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The Prevention, Diagnosis and Treatment of Ischemic Heart Disease in Women

  • LaPrincess C. Brewer
  • Rosalyn O. Adigun
  • Sharon L. Mulvagh
Chapter
First Online:

Abstract

It has been almost a quarter century since the first scientific statement on cardiovascular disease in women was published, yet cardiovascular disease remains the leading cause of death in women. Women often present with atypical symptoms which delays recognition, diagnosis and treatment. The complex interplay of gaps in knowledge, sparse sex-specific outcomes data, and limitations of current guidelines lead women to suffer poorer clinical outcomes, with higher cardiovascular morbidity and mortality. While efforts to increase awareness of differences in the presentation of heart disease in women have improved our ability to evaluate women with ischemic symptoms, sex-specific differences in the pathophysiology of heart disease continue to create diagnostic and therapeutic enigmas. As our knowledge of the differential impact of traditional risk factors in women continues to grow, a paucity of sex-specific outcomes data precludes the implementation of evidence-based interventions into clinical practice. More recently, emerging data on non-traditional risk factors unique to and/or more commonly found in women is also shedding new light on the increased burden of disease among younger women, and is an area for future research and interventions. Ultimately, there remains a need for sex and evidence-based diagnostic and therapeutic strategies to address the variances in disease presentation, pharmacokinetic and pharmacodynamics differences in women compared to men, and to identify prognostic markers that can be targets for long-term monitoring. In the interim, we need to ensure that available resources for anatomic and functional assessments of cardiovascular disease are not underutilized in women. This updated review discusses the current challenges of prevention, diagnosis and treatment of ischemic heart disease in women.

Keywords

Women Ischemic heart disease Coronary artery disease Cardiovascular diseases Epidemiology Disparities Cardiovascular risk Diagnosis Treatment 

Abbreviations

ACC

American College of Cardiology

ACEI

ACE inhibitors

ACS

Acute coronary syndromes

AHA

American Heart Association

ARB

Angiotensin receptor blockers

ARIC

Atherosclerosis Risk in Communities

ASCVD

Atherosclerotic cardiovascular disease

ATP

Adult Treatment Panel

CABG

Coronary artery bypass grafting

CAC

Coronary artery calcium

CAD

Coronary artery disease

CASS

Coronary Artery Surgery Study

CCTA

Coronary computed tomographic angiography

CMR

Cardiac magnetic resonance imaging

CONFIRM

Coronary CT Angiography Evaluation for Clinical Outcomes

CVD

Cardiovascular disease

CT

Computed tomography

ECG

Electrocardiogram

ELITE

Early versus Late Intervention Trial with Estradiol

ETT

Exercise treadmill test

FRS

Framingham risk score

HERS

Heart and Estrogen/Progestin Replacement Study

hsCRP

High-sensitivity C-reactive protein

IHD

Ischemic heart disease

IOM

Institute of Medicine

ISCHEMIA

International Study of Comparative Health Effectiveness and Invasive Approaches

KEEPS

Kronos Early Estrogen Prevention Study

MACE

Major adverse cardiac events

MHT

Menopausal hormone therapy

MI

Myocardial infarction

MPI

Myocardial perfusion imaging

MVD

Microvascular disease

NCDR

National Cardiovascular Data Registry

NHANES

National Health and Nutrition Examination Survey

NHLBI

National Heart Lung and Blood Institute

PCE

Pooled Cohort Equation

PCI

Percutaneous coronary intervention

PCOS

Polycystic ovarian syndrome

PET

Positron emission tomography

PRHI

Peripheral reactive hyperemia index

PROMISE

Prospective Multicenter Imaging Study for Evaluation of Chest Pain

ROMICAT

Rule Out Myocardial Infarction using Computer Assisted Tomography

SCORE

Systematic Coronary Risk Evaluation

SPECT

Single-photon emission computed tomography

WHI

Women’s Health Initiative

WISE

Women’s Ischemia Syndrome Evaluation

WOMEN

What is the Optimal Method for Ischemia Evaluation in Women

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Notes

Acknowledgment

The authors are grateful to Mrs. Debra Ward and Mrs. Rebecca Olson for their precious assistance with chapter preparation. Dr. Brewer is supported by the Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Scholars Program (award number K12 HD065987-07) from the National Institutes of Health (NIH) Office of Research on Women’s Health (ORWH), Mayo Clinic Women’s Health Research Center.

References

  1. 1.
    Benjamin EJ, Blaha MJ, et al. Heart disease and stroke statistics—2017 update: a report from the American Heart Association. Circulation. 2017;135(10):e146–603.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Gulati M. Improving the cardiovascular health of women in the nation: moving beyond the bikini boundaries. Circulation. 2017;135(6):495–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Shaw LJ, Bairey Merz CN, et al. Insights from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) study: part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies. J Am Coll Cardiol. 2006a;47(3 Suppl):S4–S20.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Shaw LJ, Bugiardini R, et al. Women and ischemic heart disease: evolving knowledge. J Am Coll Cardiol. 2009;54(17):1561–75.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Bairey Merz CN, Andersen H, et al. Knowledge, attitudes, and beliefs regarding cardiovascular disease in women: the women’s heart alliance. J Am Coll Cardiol. 2017;70(2):123–32.PubMedCrossRefGoogle Scholar
  6. 6.
    Institute of Medicine. Exploring the biological contributions to human health: does sex matter? Washington, DC: The National Academies Press; 2001.Google Scholar
  7. 7.
    Institute of Medicine Committee on Women’s Health Research. Women’s health research: progress, pitfalls, and promise. Washington, DC: National Academies Press (US) Copyright 2010 by the National Academy of Sciences; 2010. All rights reservedGoogle Scholar
  8. 8.
    Jackson EA, Nallamothu BK. Women are why. Circ Cardiovasc Qual Outcomes. 2017;10(2):pii: e003597.CrossRefGoogle Scholar
  9. 9.
    Kim ES, Carrigan TP, et al. Enrollment of women in National Heart, Lung, and Blood Institute-funded cardiovascular randomized controlled trials fails to meet current federal mandates for inclusion. J Am Coll Cardiol. 2008;52(8):672–3.PubMedCrossRefGoogle Scholar
  10. 10.
    Bucholz EM, Butala NM, et al. Sex differences in long-term mortality after myocardial infarction: a systematic review. Circulation. 2014;130(9):757–67.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Wenger NK. Women and coronary heart disease: a century after Herrick: understudied, underdiagnosed, and undertreated. Circulation. 2012;126(5):604–11.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Stillman AE, Gatsonis C, et al. Rationale and design of the Randomized Evaluation of patients with Stable angina Comparing Utilization of noninvasive Examinations (RESCUE) trial. Am Heart J. 2016;179:19–28.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Towfighi A, Zheng L, et al. Sex-specific trends in midlife coronary heart disease risk and prevalence. Arch Intern Med. 2009;169(19):1762–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Hess CN, Kaltenbach LA, et al. Race and sex differences in post-myocardial infarction angina frequency and risk of 1-year unplanned rehospitalization. Circulation. 2017;135(6):532–43.PubMedCrossRefGoogle Scholar
  15. 15.
    Campisi R. Noninvasive assessment of coronary microvascular function in women at risk for ischaemic heart disease. Int J Clin Pract. 2008;62(2):300–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Mack M, Gopal A. Epidemiology, traditional and novel risk factors in coronary artery disease. Cardiol Clin. 2014;32(3):323–32.PubMedCrossRefGoogle Scholar
  17. 17.
    Stampfer MJ, Colditz GA, et al. Postmenopausal estrogen therapy and cardiovascular disease: ten-year follow-up from the Nurses’ Health Study. N Engl J Med. 1991;325(11):756–62.PubMedCrossRefGoogle Scholar
  18. 18.
    Lloyd-Jones D, Adams RJ, et al. Executive summary: heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation. 2010;121(7):948.PubMedCrossRefGoogle Scholar
  19. 19.
    Feinstein M, Ning H, et al. Racial differences in risks for first cardiovascular events and noncardiovascular death: the Atherosclerosis Risk in Communities study, the Cardiovascular Health Study, and the Multi-Ethnic Study of Atherosclerosis. Circulation. 2012;126(1):50–9.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Dreyer RP, Sciria C, et al. Young women with acute myocardial infarction: current perspectives. Circ Cardiovasc Qual Outcomes. 2017;10(2):pii: e003480.CrossRefGoogle Scholar
  21. 21.
    Dreyer RP, Smolderen KG, et al. Gender differences in pre-event health status of young patients with acute myocardial infarction: a VIRGO study analysis. Eur Heart J Acute Cardiovasc Care. 2015;5(1):43–54.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Ford ES, Capewell S. Coronary heart disease mortality among young adults in the US from 1980 through 2002: concealed leveling of mortality rates. J Am Coll Cardiol. 2007;50(22):2128–32.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Hemingway H, Langenberg C, et al. Prevalence of angina in women versus men a systematic review and meta-analysis of international variations across 31 countries. Circulation. 2008;117(12):1526–36.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Zuchi C, Tritto I, et al. Angina pectoris in women: focus on microvascular disease. Int J Cardiol. 2013;163(2):132–40.PubMedCrossRefGoogle Scholar
  25. 25.
    Eastwood J-A, Johnson BD, et al. Anginal symptoms, coronary artery disease, and adverse outcomes in black and white women: the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study. J Womens Health. 2013;22(9):724–32.CrossRefGoogle Scholar
  26. 26.
    Mieres JH, Heller GV, et al. Signs and symptoms of suspected myocardial ischemia in women: results from the What Is the Optimal Method for Ischemia Evaluation in Women? Trial. J Womens Health. 2011;20(9):1261–8.CrossRefGoogle Scholar
  27. 27.
    Gulati M, Cooper-DeHoff RM, 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(9):843–50.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Sharaf BL, Pepine CJ, 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(8):937–41.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Vaccarino V. Ischemic heart disease in women many questions, few facts. Circ Cardiovasc Qual Outcomes. 2010;3(2):111–5.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Shaw LJ, Merz CN, 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. 2006b;114(9):894–904.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Shaw LJ, Shaw RE, et al. Impact of ethnicity and gender differences on angiographic coronary artery disease prevalence and in-hospital mortality in the American College of Cardiology–National Cardiovascular Data Registry. Circulation. 2008;117(14):1787–801.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Gulati M, Shaw LJ, et al. Myocardial ischemia in women: lessons from the NHLBI WISE study. Clin Cardiol. 2012;35(3):141–8.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Bransford TL, Ofili E. The paradox of coronary heart disease in African-American women. J Natl Med Assoc. 2000;92(7):327.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Mensah GA, Brown DW. An overview of cardiovascular disease burden in the United States. Health Aff. 2007;26(1):38–48.CrossRefGoogle Scholar
  35. 35.
    Berger JS, Brown DL. Gender-age interaction in early mortality following primary angioplasty for acute myocardial infarction. Am J Cardiol. 2006;98(9):1140–3.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Gupta A, Wang Y, et al. Trends in acute myocardial infarction in young patients and differences by sex and race, 2001 to 2010. J Am Coll Cardiol. 2014;64(4):337–45.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Vaccarino V, Horwitz RI, et al. Sex differences in mortality after myocardial infarction: evidence for a sex-age interaction. Arch Intern Med. 1998;158(18):2054–62.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Vaccarino V, Parsons L, et al. Sex-based differences in early mortality after myocardial infarction. N Engl J Med. 1999;341(4):217–25.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    van Loo HM, van den Heuvel ER, et al. Sex dependent risk factors for mortality after myocardial infarction: individual patient data meta-analysis. BMC Med. 2014;12(1):242.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Banks K, Lo M, et al. Angina in women without obstructive coronary artery disease. Curr Cardiol Rev. 2010;6(1):71.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Tamis-Holland JE, Lu J, et al. Sex differences in presentation and outcome among patients with type 2 diabetes and coronary artery disease treated with contemporary medical therapy with or without prompt revascularization: a report from the BARI 2D Trial (Bypass Angioplasty Revascularization Investigation 2 Diabetes). J Am Coll Cardiol. 2013;61(17):1767–76.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Handberg EM, Eastwood JA, et al. Clinical implications of the Women’s Ischemia Syndrome Evaluation: inter-relationships between symptoms, psychosocial factors and cardiovascular outcomes. Womens Health (Lond Engl). 2013;9(5):479–90.CrossRefGoogle Scholar
  43. 43.
    Leung Yinko SS, Pelletier R, et al. Health-related quality of life in premature acute coronary syndrome: does patient sex or gender really matter? J Am Heart Assoc. 2014;3(4):pii: e000901.CrossRefGoogle Scholar
  44. 44.
    Norris CM, Spertus JA, et al. Sex and gender discrepancies in health-related quality of life outcomes among patients with established coronary artery disease. Circ Cardiovasc Qual Outcomes. 2008;1(2):123–30.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Vaccarino V, Lin ZQ, et al. Gender differences in recovery after coronary artery bypass surgery. J Am Coll Cardiol. 2003;41(2):307–14.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Scheuner MT, Setodji CM, et al. Relation of familial patterns of coronary heart disease, stroke, and diabetes to subclinical atherosclerosis: the multi-ethnic study of atherosclerosis. Genet Med. 2008;10(12):879–87.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Kannel WB. Metabolic risk factors for coronary heart disease in women: perspective from the Framingham Study. Am Heart J. 1987;114(2):413–9.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Matthews KA, Crawford SL, et al. Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition? J Am Coll Cardiol. 2009;54(25):2366–73.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Mokdad AH, Ford ES, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA. 2003;289(1):76–9.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a metaanalysis of population-based prospective studies. J Cardiovasc Risk. 1996;3(2):213–9.CrossRefPubMedGoogle Scholar
  51. 51.
    Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes: a 26-year follow-up of the Framingham population. Am Heart J. 1986;111(2):383–90.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Reuterwall C, Hallqvist J, et al. Higher relative, but lower absolute risks of myocardial infarction in women than in men: analysis of some major risk factors in the SHEEP study. The SHEEP Study Group. J Intern Med. 1999;246(2):161–74.CrossRefPubMedGoogle Scholar
  53. 53.
    Lew J, Sanghavi M, et al. Sex-based differences in cardiometabolic biomarkers. Circulation. 2017;135(6):544–55.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Berry JD, Dyer A, et al. Lifetime risks of cardiovascular disease. N Engl J Med. 2012;366(4):321–9.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Sharma K, Gulati M. Coronary artery disease in women: a 2013 update. Glob Heart. 2013;8(2):105–12.CrossRefPubMedGoogle Scholar
  56. 56.
    Yang Q, Cogswell ME, et al. Trends in cardiovascular health metrics and associations with all-cause and CVD mortality among US adults. JAMA. 2012;307(12):1273–83.CrossRefPubMedGoogle Scholar
  57. 57.
    Kling JM, Miller VM, et al. Go Red for Women cardiovascular health-screening evaluation: the dichotomy between awareness and perception of cardiovascular risk in the community. J Womens Health (Larchmt). 2013;22(3):210–8.CrossRefGoogle Scholar
  58. 58.
    Mosca L, Hammond G, et al. Fifteen-year trends in awareness of heart disease in women results of a 2012 American Heart Association National Survey. Circulation. 2013;127(11):1254–63.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Kip KE, Marroquin OC, et al. Clinical importance of obesity versus the metabolic syndrome in cardiovascular risk in women: a report from the Women’s Ischemia Syndrome Evaluation (WISE) Study. Circulation. 2004;109(6):706–13.CrossRefPubMedGoogle Scholar
  60. 60.
    Karim R, Stanczyk FZ, et al. Associations between markers of inflammation and physiological and pharmacological levels of circulating sex hormones in postmenopausal women. Menopause. 2010;17(4):785–90.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Mosca L, Benjamin EJ, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the american heart association. Circulation. 2011;57(12):1404–23.Google Scholar
  62. 62.
    Ridker PM, Rifai N, et al. Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women. JAMA. 2005;294(3):326–33.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Wong ND, Pio J, et al. Distribution of C-reactive protein and its relation to risk factors and coronary heart disease risk estimation in the National Health and Nutrition Examination Survey (NHANES) III. Prev Cardiol. 2001;4(3):109–14.PubMedCrossRefGoogle Scholar
  64. 64.
    Salmon JE, Roman MJ. Subclinical atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus. Am J Med. 2008;121(10 Suppl 1):010.Google Scholar
  65. 65.
    Hall PS, Nah G, et al. Reproductive Factors and Incidence of Heart Failure Hospitalization in the Women’s Health Initiative. J Am Coll Cardiol. 2017;69:2517–26.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Mansoor H, Elgendy IY, et al. Duration of reproductive years and the risk of cardiovascular and cerebrovascular events in older women: insights from the National Health and Nutrition Examination Survey. J Womens Health (Larchmt). 2017;26(10):1047–52.  https://doi.org/10.1089/jwh.2016.6013. [Epub ahead of print]CrossRefGoogle Scholar
  67. 67.
    Lakshman R, Forouhi NG, et al. Early age at menarche associated with cardiovascular disease and mortality. J Clin Endocrinol Metab. 2009;94(12):4953–60.PubMedCrossRefGoogle Scholar
  68. 68.
    Bairey Merz CN, Johnson BD, et al. Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: a report from the NHLBI-sponsored WISE study. J Am Coll Cardiol. 2003;41(3):413–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Tanz LJ, Stuart JJ, et al. Preterm delivery and maternal cardiovascular disease in young and middle-aged adult women. Circulation. 2017;135(6):578–89.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Ray JG, Vermeulen MJ, et al. Cardiovascular health after maternal placental syndromes (CHAMPS): population-based retrospective cohort study. Lancet. 2005;366(9499):1797–803.PubMedCrossRefGoogle Scholar
  71. 71.
    Wu P, Haththotuwa R, et al. Preeclampsia and future cardiovascular health: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2017;10(2):e003497.PubMedCrossRefGoogle Scholar
  72. 72.
    Han SH, Bae JH, et al. Sex differences in atheroma burden and endothelial function in patients with early coronary atherosclerosis. Eur Heart J. 2008;29(11):1359–69.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Reis SE, Holubkov R, et al. Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study. Am Heart J. 2001;141(5):735–41.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Bairey Merz CN, Pepine CJ. Syndrome X and microvascular coronary dysfunction. Circulation. 2011;124(13):1477–80.PubMedCrossRefGoogle Scholar
  75. 75.
    Kothawade K, Bairey Merz CN. Microvascular coronary dysfunction in women: pathophysiology, diagnosis, and management. Curr Probl Cardiol. 2011;36(8):291–318.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    von Mering GO, Arant CB, et al. Abnormal coronary vasomotion as a prognostic indicator of cardiovascular events in women: results from the National Heart, Lung, and Blood Institute-Sponsored Women’s Ischemia Syndrome Evaluation (WISE). Circulation. 2004;109(6):722–5.CrossRefGoogle Scholar
  77. 77.
    Suwaidi JA, Hamasaki S, et al. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation. 2000;101(9):948–54.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Kones R. Primary prevention of coronary heart disease: integration of new data, evolving views, revised goals, and role of rosuvastatin in management. A comprehensive survey. Drug Des Devel Ther. 2011;5:325–80.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Madhok V, Fahey T. Cardiovascular risk estimation: important but may be inaccurate. BMJ. 2006;332(7555):1422.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Conroy RM, Pyorala K, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003;24(11):987–1003.PubMedCrossRefGoogle Scholar
  81. 81.
    Hippisley-Cox J, Coupland C, et al. Derivation and validation of QRISK, a new cardiovascular disease risk score for the United Kingdom: prospective open cohort study. BMJ. 2007;335(7611):136.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    NCEP. Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143.Google Scholar
  83. 83.
    Ridker PM, Buring JE, et al. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score. JAMA. 2007;297(6):611–9.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Wenger NK. The Reynolds Risk Score: improved accuracy for cardiovascular risk prediction in women? Nat Clin Pract Cardiovasc Med. 2007;4(7):366–7.PubMedCrossRefGoogle Scholar
  85. 85.
    Goff DC, Lloyd-Jones DM, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Circulation. 2014;129(25 suppl 2):S49–73.PubMedCrossRefGoogle Scholar
  86. 86.
    Gulati M, Noel Bairey Merz C. New cholesterol guidelines and primary prevention in women. Trends Cardiovasc Med. 2014;25(2):84–94.PubMedCrossRefGoogle Scholar
  87. 87.
    Cook NR, Ridker PM. Further insight into the cardiovascular risk calculator: the roles of statins, revascularizations, and underascertainment in the Women’s Health Study. JAMA Intern Med. 2014;174(12):1964–71.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Ridker PM, Cook NR. Statins: new American guidelines for prevention of cardiovascular disease. Lancet. 2013;382(9907):1762–5.PubMedCrossRefGoogle Scholar
  89. 89.
    Canto JG, Rogers WJ, et al. Association of age and sex with myocardial infarction symptom presentation and in-hospital mortality. JAMA. 2012;307(8):813–22.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Johnson BD, Shaw LJ, et al. Persistent chest pain predicts cardiovascular events in women without obstructive coronary artery disease: results from the NIH-NHLBI-sponsored Women’s Ischaemia Syndrome Evaluation (WISE) study. Eur Heart J. 2006;27(12):1408–15.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Reynolds HR, Srichai MB, et al. Mechanisms of myocardial infarction in women without angiographically obstructive coronary artery disease. Circulation. 2011;124(13):1414–25.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Abdelmoneim SS, Bernier M, et al. Assessment of myocardial perfusion during adenosine stress using real time three-dimensional and two-dimensional myocardial contrast echocardiography: comparison with single-photon emission computed tomography. Echocardiography. 2010;27(4):421–9.PubMedCrossRefGoogle Scholar
  93. 93.
    Tweet MS, Hayes SN, et al. Clinical features, management, and prognosis of spontaneous coronary artery dissection. Circulation. 2012;126(5):579–88.PubMedCrossRefGoogle Scholar
  94. 94.
    Yip A, Saw J. Spontaneous coronary artery dissection—a review. Cardiovasc Diagn Ther. 2015;5(1):37–48.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Mieres JH, Gulati M, 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(4):350–79.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical-diagnosis of coronary-artery disease. N Engl J Med. 1979;300(24):1350–8.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Gulati M, Pandey DK, et al. Exercise capacity and the risk of death in women: the St James Women Take Heart Project. Circulation. 2003;108(13):1554–9.PubMedCrossRefGoogle Scholar
  98. 98.
    Bourque JM, Holland BH, et al. Achieving an exercise workload of ≥10 metabolic equivalents predicts a very low risk of inducible ischemia: does myocardial perfusion imaging have a role? J Am Coll Cardiol. 2009;54(6):538–45.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Kohli P, Gulati M. Exercise stress testing in women: going back to the basics. Circulation. 2010;122(24):2570–80.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Hlatky MA, Pryor DB, et al. Factors affecting sensitivity and specificity of exercise electrocardiography. Multivariable analysis. Am J Med. 1984;77(1):64–71.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Alexander KP, Shaw LJ, et al. Value of exercise treadmill testing in women. J Am Coll Cardiol. 1998;32(6):1657–64.PubMedCrossRefGoogle Scholar
  102. 102.
    Kim C, Kwok YS, et al. Pharmacologic stress testing for coronary disease diagnosis: a meta-analysis. Am Heart J. 2001;142(6):934–44.PubMedCrossRefGoogle Scholar
  103. 103.
    Marwick TH, Nemec JJ, et al. Accuracy and limitations of exercise echocardiography in a routine clinical setting. J Am Coll Cardiol. 1992;19(1):74–81.PubMedCrossRefGoogle Scholar
  104. 104.
    Williams MJ, Marwick TH, et al. Comparison of exercise echocardiography with an exercise score to diagnose coronary artery disease in women. Am J Cardiol. 1994;74(5):435–8.PubMedCrossRefGoogle Scholar
  105. 105.
    Roger VL, Pellikka PA, et al. Sex and test verification bias. Impact on the diagnostic value of exercise echocardiography. Circulation. 1997;95(2):405–10.PubMedCrossRefGoogle Scholar
  106. 106.
    Arruda-Olson AM, Juracan EM, et al. Prognostic value of exercise echocardiography in 5,798 patients: is there a gender difference? J Am Coll Cardiol. 2002;39(4):625–31.PubMedCrossRefGoogle Scholar
  107. 107.
    McCully RB, Roger VL, et al. Outcome after normal exercise echocardiography and predictors of subsequent cardiac events: follow-up of 1,325 patients. J Am Coll Cardiol. 1998;31(1):144–9.PubMedCrossRefGoogle Scholar
  108. 108.
    Gerber TC, Gibbons RJ. Weighing the risks and benefits of cardiac imaging with ionizing radiation. JACC Cardiovasc Imaging. 2010;3(5):528–35.PubMedCrossRefGoogle Scholar
  109. 109.
    Min JK, Dunning A, et al. Age- and sex-related differences in all-cause mortality risk based on coronary computed tomography angiography findings results from the International Multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) of 23,854 patients without known coronary artery disease. J Am Coll Cardiol. 2011;58(8):849–60.CrossRefPubMedGoogle Scholar
  110. 110.
    Hoffmann U, Bamberg F, et al. Coronary computed tomography angiography for early triage of patients with acute chest pain: the ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) trial. J Am Coll Cardiol. 2009;53(18):1642–50.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Schlett CL, Banerji D, et al. Prognostic value of CT angiography for major adverse cardiac events in patients with acute chest pain from the emergency department: 2-year outcomes of the ROMICAT trial. JACC Cardiovasc Imaging. 2011;4(5):481–91.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Devries S, Wolfkiel C, et al. Influence of age and gender on the presence of coronary calcium detected by ultrafast computed tomography. J Am Coll Cardiol. 1995;25(1):76–82.PubMedCrossRefGoogle Scholar
  113. 113.
    Budoff MJ, Shokooh S, et al. Electron beam tomography and angiography: sex differences. Am Heart J. 2002;143(5):877–82.PubMedCrossRefGoogle Scholar
  114. 114.
    Douglas PS, Hoffmann U, et al. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med. 2015;372(14):1291–300.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    ClinicalTrials.gov. International study of comparative health effectiveness with medical and invasive approaches (ISCHEMIA).Google Scholar
  116. 116.
    Herrmann J, Kaski JC, et al. Coronary microvascular dysfunction in the clinical setting: from mystery to reality. Eur Heart J. 2012;33(22):2771–82b.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Wei J, Mehta PK, et al. Safety of coronary reactivity testing in women with no obstructive coronary artery disease. JACC Cardiovasc Interv. 2012;5(6):646–53.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Pepine CJ, Anderson RD, 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(25):2825–32.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Rossi R, Nuzzo A, et al. Prognostic role of flow-mediated dilation and cardiac risk factors in post-menopausal women. J Am Coll Cardiol. 2008;51(10):997–1002.PubMedCrossRefGoogle Scholar
  120. 120.
    Bonetti PO, Pumper GM, et al. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol. 2004;44(11):2137–41.PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    Matsuzawa Y, Sugiyama S, et al. Digital assessment of endothelial function and ischemic heart disease in women. J Am Coll Cardiol. 2010;55(16):1688–96.PubMedCrossRefGoogle Scholar
  122. 122.
    Lerman A, Sopko G. Women and cardiovascular heart disease: clinical implications from the Women’s Ischemia Syndrome Evaluation (WISE) Study. Are we smarter? J Am Coll Cardiol. 2006;47(3 Suppl):S59–62.PubMedCrossRefGoogle Scholar
  123. 123.
    Hasdai D, Cannan CR, et al. Evaluation of patients with minimally obstructive coronary artery disease and angina. Int J Cardiol. 1996;53(3):203–8.PubMedCrossRefGoogle Scholar
  124. 124.
    Taqueti VR, Shaw LJ, et al. Excess cardiovascular risk in women relative to men referred for coronary angiography is associated with severely impaired coronary flow reserve, not obstructive disease. Circulation. 2017;135(6):566–77.PubMedCrossRefGoogle Scholar
  125. 125.
    Amsterdam EA, Wenger NK, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;64(24):e139–228.PubMedCrossRefGoogle Scholar
  126. 126.
    Blomkalns AL, Chen AY, et al. Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative. J Am Coll Cardiol. 2005;45(6):832–7.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Daly C, Clemens F, et al. Gender differences in the management and clinical outcome of stable angina. Circulation. 2006;113(4):490–8.PubMedCrossRefGoogle Scholar
  128. 128.
    Dey S, Flather MD, et al. Sex-related differences in the presentation, treatment and outcomes among patients with acute coronary syndromes: the Global Registry of Acute Coronary Events. Heart. 2009;95(1):20–6.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Gehrie ER, Reynolds HR, et al. Characterization and outcomes of women and men with non-ST-segment elevation myocardial infarction and nonobstructive coronary artery disease: results from the can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines (CRUSADE) quality improvement initiative. Am Heart J. 2009;158(4):688–94.CrossRefPubMedGoogle Scholar
  130. 130.
    Steg PG, Greenlaw N, et al. Women and men with stable coronary artery disease have similar clinical outcomes: insights from the international prospective CLARIFY registry. Eur Heart J. 2012;33(22):2831–40.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy—I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists’ Collaboration. BMJ. 1994;308(6921):81–106.CrossRefGoogle Scholar
  132. 132.
    Chan AT, Manson JE, et al. Long-term aspirin use and mortality in women. Arch Intern Med. 2007;167(6):562–72.PubMedCrossRefGoogle Scholar
  133. 133.
    O’Donoghue M, Boden WE, et al. Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction: a meta-analysis. JAMA. 2008;300(1):71–80.CrossRefPubMedGoogle Scholar
  134. 134.
    Gupta A, Chui P, et al. Frequency and effects of excess dosing of anticoagulants in patients </=55 years with acute myocardial infarction who underwent percutaneous coronary intervention (from the VIRGO Study). Am J Cardiol. 2015;116(1):1–7.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Balady GJ, Ades PA, et al. Referral, enrollment, and delivery of cardiac rehabilitation/secondary prevention programs at clinical centers and beyond a presidential advisory from the American Heart Association. Circulation. 2011;124(25):2951–60.CrossRefPubMedGoogle Scholar
  136. 136.
    Lavie CJ, Milani RV. Effects of cardiac rehabilitation and exercise training on exercise capacity, coronary risk factors, behavioral characteristics, and quality of life in women. Am J Cardiol. 1995;75(5):340–3.CrossRefPubMedGoogle Scholar
  137. 137.
    Lerman A, Burnett JC Jr, et al. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation. 1998;97(21):2123–8.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Crea F, Camici PG, et al. Coronary microvascular dysfunction: an update. Eur Heart J. 2014;35(17):1101–11.CrossRefPubMedGoogle Scholar
  139. 139.
    Anderson GL, Limacher M, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004;291(14):1701–12.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Rossouw JE, Anderson GL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321–33.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Grady D, Herrington D, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: heart and estrogen/progestin replacement study follow-up (HERS II). JAMA. 2002;288(1):49–57.CrossRefPubMedGoogle Scholar
  142. 142.
    Hulley S, Grady D, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA. 1998;280(7):605–13.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Harman SM, Black DM, et al. Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial. Ann Intern Med. 2014;161(4):249–60.PubMedCrossRefGoogle Scholar
  144. 144.
    Hodis HN, Mack WJ, et al. Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med. 2016;374(13):1221–31.PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer International Publishing AG 2018

Authors and Affiliations

  • LaPrincess C. Brewer
    • 1
  • Rosalyn O. Adigun
    • 2
  • Sharon L. Mulvagh
    • 1
    • 3
  1. 1.Department of Cardiovascular MedicineMayo Clinic College of MedicineRochesterUSA
  2. 2.Cardiovascular Diseases Fellow, Department of Cardiovascular MedicineMayo Clinic College of MedicineRochesterUSA
  3. 3.Division of Cardiology, Department of MedicineDalhousie University, Nova Scotia Health AuthorityHalifaxCanada

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