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Why do women live longer than men?
Abstract
Factors responsible for the gender difference in life-span being 4-5 years in favor of women were investigated. Cardiovascular risks are responsible for a five times higher mortality and three times higher morbidity in men compared with women. Genetics demonstrate marked gender differences in chromosomal constitution and female preponderance of the life-guard telomeres on chromosomes during mitotic cell division. This difference, however, cannot explain the gender gap fully. Endogenous estradiol - acting in picomoles - provokes marked cardiovascular changes. Cardiac output increases around 20% during the second half of the menstrual cycle and in pregnancy. This continuous biological challenge during the reproductive years creates optimal cardiovascular compliance comparable to the effects of exercise. The "jogging female heart" may explain the lower incidence of cardiovascular disease before menopause and the equalization after the menopause.
... W omen live longer than men (1)(2)(3)(4). Worldwide, the average life span of women is found to be 4 to 5 years more than men (5). Women usually develop cardiovascular disorders at older ages compared to men and mostly after menopause (6). ...
... Women usually develop cardiovascular disorders at older ages compared to men and mostly after menopause (6). Overall, cancer and severe infectious disorders are less common among women compared to men (1)(2)(3)(4)(5)(6)(7). For instance, women have 40% less viral RNA than men in acute HIV infection and also a lower mortality rate in viral hepatitis (5). ...
... Overall, cancer and severe infectious disorders are less common among women compared to men (1)(2)(3)(4)(5)(6)(7). For instance, women have 40% less viral RNA than men in acute HIV infection and also a lower mortality rate in viral hepatitis (5). Recent data from the COVID-19 pandemic has been further documented that women can be less prone to severe infectious disorders (8,9). ...
Women live longer than men. Cardiovascular disorders, cancers, and serious infectious conditions are less common among women than men. Recent data also indicate that women, particularly before menopause, are less susceptible to severe COVID-19, a viral infection hitting less-healthy individuals. The superiority of women regarding health has not been completely understood and partly been explained by estradiol beneficial effects on the microenvironment of the body, notably cytokine network. Estradiol cycles are aligned with menstruation cycles, a challenge for distinguishing their individual effects on human health. Large-scale, long-term studies indicate that hysterectomy, particularly at younger ages, is associated with an increased risk of mortality, cancer, or heart disorders. The underlying mechanisms for the increased risk in hysterectomized women are hard to be investigated in animal models since only a few primates menstruate. However, blood exchange models could resemble menstruation and provide some insight into possible beneficial effects of menstruation. Sera from animal models (neutral blood exchange) and also humans that have undergone therapeutic plasma exchange enhance the proliferation of progenitor cells in the culture and contain lower levels of proinflammatory factors. If menstruation resembles a blood exchange model, it can contribute to a healthier cytokine network in women. Consequently, menstruation, independently from estradiol health beneficial effects, can contribute to greater longevity and protection against certain disorders, e.g., COVID-19, in women. Investigation of COVID-19 rate/severity in hysterectomized women will provide insight into the possible beneficial effects of menstruation in COVID-19.
... More specifically, patients with a primary diagnosis of PE (ICD-9-CM codes 415.11 or 415. 19) or with a secondary discharge diagnosis of PE associated with a primary code compatible with PE (ICD-9-CM codes 51881, 51882, 51884, 7991, 4534, 4538, 4536 78551, 4275, 4589) in the hospital discharge form were included. In order to estimate the incidence of PE events requiring hospital care, the first hospitalization in a year was considered for each subject, excluding any hospitalizations in the subsequent 365 days. ...
... Among younger age groups, males exhibited a higher incidence rate compared to females, likely influenced by physiopathological factors associated with venous thromboembolism (18). Conversely, in older age groups, females constituted a larger proportion of patients, possibly reflecting demographic trends in advanced age cohorts (19). Our data confirmed PE as predominantly affecting older individuals, with incidence rates in the over-85 exceeding over tenfold those in people under 75 (17,20,21]. ...
Background:
Pulmonary embolism poses a global health concern. Administrative databases serve as valuable sources for broad epidemiological studies on the prevalence and incidence of major diagnoses or diseases. The primary scope is to provide up-to-date insights into Pulmonary Embolism incidence trends, examining shifts in management and outcomes.
Design:
This retrospective observational study examines a 12-year dataset from hospitals in the Tuscany Region, covering the first two years of the Covid-19 pandemic.
Methods:
Administrative data from residents aged 18 and older discharged from hospital between 2010 and 2021 were used for the analysis.
Results:
Hospitalized pulmonary embolism incidence slightly declined from 2010 to 2019 (64.7 to 60.9 x 100,000; p=0.152). Males under 75 showed a higher incidence rate, while females had higher incidence rates in older age groups. In-hospital and 30-day mortality decreased from 2010 to 2019 (p=0.001 and 0.020 respectively). In 2020, 30-day mortality increased (12.4% vs 10.1%, p=0.029), while in-hospital mortality remained stable. One-year mortality was stable from 2010-2019 but increased in 2020 (32.6% vs 29.4%, p=0.037). Considering the multivariable model, one-year mortality is significantly associated with sex, age, and comorbidities.
Conclusions:
Our study shows that Pulmonary Embolism persists as a relevant burden in Tuscany region, but with improvements in management over the past decade and a decisive change in pharmacological treatment. Gender-related differences emerge, highlighting the need for a gender-specific healthcare approach.
... From a sociological perspective, these disparities lead to increased male exposure to occupational hazards, unhealthy dietary choices, and elevated alcohol and tobacco consumption-major risk factors for highly fatal non-communicable chronic diseases, ultimately leading to a reduced life expectancy in males [40]. From a genetic perspective, females have two X chromosomes, compared to males longer telomeres, and experience a slower telomere shortening process, potentially contributing to their longer lifespan [41,42]. The beneficial impact of estrogen on the vascular and lipid profiles of premenopausal females appears to delay and reduce the impact of atherosclerosis. ...
... The beneficial impact of estrogen on the vascular and lipid profiles of premenopausal females appears to delay and reduce the impact of atherosclerosis. However, the absence of estrogen after menopause may also affect certain diseases in females [41]. Additionally, testosterone has the potential to impede both the inherent and acquired immune responses, leading to a less robust immune system in males. ...
"Exercise is the best medicine" is well known, but the optimal dose of physical activity (PA) for males and females across different age groups is still unknown. This study, using data from the four waves of CHARLS, aimed to determine the optimal PA dose that reduces frailty risks among older adults across various age groups and both sexes. We created a frailty index score using 63 health-related variables and used 0.21 as the frailty cut point. Binary logistic regression was used to compare the effect of vigorous, moderate, and light intensity PA under IPAQ criteria on frailty risk. The study found that regardless of whether males or females, the optimal effect of vigorous-intensity PA in reducing the risk of frailty is consistently observed throughout the entire old age career. Moreover, the age groups at which moderate-intensity PA reduces the risk of frailty were from age 70 for males and from age 80 for females. And light-intensity PA had no effect on reducing the risk of frailty. Moderate and vigorous intensity of PA in older adults should be promoted, but guidelines and recommendations must account for optimal associations with PA dose across genders and age groups.
... The male-female health-survival paradox is not fully understood and influenced by genetic, hormonal, and immunological factors. Genetically, the presence of two X chromosomes, longer telomers and a slower shortening process are potential explanations for the longer survival in women (Eskes & Haanen, 2007;Haapanen et al., 2018). The positive effects of oestrogen on the vascular and lipid profile in women before the menopause seemed to contribute to a later and smaller impact of atherosclerosis. ...
... The positive effects of oestrogen on the vascular and lipid profile in women before the menopause seemed to contribute to a later and smaller impact of atherosclerosis. However, their deprivation after the menopause could also influence specific diseases in women (Eskes & Haanen, 2007). Furthermore, testosterone is likely to inhibit the innate and adaptative immune responses resulting in a weaker immune system in men which in turn make them more vulnerable to infections and, ultimately, death (Gubbels Bupp, 2015). ...
Background/Objective
The mechanisms, risk factors and influence of sex on the incidence of frailty components are not fully understood. The aim of this study was to analyse sex differences in factors associated with the increase in the number of frailty components.
Methods
A 12-year follow-up analysis was conducted with 1,747 participants aged ≥ 60 of the ELSA Study with no frailty at baseline. Generalised linear mixed models were used to analyse the increase in the number of frailty components stratified by sex, considering socioeconomic, behavioural, clinical and biochemical characteristics as exposure variables.
Results
The increase in the number of frailty components in both sexes was associated with an advanced age (70 to 79 years and 80 years or older), low educational level, sedentary lifestyle, elevated depressive symptoms, joint disease, high C-reactive protein levels, perception of poor vision and uncontrolled diabetes (p < 0.05). Osteoporosis, low weight, heart disease, living with one or more people and perception of poor hearing were associated with an increase in the number of frailty components in men. High fibrinogen concentration, controlled diabetes, stroke and perception of fair vision were associated with the outcome in women (p < 0.05). Obese women and men and overweight women had a lower increase in the number of frailty components compared to those in the ideal weight range.
Conclusions
Socioeconomic factors, musculoskeletal disorders, heart disease and low weight seem to sustain the frailty process in men, whereas cardiovascular and neuroendocrine disorders seem to sustain the frailty process in women.
... In our study, the number of male patients was approximately three-fold that of female patients, as in previous studies. Multiple factors are suggested to contribute to sex differences in vascular disease, such as genetic factor, hormonal fluctuation, lifestyle and environmental influences [24,27]. In our study, sex differences may have occurred due to factors such as smoking habitus (more prevalent in male) [27]. ...
... Multiple factors are suggested to contribute to sex differences in vascular disease, such as genetic factor, hormonal fluctuation, lifestyle and environmental influences [24,27]. In our study, sex differences may have occurred due to factors such as smoking habitus (more prevalent in male) [27]. ...
Objectives
Flank pain is a common symptom in the emergency department and can be caused by a variety of diseases. Renal infarction (RI) is a very rare disease, and many RI patients complain of flank pain. However, there is no definitive predictor of RI when patients complain of flank pain. This study aimed to identify the clinical factors for predicting RI in patients with flank pain.
Methods
This retrospective single-center study was conducted on patients complaining of flank pain from January 2016 to March 2020 at a South Korean tertiary care hospital. Exclusion criteria included patients who did not undergo contrast-enhanced computed tomography, age < 18 years, and trauma. Demographic and laboratory data were obtained from medical records. Logistic regression analysis was conducted to identify predictors of RI occurrence.
Results
In all, 2,131 patients were enrolled, and 39 (1.8%) had RI. From a multivariable logistic regression analysis, an age ≥ 65 years (odds ratio [OR], 3.249; 95% confidence interval [CI], 1.366–7.725; p = 0.008), male sex (OR, 2.846; 95% CI, 1.190–6.808; p = 0.019), atrial fibrillation (OR, 10.386; 95% CI, 3.724–28.961; p < 0.001), current smoker (OR, 10.022; 95% CI, 4.565–22.001; p < 0.001), and no hematuria (OR, 0.267; 95% CI, 0.114–0.628; p = 0.002) were significantly associated with the occurrence of RI.
Conclusions
Five clinical factors, i.e., age ≥ 65 years, male sex, atrial fibrillation, current smoker, and no hematuria, were significantly associated with the occurrence of RI in patients with flank pain.
... A study on the telomere length in newborns observed no differences between male and female newborns in telomere Restriction Fragment (TRF) length [18]. Other previous studies clarified the connection between gender and telomere length, especially in leukocyte telomeres that are longer in women than men [19,20]. The longer telomere in women is due to the estrogen hormone that stimulates telomerase to add telomere repeats to the ends of chromosomes [21,22]. ...
... This decrease in telomere length is further accelerated with various diseases developing with growing old [25,26]. Various studies on human models have attempted to correlate telomere length with age; a study accentuated that individuals with long telomeres lived longer than their counterparts who were subjects with shorter telomeres and of almost the same age [20,27]. However, some factors accelerate the shortening of telomeres as genetics modifications [28], older paternal age at conception [29], poor health behaviors [30], and psychological stress [31]. ...
COVID-19 is a global crisis that requires a deep understanding of infection pathways to facilitate the development of effective treatments and vaccines. Telomere, which is regarded as a biomarker for other respiratory viral infections, might influence the demographic distribution of COVID-19 infection and fatality rates. Viral infection can induce many cellular remodeling events and stress responses, including telomere specific alterations, just as telomere shortening. In brief, this letter aims to highlight the connection between telomere shortening and susceptibility to COVID-19 infection, in addition to changes in telomeric length according to the variation of age and gender of confirmed cases with COVID-19 infection. To sum up, the correlation is revealed from the available data that connect telomere length and COVID-19 infection, demonstrated in the fact that the elderly patients and males are more susceptible to COVID-19 due to shortening in their telomere length.
... Influence by physician's gender in medical procedures Differences in Genetic predisposition/heredity to CVDs/neoplasms Gender difference in disease symptoms/signs awareness Only to mention some possible reasons for such a gender difference, women, even if with diabetes, have, on average, a longer life expectancy than men being therefore burdened by all frailties associated with aging and consequently have a greater probability of being affected by cardiovascular diseases [39,43,44]. Other important aspects concern socioeconomic differences, differences in the number of risk factors for atherosclerosis, differences in the achievement of therapeutic targets for dyslipidemias, arterial hypertension or diabetes itself, which all together disadvantage women with diabetes [32,34,[45][46][47][48][49]. ...
... Older Age at DFD onset (49) Longer duration of diabetes (49) Previous history of undertreatment of diabetes and of cardiovascular risk factors (46,47) Loss of hormonal protection after menopause (41,42) Earlier, more severe or underdiagnosed peripheral vessels' atherosclerotic disease (51,56) Co-presence of multiple vascular risk factors (45,47,49,57) More co-morbidities, especially in the elderly (39,43,44) ...
Diabetic foot disease (DFD) is a complication of diabetes mellitus, characterized by multiple pathogenetic factors and bearing a very high burden of disability as well as of direct and indirect costs for individuals or healthcare systems. A further characteristic of DFD is that it is associated with a marked risk of subsequent hospitalizations for incident cardiovascular events, chronic renal failure or of all-cause mortality. Additionally, DFD is strongly linked to the male sex, being much more prevalent among men. However, even if DFD mainly affects males, several past reports suggest that females are disadvantaged as regards the risk of subsequent adverse outcomes. This review aims to clarify this point, attempting to provide an explanation for this apparent oddity: being DFD a typically male complication of diabetes but, seemingly, with a greater load of subsequent consequences for females.
... There are several potential explanations for these differences, including menopausal changes in hormones (e.g. oestrogen, testosterone, endothelin-1) [100][101][102], telomere length and attrition [103,104], exposure to oxidative stress [101,105,106], genetics (e.g. Ychromosome, X-chromosome-related mechanism, nuclear structure) [107][108][109] and epigenetic factors [108,109]. ...
... There are several potential explanations for these differences, including menopausal changes in hormones (e.g. oestrogen, testosterone, endothelin-1) [100][101][102], telomere length and attrition [103,104], exposure to oxidative stress [101,105,106], genetics (e.g. Ychromosome, X-chromosome-related mechanism, nuclear structure) [107][108][109] and epigenetic factors [108,109]. ...
Over the past three decades, considerable effort has been dedicated to quantifying the pace of ageing yet identifying the most essential metrics of ageing remains challenging due to lack of comprehensive measurements and heterogeneity of the ageing processes. Most of the previously proposed metrics of ageing have been emerged from cross-sectional associations with chronological age and predictive accuracy of mortality, thus lacking a conceptual model of functional or phenotypic domains. Further, such models may be biased by selective attrition and are unable to address underlying biological constructs contributing to functional markers of age-related decline. Using longitudinal data from the Baltimore Longitudinal Study of Aging (BLSA), we propose a conceptual framework to identify metrics of ageing that may capture the hierarchical and temporal relationships between functional ageing, phenotypic ageing and biological ageing based on four hypothesized domains: body composition, energy regulation, homeostatic mechanisms and neurodegeneration/neuroplasticity. We explored the longitudinal trajectories of key variables within these phenotypes using linear mixed-effects models and more than 10 years of data. Understanding the longitudinal trajectories across these domains in the BLSA provides a reference for researchers, informs future refinement of the phenotypic ageing framework and establishes a solid foundation for future models of biological ageing.
... Сердечный выброс увеличивается примерно на 20% во второй половине менструального цикла и во время беременности. Эта перманентная биологическая нагрузка в течение репродуктивного периода создает оптимальные условия функционирования сердечно-сосудистой системы, сравнимые с эффектом физических упражнений [9]. При этом следует отметить, что детородный период у женщин более короткий, чем у мужчин, поэтому прогнозирование преждевременного старения у них представляется особенно актуальным. ...
Background. Accelerated biological aging is associated with age-related diseases and an increased risk of mortality. Genetic predisposition may be an important factor in this process. Aim. To determine the significance of genetic polymorphisms in the VDR and COL1A1 genes in accelerated aging. Materials and methods. The study included 100 women aged 20–35 years, divided into groups with accelerated (Group 1) and normal/slow (Group 2) aging rates. We assessed biological age using V.P. Voytenko's formula. Genetic polymorphisms analyzed were: VDR 283 AG (Bsml), VDR 2 AG (Fokl), COL1A1 1546 GT, COL1A1 -1997 CA. Results. The VDR 283 AG (AA) polymorphism was associated with accelerated aging, occurring more frequently in Group 1 (18% vs 4% in Group 2, p=0.025). The COL1A1 -1997 CA polymorphism was more prevalent in Group 2 (76% vs 56% in Group 1, p=0.035). A multifactorial model identified combinations of polymorphisms that predict accelerated or slow aging with an accuracy of 0.72. Conclusion. Genetic predisposition plays a significant role in accelerated aging. Analysis of VDR and COL1A1 polymorphisms can help identify the risk of premature aging and may serve as a basis for further research and the development of new approaches to prevent age-related diseases.
... Сердечный выброс увеличивается примерно на 20% во второй половине менструального цикла и во время беременности. Эта перманентная биологическая нагрузка в течение репродуктивного периода создает оптимальные условия функционирования сердечно-сосудистой системы, сравнимые с эффектом физических упражнений [9]. При этом следует отметить, что детородный период у женщин более короткий, чем у мужчин, поэтому прогнозирование преждевременного старения у них представляется особенно актуальным. ...
Background. Accelerated biological aging is associated with age-related diseases and an increased risk of mortality. Genetic predisposition may be an important factor in this process. Aim. To determine the significance of genetic polymorphisms in the VDR and COL1A1 genes in accelerated aging. Materials and methods. The study included 100 women aged 20-35 years, divided into groups with accelerated (Group 1) and normal/slow (Group 2) aging rates. We assessed biological age using V.P. Voytenko's formula. Genetic polymorphisms analyzed were: VDR 283 A>G (Bsml), VDR 2 A>G (Fokl), COL1A1 1546 G>T, COL1A1-1997 C>A. Results. The VDR 283 A>G (AA) polymorphism was associated with accelerated aging, occurring more frequently in Group 1 (18% vs 4% in Group 2, p=0.025). The COL1A1-1997 C>A polymorphism was more prevalent in Group 2 (76% vs 56% in Group 1, p=0,035). A multifactorial model identified combinations of polymorphisms that predict accelerated or slow aging with an accuracy of 0,72. Conclusion. Genetic predisposition plays a significant role in accelerated aging. Analysis of VDR and COL1A1 polymorphisms can help identify the risk of premature aging and may serve as a basis for further research and the development of new approaches to prevent age-related diseases.
... Even when using predicted age extracted from the biopsies, it was found that women had a higher survival probability than males, consistent with established literature [81][82][83][84][85][86] . The observed ages of males were also closer to the predicted ages in our set, and this could be a feature of the sample used. ...
As global life expectancy increases, so does the burden of chronic diseases, yet individuals exhibit considerable variability in the rate at which they age. Identifying biomarkers that distinguish fast from slow ageing is crucial for understanding the biology of ageing, enabling early disease detection, and improving prevention strategies. Using contrastive deep learning, we show that skin biopsy images alone are sufficient to determine an individual's age. We then use visual features in histopathology slides of the skin biopsies to construct a novel biomarker of ageing. By linking with comprehensive health registers in Denmark, we demonstrate that visual features in histopathology slides of skin biopsies predict mortality and the prevalence of chronic age-related diseases. Our work highlights how routinely collected health data can provide additional value when used together with deep learning, by creating a new biomarker for ageing which can be actively used to determine mortality over time.
... In particular, estrogen concentrations after menopause and testosterone concentrations after middle age decrease drastically. In this regard, testosterone by potentiating the effect of growth hormone increases the risk of some age-related diseases, such as prostate cancer and cardiac hypertrophy in men (Kloner et al., 2016), while endogenous estradiol, which is the most potent estrogen hormone, causes marked cardiovascular changes in women thereby postponing the onset of cardiovascular diseases (Eskes and Haanen, 2007). Increasing evidence Arosio and A. Picca Experimental Gerontology 198 (2024) 112619 indicates that estradiol is not only involved in modulating the local and systemic inflammatory response but also plays a key role in preserving muscle health during aging (Kenny et al., 2003). ...
Aging is a dynamic process that requires a continuous response and adaptation to internal and external stimuli over the life course. This eventually results in people aging differently and women aging differently than men. The "gender paradox" describes how women experience greater longevity than men, although linked with higher rates of disability and poor health status. Recently, the concept of frailty has been incorporated into this paradox giving rise to the "sex-frailty paradox" which describes how women are frailer because they manifest worse health status but, at the same time, appear less susceptible to death than men of the same age. However, very little is known about the biological roots of this sex-related difference in frailty. Inflamm-aging, the chronic low-grade inflammatory state associated with age, plays a key pathophysiological role in several age-related diseases/conditions, including Alzheimer's disease (AD), for which women have a higher lifetime risk than men. Interestingly, inflamm-aging develops at a different rate in women compared to men, with features that could play a critical role in the development of AD in women. According to this view, a continuum between aging and age-related diseases that probably lacks clear boundaries can be envisioned in which several shared biological mechanisms that progress at different pace may lead to different aging trajectories in women than in men. It, therefore, becomes urgent to consider a holistic approach in the study of aging, and decline it from a gender medicine perspective also considering the biological roots of the sex-frailty paradox.
... Regarding characteristic effects, male older adults are significantly more likely to be in marriage and have higher educational attainment than female older adults. Perhaps the reason why more males are in marriage than females is that females have a significant advantage over males in terms of longevity due to biological and life factors [55][56][57], and therefore males can maintain their marriages longer and receive more stable support and care from their spouses [58]. This phenomenon is also visually evident in the descriptive statistics of the total sample, i.e., 87.6% of the older male samples were in marriages, while only 76.8% of the older female samples were in marriages. ...
Background
Evidence remains limited and inconsistent for assessing cognitive function in Chinese older adults (CFCOA) and inequalities in cognitive function in Chinese older adults (ICFCOA) and exploring their influencing factors and gender differences. This study aimed to identify influencing factors and inequality in CFCOA to empirically explore the existence and sources of gender differences in such inequality and analyse their heterogeneous effects.
Methods
Based on data from the China Health and Retirement Longitudinal Study (CHARLS) for three periods from 2011 to 2015, recentered influence function unconditional quantile regression (RIF-UQR) and recentered influence function ordinary least squares (RIF-OLS) regression were applied to assess influencing factors of CFCOA, while grouped treatment effect estimation, Oaxaca-Blinder decomposition, and propensity score matching (PSM) methods were conducted to identify gender differences in ICFCOA and influencing factors, respectively.
Results
The results showed heterogeneous effects of gender, age, low BMI, subjective health, smoking, education, social interactions, physical activity, and household registration on CFCOA. Additionally, on average, ICFCOA was about 19.2–36.0% higher among elderly females than among elderly males, mainly due to differences in characteristic effects and coefficient effects of factors such as marital status and education.
Conclusions
Different factors have heterogeneous and gender-differenced effects on CFCOA and ICFCOA, while the formation and exacerbation of ICFCOA were allied to marital status and education. Considering the severe ageing and the increasing incidence of cognitive decline, there is an urgent need for the government and society to adopt a comprehensive approach to practically work for promoting CFCOA and reducing ICFCOA.
... It is known that mostly poorer older adults live in nursing homes and that those who die in these facilities are mostly women [33]. This may be because women tend to outlive their husbands and have healthier lifestyles [34]. ...
Methods
We examined a quality measurement database containing de-identified cases from across Switzerland. All patients with a complete dataset treated between 2015 and 2021 were included. A case-control matching method (same age, comorbidity, sex, diagnosis, admission type, and insurance coverage) was used to evaluate the impact of pre-admission residence. The outcomes measured included complications during hospitalization, in-hospital mortality, and length of stay. Statistical significance was set at a p-value of <0.001 due to our large size of analyzed cases.
Results
We noted a higher prevalence of comorbidities and higher ASA scores among the 2130 (1.9 %) patients admitted from long-term care facilities (LTCFs). Complication rates in the LTCF group were higher than those in the home group (15 % vs. 6.9 %, p = <0.001). Pneumonia was the most frequent complication in both groups. The in-hospital mortality rate was also significantly higher in the LTCF group than the home group (5.8 % vs. 1.1 %, p = <0.001). However, matched-pair analysis showed no significant difference in complication rates and overall mortality between the two groups. Patients admitted from LTCFs even had a shorter hospital stay (7.5 ± 8.7 days vs. 8.9 ± 7.9 days, p = <0.004).
Conclusions
Despite higher complication and mortality rates among LTCF patients, the matched-pair analysis showed no significant differences in these rates between the two groups. However, patients from LTCFs were discharged earlier, indicating the effectiveness of Switzerland's care system for older adults living in nursing homes.
... Kirchgesner and colleagues noted that while advancing age correlated with a surge in opportunistic infections' absolute risk, the relative risk didn't show a signi cant rise when accounting for disease activity and other health conditions [39]. The plausible explanations for sex differences are genetically that the presence of two X chromosomes, longer telomeres and slower telomere shortening processes may give females a survival advantage [40]. ...
Background
Emerging research indicates a potential correlation between frailty, healthy diet and IBD because of overlapping mechanisms. To evaluate the individual and joint effects of frailty and healthy diet on the risk of IBD.
Methods
Data on frailty and diet were collected from a prospective cohort of 338,716 UK Biobank participants. Cox proportional-hazard regression was used to analyze the association of frailty status and dietary pattern with incident IBD. A joint effect analysis was conducted to demonstrate the potential modification effect of healthy diet on the relationship between frailty and IBD.
Results
During a median follow-up of 12.47 years, 2032 RA were identified. Compared with non-frail participants, those with pre-frailty and frailty showed a significantly increased risk of IBD, which was 13% higher in pre-frailty (95% CI: 1.03, 1.23) and 33% higher in frailty (95% CI: 1.08, 1.62), respectively. Participants with moderate and ideal dietary patterns had a significantly lower incidence of IBD compared with those with poor dietary patterns. The adjusted hazard ratios (HRs) were 0.84 (95% CI: 0.74, 0.96) and 0.76 (95% CI: 0.67, 0.88) for moderate dietary pattern and ideal dietary pattern, respectively. Moreover, individuals with non-frailty and ideal dietary pattern had a 43% (95% CI: 0.32, 0.89) reduced risk of IBD in contrast with those with frailty and poor dietary patterns.
Conclusion
The study provides evidence linking frailty and unhealthy diet to the risk of IBD. Our findings suggested that adherence to a healthy diet might attenuate the deleterious effect of frailty on IBD risk.
... This finding is consistent with previous studies [40,54]. Estrogen is hypothesized to have a protective anti-inflammatory effect [55,56]. Other studies have reported that inflammation has different roles and mechanisms in men and women (eg, for cardiovascular diseases) [57]. ...
Background:
Chronic inflammation plays a crucial role in tissue injury, osteoporosis, and fracture. The dietary inflammatory index (DII) is a tool for assessing the potential for inflammation in the diet. However, the association between the DII and fractures remains controversial from previous studies.
Objective:
We aimed to explore the correlation between the DII and fracture risk in Chinese adults.
Methods:
We included 11,999 adults (5519 men and 6480 women) who were a part of the China Health and Nutrition Survey (1997-2015) prospective cohort. A 3-day, 24-hour meal review method was used to calculate the DII score. The fractures were identified using a questionnaire. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for fractures. Subgroup, sensitivity, and restricted cubic spline analyses were performed.
Results:
During the 18 years of follow-up (median follow-up 9.0 years), 463 men and 439 women developed fractures. The median DII score was 0.64 (IQR -1.74 to 1.46) for the total sample, 0.75 (IQR -1.68 to 1.50) for men, and 0.53 (IQR -1.79 to 1.42) for women. The DII score had a positive correlation with the risk of fracture among women but not among men. For men, after adjusting for covariates, the HRs for quintiles of DII were 1, 0.96 (95% CI 0.66-1.41), 1.05 (95% CI 0.74-1.49), 0.89 (95% CI 0.62-1.26), and 0.94 (95% CI 0.67-1.34; trend: P=.62). The HRs for women were 1, 1.13 (95% CI 0.72-1.79), 1.24 (95% CI 0.83-1.86), 1.51 (95% CI 1.02-2.22), and 1.62 (95% CI 1.10-2.39; trend: P=.004). The restricted cubic spline analysis showed a significant association between fracture risk and DII score in women (overall association: P=.01); as the DII scores were >0.53, HRs showed a significant upward trend. Women aged <50 years or who are nonsmokers, who are nondrinkers, or with nonabdominal obesity had a positive association between fracture risk and the DII score. In sensitivity analyses, after excluding people with diabetes or hypertension, there was still a positive association between fracture risk and the DII score in women. Among the DII components, the DII scores of protein (trend: P=.03), niacin (trend: P=.002), and iron (trend: P=.02) showed significant associations with the risk of fracture in women.
Conclusions:
Proinflammatory diet consumption increased the fracture risk in Chinese women aged <50 years. The high consumption of anti-inflammatory foods and low consumption of proinflammatory foods may be an important strategy to prevent fractures in women.
... Moreover, females generally report more morbidity than men but, in terms of longevity, women live longer. As already stated, the link between morbidity and longevity has been defined as the "gender health paradox", 12 for which there are no clear explanation unless we turn for example to potential genetic explanatory frameworks still to be discovered. ...
Well-being is a complex and multi-faceted concept, which covers several dimensions ranging from the physical to the psychological. It also includes the environment in which an individual lives and operates, playing a role in defining the concept of well-being.
The influence of these possible well-being determinants – physical, psychological and environmental – may vary in relation to gender, providing in this way different possible outcomes
and evidences in relation to health and social policies.
This article focuses on the impact of possible well-being determinants on the female and male genders in an attempt
to illustrate the effective dimension of individual characteristics
regarding employment, socio-economic status, civil
status, overall health and education. In addition, the manuscript analyzes the influence of participation in social-related
activities, given the pro-active role these play in the promotion of health and psychological condition.
The study is based on a 2018 survey of a statistically representative sample of the Italian population, which gathered
information concerning the influence of several elements
on individual subjective well-being. The analysis reveals a
general agreement on how health status is one of the major
detrimental risk factors for decreased psychological wellbeing
in both genders. It also shows that cultural experiences
act toward preventing well-being distress, particularly
in females, leading to significant consequences in terms
of promotion of individual subjective well-being.
... This was unexpected given that research is typically dominated by male participants [75,76]. Some potential reasons for this variance could be that women live longer [77], are more likely to live in assisted care units [78], are more likely to participate in studies [79], or have altruistic considerations [80]. Moreover, the use of simulated data despite the availability of actual data highlights the need for better access to high-quality data. ...
... Then estrogen can also increase antioxidants which are protective for blood vessels. 11 The mean age in this research was 68.68±6.35 years. ...
Background: Nutritional status has been associated with cognitive function in elderly. Several anthropometric measurement, including mid upper arm circumference and calf circumference are recognized as effective means to assess nutritional status, as they have good correlation with body mass index. This study aimed to identify the association between MUAC, CC and cognitive function in elderly population.Methods: This cross sectional study involved 71 elderly subjects aged more than 60 years old. We recruited subjects from Medan Helvetia district because it has the largest aging population in Medan, North Sumatera, Indonesia. The Cognitif function was assessed using montreal cognitive assessment test Indonesian version (MoCA-INA) and visual cognitive assessment test. To examine the association between MUAC, CC and cognitive function using Kruskal Wallis test and Fisher Exact.Results: There were 42 females and 29 males. The mean age was 68.68±6.35 years. The mean MUAC was 24.3±3.25 cm and CC was 31.5±2.45 cm. There was no association between MUAC and MoCA-INA (p=0.215) and VCAT (p=0.062). There was an association between CC and MoCA-INA (p=0.040) and VCAT (p=0.019).Conclusions: There was an association between calf circumference and cognitive function while mid upper arm circumference was not. Compared to BMI, calf circumference can predict sarcopenia in the elderly. Elderly with functional impairment and impaired mobility may show a decrease in calf circumference. Sarcopenia is often associated with brain atrophy in the elderly.
... Global data shows that death rates related to COVID-19 are higher in males than in females (The Sex, Gender, and COVID-19 Project, 2021). In addition, females live longer than males due to genetic structure, chromosomes, hormones, and other ecological factors (Austad, 2006;Eskes and Haanen, 2007;Vina and Borras, 2010;Zarulli et al., 2018). For that reason, age may moderate gender difference in COVID-19 related fear and anxiety. ...
Studies conducted during the pandemic revealed strong associations between gender and COVID-19 related fear and anxiety. Females perceive coronavirus as a greater threat to personal health and population than males. The aim of the current meta-analysis is to estimate gender difference in COVID-19 related fear and anxiety. The second purpose of this study is to clarify the role of potential moderators in COVID-19 fear and anxiety. For these reasons, studies published between March 2020 and October 2021 were searched in various databases (Web of Science, SCOPUS, PubMed, and Google Scholar). In total, 315 studies met the inclusion criteria, and 60 studies for COVID-19 related fear and 23 studies for COVID-19 related anxiety were included in the current study. Cohen's d effect size values were calculated based on these individual studies showing the difference between males and females in terms of COVID-19 related fear and anxiety. Results revealed that gender has a moderate and significant effect on COVID-19 related fear (ES = 0.307) and anxiety (ES = 0.316) in favor of females. Moderator analyses showed that continent variable was a significant moderator of gender difference in COVID-19 related fear and anxiety. The highest effect size of gender differences in COVID-related fear and anxiety were obtained from the studies conducted in Europe. However, other moderators (the average age of sample, culture, timing, and population) were not statistically significant. Although this meta-analysis has a few limitations, the findings showed that COVID-19 outbreak negatively affected females more.
... Meskipun penduduk lansia di Indonesia tahun 2017 didominasi oleh perempuan (54,2%), namun untuk lansia yang bekerja ternyata didominasi oleh lakilaki (69,2%). Secara teori memang perempuan cenderung hidup lebih lama dari laki-laki (Eskes & Haanen, 2007). Hal ini dibuktikan dengan Angka Harapan Hidup perempuan di Indonesia tahun 2017 mencapai 73,06 tahun dan laki-laki hanya 69,16 tahun. ...
Pekerja lansia di Indonesia meningkat setiap tahun dan masuk peringkat 50 besar di dunia. Peningkatan jumlah penduduk lanjut usia di Indonesia menjadi indikator keberhasilan pembangunan bidang kesehatan yang ditandai dengan peningkatan angka harapan hidup (AHH). Disisi lain hal ini menjadi beban negara baik secara sosial maupun ekonomi. Usia penduduk lansia pada penelitian ini adalah 65 tahun ke atas. Tujuan penelitian adalah mendeskripsikan karakteristik sosial & demografi, dan menemukan faktor sosial & demografi yang berhubungan dengan status kerja lansia di Indonesia. Metode yang digunakan yaitu analisis deskriptif (tabel silang dan tabel frekuensi) dan analisis inferensia korelasi (uji Chi Square). Pekerja lansia di Indonesia mayoritas adalah perempuan, kawin, kepala rumah tangga, umur 65-74 tahun, bekerja di sektor informal, rata-rata jam kerja 34,23 jam per minggu, memiliki keluhan kesehatan, pendidikan rendah, tidak memiliki jaminan sosial dan hutang. Menurut uji chi square, status kerja berhubungan sedang dengan umur, jenis kelamin, status perkawinan, hubungan dengan kepala rumah tangga, jam kerja. Kemudian jaminan sosial berhubungan lemah, dan faktor lainnya (pendidikan, keluhan kesehatan, hutang, dan sektor usaha) berhubungan sangat lemah.
... Other series studying PEH patients have also shown women making up the majority of the cohort [2,15,17]. Published studies across multiple specialties have demonstrated that women tend to live longer than men due to vascular, hormonal, and genetic differences [31]. ...
Background
Elective paraesophageal hernia (PEH) repair in asymptomatic or minimally symptomatic patients ≥ 65 years of age remains controversial. The widely cited Markov Monte Carlo decision analytic model recommends watchful waiting in this group, unless the mortality rate for elective repair was to reach ≤ 0.5%; at which point, surgery would become the optimal treatment. We hypothesized that with advances in minimally invasive surgery, perioperative care, and practice specialization, that mortality threshold has been reached in the contemporary era. However, the safety net would decrease as age increases, particularly in octogenarians.
Methods
We identified 12,422 patients from the 2015–2017 ACS-NSQIP database, who underwent elective minimally invasive PEH repair, of whom 5476 (44.1%) were with age ≥ 65. Primary outcome was 30-day mortality. Secondary outcomes were length of stay (LOS), operative time, pneumonia, pulmonary embolism, unplanned intubation, sepsis, bleeding requiring transfusion, readmission, and return to OR.
Results
Patients age ≥ 65 had a higher 30-day mortality (0.5% vs 0.2%; p < 0.001). Subset analysis of patients age 65–80 and > 80 showed a 30-day mortality of 0.4% vs. 1.8%, respectively (p < 0.001). Independent predictors of mortality in patients ≥ 65 years were age > 80 (OR 5.23, p < 0.001) and COPD (OR 2.59, p = 0.04). Patients ≥ 65 had a slightly higher incidence of pneumonia (2% vs 1.2%; p < 0.001), unplanned intubation (0.8% vs 0.5%; p < 0.05), pulmonary embolism (0.7% vs 0.3%; p = 0.001), bleeding requiring transfusion (1% vs 0.5%; p < 0.05), and LOS (2.38 vs 1.86 days, p < 0.001) with no difference in sepsis, return to OR or readmission.
Conclusion
This is the largest series evaluating elective PEH repair in the recent era. While morbidity and mortality do increase with age, the mortality remains below 0.5% until age 80. Our results support consideration for a paradigm shift in the management of patients < 80 years toward elective repair of PEH.
... There is great variation among species in age-specific TL [36]. Sexual differences in TL and attrition have been suggested to contribute to sex-specific disease and mortality patterns in humans [37,38], where women typically have longer telomeres and are longer-lived (e.g., [39]). Telomerase, the enzyme that countervails telomere shortening was found to be active in stem cells, gametes and most cancer cells, but normally absent from or at very low levels in most somatic cells [40]. ...
Background
Life history theory predicts that during the lifespan of an organism, resources are allocated to either growth, somatic maintenance or reproduction. Resource allocation trade-offs determine the evolution and ecology of different life history strategies and define an organisms’ position along a fast–slow continuum in interspecific comparisons. Labord’s chameleon ( Furcifer labordi ) from the seasonal dry forests of Madagascar is the tetrapod species with the shortest reported lifespan (4–9 months). Previous investigations revealed that their lifespan is to some degree dependent on environmental factors, such as the amount of rainfall and the length of the vegetation period. However, the intrinsic mechanisms shaping such a fast life history remain unknown. Environmental stressors are known to increase the secretion of glucocorticoids in other vertebrates, which, in turn, can shorten telomeres via oxidative stress. To investigate to what extent age-related changes in these molecular and cellular mechanisms contribute to the relatively short lifetime of F. labordi , we assessed the effects of stressors indirectly via leukocyte profiles (H/L ratio) and quantified relative telomere length from blood samples in a wild population in Kirindy Forest. We compared our findings with the sympatric, but longer-lived sister species F. cf. nicosiai, which exhibit the same annual timing of reproductive events, and with wild-caught F. labordi that were singly housed under ambient conditions.
Results
We found that H/L ratios were consistently higher in wild F. labordi compared to F. cf. nicosiai . Moreover, F. labordi already exhibited relatively short telomeres during the mating season when they were 3–4 months old, and telomeres further shortened during their post-reproductive lives. At the beginning of their active season, telomere length was relatively longer in F. cf. nicosiai , but undergoing rapid shortening towards the southern winter, when both species gradually die off. Captive F. labordi showed comparatively longer lifespans and lower H/L ratios than their wild counterparts.
Conclusion
We suggest that environmental stress and the corresponding accelerated telomere attrition have profound effects on the lifespan of F. labordi in the wild, and identify physiological mechanisms potentially driving their relatively early senescence and mortality.
... where 1.08 and 1.06 were the telomere lengths adjusted for continuous age for the females and the males, respectively [54]. Eskes and Haanen [55] after noting that cardiovascular risks are responsible for five times higher mortality and three times higher morbidity in men, compared with women, pointed the role of the telomeres on chromosomes during mitotic cell division and stated that this difference cannot explain the observed life span gap fully. Then, they focused on endogenous estradiol for its role in provoking cardiovascular changes. ...
... Then estrogen can also increase antioxidants which are protective for blood vessels. 8 The subject's body mass index had a mean of 24.64 with the largest BMI group in this study, which was ≥ 23 kg/m 2 with 46 subjects (64.8%). Other relevant studies mentioned the mean BMI in the elderly is 25.1. ...
... where 1.08 and 1.06 were the telomere lengths adjusted for continuous age for the females and the males, respectively [54]. Eskes and Haanen [55] after noting that cardiovascular risks are responsible for five times higher mortality and three times higher morbidity in men, compared with women, pointed the role of the telomeres on chromosomes during mitotic cell division and stated that this difference cannot explain the observed life span gap fully. Then, they focused on endogenous estradiol for its role in provoking cardiovascular changes. ...
Background & Aims
Empirical analyses of the data available around the word concluded that women have longer life span now, when compared to the men. Available literature unfortunately could not offer full answers to this observation. The “entropic age” concept suggests that ageing related changes in the body, such as loss of molecular functions and overwhelming of the maintenance systems, may be explained in terms of entropy generation.
Methods
Telomere-length regulated entropic assessment based on metabolic activity with four different diets carried out.
Results
Estimates of the life expectancy of the women on all of these diets is longer than those of the men. Faster shortening of the telomer lengths in men was the major reason of the shorter life expectancy. The highest and the lowest life expectancy for women were estimated with Mediterranean and the vegetarian diets, respectively; men were estimated to have the longest life span with the vegetarian diet and the shortest life span with the ketogenic diet.
Conclusions
A higher rate of metabolism causes higher entropy generation and hints correlations that can be helpful in future ageing research. Faster shortening of the telomer lengths in men was the major reason of the estimation of the shorter life span for men.
... Whereas there are no available studies on the association between the DII and the hyperuricemia risk that could be used for comparison, there has been some research stressing the importance of estrogen in promoting excretion of uric acid [58][59][60]. Estrogen, in fact, has been hypothesized to have a protective anti-inflammatory effect [61,62]. As the mean age of the present study's women participants was older than the mean age at menopause among Korean women (49.2 years), the number of postmenopausal women in this study might have been the majority; if so, the results on hyperuricemia risk well might have been skewed higher [63]. ...
In previous studies, the elevated dietary inflammatory index (DII®) scores have been consistently associated with several chronic diseases. However, the relationship with hyperuricemia remains unknown. The aim of this study was to determine if the DII is associated with hyperuricemia risk. The study included 13,701 participants (men 5102; women 8599) in a large-scale cross-sectional study in South Korea. A validated semi-quantitative food frequency questionnaire (SQFFQ) was used to measure dietary intake, and blood samples were obtained to determine hyperuricemia. As the DII score increased, the hyperuricemia risk increased among women (OR 1.35, 95% CI 1.03–1.77, p trend = 0.02). However, no significant results were found for men. Women with lower BMI scores had higher risks of hyperuricemia with higher DII scores (OR 1.62, 95% CI 1.05–2.52, p trend = 0.03). As the DII increased, however, only women who consumed alcohol (“past or current drinkers”) had higher risks of hyperuricemia (OR 1.92, 1.22–3.02, p trend = 0.004). Among the DII components, intake of flavonoids showed a significant association with the hyperuricemia risk in women (OR 0.75, 0.59–0.96, p trend = 0.03). Our results suggest that higher intake of pro-inflammatory diet is significantly associated with higher risk of hyperuricemia among women. These results reinforce the importance of less pro-inflammatory habitual dietary patterns in lowering the risk of hyperuricemia and secondary afflictions such as cardiovascular diseases.
... Men's lifespan is shorter than women's (Austad, 2006;Barford, Dorling, Smith, & Shaw, 2006;Eskes & Haanen, 2007), and consequently, bedtime procrastination could be even more risky for males, because it leads to insufficient sleep, and fatigue (Kroese, Evers, et al., 2016). Moreover, females tend to engage in more health behaviors compared to males and males are more inclined to take health-related risks than females (Lippa, 2005;Umberson, 1992). ...
In the present study, the relation between bedtime procrastination and death anxiety, and also the moderator roles of gender and purpose in life were investigated. Data were collected from 245 participants through an online survey. The results revealed that gender, but not purpose in life, moderated the relation between death anxiety and bedtime procrastination. The effect of death anxiety on bedtime procrastination was significant only for males. Further, this effect was still significant even after controlling circadian energy and self-control. The findings can be explained based on the Terror Management Theory. Bedtime procrastination can be considered risk-taking behavior, and it functions as a world view for males. Moreover, males might have regarded sleep as a waste of time, and therefore, delayed bedtime to increase their non-sleeping lifetime.
... The longer life span of women seen in wealthy countries in the modern era has been frequently attributed to fixed genetic or hormonal causes (4 ). Several theories have postulated that a higher male birth rate among humans might contribute to unspecified evolutionary pressure for shorter male life spans. ...
Frailty is a dynamic and multidimensional clinical condition characterized by the depletion of system reserves, resulting in a loss of redundancy and increased vulnerability to any stressful event. This loss of resilience implies not only a poorer and more difficult recovery from baseline homeostasis but a disproportionate increase in harmful health outcomes from even minor insults. There are two models of frailty that have received the most attention within the community: the frailty phenotype and the frailty index. Frailty and comorbidity represent two distinct, but related, clinical concepts. The term comorbidity designates the co-occurrence of different noncommunicable diseases (NCDs) in the same individual. Comorbidity, however, does not only represent the sum of different NCDs, but a clinical condition in itself. In fact, it is conceived as a synergy of the different NCDs associated with worse health outcomes and a more complex clinical management than the simple sum of the individual NCDs. Evidence supports the role of frailty and comorbidity as mutual risk factors. Women have been found to acquire slightly more general comorbidities than men, but paradoxically enjoy a longer life expectancy. Women also experience poorer health which has, at least in part, been attributed to psychosocial differences. It is unclear why women live longer despite suffering higher levels of frailty. This may be due to the distinctive profile of NCDs, which may not be life-threatening in women, a lower physiological reserve in men, or other reasons.
Introduction . Biological age (BA) reflects the characteristics of the morphological and physiological state of the human body at a specific period of its life.This concept is of particular importance in reproductive medicine, because actual age does not always correlate with the state of organs and systems.
Aim : to develop a method for calculating BA for women aged 20–45 years, considering their physiological state and reproductive function.
Materials and Methods . A single-stage non-randomized cohort study was conducted. To create the BA calculation model, a study was conducted with 100 healthy women aged 20–45 years. Seventy-eight parameters were analyzed, including anamnesis data, anthropometric parameters, data of general blood test, biochemical blood test, instrumental studies, assessment of overall antioxidant status (ОAS), from which the most informative variables were selected. The model was developed using multiple linear regression.
Results . The most informative indicators for calculating BA were: ОAS, static balance time (SBT), body mass index (BMI), and number of former pregnancies. The developed BA calculation formula demonstrated high accuracy, correlating with chronological age (correlation coefficient of 0.947).
Conclusion . The proposed BA calculation method is specifically designed for women of reproductive age and shows high accuracy and correlation with chronological age. The inclusion of antioxidant protection parameters, functional state indicators, and reproductive history makes the method versatile and applicable not only in reproductive medicine but also in general medical practice, obstetrics, gynecology, and other fields.
To investigate the trends of hospital admissions concerning diseases of the eye and adnexa in Australia in the past 2 decades. This is a descriptive ecological study on the population level that examined hospitalization data for the duration between 1998 and 2021 in Australia. Hospitalization data were extracted from the National Hospital Morbidity Database. The chi-squared test was utilized to assess the difference in admission rates between the years 1998 and 2021. Hospital admission rate for diseases of the eye and adnexa increased by 1.20-fold (from 852.32 [95% confidence interval [CI] 848.16–856.47] in 1998 to 1873.72 [95% CI 1868.48–1878.96] in 2021 per 100,000 persons, P < .01). The most common cause of hospitalization for diseases of the eye and adnexa was disorders of the lens (65.7%), followed by disorders of the choroid and retina (15.6%), followed by disorders of the eyelid, lacrimal system, and orbit (7.7%). Hospital admission rate among males increased by 1.25-fold (from 737.67 [95% CI 732.18–743.16] in 1998 to 1657.19 [95% CI 1650.19–1664.20] in 2021 per 100,000 persons). Hospital admission rate among females increased less sharply by 1.03-fold (from 965.37 [95% CI 959.14–971.59] in 1998 to 1964.35 [95% CI 1956.80–1971.90] in 2021 per 100,000 persons). There are clear gender and age roles in the epidemiology of hospital admissions related to eye and adnexa disorders. Lens disorders were the most common cause of hospital admission. The admission rate increase during the past decades could be due to increases in life expectancy, lifestyle changes, and improvements in screening protocols.
Background
The difference in life expectancy and willingness to have children among married people is influenced by the different positions of people in the levels of Maslow's hierarchy of needs.
Aim
The current research was conducted to determine the relationship between the position of married people in the levels of Maslow's hierarchy of needs with their life expectancy and desire to have children.
Methods
This cross-sectional study was conducted using convenience sampling on 140 married people in the general population of Khaf City in 2022. Data were collected using an electronic questionnaire and analyzed using the SPSS-22 statistical software, Pearson correlation coefficient, and multiple regression statistical tests at a significance level of 0.05.
Results
The highest average score of Maslow's Hierarchy of needs was related to the level of basic needs (5.45±4.85), and the lowest average was related to the level of self-actualization needs (2.09±5.55). The average score of life expectancy and willingness to have children in the studied subjects was 25.41±6.62 (moderate) and 18.38±6.38 (low), respectively. There was a positive and significant correlation between the levels of Maslow's hierarchy of needs on life expectancy and the desire to have children in the studied subjects (p<0.001).
Conclusion
Basic needs are the most important needs of couples and they can directly affect life expectancy and the desire to have children. Therefore, the basic needs must be prioritized in the country's plans so that after the basic needs are met, conditions are created to improve life expectancy and the desire to have children.
The association of leukocyte telomere length (LTL) with survival to late life with intact mobility has not been adequately studied. This prospective cohort study consisted of 1451 postmenopausal women from a Women’s Health Initiative ancillary study, who were eligible, because of birth year, to survive to age 90 as of March 6, 2021. LTL was measured by Southern blot at baseline (1993–1998). Associations between LTL and survival to age 90 were evaluated using logistic regression models adjusted for socio-demographic characteristics, health factors, and lifestyle factors. Multinominal logistic regression was utilized to examine associations of LTL with survival to age 90 with or without intact mobility. Mediation analysis examined the extent to which incident coronary heart disease and stroke-mediated the association between LTL and longevity. Overall, 76.7% of women were White, and 23.3% were Black; average age at baseline was 70.4±3.5 years. Relative to death before age 90, the odds of survival to age 90 were 60% higher (OR, 1.60; 95% CI, 1.28–2.01), the odds of survival to age 90 with mobility limitation were 72% higher (OR, 1.72; 95% CI, 1.33–2.21), and the odds of survival to age 90 with intact mobility were 44% higher (OR, 1.44; 95% CI, 1.06–1.95) for every one kilobase longer LTL. Absence of CHD, stroke, or CHD/stroke mediated the association of LTL with survival to age 90 by 11.1%, 37.4%, and 31.3%, respectively; however, these findings were not significant. Longer LTL was associated with higher odds of survival to age 90 among older women.
Background:
The Internet of Things (IoT) has become integrated into everyday life, with devices becoming permanent fixtures in many homes. As countries face increasing pressure on their health care systems, smart home technologies have the potential to support population health through continuous behavioral monitoring.
Objective:
This scoping review aims to provide insight into this evolving field of research by surveying the current technologies and applications for in-home health monitoring.
Methods:
Peer-reviewed papers from 2008 to 2021 related to smart home technologies for health care were extracted from 4 databases (PubMed, Scopus, ScienceDirect, and CINAHL); 49 papers met the inclusion criteria and were analyzed.
Results:
Most of the studies were from Europe and North America. The largest proportion of the studies were proof of concept or pilot studies. Approximately 78% (38/49) of the studies used real human participants, most of whom were older females. Demographic data were often missing. Nearly 60% (29/49) of the studies reported on the health status of the participants. Results were primarily reported in engineering and technology journals. Almost 62% (30/49) of the studies used passive infrared sensors to report on motion detection where data were primarily binary. There were numerous data analysis, management, and machine learning techniques employed. The primary challenges reported by authors were differentiating between multiple participants in a single space, technology interoperability, and data security and privacy.
Conclusions:
This scoping review synthesizes the current state of research on smart home technologies for health care. We were able to identify multiple trends and knowledge gaps-in particular, the lack of collaboration across disciplines. Technological development dominates over the human-centric part of the equation. During the preparation of this scoping review, we noted that the health care research papers lacked a concrete definition of a smart home, and based on the available evidence and the identified gaps, we propose a new definition for a smart home for health care. Smart home technology is growing rapidly, and interdisciplinary approaches will be needed to ensure integration into the health sector.
Penyakit Creutzfeldt-Jakob merupakan salah satu penyakit prion pada manusia yang fatal, ditandai oleh demensia yang cepat dan progresif disertai mioklonus. Insidensi penyakit yang sangat rendah dan banyaknya gejala atipikal pada stadium awal penyakit menyulitkan penegakkan diagnosis. Belum ada laporan kasus penyakit Creutzfeldt-Jakob di Indonesia. Laki-laki berusia 56 tahun dirujuk dengan keluhan penurunan kesadaran disertai kejang. Pasien mengalami penurunan daya ingat progresif, diawali oleh perubahan perilaku, antara lain tampak bingung, iritabilitas, agresi dan insomnia.
2 ﻧﮋاد ﻋﯿﺴﯽ اﺣﺘﺮام ، 3 1 داﻧﺸﮕ ورزﺷﯽ ﻋﻠﻮم و ﺑﺪﻧﯽ ﺗﺮﺑﯿﺖ ﮔﺮوه اﺳﺘﺎدﯾﺎر. ﻗﻢ ﺎه 2 ري ﺷﻬﺮ واﺣﺪ آزاد داﻧﺸﮕﺎه ورزﺷﯽ ﻋﻠﻮم و ﺑﺪﻧﯽ ﺗﺮﺑﯿﺖ ﮔﺮوه. 3 ﺗﻬﺮان ﺗﺤﻘﯿﻘﺎت ﻋﻠﻮم واﺣﺪ ازاد داﻧﺸﮕﺎه ، ورزﺷﯽ ﻋﻠﻮم و ﺑﺪﻧﯽ ﺗﺮﺑﯿﺖ ﮔﺮوه. ﻣﻘﺎﻟﻪ: درﯾﺎﻓﺖ ﺗﺎرﯾﺦ 13 / 4 / 93 ﻣﻘﺎﻟﻪ: ﭘﺬﯾﺮش ﺗﺎرﯾﺦ 6 / 11 / 93 ﭼﮑﯿﺪه ﻫﺪف: اﻓﺰاﯾ ﺑﺎ ﺷﺪﯾﺪ ورزﺷﯽ ﺗﻤﺮﯾﻨﺎت ﮐﻪ اﺳﺖ داده ﻧﺸﺎن ﻣﻄﺎﻟﻌﺎت ﻫﻤـﺮاه اﮐﺴﯿﺪاﺗﯿﻮ اﺳﺘﺮس ﺷﺮاﯾﻂ اﯾﺠﺎد و آزاد ﻫﺎي رادﯾﮑﺎل ﺳﻄﺢ ﺶ ﺑـﻮد. ﻓﻮﺗﺒـﺎل ﺑﺎزﯾﮑﻨﺎن در ﻟﻨﻔﻮﺳﯿﺘﯽ ﮐﺎﺗﺎﻻز آﻧﺰﯾﻢ ژﻧﯽ ﺑﯿﺎن ﺗﻐﯿﯿﺮات ﺑﺮ ﺷﺪﯾﺪ ﺗﻤﺮﯾﻨﯽ ﻓﻌﺎﻟﯿﺖ اﺛﺮ ﺑﺮرﺳﯽ ﺣﺎﺿﺮ ﺗﺤﻘﯿﻖ از ﻫﺪف ﻟﺬا اﺳﺖ، ﺷﻨﺎﺳﯽ: روش ﭘﮋوﻫﺶ اﯾﻦ در 9) آﻣﺎﺗﻮر ﺟﻮان ﻓﻮﺗﺒﺎﻟﯿﺴﺖ ﻧﻔﺮ 16-18 ﺑﺎ ﻣﯿﺎن از ﺳﺎل( ﺑﻮدﻧـﺪ ﺗﺤﻘﯿـﻖ اﯾﻦ در ﺷﺮﮐﺖ داوﻃﻠﺐ ﮐﻪ زﯾﮑﻨﺎﻧﯽ ﺷﺪﯾﺪ ورزﺷﯽ آزﻣﻮن اﻧﺠﺎم از ﻗﺒﻞ ﻣﺮﺣﻠﻪ ﺳﻪ در ﺷﺪ. اﻧﺘﺨﺎب ﺳﺎده ﺗﺼﺎدﻓﯽ ﺻﻮرت ﺑﻪ GXT) Graduate Exercise Test ﺑﻌﺪ ﺑﻼﻓﺎﺻﻠﻪ ،(و ورزﺷﯽ آزﻣﻮن از 3 ﻣﻘﺪار ﺑﻪ ﺑﺎر ﻫﺮ در آن از ﺑﻌﺪ ﺳﺎﻋﺖ 4 ﺳﻄﻮح ﺳﻨﺠﺶ ﺟﻬﺖ ﻫﺎي آزﻣﻮدﻧﯽ از ﺧﻮن ﻟﯿﺘﺮ ﻣﯿﻠﯽ mRNA ﺟﻤﻊ ﮐﺎﺗﺎﻻز ﺷﺪ. آوري ﻧﺘﺎﯾﺞ: ﺳﻄﻮح داد ﻧﺸﺎن ﻫﺎ ﯾﺎﻓﺘﻪ mRNA ﻓﻌﺎﻟﯿـﺖ) از ﭘﺲ ﺑﻼﻓﺎﺻﻠﻪ ﺟﻮان ﻫﺎي ﻓﻮﺗﺒﺎﻟﯿﺴﺖ ﻟﻨﻔﻮﺳﯿﺘﯽ ﮐﺎﺗﺎﻻز 17 / 0 = p و (3) ورزﺷﯽ ﻓﻌﺎﻟﯿﺖ از ﭘﺲ ﺳﺎﻋﺖ 08 / 0 = p ﯾﺎﻓﺖ. اﻓﺰاﯾﺶ داري ﻣﻌﻨﯽ ﻏﯿﺮ ﻃﻮر ﺑﻪ (: ﮔﯿـﺮي ﻧﺘﯿﺠـﻪ و ﺑﺤﺚ ﺗﺤﻘﯿـﻖ ﻧﺘـﺎﯾﺞ اﺳـﺎس ﺑـﺮ ﻓ ﮐﻪ ﺷﺪ ﻣﺸﺨﺺ ﺳﻄﺢ دار ﻣﻌﻨﯽ ﻏﯿﺮ اﻓﺰاﯾﺶ ﺑﺎﻋﺚ ﺷﺪﯾﺪ ورزﺷﯽ ﻌﺎﻟﯿﺖ mRNA ﻟﻨﻔﻮﺳﯿﺘﯽ ﮐﺎﺗﺎﻻز ﮐـﻪ ﺷـﻮد ﻣﯽ ﻓﻮﺗﺒﺎل ﺟﻮان ﺑﺎزﯾﮑﻨﺎن روﻧﻮﯾﺴﯽ از ﭘﺲ ﻓﺮاﯾﻨﺪ در ﺳﺎزﮔﺎري دﻟﯿﻞ ﺑﻪ اﺣﺘﻤﺎﻻ اﻣﺮ اﯾﻦ mRNA ﺑﺎﺷﺪ. ﻣﯽ ﻓﻮﺗﺒﺎل ﺑﺎزﯾﮑﻨﺎن در ﻟﻨﻔﻮﺳﯿﺘﯽ ﮐﺎﺗﺎﻻز واژه ﮐﻠﯿﺪ ﻫﺎ: ژن ﺑﯿﺎن ، ﮐﺎﺗﺎﻻز ، ﺷﺪﯾﺪ ﻓﻌﺎﻟﯿﺖ ، ﻓﻮﺗﺒﺎﻟ ﯿﺴﺖ ﺟﻮان ﻫﺎي. Abstract Purpose: Studies have shown that intense exercise training associated conditions with increases levels of free radicals and oxidative stress thus the aim of this study was to investigate effect of intense exercises on Catalase Enzyme Gene Expression in soccer players. Method: Nine male soccer players amateur (16-18age) for Among the players who participated in the study volunteers were randomly selected and participated in this study. blood samples were taken in three stages, before GXT exercise test (graduate exercise test), immediately and 3 hours after exercise to determine mRNA of catalase. Results : Findings showed no significant increase in the mRNA catalase of lymphocyte in young soccer players immediate (p=0.17) and 3 hour after incremental exercise (p=0.08). Conclusion: According to the results of this study, it was determined that intense exercise training causes no significant increase in the mRNA catalase of lymphocyte in young soccer. This may be due to the adaptation process of catalase mRNA transcription lymphocytes in football players.
Die hohe Mortalität und hohe Rate an Langzeitbehinderungen nach einem erlittenen Schlaganfall verdeutlichen die Relevanz bestmöglicher Akutversorgung bei Schlaganfallpatienten. Daher ist es unentbehrlich, dass die Akuttherapie bei Schlaganfall stets überprüft und bei Bedarf optimiert wird. Der Großteil der Studien, die sich mit Verbesserungsmaßnahmen in der akuten Schlaganfallversorgung befassen, wird in großen städtischen Krankenhäusern bzw. Universitätsklinika durchgeführt. Studien zu diesem Sachverhalt, die in ländlichen Kliniken durchgeführt wurden, sind noch begrenzt vorhanden. Mit dieser Studie evaluieren wir, ob sich durch die Implementierung neuer Optimierungsmaßnahmen Verbesserungen in den relevanten Qualitätsindikatoren ergeben. Die Ergebnisse sind daher von besonderer Bedeutung, da es für nicht-universitäre Kliniken nur eine begrenzte Anzahl an Studien gibt, die sich mit dieser Thematik beschäftigen.
Background
Previous frailty studies found higher prevalence of frailty in female than in male participants. This was mainly attributed to the fact that compared to men, women show increased longevity. Recent studies have reported that the observed difference between sexes applies irrespectively of the age of older people.Objectives
To provide data on sex differences in incident frailty by applying both phenotypic and multi-domain frailty measures in the same population of Greek community-dwelling older people.DesignLongitudinal study.SettingData were drawn from the Hellenic longitudinal Investigation of Aging and Diet (HELIAD), a population-based, multidisciplinary study designed to estimate the prevalence and incidence of dementia in the Greek population.Participants1104 participants aged 65 year and above were included in this longitudinal study. This incidence cohort was reevaluated after a mean follow-up period of 3.04±0.90 years.MeasurementsFrailty was operationalized using 5 different definitions in the same population the Fried Frailty Phenotype (FFP) definition, the FRAIL Scale, the Frailty Index (FI), the Tilburg Frailty Indicator (TFI) and the Groningen Frailty Index (GFI). Frailty incidence was calculated a) for the whole sample, b) separately for men and women and c) after both age and sex stratification.ResultsAge and sex stratification revealed that irrespective of age and frailty measurement, women showed higher incidence rates of frailty than men. Specifically, frailty seems to be a condition concerning women >65 years old, but when it comes to men, it is more frequent in those aged more than 75 years old. Finally, in relation to overall frailty incidence and comparing our results to previous studies, we detected a lower frailty incidence in the Greek population.Conclusions
Differences between the two sexes indicate that when exploring the factors that are related to frailty, studies should provide data disaggregated for men and women.
Cardiovascular disease was previously considered a problem for men, despite more women dying annually from cardiovascular causes. As a result of flawed assumptions, clinical research relied on men, leading to biased guidelines and treatment protocols. Emerging evidence demonstrates that women have unique sex and gender differences that must be considered, particularly their cardiometabolic health, in a systems biology framework that can be organized into a functional medicine model of care. Our aim is to help clinicians recognize the value added by functional medicine in the assessment of women vis-à-vis cardiometabolic pathways, phenotypes, and differences in risk compared with men.
This progressive and broad-ranging handbook offers a comprehensive overview of the complex intersections between politics, gender, sport and physical activity, shining new light on the significance of gender, sport and physical activity in wider society.
Featuring contributions from leading and emerging researchers from around the world, the book makes the case that gender studies and critical thinking around gender are of particular importance in an era of increasingly intolerant populist politics. It examines important long-term as well as emerging themes, such as recent generational shifts in attitudes to gender identity in sport and the socio-cultural expectations on men and women that have traditionally influenced and often disrupted their engagement with sport and physical activity, and explores a wide range of current issues in contemporary sport, from debates around the contested gender binary and sex verification, to the role of the media and social media, and the significance of gender in sport leadership, policy and decision-making.
This book is an authoritative survey of the current state of play in research connecting gender, sport, physical activity and politics, and is an important contribution to both sport studies and gender studies. It is fascinating reading for any student, researcher, policy-maker or professional with an interest in sport, physical activity, social studies, public health or political science.
Introduction:
Multiple sclerosis (MS) is more prevalent in women than in men. The sex of the patient, and pregnancy, are reported to be associated with the clinical features of MS. The mechanism of this is unclear.
Areas covered:
This review summarizes data about sex differences in MS and the role of pregnancy. Possible mechanisms for the effects of sex and pregnancy are summarized, and practical suggestions for addressing these issues are provided.
Expert opinion:
There is considerable interdependence of the variables that are associated with MS. Men have a worse outcome of MS, and this could be due to the same factors that lead to greater incidence of neurodegenerative disease in men. The possible role of parity on the long-term outcome of MS is of interest. Future studies that look at the mechanisms of the effects of the sex of the patient on the outcome of MS are required. However, there are some actions that can be taken without further research. We can concentrate on public health measures that address the modifiable risk factors for MS and ensure that disease is controlled in women who intend to become pregnant and use appropriate disease modifying agents during pregnancy.
Objectives
To study the prognostic features of Creutzfeldt-Jakob disease (CJD) and shed light on its future therapy.
Design
Retrospective cohort study of a longitudinal national cohort of the Taiwan Centers for Disease Control.
Setting and Participants
All patients with suspected CJD are reported to the CJD surveillance unit of the Taiwan Centers for Disease Control. An expert committee discussed the reported cases and designated a consensus-based diagnosis. From 1996 to 2020, a total of 809 cases were referred to the CJD surveillance unit for confirmation; of these, 441 cases (women, n = 230) were determined to be sporadic CJD.
Methods
We investigated the clinical manifestations and laboratory findings for 400 patients diagnosed with definite or probable sporadic CJD. We used Kaplan-Meier analyses and Cox proportional hazards model to identify prognostic factors.
Results
The mean age of onset was 67 ± 9.9 years. The mean survival duration was 13.3 ± 14.2 (median 10) months. The leading clinical symptoms were myoclonus (73%) and akinetic mutism (54%). For PRNP polymorphism, 99% of patients (195/197) showed a methionine homozygous genotype at codon 129 (M129M). The sensitivity of periodic sharp wave complexes (PSWCs) on electroencephalograms (EEGs) was 59.7%. The sensitivity of cerebrospinal fluid 14-3-3 protein and total tau protein (>1200 pg/mL) were 69.7% and 75.6%, respectively. Younger patients lived longer than those aged ≥65 years [hazard ratio (HR) 0.466, P < .001]. Women had a better survival probability in the first 3 years than their male counterparts (HR 0.712, P = .005). PSWCs had a persistent negative effect on survival (HR 0.788, P < .05). Although uncommon, epileptic seizures were the only clinical prognostic factor for survival time (HR 0.768, P < .05). PSWCs can be used as an EEG biomarker for prognosis. Epileptic seizures, though not common, are the only clinical prognostic factor for a short survival.
Conclusions and Implications
We found that a lower age of onset and female gender favor the survival of patients with sCJD. PSWCs are EEG biomarkers unfavorable for survival, and so are epileptic seizures.
In majority populations in high- and middle-income countries, women live longer yet experience higher levels of frailty than men of the same age. It is unclear whether this ‘sex–frailty paradox’ is present in ethnic minority populations. In this narrative review, we explore biological, behavioural and social factors associated with mortality, morbidity and frailty in women, particularly ethnic minority women. We ascertain that natural menopause occurs earlier in women of particular ethnicities. Ethnic minority women (living in high-income countries) have more children and higher rates of chronic disease and disability, all of which are associated with frailty. In some ethnic minorities, women are less likely to engage in deleterious health behaviours such as smoking and alcohol consumption. However, in others the reverse is true. Women from migrant ethnic minorities tend to have lower levels of physical activity. With time, they can also adopt adverse behavioural patterns of the majority population. Although the evidence is sparse, sex differences in health reporting and social assets, as well as gender roles, are likely to contribute to sex differences in frailty in ethnic minorities. Overall, ethnic minority women are a particularly vulnerable group, but the majority of risk factors for frailty appear to be mutable rather than fixed. Future research may examine interventions that target frailty in different races and ethnicities at individual, population and global levels.
Objectives: This study aimed to analyze the relationship between sucrose and fiber intake and symptoms of depression in older people.
Material and Methods: The research group consisted of 813 community-dwelling subjects (221 males and 592 females, median age 75). The symptoms of depression were assessed using the Geriatric Depression Scale (GDS). Participants were divided into two subgroups according to the GDS scale. Group A: 0–5 points – no symptoms of depression (612, M:167, W:445), and group B: 6–15 points – with symptoms of depression (201, M:54, W:147). The level of nutrient consumption was assessed with a 24 h Recall Questionnaire and the software ‘Dieta 5.0’.
Results: In males, consumption of sucrose (A: 30 g (18.1–53.3), B: 62.8 g (43.2–92.6)) (median (25%–75% quartile) and % of energy from sucrose (A: 7.3% (4.8–11.9), B: 13.5% (7.8–18.6)) were significantly higher in the group with symptoms of depression. Kilocalories per 1 g of fiber intake ratios were higher in depressive groups of both males (A: 89.1 kcal/g (68.1–109), B: 103.9 kcal/g (86.1–134.1)) and females (A: 78.6 kcal/g (62.1–99.9), B: 93 kcal/g (67.1–118.3)). Females without symptoms of depression consumed significantly more fiber (17.2 g (12.9–23.1)) than females with symptoms of depression (16.1 g (11.3–20)).
Conclusions: This analysis shows increased kilocalories per 1 g of fiber intake in patients with symptoms of depression. In males, symptoms of depression were connected with higher consumption of sucrose and higher % of energy intake from sucrose. In females, greater fiber consumption was related to less frequent symptoms of depression.
• Frailty describes an individual's vulnerability to adverse health outcomes and is a useful construct that assists health professionals to understand the heterogeneity of the ageing population.
• While the pathophysiological pathways that lead to frailty are not well defined, an individual's sex appears to be a key factor influencing the ageing trajectory.
• Compared with age‐matched men, women tend to have poorer health status (ie, they are more frail) but longer life expectancy (ie, they are more resilient). It seems likely that a combination of biological, behavioural and social factors underpin this male–female health–survival paradox.
• Randomised controlled trial data for frailty interventions in older adults are emerging, with multicomponent programs incorporating exercise and nutrition‐based strategies showing promise. Pharmaceutical and other innovative therapeutic strategies for frailty are highly anticipated.
• Sex differences in the effectiveness of frailty interventions have not been addressed in the research literature to date. In the future, successful interventions may target many (if not all) biopsychosocial domains, with careful consideration of issues relevant to each sex.
The ‘male-female health-survival paradox’ is a well-described clinical phenomenon. More recently, it has been conceptualized as a ‘sex-frailty paradox’: females may be considered to be more frail (because they have poorer health status) but also less frail (because they are less vulnerable to death) than males of the same age. Here, we review potential biological, behavioral and social mechanisms underpinning sex differences in morbidity, mortality and frailty before considering the question at the center of the sex paradox – why is it that females are able to tolerate poor health better than males? We explore, in detail, a frequently cited explanation for the sex paradox that centers on sex differences in chronic disease and conclude by presenting a new approach to this old hypothesis.
Context.—
Observational studies have found lower rates of coronary heart disease
(CHD) in postmenopausal women who take estrogen than in women who do not,
but this potential benefit has not been confirmed in clinical trials.Objective.—
To determine if estrogen plus progestin therapy alters the risk for
CHD events in postmenopausal women with established coronary disease.Design.—
Randomized, blinded, placebo-controlled secondary prevention trial.Setting.—
Outpatient and community settings at 20 US clinical centers.Participants.—
A total of 2763 women with coronary disease, younger than 80 years,
and postmenopausal with an intact uterus. Mean age was 66.7 years.Intervention.—
Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone
acetate in 1 tablet daily (n=1380) or a placebo of identical appearance (n=1383).
Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment were
taking it at the end of 1 year, and 75% at the end of 3 years.Main Outcome Measures.—
The primary outcome was the occurrence of nonfatal myocardial infarction
(MI) or CHD death. Secondary cardiovascular outcomes included coronary revascularization,
unstable angina, congestive heart failure, resuscitated cardiac arrest, stroke
or transient ischemic attack, and peripheral arterial disease. All-cause mortality
was also considered.Results.—
Overall, there were no significant differences between groups in the
primary outcome or in any of the secondary cardiovascular outcomes: 172 women
in the hormone group and 176 women in the placebo group had MI or CHD death
(relative hazard [RH], 0.99; 95% confidence interval [CI], 0.80-1.22). The
lack of an overall effect occurred despite a net 11% lower low-density lipoprotein
cholesterol level and 10% higher high-density lipoprotein cholesterol level
in the hormone group compared with the placebo group (each P<.001). Within the overall null effect, there was a statistically
significant time trend, with more CHD events in the hormone group than in
the placebo group in year 1 and fewer in years 4 and 5. More women in the
hormone group than in the placebo group experienced venous thromboembolic
events (34 vs 12; RH, 2.89; 95% CI, 1.50-5.58) and gallbladder disease (84
vs 62; RH, 1.38; 95% CI, 1.00-1.92). There were no significant differences
in several other end points for which power was limited, including fracture,
cancer, and total mortality (131 vs 123 deaths; RH, 1.08; 95% CI, 0.84-1.38).Conclusions.—
During an average follow-up of 4.1 years, treatment with oral conjugated
equine estrogen plus medroxyprogesterone acetate did not reduce the overall
rate of CHD events in postmenopausal women with established coronary disease.
The treatment did increase the rate of thromboembolic events and gallbladder
disease. Based on the finding of no overall cardiovascular benefit and a pattern
of early increase in risk of CHD events, we do not recommend starting this
treatment for the purpose of secondary prevention of CHD. However, given the
favorable pattern of CHD events after several years of therapy, it could be
appropriate for women already receiving this treatment to continue.
Figures in this Article
MANY OBSERVATIONAL studies have found lower rates of coronary heart
disease (CHD) in women who take postmenopausal estrogen than in women not
receiving this therapy.1- 5
This association has been reported to be especially strong for secondary prevention
in women with CHD, with hormone users having 35% to 80% fewer recurrent events
than nonusers.6- 12
If this association is causal, estrogen therapy could be an important method
for preventing CHD in postmenopausal women. However, the observed association
between estrogen therapy and reduced CHD risk might be attributable to selection
bias if women who choose to take hormones are healthier and have a more favorable
CHD profile than those who do not.13- 15
Observational studies cannot resolve this uncertainty.
Only a randomized trial can establish the efficacy and safety of postmenopausal
hormone therapy for preventing CHD. The Heart and Estrogen/progestin Replacement
Study (HERS) was a randomized, double-blind, placebo-controlled trial of daily
use of conjugated equine estrogens plus medroxyprogesterone acetate (progestin)
on the combined rate of nonfatal myocardial infarction (MI) and CHD death
among postmenopausal women with coronary disease. We enrolled women with established
coronary disease because their high risk for CHD events and the strong reported
association between hormone use and risk of these events make this an important
and efficient study population in which to evaluate the effect of hormone
therapy.
The aim of the study was to investigate the effect of different pattern of childbearing on total mortality.
A cohort study with all currently married women aged 25 years or more at the Norwegian census in 1970 with follow up to the end of 1985. Information on childbearing was obtained by questionnaires collected by enumerators. Follow up on death was found by a linkage based on the unique Norwegian identification number, between census information and the death register in the Central Bureau of Statistics.
The study was a national population survey.
A total of 822,593 women with 11.5 million years of follow up and 112,023 deaths.
Nulliparous women had higher mortality than parous women in all age groups. Parity showed a weak association with increasing mortality among high parous women. Lowest mortality was found for parous women with 2-4 children and a late first and last birth, adjusted for socioeconomic group by level of women's education.
The findings indicate that postponed childbearing may benefit the health of women.
Because repeated injury of the endothelium and subsequent turnover of intimal and medial cells have been implicated in atherosclerosis, we examined telomere length, a marker of somatic cell turnover, in cells from these tissues. Telomere lengths were assessed by Southern analysis of terminal restriction fragments (TRFs) generated by HinfI/Rsa I digestion of human genomic DNA. Mean TRF length decreased as a function of population doublings in human endothelial cell cultures from umbilical veins, iliac arteries, and iliac veins. When endothelial cells were examined for mean TRF length as a function of donor age, there was a significantly greater rate of decrease for cells from iliac arteries than from iliac veins (102 bp/yr vs. 47 bp/yr, respectively, P < 0.05), consistent with higher hemodynamic stress and increased cell turnover in arteries. Moreover, the rate of telomere loss as a function of donor age was greater in the intimal DNA of iliac arteries compared to that of the internal thoracic arteries (147 bp/yr vs. 87 bp/yr, respectively, P < 0.05), a region of the arterial tree subject to less hemodynamic stress. This indicates that the effect is not tissue specific. DNA from the medial tissue of the iliac and internal thoracic arteries showed no significant difference in the rates of decrease, suggesting that chronic stress leading to cellular senescence is more pronounced in the intima than in the media. These observations extend the use of telomere size as a marker for the replicative history of cells and are consistent with a role for focal replicative senescence in cardiovascular diseases.
Maternal cardiovascular adaptation to pregnancy involves enormous changes. Cardiac output increases in early pregnancy, initially as a result of an increased heart rate, soon followed by an increased stroke volume. Cardiac output continues to increase until midpregnancy, and remains stable afterward, with a possible small decline in the last weeks of pregnancy. Blood pressure decreases in early pregnancy, reaching a minimum in midpregnancy, then returning to baseline levels at term. Consequently, peripheral vascular resistance is reduced throughout pregnancy. Myocardial contractility seems to be increased during all trimesters of pregnancy, thus gradually provoking the development of a mild ventricular hypertrophy. The increase in preload, which develops in concert with the increment in blood volume, leads to an increase in left atrial diameter, which also begins during early pregnancy. During labor, both cardiac output and blood pressure increase. After delivery, cardiac output initially increases, but begins to decrease within the first hour to reach baseline levels 2 weeks postpartum. Most cardiovascular parameters show their greatest changes within 2 weeks postpartum. Five months postnatally, only a mild residual ventricular hypertrophy persists.
Blood pressure decreases during early pregnancy in association with a decrease in peripheral vascular resistance and increases in renal plasma flow and glomerular filtration rate. These early changes suggest a potential association with corpora lutea function. To determine whether peripheral vasodilation occurs following ovulation, we studied 16 healthy women in the midfollicular and midluteal phases of the menstrual cycle. A significant decrease in mean arterial pressure in the midluteal phase of the cycle (midfollicular of 81.7 +/- 2.0 vs. midluteal of 75.4 +/- 2.3 mmHg, P < 0.005) was found in association with a decrease in systemic vascular resistance and an increase in cardiac output. Renal plasma flow and glomerular filtration rate increased. Plasma renin activity and aldosterone concentration increased significantly in the luteal phase accompanied by a decrease in atrial natriuretic peptide concentration. Serum sodium, chloride, and bicarbonate concentrations and osmolarity also declined significantly in the midluteal phase of the menstrual cycle. Urinary adenosine 3',5'-cyclic monophosphate (cAMP) excretion increased in the luteal compared with the follicular phase, whereas no changes in urinary cGMP or NO2/NO3 excretion were found. Thus peripheral vasodilation occurs in the luteal phase of the normal menstrual cycle in association with an increase in renal plasma flow and filtration. Activation of the renin-angiotensin-aldosterone axis is found in the luteal phase of the menstrual cycle. These changes are accompanied by an increase in urinary cAMP excretion indicating potential vasodilating mediators responsible for the observed hemodynamic changes.
We investigated the role of nitric oxide (NO) in the vascular resistance changes of normotensive and preeclamptic pregnancy. Forearm blood flow (FBF) responses to brachial artery infusion of N(G)-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor, and angiotensin II (ANG ID, an NO-independent vasoconstrictor, were determined by plethysmography in 20 nonpregnant women, 20 normotensive primigravidae, and 15 primigravidae with untreated preeclampsia. In pregnant subjects, FBF was reduced to nonpregnancy levels by infusion of norepinephrine (NE), which was then coinfused with ANG II (2, 4, and 8 ng/min) and L-NMMA (200, 400, and 800 μg/min) each for 5 min. In separate studies, responses to NE (20, 50, and 100 ng/min) were determined in 8 nonpregnant women, with FBF elevated to pregnancy levels by concomitant infusion of glyceryl trinitrate, and 10 pregnant women. Vasoconstrictor responses to L-NMMA were increased in pregnant compared with nonpregnant subjects [mean ± SE summary measure (in arbitrary units): 60 ± 7 vs. 89 ± 8, respectively; P < 0.01], whereas responses to ANG II were blunted (125 ± 11 vs. 79 ± 7, respectively; P < 0.001). Compared with normotensive pregnant subjects, preeclamptic subjects had an enhanced response to ANG II (79 ± 7 vs. 103 ± 8, respectively; P < 0.05) but no difference in response to L-NMMA (89 ± 8 vs. 73 ± 10, respectively; P = 0.30). Responses to NE were similar in pregnant and nonpregnant subjects (110 ± 20 vs. 95 ± 33, respectively; P = 0.66). During the third trimester of pregnancy, forearm constrictor responses to L-NMMA are increased. The responses to NE are unchanged, whereas responses to ANG II are blunted. Increased NO activity contributes to the fall in peripheral resistance. In preeclampsia, forearm constrictor responses to ANG II but not L-NMMA are increased compared with those in normal pregnancy. Changes in vascular NO activity are unlikely to account for the increased vascular tone in this condition.
Early pregnancy is characterized by the institution of a high-flow low-resistance circulation. In this study, we tested the hypothesis that these hemodynamic changes develop independently of changes in basal metabolic rate. In 12 healthy women, we determined and calculated once during the follicular phase (day 5 +/- 2) and at 6, 8, 10, and 12 wk of pregnancy the following variables: body weight and length, body mass index, fat-free mass (FFM), mean arterial pressure (MAP), heart rate (HR), stroke volume, cardiac output (CO), total peripheral vascular resistance (TPVR), resting energy expenditure (REE), FFM REE (REE(FFM)), and respiratory quotient (RQ). At 6 wk of gestational age, HR and CO had increased, whereas MAP and TPVR had decreased. These changes persisted throughout the study period. Meanwhile, REE, REE(FFM), RQ, FFM, and body weight did not change consistently. The changes with pregnancy in hemodynamics did not correlate with those in basal metabolic rate. In early pregnancy, the institution of a high-flow low-resistance circulation develops without a concomitant rise in basal metabolic rate. These findings support the concept that the hemodynamic changes in early pregnancy develop independently of concomitant changes in basal metabolic rate.
Does a woman's reproductive history influence her life span? This study explores the question with data from the contemporary female populations of England and Wales and Austria. It is the first comparative study to investigate the relationship between fertility and mortality late in life. We find similar patterns and age-specific trends of excess mortality in both populations: parity significantly influences longevity, as do both an early and a late birth. These differences in longevity are not explained by differences in educational or family status. The impact of a woman's reproductive history on her life span is small, however, compared to the influence of her level of education or family status.
Female sex hormones have been implicated in the cardioprotection of premenopausal women. However, the cardiovascular actions of these hormones and the effects of their natural fluctuations during the menstrual cycle are not fully understood. We studied changes in vascular function during the menstrual cycle in 15 healthy premenopausal women. Four noninvasive procedures were performed during the early follicular (EF), late follicular (LF), early luteal (EL), and late luteal (LL) phases: flow-mediated dilatation (FMD) of the brachial artery during reactive hyperemia, laser Doppler velocimetry (LDV) with direct current iontophoresis of acetylcholine (ACh) and nitroprusside, whole body arterial compliance (WBAC), and pulse wave velocity. Hormone levels were consistent with predicted cycle phase and showed that all subjects ovulated during the cycle studied. FMD, LDV with ACh, and WBAC varied cyclically, with significant increases from the F to LF phase, sharp falls in the EL phase, and significant recoveries in the LL phase. These changes were most marked for FMD [EF, 8.8 +/- 0.6% (mean +/- SEM); LF, 10.0 +/- 0.7; EL, 4.2 +/- 0.6; LL, 8.6 +/- 0.9] and the LDV response to ACh (EF, 2.7 +/- 0.2 V/min; LF, 3.3 +/- 0.4; EL, 1.8 +/- 0.3; LL, 2.7 +/- 0.4). WBAC changed similarly (EF, 0.58 +/- 0.08 arbitrary units; LF, 0.84 +/- 0.06; EL, 0.65 +/- 0.05; LL, 0.68 +/- 0.06). Sodium nitroprusside-induced vasodilatation decreased significantly from EF to EL, with no other significant difference, and pulse wave velocity did not vary significantly over the four time points. Conductance and resistance artery endothelial reactivity and smooth muscle sensitivity to nitric oxide and arterial compliance are modulated significantly in response to the changing hormonal patterns of the menstrual cycle. These findings emphasize the importance of menstrual phase in the interpretation of data on endothelial function and may provide insights into the mechanisms underlying sex differences in cardiovascular risk and other disease processes in premenopausal women.
In the year 2000, there were more than 400 million people aged 65 and over in the world--projected to increase to almost 1.5 billion by the year 2050--a close to fourfold increase compared to the 50% increase for the global population as a whole. More than 25% of these 1.5 billion elderly people are projected to be "oldest-old" (aged 80 and over). Global ageing is a triumph and a challenge. As we enter the 21st century, it will put increased economic and social demands in all countries. But if more and more individuals reach older age in good health--and remain healthy for longer--the benefits will be shared by all. Therefore, the promotion of healthy ageing and the prevention of disability in all older people must assume a central role in medical care and research as well as in the formulation of national health and social policies. Effective programs promoting healthy ageing will ensure a more efficient use of health and social services and improve the quality of life in older persons by enabling them to remain independent and productive. With prolonged life expectancy, men and women can expect to live one-third of their lives with some form of hormone deficiency. Life expectancy differences between men and women exist in various regions of the world with a mean of 4.2 years, and is projected to increase to 4.8 years by the year 2050. The ageing male, in particular, has the risk of developing gender-specific urological diseases, such as prostate cancer, benign prostate hyperplasia continence disorders (generally ignored by men) and erectile dysfunction. Hormonal changes in the ageing male are associated with changes in the body mass index, osteoporosis, and sleep and mood disorders. A significant relationship between body fat mass and both cardiovascular and overall mortality in men has been demonstrated. In some populations, at least, men may run a higher risk for cardiovascular complications than women. It is our sincere hope that the next few years will enrich us with facts and clarify the state of our present knowledge, permit us to recognize some of the missing links, give us the tools and methodology to design and plan ways to understand ageing in men, allow us to help to improve the quality of life, prevent the preventable, and postpone and decrease the pain and suffering of the inevitable.
In both men and women, circulating androgen levels decline with advancing age. Until now, results of several small studies on the relationship between endogenous androgen levels and atherosclerosis have been inconsistent. In the population-based Rotterdam Study, we investigated the association of levels of dehydroepiandrosterone sulfate (DHEAS) and total and bioavailable testosterone with aortic atherosclerosis among 1,032 nonsmoking men and women aged 55 yr and over. Aortic atherosclerosis was assessed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intimal atherosclerosis. Relative to men with levels of total and bioavailable testosterone in the lowest tertile, men with levels of these hormones in the highest tertile had age-adjusted relative risks of 0.4 [95% confidence interval (CI), 0.2-0.9] and 0.2 (CI, 0.1-0.7), respectively, for the presence of severe aortic atherosclerosis. The corresponding relative risks for women were 3.7 (CI, 1.2-11.6) and 2.3 (CI, 0.7-7.8). Additional adjustment for cardiovascular disease risk factors did not materially affect the results in men, whereas in women the associations diluted. Men with levels of total and bioavailable testosterone in subsequent tertiles were also protected against progression of aortic atherosclerosis measured after 6.5 yr (SD +/- 0.5 yr) of follow-up (P for trend = 0.02). No clear association between levels of DHEAS and presence of severe aortic atherosclerosis was found, either in men or in women. In men, a protective effect of higher levels of DHEAS against progression of aortic atherosclerosis was suggested, but the corresponding test for trend did not reach statistical significance. In conclusion, we found an independent inverse association between levels of testosterone and aortic atherosclerosis in men. In women, positive associations between levels of testosterone and aortic atherosclerosis were largely due to adverse cardiovascular disease risk factors.
Hormone replacement therapy (HRT) and antioxidant vitamins are widely used for secondary prevention in postmenopausal women with coronary disease, but no clinical trials have demonstrated benefit to support their use.
To determine whether HRT or antioxidant vitamin supplements, alone or in combination, influence the progression of coronary artery disease in postmenopausal women, as measured by serial quantitative coronary angiography.
The Women's Angiographic Vitamin and Estrogen (WAVE) Trial, a randomized, double-blind trial of 423 postmenopausal women with at least one 15% to 75% coronary stenosis at baseline coronary angiography. The trial was conducted from July 1997 to January 2002 in 7 clinical centers in the United States and Canada.
Patients were randomly assigned in a 2 x 2 factorial design to receive either 0.625 mg/d of conjugated equine estrogen (plus 2.5 mg/d of medroxyprogesterone acetate for women who had not had a hysterectomy), or matching placebo, and 400 IU of vitamin E twice daily plus 500 mg of vitamin C twice daily, or placebo.
Annualized mean (SD) change in minimum lumen diameter (MLD) from baseline to concluding angiogram of all qualifying coronary lesions averaged for each patient. Patients with intercurrent death or myocardial infarction (MI) were imputed the worst rank of angiographic outcome.
The mean (SD) interval between angiograms was 2.8 (0.9) years. Coronary progression, measured in mean (SD) change, worsened with HRT by 0.047 (0.15) mm/y and by 0.024 (0.15) mm/y with HRT placebo (P =.17); and for antioxidant vitamins by 0.044 (0.15) mm/y and with vitamin placebo by 0.028 (0.15) mm/y (P =.32). When patients with intercurrent death or MI were included, the primary outcome showed an increased risk for women in the active HRT group (P =.045), and suggested an increased risk in the active vitamin group (P =.09). Fourteen patients died in the HRT group and 8 in the HRT placebo group (hazard ratio [HR], 1.8; 95% confidence interval [CI], 0.75-4.3), and 16 in the vitamin group and 6 in the vitamin placebo group (HR, 2.8; 95% CI, 1.1-7.2). Death, nonfatal MI, or stroke occurred in 26 HRT patients vs 15 HRT controls (HR, 1.9; 95% CI, 0.97-3.6) and in 26 vitamin patients and 18 vitamin controls (HR, 1.5; 95% CI, 0.80-2.9). There was no interaction between the 2 treatment interventions.
In postmenopausal women with coronary disease, neither HRT nor antioxidant vitamin supplements provide cardiovascular benefit. Instead, a potential for harm was suggested with each treatment.
Telomeres, the non‐coding sequences at the ends of chromosomes, in the absence of telomerase, progressively shorten with each
cell division. Shortening of telomeres can induce cell cycle arrest and apoptosis. The aim of this study was to investigate
age‐ and gender‐related changes in telomere length in the rat and to detect possible tissue‐ specific rates of telomere shortening.
Changes with age in telomere lengths were assessed by Southern blotting in the kidney, pancreas, liver, lung and brain of
male and female rats. We determined the percentage of telomeres in various molecular size regions rather than measuring the
average telomere length. The latter was unable to detect telomere shortening in the tissues. The percentage of short telomeres
increased with age in the kidney, liver, pancreas and lung of both males and females, but not in the brain. Males had shorter
telomeres than females in all organs analysed except the brain, where the lengths were similar. These findings indicate that
telomeres shorten in the rat kidney, liver, pancreas and the lung in an age‐dependent manner. These data also provide a novel
mechanism for the gender‐related differences in lifespan and suggest a tissue‐specific regulation of telomere length during
development and ageing in the rat.
We investigated the role of nitric oxide (NO) in the vascular resistance changes of normotensive and preeclamptic pregnancy. Forearm blood flow (FBF) responses to brachial artery infusion of N-G-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor, and angiotensin II (ANG II), an NO-independent vasoconstrictor, were determined by plethysmography in 20 nonpregnant women, 20 normotensive primigravidae, and 15 primigravidae with untreated preeclampsia. In pregnant subjects, FBF was reduced to nonpregnancy levels by infusion of norepinephrine (NE), which was then coinfused with ANG II (2, 4, and 8 ng/min) and L-NMMA (200, 400, and 800 mu g/min) each for 5 min. In separate studies, responses to NE (20; 50, and 100 ng/min) were determined in 8 nonpregnant women, with FBF elevated to pregnancy levels by concomitant infusion of glyceryl trinitrate, and 10 pregnant women. Vasoconstrictor responses to L-NMMA were increased in pregnant compared with nonpregnant subjects [mean +/- SE summary measure tin arbitrary units): 60 +/- 7 vs. 89 +/- 8, respectively; P < 0.01], whereas responses to ANG II were blunted (125 +/- 11 vs. 79 +/- 7, respectively; P < 0.001). Compared with normotensive pregnant subjects, preeclamptic subjects had an enhanced response to ANG 11 (79 +/- 7 vs. 103 +/- 8, respectively; P < 0.05) but no difference in response to L-NMMA (89 +/- 8 vs. 73 +/- 10, respectively; P = 0.30). Responses to NE were similar in pregnant and nonpregnant subjects (110 +/- 20 vs. 95 +/- 33, respectively; P = 0.66). During the third trimester of pregnancy, forearm constrictor responses to L-NMMA are increased. The responses to NE are unchanged, whereas responses to ANG II are blunted. Increased NO activity contributes to the fall in peripheral resistance. In preeclampsia, forearm constrictor responses to ANG II but; not L-NMMA are increased compared with those in normal pregnancy. Changes in vascular NO activity are unlikely to account for the increased vascular tone in this condition.
Context Despite decades of use and considerable research, the role of estrogen
alone in preventing chronic diseases in postmenopausal women remains uncertain.
Objective To assess the effects on major disease incidence rates of the most commonly
used postmenopausal hormone therapy in the United States.
Design, Setting, and Participants A randomized, double-blind, placebo-controlled disease prevention trial
(the estrogen-alone component of the Women's Health Initiative [WHI]) conducted
in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal
women, aged 50-79 years, with prior hysterectomy, including 23% of minority
race/ethnicity.
Intervention Women were randomly assigned to receive either 0.625 mg/d of conjugated
equine estrogen (CEE) or placebo.
Main Outcome Measures The primary outcome was coronary heart disease (CHD) incidence (nonfatal
myocardial infarction or CHD death). Invasive breast cancer incidence was
the primary safety outcome. A global index of risks and benefits, including
these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer,
hip fracture, and deaths from other causes, was used for summarizing overall
effects.
Results In February 2004, after reviewing data through November 30, 2003, the
National Institutes of Health (NIH) decided to end the intervention phase
of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals
[CIs]) for CEE vs placebo for the major clinical outcomes available through
February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12)
with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39
(1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal
cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91)
with 102 cases. Corresponding results for composite outcomes were: total cardiovascular
disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures,
0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index,
1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was
an absolute excess risk of 12 additional strokes per 10 000 person-years
and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years.
The estimated excess risk for all monitored events in the global index was
a nonsignificant 2 events per 10 000 person-years.
Conclusions The use of CEE increases the risk of stroke, decreases the risk of hip
fracture, and does not affect CHD incidence in postmenopausal women with prior
hysterectomy over an average of 6.8 years. A possible reduction in breast
cancer risk requires further investigation. The burden of incident disease
events was equivalent in the CEE and placebo groups, indicating no overall
benefit. Thus, CEE should not be recommended for chronic disease prevention
in postmenopausal women.
Despite the fact that neither hormone replacement therapy (HRT) nor antioxidant vitamins have been demonstrated to benefit postmenopausal women with coronary artery disease (CAD), both measures are widely used as secondary prevention. The Women's Angiographic Vitamin and Estrogen (WAVE) trial was designed to show whether either of these measures or both together slow the progression of CAD in this setting. This randomized, double-blind trial enrolled 423 postmenopausal women with at least one coronary artery stenosed by 15% to 75%. The participants, seen at seven US and Canadian clinical centers, were randomly assigned to receive 0.625 mg daily of conjugated equine estrogen; 400 IU of vitamin E and 500 mg of vitamin C twice daily; both active treatments; or matching placebos. Women assigned to HRT who had not had a hysterectomy also received 2.5 mg daily of medroxyprogesterone acetate. Serum levels of low-density lipoprotein (LDL) cholesterol declined and levels of high-density lipoprotein (HDL) cholesterol increased in women given HRT, but vitamins had no comparable effects. The decline in mean luminal diameter (MLD) on coronary angiography was more marked in all actively treated groups than in patients given double placebos, but the differences were not statistically significant. There was no significant interaction between treatments for any angiographic outcome. Vitamin treatment was associated with a nonsignificant difference in MLD. Mortality was lowest in double placebo recipients and highest in women given both active treatments. Using a composite end point of death and nonfatal myocardial infarction, women assigned to HRT did less well than placebo recipients, although the difference was not significant. Mortality from all causes was significantly higher in women given vitamins than in those given a vitamin placebo, and a similar trend was noted for cardiovascular deaths. Neither HRT nor antioxidant vitamin supplements improved clinical outcomes in postmenopausal women with existing CAD who participated in the WAVE trial. The investigators suggest that these women be discouraged from taking both HRT and high doses of vitamins E and C.
• Evolutionary selection has equipped females with immunoregulatory genes on the × chromosome for coping with lifethreatening illness. Five immunodeficiency syndromes occur solely in males, suggesting that they arise from mutant immunoregulatory genes located on the × chromosome. These syndromes, although rare, could contribute to poorer survival of males. Females have higher serum IgM concentrations, superior ability to form antibodies to infectious agents, and experience a lower incidence of viral and bacterial infectious diseases. Preponderance of autoimmune disorders in females could arise from modified immune responses owing to estrogens. Clinical and animal studies indicate that male hormones suppress autoantibody production whereas female hormones support their production. Superior immunocompetence and survival of females is based, in part, on their being protected from mutant immunoregulatory genes located on the × chromosome.
(Am J Dis Child 133:1251-1253, 1979)
1. Changes in blood pressure during the normal menstrual cycle are not well documented, and previous studies have given conflicting results.
2. Thirty normotensive women and ten mildly hypertensive women measured their blood pressure at home each morning for 6 weeks, under standardized conditions, using a UA-751 semi-automatic sphygmomanometer. All had normal menstrual cycles and subjects entered the study at difference phases of the cycle.
3. Blood pressure was higher at the onset of menstruation than at most other phases of the cycle (systolic blood pressure, P < 0.05; diastolic blood pressure, P < 0.001). Adjusted diastolic blood pressure was higher in the follicular than in the luteal phase (mean difference 1.23 mmHg, P < 0.001). Similarly, blood pressure was lower during days 17–26 than during the remainder of the cycle (adjusted mean difference in systolic blood pressure −0.65 mmHg, P = 0.07; adjusted mean difference in diastolic blood pressure − 1.19 mmHg, P < 0.001).
4. Similar patterns were seen in normotensive and hypertensive subjects, and changes in plasma 17β-oestradiol and progesterone concentrations were also similar in the two groups.
Females of the human species live longer than males, and the longevity differential is probably not entirely explained by reasons which are presently obvious. Genotypic sex has long been suspected to affect longevity to the advantage of the female. Several recent findings about the X and Y chromosomes must be reckoned with in considering determinants of longevity which derive from genotypic sex. The advantages of having two X chromosomes are apparent, notwithstanding X-chromosome inactivation. Not only can some cells compensate for biosynthetic deficiencies of others, but also cell selection according to which X chromosome is active can occur during development according to cell viability and proliferative capacity. It has recently been observed that at least some genes on inactive X chromosomes are reactivated late in life. Details of the reactivation process must be studied to determine its significance and the effects of the process on late life survival. The recent mapping of the catalytic polypeptide of DNA-polymerase-alpha to the X chromosome calls attention to a new property of the genotype which could affect the basic ability of cells to proliferate. It is likely that this enzyme, perhaps in concert with DNA-polymerase-delta, is required for DNA replication, suggesting that two alleles for this enzyme and cell selection within the female phenotypic mosaic for DNA replication may provide a sex-linked determinant of cell proliferation which could be advantageous in late life. Much remains to be learned about the Y chromosome, although there are early results consistent with a determinant of longevity on that chromosome which operates to the male disadvantage and probably does not involve sex hormones. The genotype may be a significant determinant of longevity in humans even if it does not appear to be so in non-human animals, because causes of death are different. Determinants of longevity are based on susceptibility or vulnerability to the causes and diseases of mortality, and these differ in different species.
To study the influence of gender on peak oxygen uptake and on the hemodynamic response to dynamic exercise in essential hypertension, 45 male and 45 female patients, matched for age and blood pressure, were studied. Blood pressure was measured intra-arterially and cardiac output by the direct oxygen Fick method. Anthropometric gender differences were accounted for by statistical adjustment for height and weight. The increase of absolute and adjusted stroke volume from sitting at rest to submaximal (50 W) and to peak bicycle exercise was smaller in women than in men (P < 0.05). At 50 W, oxygen uptake (0.96 vs 0.97 l.min-1) and cardiac output (10.9 vs 11.2 l.min-1) were not different between women and men, due to the steeper exercise-induced rises of heart rate (P < 0.001) and arteriovenous oxygen difference (P < 0.05) in the women. Women reached the same peak heart rate as men (168 vs 173 b.min-1), so that the lower (P < 0.001) stroke volume (77 vs 99 ml) and cardiac output (12.9 vs 17.0 l.min-1), together with the lower hemoglobin concentration, contributed to their impaired peak oxygen uptake (P < 0.001), both before (1.35 vs 2.17 l.min-1) and after adjustment for body size (1.44 vs 2.07 l.min-1). In conclusion, at fixed submaximal exercise, women achieve the same oxygen uptake and cardiac output as men despite a lower stroke volume, through adaptations of heart rate and peripheral oxygen extraction; their peak aerobic power and cardiac output are, however, substantially lower than in men.
This study assessed whether aging is associated with progressive endothelial dysfunction, whether the pattern of any age-related decline in vascular health is different in men and women and whether any gender difference is consistent with known changes in hormonal status.
Coronary and cerebrovascular disease are much less common in young and middle-aged women compared with men, although the gender difference in death from atherosclerosis is less marked after the menopause. Endothelial dysfunction is an early event in atherogenesis and is important in dynamic plaque stenosis in later life. The effect of aging on endothelial function in men and women, however, is not well known.
We used high resolution ultrasound to study endothelium-dependent and endothelium-independent vascular responses. Brachial artery physiology was investigated in 238 subjects (103 men, 135 women; mean [+/- SD] age 38 +/- 17 years, range 15 to 72) with no known risk factors for atherosclerosis. The responses to reactive hyperemia (flow-mediated dilation, which is endothelium dependent) and to glyceryl trinitrate (an endothelium-independent dilator) were assessed for all the subjects and then for men and women separately.
On multivariate analysis for the whole group, reduced flow-mediated dilation was related to older age (r = -0.34, p < 0.0001). In men, flow-mediated dilation was preserved in subjects aged < or = 40 years but declined thereafter at 0.21%/year. In women, flow-mediated dilation was stable until the early 50s, after which it declined at 0.49%/year (p = 0.002 compared with men). In contrast, there was no significant change in the glyceryl trinitrate response with aging in either gender.
Aging is associated with progressive endothelial dysfunction in normal humans, and this appears to occur earlier in men than in women. In women, however, a steep decline commences at around the time of the menopause. This is consistent with a protective effect of estrogens on the arterial wall.
Estrogen has been reported to augment endothelium-dependent vasodilatation. The role of endogenous ovarian hormones in modulating endothelium-dependent vasodilatation, however, remains to be determined. The purpose of the present study was to investigate the effects of sex and menstrual cycle on endothelium-dependent flow-mediated vasodilatation.
Seventeen female volunteers 25.1 +/- 0.8 years old and 17 age-matched male volunteers were examined. We measured brachial artery diameters noninvasively using a 7.5-MHz ultrasound machine at rest, during reactive hyperemia, and after sublingual nitroglycerin administration. All female subjects were studied three times each, in three different phases of one menstrual cycle (M, menstrual phase; F, follicular phase; and L, luteal phase). Flow-mediated diameter (D) increase (%FMD; delta D/D x 100) in M, when serum estradiol level was low (121.9 +/- 12.5 pmol/L), was 11.22 +/- 0.58%, and the value was comparable to that in male subjects (10.60 +/- 0.75%). %FMD increased in F (18.20 +/- 0.81%, P < .01 versus M) and L (17.53 +/- 0.74%, P < .01 versus M), when serum estradiol level was high (F, 632.0 +/- 74.5 and L, 533.8 +/- 33.4 pmol/L, P < .01 versus M). Endothelium-independent vasodilatation by nitroglycerin increased in both F and L. However, the increment was smaller than that of %FMD.
Endothelium-dependent vasodilatation varies during the menstrual cycle. The endogenous estradiol may be involved in this menstrual cycle-related vasodilatation.
To evaluate the effect of endogenous estrogens on endothelial function in humans, we examined whether menopause is associated with impairment in endothelium-dependent vasodilation in normotensive and essential hypertensive women. In 73 normotensive subjects (37 women, 36 men) and 73 hypertensive patients (36 women, 37 men), we studied endothelial function by measuring forearm blood flow modifications (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms/100 mL per minute), an endothelium-dependent vasodilator, and sodium nitroprusside (1,2, and 4 micrograms/100 mL per minute), an endothelium-independent vasodilator. Women younger than 45 years had normal menstrual cycles. In essential hypertensive patients, responses to acetylcholine but not to sodium nitroprusside were significantly (P < .001) reduced compared with responses in normotensive subjects. Moreover, in both groups, vasodilation to acetylcholine showed a marked negative correlation with advancing age (normotensive subjects: r = -.88, P < .001; hypertensive patients: r = -.87, P < .001). In contrast, vasodilation to sodium nitroprusside showed a less evident negative correlation with advancing age (normotensive subjects: r = -46, P < .01; hypertensive patients: r = -.48, P < .01). However, in normally menstruating normotensive women, no endothelial dysfunction was observed, and age-related impairment in endothelium-dependent vasodilation was evident only after menopause. In normally menstruating hypertensive women, aging was associated with endothelial dysfunction although the deterioration of endothelium-dependent vasodilation was less marked than that in men. In contrast, after menopause, the age-related endothelial dysfunction in hypertensive women was similar to that observed in men. Finally, no sex-related difference in the response to sodium nitroprusside was observed in either normotensive subjects or essential hypertensive patients. Age-related endothelial dysfunction is attenuated in premenopausal normotensive and hypertensive women compared with men, whereas no sex-induced difference is observed after menopause, suggesting a protective effect of endogenous estrogens on endothelial function.
Although sex hormones appear to be importantly involved in the development of coronary heart disease, apparently no study has yet reported an alteration in an endogenous sex hormone level in relation to coronary heart disease in women. In an attempt to determine whether any sex hormone abnormality might be a factor in the development of myocardial infarction in women, estradiol and testosterone, as well as sex hormone-binding globulin, insulin, dehydroepiandrosterone sulfate, and risk factors for myocardial infarction, were measured in relation to the degree of coronary artery disease (CAD) in 60 postmenopausal women undergoing coronary angiography. In a multiple-regression analysis with the degree of CAD as the dependent variable and free testosterone (FT), estradiol, age, body mass index, systolic blood pressure, cholesterol, smoking, and insulin as independent variables in the model, only FT (P < .008) and cholesterol (P = .01) were significantly related to the degree of CAD, both positively. To exclude a possible confounding effect due to prior myocardial infarction, the multiple-regression analysis was repeated for the subgroup of 49 patients remaining after excluding the 11 patients who had ever had a myocardial infarction; again only FT (P < .04) and cholesterol (P = .05) were significantly related to the degree of CAD. Neither total testosterone in place of FT nor HDL cholesterol in place of total cholesterol in the model was significantly related to CAD. Sex hormone-binding globulin and dehydroepiandrosterone sulfate, added individually to the model, showed no significant relationship to CAD. These results raise the possibility that in women an elevated FT level may be a risk factor for coronary atherosclerosis.
Despite an overall reduction in the death rate due to cardiovascular disease (CVD) in the United States over the last several decades, the rate of decline is less for women than men and less for African-American women than white women.1 Due to an aging population, the absolute number of deaths due to CVD in women is actually increasing (Fig 1⇓).2 In the year 2000 nearly 50 million American women will be older than 50 years. Because the risk of CVD increases with age, there is a need for an increased awareness of the importance of CVD as a major public health issue for older women. The estimated direct and indirect costs of CVD and stroke in men and women combined will exceed $250 billion in 1997.2 CVD ranks first among all disease categories in hospital discharges for women. The sheer magnitude of the epidemic in women necessitates a strong emphasis on prevention to reduce the burden of CVD in our society.
Figure 1.
CVD, particularly coronary heart disease (CHD) and stroke, remains the leading killer of women in America and most developed countries. In 1994, the last year for which statistics are available, CVD claimed the lives of more than one half million women and accounted for 45.2% of all deaths in women, more than all forms of cancer combined.2 CVD is a particularly important problem among minority women. The death rate due to CVD is 69% higher in black women than white women. Misperceptions still exist that CVD is not a real problem for women, although it is estimated that 1 in 2 women will eventually die of heart disease or stroke, compared with 1 in 25 who will eventually die of breast cancer.2 This report discusses recent advances in knowledge of the occurrence, …
While estrogens protect against coronary artery disease in women, it is unclear whether they influence cardiovascular function in men. The present report describes coronary vascular abnormalities and the lipoprotein profile of a male patient with estrogen insensitivity caused by a disruptive mutation in the estrogen-receptor gene.
Stress thallium scintigraphy, echocardiography, and electron-beam computed tomography (CT) scanning of the coronary arteries and detailed lipoprotein analysis were performed. Electron-beam CT scanning of the coronary arteries showed calcium in the left anterior descending artery. Lipoprotein analysis showed relatively low levels of total (130 mg/dL), LDL (97 mg/dL), and HDL (34 mg/dL) cholesterol; apolipoprotein A-I (91.7 mg/dL); and lipoprotein(a) (4.1 nmol/L), but normal levels of triglycerides (97 mg/dL) and pre-beta-1-HDL cholesterol (61 microg/mL).
The absence of functional estrogen receptors may be a novel risk factor for coronary artery disease in men.
Severe ovarian hyperstimulation syndrome (OHSS) is consistently associated with a circulatory dysfunction characterized by arterial hypotension, low peripheral vascular resistance, and increased activity of the renin-aldosterone system. To investigate whether circulatory dysfunction also occurs in asymptomatic patients undergoing controlled gonadotropin ovarian hyperstimulation under pituitary suppression for in vitro fertilization (IVF), 12 women without clinical manifestations of OHSS underwent sequential blood, urine, and hemodynamic measurements at five study points: the 7th day of the menstrual cycle preceding IVF (study point 1 or baseline), the day when pituitary suppression was shown (study point 2), the day of hCG ovulatory injection (study point 3), the day after hCG was injected (study point 4), and 7 days after hCG administration (study point 5). Mean arterial pressure, cardiac output, peripheral vascular resistance, plasma concentrations of estradiol (E2) and aldosterone, and plasma renin activity (PRA) were measured at each study point in all women. Serum levels of nitrite/nitrate, and plasma concentration of atrial natriuretic peptide, norepinephrine, adrenomedullin, and cyclic guanosine 3'5'-monophosphate were measured in samples obtained at study points 1 and 5. Multiple follicular development during ovarian stimulation associated with increased plasma E2 concentration (mean peak plasma E2 level, 2430 +/- 428 pg/mL, range 1630-3840 pg/mL) were observed in each woman. All patients developed a significant increase in cardiac output and decrease in arterial pressure and peripheral vascular resistance, and a marked elevation in PRA and aldosterone, all indicating the development of arteriolar vasodilation. Changes in circulatory measurements were temporarily related with the increase in E2 both being detected at study points 3-5. In contrast, there was a clear chronological dissociation between the increase in plasma E2 concentration and the stimulation of the renin-aldosterone system. PRA and aldosterone only reached abnormal levels at study point 5 in association with a significant increase in plasma norepinephrine concentration. Serum levels of nitrite/nitrate and plasma concentrations of atrial natriuretic peptide, adrenomedullin, and cyclic GMP were similar at study points 1 and 5. It is concluded that the circulatory dysfunction that characterizes severe OHSS is a universal event in patients undergoing controlled ovarian hyperstimulation for IVF. Although the increase in E2 levels during IVF cycles is associated with significant circulatory changes, the circulatory dysfunction that characterizes severe OHSS is clearly unrelated to the onset of hyperestrogenemia. Arteriolar vasodilation during IVF cycles was not associated with an increased activity of the vasodilator substances atrial natriuretic peptide, adrenomedullin, and nitric oxide.
Observational studies have found lower rates of coronary heart disease (CHD) in postmenopausal women who take estrogen than in women who do not, but this potential benefit has not been confirmed in clinical trials.
To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease.
Randomized, blinded, placebo-controlled secondary prevention trial.
Outpatient and community settings at 20 US clinical centers.
A total of 2763 women with coronary disease, younger than 80 years, and postmenopausal with an intact uterus. Mean age was 66.7 years.
Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily (n = 1380) or a placebo of identical appearance (n = 1383). Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment were taking it at the end of 1 year, and 75% at the end of 3 years.
The primary outcome was the occurrence of nonfatal myocardial infarction (MI) or CHD death. Secondary cardiovascular outcomes included coronary revascularization, unstable angina, congestive heart failure, resuscitated cardiac arrest, stroke or transient ischemic attack, and peripheral arterial disease. All-cause mortality was also considered.
Overall, there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes: 172 women in the hormone group and 176 women in the placebo group had MI or CHD death (relative hazard [RH], 0.99; 95% confidence interval [CI], 0.80-1.22). The lack of an overall effect occurred despite a net 11% lower low-density lipoprotein cholesterol level and 10% higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group (each P<.001). Within the overall null effect, there was a statistically significant time trend, with more CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5. More women in the hormone group than in the placebo group experienced venous thromboembolic events (34 vs 12; RH, 2.89; 95% CI, 1.50-5.58) and gallbladder disease (84 vs 62; RH, 1.38; 95% CI, 1.00-1.92). There were no significant differences in several other end points for which power was limited, including fracture, cancer, and total mortality (131 vs 123 deaths; RH, 1.08; 95% CI, 0.84-1.38).
During an average follow-up of 4.1 years, treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease. The treatment did increase the rate of thromboembolic events and gallbladder disease. Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events, we do not recommend starting this treatment for the purpose of secondary prevention of CHD. However, given the favorable pattern of CHD events after several years of therapy, it could be appropriate for women already receiving this treatment to continue.
Normal pregnancy is characterized by reduced systemic vascular resistance, which may be mediated by nitric oxide (NO). We compared endothelial vasomotor function in 71 normal pregnant women (13 in first, 29 in middle, and 29 in last trimester) to 37 healthy age-matched controls. With external ultrasound, brachial artery diameter was measured at rest, during reactive hyperemia [with increased flow causing endothelium-dependent dilation (FMD)], and after sublingual nitroglycerin (causing endothelium-independent dilation). Compared with controls, resting flow and brachial artery diameter were significantly higher during the middle and last trimesters. Reactive hyperemia was reduced in all pregnant groups. FMD increased from the first trimester (by 26%), reaching the highest value in the last trimester (to 47% above nonpregnant values). FMD was significantly correlated to pregnancy status (nonpregnant or pregnant) and to vessel size. Nitroglycerin-induced dilation was similar in pregnant and nonpregnant women. A longitudinal study of eight women evaluated in the first, middle, and last trimesters confirmed an increase in FMD throughout pregnancy. The study supports the idea that basal and stimulated NO activity is enhanced in normal pregnancy and may contribute to the decrease in peripheral resistance.
Coronary heart disease (CHD) is markedly more common in men than in women. In both sexes, CHD risk increases with age, but the increase is sharper in women. We analyzed the extent to which major cardiovascular risk factors can explain the sex difference and the age-related increase in CHD risk.
The study cohort consists of 14 786 Finnish men and women 25 to 64 years old at baseline. The following cardiovascular risk factors were determined: smoking, serum total cholesterol, HDL cholesterol, blood pressure, body mass index, and diabetes. Risk factor measurements were done in 1982 or 1987, and the cohorts were followed up until the end of 1994. The Cox proportional hazards model was used to assess the relation between risk factors and CHD risk. CHD incidence in men compared with women was approximately 3 times higher and mortality was approximately 5 times higher. Most of the risk factors were more favorable in women, but the sex difference in risk factor levels diminished with increasing age. Differences in risk factors between sexes, particularly in HDL cholesterol and smoking, explained nearly half of the difference in CHD risk between men and women. Differences in serum total cholesterol level, blood pressure, body mass index, and diabetes prevalence explained about one-third of the age-related increase in CHD risk among men and 50% to 60% among women.
Differences in major cardiovascular risk factors explained a substantial part of the sex difference in CHD risk. An increase in risk factor levels was associated with the age-related increase in CHD incidence and mortality in both sexes but to a larger extent in women.
Telomerase activity is present in most malignant tumors and provides a mechanism for the unlimited potential for division of neoplastic cells. Although telomerase is known to be a regulated enzyme, the factors and mechanisms involved in telomerase regulation are not well understood. In the present study, we examined the effects of estrogen on telomerase activity. Telomerase activity in estrogen receptor (ER)-positive MCF-7 cells was up-regulated by the treatment with 17beta-estradiol. This activation accompanied up-regulation of the telomerase catalytic subunit, hTERT mRNA. Gel shift assays revealed that the imperfect palindromic estrogen-responsive element in the hTERT promoter specifically binds to ER. Transient expression assays using luciferase reporter plasmids containing various fragments of hTERT promoter showed that this imperfect palindromic estrogen-responsive element is responsible for transcriptional activation by ligand-activated ER. We also found that estrogen activates c-Myc expression in MCF-7 cells and that E-boxes in the hTERT promoter that bind c-Myc/Max play additional roles in estrogen-induced transactivation of hTERT. Estrogen thus activates telomerase via direct and indirect effects on the hTERT promoter. These findings may help elucidate the mechanisms of hormonal control of telomerase activity and aid understanding of the roles of sex steroids in cellular senescence and aging as well as estrogen-induced carcinogenesis.
Background:
The goal of this study was to evaluate whether endothelial dysfunction associated with acute estrogen deprivation is caused by an alteration in the L-arginine-nitric oxide (NO) pathway and oxidative stress. Methods and Results-In 26 healthy women (age, 45.7+/-5.4 years) and 18 fertile women with leiomyoma (age, 44.5+/-5.1 years), we studied forearm blood flow (strain-gauge plethysmography) changes induced by intrabrachial acetylcholine (0. 15, 0.45, 1.5, 4.5, or 15 microgram. 100 mL(-1). min(-1)) or sodium nitroprusside (1, 2, or 4 microgram. 100 mL(-1). min(-1)), an endothelium-dependent or -independent vasodilator, respectively. The NO pathway was evaluated by repeating acetylcholine during L-arginine (200 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients) or N(G)-monomethyl-L-arginine (L-NMMA; 100 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients); production of cyclooxygenase-derived vasoconstrictors was assessed by repeating acetylcholine during indomethacin (50 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients) or vitamin C (8 mg. 100 mL(-1). min(-1); 13 control subjects and 9 patients). Patients repeated the study within 1 month after ovariectomy and again after 3 months of estrogen replacement therapy (ERT; 17 beta-estradiol TTS, 50 microgram/d). Basally, vasodilation to acetylcholine was potentiated and inhibited by L-arginine and L-NMMA, respectively (P<0.05), but was unaffected by indomethacin or vitamin C. After ovariectomy, the modulating effect of L-arginine and L-NMMA disappeared, whereas indomethacin and vitamin C potentiated the response to acetylcholine (P<0.05). ERT restored L-arginine and L-NMMA effects on vasodilation to acetylcholine but prevented the potentiation caused by indomethacin or vitamin C. Response to sodium nitroprusside was unaffected by either ovariectomy or ERT.
Conclusions:
Endothelial dysfunction secondary to acute endogenous estrogen deprivation is caused by reduced NO availability. Cyclooxygenase-dependent production of oxidative stress could be responsible for this alteration.
Cardiovascular disease remains the number one killer in the United States. The face of the person with cardiovascular disease is changing. No longer is the middle-aged man at highest risk. Current data reveal that women, especially postmenopausal women, are at highest risk for cardiovascular disease. This article identifies the differences noted between men and women with cardiovascular disease, including effects in presentation, identification, and treatment.
Living in an oxygenated environment has required the evolution of effective
cellular strategies to detect and detoxify metabolites of molecular oxygen
known as reactive oxygen species. Here we review evidence that the appropriate
and inappropriate production of oxidants, together with the ability of organisms
to respond to oxidative stress, is intricately connected to ageing and life
span.
Chronological age is the primary determinant of stiffness of central arteries. Increased stiffness is an independent indicator of cardiovascular risk. The aim of this study was to determine whether telomere length, a possible index of biological aging, provides a better account than chronological age for variation in arterial stiffness, evaluated by measuring pulse pressure and aortic pulse wave velocity. The study population included 193 French subjects (120 men, 73 women), with a mean age of 56+/-11 years, who were not on any antihypertensive medications. Telomere length was evaluated in white blood cells by measuring the mean length of the terminal restriction fragments. Age-adjusted telomere length was longer in women than in men (8.67+/-0.09 versus 8.37+/-0.07 kb; P=0.016). In both genders, telomere length was inversely correlated with age (P<0.01). Multivariate analysis showed that in men, but not in women, telomere length significantly contributed to pulse pressure and pulse wave velocity variations. In conclusion, telomere length provides an additional account to chronological age of variations in both pulse pressure and pulse wave velocity among men, such that men with shorter telomere length are more likely to exhibit high pulse pressure and pulse wave velocity, which are indices of large artery stiffness. The longer telomere length in women suggests that for a given chronological age, biological aging of men is more advanced than that of women.
This review describes the structure of telomeres, the protective DNA-protein complexes at eukaryotic chromosomal ends, and several molecular mechanisms involved in telomere functions. Also discussed are cellular responses to compromising the functions of telomeres and of telomerase, which synthesizes telomeric DNA.
Aims The objective of this paper is to measure the potential burden of cardiovascular disease within the original Framingham Heart Study cohort by transforming its well-described epidemiological measures into time-based health policy measures, such as life years lost to or lived with the disease.
Methods and Results We constructed multi-state life tables of the Framingham Heart Study cohort to calculate dwelling times with a history of cardiovascular disease. Age-specific probabilities determined transitions from healthy through disease to death. For this synthetic cohort, from age 50 men (women) live on average 26 (32) years; 20 (26) free of cardiovascular disease. Allowing occupancy of more than one disease state, 50-year-old males (females) live 2·9 (1·2) years with a history of myocardial infarction, 0·93 (1·2) with a history of stroke, and 0·67 (0·93) with congestive heart failure. Having ever suffered acute myocardial infarction, stroke or congestive heart failure, life expectancy is reduced by 9 (13), 12 (15) or 16 (16) years, respectively in 60-year-old men (women).
Conclusions Transforming occurrence probabilities into time-based health measures, the prevalence of cardiovascular disease is remarkable: from age 50, 20% of remaining life expectancy is lived with the disease. Such measures are integral to appropriate health planning and assessment of the potential population health value of various treatment and prevention strategies.
X chromosome inactivation results in dosage equivalency for X-linked gene expression between males and females. However, some X-linked genes show variable X inactivation, being expressed from the inactive X in some females but subject to inactivation in other women. The human tissue inhibitor of metalloproteinases-1 ( TIMP1) gene falls into this category. As TIMP1 and its target metalloproteinases are involved in many biological processes, women with elevated TIMP1 expression may exhibit different disease susceptibilities. To address the potential impact of variable X inactivation, we analyzed TIMP1 expression levels by using an RNase protection assay. The substantial variation of TIMP1 expression observed in cells with monoallelic TIMP1 expression precluded analysis of the contribution of the inactive X to total TIMP1 RNA levels in females, so we examined expression in rodent/human somatic cell hybrids. TIMP1 expression levels varied more widely in hybrids retaining an inactive X than in those with an active X chromosome, suggesting variable retention of the epigenetic silencing mechanisms associated with X inactivation. Therefore, we investigated the contribution of methylation at the promoter to expression level variation and found that methylation of the TIMP1 promoter correlated with instability and low level expression, whereas stable TIMP1expression from the inactive X equivalent to that seen from the active X chromosome was observed when the promoter was unmethylated. Since all female cell lines examined showed methylation of the TIMP1 promoter, the contribution of expression from the inactive X appears minimal. However, as women age, they may accumulate cells stably expressing TIMP1 from the inactive X, with a resulting increase of TIMP1, which may explain some sex differences in various late-onset disorders.
Levels of fibrinogen, von Willebrand factor, d-dimer, antithrombin III, protein C, plasminogen, and plasminogen activator inhibitor were measured in 62 men and 37 women with ischemic heart disease before and after 20-min venous occlusion. Women compared with men had higher baseline levels of fibrinogen (4.046-/+0.1785 and 3.584-/+0.1591 g/l, respectively, p=0.021), von Willebrand factor (122.1-/+9.31 and 99.5-/+6.16%, respectively, p=0.035), plasminogen activator inhibitor (4.8-/+0.31 and 2.9-/+0.27 IU/l, respectively, p=0.009). Levels of antithrombin III, protein C, and plasminogen in women were higher than in men both at baseline (108.5-/+1.65 and 100.7-/+1.60 %, p=0.001; 129.1-/+2.91 and 107.2-/+3.79%, p=0.001; 113.6-/+2.13 and 104.1-/+1.89%; p=0.001, respectively) and after venous occlusion. There were no gender differences in dynamics of parameters of hemostasis during venous occlusion. Multifactorial regression analysis showed that gender was independently (of age, duration of hypertension, smoking, body mass index, and total cholesterol level) related to only antithrombin III and protein C levels.
During normal ageing, the gradual loss of telomeric DNA in dividing somatic cells can contribute to replicative senescence, apoptosis, or neoplastic transformation. In the genetic disorder dyskeratosis congenita, telomere shortening is accelerated, and patients have premature onset of many age-related diseases and early death. We aimed to assess an association between telomere length and mortality in 143 normal unrelated individuals over the age of 60 years. Those with shorter telomeres in blood DNA had poorer survival, attributable in part to a 3.18-fold higher mortality rate from heart disease (95% CI 1(.)36-7.45, p=0.0079), and an 8.54-fold higher mortality rate from infectious disease (1.52-47.9, p=0.015). These results lend support to the hypothesis that telomere shortening in human beings contributes to mortality in many age-related diseases.
Parity is associated with coronary heart disease (CHD) risk. In the present study, we assessed the associations between number of children and CHD in both women and men.
A total of 4286 women and 4252 men aged 60 to 79 years from 24 British towns were studied. Number of children was positively associated with body mass index and waist-hip ratio in both sexes. In women but not in men, number of children was inversely associated with high-density lipoprotein cholesterol and was positively associated with triglycerides and diabetes. For both sexes, similar "J" shaped associations between number of children and CHD were observed, with the prevalence lowest among those with 2 children and increasing linearly with each additional child beyond 2. For those with at least 2 children, each additional child increased the age-adjusted odds of CHD by 30% (odds ratio, 1.30; 95% confidence interval, 1.17 to 1.44) for women and by 12% for men (odds ratio, 1.12; 95% confidence interval, 1.02 to 1.22). Adjustment for obesity and metabolic risk factors attenuated the associations between greater number of children and CHD in both sexes, although in women some association remained.
Lifestyle risk factors associated with child-rearing lead to obesity and result in increased CHD in both sexes; biological responses of pregnancy may have additional adverse effects in women.
Coronary heart disease is less common in premenopausal women compared to age-matched men. This difference disappears in the post-fertile years, and is presumably related to the reduced levels of female sex hormones, with subsequent metabolic and hemodynamic modifications. Ovarian exhaustion induces a more atherogenic lipid profile, which may partly explain the increased risk of cardiovascular disease observed in post-fertile women as compared to age-matched fertile women. After the menopause, the combination of aging and estrogen deficiency negatively affects glucose metabolism. Diabetes mellitus blunts the beneficial condition associated with the female gender; furthermore, it increases the incidence of myocardial infarction, claudication and stroke in women more than in men. Finally, the unfavorable effects of menopause on the coronary risk seem to be mediated partly by changes in clotting and fibrinolytic factors.
This study investigated the effects of androgens on gene expression in male- and female-donor macrophages.
Men have more severe coronary disease than women. Androgen exposure increases foam cell formation in male but not female macrophages, and male macrophages express >4-fold more androgen receptor messenger ribonucleic acid than female macrophages. Therefore, androgen exposure may have gender-specific and potentially pro-atherogenic effects in macrophages.
Utilizing complementary deoxyribonucleic acid arrays, we studied the effects of a pure androgen (dihydrotestosterone, 40 nmol/l) on human monocyte-derived macrophages from healthy male and female donors (n = 4 hybridizations; 2 men, 2 women). Differential expression of atherosclerosis-related genes was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) in five male and five female donors. Functional corroboration of foam cell formation-related findings was undertaken by experiments using (125)I-acetylated low-density lipoprotein (AcLDL).
In male macrophages, androgen treatment produced differential up-regulation of 27 genes concentrated in five functional classes: 1) lipoprotein processing; 2) cell-surface adhesion; 3) extracellular signaling; 4) coagulation and fibrinolysis; and 5) transport protein genes. By contrast, none of 588 genes were up-regulated in female macrophages. By RT-PCR, we confirmed the gender-specific up-regulation of six of these atherosclerosis-related genes: acyl coenzyme A:cholesterol acyl transferase I, lysosomal acid lipase (LAL), caveolin-2, CD40, vascular endothelial growth factor-165 receptor, and tissue factor pathway inhibitor. Functionally, androgen-treated male macrophages showed increased rates of lysosomal AcLDL degradation, by 45% to 75% after 15 to 20 h of (125)I-AcLDL incubation (p = 0.001), consistent with increased LAL activity.
Androgens increase expression of atherosclerosis-related genes in male but not female macrophages, with functional consequences. These findings may contribute to the male predisposition to atherosclerosis.
Telomeres-the specialized DNA-protein structures at the ends of eukaryotic chromosomes-are essential for maintaining genome stability and integrity and for extended proliferative life span in both cultured cells and in the whole organism. Telomerase and additional telomere-associated proteins are necessary for preserving telomeric DNA length. Age-dependent telomere shortening in most somatic cells, including vascular endothelial cells, smooth muscle cells, and cardiomyocytes, is thought to impair cellular function and viability of the aged organism. Telomere dysfunction is emerging as an important factor in the pathogenesis of hypertension, atherosclerosis, and heart failure. In this Review, we discuss present studies on telomeres and telomere-associated proteins in cardiovascular pathobiology and their implications for therapeutics.