More Certainty With Ceramides? New Blood Test May Help ID CAD Patients Early in Disease

A simple blood test based on plasma ceramide levels may be able to accurately predict cardiovascular events in patients with suspected coronary artery disease, according to new research.

Ceramides, biologically active lipids that are carried by LDL cholesterol and disrupt vascular function, can play a dynamic role in the genesis and promotion of cardiovascular disease. Although all cells are able to produce ceramides, blood cells tend to overproduce them in individuals with excess fat levels or high caloric intakes.

Measuring and tracking LDL cholesterol is cost-effective and has for many years been the gold standard for assessing atherosclerosis progression and preventing cardiovascular events. In this new study, researchers led by Jeffrey Meeusen, PhD (Mayo Clinic, Rochester, MN), set out to explore a simple and precise way to identify patients at risk, especially those with LDL levels in the normal range, using a 12-point score based on blood ceramide levels to gauge risk of major adverse cardiovascular events over time.

Results of their 499-patient validation study were released in advance of the annual American College of Cardiology Scientific Session and are set to be presented in a poster session on March 18, 2017, in Washington, DC.

In a media telebriefing, Meeusen explained that the patients—all referred for coronary angiography at his institution—were grouped into four cohorts by risk. Over a median follow-up period of 5.9 years, 191 patients (5.1%) had a major cardiovascular event (MI, revascularization, stroke, or death), with higher risk observed in patients with higher ceramide scores, even after adjustment.

Overall Outcomes by Ceramide Risk Group

Low

(n = 87)

Intermediate

(n = 206)

Moderate

(n = 122)

High

(n = 84)

P Value

MACE

4.10%

4.20%

5.60%

8.10%

< 0.01

Adjusted OR

(95% CI)

–

1.11

(0.63-1.98)

1.50

(0.81-2.80)

2.10

(1.05-4.39)

0.03

The score held up even in subgroups of patients with LDL cholesterol < 100 mg/dL and those without diagnosed CAD.

Additionally, ceramide levels were associated with levels of overall cholesterol, LDL cholesterol, triglycerides, high-sensitivity C-reactive protein (hs-CRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2), and men tended to have high levels of ceramides.

Meeusen said the test is now available through Mayo Medical Laboratories, and though the price will vary, he estimates it won't cost more than $150 per test. As for who should be referred for the test, given the limited data supporting its use, he recommends only "fairly high risk" patients at this time. However, Meeusen predicts this test will have wider ranging clinical implications, and his group is currently working on a study in the general population.

Further research will also be necessary to determine if or how patients can best lower their ceramide levels, and whether this has any effect on clinical events, but he predicted this will include exercise recommendations and statin prescriptions. Studies are already underway looking at whether therapeutic interventions, including PCSK9 inhibitors, affect ceramide concentrations, a press release notes.

Yael L. Maxwell is Senior Medical Journalist for TCTMD and Section Editor of TCTMD's Fellows Forum. She served as the inaugural…

Meeusen J. Plasma ceramide concentrations predict risk of cardiovascular events. To be presented at: American College of Cardiology Scientific Sessions. March 18, 2017. Washington, DC.

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