COMMENTARY

Heart Disease: What's Bad for the Goose Is Bad for the Gander

Henry R. Black, MD; Martha Gulati, MD

Disclosures

September 14, 2015

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Henry R. Black, MD: Hi. I'm Dr Henry Black, adjunct professor of medicine at the New York University Langone School of Medicine. I'm here with my friend and colleague, Dr Martha Gulati. Martha, welcome.

Martha Gulati, MD: Thank you.

Dr Black: Tell us a little bit about what you do in Columbus and elsewhere.

Dr Gulati: I'm associate professor of cardiology and clinical public health at Ohio State University in Columbus, Ohio. I'm the section director of Preventive Cardiology and Women's Cardiovascular Health, so I study women, take care of women, and try to prevent heart disease in women.

CVD Risk Factors in Women vs Men

Dr Black: We worked together in the past, and among the things that you taught me—and I want you to expound on this a little bit—was whether risk factors for cardiovascular disease are different in men and women.

Dr Gulati: The traditional risk factors are pretty much the same for men and women. When you think of the common risk factors for heart disease—smoking, diabetes, high blood pressure, high cholesterol, and poor fitness level—all of them are related to heart disease in both men and women. But there are gender-specific differences.

For example, smoking adversely affects women more than it does men. If you are a woman who smokes a pack of cigarettes per day, your risk for cardiovascular events is much greater than a man's risk for the same amount of cigarettes. It's the same with diabetes. Diabetes adversely affects women and men, but more so for women.

We now have data as of this year from a very nice study[1] that came out showing that women with type 1 diabetes have a greater risk for cardiovascular disease compared with men with type 1 diabetes. It's important to know those differences.

You and I did work on fitness level and its relationship to mortality and cardiovascular disease in women,[2] and we were able to show that it also is more strongly associated with mortality in women than in men, meaning that poor fitness affects women's hearts more so than it does men's hearts.

Dr Black: The conventional teaching was that women have a sort of 10-year "grace period" before they develop heart disease at the same time as men. It was blamed on menopause or when menopause occurs. Do we still think that that is true?

Dr Gulati: We still think that is true. The sad part, though, for the United States, is that the 10 years is still a little bit of a lag for women as a mean age. The fact is that we are seeing heart disease at younger and younger ages.

I wanted to go back to one thing about the risk factors. Something that I left out is that there are certain gender-specific risk factors, and those risk factors are unique to women. They are things that just don't happen to men.

For example, preeclampsia, which is hypertension during pregnancy, is related to an increased risk for cardiovascular disease. Gestational diabetes is also now noted as a risk factor for cardiovascular disease. There are other things, such as polycystic ovary syndrome, that we think of as equivalent to the metabolic syndrome. Again, these would only happen in women, so it's important to recognize those risk factors.

Other things that also happen more frequently in women are autoimmune diseases, such as lupus and rheumatoid arthritis. These are now noted as risk factors for cardiovascular disease, but they occur disproportionately in women compared with men.

And breast cancer is obviously more of a woman's disease (not that it can't happen in men). Its relationship to heart disease is becoming more and more clear in the sense that not only do risk factors for breast cancer overlap with risk factors for heart disease, but the treatment that you receive for breast cancer, such as radiation, can accelerate your risk for cardiovascular disease. Chemotherapy agents can cause more risk for heart failure.

So it's important that we ask all those questions when we're talking to a patient and trying to assess their risk.

Differences in Treatment

Dr Black: You talk about treatment. In general, is it different for men vs women who have conventional risk factors? Do we use different lipid-lowering agents or different antihypertensives in men and women, or is it pretty much the same?

Dr Gulati: Treatments for the risk factors are the same. Nothing has shown that gender would guide specific therapy. But I think the problem is related to whether we treat women as aggressively as we do men.

Dr Black: It's interesting now that we're sort of backing off a little bit on aggressive therapy for blood pressure. Maybe not so for lipids, but it certainly is for blood pressure. Does that apply to women, too? Are women better off if we aren't as aggressive?

Dr Gulati: I think we are at fault for both. We don't treat women as aggressively in general, and we also don't treat men and women as aggressively as we should. Some new guidelines[3] that came out last year have stirred the pot a little and gave people leniency to not treat as aggressively. I think that will actually increase cardiovascular disease.

Microvascular Disease

Dr Black: I agree with you. I think we've backed off without any evidence that it was a good idea.

How about the pathophysiology? Is that likely to be the same in men and women?

Dr Gulati: That's what is most interesting to me right now about cardiovascular disease and women. When we have talked about ischemic heart disease, most people thought we were talking about obstructive coronary artery disease, meaning that you had to have a ≥ 70% lesion in your coronary vessel to actually have symptoms of angina. So when we sent a patient down to the cath lab and they didn't have an obstructive lesion, we would falsely determine that it was a false-positive.

And who were those patients? They were mostly women. In fact, it's very common that even after a heart attack or after having an abnormal stress test, women are less likely to have obstructive coronary disease.

As work evolved, we have been showing that it might actually be [lesions in] the small blood vessels, or microvascular disease, that could be causing ischemia. We have been doing studies in the cath lab measuring flow, but I think the area that is getting very interesting is not invasive testing, but doing exercise stress testing with a cardiac MRI. That's what we're doing to tease out ischemia. We are getting images where we are seeing that the subendocardial area is not getting good blood flow.

Dr Black: I see. What would you do about that if you found it?

Dr Gulati: Currently, the guidelines are saying that if patients have evidence of ischemia, we treat them like they have coronary disease. Right now, we don't know whether there is a gender-specific treatment for someone with microvascular disease. That's what the research right now is looking at. Are there drugs or medications that work specifically at the small vessels that might be unique to that population?

I'm not saying that only women get that; it's just far more common in women. But even for men, are there drugs that would target that? There are many different tests and studies going on right now that are trying to tease that out, but we don't have the answers just yet.

Statins: Good for the Goose and the Gander?

Dr Black: How about lipids or antilipid therapy? Is that different between men and women? Women are generally thought to have higher levels of high-density lipoprotein cholesterol (HDL-C), but that sort of evens out after menopause, I believe. Is that right?

Dr Gulati: Yes, that is right. HDL-C has been thought of as protective, but it's only one player, and more and more, we're getting focused on low-density lipoprotein cholesterol (LDL-C). There is something about LDL-C that increases your risk for cardiovascular disease.

With that being said, we do know that people hesitate to use statins in women. I think a lot of that, for both patients and physicians, comes from the fact that we didn't include enough women in trials. When you look at those studies, you will see that either the results were not statistically significant in women (if they did a sex analysis) or they didn't do a sex analysis. Many studies just chose not to do a sex analysis, or they didn't include women in their studies.

When you summarize as best as you can with a meta-analysis,[4] it really does show that statins reduce cardiovascular disease events, both in primary and secondary prevention in women. Right now, until we have better data, I think it's safe to use the drugs in women and to use them in the same way that we use them in men.

Do I think we need other studies on cholesterol? I think we do. I think that would put an end to all the questions and controversy within the medical community about the effectiveness of statins in women.

Obesity and Fat Distribution

Dr Black: What about obesity and being overweight? Is that more common in women now, or is the fat distribution different? And how do we address that?

Dr Gulati: Unfortunately, obesity is an epidemic in the United States, and it is more likely that a woman is obese compared with men in the US population. Whether obesity in and of itself a risk factor for heart disease is hard for us to say, because obesity tends to be linked to such things as diabetes, high blood pressure, and high cholesterol (not in everyone, but in the majority). It's hard to say for certain that obesity is a risk factor, but it is associated with all the other risk factors that we've talked about.

The type of fat distribution definitely seems to matter—for example, the metabolic syndrome, where you carry your weight in the center of your abdomen, where your stomach enters the room before you do. If you have that type of pattern, we know that it is associated with a greater risk not just for heart disease but also for diabetes, so you get two strikes against you for that. Measuring that should be part of a cardiac risk assessment.

I think a lot of us just look at body mass index (BMI), but measuring the waist circumference should really be part of our exam. For women, if the waist circumference is above 35 inches, they are in the danger zone, and for men, it's above 40 inches.

Better Training of Physicians, New and Old

Dr Black: Great. What do you think are the primary issues in getting more women involved not only in trials, which you mentioned is very important, but how do you get more women to become cardiologists and be in leadership in that area? What do you think is the trick?

Dr Gulati: I think there are so many reasons why women aren't getting the right treatment, and it's beyond just training women. I think it's about training all physicians to understand that women are at risk. It really comes down to primary care physicians. Whether women turn to their ob/gyn doctors as their primary care physicians, family physicians, or internists, everyone needs to come with a basic education and understand that women are at risk and that cardiovascular disease is their number-one killer.

From a cardiologist's standpoint, do we need to train more women? Absolutely. I think we should have more women in this field to make it more diverse and able to take care of both men and women adequately.

The differences in what's going on in women and why more women are dying of heart disease than men actually has to do with a lot of other things. There is a lot of bias in medicine, and we all know we have biases. We should be aware of them.

We know from national data—the Get With the Guidelines data,[5] for example—that when a woman comes in having a heart attack, she is less likely to get aspirin within 24 hours and she is less likely to get beta-blockers within 24 hours. She is less likely to get any type of interventional therapy compared with a man. If they do thrombolytics or percutaneous interventions, it's less likely to happen for women compared with men.

The only thing that is more likely to happen to women compared with men, on the basis of the Get With the Guidelines data, is that they are more likely to die. They are more likely to die when they present with a heart attack, probably as a result of us not being as aggressive with women. What that means to me is that we aren't educating our physicians—both those in training and those who are practicing—adequately to understand that women are at risk, too.

I always joke and say that if a man comes in with a stubbed toe, he gets an EKG. It's very hard for a woman to actually get an EKG done. People say that women present atypically. I will tell you that two thirds of women present with the typical signs and symptoms when they are having a heart attack. For the one third that present with atypical symptoms, yes, they're going to be more difficult—but even men can present with those symptoms, and they're also going to be more difficult. If the patient is at risk and you're thinking about heart disease, and you're asking yourself what is the number-one thing that can affect this individual, you will always think of it, just like we think of it in men.

There is a lot of work that we have to do. We have to train our new physicians as well as our practicing physicians. I still see medical school curricula where women and heart disease might be one special lecture or not a lecture at all, and that is the truth.

Dr Black: Martha, as always, I'm so delighted with how you've done and how much fun it was to work with you. I wish you continued success and luck on your career. Thank you very much.

Dr Gulati: Thank you, Henry.

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