to create a composite SES score at visit 1 (1987-1989). We conducted two methylation-wide association analyses to identify associations between SES (visit 1), BMI and cytosine-phosphate-guanine (CpG) sites measured at a subsequent visit (1990-1995). We then utilized structural equation modeling (SEM) to test whether identified sites mediated the association between earlier SES and BMI in sex-stratified models adjusted for demographic and risk factor covariates. Independent replication and meta-analyses were conducted using the Jackson Heart Study (JHS, n = 874, mean age 51years, 2000-2004). Three CpG sites near MAD1L1, KDM2B, and SOCS3 (cg05095590, cg1370865, and cg18181703) were suggestively associated (P-value < 1.3×10-5) in ARIC and at array-wide significance (P-value < 1.3×10-7) in a combined meta-analysis of ARIC with JHS. SEM of these three sites revealed significant indirect effects in females (P-value < 5.8×10-3), each mediating 7%-20% of the total effect of SES on BMI. Nominally significant indirect effects were observed for two sites near MAD1L1 and KDM2B in males (P-value < 3.4×10-2), mediating -17 and -22% of the SES-BMI effect. These results provide further evidence that epigenetic modifications may be a potential pathway through which SES may "get under the skin" and contribute to downstream health disparities.

Imaging-based body fat distribution and diabetic retinopathy in general US population with diabetes: an NHANES analysis (2003–2006 and 2011–2018)

BackgroundLimited studies have investigated the correlation between fat distribution and the risk of diabetic retinopathy (DR) in the general population with diabetes. The relationship between obesity and DR remains inconclusive, possibly due to using simple anthropometric measures to define obesity. This study investigates the relationships between the android-to-gynoid fat ratio (A/G ratio, measured using dual-energy X-ray absorptiometry) and DR within the US population with diabetes.MethodsThe study used a population-based, cross-sectional approach based on the 2003–2006 and 2011–2018 data of the National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression analyses were performed on participants with diabetes to evaluate the contribution of body mass index (BMI), waist-to-height ratio (WHtR), and A/G ratio to the prevalence of DR.ResultsThe prevalence of DR was 22.2, 21.2, and 17.6% among participants with A/G ratios <1.0, 1.0–1.2, and ≥1.2, respectively. After adjusting sex, age, ethnicity, diabetes duration, hemoglobin A1c level, blood pressure level, and non-high-density lipoprotein cholesterol level, a higher A/G ratio (≥1.2) was independently associated with decreased odds of DR (odds ratio [OR], 0.565; 95% CI: 0.372–0.858) compared with the A/G ratio of 1.0–1.2. Associations between a higher A/G ratio and DR remained statistically significant after adjusting for BMI (OR, 0.567; 95% CI: 0.373–0.861) and WHtR (OR, 0.586; 95% CI: 0.379–0.907). Moreover, these associations remained statistically significant in analyses using the ethnic-specific tertiles for the A/G ratio. In sex-stratified models, these correlations remained in males. There was a significant inverse association between the A/G ratio and diabetes duration in males, which persisted after multivariable adjustments (p < 0.05).ConclusionsA novel finding indicates that a higher A/G ratio is associated with a reduced likelihood of DR in males with diabetes. The results from NHANES underscore the importance of considering imaging-based fat distribution as a critical indicator in clinical practice.

Premature Death, Suicide, and Nonlethal Intentional Self-Harm After Psychiatric Discharge

There is a need for representative research on serious adverse outcomes following discharge from psychiatric hospitalization. To compare rates of premature death, suicide, and nonlethal intentional self-harm after psychiatric discharge with rates in the general population and investigate associations of these outcomes with relevant variables associated with the index psychiatric hospitalization. This retrospective cohort study included all residents from Catalonia, Spain (7.6 million population), who had psychiatric hospitalizations between January 1, 2014, and December 31, 2018, and were older than 10 years at the index (first) hospitalization. Follow-up was until December 31, 2019. Statistical analysis was performed from December 1, 2022, through April 11, 2024. Socioeconomic status, psychiatric diagnoses, duration of index hospitalization, and number of previous psychiatric hospitalizations. Postdischarge premature death (ie, all-cause death before age 70 years) and suicide (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code range X60-X84), identified using mortality data, and postdischarge nonlethal intentional self-harm, identified using electronic health record and self-harm case register data. Standardized mortality ratios (SMRs) compared rates of premature death and suicide between the cohort and the general population. Fully adjusted, multivariable, cause-specific Cox proportional hazards regression models for the 3 outcomes were fitted. A total of 49 108 patients discharged from psychiatric hospitalization were included (25 833 males [52.6%]; mean [SD] age at discharge, 44.2 [18.2] years). During follow-up, 2260 patients (4.6%) died prematurely, 437 (0.9%) died by suicide, and 4752 (9.7%) had an episode of nonlethal intentional self-harm. The overall SMR for premature death was 7.5 (95% CI, 7.2-7.9). For suicide, SMR was 32.9 (95% CI, 29.9-36.0) overall and was especially high among females (47.6 [95% CI, 40.2-54.9]). In fully adjusted sex-stratified hazard models, postdischarge premature death was associated with cognitive disorders (adjusted hazard ratio [AHR], 2.89 [95% CI, 2.24-3.74] for females; 2.59 [95% CI, 2.17-3.08] for males) and alcohol-related disorders (AHR, 1.41 [95% CI, 1.18-1.70] for females; 1.22 [95% CI, 1.09-1.37] for males). Postdischarge suicide was associated with postdischarge intentional self-harm (AHR, 2.83 [95% CI, 1.97-4.05] for females; 3.29 [95% CI, 2.47-4.40] for males), with depressive disorders (AHR, 2.13 [95% CI, 1.52-2.97]) and adjustment disorders (AHR, 1.94 [95% CI, 1.32-2.83]) among males, and with bipolar disorder among females (AHR, 1.94 [95% CI, 1.21-3.09]). Postdischarge intentional self-harm was associated with index admissions for intentional self-harm (AHR, 1.95 [95% CI, 1.73-2.21] for females; 2.62 [95% CI, 2.20-3.13] for males) as well as for adjustment disorders (AHR, 1.48 [95% CI, 1.33-1.65] for females; 1.99 [95% CI, 1.74-2.27] for males), anxiety disorders (AHR, 1.24 [95% CI, 1.10-1.39] for females; 1.36 [95% CI, 1.18-1.58] for males), depressive disorders (AHR, 1.54 [95% CI, 1.40-1.69] for females; 1.80 [95% CI, 1.58-2.04] for males), and personality disorders (AHR, 1.59 [95% CI, 1.46-1.73] for females; 1.43 [95% CI, 1.28-1.60] for males). In this cohort study of patients discharged from psychiatric hospitalization, risk for premature death and suicide was significantly higher compared with the general population, suggesting individuals discharged from psychiatric inpatient care are a vulnerable population for premature death and suicidal behavior.

The relationship between neighbourhood built characteristics, physical activity, and health-related fitness in urban dwelling Canadian adults: A mediation analysis.

ObjectivePhysical activity supportive environments have the potential to promote health-related fitness in adults. However, the extent to which neighbourhood built characteristics promote health-related fitness via physical activity has received little research attention. Therefore, our objective was to estimate the indirect and direct effects between neighbourhood built characteristics and health-related fitness mediated by physical activity. MethodsUsing cross-sectional data collected between 2014 and 2019, we merged neighbourhood built characteristics, physical activity, and health-related fitness variables, derived from two Canadian national databases. Using these data, we estimated sex-stratified covariate-adjusted path models (males: n = 983 to 2796 and females: n = 962 to 2835) to assess if accelerometer-measured light, moderate, and vigorous intensity physical activity mediated associations between objectively measured neighbourhood built characteristics (intersection density, dwelling density, points of interest, and transit density) and health-related fitness (grip strength, jump height, V̇O2max, and flexibility). Across 16 sex-specific models, we estimated 48 indirect and 16 direct effects. ResultsConcerning significant associations, for males we found that 16.6% of indirect and 18.8% of direct were negative and 4.2% of indirect and 0% of direct were positive. For females, we found that 12.5% of indirect and 0% of direct were negative and 0% of indirect and 25% of direct effects were positive. ConclusionsIndividual Canadian Active Living Environment built characteristics are positively associated with moderate-intensity physical activity and negatively associated with light-intensity physical activity. Further, associations between activity friendly neighbourhood characteristics and health related-fitness may be distinct from physical activity.

Body mass index and astigmatism: A nationwide study.

Existing research on the relationship between body mass index (BMI) and astigmatism yields inconsistent results. This study analyses this association in a nationally representative sample of adolescents. This retrospective, cross-sectional study included Israeli adolescents who underwent medical assessments before mandatory military service between 2011 and 2022. BMI was categorised based on the US age- and sex-matched percentiles. Astigmatism was categorised by magnitude [low-moderate: 0.75 to <3.00 diopters (D), high: ≥3.00 D], and axis orientation [with-the-rule (WTR), against-the-rule (ATR), or oblique (OBL)]. Sex-stratified regression models adjusted for sociodemographic variables were used. Of 935 989 adolescents evaluated, 887 325 were included [511 465 (57.6%) males, mean age 17.2 years]. Astigmatism was diagnosed in 123 675 (13.9%) adolescents, of whom 117 081 (13.2%) had low-moderate and 6594 (0.7%) had high astigmatism. WTR astigmatism was the most prevalent (8.2%), followed by ATR (4.1%) and OBL (1.6%) types. Compared with low-normal BMI (5th to 50th percentile), the adjusted ORs for total astigmatism increased with increasing BMI, peaking at 1.65 (1.57-1.74) in males and 1.74 (1.64-1.86) in females with severe obesity. ORs were accentuated for high astigmatism, reaching 3.51 (3.01-4.09) in males, and 3.45 (2.83-4.22) in females with severe obesity. WTR astigmatism demonstrated the strongest association with BMI, with ORs reaching 2.26 (2.13-2.40) in males and 2.04 (1.90-2.20) in females with severe obesity. The results persisted in a series of subgroup analyses. Obesity is associated with higher odds of astigmatism in adolescence. Further investigation into the role of weight management in astigmatism development is warranted.

Per- and Polyfluoroalkyl Substances May Be Correlated With Chlamydia trachomatis: Data From the National Health and Nutrition Examination Survey 2003-2016.

Per- and polyfluoroalkyl substances (PFAS) alter immune function increasing infectious diseases risk. We examined the relationship between PFAS and chlamydia. A total of 3965 nonpregnant adults ages 18-39 years from the National Nutrition Examination Survey 2003-2016 cycles were included. Poisson regression with robust error variance estimated the prevalence ratio and 95% confidence intervals for the association between PFAS and chlamydia. A g computation model was used to examine PFAS mixtures and chlamydia. In adjusted age and sex-stratified models, an increase in PFAS mixtures by one quintile was associated with chlamydia in older males and younger females. Associations were not observed before stratification. PFAS exposure associated with higher chlamydia prevalence, but only in stratified models suggesting biological differences by gender and age. However, small sample sizes could have affected the precision of our models.

Neighbourhood walkability and greenspace and their associations with health-related fitness in urban dwelling Canadian adults

ObjectiveMuscular strength and body composition are important components of health-related fitness (HRF). Grip strength and body fat percent, in particular, are associated with chronic disease and affected by health behaviours. Evidence suggests relationships between the neighbourhood built environment (BE) and HRF exist, however, few studies have focused on grip strength and body fat percent. Therefore, our study aimed to estimate the sex-specific associations between the neighbourhood BE, grip strength, and body fat percent among urban-dwelling Canadian adults. MethodsWe analyzed cross-sectional survey and HRF data collected in 2011-2015 from 4052 males and 7841 females (Alberta's Tomorrow Project, Canada). Grip strength and body fat percent were measured via handgrip dynamometry and bioelectrical impedance analysis, respectively. Walkability (Canadian Active Living Index) and greenness (Normalized Difference Vegetation Index) estimates were linked to participant data. Sex-stratified covariate-adjusted linear regression models estimated the associations between the BE and HRF variables. ResultsWalkability was negatively associated with grip strength and body fat percent in males (β -0.21, 95%CI: -0.31 to -0.11 and β -0.08, 95%CI: -0.15 to -0.02, respectively) and females (β -0.06, 95%CI: -0.10 to -0.01 and β -0.08, 95%CI: -0.14 to -0.02, respectively). Greenness was positively associated with grip strength in males (β 6.99, 95%CI: 3.62 to 10.36) and females (β 2.72, 95%CI: 1.22 to 4.22) but not with body fat percent. Controlling for physical activity and sitting did not attenuate these associations. ConclusionCharacteristics of the neighbourhood BE appear to be associated with muscular strength and body composition, independent of physical activity and sedentary behaviour.

Sexual minority identifiers and their perception of illicit drug use risks in the US: Results from a National Survey

PurposeThis study examined the relationship between sexual identities and perception of risks associated with illicit drug use among a nationally representative sample of US adults. MethodsWe analyzed data from five waves of the National Survey on Drug Use and Health (NSDUH, 2015–2019), with 205,418 adult participants. Six survey questions assessing participants’ perceptions of the risks associated with illicit drug use (LSD, heroin, and cocaine) were subjected to principal component analysis. Sex-stratified ordered logistic regressions were used to explore potential disparities in perceptions regarding the risk associated with illicit drug use among sexual minority identifiers. ResultsAmong male participants, approximately 11.3% and 1.8% of them perceived illicit drug use as moderate and low risks, respectively. About 6.0% of female participants perceived illicit drug use as moderate risk, and 1.1% of female participants perceived it as low risk. The sex-stratified regression models demonstrated that participants who identified as lesbian/gay or bisexual all had higher odds of reporting low perception of illicit drug use risks as compared to their heterosexual counterparts (all p < 0.01). ConclusionsIllicit drug use prevention strategies should consider risk perception disparities by sexual minority populations.

Examining the Effect of Genes on Depression as Mediated by Smoking and Modified by Sex.

Depression is heritable, differs by sex, and has environmental risk factors such as cigarette smoking. However, the effect of single nucleotide polymorphisms (SNPs) on depression through cigarette smoking and the role of sex is unclear. In order to examine the association of SNPs with depression and smoking in the UK Biobank with replication in the COPDGene study, we used counterfactual-based mediation analysis to test the indirect or mediated effect of SNPs on broad depression through the log of pack-years of cigarette smoking, adjusting for age, sex, current smoking status, and genetic ancestry (via principal components). In secondary analyses, we adjusted for age, sex, current smoking status, genetic ancestry (via principal components), income, education, and living status (urban vs. rural). In addition, we examined sex-stratified mediation models and sex-moderated mediation models. For both analyses, we adjusted for age, current smoking status, and genetic ancestry (via principal components). In the UK Biobank, rs6424532 [LOC105378800] had a statistically significant indirect effect on broad depression through the log of pack-years of cigarette smoking (p = 4.0 × 10-4) among all participants and a marginally significant indirect effect among females (p = 0.02) and males (p = 4.0 × 10-3). Moreover, rs10501696 [GRM5] had a marginally significant indirect effect on broad depression through the log of pack-years of cigarette smoking (p = 0.01) among all participants and a significant indirect effect among females (p = 2.2 × 10-3). In the secondary analyses, the sex-moderated indirect effect was marginally significant for rs10501696 [GRM5] on broad depression through the log of pack-years of cigarette smoking (p = 0.01). In the COPDGene study, the effect of an SNP (rs10501696) in GRM5 on depressive symptoms and medication was mediated by log of pack-years (p = 0.02); however, no SNPs had a sex-moderated mediated effect on depressive symptoms. In the UK Biobank, we found SNPs in two genes [LOC105378800, GRM5] with an indirect effect on broad depression through the log of pack-years of cigarette smoking. In addition, the indirect effect for GRM5 on broad depression through smoking may be moderated by sex. These results suggest that genetic regions associated with broad depression may be mediated by cigarette smoking and this relationship may be moderated by sex.

Gestational PBDE concentrations, persistent externalizing, and emerging internalizing behaviors in adolescents: The HOME study

BackgroundPolybrominated diphenyl ethers (PBDEs) are ubiquitous environmental chemicals used as flame retardants in commercial and consumer products. Gestational PBDE concentrations are associated with adverse behaviors in children; however, the persistence of these associations into adolescence remains understudied. ObjectiveWe estimated the association of gestational PBDE serum concentrations with early adolescent self- and caregiver-reported behaviors at age 12 years and determined the consistency with previously observed associations in childhood with caregiver-reported behaviors in a prospective pregnancy and birth cohort. MethodsWe measured maternal serum concentrations of five individual PBDE congeners and created a summary exposure variable (∑5BDE: 28, −47, −99, −100 and −153) during pregnancy. At age 12 years, we assessed behaviors for 237 adolescents using self- and caregiver-reports with the Behavioral Assessment System for Children-3 (BASC3). We used multivariable linear regression models to estimate covariate-adjusted associations of lipid standardized, log10-transformed gestational PBDE concentrations with BASC3 scores. We obtained estimates and 95% confidence intervals through a bootstrapping approach. We evaluated potential effect measure modification (EMM) of adolescent sex by examining sex-stratified regression models and estimating the EMM p-values. ResultsGestational PBDE concentrations were positively associated with adolescent-reported BASC3 composite indices for inattention & hyperactivity (BDE-28, -47, −99, −100, ∑5BDE), internalizing problems (BDE-28, -47, −99), functional impairment (BDE-28, ∑5BDE), and emotional symptoms (BDE-28). Gestational PBDE concentrations were positively associated with caregiver-reported BASC3 composite indices for externalizing problems (BDE-28, -47, −99, −100, −153, ∑5BDE) and behavioral symptoms (BDE-99). For caregiver reported behaviors, we observed stronger associations with gestational BDE concentrations among males, especially for executive functioning (BDE-28, -47, −99, −100, ∑5BDE). DiscussionGestational PBDE serum concentrations were associated with self-reported internalizing and externalizing behavior problems in early adolescence. Caregiver-reported externalizing behaviors recognized during childhood remain associated with gestational PBDE concentrations and persist into early adolescence. Internalizing behaviors were less recognized by caregivers.

Associations between 47 anthropometric markers derived from a body scanner and relative fat-free mass in a population-based study.

Low relative fat free mass (FFM) is associated with a greater risk of chronic diseases and mortality. Unfortunately, FFM is currently not being measured regularly to allow for individuals therapy. One reason why FFM is not being used may be related to additional equipment and resources, thus we aimed to identify easily accessible anthropometric markers related with FFM. We analyzed data of 1,593 individuals (784 women; 49.2%, age range 28-88 years) enrolled in the population-based Study of Health in Pomerania (SHIP-TREND 1). Forty-seven anthropometric markers were derived from a 3D optical body-scanner. FFM was assessed by bioelectrical impedance analysis (FFMBIA) or air displacement plethysmography (FFMADP). In sex-stratified linear regression models, FFM was regressed on anthropometric measurements adjusted for body height and age. Anthropometric markers were ranked according to the coefficient of determination (R2) derived from these regression models. Circumferences of high hip, belly, middle hip, waist and high waist showed the strongest inverse associations with FFM. These relations were stronger in females than in males. Associations of anthropometric markers with FFMAPD were greater compared to FFMBIA. Anthropometric measures were more strongly associated with FFMADP compared to FFMBIA. Anthropometric markers like circumferences of the high or middle hip, belly or waist may be appropriate surrogates for FFM to aid in individualized therapy. Given that the identified markers are representative of visceral adipose tissue, the connection between whole body strength as surrogate for FFM and fat mass should be explored in more detail.