Plasma Levels of Propionylcarnitine Improved Prediction of Heart Failure and All-Cause Mortality in Patients with Stable Coronary Artery Disease.

BACKGROUND

Plasma metabolites could be suitable as predictive biomarkers for cardiovascular pathologies or death, thereby improving the prediction of protein biomarkers. The release of acylcarnitines may be altered after coronary artery disease (CAD) in subjects with recurrent clinical outcomes, and this could be used as a prognosis tool.

METHODS

Patients with stable coronary artery disease (SCAD) who had suffered an acute coronary syndrome 6-9 months before were followed for up to 4.3 years for adverse events. Soluble pro-inflammatory/fibrotic proteins, and a panel of 13 amino acids and 13 acylcarnitines, were evaluated by ELISA and metabolomics analyses as potential predictors of a primary outcome [heart failure (HF) or death].

RESULTS

Among 139 patients (67.0 years old, BMI = 28.6 kg/m2, and 71.2% male), 25 developed the primary outcome after a mean follow-up of 2.2 years. These patients showed increased plasma levels of NT-proBNP (1300 vs. 250 pg/mL; p < 0.001), pro-inflammatory/fibrotic MCP-1 (1.7 vs. 1.4 × 102 pg/mL; p = 0.043), Gal-3 (12.7 vs. 7.9 ng/mL; p < 0.001), and NGAL (2.7 vs. 1.6 × 102 ng/mL; p < 0.001), and lower acetyl- and propionylcarnitines (0.59 vs. 0.99 µM, p = 0.007, and 3.22 vs. 6.49 × 10-2 µM, p < 0.001, respectively). Instead, plasma amino acids were not significantly changed. Through a multivariable logistic regression analysis, a combined model of age, Gal-3, and the NGAL/propionylcarnitine ratio showed the highest prediction for HF or death (AUC = 0.88, sensitivity = 0.8, and specificity = 0.81; p < 0.001).

CONCLUSIONS

Patients with SCAD led to recurrent HF or all-cause death. Interestingly, increased levels of plasma NGAL and Gal-3, and a reduction in propionylcarnitine, could predict the occurrence of these events.