Prevalence and Predictors of Cardiovascular Disease and Risk Factors in Transgender Persons in the United States.

BACKGROUND: The cardiovascular health of transgender and gender diverse (TGD) persons, a growing population in the United States, has become a subject of heightened interest. We sought to assess the prevalence and predictors of cardiovascular disease (CVD) in transgender men, transgender women, and gender nonconforming persons in the United States. METHODS: A cohort of individuals self-identified as TGD (ie, transgender or gender nonconforming) in the United States was identified using the 2018 Centers for Disease Control's Behavioral Risk Factor Surveillance Survey. RESULTS: Among the 1019 TGD individuals studied, 378 (37.1%) identified their transition status as male-to-female, 394 (38.7%) as female-to-male, and the remaining 247 (24.2%) as gender nonconforming. A total of 138 (13.5%) had reported CVD, while 881 (86.5%) did not. The prevalence of CVD in TGD individuals identified as male-to-female, female-to-male, and gender nonconforming were noted to be similar (14.6% vs. 13.5% vs. 12.1%; P = 0.69). TGD persons with CVD were older with lower annual income. They also had higher rates of smoking, lower rates of regular exercise, and higher rates of smoking and chronic medical comorbidities. Independent predictors of CVD in TGD persons included older age, diabetes, chronic kidney disease, chronic obstructive pulmonary disease, and depressive disorder. CONCLUSIONS: In this contemporary cross-sectional nationally representative survey, CVD was prevalent in nearly 14% of TGD persons. Further studies examining interventions to reduce CV risk and enhance access to medical care in the TGD population are warranted.

Complex Rab4-Mediated Regulation of Endosomal Size and EGFR Activation.

Early sorting endosomes are responsible for the trafficking and function of transferrin receptor (TfR) and EGFR. These receptors play important roles in iron uptake and signaling and are critical for breast cancer development. However, the role of morphology, receptor composition, and signaling of early endosomes in breast cancer remains poorly understood. A novel population of enlarged early endosomes was identified in breast cancer cells and tumor xenografts but not in noncancerous MCF10A cells. Quantitative analysis of endosomal morphology, cargo sorting, EGFR activation, and Rab GTPase regulation was performed using super-resolution and confocal microscopy followed by 3D rendering. MDA-MB-231 breast cancer cells have fewer, but larger EEA1-positive early endosomes compared with MCF10A cells. Live-cell imaging indicated dysregulated cargo sorting, because EGF and Tf traffic together via enlarged endosomes in MDA-MB-231, but not in MCF10A. Large EEA1-positive MDA-MB-231 endosomes exhibited prolonged and increased EGF-induced activation of EGFR upon phosphorylation at tyrosine-1068 (EGFR-p1068). Rab4A overexpression in MCF10A cells produced EEA1-positive enlarged endosomes that displayed prolonged and amplified EGF-induced EGFR-p1068 activation. Knockdown of Rab4A lead to increased endosomal size in MCF10A, but not in MDA-MB-231 cells. Nevertheless, Rab4A knockdown resulted in enhanced EGF-induced activation of EGFR-p1068 in MDA-MB-231 as well as downstream signaling in MCF10A cells. Altogether, this extensive characterization of early endosomes in breast cancer cells has identified a Rab4-modulated enlarged early endosomal compartment as the site of prolonged and increased EGFR activation. IMPLICATIONS: Enlarged early endosomes play a Rab4-modulated role in regulation of EGFR activation in breast cancer cells.

Impact of Sex on Survival and Neurologic Outcomes in Adults With In-Hospital Cardiac Arrest.

Data regarding the impact of sex on clinical outcomes in adults with in-hospital cardiac arrest (IHCA) have yielded conflicting results. We aimed to study the impact of female sex on mortality and poor neurologic outcomes in adults with IHCA. The study population included 680 consecutive patients hospitalized with IHCA who underwent ACLS-guided resuscitation from 2012 to 2018 at an academic tertiary medical center. The primary outcome of interest was in-hospital mortality. Secondary outcome of interest was favorable neurological outcome, defined as a Glasgow Outcome Score of 4 or 5. Of the 680 patients studied, 418 (61.5%) were men and 262 (38.5%) were women. Women had lower rates of coronary artery disease, previous myocardial infarction, and peripheral artery disease, and higher rates of chronic obstructive pulmonary disease and depression. Although location of cardiac arrest, initial rhythm, and duration of cardiopulmonary resuscitation were similar in both groups, women had lower rates of defibrillation. Rates of return of spontaneous circulation and receipt of targeted temperature management were similar in men and women. With respect to outcomes, women were noted to have significantly higher rates of in-hospital mortality (87.5% vs 78.0%; p = 0.001) and lower rates of favorable neurologic outcome (10.0% vs 15.8%, p = 0.030) compared with men. In multivariable analyses, female sex was independently associated with nearly two-fold higher rates of in-hospital mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.22-3.04, p = 0.005] and a trend toward lower rates of favorable neurologic outcome (OR 0.63, 95% CI 0.38-1.04, p = 0.071). In conclusion, in this prospective, contemporary registry of adults with IHCA, female sex was independently associated with nearly twofold higher rates of in-hospital mortality and a trend toward lower rates of favorable neurologic outcomes.

Relation of Body Mass Index and Gender to Left Atrial Size and Atrial Fibrillation.

Increased body mass index (BMI) and obesity are associated with greater risk of atrial fibrillation (AF). However, whether this correlation is independent and gender specific remains unclear. The objective of this study was to characterize the relation between BMI, left atrial (LA) size, and presence of AF and determine whether this association is gender specific. We prospectively studied 499 patients who underwent a transthoracic echocardiogram at an academic tertiary care medical center. Clinical and echocardiographic data were obtained. The primary outcome of interest was the presence of AF. Of 499 patients studied, 240 (48.1%) were men and 259 (51.9%) were women. Of these, 151 (30.1%) had normal BMI, 181 (36.3%) were overweight, and 167 (33.5%) were obese. Obese patients were younger and had larger LA diameters, LA areas (LAAs), and LA volumes (LAVs). Rates of AF were similar among the BMI classes in the overall population and in men and women separately. In multivariate analysis, BMI and gender were both independently associated with LA diameter, LAA, and LAV. Age (odds ratio 1.02, 95% CI 1.00 to 1.04, p = 0.023) and LA diameter (odds ratio 2.52, 95% CI 1.61 to 3.97, p <0.001) were the only determinants of the presence of AF in the overall population. BMI and gender were not independently associated with AF. In this observational study, our findings demonstrate that higher BMI and male gender were independently associated with greater LA diameter, LAA, and LAV. Older age and greater LA diameter were independently associated with higher rates of AF, whereas BMI and gender were not.