State-of-the-Art Paper
Women and Ischemic Heart Disease: Evolving Knowledge

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Evolving knowledge regarding sex differences in coronary heart disease is emerging. Given the lower burden of obstructive coronary artery disease (CAD) and preserved systolic function in women, which contrasts with greater rates of myocardial ischemia and near-term mortality compared with men, we propose the term “ischemic heart disease” as appropriate for this discussion specific to women rather than CAD or coronary heart disease (CHD). This paradoxical difference, where women have lower rates of anatomical CAD but more symptoms, ischemia, and adverse outcomes, appears linked to abnormal coronary reactivity that includes microvascular dysfunction. Novel risk factors can improve the Framingham risk score, including inflammatory markers and reproductive hormones, as well as noninvasive imaging and functional capacity measurements. Risk for women with obstructive CAD is increased compared with men, yet women are less likely to receive guideline-indicated therapies. In the setting of non–ST-segment elevation acute myocardial infarction, interventional strategies are equally effective in biomarker-positive women and men, whereas conservative management is indicated for biomarker-negative women. For women with evidence of ischemia but no obstructive CAD, antianginal and anti-ischemic therapies can improve symptoms, endothelial function, and quality of life; however, trials evaluating impact on adverse outcomes are needed. We hypothesize that women experience more adverse outcomes compared with men because obstructive CAD remains the current focus of therapeutic strategies. Continued research is indicated to devise therapeutic regimens to improve symptom burden and reduce risk in women with ischemic heart disease.

Key Words

ischemic heart disease
sex differences
women

Abbreviations and Acronyms

ACE
angiotensin-converting enzyme
ACS
acute coronary syndrome
CAC
coronary artery calcium
CAD
coronary artery disease
CCTA
coronary computed tomographic angiography
CHD
coronary heart disease
cIMT
carotid intima-media thickness
CMR
cardiac magnetic resonance
CRP
C-reactive protein
CVD
cardiovascular disease
FRS
Framingham Risk Score
hsCRP
high-sensitivity C-reactive protein
IHD
ischemic heart disease
MET
metabolic equivalent
MI
myocardial infarction
PCI
percutaneous coronary intervention
PET
positron emission tomography
STEMI
ST-segment myocardial infarction

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Dr. Shaw received grant support from GE Healthcare and Bracco Diagnostics. Dr. Merz has done consulting for Novartis, Karolinska Institute, Strategy Group, University of Pittsburgh, Pfizer, Biological Systems Processing, Kendle Internation, Inc., and the National Heart, Lung, and Blood Institute; received lecture honoraria for Northwestern University, University of California-Davis, Abbott Laboratories, CV Therapeutics, Boehringer Ingelheim, American College of Physicians, ProMedica, Mayo Clinic, and Merck; and owns stock in Boston Scientific, Medtronic, Johnson & Johnson, and Teva Pharmaceuticals. This work was supported by National Heart, Lung, and Blood Institute contracts N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, R01 HL090957-01A1, and R03 AG032631-01; a GCRC grant MO1-RR00425 from the National Center for Research Resources; and grants from the Gustavus and Louis Pfeiffer Research Foundation, Danville, New Jersey; the Women's Guild of Cedars-Sinai Medical Center, Los Angeles, California; the Edythe L. Broad Women's Heart Research Fellowship, Cedars-Sinai Medical Center, Los Angeles, California; and the Barbra Streisand Women's Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles, California.