Blood Biomarker in Women Indicates Who Has Stiffening of the Heart Muscle

Researchers at UMC Utrecht studied differences between men and women in the stiffening of the heart muscle, a condition that is often a cause of heart failure. They discovered that blood biomarkers point in different directions in men and women with the same stiffening of the heart muscle. Anne-Mar van Ommen, physician-researcher at UMC Utrecht, explains: “If we better understand the stiffening of the heart, we can also start thinking about specific treatment options for men and women.” The study was recently published in Circulation Heart Failure.

Every year, nearly 38,000 people are diagnosed with heart failure for the first time. About half of these cases are caused by stiffening of the heart muscle. Of these patients, 70% are women and 30% are men. This condition is also known as diastolic heart failure. Diastolic heart failure is a chronic condition in which the heart can no longer fill properly with blood. This can lead to symptoms such as shortness of breath and fatigue.

Anne-Mar van Ommen explains: “In this study, we examined the differences between men and women in structural changes of the heart. Over the course of life, the heart can become stiffer. This is often accompanied by thicker heart walls and reduced blood filling of the heart. Our research has shown that the underlying process differs between men and women.”

Blood Biomarkers

In the study, the researchers investigated whether there are differences in prognosis, risk factors, and biomarkers associated with stiffening of the heart muscle. Using cardiac ultrasound scans, they assessed more than 60,000 men and women for signs of heart muscle stiffening. In approximately 600 participants, the researchers also measured more than 5,000 proteins in the blood. These proteins can serve as biomarkers.

The researchers discovered that the blood biomarkers linked to stiffening of the heart muscle point in different directions in men and women. According to the researchers, this may indicate that the underlying biological mechanisms differ between the sexes. In women, inflammation appears to play an important role — not inflammation caused by bacteria or viruses, but inflammation resulting from an overactive immune system.

One particular substance, interferon alpha-5, stood out. It was associated with heart stiffening in women, but not in men. This substance is produced by a gene located on the X chromosome, of which women have two copies.

“This substance is produced through expression of genes on the X chromosome,” says Anne-Mar van Ommen. “Women have two X chromosomes, while men have one X chromosome and one Y chromosome. In women, one X chromosome is largely inactivated. However, other studies have shown that some genes on the X chromosome remain active and continue to perform their function. Surprisingly, this may also explain the high levels of interferon alpha-5 in women.”

The researchers did not identify any standout biomarkers in men. However, they did observe that protein signaling and transport processes appear to play an important role in the stiffening of the heart muscle in men.

New Insights for Future Research

The study placed strong emphasis on female participation, because diastolic heart failure occurs more frequently in women and because women are often underrepresented in medical research.

“More than half of the participants in our study were women,” says Anne-Mar van Ommen. “This allowed us to analyze the results separately for men and women.”

The researchers believe that interferon alpha-5 likely plays a major role in the stiffening of the heart muscle in women. This may help explain why heart failure associated with heart muscle stiffening occurs more frequently in women than in men.

“We hope that future studies will investigate whether existing treatments can be used at an early stage of heart stiffening,” says Anne-Mar van Ommen. “This could help prevent the condition from worsening and, particularly in women, reduce the risk of developing heart failure.”