Background Identification of patients with stable
coronary heart disease who are at significant residual risk could be helpful for targeted prevention. Our aim was to determine the prognostic value of the recently introduced
ceramide- and
phospholipid-based risk score, the Cardiovascular Event Risk Test (CERT2), in patients with stable
coronary heart disease on optimal medical
therapy and to identify biological processes that contribute to the CERT2 score. Methods and Results Plasma samples (n=11 222) obtained from the STABILITY (Stabilization of
Atherosclerotic Plaque by Initiation of
Darapladib Therapy) trial were analyzed using a tandem liquid chromatography-mass spectrometry method. STABILITY was a trial in patients with stable
coronary heart disease randomized to the
lipoprotein-associated phospholipase A2 inhibitor
darapladib or placebo on optimized medical
therapy at baseline, with a median follow-up of 3.7 years. Hazard ratios per SD for the CERT2 risk score were 1.32 (95% CI, 1.25-1.39) for major adverse cardiovascular event, 1.47 (95% CI, 1.35-1.59) for cardiovascular death, 1.32 (95% CI, 1.16-1.49) for
stroke, 1.23 (95% CI, 1.14-1.33) for
myocardial infarction, and 1.56 (95% CI, 1.39-1.76) for hospitalization due to
heart failure, when adjusted for traditional cardiovascular risk factors. CERT2 showed correlation (P<0.001, r>0.2) with inflammatory markers
high-sensitivity C-reactive protein,
interleukin 6, the
heart failure marker N-terminal pro-
B-type natriuretic peptide, and
low-density lipoprotein cholesterol. After also adjusting for levels of other prognostic
biomarkers, the CERT2 score was still independently related to the risk of cardiovascular death but not to nonfatal events. Conclusions The CERT2 risk score can detect residual risk in patients with stable
coronary heart disease and is associated with
biomarkers indicating
inflammation, myocardial
necrosis, myocardial dysfunction, renal dysfunction, and
dyslipidemia. REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT00799903.