Sex Differences In Cardiovascular Disease Research Articles

Coronary artery disease in post-menopausal women: are there appropriate means of assessment?

The recognition of sex differences in cardiovascular disease, particularly the manifestations of coronary artery disease (CAD) in post-menopausal women, has introduced new challenges in not only understanding disease mechanisms but also identifying appropriate clinical means of assessing the efficacy of management strategies. For example, the majority of treatment algorithms for CAD are derived from the study of males, focus on epicardial stenoses, and inadequately account for the small intramyocardial vessel disease in women. However, newer investigational modalities, including stress perfusion cardiac magnetic resonance imaging and positron emission tomography are providing enhanced diagnostic accuracy and prognostication for women with microvascular disease. Moreover, these investigations may soon be complemented by simpler screening tools such as retinal vasculature imaging, as well as novel biomarkers (e.g. heat shock protein 27). Hence, it is vital that robust, sex-specific cardiovascular imaging modalities and biomarkers continue to be developed and are incorporated into practice guidelines that are used to manage women with CAD, as well as gauge the efficacy of any new treatment modalities. This review provides an overview of some of the sex differences in CAD and highlights emerging advances in the investigation of CAD in post-menopausal women.

Sex Hormones and Change in N-Terminal Pro-B-Type Natriuretic Peptide Levels: The Multi-Ethnic Study of Atherosclerosis.

Sex hormones may influence sex differences in cardiovascular disease (CVD). N-terminal pro-B-type natriuretic peptide (NT-proBNP), a predictor of CVD, is higher in women than men, which may relate to sex hormones. To evaluate whether total testosterone (T), bioavailable T, free T, estradiol, dehydroepiandrosterone (DHEA), and SHBG are associated with NT-proBNP. Cohort study. Cross-sectional sample included 2371 postmenopausal women and 2688 men free of CVD, of which 2041 women and 2348 men were included longitudinally. NT-proBNP at baseline (2000 to 2002) and one or more repeat NT-proBNPs (through 2012). Analyses adjusted for CVD risk factors. Women had higher NT-proBNP than men (median 79.9 vs 38.5 pg/mL). Cross-sectionally, higher bioavailable T, free T, DHEA, and lower SHBG levels were independently associated with lower NT-proBNP among both women and men (all P < 0.05). Higher total T in women and estradiol in men were also associated with lower NT-proBNP (both P < 0.05). Longitudinally, in women, higher total T, bioavailable T, free T, DHEA, and lower estradiol and SHBG were associated with greater 10-year increase in NT-proBNP (all P < 0.05). In men, higher free T and estradiol were associated with greater NT-proBNP increase (both P < 0.05). A more androgenic sex hormone pattern was inversely associated with NT-proBNP cross-sectionally and may contribute to sex differences in NT-proBNP. Longitudinally, a more androgenic sex hormone pattern was associated with greater increase in NT-proBNP in women, which may reflect a mechanism for CVD risk after menopause.

Sex-related differences in characteristics, management and in-hospital outcome in sub-saharan patients with acute coronary syndrome

Background: Coronary heart disease remains the leading cause of morbidity and mortality in both men and women worldwide. Cardiovascular disease (CVD) is on the rise in sub-saharan countries that are currently undergoing rapid urbanization, industrialization, and lifestyle changes. Recently, knowledge regarding sex differences in CVD has evolved. Although, data on the incidence of acute coronary syndrome (ACS) in sub-saharan are not rare, few focused closely on sex differences. The purpose of this study was to examine sex-related differences in characteristics, management and inhospital outcome in sub-saharan with acute coronary syndrome. Methods: This was a retrospective study conducted at the cardiology department of Principal Hospital of Dakar over a period of 60 months (January 1st 2010 to December 31st 2014), in Dakar, Senegal. Two hundred and seven medical records of patients admitted for ACS based on anginal pain at rest, suggestive electrocardiographic changes and elevated troponin I levels, were included. We studied data on age, risk factors, symptoms, the time delay before admission, the management given, the vital parameters as as well as evolution during hospitalization. Medical records were then stratified into two categories (males and females) to study diferences. The studied parameters were entered into an electronic questionnaire using Epi Info version 3.3.5 of the World Health Organization. Results: Hospital prevalence of ACS was 6.09% with a sex ration M/F of 1.62(159/98). there was an overall rates increase of admissions for ACS in both men and women . The mean age of patients was 67.5 ± 10.1 years with a range of 44 and 93 years. Females were older than males ( p=0.08) with a greatest incidence of ACS in those aged 60 to 69 years. Women had a higher prevalence of risks, such as diabetes, hypertension, dyslipidemia, and obesity than men. In addition, there are sex differences in an order of importance related to risk factors for ACS. Hypertension, diabetes, and obesity are the most important risk factors in women, whereas current smoking, hypertension and diabetes are the important risk factors in men. Chest pain was present in 249 patients (97%). Typical anginal pain was more common in men than women (76.1% vs 52.1%), this difference was statistically significant (p=0.000). The average time delay before medical care was given was 29.09 ± 8.5 hours. This time delay was higher in women than men ( 53.9 ± 18 hours vs 26.4 ± 12.3 hours; p= 0.005) Mean troponin I level found was 1.9 ± 2.8 ng/ml, Creatine phosphokinase and Creatine phosphokinase-MB measured 824 ± 909.7 UI/l and 141.3 ± 245.9 UI/l respectively. Troponin I level was higher in men than women. Mean total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol and, triglyceride were 2.06 ± 0.25 g/l, 0.90 ± 0.2g/l, 0.90 ± 0.20 g/l, and 1.44 ± 0.20 g/l respectively. LDL cholesterol was higher in women than in men. Electrocardiogram revealed an ACS with persistent ST-elevation in 143 patients (90 males vs 53 females) and non ST-elevation ACS in 114 patients (69 males vs 45 females). Concerning treatment, thrombolysis using streptokinase was performed in 33 patients, accounting for 12.8% of patients with ST-elevation. Thrombolysis was performed in 10.2% of females compared to 14.5% of males (p=0.32). Six deaths (6.1%) were recorded in women and 10 (6.3% ) in men. Complications was dominated by pulmonary oedema. Conclusion: Our study confirms that acute coronary syndrome is not a “man’s only” disease in sub-sahara. Although in our study there was no difference in mortality, atypical presentation and low elevations in biomarker were responsible of long time delay before medical care in women.

Biological Sex Modulates the Adrenal and Blood Pressure Responses to Angiotensin II.

The relationship between biological sex and aldosterone on blood pressure (BP) is unclear. We hypothesized that sex would modify the interaction between aldosterone and vascular responses to salt intake and angiotensin II (AngII). To test this hypothesis, in 1592 subjects from the well-controlled Hypertensive Pathotype cohort, we compared responses of women and men to chronic (BP and aldosterone levels in response to dietary salt) and acute (BP, renal plasma flow, and aldosterone responses to AngII infusion) manipulations. Women had a 30% higher salt sensitivity of BP than men (P<0.0005) regardless of age or hypertension status, a greater BP response to AngII, and a 15% greater aldosterone response to AngII on both restricted and liberal salt diets (P<0.005). Furthermore, there was an interaction (P=0.003) between sex and aldosterone on BP response to AngII. Women also had a greater (P<0.01) increment in renal plasma flow in response to AngII than men. To assess potential mechanisms for this sex effect, we compared aldosterone responses to AngII or potassium from rat zona glomerulosa cells and observed greater aldosterone production in female than male zona glomerulosa cells basally and in response to both agonists (P<0.0001). In a rodent model of aldosterone-mediated cardiovascular disease induced by increased AngII and low NO, circulating aldosterone levels (P<0.01), myocardial damage (P<0.001), and proteinuria (P<0.05) were greater in female than male rats despite having similar BP responses. Thus, increased aldosterone production likely contributes to sex differences in cardiovascular disease, suggesting that women may be more responsive to mineralocorticoid receptor blockade than men.

Sex-Specific Physiology and Cardiovascular Disease.

Sex differences in cardiovascular diseases can be classified as those which are specific to one sex and those that differ in incidence, prevalence, etiology, symptomatology, response to treatment, morbidity, and mortality in one sex compared to the other. All sex differences in cardiovascular conditions have their basis in the combined expression of genetic and hormonal differences between women and men. This chapter addresses how understanding basic mechanisms of hormone responses, imaging diagnostics, and integration of genomics and proteomics has advanced diagnosis and improved outcomes for cardiovascular conditions, apart from those related to pregnancy that are more prevalent in women. These conditions include obstructive coronary artery disease, coronarymicrovasculardysfunction, spontaneous coronary artery dissection, diseases of the cardiac muscle including heart failure and takotsubo cardiomyopathy, and conditions related to neurovascular dysregulation including hot flashes and night sweats associated with menopause and effects of exogenous hormones on vascular function. Improvement in technologies allowing for noninvasive assessment of neuronally mediated vascular reactivity will further improve our understanding of the basic etiology of the neurovascular disorders. Consideration of sex, hormonal status, and pregnancy history in diagnosis and treatment protocols will improve prevention and outcomes of cardiovascular disease in women as they age.

Utility of Imaging in Risk Stratification of Chest Pain in Women.

Recent decades have seen a growing recognition that the understanding of sex differences in cardiovascular disease (CVD) is vital to optimal diagnosis and management, particularly of women (Mosca et al. Circulation 124:2145-54, 2011). There is simultaneously an increasing appreciation of the multifactorial nature of ischemic heart disease (IHD) in many patients, in whom disease may extend beyond the epicardial coronaries. While obstructive coronary artery disease (CAD) remains underdiagnosed in women and still represents a major burden of disease, women also present with nonobstructive CAD more commonly than men (Patel et al. N Engl J Med 362:886-95, 2010). Indeed, microvascular dysfunction, coronary artery vasospasm, and coronary dissections contribute to a larger proportion of IHD in women than men (Bairey Merz et al. J Am Coll Cardiol 47:S21-9, 2006). Here, we review the symptom presentation of women with IHD and the noninvasive modalities used to risk stratify women with suspected IHD.

Sex differences in cardiovascular disease - Impact on care and outcomes.

Sex differences in cardiovascular disease - Impact on care and outcomes.

Sex Hormones and Sex Chromosomes Cause Sex Differences in the Development of Cardiovascular Diseases.

This review summarizes recent evidence concerning hormonal and sex chromosome effects in obesity, atherosclerosis, aneurysms, ischemia/reperfusion injury, and hypertension. Cardiovascular diseases occur and progress differently in the 2 sexes, because biological factors differing between the sexes have sex-specific protective and harmful effects. By comparing the 2 sexes directly, and breaking down sex into its component parts, one can discover sex-biasing protective mechanisms that might be targeted in the clinic. Gonadal hormones, especially estrogens and androgens, have long been found to account for some sex differences in cardiovascular diseases, and molecular mechanisms mediating these effects have recently been elucidated. More recently, the inherent sexual inequalities in effects of sex chromosome genes have also been implicated as contributors in animal models of cardiovascular diseases, especially a deleterious effect of the second X chromosome found in females but not in males. Hormonal and sex chromosome mechanisms interact in the sex-specific control of certain diseases, sometimes by opposing the action of the other.

Mechanistic Pathways of Sex Differences in Cardiovascular Disease.

Major differences between men and women exist in epidemiology, manifestation, pathophysiology, treatment, and outcome of cardiovascular diseases (CVD), such as coronary artery disease, pressure overload, hypertension, cardiomyopathy, and heart failure. Corresponding sex differences have been studied in a number of animal models, and mechanistic investigations have been undertaken to analyze the observed sex differences. We summarize the biological mechanisms of sex differences in CVD focusing on three main areas, i.e., genetic mechanisms, epigenetic mechanisms, as well as sex hormones and their receptors. We discuss relevant subtypes of sex hormone receptors, as well as genomic and nongenomic, activational and organizational effects of sex hormones. We describe the interaction of sex hormones with intracellular signaling relevant for cardiovascular cells and the cardiovascular system. Sex, sex hormones, and their receptors may affect a number of cellular processes by their synergistic action on multiple targets. We discuss in detail sex differences in organelle function and in biological processes. We conclude that there is a need for a more detailed understanding of sex differences and their underlying mechanisms, which holds the potential to design new drugs that target sex-specific cardiovascular mechanisms and affect phenotypes. The comparison of both sexes may lead to the identification of protective or maladaptive mechanisms in one sex that could serve as a novel therapeutic target in one sex or in both.

The VCD Mouse Model of Menopause and Perimenopause for the Study of Sex Differences in Cardiovascular Disease and the Metabolic Syndrome.

In females, menopause, the cessation of menstrual cycling, is associated with an increase in risk for several diseases such as cardiovascular disease, osteoporosis, diabetes, the metabolic syndrome, and ovarian cancer. The majority of women enter menopause via a gradual reduction of ovarian function over several years (perimenopause) and retain residual ovarian tissue. The VCD mouse model of menopause (ovarian failure in rodents) is a follicle-deplete, ovary-intact animal that more closely approximates the natural human progression through perimenopause and into the postmenopausal stage of life. In this review, we present the physiological parameters of how to use the VCD model and explore the VCD model and its application into the study of postmenopausal disease mechanisms, focusing on recent murine studies of diabetic kidney disease, the metabolic syndrome, and hypertension.

Heart Disease in WomenNandaNavin C., KeserNurgul, 513 pages. New Delhi, India: Jaypee Brothers Medical Publishing Ltd. 2015. $184.00, ISBN-13: 978-9351522942

Navin C. Nanda, Nurgul Keser, 513 pages. New Delhi, India: Jaypee Brothers Medical Publishing Ltd. 2015. $184.00, ISBN-13: 978-9351522942 Heart disease is the leading cause of death among women. In comparison with men, women have greater cardiovascular mortality, report more morbidity, and have greater reductions in quality of life. Furthermore, sex disparities in cardiovascular health exist among women of all ages, socioeconomic backgrounds, and racial subgroups, which likely reflect both lingering diagnostic and treatment disparities, and underlying biological sex differences, as well. For example, there is a largely female predominance of stress-induced (Takotsubo) cardiomyopathy after menopause, a greater occurrence of heart failure with preserved ejection fraction, particularly in elderly women, and a higher incidence of rheumatic mitral stenosis among women in developing countries. In addition, after 55 years of age, hypertension is more prevalent in women than in men, particularly in black women. Clinical outcomes also differ by sex. Women with atrial fibrillation have a higher risk of thromboembolic events in comparison with men, and, among individuals younger than 55 years of age, the rate of acute myocardial infarction in the past decade has declined in men, but not in women. As the importance and impact of cardiovascular disease in women is increasingly recognized, we are learning how heart disease is distinct between the sexes, both in its pathophysiology and in our ability to diagnose and treat women. To better understand and appreciate sex differences in cardiovascular disease, there needs to be a compilation of current knowledge and an accessible tool that …

Sex Differences in Correlates of Intermediate Phenotypes and Prevalent Cardiovascular Disease in the General Population.

There are marked sex differences in cardiovascular disease (CVD) manifestation. It is largely unknown how the distribution of CVD risk factors or intermediate phenotypes explain sex-specific differences. In 5000 individuals of the population-based Gutenberg Health Study, mean age 55 ± 11 years, 51% males, we examined sex-specific associations of classical CVD risk factors with intima-media thickness, ankle-brachial index, flow-mediated dilation, peripheral arterial tonometry, echocardiographic, and electrocardiographic variables. Intermediate cardiovascular phenotypes were related to prevalent CVD [coronary artery disease, heart failure, stroke, myocardial infarction, lower extremity artery disease (LEAD) N = 561]. We observed differential distributions of CVD risk factors with a higher risk factor burden in men. Manifest coronary artery disease, stroke, myocardial infarction, and LEAD were more frequent in men; the proportion of heart failure was higher in women. Intermediate phenotypes showed clear sex differences with more beneficial values in women. Fairly linear changes toward less beneficial values with age were observed in both sexes. In multivariable-adjusted regression analyses, age, systolic blood pressure, and body mass index were consistently associated with intermediate phenotypes in both sexes with different ranking according to random forests, maximum model R(2) 0.43. Risk factor-adjusted associations with prevalent CVD showed some differences by sex. No interactions by menopausal status were observed. In a population-based cohort, we observed sex differences in risk factors and a broad range of intermediate phenotypes of non-invasive cardiovascular structure and function. Their relation to prevalent CVD differed markedly. Our results indicate the need of future investigations to understand sex differences in CVD manifestation.

Sex-associated differences in the modulation of vascular risk in patients with asymptomatic carotid stenosis.

In this study, we aimed to identify determinants of the different sex-related stroke risk in subjects with asymptomatic internal carotid artery (ICA) stenosis. In all, 492 women (44.4%) and 617 men (55.6%), with unilateral ⩾ 60% asymptomatic ICA stenosis, were prospectively evaluated with a median follow-up of 37 months (interquartile range, 26 to 43). Vascular risk profile, plaque characteristics, stenosis progression, and common carotid artery intima-media thickness were investigated. Outcome measure was the occurrence of ischemic stroke ipsilateral to ICA stenosis. Myocardial infarction, contralateral stroke and transient ischemic attack were considered as competing events. The incidence rate of ipsilateral stroke over the entire follow-up period was 0.16%: 0.09% (95% confidence interval (CI) 0.05 to 0.15) in women and 0.22% (95% CI 0.17 to 0.29) in men (log-rank test, P<0.001). Stenosis progression significantly influenced the risk of ipsilateral stroke in both men (subhazard ratio, SHR, 8.99) and women (SHR 4.89). Stenosis degree (71% to 90%, SHR 2.35; 91% to 99%, SHR 3.38) and irregular plaque surface (SHR 2.32) were relevant risk factors for ipsilateral stroke only in men. Our findings suggest that characteristics of the stenosis and plaque exert a different effect in modulating vascular risk in the two sexes. Understanding sex differences in cardiovascular disease could help to target sex-specific future therapies.

ACUTE CORONARY SYNDROME PATIENTS ADMITTED TO CARDIOLOGY VERSUS NON-CARDIOLOGY WARDS: VARIATIONS IN TREATMENT AND OUTCOME

with more feminine gender scores (tertile 3) were more likely to be women, be unmarried, report high anxiety and depression, low stress management abilities, as well as more diabetes, hypertension, family history of CAD and prior CVD events before the index ACS than patients with more androgynous (tertile 2) and masculine (tertile 1) gender scores. Of the 35 (3%) patients with recurrent ACS at one year, the proportion was higher in tertile 3 (5%) than in the less feminine tertiles of the gender score: tertiles 2 (2%) and 1 (2%). This difference persisted after multivariable adjustment; patients in tertile 3 remained at greater risk of recurrent ACS than patients in tertiles 2 and 1 (HR1⁄44.50, 95% CI: 1.05-19.27, p1⁄40.04). Factors that moderated the association between feminine gender and recurrent ACS included anxiety,marital status and access to ACS care at baseline.Of note, recurrent ACS did not vary by sex: 3% in bothmales and females. CONCLUSION: In younger patients with ACS, feminine gender, but not female sex, is associated with recurrent ACS. Increased anxiety and poorer access to care in men and women with strong feminine gender characteristics may help explain this association. Studies of sex differences in cardiovascular disease should consider gender-based conceptual frameworks.

Estrogen regulation of protein expression and signaling pathways in the heart.

Sex differences in cardiovascular disease and cardiac physiology have been reported in humans as well as in animal models. Premenopausal women have reduced cardiovascular disease compared to men, but the incidence of cardiovascular disease in women increases following menopause. Sex differences in cardiomyocytes likely contribute to the differences in male–female physiology and response to disease. Sex differences in the heart have been noted in electrophysiology, contractility, signaling, metabolism, and cardioprotection. These differences appear to be due, at least in part, to differences in gene and protein expression as well as in posttranslational protein modifications. This review will focus primarily on estrogen-mediated male–female differences in protein expression and signaling pathways in the heart and cardiac cells. It should be emphasized that these basic differences are not intrinsically beneficial or detrimental per se; the difference can be good or bad depending on the context and circumstances.

“Sex‐specific microRNA networks in cardiac hypertrophy”

Sex differences in cardiovascular disease, susceptibly and progressively, including left ventricular hypertrophy (LVH) and subsequent heart failure, have been well documented. MicroRNAs (miRNAs), which have been shown to be regulated during LVH, might provide insight into these sex differences. To establish sex‐specific miRNA profiles in LVH, male and female C57BL6 mice were subjected to transaortic constriction (TAC). Two‐weeks postsurgery, mice were euthanized and heart weights were determined. Male mice had significantly greater levels of cardiac hypertrophy as compared to female mice. Total RNA was isolated from left ventricular tissue samples, and next generation sequencing was performed on small RNAs. Comparing miRNA expression data from TAC, sham surgical, and non‐surgical animals, we have established unique sex‐specific miRNA expression profiles in left ventricular hypertrophy and in a non‐surgical state. We have used these profiles to establish potential signaling networks responsible for sex‐differences. Functional significance of networks known to influence cardiac hypertrophy, including TGFβ and MCIP1, are currently being investigated. It is anticipated that establishment of sex‐specific miRNA networks will aid in the use of miRNAs as diagnostic and therapeutic targets for LVH.NIH 5P20RR016481–12, 8P20GM103436–12, R15HL108192–02

Women and Heart Failure: An Emerging Venus-Mars Concept

Some of the most profound sex differences in cardiovascular disease are evident in the syndrome of heart failure. Certain heart failure conditions have a unique predilection for women, such as heart failure with preserved ejection fraction and apical ballooning syndrome; or are exclusive to women, such as peripartum cardiomyopathy. Overall, there are notable differences between women and men in terms heart failure disease burden, risk factors, clinical presentation and prognosis. Yet, women remain under-represented in heart failure clinical trials. Important knowledge gaps exist in our understanding of the pathophysiologic basis for these sex differences and potential for effective sex-specific management strategies.

Aromatase Gene Polymorphisms Are Associated with Survival among Patients with Cardiovascular Disease in a Sex-Specific Manner

Introduction CYP19A1 encodes aromatase, the enzyme responsible for the conversion of androgens to estrogens, and may play a role in variation in outcomes among men and women with cardiovascular disease. We sought to examine genetic variation in CYP19A1 for its potential role in sex differences in cardiovascular disease outcomes.MethodsCaucasian individuals from two independent populations were assessed: 1) a prospective cohort of patients with acute coronary syndromes with 3-year mortality follow-up (n = 568) and 2) a nested case-control study from a randomized, controlled trial of hypertension patients with stable coronary disease in which the primary outcome was death, nonfatal myocardial infarction (MI) or nonfatal stroke (n = 619). Six CYP19A1 SNPs were genotyped (-81371 C>T, -45965 G>C, M201T, R264C, 80 A>G, and +32226 G>A). The sex*genotype interaction term was assessed for the primary outcome and compared by genotype in men and women when a significant interaction term was identified.ResultsWe identified a significant interaction between -81371 C>T and sex (p = 0.025) in the ACS population. The variant allele was associated with a 78% increase in mortality in men (HR 1.78, 95% confidence interval [CI] 1.08-2.94) and a nonsignificant 42% decrease in mortality among women (HR 0.58, 95% CI 0.22-1.54). We identified a similar association in the hypertensive CAD group, the -81371 C>T*sex interaction term was p<0.0001, with an associated 65% increase in death, MI, or stroke (HR 1.65, 95% CI 1.00-2.73) in men and a 69% decrease (HR 0.31, 95% CI 0.16-0.6) in women.ConclusionsUsing two independent populations, this study is the first to document a significant interaction between CYP19A1 genotype and sex on cardiovascular outcomes. These findings could illuminate potential mechanisms of sex differences in cardiovascular disease outcomes.

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.

Sex differences in the impact of diabetes on mortality in chronic dialysis patients

Although females have a survival advantage in the general population, women undergoing dialysis have similar mortality to men. Because the reasons for this difference are unknown, we hypothesized that sex differences in cardiovascular disease (CVD) risk profile exist at dialysis initiation and that the association of such risk factors with mortality differs between sexes. This study was a prospective observational cohort study (NECOSAD) of incident dialysis patients with 5 years of follow-up where we calculated male:female odds ratios (OR) and relative risks of mortality (hazard ratio, HR) for the presence of CVD risk factors at the start of dialysis. We also examined the presence of interaction between sex and CVD risk factors in their association with mortality. In 1577 patients (61% men, 60 ± 15 years), men presented more CVD co-morbidity [OR: 1.88 (95% CI: 1.51, 2.35)] but less diabetes mellitus (OR: 0.70 [0.55, 0.89]) than women. Both sexes presented equal survival [HR 0.98 (0.83, 1.16)]. Women with diabetes had a higher mortality risk [HR 2.93 (2.27, 3.79)] than their male counterparts [HR 1.99 (1.52, 2.59)], showing an interaction effect between sex and diabetes [relative excess risk due to interaction 1.18 (0.37, 2.00)]. Despite a lower prevalence of CVD, women starting dialysis had the same mortality risk as men. The mortality risk was strikingly higher in diabetic women than diabetic men. This excess mortality may help explain why dialysis cancels out the female survival advantage. Our study identifies a high-risk group of patients that may warrant further investigation and intensified therapeutic care.