High apo-CIII level correlates with poor lipid status, pro-inflammatory and fibrotic biomarker profile, and adverse cardiovascular outcome in patients with recent acute coronary syndrome

Background Apo-CIII regulates triglyceride-rich lipoprotein metabolism and has been associated with cardiovascular risk. Purpose To investigate the role of apo-CIII as a biomarker and potential treatment target in high-risk patients with recent acute coronary syndrome (ACS). Methods 200 patients with recent ACS undergoing PCI within 4 weeks of index event were recruited. Each patient made two visits to the research unit: within 4 weeks (V1) and 4 months after the index event (V2). At each visit, blood samples were taken for comprehensive biomarker assessment using, for example, the Olink Proteomics platform. All patients were clinically followed up for 5.5 years for major adverse cardiovascular events (MACE), defined as death, non-fatal MI, stroke, and acute revascularization. Results Plasma apo-CIII levels are strongly correlated between the visits (r=0.72, p<0.0001) with significantly higher levels at V2 compared to V1 (p<0.05) (Fig 1A). As expected, apo-CIII levels are positively correlated with triglycerides, LDL-c, ApoB, and remnant cholesterol levels at both visits. Apo-CIII levels at the more stable phase (V2) are also correlated with markers of inflammation and fibrosis, as measured by CHI3L1 (r=0.26, p=0.0007) (Fig 1B), cathepsin D (r=0.31, p<0.0001) (Fig 1C), and galactin-3 (r=0.21, p=0.007) (Fig 1D). Patients who experienced MACE had significantly higher levels of apo-CIII at visit 2 than those who were event-free (p<0.05). Using the ROC-identified optimal cut-off value of 2.77 mg/dL, patients above this cut-off had a significantly higher event rate during the follow-up, even after adjustment for age and LDL level (p<0.05, HR=2.28) (Fig 2). Conclusions High apo-CIII levels in well-treated post-ACS patients on optimal standard therapy are associated with poor lipid and inflammatory status, and worse CV outcome.