Sex Differences In Risk Research Articles

Absence of Consistent Sex Differences in Outcomes From Symptomatic Carotid Endarterectomy and Stenting Randomized Trials.

CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) reported a higher periprocedural risk for any stroke, death, or myocardial infarction for women randomized to carotid artery stenting (CAS) compared with women randomized to carotid endarterectomy (CEA). No difference in risk by treatment was detected for women relative to men in the 4-year primary outcome. We aimed to conduct a pooled analysis among symptomatic patients in large randomized trials to provide more precise estimates of sex differences in the CAS-to-CEA risk for any stroke or death during the 120-day periprocedural period and ipsilateral stroke thereafter. Data from the Carotid Stenosis Trialists' Collaboration included outcomes from symptomatic patients in EVA-3S (Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis), SPACE (Stent-Protected Angioplasty Versus Carotid Endarterectomy in Symptomatic Patients), ICSS (International Carotid Stenting Study), and CREST. The primary outcome was any stroke or death within 120 days after randomization and ipsilateral stroke thereafter. Event rates and relative risks were estimated using Poisson regression; effect modification by sex was assessed with a sex-by-treatment-by-trial interaction term, with significant interaction defined a priori as P≤0.10. Over a median 2.7 years of follow-up, 433 outcomes occurred in 3317 men and 1437 women. The CAS-to-CEA relative risk of the primary outcome was significantly lower for women compared with men in 1 trial, nominally lower in another, and nominally higher in the other two. The sex-by-treatment-by-trial interaction term was significant (P=0.065), indicating heterogeneity among trials. Contributors to this heterogeneity are primarily differences in periprocedural period. When the trials are nevertheless pooled, there were no significant sex differences in risk in any follow-up period. There were significant differences between trials in the magnitude of sex differences in treatment effect (CAS-to-CEA relative risk), indicating pooling data from these trials to estimate sex differences might not be valid. Whether sex is acting as an effect modifier of the CAS-to-CEA treatment effect in symptomatic patients remains uncertain. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00190398 (EVA-3S) and NCT00004732 (CREST). URL: https://www.isrctn.com; Unique identifier: ISRCTN57874028 (SPACE) and ISRCTN25337470 (ICSS).

Potentially Inappropriate Drug Duplication in a Cohort of Older Adults with Dementia

BackgroundConcurrent use of 2 nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, loop diuretics, angiotensin-converting enzyme inhibitors, or anticoagulants is considered potentially inappropriate by Screening Tool of Older Persons' Prescriptions and Screening Tool to Alert to Right Treatment criteria.ObjectiveThe objective was to examine drug duplication in a cohort of older adults with dementia.MethodsCohort entry for Nova Scotia Seniors’ Pharmacare Program beneficiaries was the date an International Classification of Diseases ninth edition or 10th edition code for dementia was recorded in accessed databases between March 1, 2005, and March 31, 2015. Medication dispensation and sociodemographic data were captured from the Nova Scotia Seniors’ Pharmacare Program database between April 1, 2010, and March 31, 2015. Duplication was considered when 2 drugs from the same class were dispensed such that the supply in the patient's possession could overlap for more than 30 days. We reported number of cases of duplication and duration of overlap. Sex differences in drug duplication were assessed with bivariate logistic regression.ResultsIn the cohort of 28,953 Nova Scotia Seniors’ Pharmacare Program beneficiaries with dementia, we documented concurrent use in 101 (1.7%) nonsteroidal anti-inflammatory drugs users (mean duration = 75.6 days), 95 (1.0%) selective serotonin reuptake inhibitors users (mean duration = 146.6 days), 5 (0.07%) loop diuretic users (mean duration = 530.6 days), 183 (2.0%) angiotensin-converting enzyme inhibitor users (mean duration = 123.9 days), and 160 (3.5%) anticoagulant users (mean duration = 63.6 days). Nonsteroidal anti-inflammatory drug pairs were most commonly celecoxib with naproxen or diclofenac. Selective serotonin reuptake inhibitors duplication was most commonly sertraline with citalopram. No sex differences in risk for drug duplication were identified.ConclusionsDrug duplication was identified in a cohort of older adults with dementia and is a feasible target for intervention. (Curr Ther Res Clin Exp. 2021; 82:XXX–XXX)

Sex Differences in Extrahepatic Outcomes After Antiviral Treatment for Hepatitis C.

Despite recognized differences in the rates of cardiovascular and renal disease between men and women in the general population, studies of the downstream effects of antiviral treatment for hepatitis C (HCV) have not investigated differences in outcomes based on sex. We analyzed sex differences in risk of acute coronary syndrome (ACS), end-stage renal disease (ESRD), and ischemic stroke by treatment and response in a large US-based multisite cohort of HCV patients. Observation started at the HCV diagnosis date (untreated) or last antiviral treatment start (treated). Treatment selection bias was addressed using an inverse probability-weighting approach. We estimated the effect of treatment on the cumulative incidence of outcomes using the Fine-Gray method (subdistribution hazard ratios [sHR] and 95% confidence intervals [95% CI]). Death was a competing risk. Roughly 40% of 15,295 HCV patients were women. After controlling for other risk factors, sustained virological response (SVR) (interferon-based [IFN] or direct-acting antiviral [DAA]) significantly reduced risk of all outcomes, particularly among female patients. Female patients who achieved SVR after IFN-based treatment had significantly lower risk of ACS compared with male patients with SVR from either treatment type (sHR 0.45 [95% CI 0.35-0.59] vs 0.81 [95% CI 0.69-0.96, for DAA SVR] and sHR 0.72 [95% 0.62, 0.85, for IFN SVR]). Successful treatment seemed to be most protective against ESRD; female patients who achieved SVR were at 66%-68% lower risk than untreated patients (sHR 0.32 [95% CI 0.17-0.60 for DAA SVR] and 0.34 [95% CI 0.20-0.58 for IFN SVR]), whereas men were at 38%-42% lower risk (sHR 0.62 [95% CI 0.46-0.85 for DAA SVR] and 0.58 [95% CI 0.43-0.76 for IFN SVR]). IFN treatment failure significantly increased risk of all outcomes by 50%-100% among female patients. Compared with no treatment, female patients who experienced IFN treatment failure were at 63% increased risk of ACS (sHR 1.63 [95% CI 1.35-1.96]), almost twice the risk of ESRD (sHR 1.95 [95% CI 1.43-2.66]) and 51% increased risk of stroke (sHR 1.49 [95%CI 1.11-2.00]). SVR reduced the risk of extrahepatic complications, particularly in females. The significantly increased risk associated with IFN TF in women-a subset who represented roughly 10% of that group-underscores the importance of prioritizing these patients for DAA treatment irrespective of the fibrosis stage.

Abstract 15749: Sex-differences in Coronary Heart Disease Between Individuals With Familial Hypercholesterolemia and Controls in Norway During 1992-2017

Introduction: During the last 30 years, treatment of familial hypercholesterolemia (FH) has been revolutionized, but it is not known if both sexes equally benefit in these advances, and whether this could have affected the sex difference in risk of coronary heart disease (CHD). We aimed to study sex difference in the risk of CHD between men and women with FH compared to non-FH men and women. Methods: We obtained data on CHD hospitalization and death from Norwegian health registries in 4,525 individuals diagnosed with FH between 1992 and 2014 and an age and sex matched control population of 88,892. The sex distribution was about 50/50 between women and men, and the mean age at start of follow-up was 36 years. Results: The cumulative incidence of CHD (FH vs. non-FH controls) in women and men are shown in Figure 1 with a clear increased risk in FH compared to controls. The cumulative incidence starts to increase at a younger age in men compared with women, both in FH and non-FH controls. This corresponds to an age adjusted 2.6-fold higher risk of CHD in men compared with women in both the FH and control population. In the FH population, men aged 20-39 years had a hazard ratio (HR) of 5.3 (95% CI: 2.6-10.9) compared with women, whereas the corresponding HR between women and men in non-FH controls was 3.7 (95% CI: 2.6-5.3). There was no significant interaction between sex and FH status, indicating that the excess risk in men was similar in FH and non-FH controls. Stratified by sex and adjusted for age, we found that both men and women with FH had a 2-fold higher risk of CHD than controls. The highest excess risk was observed in ages 20-30 years with a of HR= 4.5 (95% CI: 2.2-9.2) and a HR of= 5.5 (95%CI: 4.60-9.34) in women and men, respectively. Conclusions: The risk of CHD among individuals with FH was higher in men than in women in all age groups presented, with no differences between the FH sample and the non-FH controls. However, the relative risk in FH compared with controls was similar for both sexes.

No Sex Differences in Risk for Lower-Extremity Musculoskeletal Injury in Concussed Amateur Rugby Players

To examine sex differences between concussion and lower-extremity musculoskeletal injury (LE-MSI) in community male and female rugby players. There is an ∼2x elevated risk of post-concussion subsequent MSI in high school through professional athletes. However, the effect of sex on risk is inconsistent and sparse, and rugby provides an ideal population as it's the only collision sport with the same rules for both sexes. 1,037 rugby players (31.6 + 11.3 years, 59.1% male), with at least one year of rugby playing experience, participated in this study, completing an online injury history questionnaire to ascertain concussion (yes/no) and LE-MSI (yes/no) history. A chi-squared test was performed to determine the association between concussion and any LE-MSI; significant findings were followed up with a post hoc odds ratio test. A binary logistic regression with any LE-MSI (yes/no) as the outcome and concussion (yes/no) and sex (male/female) as predictors was performed to determine if there was a sex by concussion interaction. There was a significant association between concussion and any LE-MSI for all groups (Overall: ?(1) =13.06, p < 0.001, OR = 2.30 [95% CI: 1.45-3.65]; Males: ?(1) =7.43 p = 0.006, OR = 2.21 [95% CI: 1.24-3.96]; and Females: ?(1) = 5.78, p = 0.016, OR = 2.48 [95% CI: 1.16-5.31]). However, there were no differences for risk of LE-MSI between males and females (p = 0.99, R2 = 0.024). Both male and female community rugby players had a 2x greater risk of LE-MSI, given a history of concussion compared to those without a history of concussion, which aligns with previous studies focused on collegiate athletes. However, there was no difference in risk of LE-MSI between sexes, contrary to smaller, but more controlled studies. Future research should investigate the potential physiological mechanisms for increased risk of LE-MSI.

Regulation of risky decision making by gonadal hormones in males and females.

Psychiatric diseases characterized by dysregulated risky decision making are differentially represented in males and females. The factors that govern such sex differences, however, remain poorly understood. Using a task in which rats make discrete trial choices between a small, "safe" food reward and a large food reward accompanied by varying probabilities of footshock punishment, we recently showed that females are more risk averse than males. The objective of the current experiments was to test the extent to which these sex differences in risky decision making are mediated by gonadal hormones. Male and female rats were trained in the risky decision-making task, followed by ovariectomy (OVX), orchiectomy (ORX), or sham surgery. Rats were then retested in the task, under both baseline conditions and following administration of estradiol and/or testosterone. OVX increased choice of the large, risky reward (increased risky choice), an effect that was attenuated by estradiol administration. In contrast, ORX decreased risky choice, but testosterone administration was without effect in either ORX or sham males. Estradiol, however, decreased risky choice in both groups of males. Importantly, none of the effects of hormonal manipulation on risky choice were due to altered shock sensitivity or food motivation. These data show that gonadal hormones are required for maintaining sex-typical profiles of risk-taking behavior in both males and females, and that estradiol is sufficient to promote risk aversion in both sexes. The findings provide novel information about the mechanisms supporting sex differences in risk taking and may prove useful in understanding sex differences in the prevalence of psychiatric diseases associated with altered risk taking.

Cholesteryl Ester Transfer Protein Impairs Triglyceride Clearance via Androgen Receptor in Male Mice.

Elevated postprandial triacylglycerols (TAG) are an important risk factor for cardiovascular disease. Men have higher plasma TAG and impaired TAG clearance compared to women, which may contribute to sex differences in risk of cardiovascular disease. Understanding mechanisms of sex differences in TAG metabolism may yield novel therapeutic targets to prevent cardiovascular disease. Cholesteryl ester transfer protein (CETP) is a lipid shuttling protein known for its effects on high‐density lipoprotein (HDL) cholesterol levels. Although mice lack CETP, we previously demonstrated that transgenic CETP expression in female mice alters TAG metabolism. The impact of CETP on TAG metabolism in males, however, is not well understood. Here, we demonstrate that CETP expression increases plasma TAG in males, especially in very‐low density lipoprotein (VLDL), by impairing postprandial plasma TAG clearance compared to wild‐type (WT) males. Gonadal hormones were required for CETP to impair TAG clearance, suggesting a role for sex hormones for this effect. Testosterone replacement in the setting of gonadectomy was sufficient to restore the effect of CETP on TAG. Lastly, liver androgen receptor (AR) was required for CETP to increase plasma TAG. Thus, expression of CETP in males raises plasma TAG by impairing TAG clearance via testosterone signaling to AR. Further understanding of how CETP and androgen signaling impair TAG clearance may lead to novel approaches to reduce TAG and mitigate risk of cardiovascular disease.

Sex differences in the risk of diabetes mellitus among individuals with psoriasis: A retrospective cohort study in Québec, Canada

Sex differences in the risk of diabetes mellitus among individuals with psoriasis: A retrospective cohort study in Québec, Canada

Approaching Sex Differences in Cardiovascular Non-Coding RNA Research.

Cardiovascular disease (CVD) is the biggest cause of sickness and mortality worldwide in both males and females. Clinical statistics demonstrate clear sex differences in risk, prevalence, mortality rates, and response to treatment for different entities of CVD. The reason for this remains poorly understood. Non-coding RNAs (ncRNAs) are emerging as key mediators and biomarkers of CVD. Similarly, current knowledge on differential regulation, expression, and pathology-associated function of ncRNAs between sexes is minimal. Here, we provide a state-of-the-art overview of what is known on sex differences in ncRNA research in CVD as well as discussing the contributing biological factors to this sex dimorphism including genetic and epigenetic factors and sex hormone regulation of transcription. We then focus on the experimental models of CVD and their use in translational ncRNA research in the cardiovascular field. In particular, we want to highlight the importance of considering sex of the cellular and pre-clinical models in clinical studies in ncRNA research and to carefully consider the appropriate experimental models most applicable to human patient populations. Moreover, we aim to identify sex-specific targets for treatment and diagnosis for the biggest socioeconomic health problem globally.

Low Risk of Progression of Barrett's Esophagus to Neoplasia in Women.

Men are at a higher risk for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), but little is known about BE progression to dysplasia and EAC in women. We performed a retrospective, multicenter cohort study to assess risk of BE progression to dysplasia and EAC in women compared with men. We also investigated comorbidities, medication use, and endoscopic features that contribute to sex differences in risk of BE progression. We collected data from large cohort of patients with BE seen at 6 centers in the United States and Europe, followed for a median 5.7 years. We obtained demographic information (age, sex, ethnicity), clinical history (tobacco use, body mass index, comorbidities), endoscopy results (procedure date, BE segment length), and histopathology findings. Neoplasia was graded as low-grade dysplasia, high-grade dysplasia (HGD), or EAC. Rates of disease progression between women and men were compared using χ2 analysis and the Student t test. Multivariable logistic regression was used to assess the association between sex and disease progression after adjusting for possible confounding variables. Of the total 4263 patients in the cohort, 2145 met the inclusion criteria, including 324 (15%) women. There was a total of 34 (1.6%) incident EACs, with an overall annual incidence of 0.3% (95% confidence interval: 0.2%-0.4%). We found significant differences between women and men in annual incidence rates of EAC (0.05% for women vs. 0.3% in men; P=0.04) and in the combined endpoint of HGD or EAC (0.1% for women vs. 1.1% for men; P<0.001). Female gender was an independent predictor for reduced progression to HGD or EAC when rates of progression were adjusted for body mass index, smoking history, race, use of aspirin, nonsteroidal anti-inflammatory drugs, proton-pump inhibitors, or statins, hypertriglyceridemia, BE length, and histology findings at baseline (hazard ratio: 0.11; 95% confidence interval: 0.03-0.45; P=0.002). In a multicenter study of men versus women with BE, we found a significantly lower risk of disease progression to cancer and HGD in women. The extremely low risk of EAC in women with BE (0.05%/y) indicates that surveillance endoscopy may not be necessary for this subgroup of patients with BE.

Sex differences in risk of Alzheimer's disease in adults with Down syndrome.

IntroductionAdults with Down syndrome (DS) older than 40 have Alzheimer's disease (AD) neuropathology and high risk for dementia, but little is known about the relationship of sex to AD risk in this population.MethodsUsing nonparametric methods and Cox proportional hazards models we analyzed differences in incidence of dementia, by sex, presence of an apolipoprotein E (APOE) ε4 or ε2 allele, and dementia duration and decline in 246 adults over 40 with DS.ResultsThere was no significant sex difference in risk of AD or rate of cognitive decline. APOE ε4 allele significantly increased risk of AD irrespective of sex. No significant interactions were found between sex and APOE status on AD risk. Among those who died, dementia duration was significantly longer in women.DiscussionThis study showed no effect of sex nor interaction between sex and APOE for risk of AD in adults with DS; however, women had longer dementia duration.

Sex differences in adult famine mortality in medieval London.

Recurrent famine events during the medieval period might have contributed to excess mortality during the Black Death in London, England (c. 1349-1350). Previous research using conventional methods of age estimation revealed that adult males experienced lower risks of mortality under "normal" (attritional) but not famine mortality conditions following the Black Death. However, given the biases inherent in conventional age estimation methods, this study reassesses sex differences in risks of medieval adult famine mortality using ages estimated via transition analysis, which avoids some of the limitations of conventional age estimation methods. We apply hazards analysis (the Gompertz model of adult mortality) to ages estimated for human skeletal remains (n = 1245) from London cemeteries dated to the pre-Black Death (c. 1000-1250 CE) and post-Black Death (c. 1350-1540 CE) periods. The results reveal no sex differences in risks of mortality before the Black Death but indicate that adult males faced lower risks of mortality after the Black Death during conditions of normal and famine mortality. These findings largely support those of our previous research, which suggested that selective mortality during the Black Death or sex-biased improvements in standard of living following the epidemic reduced risk of mortality for adult males in the post-Black Death period under normal mortality conditions. However, the use of transition analysis age estimates also revealed a reduced risk of mortality for post-Black Death adult males under famine conditions.

P3681Apparent sex differences in risk of life-threatening events in arrhythmogenic cardiomyopathy are related to exercise habits

Abstract Background Arrhythmogenic cardiomyopathy (AC) is an inheritable heart disease characterized by high risk of ventricular arrhythmias and exercise intolerance. Male sex is associated with higher risk of life-threatening events. However, this may be challenged by the fact that men exercise more than women. Purpose To assess whether the sex differences in arrhythmic outcome in AC-patients are driven by sex differences in exercise exposure. Methods We included AC-patients diagnosed between 1997 and 2017 in a longitudinal cohort study. We assessed exercise habits during the preceding 3 years before inclusion, and exercise dose was expressed as metabolic equivalent hours per week (MET-hours/week). Life-threatening events were defined as sustained ventricular tachycardia, aborted cardiac arrest or appropriate therapy from an implantable cardioverter-defibrillator at the time of diagnosis and prospectively during follow-up. Results We included 170 AC-patients (52% probands, 44% female, age 41±16 years). Males had higher exercise doses than female patients (36 [IQR, 14 to 54] vs. 12 [IQR, 8 to 22] MET-hours/week; P&lt;0.001). Fifty-seven patients (34%) had previous life-threatening events, and 45 (26%) had life-threatening events during 5.7 (IQR, 2.8 to 9.4) years of follow-up. Male sex seemed to be a marker of previous life-threatening events (OR 2.0 [95% CI, 1.0 to 3.8]; P&lt;0.05), but not when adjusted for exercise dose (Adjusted OR 1.3 [95% CI, 0.6 to 2.7]; P=0.44). Male sex also seemed to be a predictor of life-threatening events during follow-up (HR 2.0 [95% CI 1.0 to 3.9]; P=0.04) (Figure, left panel), but not when adjusted for exercise dose (Adjusted HR 1.5 [95% CI 0.8 to 3.0]; P=0.26) (Figure, right panel). Conclusions Sex differences in arrhythmic risk in AC were attributable to higher exercise doses in male AC-patients. This highlights the importance of exercise assessment in these patients, and challenges the current opinion of male sex as a risk factor in itself. Risk stratification based on sex may underestimate the risk of physically active female AC-patients. Acknowledgement/Funding This study was supported by Center for Cardiological Innovation funded by the Norwegian Research Council

Anthropometric changes and risk of diabetes: are there sex differences? A longitudinal study of Alberta’s Tomorrow Project

ObjectivesTo characterise the sex-specific difference in the association between anthropometric changes and risk of diabetes in the general population in Canada.Setting and participantsFrom 2000 to 2008, Alberta’s Tomorrow Project (ATP)...

Methylomic profiles reveal sex-specific differences in leukocyte composition associated with post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a debilitating mental disorder precipitated by trauma exposure. However, only some persons exposed to trauma develop PTSD. There are sex differences in risk; twice as many women as men develop a lifetime diagnosis of PTSD. Methylomic profiles derived from peripheral blood are well-suited for investigating PTSD because DNA methylation (DNAm) encodes individual response to trauma and may play a key role in the immune dysregulation characteristic of PTSD pathophysiology. In the current study, we leveraged recent methodological advances to investigate sex-specific differences in DNAm-based leukocyte composition that are associated with lifetime PTSD. We estimated leukocyte composition on a combined methylation array dataset (483 participants, ∼450 k CpG sites) consisting of two civilian cohorts, the Detroit Neighborhood Health Study and Grady Trauma Project. Sex-stratified Mann-Whitney U test and two-way ANCOVA revealed that lifetime PTSD was associated with significantly higher monocyte proportions in males, but not in females (Holm-adjusted p-val < 0.05). No difference in monocyte proportions was observed between current and remitted PTSD cases in males, suggesting that this sex-specific difference may reflect a long-standing trait of lifetime history of PTSD, rather than current state of PTSD. Associations with lifetime PTSD or PTSD status were not observed in any other leukocyte subtype and our finding in monocytes was confirmed using cell estimates based on a different deconvolution algorithm, suggesting that our sex-specific findings are robust across cell estimation approaches. Overall, our main finding of elevated monocyte proportions in males, but not in females with lifetime history of PTSD provides evidence for a sex-specific difference in peripheral blood leukocyte composition that is detectable in methylomic profiles and that may reflect long-standing changes associated with PTSD diagnosis.

Sugar in mind: Untangling a sweet and sour relationship beyond type 2 diabetes.

It is widely recognised that type 2 diabetes (T2D) represents a major disease burden but it is only recently that its role in neurodegeneration has attracted more attention. This research has shown that T2D is associated with impaired cerebral health, cognitive decline and dementia. However, the impact on the brain of progressive metabolic changes associated with the pre-clinical development of the disease is less clear. The aim of this review is to comprehensively summarise how the emergence of risk factors and co-morbid conditions linked to the development of T2D impact cerebral health. Particular attention is directed at characterising how normal but elevated blood glucose levels in individuals without T2D contribute to neurodegenerative processes, and how the main risk factors for T2D including obesity, physical activity and diet modulate these effects. Where available, evidence from the animal and human literature is contrasted, and sex differences in risk and outcomes are highlighted.

Sex differences in the expression of cell adhesion molecules on microvesicles derived from cultured human brain microvascular endothelial cells treated with inflammatory and thrombotic stimuli

BackgroundThere are sex differences in risk for stroke and small vessel ischemic disease in the brain. Microvesicles (MV) derived from activated cells vary by cell of origin and the stimulus initiating their release. MV released from cells activated by inflammatory and thrombotic factors have the potential to disrupt endothelial cells of the brain microvasculature. Therefore, experiments were designed to identify sex differences in the phenotype of MV released from cultured human brain microvascular endothelial cells (HBMEC) in response to inflammatory and thrombotic stimuli.MethodsCultured HBMEC derived from 20- to 30-year-old male and female donors were treated for 20 h with medium supplemented with tumor necrosis factor alpha (TNFα; 20 ng/ml), thrombin (THR; 2 U/ml), or vehicle (i.e., control). MV were isolated from the conditioned media by high-speed centrifugation and quantified by digital flow cytometry by labeling with fluorophore-conjugated primary antibodies against PECAM-1, integrin αvβ3, ICAM-1, E-selectin, or MCAM. In addition, temporal uptake of labeled MV into control HBMEC was examined by confocal microscopy.ResultsUnder control conditions, male HBMEC released fewer MV expressing each antigen, except for PECAM-1, than female cells (P < 0.05). Neither TNFα nor THR reduced cell viability. However, TNFα induced apoptosis in female and male cells, whereas THR increased apoptosis marginally only in male cells. TNFα increased expression of all antigens tested on MV in male cells, but only increased expression of integrin αvβ3, ICAM-1, and E-selectin on MV from female cells. THR increased expression of PECAM-1, ICAM-1, and MCAM-1 on MV from male but not female cells. MV were internalized and localized to lysosomes within 90 min after their application to HBMEC.ConclusionsThere are sex differences in expression of cell adhesion molecules on MV released from HBMEC under control conditions and upon activation by TNFα or THR. MV taken up by unstimulated HBMEC may impact the integrity of the brain microvasculature and account, in part, for sex differences in vascular pathologies in the brain.

0755 Sleep Disorder Diagnosis and Sex Differences in Risk of Depressive Symptoms in an Adolescent Sleep Clinic Patient Sample

0755 Sleep Disorder Diagnosis and Sex Differences in Risk of Depressive Symptoms in an Adolescent Sleep Clinic Patient Sample

Sex Differences in 1-Year Rehospitalization for Heart Failure and Myocardial Infarction After Primary Percutaneous Coronary Intervention

It is unclear whether universal access to primary percutaneous coronary intervention (pPCI) may reduce sex differences in 1-year rehospitalization for heart failure (HF) and myocardial infarction (MI) after ST-elevation myocardial infarction (STEMI). We studied 7,597 consecutive STEMI patients (13.8% women, n = 1,045) who underwent pPCI from January 2007 to December 2013. Cox regression models adjusted for competing risk from death were used to assess sex differences in rehospitalization for HF and MI within 1 year from discharge. Compared with men, women were older (median age 67.6 vs 56.0 years, p < 0.001) with higher prevalence of co-morbidities and multivessel disease. Women had longer median door-to-balloon time (76 vs 66 minutes, p < 0.001) and were less likely to receive drug-eluting stents (19.5% vs 24.1%, p = 0.001). Of the medications prescribed at discharge, fewer women received aspirin (95.8% vs 97.6%, p = 0.002) and P2Y12 antagonists (97.6% vs 98.5%, p = 0.039), but there were no significant sex differences in other discharge medications. After adjusting for differences in baseline characteristics and treatment, sex differences in risk of rehospitalization for HF attenuated (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.79 to 1.40), but persisted for MI (HR 1.68, 95% CI 1.22 to 2.33), with greater disparity in patients aged ≥60 years (HR 1.83, 95% CI 1.18 to 2.85) than those aged <60 years (HR 1.45, 95% CI 0.84 to 2.50). In conclusion, in a setting of universal access to pPCI, the adjusted risk of 1-year rehospitalization for HF was similar in both sexes, but women had significantly higher adjusted risk of 1-year rehospitalization for MI, especially older women.

Sex Differences in Risk Factors for Incident Atrial Fibrillation (from the Reasons for Geographic and Racial Differences in Stroke [REGARDS] Study)

We examined whether the sex differences in atrial fibrillation (AF) is related to difference in risk factors leading to AF or due to a differential impact of the same risk factors in 11,806 participants (55.2 % women) from the REGARDS study. Incident AF was ascertained by electrocardiograms and medical history at a follow-up examination. Backwards elimination logistic regression was used to identify AF risk factors in men and women, separately. Over a median follow-up of 9.0years, 588 (11.1%) men and 428 (6.6%) women (p value <0.001) developed AF. Men had a higher risk of AF than women (age and race adjusted odds ratio [OR] [95% confidence interval (CI)]: 1.61 [1.26, 1.75]). Age, white race, height, weight, use of blood pressure lowering medications and history of cardiovascular disease were identified by backward elimination as AF risk factors shared by both sexes. On the other hand, diabetes was an AF risk factor in women but not in men. Among the shared risk factors between men and women, only age showed a stronger association in women than in men [Interaction p-value = 0.003]. Adjustment for the shared risk factors eliminated the sex difference in AF risk (OR [95% CI]: 0.90 [0.74, 1.09]), which was more noticeable in those younger than the median age (62 years) compared to those who were older (interaction p value 0.003). In conclusion, women and men share several AF risk factors, and these shared risk factors explain the sex differences. However, age association with AF differs by sex, and age modifies the associations between sex and other AF risk factors.