February is American Heart Month. According to DeLisa Fairweather, Ph.D., it’s a critical time in the fight against heart disease, the leading cause of death for both men and women in the U.S. She and her research team at Mayo Clinic’s Florida campus are taking a new approach – they’re exploring how heart disease develops in men versus women, with the goal of finding new diagnostic tests and individualized therapies based on these sex differences.

Their goal is to more accurately predict those men and women at risk for developing heart disease, allowing for earlier intervention with lifestyle changes, screening and more precise therapies.

“Men are more likely to develop heart disease than women. That’s because the male hormone testosterone drives the disease, while the female hormone estrogen protects against it. Women develop heart disease as a result of other conditions such as hypertension (high blood pressure) or kidney disease. Evidence from research reflects these differences, but our current diagnostic tests and therapies don’t. By exploring sex differences, we will capture vital information that has been missed,” says Dr. Fairweather.

DeLisa Fairweather, Ph.D.

With support in part from Mayo Clinic Center for Individualized Medicine, Dr. Fairweather will use genetic testing to identify which genetic variants are linked to men’s and women’s risk for heart disease,

“We’ll use these genetic variants to develop more accurate diagnostic tests and targeted therapies that will help us treat patients sooner and prevent heart failure. Our findings will also provide insights into sex differences for other chronic inflammatory conditions caused by infections – from cancer to autoimmune diseases like lupus and rheumatoid arthritis,” says Dr. Fairweather.

First – a closer look at myocarditis

Initially, Dr. Fairweather and her team will explore sex differences in myocarditis, the leading cause of heart failure in adults under the age of 50. Myocarditis is most commonly caused by the same virus that causes hand-foot-and-mouth disease in young children. In patients with myocarditis, the virus causes inflammation, making it difficult for the heart to pump blood or maintain a normal rhythm. It can lead to serious, chronic conditions such as dilated cardiomyopathy (an enlarged heart) and ultimately require a patient to undergo a heart transplant.

“Myocarditis is difficult to diagnose. While we believe it is a relatively rare condition that most frequently occurs in men, our research will help uncover the underlying disease processes taking place. By developing a better diagnostic test based on sex differences, we may discover the genes that cause myocarditis in women, which currently are not known,” says Dr. Fairweather.

In her Translational Cardiovascular Disease Research Laboratory, Dr. Fairweather has developed a mouse model that has accurately reproduced the disease timeline and processes seen in humans with myocarditis, providing a valuable tool to study the factors leading to disease.

The team will first explore the role of mast cells – the same cells known to control our responses to irritants that cause allergies.

“Mast cells are unique because they interact with our immune system, our hormones and our environment, making them an ideal window into the underlying processes that cause myocarditis. We know they play a key role in patients who progress to heart failure. Genetic testing will help us understand the genetic variants that predispose men and women to develop myocarditis,” says Dr. Fairweather.

Uncovering sex differences in other types of heart disease           

According to Dr. Fairweather, the myocarditis study is only the first step in understanding how heart disease develops in each individual patient. Her team’s findings could help shed light on many types of heart disease.

“Our next step will be to confirm our lab results in the clinical setting. We’ll examine data for patients with myocarditis and other types of heart disease who are participants in the Mayo Clinic Biobank. We’ll also apply our results to several ongoing research efforts in heart disease,” says Dr. Fairweather.

Dr. Fairweather’s research is also supported through grants from the National Institutes of Health and American Heart Association.

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Save the date for this year’s Individualizing Medicine Conference. It will be held Sept. 12-13, 2018.

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