Impact Of Sex Differences Research Articles

Sex differences in patients with atrial fibrillation and acute coronary syndrome or undergoing PCI: a real-world study

Background In patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI), female patients have a worse short-term prognosis than male patients has been consistently concluded in many studies. However, the impact of sex differences on long-term prognosis remains uncertain. Additionally, women are underrepresented in clinical trials exploring optimal antithrombotic strategies in patients with atrial fibrillation (AF) and ACS or PCI. To bridge this gap, this study aimed to investigate sex differences in clinical characteristics, treatment, and long-term clinical outcomes in patients with AF and ACS or PCI. Patients and methods This study included a total of 1237 patients with AF and ACS and 539 patients with AF and stable coronary artery disease (SCAD) who underwent PCI at the Fuwai Hospital of the Chinese Academy of Medical Sciences from January 2017 to December 2019. Patients were followed up until the end of 2021 to observe the occurrence of major adverse cardiovascular events (MACE). The relationship between sex and MACE was evaluated using Cox regression models and Kaplan–Meier’s survival curves. Results In patients with AF and ACS, multivariable COX regression analysis revealed that female patients were independently associated with a higher risk of MACE (HR = 1.45, 95% CI 1.11–1.89, p = .006). However, in AF patients with SCAD who underwent PCI, the analysis showed that female patients were not independently associated with MACE risk (HR = 1.12, 95% CI 0.62–2.03, p = .717). Conclusions In patients with AF and ACS, females have a significantly higher risk of long-term MACE compared to males. However, among patients with AF and SCAD who underwent PCI, there was no significant difference in long-term MACE risk between males and females.

The impact of sex differences on stroke risk factors and 3-month outcomes in patients receiving thrombolytic therapy for acute ischemic stroke

BackgroundAcute ischemic stroke (AIS) is a major public health issue, and women have a disproportionate share of stroke-related disability and mortality, which is poorly understood. This study aimed to determine the effect of sex differences on AIS treated by thrombolysis using recombinant tissue plasminogen activator (rTPA). The study included 134 AIS patients eligible for rTPA. Risk factors, clinical presentation, thrombolysis response, complications, and outcomes were recorded. The outcomes were measured using the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) 3 months after stroke. The incidence of intracranial haemorrhage was also determined.ResultsAmong 134 AIS patients treated with rTPA (59% male, 41% female), females had higher rates of hypertension (67.3% versus 49.4%, p = 0.040) and atrial fibrillation (AF) (12.7% versus 2.5%, p = 0.020), while smoking was more prevalent in males (31.6% versus 0%, p < 0.0001). Cardioembolism was more frequent in females than in males (23.6% versus 6.3%, p = 0.004). Females also had shorter onset-to-door (110.7 ± 63 versus 131.1 ± 50.2 min, p = 0.035) and onset-to-needle times (151.6 ± 66.5 versus 173.7 ± 50.6 min, p = 0.046). Both sexes showed significant improvements in NIHSS (males: 11.58 ± 3.7 to 6.05 ± 5.6; females: 11.64 ± 4.7 to 6.9 ± 5.9; p < 0.0001) and mRS scores (males: 3.34 ± 1.05 to 2.03 ± 2; females: 3.53 ± 1 to 2.02 ± 2; p < 0.0001) over 3 months, with no significant differences between sexes. Predictors of poor outcome (mRS 3–6) differed: diabetes mellitus (DM) (OR 7.79, p = 0.002) and longer door-to-needle time (OR 1.04, p = 0.008) for males, and hemorrhage (OR 9.41, p = 0.048) for females. Hemorrhage predicted mortality in males (OR 27.08, p < 0.0001), while AF was associated with increased mortality in females (OR 8.06, p = 0.024).ConclusionsThis study revealed sex-specific differences in AIS risk factors, aetiology, and rTPA treatment timelines, although post-treatment improvements were comparable between sexes. Notably, outcome predictors and mortality factors differed by sex. These findings emphasize the need for sex-specific considerations in AIS management and risk assessment.

Rat Model of Menopausal/Andropausal Hypertension with Different Sensitivities to Non-Genomic Antihypertensive Responses of Female and Male Sex Steroids

Introduction: Hypertension is prevalent in older women and men, but the impact of sex differences is unclear. Methods: Blood pressure (BP) was evaluated weekly for 15 weeks using tail-cuff plethysmography in intact or gonadectomized female and male rats. Similarly, gonadectomized rats were subcutaneously treated daily for 15 weeks with estradiol in females or testosterone in males. Treatment with estrogen in males and androgen in females for BP was also examined. The non-genomic antihypertensive potency and efficacy of different sex steroids were determined; catheters were implanted in the carotid artery of hypertensive rats for BP recording with bolus injections in the jugular vein at cumulative doses (1 × 10−7−1 × 10−4M kg−1 min−1) of dehydroepiandrosterone (DHEA), estradiol, testosterone, or 5β-dihydrotestosterone (5β-DHT). Results: Data showed a time-dependent increase in BP after gonadectomy in female and male rats until hypertension values were reached. Males are more sensitive to the development of hypertension than females. The increases in BP in females and males were completely prevented by estradiol or testosterone, respectively. Testosterone completely prevented hypertension in females, whereas estradiol only partially in males. Antihypertensive potencies in conscious hypertensive rats were DHEA = 5β-DHT = testosterone >> estradiol, in females and DHEA = 5β-DHT >> testosterone >> estradiol in males. The efficacy was DHEA = 5β-DHT = testosterone >> estradiol in females and 5β-DHT = DHEA >> testosterone >> estradiol in males. Conclusion: Gonadectomized males developed hypertension faster than females, suggesting that androgen deficiency plays an important role in BP reduction. Antihypertensive responses of steroids are structure-dependent; estradiol demonstrated the lowest potency, whereas 5β-DHT was a potent antihypertensive without estrogenic and androgenic actions, suggesting it is as a therapeutic candidate for controlling hypertension in both sexes.

Trauma, resilience and significant relationships: Sex differences in protective factors for military mental health.

Military service is historically a male-dominated occupation, as such, the majority of research examining the development of mental disorder in Australian Defence Force members has had primarily male samples. While there have been mixed findings internationally regarding sex differences in rates of mental disorder and subthreshold symptoms among military personnel, across studies, the evidence tends to suggest that female military members are at least as likely as males to experience subthreshold mental health symptoms and have similar or higher rates of posttraumatic stress disorder despite the differences in roles during service. What is less understood is the impact of sex differences in symptom emergence over time and in predictors of clinical disorder. The sample included a longitudinal cohort of Australian Defence Force members (N = 8497) surveyed at Time 1 (2010) and followed up at Time 2 (2015) on measures of anger, self-perceived resilience, trauma exposure, deployment exposure, suicidality, help-seeking, relationship satisfaction and mental health disorder symptoms. Outcomes included Subthreshold Disorder (above the optimal screening cut-off on the 10-item Kessler distress scale or posttraumatic stress disorder checklist) and Probable Disorder (above the epidemiological cut-off on the 10-item Kessler distress scale or posttraumatic stress disorder checklist). Results found that while lifetime trauma exposure remained the strongest predictor of later probable disorder emergence among both males and females, for females specifically, self-reported resilience was also a significant protective factor. In contrast, being in a significant relationship at Time 1 was a protective factor against the development of subthreshold disorder in males. For the first time, sex differences in mental health symptom emergence over time have been explored in a large Australian cohort of military members. The capacity to adapt and bounce back after adversity emerged as a proactive factor against poor mental health for females in the military and could be addressed as part of routine skills training. Social support from significant relationship was particularly important for males' mental health, suggesting that maintaining positive relationships and supporting military spouses and partners are critical for males' mental health.

Sex differences and long-term clinical outcomes after transcatheter aortic valve replacement: A SWEDEHEART study

Previous studies on the impact of sex differences after transcatheter aortic valve replacement (TAVR) have shown conflicting results. The aim was to analyze the risk of long-term mortality, heart failure hospitalization, myocardial infarction, stroke, bleeding and aortic valve reintervention in females versus males after TAVR. This nationwide, population-based cohort study included all patients who underwent TAVR in Sweden between 2008 and 2022 from the SWEDEHEART register. Additional baseline and outcome data were gathered from other national health data registers. Regression standardization was used to adjust for differences between the sexes. Of 10,475 patients, 4,886 (47%) were female and 5,589 (53%) were male. The mean age was 81 years. The cumulative incidence of mortality at 1, 5, and 10 years was 8% vs. 10%, 38% vs. 45%, and 75% vs. 82% for females and males, respectively. After regression standardization, the risk of all-cause mortality was lower for females (absolute difference at 10 years of 6.4%, 95% confidence interval [CI] 4.4%-8.4%). The mean follow up was 3.1 years (maximum 14.1 years). Females also had a lower risk of major bleeding than males (absolute survival difference at 10 years of 4.0%, 95% CI 1.9%-6.2%), but there was no difference in the risk of heart failure, myocardial infarction, stroke, or reintervention between the sexes. Females had a higher survival rate and a lower bleeding risk than males after TAVR. Sex-specific factors are important to consider in the management of patients after TAVR.

#2526 Sex differences in chronic kidney disease-related complications and mortality across levels of glomerular filtration rate

Abstract Background and Aims Chronic kidney disease (CKD) is a growing global health concern. In recent years, studies have increasingly focused on the differential risk profile of diseases between men and women. Current evidence suggests that sex-linked biological and behavioral differences may play a key role in influencing the incidence, prevalence, and outcomes of diseases. Similarly, previous studies have demonstrated a differential risk profile in the prevalence, progression, and outcomes of CKD between men and women. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented. Method We investigated sex-specific disparities in CKD-related complications and mortality according to eGFR levels. We analyzed NHANES data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150 ml/min per 1.73 m². The outcomes were CKD-related complications (hypertension, anemia, CV diseases, acidosis, hyperphosphatemia, hyperparathyroidism) and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios (ORs) and hazard ratios (HRs) for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance. Values of eGFR over which the log-odds (for CKD-related complications outcomes) or log-hazard (for all-cause and cause-specific mortality outcomes) was found to be significantly different from zero (i.e., 95% CI for the smooth term did not contain zero) were identified as thresholds of statistical significance. Results The study included 49, 562 participants (50.31% women, 49.68% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modeling eGFR as a natural spline revealed varied significance thresholds between sexes for anemia and hyperparathyroidism. We found a significantly (P &amp;lt; 0.05) higher proportion of women with anemia downstream an eGFR cut-off of 69 mL/min per 1.73 m2, which was lower than the cut-off in men; a significantly higher proportion of men with anemia was observed downstream an eGFR cut-off of 76 mL/min per 1.73 m2. However, the relationship was more pronounced in women than in men; thus, at an eGFR cut-off of 41 mL/min per 1.73 m2, the proportion of women with anemia was significantly higher (P &amp;lt; .05) (Figure). Similarly, a higher proportion of women with hyperparathyroidism were observed downstream an eGFR cut-off of 73 mL/min per 1.73 m2, which was lower than in men; a significantly higher proportion of men (P &amp;lt; .05) was observed downstream an eGFR cut-off of 89 mL/min per 1.73 m2 (Figure). Furthermore, although no sex differences were observed in terms of eGFR thresholds for hyperphosphatemia, a more pronounced relationship was observed in men. Thus, at an eGFR cut-off of 38 mL/min per 1.73 m2, the proportion of men with hyperphosphatemia was significantly higher (P &amp;lt; .05) than that of women (Figure). We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR Conclusion Research shows sex disparities in most CKD-related complications. Men develop anemia and hyperparathyroidism earlier, women show steeper anemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.

Impact of Sex Differences on Clinical Outcomes in Patients Following Primary Revascularization for Acute Myocardial Infarction - Insights From the Japanese Nationwide Registry.

Women with acute myocardial infarction (AMI) often present a worse risk profile and experience a higher rate of in-hospital mortality than men. However, sex differences in post-discharge prognoses remain inadequately investigated. We examined the impact of sex on 1-year post-discharge outcomes in patients with AMI undergoing percutaneous coronary intervention. We extracted patient-level data for the period January 2017-December 2018 from the J-PCI OUTCOME Registry, endorsed by the Japanese Association of Cardiovascular Intervention and Therapeutics. One-year all-cause and cardiovascular mortality and major adverse cardiovascular events were compared between men and women. In all, 29,856 AMI patients were studied, with 6,996 (23.4%) being women. Women were significantly older and had a higher prevalence of comorbidities than men. Crude all-cause mortality was significantly higher among women than men (7.5% vs. 5.4% [P<0.001] for ST-elevation myocardial infarction [STEMI]; 7.0% vs. 5.2% [P=0.006] for non-STEMI). These sex-related differences in post-discharge outcomes were attenuated after stratification by age. Multivariate analysis demonstrated an increase in all-cause mortality in both sexes with increasing age and advanced-stage chronic kidney disease (CKD). Within this nationwide cohort, women had worse clinical outcomes following AMI than men. However, these sex-related differences in outcomes diminished after adjusting for age. In addition, CKD was significantly associated with all-cause mortality in both sexes.

Sex differences in chronic kidney disease-related complications and mortality across levels of glomerular filtration rate.

Chronic kidney disease (CKD) is a growing global health concern. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented. We investigated sex-specific disparities in CKD-related complications and mortality according to eGFR levels. We analyzed NHANES data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150ml/min per 1.73m². The outcomes were CKD-related complications (hypertension, anaemia, CV diseases, acidosis, hyperphosphatemia, hyperparathyroidism) and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios (ORs) and hazard ratios (HRs) for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance. The study included 49558 participants (50.3% women, 49.7% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modelling eGFR as a natural spline revealed varied significance thresholds between sexes for anaemia and hyperparathyroidism. Additionally, the eGFR-hyperphosphatemia association was more pronounced in men. We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR in women). Research shows sex disparities in most CKD-related complications. Men develop anaemia and hyperparathyroidism earlier, women show steeper anaemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.

Impact of sex differences on the feasibility and safety of distal radial access for coronary procedures: a multicenter prospective observational study.

Conventional transradial access in women is associated with a lower success rate and a higher incidence of spasm compared to men. To date, the effect of sex on the performance of distal radial access (DRA) has not been fully elucidated. The aim of this study was to assess the impact of sex on catheterization success and other performance parameters of DRA procedures. This is a prospective three-center observational study. From August 2020 to September 2022, data from all consecutive patients who underwent DRA for coronary procedures were collected. A total of 868 procedures were registered and stratified into two groups according to sex: women (n = 258) and men (n = 610). Female patients had less favorable baseline characteristics than male patients in terms of absent or weak pulse (29% vs. 17%; P < 0.001), distal radial diameter (2.2 ± 0.3 vs. 2.4 ± 0.4 mm; P < 0.001) and proximal radial diameter (2.5 ± 0.7 vs. 2.7 ± 0.7 mm; P = 0.001). No differences in success rates were found in women compared to men (94.2% vs. 96.6%; P = 0.135), with a higher presence of arterial spasm in women (5.8% vs. 3.0%; P = 0.044). The preprocedural ultrasound evaluation was the only predictor of DRA success [odds ratio = 20.0 (4.739-83.333); P < 0.001]. In patients undergoing coronary procedures, the success rate of DRA was high regardless of sex, with a higher incidence of arterial spasm in women.

Impact of Sex on Thrombectomy Outcomes in Ischemic Stroke: A Propensity Score‐Matched Study, Systematic Review, and Meta‐Analysis

Background Women are underrepresented in stroke thrombectomy trials, and the impact of sex differences in outcomes after stroke thrombectomy is unclear. We performed a multicenter propensity matching study to define sex‐related differences in outcome after endovascular thrombectomy and integrated results in a meta‐analysis. Methods We included patients with anterior circulation large vessel occlusion consecutively treated with thrombectomy at 2 Comprehensive Stroke Centres (2016–2023). Selection criteria reflected international guidelines. Through systematic review we selected all studies reporting endovascular thrombectomy outcomes in anterior circulation large vessel occlusion stroke, applying propensity score matching. MEDLINE, EMBASE, and Cochrane CENTRAL were searched up to August 15, 2023 according to predefined protocol (OSF.io/je3da). Data were extracted by 2 independent raters, pooled estimates calculated according to random‐effect modeling meta‐analysis and reported as odds ratio (OR) and standard 95% CI. Outcomes were good functional outcome, defined as modified Rankin Scale score 0–2 at 90 days after stroke, and symptomatic intracranial hemorrhage, adjudicated according to European Cooperative Acute Stroke Study II criteria. Results After matching, 698 patients (349 women versus 349 men) had similar cardiovascular risk factors, baseline features, and treatment approach. No significant differences were found for good functional outcome (OR = 0.89, 95% CI = 0.66–1.2) and symptomatic intracranial hemorrhage (OR = 1.00, 95% CI = 0.44–2.26) in the cohort study by sex. Systematic review identified 3 studies (n = 3706), all of high quality. No differences emerged in rates of good functional outcome (OR = 1.00, 95% CI = 0.79–1.21) or symptomatic intracranial hemorrhage (OR = 0.85, 95% CI = 0.60–1.19) depending on sex. Conclusion Women receiving endovascular thrombectomy for anterior circulation large vessel occlusion related stroke have similar rates of good functional outcome and symptomatic intracranial hemorrhage compared to men.

Impact of Sex Differences on the Outcomes of Coronary Invasive Physiological Assessment: Long-Term Follow-Up in a Brazilian Population.

This study aimed to evaluate the rate of major adverse cardiac events (MACEs; the sum of death, myocardial infarction, and revascularization rates) according to interventional strategies guided by invasive physiological methods in both sexes in a Brazilian population during long-term follow-up for an average of 2 years. This retrospective single-center study included 151 consecutive patients (232 lesions) between January 2018 and January 2022. The participants were divided into two groups: the female group (FG), comprising 59 patients with 88 lesions, and the male group (MG), comprising 92 patients with 144 lesions. The FG had a greater mean age (FG: 67.96 ± 13.12 vs. MG: 62.36 ± 12.01 years, p = 0.009) and lower mean creatinine clearance (FG: 79.35 ± 38.63 vs. MG: 92.02 ± 38.62 mL/min, p = 0.02) than did the MG. The percentage of lesions in the left main coronary artery was higher in the FG than in the MG (12.5% vs. 2.78%, p = 0.006). The mean follow-up time was longer in the MG than in the FG (795.61 ± 350 vs. 619.19 ± 318 days, respectively; p = 0.001). MACE occurred in 11.86% and 13.04% of patients in the FG and MG, respectively (p = 0.850). Secondary outcomes, such as death, reinfarction, and the need for new revascularization, showed no significant between-sex differences. Our study demonstrated the safety of invasive physiological methods to determine coronary revascularization in both male and female patients in a Brazilian population, as evidenced by the low rates of adverse cardiac events and death after a long-term follow-up.

Impact of sex on antidepressant discontinuation in groups of similar cytochrome P450 phenotypes.

Although there are studies assessing reasons for antidepressant discontinuation, little is known about the impact of sex differences or cytochrome P450 phenotypes. Our objective is to assess discontinuation rates between males and females and whether CYP450 phenotype influences discontinuation. This is a retrospective review of patients previously enrolled in the Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment database with major depressive disorder. Patients were evaluated for antidepressants trialed between January 1, 2009, and September 30, 2019. Survival analyses with competing risks were used to analyze discontinuation reasons. A Kaplan-Meier estimation method was used to assess the time to discontinuation and discontinuation rates. Analyses were also completed to assess discontinuation between men and women by phenotypic groups. All tests were two-sided, and p-values ≤ .05 were considered statistically significant. There were 620 antidepressant discontinuation events discovered from 1015 antidepressant trials included. Overall, the median time to discontinuation for males was 2.6 years and 1.9 years for females (hazard ratio [HR] 0.97 [95% confidence interval (CI): 0.80, 1.19], p = .77). The risk of discontinuation was not different between males and females in any of the phenotype groups, which was consistent in the multivariable analyses. Concomitant use of medications that inhibited or induced antidepressant metabolism increased the overall risk of discontinuation (HR 1.45, 95% CI [1.06, 1.99], p = .020) in a time-dependent analysis. We did not detect a significant difference in risk of antidepressant discontinuation rates between males and females even when accounting for cytochrome P450 phenotype. Future studies should account for whether medications that inhibit or induce antidepressant metabolism may be a crucial factor in antidepressant discontinuation.

Binary Gender Differences in Quality of Life and Social Supports Among Individuals with Immune Thrombocytopenia (ITP): Data from the ITP Natural History Study Registry

BACKGROUND AND AIMS Immune thrombocytopenia (ITP) is an autoimmune bleeding condition characterized by low platelet count and a range of bleeding risks. Patients with ITP often report their quality-of-life (QoL) is negatively impacted by fatigue, mental health, and changes in their physical appearance. Research on impact of sex differences on QoL for ITP patients is limited. Studies show the importance of social support systems for patients with rare disease, but variation in social support between male and female ITP patients have not been reported. Using patient inputted registry data, we highlight binary gender differences in social support and ITP disease impact on survey participants overall health related QoL. METHODS This is a prospective cohort study of self-reporting adults with ITP registered in the ITP Natural History Study Registry. Data were collected using responses from three surveys within the Registry up to July 3, 2023. Participants were included in the study if they completed all three surveys. Data was analyzed with descriptive statistics and chi-squared tests. Majority of questions asked were based on a Likert scale. Responses were divided into the following categories: ‘Social Supports’, ‘Physical health’, ‘Emotional health’, and overall health related QoL (HRQoL). RESULTS Four hundred and sixty participants were included in the study; 358 (78%) were females over 18 years of age and 102 (22%) were males over 18 years of age. Most participants were from the US (382; 83%) and between ages 18-100 years (mean age 47 years). Social Supports: Women and men reported similar levels of social support.Within the prior seven days, 280 (90%) females and 80 (79%) males reported they had someone to listen to them ‘often’ or ‘always’ (n = 354 (females), 102 males). Two hundred and seventy-nine (78%) females and 77 (72%) males reported they had someone to confide in ‘often’ or ‘always’ (n = 354 (females), 102 males), and 233 (63%) females and 71 (71%) males reported they had someone in their life who understands them ‘often’ or ‘always’ (n = 355 (females), 102 males). Physical health: Women reported significantly more limitations in activities due to physical health compared to men (85; 23% vs 8; 8%; p = .0004) (n = 358 (females); 102 (males). Women reported higher average fatigue levels (109; 19% vs 15; 14%; p = .0015), and greater frequency of feeling tired compared to men (207; 58% vs 27; 27%; p = .00001). Emotional health: Women reported significantly higher levels of negative mental health ‘often’ or ‘always’ impacting mood and ability to think compared to men (201; 57% vs 38; 38%; p = .000618) (n = 356 (females); 102 (males), and reported being bothered ‘often’ or ‘always’ by emotional problems such as feeling anxious, depressed, or irritable, more than men (76; 21% vs 12; 12%; p = .032). Overall HRQoL: Men reported overall HRQoL as either ‘very good’ or ‘excellent’ more than women (179; 50% vs 59; 59%). The difference was not statistically significant. CONCLUSION Our study demonstrates adult females and males with ITP have differences in reported HRQoL. Both reported similar levels of social support, such as having someone who understands their problems and can listen. Despite this, females reported higher frequencies of being limited in doing various activities, feeling tired, mental health struggles, and emotional problems. This study offers novel insight into experiences between adult women and men with ITP. Comparisons with non-ITP participants would be helpful to include in future studies to investigate whether sex differences in HRQoL are in fact due to the ITP itself. Future treatment plans may consider which HRQoL factors are impacted most by ITP and could tailor management approaches accordingly.

Impact of sex differences on cardiac injury in critically ill patients with COVID-19

BackgroundCOVID-19 infections are associated with accrued inflammatory responses which may result in cardiac injury. Immune response to infection appears different between men and women, suggesting that COVID-19 patients’ outcomes may differ according to biological sex. However, the impact of biological sex on the occurrence of cardiac injury during intensive care unit (ICU) stay in COVID-19 patients remain unclear.MethodsIn this multicenter and prospective study, we included consecutive patients admitted to ICU for severe COVID-19 pneumonia, during the first two pandemic waves. Biological, electrocardiogram (ECG) and echocardiographic variables were collected on ICU admission. Cardiac injury was defined by increased troponin above 99th percentile of upper norm value and newly diagnosed ECG and/or echocardiographic abnormalities. The primary endpoint was the proportion of patients with cardiac injury during ICU stay according to biological sex. The impact of biological sex on other subsequent clinical outcomes was also evaluated.ResultsWe included 198 patients with a median age of 66 (56–73) years, 147 (74%) patients were men and 51 (26%) were women. Overall, 119 (60%) patients had cardiac injury during ICU stay and the proportion of patients with cardiac injury during ICU stay was not different between men and women (60% vs. 61%, p = 1.00). Patients with cardiac injury during ICU stay showed more cardiovascular risk factors and chronic cardiac disease and had a higher ICU mortality rate. On ICU admission, they had a more marked lymphopenia (0.70 (0.40–0.80) vs. 0.80 (0.50–1.10) × 109/L, p < 0.01) and inflammation (C-Reactive Protein (155 (88–246) vs. 111 (62–192) mg/L, p = 0.03); D-Dimers (1293 (709–2523) vs. 900 (560–1813) µg/L, p = 0.03)). Plasmatic levels of inflammatory biomarkers on ICU admission correlated with SAPS-2 and SOFA scores but not with the different echocardiographic variables. Multivariate analysis confirmed cardiovascular risk factors (OR = 2.31; 95%CI (1.06–5.02), p = 0.03) and chronic cardiac disease (OR = 8.58; 95%CI (1.01–73.17), p = 0.04) were independently associated with the occurrence of cardiac injury during ICU stay, whereas biological sex (OR = 0.88; 95%CI (0.42–1.84), p = 0.73) was not. Biological sex had no impact on the occurrence during ICU stay of other clinical outcomes.ConclusionsMost critically ill patients with COVID-19 were men and experienced cardiac injury during ICU stay. Nevertheless, biological sex had no impact on the occurrence of cardiac injury during ICU stay or on other clinical outcomes.Clinical trial registration NCT04335162

Abstract 12630: Sex Differences in Patients Hospitalized With Acute Pulmonary Embolism - A Single Center Experience

Background: Acute pulmonary embolism (APE) is the third leading cause of cardiovascular death following stroke and myocardial infarction. Data regarding the impact of sex differences on the presentation, management, and outcomes of patients with (APE) remains limited. This study aimed to identify baseline characteristics and treatment strategies in males (M) versus females (F) from a single center experience. Methods: We retrospectively analyzed patients who underwent evaluation by our institutional pulmonary embolism response team for APE between 3/1/2016 and 1/1/2022. Baseline characteristics, biomarkers, and outcomes of interest were compared using Pearson’s Chi-squared test for categorical variables and Wilcoxon rank sum test for continuous variables. Results: The cohort included 886 patients, of whom 48.6% were females. The mean age was (61 ± 16) years. Males were more likely to be smokers (41% vs. 26 %; p&lt;0.001), have a lower Body Mass Index (BMI) (31 ± 9 kg/m 2 , vs 33 ±10; p=0.01) and were more likely to have a history of prior stroke (12% vs 7.9%; p=0.04). The mean brain natriuretic peptide (BNP) on presentation was significantly higher in females (361 ± 624 pg/ml vs 281 ± 505; p=0.019). The mean d-dimer (F: 7,041 ± 6,438 ng/ml vs M: 9,063 ±11,447; p=0.13), troponin I (F: 1.60 ± 15.58 ng/ml vs M: 0.72±4.11; p=0.3), and lactic acid (F: 2.58 ± 3.20 mm/l vs M: 2.42 ± 2.43; p=0.6) were similar between both groups. PE severity (massive: 5.3% vs 6.4%; submissive: 58% vs: 55%; P=0.8) was similar between females and males. There were also no sex-based differences in the use of advanced therapies or outcomes. (Figure 1) Conclusion: In our APE cohort from a single center tertiary care center, sex differences in comorbidity profile (BMI, tobacco use, history of stroke) were observed. Females had a significantly higher BNP consistent with prior published literature. However, there were no sex-based disparities in PE severity, management, escalation of advanced therapies or outcomes.

The impact of sex differences on 3-year outcomes of patients with non-ST-segment elevation myocardial infarction after successful stent implantation according to symptom-to-balloon time

BackgroundBecause no data are available, we compared the 3-year outcomes of patients with non-ST-elevation myocardial infarction (NSTEMI) based on sex and symptom-to-balloon time (SBT). MethodsThis study included 4910 patients who were divided into two groups based on SBT: SBT <48 h (n = 3,293, 67.1%) and SBT ≥48 h (n = 1,617, 32.9%). The primary outcome was all-cause death during the 3-year follow-up period. The secondary outcome was major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction, or repeat coronary revascularization. ResultsAfter adjustment, the in-hospital mortality rates for males and females in the SBT <48 h and SBT ≥48 h groups were similar. During a 3-year follow-up period, females in the SBT <48 h group had significantly higher rates of all-cause death (adjusted hazard ratio [aHR], 1.482; P = 0.006), cardiac death (CD, aHR, 1.617; P = 0.009), and MACE (aHR, 1.268; P = 0.024) than those males in the same groups. Females and males in the SBT ≥48 h group did not differ significantly in the primary and secondary outcomes. In males, the rates of all-cause death (P = 0.008) and CD (P = 0.024) were significantly higher in the SBT ≥48 h group than in the SBT <48 h group. ConclusionsThis study has identified a higher 3-year mortality rate in female patients with NSTEMI and SBT <48 h compared to their male counterparts. As such, a more preventive approach may be required to reduce mortality in these female patients.

Sex Differences in Murray Law-Based Quantitative Flow Ratio Among Patients With Intermediate Coronary Lesions.

Background The Murray law-based quantitative flow ratio (μQFR) is a novel technique that simulates fractional flow reserve (FFR) from a single angiographic view. However, the impact of sex differences on the diagnostic performance of μQFR has not been investigated. Methods and Results In this study, FFR and μQFR were assessed in 497 intermediate stenoses (30%-70% by visual estimation) from 460 patients (34.3% female). Physiological significance was defined as FFR ≤0.80 or μQFR ≤0.80. After adjusting for potential confounders, female sex was independently associated with higher FFR (P=0.048 and 0.026, respectively) and μQFR (P=0.001 for both) in both fully adjusted and stepwise backward models. μQFR provided superior diagnostic accuracy compared with angiography alone for detecting FFR ≤0.80 in both women (area under the curve, 0.93 [95% CI, 0.88-0.97] versus 0.80 [95% CI, 0.73-0.86]; P=0.001) and men (area under the curve, 0.88 [95% CI, 0.84-0.92] versus 0.73 [95% CI, 0.68-0.78]; P<0.001), with comparable performance between the sexes (P=0.175). In the multivariable analysis, sex was not a significant factor contributing to the overall disagreement between FFR and μQFR. Conclusions Regardless of angiographic stenosis severity, women tend to have higher FFR and μQFR values than men. Furthermore, μQFR performs similarly well in both sexes and offers improved diagnostic accuracy over angiography alone, indicating its potential as a reliable, wire-free tool to identify functional ischemia.

Exploring sex disparities in cardiovascular disease risk factors using principal component analysis and latent class analysis techniques

BackgroundThis study used machine learning techniques to evaluate cardiovascular disease risk factors (CVD) and the relationship between sex and these risk factors. The objective was pursued in the context of CVD being a major global cause of death and the need for accurate identification of risk factors for timely diagnosis and improved patient outcomes. The researchers conducted a literature review to address previous studies' limitations in using machine learning to assess CVD risk factors.MethodsThis study analyzed data from 1024 patients to identify the significant CVD risk factors based on sex. The data comprising 13 features, such as demographic, lifestyle, and clinical factors, were obtained from the UCI repository and preprocessed to eliminate missing information. The analysis was performed using principal component analysis (PCA) and latent class analysis (LCA) to determine the major CVD risk factors and to identify any homogeneous subgroups between male and female patients. Data analysis was performed using XLSTAT Software. This software provides a comprehensive suite of tools for Data Analysis, Machine Learning, and Statistical Solutions for MS Excel.ResultsThis study showed significant sex differences in CVD risk factors. 8 out of 13 risk factors affecting male and female patients found that males and females share 4 of the eight risk factors.Identified latent profiles of CVD patients, suggesting the presence of subgroups among CVD patients. These findings provide valuable insights into the impact of sex differences on CVD risk factors. Moreover, they have important implications for healthcare professionals, who can use this information to develop individualized prevention and treatment plans. The results highlight the need for further research to elucidate these disparities better and develop more effective CVD prevention measures.ConclusionsThe study explored the sex differences in the CVD risk factors and the presence of subgroups among CVD patients using ML techniques. The results revealed sex-specific differences in risk factors and the existence of subgroups among CVD patients, thus providing essential insights for personalized prevention and treatment plans. Hence, further research is necessary to understand these disparities better and improve CVD prevention.

Sex differences on multikinase inhibitors toxicity in patients with advanced gastroenteropancreatic neuroendocrine tumours

PurposeThere is an increasing interest in the role of sex and gender in cancer patients. The impact of sex differences in oncological systemic therapies is still unknown, and there is a lack of evidence specially in uncommon neoplasms like neuroendocrine tumours (NET). In the present study, we combine the differential toxicities by sex in five published clinical trials with multikinase inhibitors (MKI) in gastroenteropancreatic (GEP) NET. MethodsWe performed a pooled univariate analysis of reported toxicity in patients treated in five phase 2 and phase 3 clinical trials with MKI in the GEP NET setting: sunitinib (SU11248, SUN1111), Pazopanib (PAZONET), sorafenib-bevacizumab (GETNE0801) and Lenvatinib (TALENT). Differential toxicities between male and female patients were evaluated considering relationship with study drug and different weights of each trial by random effect adjustment. ResultsWe found nine toxicities which were more frequent in female patients (leukopenia, alopecia, vomiting, headache, bleeding, nausea, dysgeusia, neutrophil count decreased and dry mouth) and two toxicities being more frequent in male patients (Anal Symptoms and Insomnia). Asthenia and diarrhoea were the only severe (Grade 3–4) toxicities more frequent in female patients. ConclusionsSex-related differences in toxicity with the MKI treatment require targeted information and individualised management of patients with NET. Differential reporting of toxicity should be promoted when clinical trials are published.

Abstract 645: Impact of sex differences on cross-talk between the gut microbiome, CEACAMs, and TGF-β signaling in cancers

Abstract Background: Sex differences, microbiome alterations and obesity are prominent factors modulating gastrointestinal (GI) cancers, such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). However, there is a limited understanding of the interactions between intestinal epithelial and immune cells that participate in the regulation of the microbiome and the prevention or promotion of inflammation and the development of cancer. CEACAM proteins are immune and epithelial cell regulators, and some CEACAMs (CEACAM1, 3, 5, and 6) bind to pathogenic microbes. CEACAMs and mutations of the encoding genes are potential drivers of microbiome changes through altered regulation of host-immune response, through a mechanism that we hypothesize involves TGF-β signaling. We found that genetic alterations in CEACAM-encoding genes correlate with scores of TGF-β pathway activity in GI cancers in The Cancer Genome Atlas (TCGA). Furthermore, nearly 40% of human GI cancers have genetic alterations in components and regulators of the TGF-β pathway. We, therefore, investigated crosstalk between pathogen-binding CEACAM1, the gut microbiome, and the multifunctional intrinsically disordered protein βII-spectrin (SPTBN1), a Smad3 adaptor in driving CRC and liver cancers. Methods: The DNA from fecal samples collected from wild-type mice or TGF-β signaling-deficient mice Smad4+/-Sptbn1+/- were analyzed through shotgun metagenomics sequencing to identify changes in gut microbiota composition. We examined CEACAM expression, changes in the T cell populations, liver inflammation, and cancer in tissues from liver-specific βII-spectrin knockout (LSKO) mice fed a Western diet. Results: Mice heterozygous for the Sptbn1 gene (Sptbn1+/-) combined with heterozygosity of Smad4 (Smad4+/-Sptbn1+/-) spontaneously developed GI cancers, in the C57BL/6J genetic background. These mice exhibit an increased bacterial species associated with CRC in humans (C. septicum) and decreased commensal gut microbes associated with a healthy microbiome (B. vulgatus, P. distasonis). In addition, male Sptbn1+/- mice spontaneously developed HCC and showed reduced regulatory T (Treg) cells, whereas female mice did not, suggesting that βII-spectrin has a role in immune cell homeostasis that may affect tumor suppression. Single cell analyses revealed that Ceacam1 expression decreases in hepatocytes in mice fed a Western diet. CEACAM1 levels are restored to normal in tissues from liver-specific βII-spectrin knockout (LSKO) mice. Furthermore, we observed diet-induced changes in the T cell populations, liver inflammation, and cancer are also blocked in LSKO mice. Conclusion: Our study highlights how two critical pathways, TGF-β signaling and immune mediators CEACAM1 and 5, can drive inflammation and cancer through microbiome alterations with host sex having marked impact on the relevant signaling pathways. Citation Format: Krishanu Bhowmick, Addison Klebanov, Sahara John, Xiaochun Yang, Xiyan Xiang, Anil Vegesna, Kazufumi Ohshiro, James M. Crawford, Nicole Beauchemin, Raja Mazumder, Keith A. Crandall, Lopa Mishra. Impact of sex differences on cross-talk between the gut microbiome, CEACAMs, and TGF-β signaling in cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 645.