Stable Ischemic Heart Disease in Women
- 120 Downloads
Purpose of the review
Paradoxically, although women have a lower burden of coronary atherosclerosis, they experience more symptoms, more frequent hospitalizations, and a worse prognosis compared to men. This is in part due to biological variations in pathophysiology between the two sexes, and in part related to inadequate understanding of these differences, subconscious referral bias, and suboptimal application of existing women-specific guidelines. We sought to review the contemporary literature and provide an update on risk assessment, diagnosis, and management of IHD in women.
IHD in women is often secondary to diffuse non-obstructive atherosclerosis, coronary spasm, inflammation, and endothelial and microvascular dysfunction, and less commonly due to the male pattern of flow-limiting epicardial stenosis. Both IHD patterns likely represent sex-specific manifestations of the same disease process. Additionally, there is a differential expression of risk factors and symptoms between men and women. Application of male-pattern IHD risk factors and presentation to women contributes to under-recognition, under-testing, and under-treatment of IHD in women compared to men. Traditional diagnostic evaluation has focused on detection of epicardial disease, amenable to revascularization. Our improved understanding of sex-specific pathophysiology of IHD has enabled us to also develop tools for detection of microvascular disease. Advances in stress MRI, flow quantification on stress PET, and provocative invasive angiography have filled this void and offer important diagnostic and prognostic information.
Despite our improved understanding of sex-specific differences in presentation, risk factors, pathophysiology, diagnostic testing, and management strategies of IHD, women with IHD continue to experience worse outcomes than men. This disparity underscores the need for improved research and understanding of biological sex differences, elimination of subconscious gender bias in referral patterns, and improved application of existing research into clinical practice.
KeywordsIschemic heart disease Women Sex differences Microvascular disease Coronary artery disease Diagnostic imaging
The authors wish to thank Mr. Guy Bolling for his editorial assistance.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 10.Vaccarino V, Badimon L, Corti R, et al. Ischaemic heart disease in women: are there sex differences in pathophysiology and risk factors?: position paper from the Working Group on Coronary Pathophysiology and Microcirculation of the European Society of Cardiology. Cardiovasc Res. 2010;90:9–17.CrossRefPubMedPubMedCentralGoogle Scholar
- 23.•• Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016;37:2315–81. European guideline on primary and secondary prevention of IHD. Sex specific differences in conventional risk factors and novel female-predominant risk factors are highlighted.CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd-Jones DM, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: a guideline from the American Heart Association. J Am Coll Cardiol. 2011;57:1404–23.CrossRefPubMedPubMedCentralGoogle Scholar
- 25.•• Bairey Merz CN, Andersen H, Sprague E, et al. Knowledge, attitudes, and beliefs regarding cardiovascular disease in women: the Women’s Heart Alliance. J Am Coll Cardiol. 2017;70:123–32. Although IHD is the leading cause of mortality in women, awareness in public and medical community is still sub-optimal. Campaigns, physician education and additional investment in women’s IHD research is warranted.CrossRefPubMedGoogle Scholar
- 30.Finks S. Cardiovascular disease in women. In: Richardson M, Chessman KH, Chant C, editors. Pharmacotherapy self-assessment program. 7th ed. Kansas City: American College of Clinical Pharmacy; 2010. p. 179–99.Google Scholar
- 34.Lichtman JH, Leifheit EC, Safdar B, Bao H, Krumholz HM, Lorenze NP, et al. Sex differences in the presentation and perception of symptoms among young patients with myocardial infarction: evidence from the VIRGO study (variation in recovery: role of gender on outcomes of young AMI patients). Circulation. 2018;137:781–90.CrossRefPubMedGoogle Scholar
- 38.Pepine CJ, Anderson RD, Sharaf BL, Reis SE, Smith KM, Handberg EM, et al. Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women’s Ischemia Syndrome Evaluation) study. J Am Coll Cardiol. 2010;55:2825–32.CrossRefPubMedPubMedCentralGoogle Scholar
- 42.Sharaf BL, Pepine CJ, Kerensky RA, Reis SE, Reichek N, Rogers WJ, et al. Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation [WISE] study angiographic core laboratory). Am J Cardiol. 2001;87:937–41.CrossRefPubMedGoogle Scholar
- 43.• Kenkre TS, Malhotra P, Johnson BD, et al. Ten-year mortality in the WISE study (Women’s Ischemia Syndrome Evaluation). Circ Cardiovasc Qual Outcomes. 2017;10:e003863. 10-year outcome in a landmark study evaluating symptomatic women with nonobstructive coronary artery disease. This angiographic finding is not benign and associated with increased risk compared to asymptomatic women.Google Scholar
- 47.Boardman HM, Hartley L, Eisinga A, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal woman. Cochrane Database Syst Rev. 2015;3:CD002229.Google Scholar
- 48.•• Mieres JH, Gulati M, Bairey Merz N, et al. Role of noninvasive testing in the clinical evaluation of women with suspected ischemic heart disease: a consensus statement from the American Heart Association. Circulation. 2014;130:350–79. A consensus statement highlighting the algorithm for non-invasive stress testing in women at risk for IHD.CrossRefPubMedGoogle Scholar
- 49.Fihn SD, Blankenship JC, Alexander KP, et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2014;130:1749–67.CrossRefPubMedGoogle Scholar
- 53.Sanders GD, Patel MR, Chatterjee R, et al. AHRQ future research needs papers. Noninvasive technologies for the diagnosis of coronary artery disease in women: future research needs: identification of future research needs from comparative effectiveness review no 58. Rockville: Agency for Healthcare Research and Quality (US); 2013.Google Scholar
- 59.Einstein AJ, Blankstein R, Andrews H, Fish M, Padgett R, Hayes SW, et al. Comparison of image quality, myocardial perfusion, and left ventricular function between standard imaging and single-injection ultra-low-dose imaging using a high-efficiency SPECT camera: the MILLISIEVERT study. J Nucl Med. 2014;55:1430–7.CrossRefPubMedPubMedCentralGoogle Scholar
- 64.Greenwood JP, Motwani M, Maredia N, et al. Comparison of cardiovascular magnetic resonance and single-photon emission computed tomography in women with suspected coronary artery disease from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease (CE-MARC) trial. Circulation. 2013;129:1129–38.CrossRefPubMedGoogle Scholar
- 73.Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58:e44–122.CrossRefPubMedGoogle Scholar
- 78.Gulati M, Cooper-DeHoff RM, McClure C, et al. Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women’s Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project. Arch Intern Med. 2009;169:843–50.CrossRefPubMedPubMedCentralGoogle Scholar
- 81.Shaw LJ, Merz CNB, Pepine CJ, et al. The economic burden of angina in women with suspected ischemic heart disease. Results from the National Institutes of Health–National Heart, Lung, and Blood Institute–sponsored Women’s Ischemia Syndrome Evaluation. Circulation. 2006;114:894–904.CrossRefPubMedGoogle Scholar
- 82.Roswell RO, Kunkes J, Chen AY, Chiswell K, Iqbal S, Roe MT, et al. Impact of sex and contact-to-device time on clinical outcomes in acute ST-segment elevation myocardial infarction—findings from the National Cardiovascular Data Registry. J Am Heart Assoc. 2017;6:e004521.CrossRefPubMedPubMedCentralGoogle Scholar
- 83.Mosca L, Hammond G, Mochari-Greenberger H, Towfighi A, Albert MA, on behalf of the American Heart Association Cardiovascular Disease and Stroke in Women and Special Populations Committee of the Council on Clinical Cardiology, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Council on High Bloo. Fifteen-year trends in awareness of heart disease in women: results of a 2012 American Heart Association national survey. Circulation. 2013;127:1254–63. e1–29Google Scholar
- 84.Leifheit-Limson EC, D'Onofrio G, Daneshvar M, et al. Sex differences in cardiac risk factors, perceived risk, and health care provider discussion of risk and risk modification among young patients with acute myocardial infarction. The VIRGO Study J Am Coll Cardiol. 2015;66:1949–57.CrossRefPubMedGoogle Scholar
- 85.Shah AS, Griffiths M, Lee KK, et al. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study. Bmj. 2015;g7873:350.Google Scholar