Apolipoprotein screening by LC-MRM-MS for the prediction of cardiovascular death in patients with chronic systolic heart failure

Abstract

Risk stratification in systolic chronic heart failure (HF) is critical to identify the patients who may benefit the most from advanced HF therapies. We aimed identifying new biomarkers to improve prognosis evaluation and help to better understand HF physiopathology. Proteomic analysis of plasma from a case/control population of 198 patients with chronic systolic HF (ejection fraction < 45%): 99 patients who died from cardiovascular cause within 3 years and 99 patients alive at 3 years (matched on age, sex and HF etiology), identified 3 apolipoproteins (Apo) associated with cardiovascular death. Apo screening (panel of 15 Apo: Apo-A1, -A2, -A4, -B100, -C1, -C2, -C3, -C4, -D, -E, -F, -H, -J, -L1 and -M) was then targeted using LC-MRM-MS in order to quantify their circulating levels. In the final statistical model, 4 Apo remained independently associated with the occurrence of cardiovascular death. The Apo-B100 was negatively associated (OR = 0.50). The Apo-C1, -J and -M were positively associated (OR = 2.22, OR = 2.25 and OR = 4.30, respectively). Net reclassification improvement and integrated discrimination improvement indexes demonstrated that Apo-B100, -C1, -J and -M significantly improved the prediction of cardiovascular death. There was no interaction between patients with and those without ischemic HF. Our results showed that a screening of Apo using LC-MRM-MS might be useful in clinical practice for risk stratification of patients with chronic systolic HF. Further research is needed to better understand the role of these Apo in left ventricle remodeling and HF physiopathology.