Cardiology Today Anniversary

2 decades of women-patterned heart disease

A Cardiology Today Editorial Board Member discusses how far cardiologists have come in managing heart disease in women.

Editor’s Note: Cardiology Today is celebrating its 20th anniversary in 2017. We are reaching out to experts in cardiology for their take on changes in CV medicine since the publication launched in 1997. In this issue, C. Noel Bairey Merz, MD, FACC, FAHA, FESC, focuses on women-patterned heart disease.

Twenty years ago, our understanding of women-patterned heart disease was pretty close to zero, with the exception of what we called cardiac syndrome X. That was the genesis of NHLBI’s decision to fund the WISE study. Patients with cardiac syndrome X were overwhelmingly women. They had angina and an abnormal stress test, but they had normal angiograms. Calling it “syndrome X” meant we did not know what it was.

Major advances

The advances in our understanding of women-patterned heart disease over the past 20 years have been huge. They were nicely summarized by Cardiology Today Editorial Board Member Nanette K. Wenger, MD, MACC, MACP, FAHA, when she won the American Heart Association’s James B. Herrick Award in 2012; her address was published in Circulation.

Such advances include that CHD risk is higher in women with diabetes than in men with diabetes; women with CHD have more unfavorable outcomes than men with CHD, including a higher risk for death after MI; women have a greater burden of angina but less severe obstructive CAD than men; women with stable CHD have more MIs than men with stable CHD; among patients with ACS, women undergo angiography, PCI and CABG less often than men; absence of obstructive CAD, more common in women, contributes to underutilization of optimal medical therapy; the WISE study identified that coronary microvascular disease and myocardial ischemia without obstructive CAD are common in women; and among patients with MI, women are more likely than men to have recurrent MIs or HF.

C. Noel Bairey Merz, MD, FACC, FAHA, FESC
C. Noel Bairey Merz

We learned much because of WISE, but other investigators replicated our results and extended them beyond coronary microvascular dysfunction to include conditions such as takotsubo cardiomyopathy, which was essentially unrecognized in the United States 20 years ago; spontaneous coronary artery dissection, or SCAD, which primarily impacts women, could account for as many as 3% to 5% of all MIs in women, and may not be optimally treated with traditional methods such as stenting; and HF with preserved ejection fraction. Twenty years ago, HFpEF was a blip on the radar screen and thought to be false-positive HF. It was thought that the patient could not possibly be in HF if they had normal EF.

Improvements in treatment

We are doing better in treating women with heart disease thanks to guidelines recommending optimal medical therapy and therapeutic lifestyle change. Twenty years ago, women were consistently identified late, often identified as having false-positive MIs, and less likely treated with guideline-directed therapies. Because of electronic health records and quality initiatives, we are now judged on use of guideline therapies, which is good. That has altered the trajectory of heart disease for women by closing treatment gaps. Finally, women are getting treated with optimal medical therapy and therapeutic lifestyle change. The most recent AHA report on CVD annual deaths per capita shows that men and women are now equal. There was an epidemic of a surplus of CVD deaths in women starting in the 1980s; 1984 was when the curves crossed. In 2015, the most recent year for which data are available, we are back to parity. Prior to the 1980s, women had fewer CVD deaths than men, so parity is probably not what would happen if we fully understood women-patterned heart disease and treated women according to evidence-based guidelines.

Gaps remain

Going forward, we will continue to work to close both knowledge and treatment gaps. One area of persistent and growing gaps is in premenopausal women younger than 55 years. The VIRGO study clearly demonstrated that younger women with MI are less treated, and if they are diabetic, they were more likely to be told to lose weight, while men with diabetes, who were more overweight, were more often provided with statins prior to the MI. This is an indicator of gender bias in the use of evidence-based guidelines.

A survey by the Women’s Heart Alliance also demonstrated that physicians still do not rank CVD as the top health care concern for women. Heart disease remains rated after breast cancer and weight management. We have a physician education gap that continues to need to be addressed.

The WISE investigators and others are looking to conduct randomized controlled trials to specific female phenotypes to understand and inform guidelines. For example, Cardiology Today Chief Medical Editor Carl J. Pepine, MD, MACC, and I were recently awarded funding for the WARRIOR trial by the Department of Defense. This will be a 4-year randomized controlled trial of women with signs and symptoms of ischemia but no obstructive CAD, who will be randomly assigned to receive therapies that we found in pharmacologic probe trials to be effective for coronary microvascular dysfunction, including high-intensity statins and maximally tolerated ACE inhibitors or angiotensin receptor blockers plus a baby aspirin.

We need to do a lot more work on HFpEF. Research is proceeding at a snail’s pace and the patient population is still predominantly women, although men are catching up.

– C. Noel Bairey Merz, MD, FACC, FAHA, FESC

Cardiology Today Editorial Board Member

Cedars-Sinai Heart Institute

Disclosure: Bairey Merz reports honoraria and/or consultant fees were paid to her institution by Kaiser Permanente, Practice Point Communications, PriMed and Sanofi.

Editor’s Note: Cardiology Today is celebrating its 20th anniversary in 2017. We are reaching out to experts in cardiology for their take on changes in CV medicine since the publication launched in 1997. In this issue, C. Noel Bairey Merz, MD, FACC, FAHA, FESC, focuses on women-patterned heart disease.

Twenty years ago, our understanding of women-patterned heart disease was pretty close to zero, with the exception of what we called cardiac syndrome X. That was the genesis of NHLBI’s decision to fund the WISE study. Patients with cardiac syndrome X were overwhelmingly women. They had angina and an abnormal stress test, but they had normal angiograms. Calling it “syndrome X” meant we did not know what it was.

Major advances

The advances in our understanding of women-patterned heart disease over the past 20 years have been huge. They were nicely summarized by Cardiology Today Editorial Board Member Nanette K. Wenger, MD, MACC, MACP, FAHA, when she won the American Heart Association’s James B. Herrick Award in 2012; her address was published in Circulation.

Such advances include that CHD risk is higher in women with diabetes than in men with diabetes; women with CHD have more unfavorable outcomes than men with CHD, including a higher risk for death after MI; women have a greater burden of angina but less severe obstructive CAD than men; women with stable CHD have more MIs than men with stable CHD; among patients with ACS, women undergo angiography, PCI and CABG less often than men; absence of obstructive CAD, more common in women, contributes to underutilization of optimal medical therapy; the WISE study identified that coronary microvascular disease and myocardial ischemia without obstructive CAD are common in women; and among patients with MI, women are more likely than men to have recurrent MIs or HF.

C. Noel Bairey Merz, MD, FACC, FAHA, FESC
C. Noel Bairey Merz

We learned much because of WISE, but other investigators replicated our results and extended them beyond coronary microvascular dysfunction to include conditions such as takotsubo cardiomyopathy, which was essentially unrecognized in the United States 20 years ago; spontaneous coronary artery dissection, or SCAD, which primarily impacts women, could account for as many as 3% to 5% of all MIs in women, and may not be optimally treated with traditional methods such as stenting; and HF with preserved ejection fraction. Twenty years ago, HFpEF was a blip on the radar screen and thought to be false-positive HF. It was thought that the patient could not possibly be in HF if they had normal EF.

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Improvements in treatment

We are doing better in treating women with heart disease thanks to guidelines recommending optimal medical therapy and therapeutic lifestyle change. Twenty years ago, women were consistently identified late, often identified as having false-positive MIs, and less likely treated with guideline-directed therapies. Because of electronic health records and quality initiatives, we are now judged on use of guideline therapies, which is good. That has altered the trajectory of heart disease for women by closing treatment gaps. Finally, women are getting treated with optimal medical therapy and therapeutic lifestyle change. The most recent AHA report on CVD annual deaths per capita shows that men and women are now equal. There was an epidemic of a surplus of CVD deaths in women starting in the 1980s; 1984 was when the curves crossed. In 2015, the most recent year for which data are available, we are back to parity. Prior to the 1980s, women had fewer CVD deaths than men, so parity is probably not what would happen if we fully understood women-patterned heart disease and treated women according to evidence-based guidelines.

Gaps remain

Going forward, we will continue to work to close both knowledge and treatment gaps. One area of persistent and growing gaps is in premenopausal women younger than 55 years. The VIRGO study clearly demonstrated that younger women with MI are less treated, and if they are diabetic, they were more likely to be told to lose weight, while men with diabetes, who were more overweight, were more often provided with statins prior to the MI. This is an indicator of gender bias in the use of evidence-based guidelines.

A survey by the Women’s Heart Alliance also demonstrated that physicians still do not rank CVD as the top health care concern for women. Heart disease remains rated after breast cancer and weight management. We have a physician education gap that continues to need to be addressed.

The WISE investigators and others are looking to conduct randomized controlled trials to specific female phenotypes to understand and inform guidelines. For example, Cardiology Today Chief Medical Editor Carl J. Pepine, MD, MACC, and I were recently awarded funding for the WARRIOR trial by the Department of Defense. This will be a 4-year randomized controlled trial of women with signs and symptoms of ischemia but no obstructive CAD, who will be randomly assigned to receive therapies that we found in pharmacologic probe trials to be effective for coronary microvascular dysfunction, including high-intensity statins and maximally tolerated ACE inhibitors or angiotensin receptor blockers plus a baby aspirin.

We need to do a lot more work on HFpEF. Research is proceeding at a snail’s pace and the patient population is still predominantly women, although men are catching up.

– C. Noel Bairey Merz, MD, FACC, FAHA, FESC

Cardiology Today Editorial Board Member

Cedars-Sinai Heart Institute

Disclosure: Bairey Merz reports honoraria and/or consultant fees were paid to her institution by Kaiser Permanente, Practice Point Communications, PriMed and Sanofi.

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