Gender differences in the metabolic syndrome and their role for cardiovascular disease

Summary Women live longer than men and develop cardiovascular disease (CVD) at an older age. The metabolic syndrome represents a major risk factor for the development of CVD, and gender¹ differences in this syndrome may contribute to gender differences in CVD. In recent years, the metabolic syndrome has been more prevalent in men than in women. Prevalence is increasing and this increase has been steeper in women, particularly in young women, during the last decade. The contributions of the different components of the metabolic syndrome differ between genders and in different countries. In a recent survey in Germany, 40% of the adult population had been diagnosed with disturbed glucose tolerance or type 2 diabetes. Undiagnosed diabetes was more frequent in men than in women, and risk factors for undiagnosed diabetes differed between the sexes. Worldwide, in individuals with impaired glucose tolerance, impaired fasting glucose was observed more frequently in men, whereas impaired glucose tolerance occurred relatively more often in women. Lipid accumulation patterns differ between women and men. Premenopausal women more frequently develop peripheral obesity with subcutaneous fat accumulation, whereas men and postmenopausal women are more prone to central or android obesity. In particular, android obesity is associated with increased cardiovascular mortality and the development of type 2 diabetes. Visceral adipocytes differ from peripheral adipocytes in their lipolytic activity and their response to insulin, adrenergic and angiotensin stimulation and sex hormones. Visceral fat is a major source of circulating free fatty acids and cytokines, which are directly delivered via the portal vein to the liver inducing insulin resistance and an atherogenic lipid profile. Inflammation increases cardiovascular risk particularly in women. A relatively greater increase in cardiovascular risk by the appearance of diabetes in women has been reported in many studies. Thus, the presently available data suggest that the pathophysiology of the metabolic syndrome and its contribution to the relative risk of cardiovascular events and heart failure show gender differences, which might be of potential relevance for prevention, diagnostics, and therapy of the syndrome. ¹ "Gender" is used to include biological sex as well as gender in its strict sense Supported by the DFG (grants to V. Regitz–Zagrosek) and the BMBF (Competence Network Heart Failure) An erratum to this article can be found at     

Sex differences in cardiovascular disease risk and exercise in type 2 diabetes

Diabetes currently affects approximately 14% of the US population, and cardiovascular disease (CVD) is a leading cause of morbidity and mortality in those with diabetes. Although in the general population women are at lower risk than men for CVD, women have a disproportionately greater increase in risk for CVD than do men in the context of diabetes. Physical activity is considered a cornerstone in the prevention and treatment of CVD and its risk factors, but greater barriers to physical activity may exist for women with diabetes compared to their male counterparts. In this article, we review sex differences in CVD incidence and risk among diabetics, sex differences in physical activity behaviors, cardiovascular abnormalities and impaired exercise capacity in women living with diabetes, and the effects of exercise on prevention and treatment of CVD in diabetic women. Finally, we discuss future research needed to clarify potential sex differences in the cardiovascular effects of diabetes and to establish ways to reduce the barriers to exercise in women with diabetes.     

Cultural challenges to secondary prevention: implications for Saudi women

Like other highly developed countries, cardiovascular disease (CVD) and coronary heart disease (CHD) are major health problems in Saudi Arabia. The aetiology of cardiovascular disease (CVD) burden within the Saudi population is similar to Western countries with atherosclerosis, hypertension, ischemic heart disease and diabetes highly prevalent with the main risk factors being smoking, obesity and inactivity. There are differences between Saudi men and women in epidemiology, risk factors and health service provision for CHD. These sex and gender based factors are important in considering the health and well-being of Saudi women. Currently, there is Limited focus on the cardiovascular health of Saudi women. The aim of this paper is to examine culturally specific issues for Saudi women and the implications for secondary prevention.     

Gender‐specific features of plasmatic and circulating cell alterations as risk factors in cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of death in the Western countries. Several epidemiological studies have hypothesized a gender disparity in the pathogenesis and progression of CVD. For instance, women develop CVD when they are about 10 years older than men and, typically, after menopause. However, considering that women are often excluded from research studies, sex differences in CVD remains a frontier for discovery. Very important is thus the identification of risk factors allowing us to diagnose or predict cardiovascular events taking into account gender disparities. In this review, we will examine some of the major challenges in the discovery and validation of cardiovascular biomarkers in a gender perspective. In particular, we will consider classical (hypertension, smoking, diabetes, dyslipidemia, physical inactivity) and novel (inflammation markers, markers of endothelial dysfunction, markers of coronary disease) risk factors reporting gender differences. The aim of this review was to provide an overview on current knowledge on sex‐associated cardiovascular determinants with the aim to improve CVD diagnostic and prognostic clinical courses and to develop new and gender‐biased prevention strategies.     

Hypertensive Disorders of Pregnancy and Risk of Future Cardiovascular Disease in Women

Cardiovascular disease continues to be the leading cause of mortality in women globally. In addition to traditional risk factors, some sex-specific conditions increase the burden of cardiovascular disease in women. With this literature review, we aimed to review evidence on associations between hypertensive disorders of pregnancy and risk of cardiovascular disease in later life. After a database search and application of inclusion and exclusion criteria, 11 studies were included in the review. Our findings suggest that a history of preeclampsia, gestational hypertension, or elevated systolic blood pressure alone during pregnancy is consistently associated with increased risk of developing and dying from myocardial infarction, heart failure, hypertension, and/or stroke in later life. Nurses and other health care providers should be aware of the cardiovascular risk associated with hypertensive disorders of pregnancy and engage women at risk in discussions about health promotion strategies and interventions to address modifiable cardiovascular disease risk factors.     

Advances in understanding gender difference in cardiometabolic disease risk

Gender differences exist in cardiovascular or metabolic disease risk, beyond the protective effect of estrogens, mostly burdening the postmenopausal female. We aimed to review herein sex differences in pro-inflammatory states, the independence of inflammation from insulin resistance, differences in high-density lipoprotein dysfunction, in gene-environment interactions, and in the influence of current and former smoking on cardiometabolic risk. Sex differences in absorption of long-chain fatty acids are highlighted. Differences exist in the first manifestation of cardiovascular disease, men being more likely to develop coronary heart disease as a first event, compared to women who have cerebrovascular disease or heart failure as a first event. Autoimmune activation resulting from pro-inflammatory states, a fundamental mechanism for numerous chronic diseases in people prone to metabolic syndrome, is much more common in women, and these constitute major determinants. Therapeutic approaches to aspects related to sex difference are briefly reviewed.     

Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham study

This report examines prospectively, in the Framingham cohort, the relation of diabetes and impaired glucose tolerance to each of the cardiovascular sequelae, taking into account age, sex, and associated cardiovascular risk factors. The incidence of cardiovascular disease, as well as the levels of cardiovascular risk factors, were found to be higher in diabetic than in nondiabetic men and women. The relative impact of diabetes on coronary heart disease, peripheral vascular disease, or stroke incidence was the same in men and women, but for cardiovascular mortality and cardiac failure the impact is greater for women. Present evidence suggests that alleviation of associated cardiovascular risk factors is the most promising course in reducing cardiovascular sequelae in diabetic patients.     

Computers in medicine. Virtual rehabilitation: dream or reality?

Coronary heart disease is the number one cause of death for men and women in the United States and internationally. Identification of persons at risk for cardiovascular disease and reduction of cardiovascular risk factors are key factors in managing this tremendous societal burden. The internet holds great promise in helping to identify and manage persons at high risk of a cardiac or vascular event. The Internet has the capability to assess risk and provide support for cardiovascular risk reduction for large numbers of persons in a cost effective and time efficient manner. The purpose of this report is to describe important advances in the use of the Internet in identifying persons at risk for a cardiovascular event and in the Internet's ability to provide interventions designed to reduce this risk.     

Sex-specific and hormone-related differences in vascular remodelling in atherosclerosis

Atherosclerosis, a lipid-driven inflammatory disease, is the main underlying cause of cardiovascular diseases (CVDs) both in men and women. Sex-related dimorphisms regarding CVDs and atherosclerosis were observed since more than a decade ago. Inflammatory mediators such as cytokines, but also endothelial dysfunction, vascular smooth muscle cell migration and proliferation lead to vascular remodelling but are differentially affected by sex. Each year a greater number of men die of CVDs compared with women and are also affected by CVDs at an earlier age (40–70 years old) while women develop atherosclerosis-related complications mainly after menopause (60+ years). The exact biological reasons behind this discrepancy are still not well-understood. From the numerous animal studies on atherosclerosis, only a few include both sexes and even less investigate and highlight the sex-specific differences that may arise. Endogenous sex hormones such as testosterone and oestrogen modulate the atherosclerotic plaque composition and the frequency of such plaques. In men, testosterone seems to act like a double-edged sword as its decrease with ageing correlates with an increased risk of atherosclerotic CVDs, while testosterone is also reported to promote inflammatory immune cell recruitment into the atherosclerotic plaque. In premenopausal women, oestrogen exerts anti-atherosclerotic effects, which decline together with its level after menopause resulting in increased CVD risk in ageing women. However, the interplay of sex hormones, sex-specific immune responses and other sex-related factors is still incompletely understood. This review highlights reported sex differences in atherosclerotic vascular remodelling and the role of endogenous sex hormones in this process.     

Is Female Sex a Risk Factor for Red Blood Cell Alloimmunization After Transfusion? A Systematic Review

Large scale red blood cell (RBC) antigen genotyping of donors is currently well developed. There is scarce information, however, to select patients who might benefit from preemptive extended RBC antigen-matched transfusions. Female sex has been proposed as a risk factor for RBC alloimmunization after transfusion. To asses whether females respond differently to RBC alloantigens compared with males, we conducted a literature review on RBC alloimmunization. Clinical studies on RBC alloimmunization incidence were searched for in databases from 1950 through 2011. Studies were included when data were available to calculate the female-to-male risk ratio for alloimmunization. Based on the reported age, adult patients (>18 years) were distinguished from pediatric patients (≤18 years), and articles were analyzed according to disease categories. Thirty articles fulfilled the inclusion criteria. The Mantel-Haenszel risk ratio estimate of combined adult studies showed that women with sickle cell disease had an increased relative risk (27%) on RBC alloantibodies compared with men. Other groups showed equal alloimmunization risk in women and men. Women slightly more often than men possess RBC antibodies. This is likely explained by more exposure to immunizing events through pregnancy and/or transfusions in females with sickle cell disease. The results support the current policy implemented in many countries for Rhesus/Kell matching in patients with a hemoglobinopathy irrespective of sex. Thus, based solely on sex difference, the results do not justify recommending additional matching for women, besides preemptive K and c antigen matching for women during the (pre-) fertile age, as already applied in many European countries for the prevention of fetal morbidity.     

Nonalcoholic fatty liver disease shows significant sex dimorphism

Nonalcoholic fatty liver disease (NAFLD), which has been renamed metabolic dysfunction-associated fatty liver disease, is a growing global medical problem. The incidence of NAFLD and its associated end-stage liver disease is increasing each year, and many research advancements have been achieved to date. This review focuses on the current knowledge of the sex differences in NAFLD and does not elaborate on areas without differences. Studies have revealed significant sex differences in the prevalence, influencing factors, pathophysiology, complications and therapies of NAFLD. Men have a higher incidence than women. Compared with women, men exhibit increased visceral fat deposition, are more susceptible to leptin resistance, lack estrogen receptors, and tend to synthesize fatty acids into fat storage. Male patients will experience more severe hepatic fibrosis and a higher incidence of liver cancer. However, once NAFLD occurs, women show a faster progression of liver fibrosis, higher levels of liver cell damage and inflammation and are less likely to undergo liver transplantation than men. In general, men have more risk factors and more severe pathophysiological reactions than women, whereas the development of NAFLD is faster in women, and the treatments for women are more limited than those for men. Thus, whether sex differences should be considered in the individualized prevention and treatment of NAFLD in the future is worth considering.     

Normotensive women with type 2 diabetes and microalbuminuria are at high risk for macrovascular disease

OBJECTIVE: The excess risk of macrovascular disease and death associated with diabetes seems higher in women than in men. The pathogenesis for this risk difference has not been fully elucidated. We investigated whether female sex was associated with macrovascular disease and death, independently of known risk factors related to type 2 diabetes, nephropathy, or retinopathy in normotensive patients with type 2 diabetes and microalbuminuria. RESEARCH DESIGN AND METHODS: We conducted a prospective, prolonged follow-up study of a subgroup of 67 diabetic patients (46 men and 21 women) without established cardiovascular disease who participated in a larger clinical trial. Data were collected on current and past health, medication use, blood pressure, renal function, and HbA(1c) during the follow-up period of 4.7 +/- 0.8 (means +/- SE) years. The end point was a composite of death, cardiovascular disease, cerebrovascular events, and peripheral artery disease. RESULTS: Of the women, eight (38.1%) met the end point compared with six (13.4%) of the men (P = 0.02 for difference in event-free survival). The hazard ratio of women relative to men was 3.19 (95% CI 1.11-9.21), which further increased after adjusting for age, systolic blood pressure, BMI, smoking, total-to-HDL cholesterol ratio, urinary albumin excretion, and retinopathy. CONCLUSIONS: In our study population of normotensive patients with type 2 diabetes and microalbuminuria, female sex was associated with increased risk of fatal and nonfatal cardiovascular disease, independent of the classical cardiovascular risk factors, the severity of nephropathy or presence of retinopathy, or health care utilization.     

Breast arterial calcifications as a cardiovascular risk marker in women

Cardiovascular disease and breast cancer are the two main causes of mortality in women. Mammography as a screening test for breast cancer is recommended for all women from the age of 40 to 50 years. Mammographically detected breast arterial calcifications are currently considered an incidental finding without clinical importance, since they are not associated with an increased risk of breast cancer. However, recent studies have shown that breast arterial calcifications on mammograms have been associated with cardiovascular risk factors and atherosclerotic cardiovascular disease. These results suggest that breast arterial calcifications, detected during routine mammography, are a noteworthy finding that could be valuable in identifying asymptomatic women at increased cardiovascular risk.     

Gender differences in knowledge, attitudes, and beliefs about heart disease

The purpose of this article is to review the literature on gender differences in knowledge, attitudes, and beliefs about heart disease. Despite the significant problem of cardiac disease among women, surveys of women's knowledge, attitudes, and beliefs about the risks of heart disease have continually identified substantial gaps in women's knowledge. Overall, knowledge of heart disease, identification of risk factors for coronary artery disease, signs and symptoms of acute myocardial infarction (AMI) was poor for both men and women. The perception that women are less knowledgeable than men about heart disease was not consistent in the literature reviewed. In fact, in some studies, women were more knowledgeable than men in the identification of risk factors and less common symptoms of AMI.     

Breast arterial calcifications as a cardiovascular risk marker in women

Cardiovascular disease and breast cancer are the two main causes of mortality in women. Mammography as a screening test for breast cancer is recommended for all women from the age of 40 to 50 years. Mammographically detected breast arterial calcifications are currently considered an incidental finding without clinical importance, since they are not associated with an increased risk of breast cancer. However, recent studies have shown that breast arterial calcifications on mammograms have been associated with cardiovascular risk factors and atherosclerotic cardiovascular disease. These results suggest that breast arterial calcifications, detected during routine mammography, are a noteworthy finding that could be valuable in identifying asymptomatic women at increased cardiovascular risk.     

Effect of Low Birth Weight on Women’s Health

PurposeThe theory of the developmental origins of health and disease hypothesizes that low birth weight (≤5.5 lb) indicative of poor fetal growth is associated with an increased risk of chronic, noncommunicable disease in later life, including hypertension, type 2 diabetes mellitus, and osteoporosis. Whether women are at greater risk than men is not clear. Experimental studies that mimic the cause of slow fetal growth are being used to examine the underlying mechanisms that link a poor fetal environment with later chronic disease and investigate how sex and age affect programmed risk. Thus, the aims of this review are to summarize the current literature related to the effect of low birth weight on women’s health and provide insight into potential mechanisms that program increased risk of chronic disease across the lifespan.MethodsA search of PubMed was performed with the keywords low birth weight, women’s health, female, and sex differences; additional terms included blood pressure, hypertension, renal, cardiovascular, obesity, glucose intolerance, type 2 diabetes, osteoporosis, bone health, reproductive senescence, menopause, and aging.FindingsThe major chronic diseases associated with low birth weight include high blood pressure and cardiovascular disease, impaired glucose homeostasis and type 2 diabetes, impaired bone mass and osteoporosis, and early reproductive aging.ImplicationsLow birth weight increases the risk of chronic disease in men and women. Low birth weight is also associated with increased risk of early menopause. Further studies are needed to fully address the effect of sex and age on the developmental programming of adult health and disease in women across their lifespan.     

Management and prevention of cardiovascular disease in women

Cardiovascular disease, including coronary artery disease, hypertension, and stroke, is the number one killer of men and women in the United States and Canada. In the United States, cardiovascular disease accounts for more deaths in women, compared with men, every year since 1984. Unfortunately, many women are unaware of their risk for developing cardiovascular disease. This article reviews the statistics of this disease, identifies the risk factors, and reviews the evidence-based guidelines for prevention of cardiovascular disease in women.     

Sex differences in the relationship between inflammatory and hemostatic biomarkers and metabolic syndrome: British 1958 Birth Cohort

Summary. Background: Circulating levels of C‐reactive protein (CRP), fibrinogen, fibrin D‐dimer, tissue plasminogen activator antigen (t‐PA) and von Willebrand factor (VWF) are associated with incident coronary heart disease (CHD). However, their associations with metabolic syndrome and its components in large populations of men and women have not been well defined. Objectives: We compare the sex associations of these biomarkers with established CHD risk factors, metabolic syndrome and its components in a large cohort. Patients and Methods: 8302 men and women aged 45 years from the British 1958 birth cohort provided a blood sample. Analyses were restricted to 3457 men and 3464 women with complete data on all risk factors and no history of cardiovascular disease. Multiple regression analyses adjusted for smoking, social class, alcohol consumption and variables related to biomarker measurement error. Results: Adjusted sex differences in levels of all biomarkers (except VWF) varied according to presence/absence of metabolic syndrome, its components and obesity (BMI ≥30 kg m^?2). Associations in women were up to twice as strong for CRP, fibrinogen and t‐PA with markers of obesity (body mass index, waist circumference), blood pressure, blood lipids and metabolic syndrome. D‐dimer showed weaker associations and less heterogeneity by sex. There was no evidence of sex interaction in associations with VWF. Conclusions: Associations between CRP, fibrinogen and t‐PA and metabolic syndrome and its components were stronger in women than in men. Understanding the reasons for these differences across sex will be important in understanding the pathophysiology of cardiovascular and metabolic disease in men and women.     

不同干预方法对重度子痫前期病史妇女心血管疾病危险因素水平的影响

目的探讨不同干预方法对重度子痫前期病史妇女心血管疾病危险因素水平的影响。方法选取2006年11月至2008年11月收治的78例有重度子痫前期病史的妇女作为研究对象,根据对其所采取的干预方法不同,将其分为观察组和对照组各39例。对照组采用常规的肥胖干预方法进行干预,观察组患者采用标准行为疗法（SBT）,比较2组受试者经过3个月干预后的心血管疾病相关危险因素水平的改善情况,评价不同的干预方法对重度子痫前期病史妇女心血管疾病危险因素的干预效果。结果2组患者经干预后,心血管疾病危险因素（收缩压、体质量、腰围、空腹血糖、总胆固醇,高密度脂蛋白）均较干预前有明显改善,但观察组患者改善程度明显优于对照组患者,差异有统计学意义。结论标准行为疗法对于重度子痫前期病史妇女心血管疾病危险因素的干预效果明显优于常规干预方法,值得临床推广应用。