Sex Differences In Prognosis Research Articles

Abstract 4137939: Mosaic loss of Y chromosome is associated with increased all-cause mortality in patients with ST-segment elevation myocardial infarction

Introduction: Mosaic loss of Y chromosome (LOY), a common subtype of somatic mosaicism, is characterized as loss of the entire Y chromosome in a mosaic manner and increases with age. Accumulating evidence has manifested the positive link between LOY and shorter life expectations in elderly men as well as common age-associated diseases, such as cancer and cardiovascular diseases. Experimental studies also demonstrated that hematopoietic LOY in mice induced cardiac fibrosis and led to increased mortality. However, little is known about LOY and prognosis of ST-segment elevation myocardial infarction (STEMI). Hypothesis: We hypothesized that LOY may be associated with lower survival rate of patients with STEMI. Aims: Investigating the impact of LOY in peripheral blood cells on prognosis of patients with STEMI. Methods: This study prospectively enrolled 928 males and 272 females undergoing primary percutaneous coronary intervention for STEMI. LOY was measured in 928 males using droplet digital polymerase chain reaction technique. Results: During a median follow-up of 3.99 years, 93 males (10.0%) and 45 females (16.5%) died. After adjusting for traditional cardiovascular risk factors, the risk of all-cause mortality in males with LOY ≥ 18% (the 90th percentile of LOY) increased to 2.45 (95% confidence intervals [CI]: 1.16–5.15, P = 0.018), 2.11 (95% CI: 1.11–4.01, P = 0.024), and 1.88 (95% CI: 1.02–3.45, P = 0.043) times during 1-, 2-, and 3-year follow-up, respectively, compared to males with LOY < 18%. Among males without prior MI, those with LOY ≥ 18% had an increased risk of all-cause mortality compared to those with LOY < 18% (adjusted hazard ratio 1.93, 95% CI: 1.01–3.67; P = 0.045); this was not observed for males with prior MI. Female patients had a 1.71-fold (95%CI: 1.04–2.81; P = 0.035) increased risk of all-cause mortality than males with LOY < 18%, whereas the risk was similar to males with LOY ≥ 18%. Conclusion: LOY was associated with an increased risk of all-cause mortality in male STEMI patients, particularly in those without prior MI. Detecting LOY in STEMI patients could help further refine sex differences in prognosis and assist in identifying male patients with better prognoses.

Sex differences in prognosis of primary bone cancer: a propensity score-matched study

Abstract Objectives Sex differences in survival in primary bone cancer have not been fully explored. Hence, this study was conducted to investigate the impact of sex on survival outcomes in patients with primary bone cancer. Methods The Surveillance, Epidemiology, and End Results (SEER)-17 database was used to identify patients with primary bone cancer. One-to-one propensity score matching (PSM) was employed to balance baseline characteristics. Kaplan-Meier curves and log-rank tests were used to evaluate differences in cancer-specific survival (CSS) and overall survival (OS) between sexes. Multivariate Cox regression analysis was performed to verify the independent effect of sex on survival, and sensitivity analysis was performed to determine the robustness of the results. Results A total of 8,791 patients were included, with 4,928 males (56.1 %) and 3,863 females (43.9 %), and a median follow-up time of 38 months. After PSM, 3,812 males and 3,812 females were included in the study, with balanced baseline characteristics between the groups. Post-PSM, females show significantly better CSS (HR=0.88, 95 % CI, 0.81–0.96, p=0.004) and OS (HR=0.87, 95 % CI, 0.81–0.94, p<0.001) compared to males. In multivariable Cox regression, the female sex was identified as an independent protective factor for both CSS (HR=0.86, 95 % CI, 0.79–0.94, p<0.001) and OS (HR=0.83, 95 % CI, 0.77–0.89, p<0.001). Conclusions Based on the analysis of SEER data with a large sample size, this study revealed that female patients with primary bone cancer have significantly better survival compared to males.

Intravascular Imaging–Guided Optimization of Complex Percutaneous Coronary Intervention by Sex

There have been heterogeneous results related to sex differences in prognosis after percutaneous coronary artery intervention (PCI) for complex coronary artery lesions. To evaluate potential differences in outcomes with intravascular imaging-guided PCI of complex coronary artery lesions between women and men. This prespecified substudy evaluates the interaction of sex in the investigator-initiated, open-label, multicenter RENOVATE-COMPLEX-PCI randomized clinical trial, which demonstrated the superiority of intravascular imaging-guided PCI compared with angiography-guided PCI in patients with complex coronary artery lesions. The trial was conducted at 20 sites in Korea. Patients with complex coronary artery lesions undergoing PCI were enrolled between May 2018 and May 2021, and the median (IQR) follow-up period was 2.1 (1.4-3.0) years. Data were analyzed from December 2022 to December 2023. After diagnostic coronary angiography, eligible patients were randomly assigned in a 2:1 ratio to receive intravascular imaging-guided PCI or angiography-guided PCI. The choice and timing of the intravascular imaging device were left to the operators' discretion. The primary end point was target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Secondary end points included individual components of the primary end point. Of 1639 included patients, 339 (20.7%) were women, and the mean (SD) age was 65.6 (10.2) years. There was no difference in the risk of the primary end point between women and men (9.4% vs 8.3%; adjusted hazard ratio [HR], 1.39; 95% CI, 0.89-2.18; P = .15). Intravascular imaging-guided PCI tended to have lower incidence of the primary end point than angiography-guided PCI in both women (5.2% vs 14.5%; adjusted HR, 0.34; 95% CI, 0.15-0.78; P = .01) and men (8.3% vs 11.7%; adjusted HR, 0.72; 95% CI, 0.49-1.05; P = .09) without significant interaction (P for interaction = .86). In patients undergoing complex PCI, compared with angiographic guidance, intravascular imaging guidance was associated with similar reduction in the risk of target vessel failure among women and men. The treatment benefit of intravascular imaging-guided PCI showed no significant interaction between treatment strategy and sex. ClinicalTrials.gov Identifier: NCT03381872.

Sex Differences in Prognosis of Childhood Arterial Ischemic Stroke: Results From Chinese Pediatric Ischemic Stroke Registry Multicenter Registry

BackgroundCurrent studies on the impact of sex in the prognosis of childhood arterial ischemic stroke (AIS) are limited. We aimed to explore the sex differences in outcomes in patients with childhood AIS. MethodsA retrospective analysis was conducted using the prospective data from the Chinese Pediatric Ischemic Stroke Registry. Baseline characteristics between sexes were compared in the total population cohort, propensity score (PS)-matched cohort, and inverse probability of treatment weighting cohort. Multivariate logistic regression and ordinal regression were used to analyze the association of sex with outcomes. Mixed-effects regression model was applied to further analyze the improvement in pediatric modified Rankin Scale (mRS) scores between sexes from 90 days to one year. Survival analysis was used to estimate the recurrence rates during the follow-up period. ResultsA total of 468 patients were finally included. Multivariate logistic regression showed that there were no significant differences between females and males in achieving favorable outcome (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.63 to 1.72), functional independence (OR 0.98, 95% CI 0.59 to 1.63), or shift to worse pediatric mRS scores (OR 0.83, 95% CI 0.59 to 1.17) at 90-day. Mixed-effects regression and survival analysis indicated that females and males exhibited comparable functional recovery from 90 days to one year and had similar recurrent risk during the follow-up period. ConclusionsThis nationally-representative observational study indicated that both male and female pediatric patients with AIS exhibited comparable similar clinical outcomes at 90 days, as well as similar improvements and risks of recurrence during the follow-up period.

Sex differences in clinical characteristics and long-term outcome in patients with heart failure: data from the KorAHF registry.

Sex differences in the prognosis of heart failure (HF) have yielded inconsistent results, and data from Asian populations are even rare. This study aimed to investigate sex differences in clinical characteristics and long-term prognosis among Korean patients with HF. A total of 5,625 Korean patients hospitalized for acute HF were analyzed using a prospective multi-center registry database. Baseline clinical characteristics and long-term outcomes including HF readmission and death were compared between sexes. Women were older than men and had worse symptoms with higher N-terminal pro B-type natriuretic peptide levels. Women had a significantly higher proportion of HF with preserved ejection fraction (HFpEF). There were no significant differences in in-hospital mortality and rate of guideline-directed medical therapies in men and women. During median follow- up of 3.4 years, cardiovascular death (adjusted hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.07-1.78; p = 0.014), and composite outcomes of death and HF readmission (adjusted HR, 1.13; 95% CI, 1.01-1.27; p = 0.030) were significantly higher in men than women. When evaluating heart failure with reduced ejection fraction (HFrEF) and HFpEF separately, men were an independent risk factor of cardiovascular death in patients with HFrEF. Clinical outcome was not different between sexes in HFpEF. In the Korean multi-center registry, despite having better clinical characteristics, men exhibited a higher risk of all-cause mortality and readmission for HF. The main cause of these disparities was the higher cardiovascular mortality rate observed in men compared to women with HFrEF.

Is There a Sex Difference in the Prognosis of Hypertrophic Cardiomyopathy? A Systematic Review and Meta-Analysis.

Background It is still unclear whether there is a sex difference in the prognosis of patients with hypertrophic cardiomyopathy (HCM). Therefore, we performed a meta-analysis to elucidate the association between sex and adverse outcomes in patients with HCM. Methods and Results The PubMed, Cochrane Library, and Embase databases were used to search for studies on sex differences in prognosis in patients with HCM up to August 17, 2021. Summary effect sizes were calculated using a random effects model. The protocol was registered in PROSPERO (International prospective register of systematic reviews) (registration number- CRD42021262053). A total of 27 cohorts involving 42 365 patients with HCM were included. Compared with male subjects, female subjects had a higher age at onset (mean difference=5.61 [95% CI, 4.03-7.19]), a higher left ventricular ejection fraction (standard mean difference=0.09 [95% CI, 0.02-0.15]) and a higher left ventricular outflow tract gradient (standard mean difference=0.23 [95% CI, 0.18-0.29]). The results showed that compared with male subjects with HCM, female subjects had higher risks of HCM-related events (risk ratio [RR]=1.61 [95% CI, 1.33-1.94], I2=49%), major cardiovascular events (RR=3.59 [95% CI, 2.26-5.71], I2=0%), HCM-related death (RR=1.57 [95% CI, 1.34-1.82], I2=0%), cardiovascular death (RR=1.55 [95% CI, 1.05-2.28], I2=58%), noncardiovascular death (RR=1.77 [95% CI, 1.46-2.13], I2=0%) and all-cause mortality (RR=1.43 [95% CI, 1.09-1.87], I2=95%), but not atrial fibrillation (RR=1.13 [95% CI, 0.95-1.35], I2=5%), ventricular arrhythmia (RR=0.88 [95% CI, 0.71-1.10], I2=0%), sudden cardiac death (RR=1.04 [95% CI, 0.75-1.42], I2=38%) or composite end point (RR=1.24 [95% CI, 0.96-1.60], I2=85%). Conclusions Based on current evidence, our results show significant sex-specific differences in the prognosis of HCM. Future guidelines may emphasize the use of a sex-specific risk assessment for the diagnosis and management of HCM.

Impact of Body Mass Index on Survival Depending on Sex in 14,688 Patients with Gastric Cancer in a Tertiary Hospital in South Korea.

The incidence and prognosis of gastric cancer (GC) shows sex difference. This study aimed to evaluate the effect of body mass index (BMI) on GC survival depending on sex. The sex, age, location, histology, TNM stages, BMI, and survival were analyzed in GC patients from May 2003 to February 2020 at the Seoul National University Bundang Hospital. Among 14,688 patients, there were twice as many males (66.6%) as females (33.4%). However, under age 40 years, females (8.6%) were more prevalent than males (3.1%). Cardia GC in males showed a U-shaped distribution for underweight (9.6%), normal (6.4%), overweight (6.1%), obesity (5.6%), and severe obesity (9.3%) but not in females (p=0.003). Females showed decreased proportion of diffuse-type GC regarding BMI (underweight [59.9%], normal [56.8%], overweight [49.5%], obesity [44.8%], and severe obesity [41.7%]), but males did not (p<0.001). Both sexes had the worst prognosis in the underweight group (p<0.001), and the higher BMI, the better prognosis in males, but not females. Sex differences in prognosis according to BMI tended to be more prominent in males than in females in subgroup analysis of TNM stages I, II, and III and the operative treatment group. GC-specific survival was affected by BMI in a sex-dependent manner. These differences may be related to genetic, and environmental, hormonal factors; body composition; and muscle mass (Trial registration number: NCT04973631).

Microsatellite instability and sex differences in resectable gastric cancer – A pooled analysis of three European cohorts

ObjectiveBiological sex differences in cancer are increasingly acknowledged. Here, we examined these differences in clinicopathological characteristics and survival in microsatellite instability (MSI)-high and microsatellite stable (MSS) gastric cancer (GC). DesignWe analysed MSI status by polymerase chain reaction (PCR) and/or mismatch repair (MMR) status by immunohistochemistry in a pooled analysis of individual patient data from one retrospective cohort from Cologne, and the randomised phase III clinical trials D1/D2 and CRITICS. All patients had resectable adenocarcinoma of the stomach and/or gastro-oesophageal junction. Patients were treated with either surgery only or perioperative chemo(radio)therapy. ResultsMSI and/or MMR analyses on 1307 tumours resulted in 1192 (91.2%) MSS and/or MMR proficient (MMRP) [median age, 65 years; 759 males (63.7%); 619 treated with surgery only (51.9%)], and 115 (8.8%) MSI-high [median age, 69 years; 67 males (58.3%); 76 treated with surgery only (66.1%)] GC cases. Males had shorter overall survival (OS) than female MSI-high GC (5-year OS 34.7% vs. 69.7%; hazard ratio (HR) 2.68, 95%CI 1.60 to 4.49; p < 0.001). Females with MSI-high had longer OS than those with MSS/MMRP GC (HR 0.61, 95%CI 0.41 to 0.92; p = 0.02). Males with MSI-high did not have longer OS than those with MSS/MMRP GC (HR 1.26, 95%CI 0.94 to 1.69; p = 0.12). ConclusionsMSI-high GC males had a significantly worse prognosis compared to their female counterparts in three independent cohorts. In addition, the favourable prognostic value of MSI was only seen in females and not in males. These observations emphasise the need to consider sex differences in prognosis and treatment effects in oncology. Clinical trial registrationThe CRITICS trial is registered at ClinicalTrials.gov, number NCT00407186; EudraCT, number 2006-004130-32; and CKTO, 2006-02.

Sex Differences in Prognosis in Heart Failure with Preserved and Mid-Range Ejection Fraction: A Systematic Review and Meta-Analysis

Sex Differences in Prognosis in Heart Failure with Preserved and Mid-Range Ejection Fraction: A Systematic Review and Meta-Analysis

Sex differences in prognosis of significant secondary mitral regurgitation.

AimsSecondary mitral regurgitation (MR) is more frequent in men than in women. However, little is known about differences in prognosis between men and women with secondary MR. The objective of this study is to investigate the sex distribution of secondary MR and the prognostic differences between sexes.MethodsPatients with significant secondary MR, of both ischaemic and non‐ischaemic aetiologies, were identified through the departmental electronic patient files and retrospectively analysed. The primary endpoint was all‐cause mortality.ResultsA total of 698 patients (mean age 66 ± 11 years) with significant secondary MR were included: 471 (67%) men and 227 (33%) women. Ischaemic heart failure was significantly more common in men (61%), whereas non‐ischaemic heart failure was more prevalent in women (63%). Women had significantly smaller left ventricular (LV) volumes when compared with men and more preserved LV systolic function when assessed with LV global longitudinal strain (GLS; 8.5 ± 4.1% vs. 7.5 ± 3.6%; P = 0.004). Women more often underwent surgical mitral valve repair (34%) when compared with men (26%), although no differences were observed for transcatheter mitral valve repair. During a median follow‐up of 57 [interquartile range 29–110] months, 373 (53%) patients died. Women showed significantly lower mortality rates at 1‐, 2‐ and 5‐year follow‐up (9%, 16% and 33% vs. 10%, 20% and 42%) when compared with men (P = 0.001).ConclusionsSignificant secondary MR is more frequently observed in men as compared with women and is associated with worse prognosis.

Time-varying effect of sex on prognosis of lung adenocarcinoma surgical patients in China.

BackgroundLittle is known about the prognostic advantage of sex for pulmonary adenocarcinoma among Chinese patients. In this study, we aimed to investigate the true sex differences in prognosis by adjusting for confounders and to explore whether the differences were time‐varying.MethodsWe identified 4438 lung adenocarcinoma patients who underwent surgery at a regional Cancer Center of China from 2008 to 2016, retrospectively. Sex, age group, smoking history, year of diagnosis and pathological stage were collected. Time‐dependent Cox regression models with inverse probability of treatment weighting (IPTW) based on propensity score were used to assess the effect of sex and account for confounders. Landmark analyses were conducted to assess survival before, and after, five years.ResultsOf these patients, 1761 (39.7%) were men and 2677 (60.3%) were women. Median follow‐up time was 52.6 months. After IPTW adjustment, women were found to have significantly better survival than men varying with time in both crude and IPTW models (hazard ratio [HR] [t] = 0.453*1.015t, where t is the length of time from treatment and its unit is month, p < 0.001). Women had significantly better survival than men within 0–5 years after surgery (HR = 0.763, 95% CI: 0.649–0.897, p = 0.001), whereas there was no difference after five years (HR = 1.135, 95% CI: 0.803–1.605, p = 0.472). In subgroup analysis, women in the 61–71+ age group, in the more than 20 year packs group, pathological stage 0–IB group, and 2013–2016 diagnosis period group revealed the same prognostic pattern.ConclusionsCompared with men, women had better survival after surgical resection of lung adenocarcinoma, especially those who were older and nonsmokers or heavy‐smokers and were pathological stage 0–IB in early years, while the advantage for women diminished with time.

Female patients with follicular lymphoma have a better prognosis if primary remission lasts over 24 months

Findings regarding the role of sex in follicular lymphoma (FL) are contradictory and the prognostic value of sex among patients with early progression of disease (POD) remains unclear. We collected real-life data from nine hospitals in Finland and Spain including 1020 FL patients to study the influence of sex on disease outcome. The median follow-up duration was 67 months (range 0–226 months). Female patients showed better progression-free survival (PFS) (hazard ratio [HR], 0.720; 95% confidence interval [CI], 0.588–0.881), disease-specific survival (DSS) (HR, 0.653; 95% CI, 0.448–0.951), and overall survival (OS) (HR, 0.653; 95% CI, 0.501–0.853) than male patients. However, there were no significant sex differences in prognosis in patients with early POD. This study strengthens the understanding that male sex is an adverse prognostic factor for FL. However, this difference does not apply to patients with early POD.

Abstract 6569: Regulatory networks of liver carcinoma reveal sex specific patterns of gene regulation

Abstract Despite pronounced sex differences in cancer incidence, severity, and response to treatment, most current approaches to clinical management, as well as therapeutics development and selection, are sex-independent. For most cancer types, including liver cancer, males have a higher risk of developing the disease and a lower survival rate than women. However, the molecular features that drive these sex differences are poorly understood. We inferred patient-specific regulatory networks of liver hepatocellular carcinoma using data from TCGA. By comparing the female and male networks, we found marked sex differences in transcriptional regulatory processes relevant to disease development, progression, and response to therapy. We found that oncogenes have significantly higher regulatory targeting in males, while tumor suppressor genes have significantly higher targeting in females. Many “hallmark” cancer pathways, including the HEDGEHOG, WNT, and TGF-β signaling pathways, were significantly more highly targeted in males, while drug metabolism and immune related pathways were enriched for genes highly targeted in females. We also evaluated sex-biased somatic mutation patterns using mutation and copy number alteration data in TCGA. By summarizing mutations found in genes into pathway mutation scores, we found sex-biased mutation profiles for many pathways, providing additional support for biological sex differences associated with WNT, NOTCH, TGF-β, and HEDGEHOG signaling pathways. Our analysis uncovered patterns of gene regulation that differentiate male and female liver cancer and may be associated with sex differences in prognosis and treatment response. These findings provide insight into the mechanisms that drive clinically observed sex differences and underscore the importance of considering sex as a factor influencing disease etiology and in developing and prescribing therapies. Our network approach can provide insights into why some therapies have differential effect in males and females, and suggest new ways to optimize drug response in each sex. Citation Format: Camila M. Lopes-Ramos, Marieke Kuijjer, Kimberly Glass, Dawn DeMeo, John Quackenbush. Regulatory networks of liver carcinoma reveal sex specific patterns of gene regulation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6569.

Sex differences in the prognosis after surgery for esophageal squamous cell carcinoma and adenocarcinoma

Some investigations suggest a better prognosis in women compared to men with esophageal cancer but these differences are uncertain. The aim of our study was to clarify whether sex influences the prognosis after esophagectomy for esophageal squamous cell carcinoma and esophageal adenocarcinoma. A population-based and nationwide cohort study included almost all patients who underwent esophagectomy for esophageal cancer in Sweden in 1987-2010, with follow-up until 2016. Patients' sex was analyzed in relation to risk of mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for calendar period, age, education, comorbidity, tumor stage, neoadjuvant therapy, and surgeon volume. Among 1,816 participants, 1,024 (56%) had esophageal squamous cell carcinoma (355 [35%] women), and 792 (44%) had esophageal adenocarcinoma (103 [13%] women). Compared to men, women had a decreased overall all-cause mortality in esophageal squamous cell carcinoma (HR = 0.73, 95% CI 0.63-0.85). Stratified analyses showed decreased mortality limited to women aged >55 years (HR = 0.71, 95% CI 0.61-0.83), but in all tumor stages, particularly stages 0-I (HR = 0.54, 95% CI 0.37-0.79). Women also had decreased 90-day all-cause mortality, 5-year all-cause mortality, and 5-year disease-specific mortality in esophageal squamous cell carcinoma compared to men. For esophageal adenocarcinoma, no sex differences were found for any of the mortality outcomes. Thus, women who undergo esophagectomy for esophageal squamous cell carcinoma seem to have better prognosis than men, especially those with early tumor stages, whereas no sex differences in prognosis were found for esophageal adenocarcinoma.

Sex differences in prognosis and quality of life in myasthenia gravis

Background: The occurrence of myasthenia gravis (MG) is influenced by sex and age, whereas little attention has been paid to sex differences in disease prognosis and quality of life (QOL) in MG patients.

Acknowledging the Risk for Traumatic Brain Injury in Women Veterans.

Since the Iraq and Afghanistan wars began, an unprecedented number of women have been engaging in combat operations. Likewise, the number of women using Department of Veterans Affairs (VA) services has doubled since 2001. Military service, and deployment to combat in particular, poses certain risks for traumatic brain injury (TBI)-for all service members. However, women may have additional military and nondeployment risk factors such as intimate partner violence (IPV). We briefly review the definition and classification issues related to TBI, as well as common acute and chronic health symptoms after TBI. Specific sex differences in prognosis after TBI, in particular the neurobehavioral symptoms, are also reviewed. We then focus on the emerging literature regarding TBI in women veterans including the etiologies, outcomes, and unique challenges this population faces. The article concludes with suggestions for enhanced screening by VA and non-VA providers alike, as well as directions for future research and clinical inquiry.

Sex Differences in Mortality Associated With Computed Tomographic Angiographic Measurements of Obstructive and Nonobstructive Coronary Artery Disease

Background— Sex differences exist in the prevalence and severity of obstructive coronary artery disease (CAD). Limited data are available to explore sex differences in prognosis with coronary computed tomographic angiographic (CCTA) measurements of CAD including novel nonobstructive plaque extent. Methods and Results— A total of 1127 consecutive patients were clinically referred to 16-slice CCTA and followed for the occurrence of all-cause death. Time to death was calculated by univariable and multivariable Cox proportional hazard models. Four-year survival (92.1%) was similar by sex ( P =0.52). Women more often had no coronary stenosis (54%) as compared with men (28%) ( P &lt;0.0001). Mortality worsened for both women ( P &lt;0.0001) and men ( P =0.002) by the number of vessels with ≥50% stenosis. For women, overall mortality ranged from 3.5% for no CAD to 25.0% for women with 3-vessel plus left main obstructive CAD ( P &lt;0.0001). For men, overall mortality ranged from 2.7% for no CAD to 17.4% for males with 3-vessel plus left main obstructive CAD ( P =0.002). Nonobstructive disease was prevalent in women (range, 24% to 66%) and men (range, 45% to 74%) ages 45 to ≥80 years. Nonobstructive CAD extent was a significant estimator of all-cause mortality when added to a model containing pretest CAD likelihood and obstructive CAD extent ( P =0.039). For men, in a risk-adjusted model including pretest CAD likelihood and obstructive CAD, the number of nonobstructive lesions was not a significant estimator of mortality ( P =0.9). For women, the relative hazard for mortality, in a multivariable model, was 1.3 per nonobstructive lesion ( P =0.003), including pretest CAD likelihood and obstructive CAD as covariates. For women, risk-adjusted median mortality ranged from 2.9% to 10.9% for none to ≥4 nonobstructive lesions ( P &lt;0.0001). Conclusions— Based on our preliminary analyses, CCTA obstructive and nonobstructive CAD adds incremental value to clinical assessment for risk stratification. Moreover, the extent of nonobstructive CAD by CCTA predicts mortality in women but not in men and may be helpful to optimize therapeutic strategies for women.

Sex differences in illness incidence, prognosis and mortality: Issues and evidence

This paper reviews current research and presents new evidence concerning sex differences in morbility and mortality. Attention is focused primarily on the following topics: (1) sex differences in incidence, prognosis and mortality for several major types of chronic disease, (2) causes of sex differences in morbility and mortality, (3) sex differences in physician visits and (4) a methodological issue, whether there are sex differences in reporting morbility. Relationships between sex differences in incidence, prognosis and mortality have been analyzed for various types of cancer, ischemic heart disease and rheumatoid arthritis. There was little or no correlation between sex differences in incidence and sex differences in prognosis. Sex differences in prognosis were generally smaller than sex differences in incidence. In most cases, sex differences in prognosis made a relatively small contribution to sex differences in mortality, and sex differences in incidence were the primary determinant of sex differences in mortality. These patterns indicate that the causes of sex differences in incidence frequently have little effect on sex differences in prognosis. Reasons for this are discussed in the text. The causes of sex differences in morbility and mortality are discussed, with attention to the contributions of genetic and environmental factors, sex roles, sex differences in stress responses and sex differences in risk-taking and preventive behaviors. One conclusion is that, although men take more risks of certain types, there does not appear to be a consistent sex difference in propensity to take risks or to engage in preventive behavior. Rather sex differences in risk-taking and preventive behavior vary depending on the specific behavior and the culture considered. Sex differences in physician visit rates are influenced by a variety of biological and cultural factors. For example, women's more complex and demanding reproductive functions are a major reason for women's higher rates of physician visits, at least in Western countries. The importance of cultural factors is indicated by the cross-cultural and historical variation in sex differences in physician visit rates. In order to test whether there are sex differences in the reporting of health and illness, discrepancies between self-report and medically-evaluated morbidity measures have been assessed for males and females in twelve studies. These data indicate that sex differences in reporting vary depending on the particular type of morbidity measure considered. For example, for self-ratings of general health women may be more predisposed than men to rate their health poor, but no significant sex differences were observed in reporting of physician visits or hospital admissions. The evidence discussed in this paper illustrates the diversity and complexity of factors that influence sex differences in morbidity and mortality. A major challenge for research in this area is to derive explanations of sex differences in morbidity and mortality that are as broad and general as possible and yet take adequate account of the real complexity of the data.

Sex differences in prognosis of childhood T-cell leukemia.

Bone marrows of 41 untreated children and adolescents with acute lymphocytic leukemia were studied by combined immunologic and histochemical methods at the time of diagnosis. Eleven were classified as T-cell lymphoblastic leukemias (27%) on the basis of cytochemical stains and E-rosette assay. The patients in this group has low median age of 8 years, relatively low median WBC of 13.4 x 10(3)/cc, 6/11 were female, and only 2/5 males had a mediastinal mass. The girls had a lower median age than boys (7 vs 9 years), none had mediastinal masses or extramedullary involvement, and their survival was greater than 27 months compared to 14 months for the boys (P less than 0.01). All patients were enrolled and treated on the (then) currently active CCSG protocols for ALL. This study emphasizes the fact that not all patients with T-cell ALL have poor prognosis, that sex could be an important factor affecting survival, and that the difference in survival could not be adequately explained by differences in the initial WBC.

Cancer of the tongue, mouth, and pharynx. Sex differences in prognosis following radio-therapy: Marion H. Russell. Brit. M. J. 1: 430, 1954

Cancer of the tongue, mouth, and pharynx. Sex differences in prognosis following radio-therapy: Marion H. Russell. Brit. M. J. 1: 430, 1954