Sex Differences In Mortality Research Articles

Sex differences in mortality: results from a population-based study of 12 longitudinal cohorts

BACKGROUND:Women generally have longer life expectancy than men but have higher levels of disability and morbidity. Few studies have identified factors that explain higher mortality in men. The aim of this study was to identify potential factors contributing to sex differences in mortality at older age and to investigate variation across countries.METHODS:This study included participants age ≥ 50 yr from 28 countries in 12 cohort studies of the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) consortium. Using a 2-step individual participant data meta-analysis framework, we applied Cox proportional hazards modelling to investigate the association between sex and mortality across different countries. We included socioeconomic (education, wealth), lifestyle (smoking, alcohol consumption), social (marital status, living alone) and health factors (cardiovascular disease, diabetes, mental disorders) as covariates or interaction terms with sex to test whether these factors contributed to the mortality gap between men and women.RESULTS:The study included 179 044 individuals. Men had 60% higher mortality risk than women after adjustment for age (pooled hazard ratio [HR] 1.6; 95% confidence interval 1.5–1.7), yet the effect sizes varied across countries (I2 = 71.5%, HR range 1.1–2.4). Only smoking and cardiovascular diseases substantially attenuated the effect size (by about 22%).INTERPRETATION:Lifestyle and health factors may partially account for excess mortality in men compared with women, but residual variation remains unaccounted for. Variation in the effect sizes across countries may indicate contextual factors contributing to gender inequality in specific settings.

Sex Differences in Stroke Hospitalization Incidence, 30-Day Mortality, and Readmission in a Regional Medical Center in the Southwestern United States

This study explores sex differences in ischemic stroke hospitalization incidence, 30-day mortality, and 30-day readmission in a southwestern US medical center. Ischemic stroke admissions in a regional medical center in the southwestern United States were obtained for a 6.5-year time frame (N = 1968). Logistic regression models examine the adjusted effects of sex on 30-day mortality and 30-day readmission outcomes among individuals hospitalized for ischemic stroke. Findings confirm that although women experience higher mortality than men (9.1% vs 6.7%), the sex disparity in mortality is explained by the age distribution of strokes. Women experience far more strokes and deaths because of stroke at older ages. No differences in principal procedure or 30-day readmission emerged. Men experienced higher stroke hospitalization incidence, although women exhibited higher 30-day mortality. Age composition explained sex differences in mortality, but higher male stroke hospitalization incidence represents a larger public health issue that suggests the need for behavioral change at the population level. No meaningful sex differences emerged in treatment, mortality, or readmission.

Are human natal sex ratio differences across the world adaptive? A test of Fisher's principle

Fisher's principle states that natural selection favours an equal number of male and female births at the population level, unless there are sex differences in rearing costs or sex differences in mortality before the end of the period of parental investment. Sex differences in rearing costs should be more pronounced in low- than in high-resource settings. We, therefore, examined whether human development index and sex differences in child mortality contribute to the natural variation in human sex ratio at birth across the globe. As predicted by Fisher's principle, the proportion of male births increased with both increasing male-biased childhood mortality and level of development of each country. However, these relationships were absent after accounting for spatial autocorrelation in the residuals, which our inference is conditioned on. This work shows how the failure to account for residual spatial autocorrelation can lead to incorrect conclusions regarding support for predictions from sex allocation theory.

Abstract 13: Sex Differences in Mortality Among Patients With Covid-19 Related Stroke

Introduction: Overall poor COVID-19 outcomes have been reported among males. We evaluated sex differences in mortality among patients with stroke related to COVID-19. Methods: Utilizing pooled deidentified data from 30 healthcare organizations, we identified COVID-19 patients via ICD-10 diagnosis or documented laboratory confirmation of SARS-CoV-2 RNA or antibodies. Patients with ICD-10 diagnoses of ischemic stroke or intracerebral hemorrhage within 30 days before or after the COVID-19 event were flagged. Male and female patients were propensity score (PS) matched on other demographic and comorbidity variables. Risk Ratio (RR) and 95% Confidence Interval (CI) for association between sex and 90-day mortality is reported. Kaplan-Meier analyses with log rank test (LRT) were conducted for time-to-death. As a sensitivity analysis, we only included a smaller sub-set with first instance of IS or ICH ± 30-days of COVID-19 diagnosis. Results: Among 149,410 COVID-19 patients, 1,618 (1.1%) had a stroke diagnosis ± 30-days of confirmed COVID-19. Of whom, 1,609 patients (847 males and 762 females) were included in primary analyses. Females were older (67.7 vs. 65.7 years) and were more likely to be of black race (34.1% vs. 27.6%). Females had a significantly higher proportion of chronic pulmonary disease (38.8% vs. 28.8%) and obesity (34.2% vs. 24.8%); whereas males had higher proportion of alcohol abuse (8.5% vs. 3.8%). A 1:1 PS algorithm yielded an optimally matched sample of 634 males and females each, balanced on all covariates. In the matched sample, 11.7% of females and 15.8% of males experienced 90-day mortality; RR (CI): 1.35 (1.02 - 1.78), LRT p value 0.04. Higher risk of 90-day mortality among males with COVID-19 and stroke was maintained in the sensitivity analyses, RR (CI): 1.47 (1.06 - 2.00), LRT p value = 0.03 (graphic). Conclusion: Future studies examining the socio-demographic and biological mechanisms for poor stroke outcomes among males with COVID-19 are needed.

Hospital- and Patient-Level Characteristics Associated With Unplanned Readmissions and In-Patient Mortality in Men and Women With Alcoholic Cardiomyopathy

The aims of the study were to (a) determine rates of early, late, and overall 30-day all-cause readmission for women and men with the diagnosis of alcoholic cardiomyopathy (ACM), (b) examine hospital- and patient-level characteristics associated with the risk of readmission and how these factors differed by sex, and (c) examine the association between sex and in-patient mortality during readmission. We conducted a multi-year cross-sectional analysis of adult (≥18 years) inpatient hospitalizations in the United States. Descriptive statistics including frequencies and percentages were used to describe the study population, stratified by sex. We then used Poisson regression with robust error variance estimation to estimate risk ratios (RRs) and 95% confidence intervals (CIs) that represented the associations between sex and likelihood of 30-day all-cause readmission and inpatient mortality. Among more than 116 million hospitalizations, there were 53,207 ACM-related hospitalizations (45,573 men and 7,634 women). Thirty-day all-cause readmission rates following an ACM-related index hospitalization were similar between men (20.3%) and women (20.5%). For men and women, cancer, hepatitis, chronic renal failure, cirrhosis, asthma, and anemia were associated with a higher risk of readmission. Although crude in-hospital mortality rates were higher among women (6.6%) than men (4.3%), there were no sex differences in mortality after adjusting for confounders (RR = 1.26, 95% CI [0.88, 1.81]). Although men are more likely to be hospitalized for ACM, readmission risk is high (approximately 20%) and is similar in men and women following hospitalization for ACM. Hospital care transition programs that include a multidisciplinary approach are needed to help prevent these readmissions and associated morbidity and mortality.

Accounting for Smoking in Forecasting Mortality and Life Expectancy.

Smoking is one of the main risk factors that has affected human mortality and life expectancy over the past century. Smoking accounts for a large part of the nonlinearities in the growth of life expectancy and of the geographic and sex differences in mortality. As Bongaarts (2006) and Janssen (2018) suggested, accounting for smoking could improve the quality of mortality forecasts due to the predictable nature of the smoking epidemic. We propose a new Bayesian hierarchical model to forecast life expectancy at birth for both sexes and for 69 countries with good data on smoking-related mortality. The main idea is to convert the forecast of the non-smoking life expectancy at birth (i.e., life expectancy at birth removing the smoking effect) into life expectancy forecast through the use of the age-specific smoking attributable fraction (ASSAF). We introduce a new age-cohort model for the ASSAF and a Bayesian hierarchical model for non-smoking life expectancy at birth. The forecast performance of the proposed method is evaluated by out-of-sample validation compared with four other commonly used methods for life expectancy forecasting. Improvements in forecast accuracy and model calibration based on the new method are observed.

Sex differences in mortality and 90-day readmission rates after transcatheter aortic valve replacement: a nationwide analysis from the USA.

To assess gender differences in in-hospital mortality and 90-day readmission rates among patients undergoing transcatheter aortic valve replacement (TAVR) in the USA. Hospitalizations for TAVR were retrospectively identified in the National readmissions database (NRD) from 2012 to 2017. Gender based differences in in-hospital mortality and 90-day readmissions were explored using multivariable logistic regression models. During the study period, an estimated 171 361 hospitalizations for TAVR were identified, including 79 722 (46.5%) procedures in women and 91 639 (53.5%) in men. Unadjusted in-hospital mortality and 90-day all-cause readmissions were significantly higher for women compared with men (2.7% vs. 2.3%, P = 0.002; 25.1% vs. 24.1%, P = 0.012, respectively). After adjusting for baseline characteristics, women had 13% greater adjusted odds of in-hospital mortality [adjusted odds ratio (aOR): 1.13, 95% confidence interval (CI): 1.02-1.26, P = 0.017], and 9% greater adjusted odds of 90-day readmission compared with men (aOR: 1.09, 95% CI: 1.05-1.14, P < 0.001). During the study period, there was a steady decrease in-hospital mortality (5.3% in 2012 to 1.6% in 2017; Ptrend < 0.001) and 90-day (29.9% in 2012 to 21.7% in 2017; Ptrend < 0.001) readmission rate in both genders. In-hospital mortality and readmission rates for TAVR hospitalizations have decreased over time across both genders. Despite these improvements, women undergoing TAVR continue to have a modestly higher in-hospital mortality, and 90-day readmission rates compared with men. Given the expanding indications and use of TAVR, further research is necessary to identify the reasons for this persistent gap and design appropriate interventions.

Sex Differences in Mortality After Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-analysis

Evidence describing and quantifying sex-based differences in cardiac surgical techniques and outcomes is scant. The aim of this review was to determine whether there is contemporary evidence for short and longer-term differences in sex-based mortality after CABGs.

Sex Differences in Mortality Among People with End-Stage Kidney Disease: Bi-National Data-Linkage Cohort Study

IntroductionFemale life expectancies consistently exceed males in the general population. Yet, this survival advantage may not persist in the presence of a chronic disease due to biological differences or healthcare inequities.&#x0D; Objectives and ApproachWe aimed to explore sex differences in mortality among people with end-stage kidney disease (ESKD). T he entire ESKD population in Australia, 1980-2013, and New Zealand,1988-2012, were included from the Australian and New Zealand Dialysis and Transplant Registry. Data linkage to national death registers was undertaken to ascertain deaths and their causes. We estimated relative measures of survival, including standardized mortality ratios (SMR), relative survival and expected life years lost, using general population data to account for background mortality, adjusting for country, age, sex and year.&#x0D; ResultsOf 60,823 ESKD patients, there were 25,042 females (41%) and 35,781 males (59%). Mortality sex differences within the ESKD population were minor, but once compared to the general population, female ESKD patients had more excess deaths, worse relative survival and greater life years lost compared to male ESKD patients. Females had 11.5 SMR (95%CI:11.3-11.7) and males had 6.7 SMR (95%CI:6.7-6.8), with greater disparity among younger ages and from certain causes. Relative survival was consistently lower in females, with adjusted excess mortality 9% higher (95%CI:7-12%) in ESKD females. Average life years lost was 4-5 years greater in ESKD females compared to males across all ages. Kidney transplantation reduced the sex differences in excess mortality, with similar relative survival (p=0.42) and average life years lost reduced to 3-4 years for females.&#x0D; Conclusion / ImplicationsThe impact of ESKD is more profound for women than men with greater excess mortality, however kidney transplantation attenuates these differences. Our findings show that chronic diseases and sex can compound to produce worse outcomes where women lose their survival advantage in the presence of ESKD.

Sex differences in crude mortality rates and predictive value of intensive care unit-based scores when applied to the cardiac intensive care unit.

Limited data exists regarding sex differences in outcome and predictive accuracy of intensive care unit-based scoring systems when applied to cardiac intensive care unit patients. We reviewed medical records of patients admitted to cardiac intensive care unit from 1 January 2011-31 December 2016. Sex differences in mortality rates and the performance of intensive care unit-based scoring systems in predicting in-hospital mortality were analyzed. Calibration was assessed by the Hosmer-Lemeshow test and locally weighted scatterplot smoothing curves. Discrimination was assessed using the c statistic and receiver-operating characteristic curve. Among 6963 patients, 2713 (39%) were women. Overall in-hospital and cardiac intensive care unit mortality rates were similar in women and men (9.1% vs 9.4%, p=0.67 and 5.9% vs 6%, p=0.88, respectively) and in age and major diagnosis subgroups. Of the scoring systems, Acute Physiology and Chronic Health Evaluation III and Sequential Organ Failure Assessment had poor calibration (Hosmer-Lemeshow p value <0.001), while Simplified Acute Physiology Score II performed better (Hosmer-Lemeshow p value 0.09), in both women and men. All scores had good discrimination (C statistics >0.8). In the subgroups of acute myocardial infarction and heart failure patients, all scores had good calibration (Hosmer-Lemeshow p>0.001) and discrimination (C statistic >0.8) while in diagnosis subgroups with highest mortality, the calibration varied among scores and by sex, and discrimination was poor. No sex differences in mortality were seen in cardiac intensive care unit patients. The mortality predictive value of intensive care unit-based scores is limited in both sexes and variable among different subgroups of diagnoses.

Abstract 13648: Sex Differences in Modifiable Risk Factors and Severity of Coronary Artery Disease

Introduction: It is still unknown whether traditional risk factors may have a sex specific impact on coronary artery disease (CAD) burden. Hypothesis: We sought to investigate at individual level whether there are sex differences in the four modifiable traditional cardiovascular risk factors and how these differences may impact the CAD and outcomes in ACS. Methods: We identified 14,793 patients who underwent coronary angiography for acute coronary syndromes in the ISACS-TC registry (NCT01218776) from 2010 to 2019. Main outcome measure was the association between traditional risk factors and severity of CAD and its relationship with 30-day mortality. The relative risk (RR) ratios and 95% CI were calculated from the ratio of the absolute risks of women versus men using inverse probability of weighting. Estimates were compared by test of interaction on the log scale. Severity of CAD was categorized as obstructive (≥50% stenosis) versus nonobstructive CAD. Results: The RR ratios for obstructive CAD in women versus men among nondiabetic people was 0.49 (95%CI 0.41-0.60) and diabetic people was 0.89 (95%CI 0.62-1.29); interaction by diabetes status: p=0.018. Exposure to smoking shifted the RR ratios from 0.50 (95%CI 0.4 -0.61) in nonsmokers to 0.75 (95%CI 0.54-1.03) in current smokers; interaction by smoking status: p=0.018. There were no significant sex-related interactions with hypercholesterolemia and hypertension. Women with obstructive CAD had higher 30-day mortality rates than men (RR 1.75, 95%CI 1.48-2.07). No sex differences in mortality were observed in patients with nonobstructive CAD. Conclusions: Obstructive CAD in women signifies a higher risk for mortality compared with men. Current smoking and diabetes disproportionally increase the risk of obstructive CAD in women. Achieving the goal of improving cardiovascular health in women still require intensive efforts toward further implementation of lifestyle and treatment interventions.

Sex differences in COVID-19 case fatality: do we know enough?

Sex differences in COVID-19 case fatality: do we know enough?

Sex Differences in the Mortality Risk of Elderly Patients with Systolic Heart Failure in Taiwan.

Sex differences in heart failure mortality might be affected by age, race, and treatment response. Many large studies in Western countries have shown conflicting results, however few studies have been conducted in Asian patients. We prospectively investigated the mortality risk in a multicenter cohort of 1,093 male and 416 female heart failure patients with reduced ejection fraction (HFrEF) hospitalized for worsening symptoms in Taiwan between 2013 and 2015. Kaplan-Meier curve and Cox proportional regression analyses were used to determine the one-year mortality risk by sex. There were no significant differences in major adverse cardiovascular events, re-admission rate, and mortality between sexes in the overall cohort and the young subgroup during one-year of follow-up. In the elderly subgroup, the overall and cardiac mortality rate of the male patients were higher than those of the female patients (p = 0.035, p = 0.049, respectively). We found that the prognostic effect of old age on overall mortality rate appeared to be stronger in the male patients (p < 0.0001) than in the female patients (p = 0.69) in Cox regression analysis and Kaplan-Meier survival curves. Male sex was a risk factor for all-cause mortality in the elderly (hazard ratio: 1.50, 95% confidence interval 1.02-2.25) independently of systolic blood pressure, diabetes mellitus, hemoglobin concentration, kidney function, and medications. In the Taiwan HFrEF registry, the highest mortality risk was observed in male patients aged 65 years or more. Clinicians need to pay more attention to these patients.

Sex sub analysis from observational multicenter registry of patients treated with Impella mechanical circulatory support device in Italy: the IMP-IT women

Abstract Background Women-specific data on safety, effectiveness, and outcomes for mechanical support in the setting of cardiogenic shock (CS) and high-risk percutaneous coronary intervention (HR-PCI) are still unsettled. The IMP-IT study was a multicenter observational national registry that enrolled all patients treated with Impella 2.5, Impella CP, Impella 5.0 and Impella RP, both for CS and HR-PCI indications, across 17 Italian centers from 2004 to June 2018 Purpose To analyze the characteristics of female population enrolled in IMP-IT registry and to assess differences in presentation, timing to interventions and outcomes between men and women. Methods The Women-IMP-IT study is a multicenter observational national registry focusing on female population enrolled in IMP-IT study. Baseline, procedural and hemodynamics characteristics, such as outcome were collected. Differences between men and women were examined. Results Mean age of female population was 66.9±16.1 years, Body mass index was 26.3±5.5 kg/m2. There was a higher rate of cardiogenic shock (66.7% vs. 49.1%; p=0.06), NSTEMI (18% vs 9%, p=0.03) and acute myocarditis (9.6% vs 1.4%, p=0.01) in women vs men, associated with a lower rate of protected PCI (33.3% vs 50.9%, p=0.06). We did not observed a statistically difference in device related complications (27.4% vs 23.3%; p=0.50), respectively in women compared to men. In particular, no differences were observed in access site bleedings (10.8% vs 9%; p=0.70) and life threatening or severe bleeding (15.3% vs 11.4%; p=0.40). At one year, all-cause death rate was 45.1% in women vs 30.1% in men (p=0.016), and cardiac death rate was 42.5% in women and 27.5% in men (p=0.013). At 1-year no significant difference was observed in the rate of myocardial infarction (3.7% vs 2.3%; p=0.44), stroke (3.7% vs 2.6%; p=0.70), heat-failure hospitalization (7.7% vs 7.5%; p=1.0), need for left ventricular assist device or heart transplantation (1.3% vs 5.5%; p=0.21). Conclusions In our series, use of Impella is CS and HR-PCI is increasing in female population. Sex-differences in mortality are mostly explained by clinical differences at presentation. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): EAPCI Education and Training Grants

Sex Differences in Modifiable Risk Factors and Severity of Coronary Artery Disease.

BackgroundIt is still unknown whether traditional risk factors may have a sex‐specific impact on coronary artery disease (CAD) burden.Methods and ResultsWe identified 14 793 patients who underwent coronary angiography for acute coronary syndromes in the ISACS‐TC (International Survey of Acute Coronary Syndromes in Transitional Countries; Clini​calTr​ials.gov, NCT01218776) registry from 2010 to 2019. The main outcome measure was the association between traditional risk factors and severity of CAD and its relationship with 30‐day mortality. Relative risk (RR) ratios and 95% CIs were calculated from the ratio of the absolute risks of women versus men using inverse probability of weighting. Estimates were compared by test of interaction on the log scale. Severity of CAD was categorized as obstructive (≥50% stenosis) versus nonobstructive CAD. The RR ratio for obstructive CAD in women versus men among people without diabetes mellitus was 0.49 (95% CI, 0.41–0.60) and among those with diabetes mellitus was 0.89 (95% CI, 0.62–1.29), with an interaction by diabetes mellitus status of P =0.002. Exposure to smoking shifted the RR ratios from 0.50 (95% CI, 0.41–0.61) in nonsmokers to 0.75 (95% CI, 0.54–1.03) in current smokers, with an interaction by smoking status of P=0.018. There were no significant sex‐related interactions with hypercholesterolemia and hypertension. Women with obstructive CAD had higher 30‐day mortality rates than men (RR, 1.75; 95% CI, 1.48–2.07). No sex differences in mortality were observed in patients with nonobstructive CAD.ConclusionsObstructive CAD in women signifies a higher risk for mortality compared with men. Current smoking and diabetes mellitus disproportionally increase the risk of obstructive CAD in women. Achieving the goal of improving cardiovascular health in women still requires intensive efforts toward further implementation of lifestyle and treatment interventions.RegistrationURL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01218776.

1788P Persistent sex-differences in lung cancer mortality between 2001 and 2017 in the US and EU

The lung is the most common site of cancer and has the highest worldwide cancer-related mortality. Advancements in lung cancer screening, new therapeutics, and guideline driven care over the past two decades have resulted in improvements in mortality. Few studies have reported on lung cancer trends in the 21st century. This study assessed the difference between lung cancer mortality by gender in the United States (US) and European Union (EU). We utilized the World Health Organization (WHO) Mortality Database for European mortality data and Center for Disease Control (CDC) Wonder database for US mortality data. We extracted lung cancer mortality data from 2000 to 2017 based on ICD 10 system. Crude mortality rates were dichotomized by sex and reported by year. We computed Age Standardized Death Rates (ASDRs) per 100,000 population using the World Standard Population (and USA standard population for CDC mortality). We computed the ratio of male to female mortality over the observation period. We analyzed data from a total of 26 EU countries and the US, of which 6 countries had data till 2017, 12 till 2016, 7 till 2015 and 2 till 2014. All countries had greater mortality in men compared to women in all years. All countries had an overall decrease in the ratio of male-to-female mortality over the observation period. Specifically, in 2000, the median male-to-female mortality was 5.35 (IQR 3.65, 6.06) and for the most recent observation the median male-to-female mortality ratio was 2.26 (1.92, 4.05). The countries with the greatest current disparity in lung cancer mortality were Lithuania (5.51), Latvia (5.00), and Bulgaria (4.4). The countries with the smallest difference in mortality between sexes were Sweden (1.1), Denmark (1.13), United Kingdom (1.39). The median percentage change for all countries was – 44.45 (-50.44, - 30.56). The countries with the greatest percentage change were Spain (- 55.19), Belgium (-55.18), Cyprus (-53.64). The countries with the smallest percentage change were Bulgaria (-21.65), USA (-22.05), and Portugal (-25.46). This study reports a decrease in the ratio of male-to-female mortality over the observation period across the EU and US. The greatest sex differences in mortality were in Eastern European countries and the smallest differences were in Northern Europe.

Diferencias en mortalidad intrahospitalaria tras IAMCEST frente a IAMSEST por sexo. Tendencia durante once años en el Sistema Nacional de Salud

Introduction and objectivesConflicting results have been reported on the possible existence of sex differences in mortality after myocardial infarction (MI). There is also a scarcity of data on the impact of sex on outcomes after ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). The aim of this study was to analyze sex difference trends in sex-related differences in mortality for STEMI and NSTEMI. MethodsA retrospective analysis of 445 145 episodes of MI (2005-2015) was carried out using information from the Spanish National Health System. The incidence rates were expressed as events per 10 000 person-years. The denominators (age-specific groups) were obtained from the nationwide census. We calculated crude and adjusted (multilevel logistic regression) mortality. Poisson regression analysis was used to study temporal trends for in-hospital mortality. ResultsA total of 69.8% episodes occurred in men. The mean age in men was 66.1±13.3 years, which was significantly younger than in women, 74.9±12.1 (P<.001). A total of 272 407 (61.2%) episodes were STEMI, and 172 738 (38.8%) were NSTEMI. Women accounted for 28.8% of STEMI and 33.9% of NSTEMI episodes (P <.001). The effect of female sex on risk-adjusted models for in-hospital mortality was the opposite in STEMI (OR for women, 1.18; 95%CI, 1.14-1.22; P <.001) and NSTEMI (OR for women, 0.85; 95%CI, 0.81-0.89; P <.001). MI hospitalization rates were higher in men than in women for all age groups [20 vs 7.7 per 10 000 individuals aged 35-94 years (P <.001)], with a trend to diminish in both sexes. ConclusionsWomen had a slight but significantly increased risk of in-hospital mortality after MI, but the effect of sex depended on MI type, with women exhibiting higher mortality for STEMI and lower mortality for NSTEMI

Oestrogen-mediated upregulation of the Mas receptor contributes to sex differences in acute lung injury and lung vascular barrier regulation.

Epidemiological data from the SARS-CoV-2 outbreak suggest sex differences in mortality and vulnerability; however, sex-dependent incidence of acute respiratory distress syndrome (ARDS) remains controversial and the sex-dependent mechanisms of endothelial barrier regulation are unknown. In premenopausal women, increased signalling of angiotensin (Ang)(1-7) via the Mas receptor has been linked to lower cardiovascular risk. Since stimulation of the Ang(1-7)/Mas axis protects the endothelial barrier in acute lung injury (ALI), we hypothesised that increased Ang(1-7)/Mas signalling may protect females over males in ALI/ARDS.Clinical data were collected from Charité inpatients (Berlin) and sex differences in ALI were assessed in wild-type (WT) and Mas-receptor deficient (Mas-/- ) mice. Endothelial permeability was assessed as weight change in isolated lungs and as transendothelial electrical resistance (TEER) in vitroIn 734 090 Charité inpatients (2005-2016), ARDS had a higher incidence in men as compared to women. In murine ALI, male WT mice had more lung oedema, protein leaks and histological evidence of injury than female WT mice. Lung weight change in response to platelet-activating factor (PAF) was more pronounced in male WT and female Mas-/- mice than in female WT mice, whereas Mas-receptor expression was higher in female WT lungs. Ovariectomy attenuated protection in female WT mice and reduced Mas-receptor expression. Oestrogen increased Mas-receptor expression and attenuated endothelial leakage in response to thrombin in vitro This effect was alleviated by Mas-receptor blockade.Improved lung endothelial barrier function protects female mice from ALI-induced lung oedema. This effect is partially mediated via enhanced Ang(1-7)/Mas signalling as a result of oestrogen-dependent Mas expression.

Sex Differences in Mortality Rates and Underlying Conditions for COVID-19 Deaths in England and Wales

ObjectiveTo address the issue of limited national data on the prevalence and distribution of underlying conditions among COVID-19 deaths between sexes and across age groups. Patients and MethodsAll adult (≥18 years) deaths recorded in England and Wales (March 1, 2020, to May 12, 2020) were analyzed retrospectively. We compared the prevalence of underlying health conditions between COVID and non–COVID-related deaths during the COVID-19 pandemic and the age-standardized mortality rate (ASMR) of COVID-19 compared with other primary causes of death, stratified by sex and age group. ResultsOf 144,279 adult deaths recorded during the study period, 36,438 (25.3%) were confirmed COVID deaths. Women represented 43.2% (n=15,731) of COVID deaths compared with 51.9% (n=55,980) in non-COVID deaths. Overall, COVID deaths were younger than non-COVID deaths (82 vs 83 years). ASMR of COVID-19 was higher than all other common primary causes of death, across age groups and sexes, except for cancers in women between the ages of 30 and 79 years. A linear relationship was observed between ASMR and age among COVID-19 deaths, with persistently higher rates in men than women across all age groups. The most prevalent reported conditions were hypertension, dementia, chronic lung disease, and diabetes, and these were higher among COVID deaths. Pre-existing ischemic heart disease was similar in COVID (11.4%) and non-COVID (12%) deaths. ConclusionIn a nationwide analysis, COVID-19 infection was associated with higher age-standardized mortality than other primary causes of death, except cancer in women of select age groups. COVID-19 mortality was persistently higher in men and increased with advanced age.

Men and COVID-19: A Biopsychosocial Approach to Understanding Sex Differences in Mortality and Recommendations for Practice and Policy Interventions

Data suggest that more men than women are dying of coronavirus disease 2019 (COVID-19) worldwide, but it is unclear why. A biopsychosocial approach is critical for understanding the disproportionate death rate among men. Biological, psychological, behavioral, and social factors may put men at disproportionate risk of death. We propose a stepwise approach to clinical, public health, and policy interventions to reduce COVID-19–associated morbidity and mortality among men. We also review what health professionals and policy makers can do, and are doing, to address the unique COVID-19–associated needs of men.