Ceramides Can Predict Who Will Develop Heart Disease, Study Finds

A class of lipids called ceramides could tip off physicians that a patient will develop heart disease, even for those with no current blockage or low cholesterol levels, according to findings being presented this week at the 66^th American College of Cardiology (ACC) Scientific Session.

The study from the Mayo Clinic found that the presence of ceramides could predict who would have major cardiovascular (CV) events such as a heart attack, stroke, surgery to open blocked arteries, or CV death. Those with the highest levels of ceramides were found to have a 3-fold or 4-fold greater risk of suffering a CV event, compared with those with a low ceramide score, independent of their levels of low-density lipoprotein (LDL) cholesterol or the presence of blockage in the arteries.

Jeff Meeusen, PhD, a clinical chemist and codirector of Cardiovascular Laboratory Medicine at Mayo Clinic, told a briefing of reporters ahead of the ACC meeting that because the study was based on data from patients who were referred for coronary angiography—meaning they already had some risk factor—it’s too soon to say if a ceramide test would become routine for the general population. But Meeusen, the lead author, said other studies are in the pipeline that could answer this question. Measuring ceramides, which is a simple blood test, costs about $150 but varies, he said.

“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,” Meeusen said in a statement. “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 healthier.”

Mayo Clinic is already using ceramide scores to stratify patients for treatment. Some receive a high-dose statin or a consultation from a nutritionist. Studies underway are showing which might benefit from a PCSK9 inhibitor.

Meeusen compared the action of cholesterol, which simply blocks the artery, to that of ceramides, which are dynamic and actively promote clotting. Too many calories and fats can increase ceramide levels in the blood.

The Mayo Clinic study involved 499 patients who took a ceramide test, of whom roughly half (46%) had evidence of a coronary blockage. Patients were measured for 4 types of ceramides at baseline on a 12-point scale and grouped in 4 risk categories: low (0-2), intermediate (3-6), moderate (7-9), and high (10-12).

Researchers studied the patients for an average of 8 years. Overall, 5.1% of the patients had a major CV event (heart attack, stroke, revascularization, or death) during the study period. The risk of having an event increased along with the ceramide level in the blood; researchers found that for every 1-point increase on the ceramide score, the risk level rose by 9%. Event rates doubled among those with the highest ceramide score compared with the lowest (8.1% vs 4.1%). Rising ceramide levels were also associated with total cholesterol.

Those who had no coronary artery disease at angiography had CV rates of 3.1%, but within this group, those with high ceramide levels had CV rates of 7.8% compared with 2.2%. The same was true among those with low LDL cholesterol but high ceramide scores—those at the highest levels had CV events of 16.4%, compared with 3.7% among those with low LDL cholesterol (<100 mg/dL).

“Ceramides continued to be significant and independently associated with disease even after adjusting for traditional and novel cardiovascular risk factors,” Meeusen said. From what the researchers can tell, these lipids “are much more important than previously recognized.”