Testing for Ceramides Helps Predict Cardiovascular Events

Although previous research 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 healthy low levels of low-density lipoprotein (LDL). It showed that ceramides could predict major cardiovascular events—heart attack, stroke, revascularization (procedure to open blocked arteries), and death. Individuals with the highest levels of blood ceramides were found to have a 3-4 fold greater risk of suffering a cardiovascular event compared with those with the lowest ceramide score, regardless of LDL level or presence of a blockage in heart arteries.

“Measuring ceramides in the blood appears to be a new, potentially better marker than LDL in predicting first and repeat cardiac events,” said study lead-author Jeff Meeusen, PhD, Mayo Clinic, offering “another piece of information to help identify individuals who might need a little more attention, guide treatment decisions, and keep patients motivated.”

Dr. 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, but ceramides tend to accumulate in 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 which only 46% were found to have evidence of a blockage. Patients were grouped into four categories according to their blood ceramide levels - low, intermediate, moderate, or high.

Participants were prospectively followed for an average of 8 years. Overall, 5.1% of patients had a major cardiovascular event during the study timeframe. However, the risk of having an event was progressively higher as ceramide levels increased: for each 1-point increase in the ceramide score, risk rose by 9%—even after fully adjusting for other risk factors (including age, sex, high blood pressure, smoking, total cholesterol, HDL and markers of inflammation). The rate of events was double among people with the highest ceramide score compared with those with the lowest. 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%. But those with the highest levels of ceramides were 4 times more likely to have an event compared with those with the lowest levels. A similar trend was seen among people with low LDL levels (<100 mg/dL).

“Ceramides continued to be significant and independently associated with disease even after adjusting for traditional and novel cardiovascular risk factors,” said Dr. Meeusen. 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. And “knowing their ceramide score can improve therapeutic compliance and patient motivation, particularly since the numbers improve within a few weeks,” he said.

The new test is available through Mayo Medical Laboratories. The present study is the first to test its clinical utility. Dr. Meeusen presented the study “Plasma Ceramide Concentrations Predict Risk of Cardiovascular Events” at ACC’s 2017 Annual Scientific Session (Washington, DC, USA; March 17-19).