Levels of Ceramides in the Blood

Help Predict Cardiovascular Events

Researchers say new marker can help identify
patients at high risk of first cardiac events, even if
they have low LDL or no evidence of heart blockages
Mar 09, 2017
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Contact: Nicole Napoli, nnapoli@acc.org, 202-375-6523 Font Size
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Measuring concentrations of a class of lipids known as ceramides in the blood may hold the
key to helping clinicians identify individuals with suspected coronary heart disease who need treatment or
should be followed more closely, according to research scheduled for presentation at the American College of
Cardiology’s 66th Annual Scientific Session.
Although previous research conducted outside the U.S. has shown elevated ceramide levels among people
with confirmed heart disease or post-heart attack, this is the first study to show its predictive power among
people with no blockages and in those with low levels of low-density lipoprotein (LDL), the so-called “bad”
cholesterol.
Study data show that ceramides were able to predict major cardiovascular events—heart attack, stroke,
revascularization (a procedure or surgery to open blocked arteries) and death—among patients with and
without evidence of blockages and in those with low LDL, often relied on as the gold standard for
benchmarking risk. In fact, individuals with the highest levels of blood ceramides were found to have a
threefold to fourfold greater risk of suffering a cardiovascular event compared with those with the lowest
ceramide score, regardless of their LDL cholesterol level or the presence of a blockage in the heart’s
arteries.

“Based on our findings, measuring ceramides in the blood appears to be a new, potentially better marker
than LDL in predicting first and repeat cardiac events in both patients with and without established coronary
blockages,” said Jeff Meeusen, PhD, a clinical chemist and co-director of Cardiovascular Laboratory Medicine
at Mayo Clinic, and the study’s lead author. “Heart disease remains the number one killer in the United
States. Measuring ceramides offers another piece of information to help identify individuals who might need a
little more attention, guide treatment decisions and keep patients motivated to [live heart healthier].”
Meeusen said that unlike cholesterol, which is fairly inert, acting like a clog in the arteries, ceramides play an
active role in the cardiovascular disease process by attracting and drawing inflammatory cells and promoting
clotting. All cells have the ability to make ceramides; however, ceramide levels tend to accumulate in the
blood when we have too much fat or consume excess calories.
The study included 499 patients at Mayo Clinic who were referred for coronary angiography to check for
possible blockages in the heart’s arteries, of whom only half (46 percent) were found to have evidence of a
blockage. Coronary artery disease was defined as 50 percent stenosis, or narrowing, in one or more artery.
Patients were similar in age and with regard to blood pressure, smoking status and high-density lipoprotein
(HDL), the “good” cholesterol; those who had diabetes or a previous heart attack, stroke or procedure to
open narrowed coronary arteries were excluded. Researchers measured four different types of ceramides in
the blood at baseline and combined the values into a 12-point scale. Patients were grouped into four risk
categories according to their ceramide levels: low (0-2), intermediate (3-6), moderate (7-9) and high (10-
12).
Researchers prospectively followed study participants for an average of eight years and recorded occurrences
of heart attack, stroke, revascularization and death. Overall, 5.1 percent of patients had a major
cardiovascular event during the study timeframe. However, the risk of having an event was progressively
higher as the level of ceramides in the blood increased; for each one-point increase in the ceramide risk
score, the risk rose by 9 percent—a trend that remained even after fully adjusting for other risk factors
including age, sex, high blood pressure, smoking, total cholesterol, HDL and markers of inflammation. In
fact, the rate of events was double among people with the highest ceramide score compared with those with
the lowest (8.1 versus 4.1 percent, respectively). Total cholesterol also increased with rising ceramide scores
and males were less likely to have high levels of ceramides.
Among those without coronary artery disease upon angiography, the rate of cardiovascular events was only
3.1 percent, lower than the average overall. But when researchers examined cardiovascular disease in this
population by ceramide scores, people with the highest levels of ceramides were four times more likely to
have an event compared with those with the lowest (7.8 versus 2.2 percent, respectively). A similar trend
was seen among people with low LDL levels (<100 mg/dL), typically considered a good LDL target. In this
group, the rate of heart attack, stroke and revascularization, and death was 3.7 percent among those with a
low ceramide score but jumped to 16.4 percent in people with the highest ceramide levels.

“Ceramides continued to be significant and independently associated with disease even after adjusting for
traditional and novel cardiovascular risk factors,” Meeusen said. “[Based on what we are seeing,] ceramides
appear to be much more important than previously recognized.”
Cardiologists at Mayo Clinic are already routinely checking ceramides using the new test released in August
2016 as a way to further risk stratify patients who may otherwise not receive treatment but would remain at
high risk for a serious cardiac event. These are patients who could benefit from more intensive treatment, for
example: a higher-dose statin, a nutritionist consult or formal exercise therapy, Meeusen said.

“Knowing their ceramide score can improve therapeutic compliance and patient motivation, particularly since
the numbers improve within a few weeks,” he said.
Additional studies are currently underway to investigate whether checking ceramides can help prevent or
delay the onset of cardiovascular disease, as well as the use of therapeutic interventions, including PCSK9
inhibitors, on ceramide concentrations.
The trial was funded by Mayo Clinic. The new test is available through Mayo Medical Laboratories. The
present study is also the first to test its clinical utility.
Meeusen will present the study, “Plasma Ceramide Concentrations Predict Risk of Cardiovascular Events,” on
Saturday, March 18, at 1:30 p.m. ET at Poster Hall C at the American College of Cardiology’s 66th Annual
Scientific Session in Washington. The meeting runs March 17-19.
The ACC’s Annual Scientific Session, which in 2017 will be March 17-19 in Washington, brings together
cardiologists and cardiovascular specialists from around the world to share the newest discoveries in
treatment and prevention. Follow @ACCCardioEd, @ACCMediaCenter and #ACC17 for the latest news from
the meeting.
The American College of Cardiology is a 52,000-member medical society that is the professional home for the
entire cardiovascular care team. The mission of the College is to transform cardiovascular care and to
improve heart health. The ACC leads in the formation of health policy, standards and guidelines. The College
operates national registries to measure and improve care, offers cardiovascular accreditation to hospitals and
institutions, provides professional medical education, disseminates cardiovascular research and bestows
credentials upon cardiovascular specialists who meet stringent qualifications.