In conversation about cardiovascular disease in women

In cardiovascular disease research, statistics and approaches aimed at men often prevail. Prof. Hester den Ruijter dedicates her scientific career to getting to the bottom of cardiovascular disease in women. In this interview, she reveals her motivations and the challenges she faces to close this gap. We also dive deeper into the biological basis of these diseases, and how that knowledge can lead to improved diagnostics and treatments.

Introducing

Prof. Hester den Ruijter has been researching cardiovascular disease for more than 15 years. In recent years she has focused on cardiovascular disease in women, and since 2020 she has been a professor in this field.

“Many people think I’m a cardiologist, but I’m not,” she says with a broad smile. “I was trained as a researcher at Wageningen University. There I studied food toxicology: the harmful effects of toxins in our food. Later I trained as a clinical epidemiologist at the UMC Utrecht. With this broad scientific base, I now try to find out the cause of diseases in women so that we can improve their diagnosis and treatment.”

Why are you doing research on cardiovascular disease in women?

“The biggest motivation for my research is justice. We still have insufficient knowledge about how cardiovascular diseases develop and manifest in women. Scientific studies on these diseases often lack female participants. As a result, we often cannot properly investigate the possible differences between men and women. This creates uncertainty about the effects of new drugs in women, and whether they are comparable to men.

An example is the drug colchicine that prevents inflammation. This drug has recently been tested in people who already have cardiovascular disease. It appears to improve the outlook of these patients, which is good news. But if you look at this scientific study in detail, you see that the group of women in the study is so small that you can’t say for sure whether the drug is as effective in them as it is in men.

I find that hard to accept. It my mission to understand what is different in women and help close this gap. I am also committed to raising awareness: I want women to know what problems they may face and the risks.

My curiosity fuels my commitment. There is a huge scientific field ahead of us in which so much can still be discovered. I get great satisfaction from working with my team and mentoring young researchers. Together we can make a positive change in the understanding and management of cardiovascular disease in women.”

What challenges are there in the diagnosis of cardiovascular disease in women?

“Women are more likely to have a chronic form of cardiovascular disease. That means the disease develops slowly over a longer period of time. The symptoms they experience develop gradually and persist. So the disease can be present for a while without you noticing it. This is different from a sudden heart attack, where we immediately think of emergency care. We see such an acute, rapid form of cardiovascular disease more often in men. As a result, women are often diagnosed late.

Another factor is that in science we often look first at acute problems and only later at chronic diseases. As a result, we have fallen behind in understanding the specific symptoms that come with the female body. By now we all know the stories of women who were reassured for years that their symptoms were not from the heart, but later were found to have cardiovascular disease. Especially women with poor blood flow to the small blood vessels in the heart have experiences like this. Personally, my hair stands on end when I hear stories of women who are sent away thinking everything is fine, when afterwards it wasn’t.”

What can women themselves look out for?

“I have talked to many women about this issue. They often told me that they had a strong intuitive feeling that something was not right with their health. A ‘nonplussed feeling.’ Even after they visited the doctor, that feeling continued to gnaw at them, as if something was wrong.

I think it’s very important to take that inner voice seriously. If you have such a feeling, it is smart to listen and act on it carefully. So, trust your own intuition and give it a voice. Don’t hesitate to contact your doctor again if you have any concerns, to discuss it.”

What about the difference in side effects of medications between women and men?

“That’s an interesting question. There are two sides to this story. Women tend to suffer more side effects. Sometimes they even stop medication altogether because of those side effects. That’s unfortunate, because by doing so they also miss out on the benefits that the medications offer. Then you want to see which dosage or which medicine will do.

On the other hand, we also have to deal with women who are prescribed too low a dose or no medication at all, even though they need it. An example is cholesterol-lowering drugs, where this occurs regularly.”

You do a lot of research on arterial calcification. Why?

Calcification in the arteries is the cause of many different types of cardiovascular disease. Between men and women, we see interesting differences. In women, calcifications are more often in different places in the blood vessel, with less bleeding than in men.

We found that the cells that play a role in calcifications are different in women than in men. In women, smooth muscle cells are more often involved. This difference, in turn, gives us opportunities to develop new treatments.”

So what are the underlying mechanisms of arterial calcification?

“We have done a lot of research into which genes are involved in calcification. These appear to be different genes in women than in men. We’ve also looked at something called epigenetics. This is about how environmental factors affect our DNA. We can see this by looking at small particles that attach to DNA in specific places. Those particles are called methyl groups. We have found that there are differences in epigenetics between men and women that can affect the risk of calcification.

Of interest here is the so-called “cell-free DNA. This is DNA that is loose in our blood. It comes from cells that have died and released their contents into the blood. This cell-free DNA also has those methyl groups bound to it. It gets a little complicated to explain, but I tell this because we can do important things with this! This is because arteriosclerosis also releases this cell-free DNA with those specific methyl groups. So you find that in the blood of women with severe cardiovascular disease. The methyl groups can tell us how active and potentially dangerous the arterial calcifications are.

Our ultimate goal is to create a test that can measure this, predicting whether someone is at high risk for serious arterial problems. We recently received an important grant, the ERC Proof of Concept Grant, to further develop this idea.”

You want to bridge the gap between research in the laboratory and research with patients. How are you tackling that?

“That’s quite a challenge, I must say. But a very useful connection to make. It starts in the clinic: the doctor makes the diagnosis and collects blood and tissue from the patient. That is stored in a biobank: a large database with all kinds of patient material. In our laboratory, we start working with that material. Through the tests we develop, that knowledge can flow back to the clinic. This is called “translational research. It closes the gap between scientific discoveries and tangible benefits for patients and health care.

It’s quite a stretch. If we have a pilot version of a test to detect cardiovascular disease, we can’t produce those tests ourselves on a large scale. That requires collaboration, with companies that are going to invest in this and then manufacture the test.”

Imagine it’s the year 2035. What will diagnosis and treatment for cardiovascular disease in women look like then?

“In 2035, we have better techniques to detect cardiovascular disease in women. We will also have better treatments for the kinds of cardiovascular diseases that are especially prevalent in women. We won’t just be doing more symptom control and symptom relief with existing medications, but can really address these diseases at the root cause. This will give many women a better and healthier life.

By then, we will also have a number of tests that doctors can use to more accurately predict the risk of cardiovascular problems in women. This may eventually lead to preventive measures, which we hope will help us avert the onset of cardiovascular disease in women.”