New biomarker may be able to predict risk in women

• Cardiovascular disease (CVD) is strongly linked to inflammation, and inflammatory markers may indicate whether someone is at risk of developing CVD.
• Anti-inflammatory antibodies are associated with protection against CVD in men.
• A new study has found that low levels of one anti-inflammatory antibody — IgM anti-PC — are also associated with atherosclerosis and heart attacks in older women, while higher levels appear to have a protective effect.
• The researchers suggest that this finding could be used to identify women at risk of CVD, and may even form the basis of a vaccine against atherosclerosis.

Cardiovascular diseases (CVDs) are conditions that affect the circulatory system — the heart, arteries, veins, and capillaries. They are the leading cause of death worldwide, with the World Health Organization reporting that they are responsible for 17.9 million deaths each year.

Identifying those at risk is an effective way of preventing premature death from CVD, and new findings from the Karolinska Institutet in Sweden may point toward one way of identifying women at higher risk of CVD.

In this latest study, published in the Journal of the American College of Cardiology, they investigated the effects of IgM anti-PC in postmenopausal women.

They found that higher levels of the antibody protected the women against CVD, and low levels were associated with both atherosclerosis and heart attack (myocardial infarction/MI).

“This study found an association in women between levels of an antibody against phosphorylcholine (a component of cell membranes and lipoproteins that may mediate chronic blood vessel inflammation and resulting atherosclerosis), and future cardiovascular disease. This finding is quite novel and could represent a marker that could be used to help assess someone’s risk of developing heart disease.”

— Cheng-Han Chen, MD, board certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA

Although it is commonly thought that heart disease affects more men than women, the Centers for Disease Control and Prevention (CDC) report that it is the leading cause of death for women in the United States. It can occur at any age, but hormonal changes following menopause increase the likelihood of coronary artery disease — the build-up of plaques in the arteries that can lead to heart attack.

In this latest study, researchers measured the levels of IgM anti-PC in 932 women from the Swedish Mammography Cohort, to determine whether there was a link between this anti-inflammatory antibody and CVD. The women had a mean age of 67, and no history of heart disease.

All the women filled out questionnaires about their health, lifestyle, and diet at the time of enrollment in the study. Researchers calculated their body mass index (BMI) and recorded whether they had diabetes, high blood pressure, or high cholesterol.

From blood samples taken after a 12-hour fast, the researchers assessed their levels of IgM anti-PC. They then divided the women into 5 equal-sized groups, based on their level of IgM anti-PC. The lowest group had a mean level of 20±6 U/mL, the highest had a mean of 161±96 U/mL of IgM anti-PC.

They followed up with the participants for 16 years until December 31, 2020, or until one of the following events — composite CVD, ischemic heart disease, myocardial infarction, ischemic stroke, or death.

Of the 932 women in the study, 113 developed composite CVD, 69 developed ischemic heart disease, 44 had heart attacks, and 50 had ischemic strokes.

The women with the highest levels of IgM anti-PC had a 73% lower risk of CVD than those in the group with the lowest levels. The reduction was most evident in the risk of ischemic heart disease and heart attack (MI).

Lead author Johan Frostegård, Professor of Medicine, Institute of Environmental Medicine, Head of Unit of Immunology and Chronic Disease, Karolinska Institutet, explained the findings to Medical News Today:

“I think CVD and atherosclerosis are inflammatory conditions where immunity is central. Here’s a hypothesis about this: where anti-PC is in focus, we described several potential mechanisms, anti-inflammatory and increasing clearance of dead cells and also inhibiting oxidized low-density lipoprotein deleterious effects.”

“Women have higher anti-PC than men and get CVD later in life. I think the findings could be highly significant for both prevention and treatment among women,” he added.

The team behind this study is currently working on a more extensive study with both men and women to determine what level of anti-PC can be used to determine CVD risk.

“Larger prospective studies would be needed to both confirm this finding and to determine the levels of the antibodies that provide risk discrimination.”
— Cheng-Han Chen, MD

In a study in wild brown bears, Frostegård and his team found that hibernating bears have very high anti-PC levels, and do not seem to develop atherosclerosis or CVD, despite high levels of obesity before hibernation. This finding, together with other research, has led him to suggest that immunization might be a way to increase anti-PC levels in people whose levels are low.

“If there’s a vaccine to raise anti-PC, those with lower levels could be more eligible [for] vaccination.”

He suggested that the vaccine could be given in middle age, or possibly earlier as atherosclerosis builds up slowly, and that it might also be useful against other diseases characterized by chronic inflammation.

However, Chen sounded a note of caution:

“It is too early to know whether the anti-PC antibodies provide a direct protective effect on developing heart disease, or whether it is simply a marker of future risk. Vaccines that raise the levels of anti-PC antibodies would only be useful in the former case.”