Red meat and high-starch foods like mashed potatoes were the family fare while Stephanie Blendermann was growing up in Long Island, New York. Her father was a butcher after all, and a smoker, who eventually required bypass surgery for clogged arteries. And tragically, three of her sisters died prematurely (in their 40s and 50s) from heart attacks. So as she approached 65, even though her LDL (or “bad”) cholesterol levels were fine, Stephanie was concerned her family history might catch up with her. At Mayo Clinic, she underwent ceramide testing, a novel assay that can reveal more about heart disease and stroke risk than standard lipid tests.

“I’m sure my sisters’ early deaths were partly from lifestyle, and from smoking, which I never took up,” says Stephanie, a real estate agent based in Prior Lake, Minnesota, who specializes in executive relocation for top corporations. “It’s pretty devastating to think here I am now, just about 65, and they didn't get to live full lives and see all the things I've seen.”

Stephanie came under the care of cardiologist Vlad Vasile, M.D., Ph.D., co-director of Mayo Clinic’s Clinical Specialty Laboratory and medical director of the Cardiovascular Health Clinic, who recommended ceramide testing. “Coronary artery disease and plaque formation are both very complex processes,” says Dr. Vasile. “I think the more tests we have, to assess cardiovascular risk of a specific patient, the better off we are. One of these tests is the ceramide score that we developed here at Mayo Clinic, and I use it extensively in my practice.”

Ceramides are sphingolipids, found everywhere in our body. Though they are “ubiquitously expressed,” the test focuses primarily on three ceramides of cardiovascular interest. “The beauty of these three ceramides is they’re involved in different pathways,” says Dr. Vasile. “All of them are involved in plaque formation, some reflect inflammation, some of these ceramides reflect the bad cholesterol, and some coagulation or thickening of the blood.”

Jeff Meeusen, Ph.D., co-director of the Clinical Specialty Laboratory, chimes in: “I think ceramides are a very biologically active group of signal molecules. So, whereas cholesterol is more or less a scaffolding, a building block that the cells can use to make other things, these ceramides seem to be specific actors in these different roles. So when they're imbalanced they seem to have a stronger physiological signal that informs our ceramide test.”

A simple number correlates with heart attack risk

The ceramide test uses liquid chromatography-mass spectrometry technology, which sorts through complex molecular compounds and then renders an algorithmic score — a simple number that places the patient in a “bucket” of risk. For clinicians, it’s easy to interpret because this number is correlated with one of four categories of risk, from low risk to very high risk.

Stephanie’s ceramide score was an 8, which put her at higher risk for a heart attack. The score was “eye-opening” to her because she had long ago cut out red meat and was staying active. Still, she noticed shortness of breath on walks, especially when trying to take hills, as well as achiness and a lack of energy.     

“I couldn't figure out what was wrong with me,” says Stephanie, who also suffers from a connective tissue disorder, a chronic inflammatory condition that can contribute to coronary plaque formation. “I just knew I wasn’t myself. But I wasn’t having heart pain or anything else. And I just figured the achiness was from the statin I was on. But we found out from the ceramide test that I have certain ceramides where you get a thickening of the blood in your body, in your arteries and whatnot. And it just doesn’t let the body act as efficiently as it should even though my cholesterol was going down.”     

Ceramide testing is not the only assay for assessing cardiovascular risk. Cardiologists like Dr. Vasile also use traditional blood tests like the lipid panel and lipoproteins as blood biomarkers to indicate coronary artery disease risk factors. There’s also a coronary calcium score and ECG chest X-ray, among others.

“We’re looking at many, many things, not just one parameter,” emphasizes Dr. Vasile. “We also have certain calculators where we plug in all these clinical parameters, like blood data such as cholesterol, and the demographics of the patient. And these calculators render a certain risk for developing heart attacks and strokes within the next 10 years, or over the lifetime, for example. But we know very well that these calculators are far from being perfect. There is a lot of criticism with these calculators because coronary artery disease and plaque formation are, as I’ve said, very complex processes.”

Dr. Vasile puts a high value on ceramide testing because it rises above such calculators to better inform him on treatment plans for patients like Stephanie. “When you look at a traditional biomarker, such as a lipid profile, it really only looks at the LDL or bad cholesterol that deposits on the plaque,” he says. “So it’s just one risk factor out of the many risk factors. But the ceramide score is a more comprehensive biomarker because it looks at three different pathways that are involved in plaque formation. So, I trust the ceramide score more than just a simple biomarker like the lipid profile.”

Dr. Meeusen adds, “We would still recommend starting with the standard lipid assessment and other risk factors. And when there is intermediate risk and you’re trying to gauge how aggressive you want to take your treatment plan, the ceramide test is designed to help with that scenario.”

A new lease on life

Once he knew Stephanie’s ceramide test score, Dr. Vasile refined her statin medication. “Mrs. Blendermann’s ceramide score of 8 placed her at high cardiovascular risk,” he says. “So this number told me that we needed to be aggressive. We needed to not only address her lifestyle with diet and exercise, but we also needed to be more aggressive with lowering her lipids, her LDL cholesterol.”

The LDL target for the average population should be less than 100 milligrams per deciliter. But given Stephanie’s ceramide score, Dr. Vasile recommended an LDL target of less than 70 milligrams per deciliter. A higher LDL level is always correlated with heart attacks and strokes; thus, the lower the LDL, the lower the risk of developing these events down the line.

As for lifestyle changes, Dr. Vasile recommended that Stephanie improve her dietary habits. “When I first saw her, she was not following a perfect diet, but she was not on a bad diet either,” he says. “We did have her talk with our dietician in the Cardiovascular Health Clinic, who recommended a Mediterranean diet, and she really changed her diet accordingly. We also recommended initiation of a systematic aerobic exercise. She talked with our cardiovascular physiologist who tailored her exercise program at home. So she did both these things. She is a very compliant patient.”

Dr. Meeusen also advocates diet and exercise. “People with high ceramides received a stronger benefit than those with normal ceramides when they were on the Mediterranean diet intervention,” he says. “The ceramide score can respond quickly to improved diet and increased exercise, which can motivate patients to maintain their healthy lifestyle changes.”

Today, Stephanie feels like a new person who is better able to enjoy her active life. And she now looks forward to many years ahead. “My ceramide test score really put me in high gear to make changes,” she says. “It’s amazing how you can adjust your way of thinking and desires of what you want to eat. And with Dr. Vasile’s treatment, it’s made a remarkable difference, really a remarkable difference.”

It’s also a little bittersweet for Stephanie, who adds, “Had my sisters had ceramide testing, and had they had this type of great medicine at Mayo, I think that would have given them longer lives.”