The Curbsiders podcast

#153 Heart Disease in Women with Dr Bairey Merz

June 3, 2019 | By

Rethink the paradigm of coronary artery disease in women

Expand your idea of ischemic heart disease to include non-obstructive patterns, which as our guest, Dr Noel Bairey Merz, a clinical investigative cardiologist whose multiple roles include Director of the Barbra Streisand Women’s Heart Center and the Preventive Cardiac Center at the Smidt Cedars-Sinai Heart Institute, shares with us, is incredibly common, especially in women.  Learn to recognize heart disease in women and treat according to guidelines, preventing unnecessary IHD mortality in our female (and some male) patients. We review a variety of non-obstructive pathologies and the best techniques to evaluate them.

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Written and produced by: Shreya Trivedi MD, Molly Heublein MD

Hosts: Paul Williams MD, FACP; Shreya Trivedi MD; Molly Heublein MD

Edited by: Matthew Watto MD, FACP; Emi Okamoto MD

Graphics by: Hannah Abrams

Guest: Dr. C Noel Bairey Merz MD, FACC, FAHA

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Time Stamps

  • 00:00 Intro, disclaimer and guest bio
  • 04:36 Guest one-liner; Advice for success in research and clinical practice
  • 07:07 A case of shortness of breath and chest tightness; Why the paradigm of obstructive coronary artery disease is flawed.
  • 12:04 Why is there a sex difference in ischemic heart disease?
  • 14:52 How to recognize ischemic heart disease in women; Are certain symptoms more likely in women; Categorizing angina
  • 20:13 Who needs stress testing?; Screening for ischemic heart disease in women
  • 24:52 How guidelines make good doctors great doctors
  • 27:00 Diagnosis of NSTEMI in a woman without obstructive coronary disease
  • 29:33 Medical therapy for non-obstructive ischemic heart disease
  • 33:18 Additional testing: Cardiac MRI for myocarditis; perfusion reserve testing; CT coronary angiograms
  • 35:48 How current non-invasive techniques fail to identify microvascular ischemic heart disease in women
  • 39:10 Antianginal therapy
  • 41:40 HFpEF in women
  • 47:10 Weight loss for paroxysmal atrial fibrillation
  • 48:45 New nomenclature for ischemic heart disease
  • 50:18 Take home points
  • 52:40 Outro

Heart Disease in Women Pearls

  1. Cardiovascular disease is the leading cause of death among women.
  2. Don’t overlook a heart attack in women- chest pain with EKG changes and a troponin rise is an MI even with clean coronaries.  We need to label it correctly, find out the underlying diagnosis, and treat it.
  3. Focusing on obstructive coronary artery disease misses 30-40% of women and 5-10% of men with ischemic heart disease (IHD).
  4. Expand your differential of IHD to include MINOCA (MI with nonobstructive coronary arteries) which is an umbrella term to include microvascular disease, dissection, myocarditis, and others.
  5. Don’t ignore chest pain in women with risk factors, women with atypical chest pain are just as likely to have ACS as those with typical angina.  
  6. Start evaluation with a stress EKG in most patients, but consider next step evaluations like coronary CTA or coronary MRI to help evaluate further in persistently symptomatic patients.
  7. Routinely following guidelines helps us overcome our implicit biases that disadvantage women.
Heart disease in women in different. Graphic by Hannah R Abrams
Heart disease in women in different. Inforaphic by Hannah R Abrams

Heart disease in women is different.

The paradigm of ischemic heart disease (IHD) has been focused on obstructive atherosclerosis of the large epicardial arteries. Our stress imaging looks at wall motion abnormalities caused by blockages in the large coronary arteries, and interventional cardiology focuses on addressing these. This paradigm misses 30-40% of women with heart disease and

5-10% of men, because it overlooks nonobstructive coronary disease (Galuti 2012).

A woman with chest pain, EKG changes (including STEMI), and an elevated troponin has had a myocardial infarction, even without evidence of obstructive coronary arteries on catheterization  (Bugiardini, 2005).  This meets WHO criteria for an MI (Mendis, 2011), and should be labeled, diagnosed, and treated appropriately.

Words Matter

Think about shifting our language, ischemic heart disease is a more encompassing term, as opposed to coronary artery disease (CAD) or coronary heart disease (CHD) which focuses on obstructive disease.

Women and men lay down atherosclerotic plaque differently

Think of how reproductive hormones influence fat deposition: men with focal visceral fat/abdominal obesity vs. women with diffuse obesity.  

Male pattern ischemic heart disease- “lumpy bumpy” plaque, followed by remodeling, which is visible on angiography sooner.

Female pattern ischemic heart disease–  diffuse, smooth, concentric atherosclerosis which is sometimes invisible to angiography.

Hypotheses as to why sex differences in ischemic heart disease exist

Hormones probably have an impact. The balance of sex hormones (testosterone/estrogen) predicts IHD risk. (Zhao 2018)

Women have different patterns of vascular dysfunction and constriction (including more prone to migraines and Raynaud’s). (Sullivan 2018)

Immune mediated changes occur, driving inflammation in different ways between the sexes.  (Fairweather 2015)


Myocardial infarction with non-obstructive coronary arteries (MINOCA) is an umbrella term which includes diverse etiologies including microvascular changes, spontaneous coronary artery dissection (SCAD), vasospastic angina, plaque rupture or erosion, thromboembolism, takotsubo cardiomyopathy, unrecognized myocarditis, and other forms of type-2 myocardial infarction (Agewall 2017). It is important to continue to try to differentiate the underlying cause as it changes treatment.

Atherosclerotic Disease

10-15% of NSTEMI and 5% of STEMI are MINOCA (Agewall 2017). These should be treated with guideline therapy.

Spontaneous Coronary Artery Dissection

The true prevalence of spontaneous coronary artery dissection (SCAD) is not known, but is more common in younger women, maybe 20% of MI in this demographic is SCAD. Treatment is just aspirin (no need to treat with statins), and patients are not usually left with persistent chest pain.  (Ahmed 2017)


Myocarditis is another cause for chest pain and positive troponin. Cardiac MRI may show evidence this. (Dastidar 2015)


Embolism to coronaries can cause MINOCA, often due to underlying autoimmune disease, valvular disease, or arrhythmia. (Agewall 2017)

Symptoms of ischemic heart disease

Typical angina (substernal pressure, worse with exercise/stress, relieved with rest/nitroglycerin),  atypical angina (two of three characteristics of typical angina), and non-anginal (one or no characteristics of typical angina) chest pain do not reliably differentiate cardiac from noncardiac chest pain (Herman 2010). Do not ignore non-classical chest pain.  

Women may complain of more rest chest pain, particularly when under stress. Seattle Angina Questionnaire can improve diagnosis and treatment.


Stress testing

Any women over age 50 and men over age 40 with new chest pain should be evaluated- they are at intermediate risk of ischemic heart disease. Guidelines suggest if the patient can walk and has a normal resting EKG, the first choice option is an exercise EKG stress test (Wolk 2014).

Stress testing provides clinically valuable points of information:

  1. Poor functional capacity (if patient cannot get out of 2 stages of a 6 minute Bruce Protocol, this is poor predictor)
  2. Reproduction of symptoms (angina, dyspnea)
  3. ST segment changes
  4. Abnormal imaging response (if obtained)

These 4 elements are all useful in predicting the likelihood of IHD, and any abnormality can be clinically significant. Review the stress tests carefully, as often risk determination is focused on only imaging.   

Use the Duke treadmill score to help calculate risk.

Coronary CT angiography

If the patient cannot exercise or has an abnormal resting EKG, guidelines suggest coronary CT angiography (CCTA) as an alternative option (Wolk 2014). The SCOT-HEART trial showed that adding CCTA to standard care had an advantage of improved mortality, driven by more treatment in the CCTA group.

Dr Merz reminds us that a CCTA may be read as “normal”- not showing significant blockage- but could still show calcified or noncalcified plaque more diffusely.  She recommends it is important to review the full report and/or discuss with a radiologist or cardiologist.

Coronary imaging often focuses on male pattern/obstructive CAD

Invasive coronary angiography is a lumenogram- all you see is the dye, not the walls of the artery which primarily identifies obstructive CAD.

Echocardiograms show wall motion abnormality- microvascular dysfunction is often homogeneous, if many arterioles are involved- can miss ⅔ of microvascular disease (Nihoyannopoulos 1991; Mittal 2015).  

SPECT- compares normal to abnormal, just like you can miss triple vessel disease you can miss microvascular disease (Cassar 2009).  


In a patient with normal evaluation but persistent symptoms, Dr Merz suggests considering cardiac MRI or PET which can be more sensitive for microvascular perfusion abnormalities and finding other pathologies.  


AHA/ACC guidelines for secondary prevention in patients who have had acute coronary syndrome: Prescribe the 4 “magic pills” 1. low dose aspirin,  2. ACE-I/ARB (for HTN or for infarct/wall motion abnormality), 3. beta-blockers (for persistent symptoms), 4. high intensity statin (20-40 mg of rosuvastatin, 40-80 mg of atorvastatin) to reduce recurrence and morbidity.

Disparities in treating heart disease in women are improving.

Through the 1980s-1990s, a significant health disparity existed, with more women dying of coronary vascular disease than men.  The VIRGO study evaluated women and men who both had early MI. This study evaluated a large population with MINOCA, and noted health disparities in treatment, with lower rates of appropriate secondary prevention treatment prescriptions (Safdar 2018).

Follow Your Guidelines

Dr Merz feels “Guidelines make good doctors great doctors, and make good health systems great health systems.”  Being aware of guidelines and using electronic health records to trigger reminders for treatment can help make sure everyone receives appropriate care, and has helped level outcomes for women with ischemic heart disease.

Therapy in Reproductive-Age Women

Dr Merz feels reproductive-age women should be trusted to control their contraception. A shared decision making discussion should happen- if a woman is high risk, don’t automatically withhold medication (ie statin) even if young.

Goals and Learning Objectives


Listeners will rethink their understanding of ischemic heart disease and learn the basics of diagnosis and management for myocardial infarction with nonobstructive coronary artery disease in women.

Learning Objectives

After listening to this episode listeners will…

  1. Describe how ischemic heart disease presents differently in women than men
  2. Recognize the importance of changing language to ischemic heart disease instead of coronary artery disease
  3. Differentiate the risk-stratification modalities that may be more valuable in women
  4. Appreciate in the health disparities in the way women are managed
  5. Recognize the best practices in management of women with heart disease


Dr Bairey Merz reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.

  1. Gulati, Martha et al. Myocardial ischemia in women: lessons from the NHLBI WISE study. Clinical cardiology vol. 35,3 (2012): 141-8. doi:10.1002/clc.21966
  2. Bugiardini R and Bairey Merz CN. Angina with “normal” coronary arteries: a changing philosophy. JAMA. 2005. []
  3. Mendis S et al. World Health Organization definition of myocardial infarction: 2008-2009 revision. Int J Epidemiol. 2011. []
  4. Bairey Merz CN et al. Insights from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study: Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease. J Am Coll Cardiol. 2006. []
  5. Shaw LJ 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. 2006. []
  6. Safdar B et al. Presentation, Clinical Profile, and Prognosis of Young Patients With Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): Results From the VIRGO Study. J Am Heart Assoc. 2018. []
  7. Hermann LK et al. Comparison of frequency of inducible myocardial ischemia in patients presenting to emergency department with typical versus atypical or nonanginal chest pain. Am J Cardiol. 2010. []
  8. Fairweather D. Sex differences in inflammation during atherosclerosis. ClinMed Insights Cardiol. 2015. []
  9. Ahmed, B. and Creager, M. A. Alternative causes of myocardial ischemia in women: An update on spontaneous coronary artery dissection, vasospastic angina and coronary microvascular dysfunction. Vascular Medicine. 2017. [[]
  10. Dastidar AG et al. The Role of Cardiac MRI in Patients with Troponin-Positive Chest Pain and Unobstructed Coronary Arteries. Curr Cardiovasc Imaging Rep. 2015 []
  11. Stefan Agewall et al. ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. European Heart Journal. 2017. []
  12. Chan PS et al. Development and validation of a short version of the Seattle angina questionnaire. Circ Cardiovasc Qual Outcomes. 2014/ []
  13. Wolk MJ et al. ACCF/AHA/ASE/ASNC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2013 multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease. J Am Coll Cardiol. 2014. []
  14. Sullivan S et al. Sex Differences in Hemodynamic and Microvascular Mechanisms of Myocardial Ischemia Induced by Mental Stress. Arterioscler Thromb Vasc Biol. 2018. []
  15. Zhao D et al. Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women. J Am Coll Cardiol. 2018. []
  16. Kushner FG et al. 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention. Circulation. 2009. []
  17. SCOT-HEART Investigators et al. Coronary CT Angiography and 5-Year Risk of Myocardial Infarction. N Engl J Med. 2018. []
  18. Anderson JL et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction. J Am Coll Cardiol. 2007. []


Bairey Merz, C Noel. “#153 Heart Disease in Women”. The Curbsiders Internal Medicine Podcast June 3, 2019

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