Abstract
Background
Both levels of protein and lipid biomarkers have been found associated with cardiovascular outcomes in patients with stable coronary heart disease (CHD). There are few large-scale studies comparing the prognostic value of and interactions between these two groups of biomarkers in CHD.
Methods
In the 15,828 CHD patients included in the STABILITY trial 10,205 provided plasma samples at baseline allowing measurements of distinct ceramide and phospholipid species by mass spectrometry and markers of cardiac dysfunction (N-terminal pro-B-type natriuretic peptide [NT-proBNP]), high sensitivity cardiac troponin-T [cTnT-hs]), renal dysfunction (cystatin-C), oxidative stress (growth differentiation factor 15 [GDF-15]) by electro-immunoassays. During 3.7 years median follow-up, 1291 CVD, MI, and stroke events occurred. A previously developed ceramide and phospholipid species based risk score (CERT) and its associations to outcomes before and after adjustment were evaluated by Cox-regression models.
Results
The CERT model was significantly associated to all cardiovascular outcomes before and after adjustment for clinical characteristics and routine laboratory tests. However, the associations were attenuated after adjustment for other prognostic biomarkers. The data are summarized in Table 1 below.
Table 1. HR per 1 SD increase in CERT HR (95% CI) p-value MACE Model 1 1.30 (1.24–1.37) <0.0001 Model 2 1.23 (1.16–1.31) <0.0001 Model 3 1.08 (1.02–1.15) 0.0120 CVD Death Model 1 1.57 (1.45–1.69) <0.0001 Model 2 1.38 (1.26–1.50) <0.0001 Model 3 1.14 (1.04–1.26) 0.0052 MACE = CVD death, stroke and MI. Model 1 includes score and randomized treatment. Model 2 includes score, randomized treatment, age, gender, and prior (MI, coronary revas., multivessel CHD), B/L diabetes, hypertension, history of smoking, PVD, region, B/L systolic BP, B/L BMI, HB, WBC, CKD-EPI, LDL-C, HDL-C and TG. Model 3 includes the following covariates in addition to Model 2: TnT-hs, proBNP, Cystatin-C, CRP-hs and IL-6.
Conclusion
A ceramide/phospholipids based risk score is associated with the risk of fatal and non-fatal cardiovascular events in patients with stable CHD. The score is attenuated by adjustment for biomarkers indicating cardiorenal dysfunction and inflammatory activity and may be related to underlying mechanisms for adverse outcomes in stable CHD.
Acknowledgement/Funding
The original STABILITY study was funded by GlaxoSmithKline
Development and Validation of a Protein-Based Risk Score for Cardiovascular Outcomes Among Patients With Stable Coronary Heart Disease