State of the Science in Women's Cardiovascular Disease: A Canadian Perspective on the Influence of Sex and Gender
2020; Wiley; Volume: 9; Issue: 4 Linguagem: Inglês
10.1161/jaha.119.015634
ISSN2047-9980
AutoresColleen M. Norris, Cindy Ying Yin Yip, Kara Nerenberg, Marie‐Annick Clavel, Christine Pacheco, Heather J.A. Foulds, Marsha Hardy, Christine A. Gonsalves, Shahin Jaffer, Monica Parry, Tracey J. F. Colella, Abida Dhukai, Jasmine Grewal, Jennifer Price, Anna Levinsson, Donna Hart, Paula Harvey, Harriette G.C. Van Spall, Hope Sarfi, Tara Sedlak, Sofia B. Ahmed, Carolyn Baer, Thais Coutinho, Jodi D. Edwards, Courtney R. Green, Amy A. Kirkham, Kajenny Srivaratharajah, Sandra M. Dumanski, Lisa Keeping‐Burke, Nadia Lappa, Robert D. Reid, Helen Mary Robert, Graeme N. Smith, Michelle Martin‐Rhee, Sharon L. Mulvagh,
Tópico(s)Sex and Gender in Healthcare
ResumoHomeJournal of the American Heart AssociationVol. 9, No. 4State of the Science in Women's Cardiovascular Disease: A Canadian Perspective on the Influence of Sex and Gender Open AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialOpen AccessReview ArticlePDF/EPUBState of the Science in Women's Cardiovascular Disease: A Canadian Perspective on the Influence of Sex and Gender Colleen M. Norris, PhD, MSc, BScN, RN, Cindy Y. Y. Yip, PhD, MASc, PMP, Kara A. Nerenberg, MD, MSc, Marie‐Annick Clavel, DVM, PhD, Christine Pacheco, MD, MSc, Heather J. A. Foulds, PhD, MSc, CEP, Marsha Hardy, MSW, RSW, Christine A. Gonsalves, PhD, Shahin Jaffer, MD, MHSc, Monica Parry, MEd, MSc, PhD, NP‐Adult, CCN(C), Tracey J. F. Colella, RN, PhD, Abida Dhukai, NP, PhD Candidate, Jasmine Grewal, MD, Jennifer A. D. Price, PhD, RN, CCN(C), Anna L. E. Levinsson, PhD, Donna Hart, BA, RSW, Paula J. Harvey, BMBS, PhD, Harriette G. C. Van Spall, MD, MPH, Hope Sarfi, Tara L. Sedlak, MD, Sofia B. Ahmed, MD, MMSc, Carolyn Baer, MD, Thais Coutinho, MD, Jodi D. Edwards, PhD, Courtney R. Green, PhD, MSc, Amy A. Kirkham, PhD, Kajenny Srivaratharajah, MD, MSc, Sandra Dumanski, MD, Lisa Keeping‐Burke, RN, PhD, Nadia Lappa, BEng, Robert D. Reid, PhD, MBA, Helen Robert, BComm, Graeme Smith, MD, PhD, Michelle Martin‐Rhee, PhD and Sharon L. Mulvagh, MD, FRCPC, FACC, FASE, FAHA Colleen M. NorrisColleen M. Norris Faculty of Nursing, , University of Alberta, , Edmonton, , Alberta, , Canada , Cindy Y. Y. YipCindy Y. Y. Yip Heart and Stroke Foundation of Canada, , Toronto, , Ontario, , Canada , Kara A. NerenbergKara A. Nerenberg Department of Medicine/Division of General Internal Medicine, , University of Calgary, , Alberta, , Canada , Marie‐Annick ClavelMarie‐Annick Clavel Institut Universitaire de Cardiologie et Pneumologie de Québec, , Quebec, , Canada , Christine PachecoChristine Pacheco Hôpital Pierre‐Boucher, , University of Montréeal, , Montreal, , Quebec, , Canada , Heather J. A. FouldsHeather J. A. Foulds College of Kinesiology, , University of Saskatchewan, , Saskatoon, , Saskatchewan, , Canada , Marsha HardyMarsha Hardy Canadian Women's Heart Health Alliance, , Ottawa, , Ontario, , Canada , Christine A. GonsalvesChristine A. Gonsalves Interdisciplinary Human Studies, , Laurentian University, , Sudbury, , Ontario, , Canada , Shahin JafferShahin Jaffer Department of Medicine/Community Internal Medicine, , University of British Columbia, , Vancouver, , British Columbia, , Canada , Monica ParryMonica Parry Lawrence S. Bloomberg Faculty of Nursing, , University of Toronto, , Ontario, , Canada , Tracey J. F. ColellaTracey J. F. Colella University Health Network/Toronto Rehab Cardiovascular Prevention and Rehabilitation Program, , Toronto, , Ontario, , Canada , Abida DhukaiAbida Dhukai Lawrence S. Bloomberg Faculty of Nursing, , University of Toronto, , Ontario, , Canada , Jasmine GrewalJasmine Grewal Division of Cardiology, , University of British Columbia, , Vancouver, , British Columbia, , Canada , Jennifer A. D. PriceJennifer A. D. Price Lawrence S. Bloomberg Faculty of Nursing, , University of Toronto, , Ontario, , Canada Women's College Research Institute, , Women's College Hospital, , Toronto, , Ontario, , Canada , Anna L. E. LevinssonAnna L. E. Levinsson Montreal Heart Institute, , Montreal, , Quebec, , Canada Beaulieu‐Saucier Université de Montréal Pharmacogenomics Centre, , Montreal, , Quebec, , Canada Faculty of Medicine, , Université de Montréal, , Montreal, , Quebec, , Canada , Donna HartDonna Hart Canadian Women's Heart Health Alliance, , Ottawa, , Ontario, , Canada , Paula J. HarveyPaula J. Harvey Canadian Women's Heart Health Alliance, , Ottawa, , Ontario, , Canada Women's College Research Institute and Division of Cardiology, , Department of Medicine Women's College Hospital, , University of Toronto, , Ontario, , Canada , Harriette G. C. Van SpallHarriette G. C. Van Spall Division of Cardiology, , Department of Medicine, , McMaster University, , Hamilton, , Ontario, , Canada , Hope SarfiHope Sarfi Canadian Women's Heart Health Alliance, , Ottawa, , Ontario, , Canada , Tara L. SedlakTara L. Sedlak Leslie Diamond Women's Heart Centre, , Vancouver General Hospital, , University of British Columbia, , Vancouver, , British Columbia, , Canada , Sofia B. AhmedSofia B. Ahmed Department of Medicine and Libin Cardiovascular Institute, , University of Calgary, , Alberta, , Canada , Carolyn BaerCarolyn Baer Division of General Internal Medicine, , Department of Medicine, , Moncton Hospital, , Dalhousie University, , Halifax, , Nova Scotia, , Canada , Thais CoutinhoThais Coutinho Division of Cardiac Prevention and Rehabilitation, , Division of Cardiology and Canadian Women's Heart Health Centre, , University of Ottawa Heart Institute, , Ottawa, , Ontario, , Canada , Jodi D. EdwardsJodi D. Edwards School of Epidemiology and Public Health, , University of Ottawa and University of Ottawa Heart Institute, , Ottawa, , Ontario, , Canada , Courtney R. GreenCourtney R. Green Society of Obstetricians and Gynaecologists of Canada, , Ottawa, , Ontario, , Canada , Amy A. KirkhamAmy A. Kirkham Department of Biomedical Engineering, , University of Alberta, , Edmonton, , Alberta, , Canada , Kajenny SrivaratharajahKajenny Srivaratharajah Division of General Internal Medicine, , Department of Medicine, , McMaster University, , Hamilton, , Ontario, , Canada , Sandra DumanskiSandra Dumanski Department of Medicine, , University of Calgary, , Alberta, , Canada , Lisa Keeping‐BurkeLisa Keeping‐Burke University of New Brunswick, , Saint John, , New Brunswick, , Canada , Nadia LappaNadia Lappa Canadian Women's Heart Health Alliance, , Ottawa, , Ontario, , Canada , Robert D. ReidRobert D. Reid Division of Cardiac Prevention and Rehabilitation, , Division of Cardiology and Canadian Women's Heart Health Centre, , University of Ottawa Heart Institute, , Ottawa, , Ontario, , Canada , Helen RobertHelen Robert Canadian Women's Heart Health Alliance, , Ottawa, , Ontario, , Canada , Graeme SmithGraeme Smith Department of Obstetrics and Gynecology, , Kingston Health Sciences Centre, , Queen's University, , Kingston, , Ontario, , Canada , Michelle Martin‐RheeMichelle Martin‐Rhee Heart and Stroke Foundation of Canada, , Toronto, , Ontario, , Canada and Sharon L. MulvaghSharon L. Mulvagh *Correspondence to: Sharon L. Mulvagh, MD, Division of Cardiology, Department of Medicine, Dalhousie University, Queen Elizabeth II Health Sciences Centre, Halifax Infirmary Site, 1796 Summer St, Room 2148.5, Halifax, NS, Canada B3H 3A7. E‐mail: E-mail Address: sha[email protected] Division of Cardiology, , Dalhousie University, , Halifax, , Nova Scotia, , Canada Department of Cardiovascular Medicine, , Mayo Clinic, , Rochester, , MN Originally published17 Feb 2020https://doi.org/10.1161/JAHA.119.015634Journal of the American Heart Association. 2020;9:e015634Cardiovascular disease (CVD) is the leading cause of premature death for women in Canada.1 Although it has long been recognized that estrogen impacts vascular responses in women, there is emerging evidence that physiologic and pathophysiologic cardiovascular responses are uniquely affected across the spectrum of a woman's life. Despite a global understanding that manifestations and outcomes of CVD are known to differ between men and women, uptake of the recognition of sex and gender influences on the clinical care of women has been slow or absent.2To highlight the need for better research, diagnosis, treatment, awareness, and support of women with CVD in Canada, the Canadian Women's Heart Health Alliance (CWHHA), supported by the University of Ottawa Heart Institute, and in collaboration with the Heart and Stroke Foundation of Canada (HSFC), undertook a comprehensive review of the evidence on sex‐ and gender‐specific differences in comorbidities, risk factors, disease awareness, presentation, diagnosis, and treatment across the entire spectrum of CVD. The intent of this review was not to directly compare women and men on epidemiological and outcome measures of CVD, but to synthesize the state of the evidence for CVD in women and identify significant knowledge gaps that hinder the transformation to clinical practice and care that is truly tailored for women, a significant health challenge that has only been recognized in Canada relatively recently. This review highlights the scarcity of Canadian data on CVD in women as part of the ongoing struggle to increase awareness of and improve outcomes for women with CVD. Because of a paucity of published Canada‐specific evidence, the purpose of this review is to provide an infrastructure to summarize world‐wide published evidence, including knowledge gaps that must be understood to then make effective recommendations to alleviate the glaring "unders" of CVD for women in Canada: under‐aware, under‐diagnosed and under‐treated, under‐researched, and under‐support.3The Writing GroupThe writing group comprised members of the Knowledge Translation and Mobilization and Health Systems and Policy Working Groups of the CWHHA, a volunteer professional organization whose vision and mission is to improve women's cardiovascular health across their lifespan by supporting clinicians, scientists, patients, and decision makers to work collaboratively to implement evidence and transform clinical practice and public policy related to women's cardiovascular health in Canada. The CWHHA membership identified as a high priority the need for an environmental scan of CVD in women in Canada from which a scientific statement could be developed to summarize critical sex‐ and gender‐specific issues in CVD diagnosis, treatment, and outcomes.As a key collaborator with CWHHA, HSFC staff complemented the writing group. HSFC is the Canadian counterpart to the American Heart Association (AHA) and is dedicated to policy and advocacy, system change, knowledge translation, public awareness and education, and CVD research. In recent years, HSFC identified women's heart and brain health as a priority, forming a Women's Research Network consisting of cardiovascular experts from across Canada and launching a women's cardiovascular awareness campaign in 2018.All writing group members have in‐depth expertise on CVD among women. After 2 national planning teleconferences of the 2 CWHHA working groups, a topic outline based on the scope of the problem was developed. Writers were selected on the basis of experience and expertise to complete evidence‐based summaries of their assigned topic areas. The writing group members had opportunities to comment on and approve the report, which also underwent extensive peer review by members of Canadian Women's Heart and Brain Health Research Steering Committee and HSFC.Administrative data were obtained from the Canadian Institute for Health Information (CIHI) and analyzed by HSFC authors. Components of the demographic material were based on comparative data and information obtained from CIHI for the most recently available years, 2016 to 2017.In this comprehensive review, CVD refers to diseases, disorders, syndromes, and conditions that affect the heart and blood vessels. Canadian vital statistics and hospitalization administrative data were extracted using International Classification of Diseases, Tenth Revision (ICD‐10), codes (Data S1; Tables S1 and S2). When available, studies with Canadian data were prioritized for inclusion in this review to provide a Canadian perspective. When unavailable, studies with data from outside of Canada were included. Because of the lack of Canadian data covering the full scope of topics included, it is not intended for this to be a systematic literature review. On the basis of the specific subject matter and the available evidence, various search strategies were used. Please see Table S3 for a detailed list of the sources and keywords used for literature searches. Quality of studies searched was appraised by authors' expert opinions, with top prioritization for those studies reporting data from high‐quality systematic reviews or meta‐analyses and/or primary data from randomized controlled, prospective, or retrospective observational cohort, or case‐control studies; studies published within the past decade were also given priority. Although the terms sex and gender are often used interchangeably in the available literature, we recognize that they have distinct definitions and attempted to clarify when the differentiating information was available. Sex refers to biological constructs that are primarily associated with physical and physiological features, including hormones, genes, and anatomical and physiological characteristics, and is usually categorized as woman or man. Gender refers to socially constructed roles, behaviors, expressions, and identities.Scope of the ProblemThe stunning lack of research specifically oriented to women and the under‐representation of women in CVD research studies are significant contributing factors to the underrecognition, under‐diagnosis, under‐treatment, and under‐support of women with CVD in Canada. To illustrate the full scope of the problem, this review begins with an appraisal of the currently inadequate evidence to support female‐specific clinical guidelines and recommendations for CVD in Canada. This is followed by an assessment of the present burden of CVD on women in Canada and an analysis of how sex‐ and gender‐specific differences in comorbidity, risk factors, and a lack of awareness on the part of women and their healthcare providers all contribute to the slow progress made in advancing the cardiovascular health of women in Canada. A thorough examination of the multitude of sex‐ and gender‐specific differences in presentation, diagnosis, and treatment across the full spectrum of CVD highlights the urgent need to drive more research and transform clinical practice to improve the cardiovascular health of women. The authors conclude with a discussion of future directions and the action needed on multiple fronts to achieve sex and gender equity for women's cardiovascular health to correct the glaring "unders" of CVD for women in Canada.Clinical Practice Guidelines and RecommendationsAn inadequate evidence base to support the development of comprehensive sex‐ and gender‐specific guidelines or recommendations for the treatment of CVD is a global problem; there are few Canadian, United States, or international CVD guidelines that are women specific. This speaks to the importance of stratifying research results by sex so as to discern sex‐specific implications. Health Canada recommends that women be included as participants in health research and clinical trials, to provide evidence for the crucial impact of sex and gender. Organizations such as HSFC, Canadian Cardiovascular Society, and Hypertension Canada have developed CVD clinical practice guidelines and position statements, but they contain limited information on sex‐specific care. The Canadian Institutes of Health Research and HSFC recognize the importance of women's participation by mandating sex‐ and gender‐based analysis and reporting in funded research.In 2018, the Canadian Cardiovascular Society led an initiative to determine the feasibility of developing a process to consider sex and gender in guidelines, specifically to manage ST‐segment–elevation myocardial infarction (STEMI) in short‐term care. Despite concluding that implementing a systematic process to appraise sex‐specific evidence for clinical practice guidelines was feasible, inadequate enrollment and reporting by sex hindered a comprehensive assessment of the quality of evidence and strength of recommendations.2In the United States, women‐specific CVD prevention guidelines were published in 2004 and updated in 2007 and 2011. Recent guidelines, scientific statements, and advisories addressing CVD in women include the following: 2014: Guidelines for the prevention of stroke in women: A statement for healthcare professionals from the AHA/American Stroke Association;2014: Role of noninvasive testing in the clinical evaluation of women with suspected ischemic heart disease (IHD): A consensus statement from the AHA;2016: Acute myocardial infarction (MI) in women: A scientific statement from the AHA;2018: Spontaneous coronary artery dissection (SCAD): current state of the science: A scientific statement from the AHA; 2018: Promoting risk identification and reduction of CVD in women through collaboration with obstetricians and gynecologists: A presidential advisory from the AHA and the American College of Obstetricians and Gynecologists.The 2016 European Guidelines on Cardiovascular Disease Prevention in Clinical Practice4 provided some recommendations tailored specifically to women, using evidence from 8 risk estimation systems (Framingham, SCORE, ASSIGN‐SCORE, QRISK1 and QRISK2, PROCAM, Pooled Cohort Studies Equations, CUORE, and Globorisk). Several sex‐specific cutoffs for CVD risk factors were recommended.Although CVD risk factor and population prevalence may differ across the globe, evidence suggests that there are similarities in the unique aspects of pathophysiological characteristics of CVD in women globally. Thus, although a united effort would benefit development of strategies to accelerate the improvement of cardiovascular outcomes for women, individual populations must study and understand their specific CVD burdens.Burden of CVD among Women in CanadaAlthough some progress has been made in raising awareness of women's cardiovascular health, CVD continues to be a major leading cause of death for women in Canada.5 The top 3 CVD‐related causes of death for women in Canada are IHD, stroke, and heart failure (HF), as shown in Table 1. Overall, female CVD mortality is proportional to the populations in individual provinces and territories (Table S4) without a clear disproportion for any geographic region.Table 1. Number of Women in Canada With Mortality Caused by CVD, 2016Province/TerritoryIHD including MIMI onlyStrokeHeart FailureVascular DiseaseAFValvular Heart DiseaseArrhythmiaPADCongenital Heart DiseaseNewfoundland and Labrador25580120503030355510Prince Edward Island80152010151010………Nova Scotia460175270705585401515…New Brunswick305140170903540202015…Quebec56002080242080062067555012021060Ontario510200275125508040152020Manitoba4601402201554575351015…Saskatchewan1475445510240170155100203015Alberta17058101050390195340255757020British Columbia……105………………Yukon1055…………………Northwest Territories5………………………Nunavut2890160015208952653255003703520TOTAL13 755569065902830148018151585650415145John Wiley & Sons, LtdData source: Statistics Canada, 2016. Deaths by province for selected International Classification of Diseases, Tenth Revision, With Canadian Enhancements (ICD‐10‐CA), codes (see Table S1), custom tabulation January 1, 2016, to December 1, 2016. Received May 2019. Only sample sizes of ≥5 are shown. A sample size of 51 y, %91.488.997.294.566.776.492.565.322.7Discharged home, %42.042.034.069.072.057.076.088.072.0 Admitted to inpatient care from emergency department, %56.057.066.031.027.041.024.011.025.0John Wiley & Sons, LtdData source: Heart and Stroke Foundation of Canada's analysis of Canadian Institute for Health Information's National Ambulatory Care Reporting System data, April 1, 2016, to March 31, 2017. Data include all facilities in Ontario and Yukon and available facilities in Prince Edward Island, Nova Scotia, Manitoba, Saskatchewan, and British Columbia. Age 51 years stratification was selected as approximate average age of menopause, to characterize premenopausal and postmenopausal populations.Table 3. Most Responsible Diagnosis Reported in Women Admitted for Inpatient Acute Care in 2016VariableIschemic Heart DiseaseHeart FailureStrokeAtrial FibrillationArrhythmiaVascular Disease (Including Peripheral Artery Disease)Valvular Heart DiseaseCongenital Heart DiseasePeripheral Artery Disease OnlyNo. of female admissions to inpatient acute care32 96924 60419 18399987124475045061807308Those with comorbid hypertension, %54.036.056.028.028.026.038.06.020.0Those with comorbid diabetes mellitus, %34.038.026.020.020.010.022.02.04.0Aged ≤51 years, %7.03.08.04.016.09.08.086.011.0Aged >51 years, %93.097.092.096.084.091.092.014.089.0 Discharged home, %66.073.051.088.080.074.080.085.075.0John Wiley & Sons, LtdData source: Heart and Stroke Foundation of Canada's analysis of Canadian Institute for Health Information's Discharge Abstract System data, April 1, 2016, to March 31, 2017. Only data from Quebec were not accessible and, therefore, are not included.Since 2016, there have been several publications summarizing CVD differences in women, derived primarily from US data resources.6 Unfortunately, there is a paucity of such data pertaining specifically to women in Canada, and it is the purpose of this review to focus attention on the need to examine the underlying sex‐specific aspects of CVD in women in Canada, by summarizing what is currently known in the broader North American context and highlighting knowledge gaps specifically for women in Canada. Thus, as described in The Writing Group, the remainder of this review will present a synthesis of sex‐ and gender‐unique aspects of CVD in the published literature, including Canadian‐specific data when available, while underscoring their paucity and the need for additional research.Sex‐ and Gender‐Specific Differences in CVD ComorbidityCertain comorbid conditions affect women differently than men (Table 4).7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 Women with HF have a 24% higher risk of AF than men, whereas women with valvular heart disease (VHD) have a 47% higher risk of AF than men.33 Canadian women, and especially those who are younger, are more likely than men to die within 1 year after an acute MI.34Table 4. Comorbid Conditions Associated With an Increased Risk of CVD in WomenComorbid ConditionImpact on Women's Heart HealthPolycystic ovary syndromeAssociated with obesity, insulin resistance, hyperinsulinemia,8 metabolic syndrome,8, 9 dyslipidemia,10, 11 impaired glucose tolerance, type 2 diabetes mellitus,12 and obstructive sleep apnea.13, 14Autoimmune disorders (eg, rheumatoid arthritis and systemic lupus erythematosus)2 to 10 times more common in women.15Associated systemic inflammation increases the risk of premature atherosclerotic CVD, as well as many other cardiovascular disorders of the myopericardium, valves, and conduction system.16Associated chest, jaw, neck, shoulder, or back pain; fatigue; dyspnea; and exhaustion can be difficult to differentiate from clinical CVD symptoms and may delay recognition of a CVD diagnosis.17Breast cancerBreast cancer survivors are more likely to die from CVD.19, 20, 21Cancer treatment–related cardiac toxicity can occur with anthracycline‐based chemotherapy, trastuzumab‐targeted therapy, and radiation therapy (left‐sided breast cancer); noninvasive cardiac testing can be used to detect cardiovascular toxicity.20Chronic kidney diseaseWomen with reduced kidney function are at greater risk of CVD than men.21Hypertensive disorders of pregnancy and gestational diabetes mellitus increase the risk of chronic kidney disease progression.22Women on dialysis have a CVD mortality rate similar to age‐matched men.23DepressionIncidence is 2 times higher in women than in men.24, 25Increases a women's risk for a cardiac event by 50% to 70%26, 27 and correlates with fatal cardiac events in postmenopausal women.28Almost 2 times more women than men experience depression after cardiac diagnosis29, 30; younger women are particularly susceptible.31Post‐MI depression increases by 2 to 3 times the risk of all‐cause mortality, cardiac mortality, and cardiac morbidity.32John Wiley & Sons, LtdCVD indicates cardiovascular disease; MI, myocardial infarction.Risk FactorsTraditionalSmoking, hypertension, diabetes mellitus, obesity, unhealthy dietary patterns, sedentary behavior, excess alcohol consumption, plasma apolipoproteins, and psychosocial factors account for 96% of the population‐attributable risks of MI among women.35 The sex‐specific impacts of selected traditional CVD risk factors are shown in Table 5.35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46Table 5. Traditional CVD Risk Factors and Their Impact on Women's Cardiovascular HealthTraditional Risk FactorImplications for WomenSmokingSingle‐most modifiable risk factor for developing MI.35Increases the risk of CVD in women aged 60 years.36Poorer hypertension control in women than men aged >60 years.37Women treated with antihypertensive medications have higher systolic blood pressures than men.37Additive interaction between current smoking and hypertension on IHD incidence in women.38Diabetes mellitusWomen with diabetes mellitus are at a 2 to 4 times greater risk for IHD compared with men with diabetes mellitus.39, 40ObesityMore women than men in Canada are overweight and obese.41Metabolic effects of obesity are associated with increased CVD risk.41Physical inactivityAcross all ages, women are less physically active42 and spend more time in sedentary activities.43CholesterolLow HDL cholesterol is a stronger predictor of IHD mortality in women than in men, especially in women aged ≥65 years.44Elevated LDL cholesterol, a strong predictor of IHD risk in women aged 35 years who have numerous cardiovascular risk factors, especially smoking.48Pregnancy creates a natural stress on the cardiovascular system, with structural and hemodynamic changes to accommodate increased blood volume and cardiac output. These normal physiologic changes often unmask or exacerbate prepregnancy cardiac and brain conditions (eg, congenital heart disease and VHD) or lead to the development of new cardiac conditions (eg, arrhythmia, pregnancy‐associated MI, peripartum cardiomyopathy, aortic dissection, and aneurysm). As a result, CVD is a leading cause of maternal morbidity and mortality during pregnancy and postpartum. Hypertensive disorders of pregnancy, gestational diabetes mellitus, preterm birth, and infertility are independent sex‐specific CVD risk factors associated with subsequent premature atherosclerotic CVD, arrhythmia, and HF.49Premature menopause occurs before the age of 40 years and may be spontaneous as a result of primary or secondary ovarian insufficiency or surgical after bilateral oophorectomy. In general, women are at lower risk of CVD than age‐matched men during their reproductive years, but this advantage disappears after menopause.50 There are conflicting data as to whether the type of menopause (spontaneous versus surgical) affects CVD risk. Early (at age 40–45 years) and especially premature menopause are associated with increased CVD morbidity and mortality.50 The adverse effects of menopause on cardiovascular health are largely attributed to hypoestrogenemia.50 This includes an atherogenic cardiometabolic profile with impaired glucose tolerance, an increase in total and low‐density lipoprotein cholesterol and lipoprotein(a), a decrease in high‐density lipoprotein cholesterol, an elevated blood pressure, an increase in central obesity, and a
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