For much of his life, Mark Kocak kept in great shape, lifting weights, doing aerobics and yoga, all while being an avid runner. But as he approached his 60s, Mark found himself dealing with high LDL (or “bad”) cholesterol. His primary care doctor recommended he go on a statin, but Mark refused, until one day, “I felt a little weird and thought maybe I was having a heart attack,” Mark says. Though the episode was a false alarm, it served as a wake-up call for Mark.

“My primary doctor, for the last few years, had been recommending I go to a cardiologist because of my high cholesterol and things like that, and I'd been kind of kicking the can down the road,” says Mark, now 62 and recently retired from teaching health and physical education at a junior high school in southwest Minnesota. “But when I had that scare with my heart, I decided I better see one. And I knew right away where I wanted to go, and that was Mayo Clinic.”

At Mayo, Mark came under the care of preventive cardiologist Vlad Vasile, M.D., Ph.D., co-director of Mayo’s Clinical Specialty Laboratory, who recommended he undergo ceramide testing. A novel assay developed at Mayo, ceramide testing can reveal more about heart disease and stroke risk than standard lipid tests. 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, who also serves as medical director of Mayo Clinic’s Cardiovascular Health Clinic. “All of them are involved in plaque formation. Some reflect inflammation, some reflect the bad cholesterol, and some reflect coagulation or thickening of the blood.”

Jeff Meeusen, Ph.D., who co-directs Mayo’s Clinical Specialty Laboratory alongside Dr. Vasile, believes ceramides to be “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,” he says. “When they’re imbalanced they seem to have a stronger physiological signal that informs our ceramide test.”

Moving beyond the gray area of risk calculators

Mayo Clinic’s ceramide test uses liquid chromatography-mass spectrometry technology to sort through complex molecular compounds and render 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 risk categories, from low to very high risk. The test is also available to physicians outside of Mayo Clinic; one need only send in a patient’s blood specimen to receive their ceramide score.

“I would say about half of our ceramide test orders are external and the other half are from Mayo Clinic physicians,” Dr. Meeusen says. “But because we are the only center offering this test right now, very few physicians know about it. At the same time, there’s quite a bit of literature building up in its support.”

When Mark came to Dr. Vasile, besides high cholesterol, he also had stage 1 hypertension.

“His LDL level was 137, which was not really at goal,” Dr. Vasile says. “And he has a family history of premature coronary artery disease in first-degree relatives, so I ran the ASCVD calculator (a tool that estimates a patient’s 10-year risk of heart attack), which put him in a gray area of intermediate risk.”

Cardiologists like Dr. Vasile also use chest imaging and traditional blood tests to indicate coronary artery disease risk factors. But even this testing is limited, as are current risk calculators.

“We’re looking at many, many things, not just one parameter,” Dr. Vasile says. “With these calculators, we plug in all these clinical parameters, like blood data such as cholesterol, the demographics of the patient, and these calculators render a certain risk for developing heart attacks and strokes within a certain time span. But we know very well that these calculators are far from being perfect. There is a lot of criticism with such calculators because coronary artery disease and plaque formation are very complex and multifactorial processes.”

Dr. Vasile continues, “So, here’s this patient, Mr. Mark Kocak, who comes to me with a high LDL cholesterol of 137 mg/dL and a strong family history of heart disease. He’s also at higher risk because he’s a male. Should I target for him an LDL of less than 100, or should I be more aggressive and target an LDL of less than 70? The ASCVD risk calculator was not very helpful in this situation because it ignores family history completely, and so I needed more information.”

Targeting LDL numbers to fit the individual

This is where ceramide testing becomes invaluable for Dr. Vasile. It’s a tool that helps him push through these gray area scenarios and better individualize treatment plans for patients. Mark’s ceramide score was zero, which placed him at low cardiovascular risk — unlike another patient of Dr. Vasile, Stephanie Blendermann, whose score was an 8, which put her at high risk.

“So, his score was in opposition to Mrs. Blendermann’s, who had a high score and a similar family history,” Dr. Vasile says. “This told me that Mr. Kocak’s family history probably doesn’t have a significant influence on him. So, we jointly decided that because his ceramide score was zero, we shouldn’t be as aggressive with him as we were for Mrs. Blendermann, whose LDL we targeted at less than 70 milligrams per deciliter. His score told us we should target an LDL number of less than 100, which is the risk category for the average person walking the street.” 

Higher LDL levels are correlated with heart attacks and strokes; thus, the lower the LDL, the lower the risk of developing these events down the line. To reduce Mark’s risk and bring his LDL to goal, Dr. Vasile recommended a statin and medication for hypertension.

“Without that ceramide score, I wouldn't be able to completely say, ‘Yeah, I want this patient’s LDL to be below 100 or below 70,’” Dr. Vasile says. “And to reach that specific goal for the LDL, it does make a difference as far as what dose of statin you are on.”

Though his ceramide score put him at low risk, Mark heeded Dr. Vasile’s recommendation to go on meds to further decrease his chances of an event. “If a statin and then a low-dose hypertension pill can keep a heart attack at bay, it’s sort of a no-brainer,” Mark says. “I agreed with him on that, and it was part of our preventative plan.”

Dr. Vasile also urged Mark to continue his aerobic exercise program, weight training, and yoga, and had him talk with a dietician in Mayo’s Cardiovascular Health Clinic, who recommended he begin following a Mediterranean diet. Meanwhile, Mark continues to run, though he’s taking it a bit easier these days. “I’m down to 5 and 10Ks,” he says. “Those are a lot more comfortable at this age.” 

As part of his preventative plan, Mark will be re-tested for his ceramide score on follow-up visits with Dr. Vasile so that any change can be caught early, and his treatment adjusted accordingly. Although he resisted taking medications for a time, Mark says, “I've always tried to be proactive. An ounce of prevention is worth a pound of cure, and I think medicine’s trying to head that way, getting in on the front end of preventing things, versus having to deal with the aftermath. But Mayo is just an amazing place, leading the way. My family is really blessed to have a facility like this so close to home.”