Awareness of women’s heart health has increased, but more research, outreach required

Although it is the No. 1 killer of women, CVD has long been overlooked and underrepresented as a significant threat to women’s health. The common misconception that CVD primarily affects men has prevailed for most of modern medical history and, until as recently 2004, there was no large-scale public awareness campaign dedicated to women’s heart health.

“Prior to 2004, most women and many doctors — including cardiologists — thought that heart disease was a ‘man’s disease,’ and were not even looking for heart disease in women,” Gina Lundberg, MD, FACC, clinical director of Emory Women’s Heart Center at Emory University, told Cardiology Today. “Women just didn’t know heart disease was the No. 1 killer; they were more concerned with what is called ‘bikini medicine’ — breast cancer, uterine cancer, ovarian cancer. But we know that particularly after menopause, which, nowadays, is almost half your life, there is generally worsening of BP, cholesterol, diabetes and other CV risk factors.”

Over the past 20 years, campaigns such as the American Heart Association’s Go Red for Women campaign and the NHLBI’s Heart Truth program have brought public attention to the life-threatening reality of CVD in both sexes.

Most recently, the CV-related deaths of celebrities such as Carrie Fisher from cardiac arrest have reinforced this message to the public. Overall, clinicians agree that awareness of women’s heart health has advanced exponentially, but there is still room for improvement.

Source: Cleveland Clinic; reprinted with permission.

“The biggest stride we’ve made is increased awareness among physicians and patients in regards to women and heart disease,” Leslie Cho, MD, FACC, director of the Cleveland Clinic’s Women’s Cardiovascular Center, said. “This is due to tremendous work done by AHA physician and patient advocacy groups for the past decade-plus. However, women still come to the ED 30 minutes later with [MI] compared to men, and they don’t get screenings earlier.”

Broad reach

The increased awareness of women’s heart health over the years is the culmination of the tireless efforts of various research organizations, patient awareness initiatives and support groups.

“The AHA’s Go Red for Women campaign has done so much to increase awareness,” Nieca Goldberg, MD, cardiologist and director of the Joan H. Tisch Center for Women’s Health at NYU Langone Medical Center, told Cardiology Today.

A predecessor of AHA’s Go Red for Women campaign was the NHLBI’s Heart Truth program; both use a red dress as a logo.

In addition, Pamela S. Douglas, MD, professor of medicine and the Ursula Geller Professor for Research in Cardiovascular Disease at Duke University School of Medicine, said the WomenHeart initiative has made significant strides in training women’s heart health advocates.

“[The WomenHeart initiative has] a very robust women’s heart health advocate training program that has trained hundreds of women,” she told Cardiology Today.

Other groups have promoted women’s heart health though legislative advocacy, heart disease screening programs and funding of research on sex-based differences in CV issues (see Sidebar on next page).

Sex-specific patterns

In addition to the significant contributions made by these groups in alerting the public to the importance of women’s heart health, researchers have also gained ground in recent years to better understand the distinct physiological mechanisms of CVD in women.

“We have learned that there are various mechanisms for [MI] in women, that they don’t necessarily have typical obstructive disease where they need coronary stents,” Goldberg said. “In many cases, women have nonobstructive disease and their ischemia is due to microvascular ischemia, the smaller blood vessels.”

This knowledge was gleaned in part through the WISE study, which was sponsored by the NHBLI and conducted from 1996 to 2001, with multiple continuing projects, including WISE-CVD from 2009 to 2015.

“We have identified female-pattern ischemic heart disease, including coronary microvascular dysfunction, Takotsubo cardiomyopathy (also known as “broken heart syndrome”) and HF with preserved ejection fraction, but female-pattern ischemic heart disease is not yet adequately understood,” C. Noel Bairey Merz, MD, FACC, director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center and chair of the WISE study, said in an interview.

“We are also studying four adverse pregnancy outcomes in women, but we don’t yet have sufficient understanding of the mechanisms of these four outcomes, and we don’t yet have evidence-based therapies,” she said.

Bairey Merz and colleagues identified the four adverse pregnancy outcomes — pregnancy-induced hypertension, preeclampsia, eclampsia and gestational diabetes — in a 2015 report published in Seminars in Perinatology.

Cho said autoimmune disease, which occurs disproportionately in women, has been linked to CVD.

“Autoimmune disease is mostly a women’s disease — 80% of autoimmune patients are women, and most of these patients have two to three times increased risk for CVD,” she said. “We are still trying to understand why autoimmune disease — and thus increased inflammation, which increases risk for CVD — occurs so much more frequently in women.”

Debate on symptoms

The conventional wisdom in recent years is that women may overlook their own CVD due to more subtle symptoms than those experienced by men, particularly in the case of acute MI.

“Instead of the classic symptoms of tightness or pressure in the center of the chest that radiates down the arm and up the neck, women may be describing just extreme breathlessness, or the pressure is lower down in the chest so they mistake it for a stomach ailment, or upper back pressure,” Goldberg said.

According to Bairey Merz, a member of the Cardiology Today Editorial Board, “women are less likely to report chest pain and are more likely to report indigestion, shortness of breath and/or fatigue.”

However, Douglas said she is not entirely convinced that women’s heart disease symptoms are necessarily different from those of men, especially in cases of nonacute disease.

“Most of the past work was done on patients presenting with [MI] or patients with known CAD,” she said. “When people have dramatic ECG changes and abnormal blood enzymes, it’s not that hard to make the diagnosis. What is even harder is when someone presents with a less specific symptom, like a chest pain or shortness of breath. What we found was that the symptoms women were getting stress tests for were exactly the same as the ones men were getting stress tests for.”

In the study, Douglas and colleagues assessed 8,966 patients (4,720 women, 4,246 men) who underwent noninvasive testing in the PROMISE trial, a randomized study of assessment strategies in patients with suspected nonacute CAD. They found that although women with stable CAD had a higher risk factor burden vs. men, both sexes had a similar prevalence of chest pain.

“The women were presenting with chest pain symptoms; the symptoms were really not atypical or non-chest pain symptoms,” she said. “The myth is out there that women experience heart disease differently, and I’m not sure that’s true.”

Knowledge gaps remain

Although much more is known today about women’s heart health, both by patients and physicians, knowledge gaps remain.

Goldberg said a better understanding of the role stress plays in CV risk is needed. However, she said, one recent analysis of PET scans of the brains of people with emotional stress showed they had an increase in inflammatory factor, which confers elevated risk for atherosclerosis.

Women tend to handle stress differently, in ways that may not be healthy, according to Goldberg.

Despite widespread information on the hazards of smoking in terms of heart disease risk, Goldberg said this message may not be fully reaching younger women.

“I’m concerned about the issue of so many young people smoking, so it’s really important to counsel women on smoking cessation, and offer them assistance in what can be done, whether it’s pharmaceuticals, nicotine replacement or counseling,” she said. “A multifaceted approach is really needed.”

As a preventive cardiologist, Lundberg also emphasizes the importance of healthy lifestyles.

“That’s where we are missing out — women come in and they’re 55 years old, they’re 40 lb overweight, their BP is up, their cholesterol is elevated, and they ask, ‘What can I do?’” Lundberg said. “All I can think is, I wish when those patients had turned 40 [years old], they had started exercising and eating healthy.”

Management approaches

Although the ability to fully optimize CV care for women will be contingent on future studies, some information is known on sex-specific diagnostic and treatment approaches.

Douglas cited another recent study she and her colleagues conducted on the prognostic value of noninvasive imaging tests in women, specifically comparing regular stress testing to CT angiography.

“We found that there were many more positive stress tests in women than positive CT scans, and that a positive stress test meant less in terms of predicting new events, which is consistent with them being false positives,” she said. “What we determined is that it’s probably prognostically better when a woman gets symptoms suspicious for coronary disease to actually do a CT scan as opposed to doing a stress test, because the stress tests are so inaccurate in women.”

Bairey Merz noted that blood tests might also benefit from a sex-specific analysis. “There are data that demonstrate such tests should take sex into consideration. Most evident is the troponin blood test, in which the current male-pattern standards may miss as many as many as 20% of [MI] in women,” she said.

Dosing of certain medications may need to be adjusted to be suitable for women, who typically have a smaller body size than men, Douglas said.

Because women tend to report more side effects from CV drugs vs. men, this may be another area in which treatments may be customized to women, Goldberg said.

“It would be great for us to know, when the medicines are released ... whether the side-effect profile is different,” she said.

Intolerance of statins, among the most beneficial CV prevention medications, appears to be more common in women. One analysis found the most common cause of statin intolerance is myalgia, which been reported in about 20% of women in some studies.

Lundberg also emphasized the importance of recognizing and overcoming the sex-specific social factors that may obscure or delay a diagnosis of heart disease.

“We are working toward sex-specific outcomes, and we’re also looking at a lot of the social limiters of why women don’t get help,” she said. “Are they too busy taking care of their kids to be worried about their cholesterol and BP? Or are they too busy taking care of aging parents, or are they just unable to get time off work?”

Avenues of research

There are currently many aspects of women’s heart health that are being researched, and many more that will be investigated soon. Still, according to Goldberg, the most important priority in women’s heart health research is that it continues to be supported and funded.

“It’s not about which areas of research are pursued, but rather making sure we have researchers who devote their time to focusing on research efforts for women in heart disease,” she said.

Cho said she would like to see additional research on autoimmune diseases, as well as HFpEF. She added that research to gain a better understanding of the role of hormones in CV health would be important.

Hormones is an area that is not fully understood, according to Lundberg.

“We haven’t yet figured out the issue of whether hormones [are] actually protect us,” she said. “So the pendulum swings too far one way, then too far the other way.”

Some studies on hormones currently being conducted, including the KEEPS, ELITE and SMART studies, so far have yielded similar takeaways.

Although there is now more of a focus on including women in large studies, Lundberg said she would also like to see a shift in how data on women are analyzed.

For example, Cho said, “We still don’t have a good understanding of medication side effects, disease manifestation, and outcomes in women. This is because most of the studies have been done in men, and data extrapolated to women.”

Lundberg said as proud as she is of how much women’s heart health has advanced over the years, she ultimately looks forward to the day when the field advances beyond “women’s heart health.”

“Our long-term goal is that all patients get excellent care regardless of gender or race or ethnicity,” she said. “My dream is that one day we don’t have to talk about heart disease in women, because it will be recognized and treated appropriately in all individuals.” – by Jennifer Byrne

• References:
• Hemal K, et al. JACC Cardiovasc Imaging. 2016;doi:10.1016/j.jcmg.2016.02.001.
• Mehta PK, et al. Semin Perinatol. 2015;doi:10.1053/j.semperi.2015.05.005.
• Nguyen PK, et al. J Nucl Cardiol. 2010;doi:10.1007/s12350-010-9315-2.
• Pagidipati NJ, et al. J Am Coll Cardiol. 2016;doi:10.1016/j.jacc.2016.03.523.
• Shaw LJ, et al. J Am Coll Cardiol. 2006;doi:10.1016/j.jacc.2005.01.072.
• Tawakol A, et al. Lancet. 2017;doi:10.1016/S0140-6736(16)31714-7.
• Zhang H, et al. Ann Intern Med. 2013;doi:10.7326/0003-4819-158-7-201304020-00004.

• For more information:
• C. Noel Bairey Merz, MD, FACC, can be reached at Advanced Health Sciences Pavilion, A3600 127 S. San Vicente Blvd., Los Angeles, CA 90048; email: noel.baireymerz@cshs.org.
• Leslie Cho, MD, FACC, can be reached at G Building, 9500 Euclid Ave., Cleveland, OH 44195; email: chol@ccf.org.
• Pamela S. Douglas, MD, can be reached at 7022 North Pavilion DUMC, Durham, NC 27715; email: pamela.douglas@duke.edu.
• Nieca Goldberg, MD, can be reached at 207 E. 84th St., New York, NY 10128; email: nieca.goldberg@nyumc.edu.
• Gina Lundberg, MD, FACC, can be reached at 137 Johnson Ferry Road SE #1200, Marietta, GA 30068; email; gina.lundberg@emory.edu.

Disclosures: Bairey Merz reports honoraria and/or consultant fees were paid to her institution by Kaiser Permanente, Practice Point Communications, PriMed and Sanofi. Cho, Douglas and Lundberg report no relevant financial disclosures. Goldberg reports receiving honoraria from Sanofi.