Estrogen-Based Gender-Affirming Hormone Therapy and Subclinical Cardiovascular Disease in Transgender Women with HIV.

Purpose: Transgender women (TW) are disproportionately affected by HIV infection and cardiovascular disease (CVD). This study evaluated whether estrogen-based gender-affirming hormone therapy (GAHT) in TW with HIV (TWH-GAHT) is associated with indices of subclinical CVD. Methods: Of the 40 HIV-seropositive persons enrolled, 20-60 years of age, on antiretroviral treatment with undetectable viral load, assessments were performed on 15 TWH; of these persons, 11 were GAHT treated. These TWH-GAHT were matched with HIV+ cisgender men and women based on age, ethnicity/race, body mass index, and antihypertensive medication use. Sex hormones, and cardiometabolic (waist circumference, blood pressure, insulin resistance, lipid profile, and C-reactive protein), vascular (flow-mediated dilation [FMD] and arterial stiffness), and proinflammatory measures were obtained. Results: TWH-GAHT displayed elevated estradiol and suppressed testosterone levels relative to normative ranges. Analyses indicated the TWH-GAHT displayed lower low-density lipoprotein compared with cisgender groups (p < 0.05). Although no difference was seen on FMD, the central augmentation index of aortic stiffness was higher in cisgender HIV+ women than cisgender HIV+ men (p < 0.05). No other group difference on subclinical CVD markers was observed. For TWH, partial correlations indicated associations of certain sex hormones with selected cardiometabolic outcomes and the inflammatory cytokine, interleukin-8. Conclusion: When well matched to HIV+ cisgender men and women, subclinical CVD pathophysiology did not appear elevated in TWH-GAHT, although tendencies emerged suggesting that some subclinical CVD indices may be higher, but others lower than cisgender groups. Longitudinal studies of TWH are needed to more precisely evaluate the moderating effect of GAHT on cardiometabolic pathophysiology.

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

OBJECTIVE: Vital 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. METHODS: The 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. RESULTS: Of 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. CONCLUSION: Results 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.

Abacavir antiretroviral therapy and indices of subclinical vascular disease in persons with HIV.

OBJECTIVE: Indices of cardiovascular disease (CVD) risk, vascular endothelial dilation, arterial stiffness and endothelial repair were examined in persons with HIV (PWH) on an antiretroviral therapy (ART) that included abacavir (ABC+) in comparison with PWH on ART without abacavir (ABC-), and with HIV seronegative (HIV-) individuals. APPROACH: The 115 participants (63% men), aged 30-50 years, did not have CVD, metabolic, endocrine, or chronic renal conditions. PWH were on stable ART for six-months or more. Vascular assessments included flow-mediated dilation (FMD), aortic, radial and femoral arterial stiffness (cAIx, crPWV, cfPWV), and thigh and calf arterial compliance (Vmax50). Endothelial repair was indexed by endothelial progenitor cell colony forming units (EPC-CFU). Traditional CVD risk measures included blood pressure, central adiposity, lipids, insulin resistance (HOMA-IR), CRP and ASCVD score. Analyses controlled for demographics (age, sex, education), medications (antihypertensive, statin/fibrate, antipsychotic), and substance abuse (ASSIST). RESULTS: No group differences were observed in central adiposity, HOMA-IR, CRP, or ASCVD risk score. However, the ABC- group displayed greater dyslipidemia. The ABC+ group displayed no difference on FMD, cAIx, cfPWV or calf Vmax50 compared with other groups. When CD4 count and viral load were controlled, no additional differences between the ABC+ and ABC- groups emerged. Analyses of crPWV and thigh Vmax50 suggested supported by a trend toward lower EPC-CFU in the HIV+ groups than the HIV- group. CONCLUSIONS: Findings indicate that ABC treatment of 30-50 year-old PWH on stable ART is not likely to contribute in a robust way to higher CVD risk.

A genetic association study of tobacco withdrawal endophenotypes in African Americans.

Genome-wide association (GWA) genetic epidemiology research has identified several variants modestly associated with brief self-report smoking measures, predominately in European Americans. GWA research has not applied intensive laboratory-based measures of smoking endophenotypes in African Americans-a population with disproportionately low quit smoking rates and high tobacco-related disease risk. This genetic epidemiology study of non-Hispanic African Americans tested associations of 89 genetic variants identified in previous GWA research and exploratory GWAs with 24 laboratory-derived tobacco withdrawal endophenotypes. African American cigarette smokers (N = 528; ≥10 cig/day; 36.2% female) completed two counterbalanced visits following either 16-hr of tobacco deprivation or ad libitum smoking. At both visits, self-report and behavioral measures across six unique "sub-phenotype" domains within the tobacco withdrawal syndrome were assessed (Urge/Craving, Negative Affect, Low Positive Affect, Cognition, Hunger, and Motivation to Resume Smoking). Results of the candidate variant analysis found two significant small-magnitude associations. The rs11915747 alternate allele in the CAD2M gene region was associated with .09 larger deprivation-induced changes in reported impulsivity (0-4 scale). The rs2471711alternate allele in the AC097480.1/AC097480.2 gene region was associated with 0.26 lower deprivation-induced changes in confusion (0-4 scale). For both variants, associations were opposite in direction to previous research. Individual genetic variants may exert only weak influences on tobacco withdrawal in African Americans. Larger sample sizes of non-European ancestry individuals might be needed to investigate both known and novel loci that may be ancestry-specific. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Elucidating mechanisms of quality-of-life disparities in Hispanic women with breast cancer: An examination of disease stage, coping, and affect.

OBJECTIVES: Compared to non-Hispanic white (NHW) women, Hispanic women with breast cancer (BCa) are more likely to be diagnosed at later stages of disease and experience reduced quality of life (QOL) following diagnosis. We hypothesized that the demands of later-stage disease results in a perceived inability to cope and greater distress for Hispanic women, resulting in decreased QOL. METHODS: Hispanic (51%) and NHW (49%) women (N = 198) with newly diagnosed stage 0-3 BCa in Miami were enrolled in two trials between 2006 and 2019. In this cross-sectional analysis, a multiple-group structural equation modeling approach was applied to baseline measures of coping confidence (Measure of Current Status Scale), negative and positive affect (Affect Balance Scale), QOL (Functional Assessment of Cancer Therapy - Breast), and disease stage. RESULTS: In our model, later-stage disease was not associated with worse QOL for Hispanic or NHW women. However, there were differences between Hispanic and NHW women on the path from disease stage to (1) coping confidence, (2) positive affect, and (3) negative affect, such that later disease stage was associated with lower coping confidence (b[SE] = -1.75[0.59], p = 0.002), less positive affect (b[SE] = -0.21[0.10], p = 0.026), and greater negative affect (b[SE] = 0.15[0.08], p = 0.052) among Hispanic, but not NHW, women. In addition, an indirect effect was found from greater stage to poorer QOL via less positive affect among Hispanic women only (b[SE] = -0.49[0.24], p = 0.041). CONCLUSIONS: This data supports our theory that Hispanic women experience worse emotional distress at later-stage disease than do NHW women, in turn impacting QOL.

Longitudinal Associations Between Anhedonia and Body Mass Index Trajectory Groups Among Adolescents.

PURPOSE: Although evidence suggests that anhedonia-a reduced ability to experience pleasure in response to rewarding stimuli-may predict weight gain during adolescence, it remains unclear whether changes in anhedonia during adolescence are associated with changes in body mass index (BMI). This study examines longitudinal associations between changes in anhedonia and developmental trajectories of BMI during adolescence. METHODS: Self-report measures of anhedonia and BMI were collected at five semiannual assessments among students from 10 high schools in Los Angeles, CA, area (N = 3,396) followed up from the 9th grade to the 11th grade. Four BMI trajectories were identified using growth mixture modeling: (1) stable normative weight; (2) overweight to normative weight (i.e., decreasing BMI); (3) overweight to chronically obese (increasing BMI); and (4) normative weight to overweight (increasing BMI). Latent growth curve modeling estimated baseline level and changes in anhedonia. A multinomial logistic regression model tested associations of baseline level and slope of anhedonia with the four BMI trajectory groups. RESULTS: Compared with the stable normative BMI trajectory group, each 1-unit standard deviation increase in anhedonia slope increased the odds of membership in the overweight to chronically obese group (odds ratio [OR] [95% confidence interval {CI}] = 1.29 [1.09-1.49], p < .001) and in the normative weight to overweight group (OR [95% CI] = 1.28 [1.04-1.53], p = .006), and decreased the odds of membership in the overweight to normative weight group (OR [95% CI] = .78 [.57-.95], p = .01). CONCLUSIONS: Across a 2-year period of high school, the rate of change in anhedonia is associated with certain BMI trajectories linked with poorer metabolic health. Increasing anhedonia may be an important risk factor to consider in adolescent obesity prevention.

Rewarding effects of physical activity predict sensitivity to the acute subjective effects of d-amphetamine in healthy volunteers.

While individual differences in reward sensitivity are believed to generalize across drugs and alternative rewards, this notion has received little empirical attention in human research. Here, we tested whether individual differences in the subjective rewarding effects of physical activity were associated with the subjective response to d-amphetamine administration. Healthy volunteers ( n=95; age 18-35 years) completed questionnaires measuring the self-reported pleasurable effects of physical activity and other covariates, and this was followed by two double-blind counterbalanced sessions during which they received either 20 mg oral d-amphetamine or placebo. Subjective drug effects measures were collected before and repeatedly after drug administration. Subjective d-amphetamine-related effects were then reduced via principal components analysis into latent factors of "positive mood," "arousal," and "drug high." Multiple regression models controlling for placebo-related scores, session order, demographics, body mass index, level of physical activity, and use of other drugs showed that degree of self-reported physical activity reward was positively associated with d-amphetamine-induced positive mood and arousal ( ßs≥0.25, ps≤0.04), but was not associated with d-amphetamine-induced changes in drug high ( ß=0.13, p=0.24). These results provide novel evidence suggesting that individual differences in reward sensitivity cross over between d-amphetamine reward and physical activity reward in humans.

Pharmacogenetics of stimulant abuse liability: association of CDH13 variant with amphetamine response in a racially-heterogeneous sample of healthy young adults.

RATIONALE: A previous genome-wide association study (GWAS) in a predominately Caucasian sample of healthy young adults linked greater amphetamine-induced rewarding effects with the rs3784943 G allele of the cadherin 13 (CDH13; i.e., a cell adhesion molecule implicated in neuronal connectivity) gene. This association has not been subsequently examined, nor has it been studied in Asian populations, which may have greater frequencies of the risk allele. OBJECTIVE: The objective of this study was to examine the association of rs3784943 with amphetamine response in a racially heterogeneous sample (37 % Asian) of healthy young adults. METHODS: Participants (N = 84; 18-35 years old) genotyped for rs3784943 completed counterbalanced sessions involving 20 mg oral d-amphetamine or placebo administration. At both sessions, cardiovascular and subjective drug effects measures were collected. RESULTS: In the combined racially heterogeneous sample, amphetamine (vs. placebo) effects were significantly greater on "Feel Drug" ratings (p < 0.05) and marginally greater on "Feel High" ratings and systolic blood pressure (p < 0.10) in G/A + G/G genotypes than A/A genotypes. The G allele was more common among Asian than other racial groups. Among the subsample of Asian participants (N = 31), drug effects were significantly greater on Feel Drug (p < 0.05) and marginally greater on Feel High and heart rate (p < 0.10) among Asians with G/A + G/G (vs. A/A) genotypes. CONCLUSIONS: In concert with a previous GWAS result, this candidate gene study provides convergent evidence implicating CDH13 rs3784943 variant in d-amphetamine's drug effect profile and suggests generalization to Asian populations. CDH13 and genes coding for other cell adhesion molecules may be worthy of study in the biology of psychostimulant abuse liability.