Abstract Body (Do not enter title and authors here): Background: Although PCSK9 inhibitors have demonstrated significant cardiovascular benefits, the prognostic role of circulating PCSK9 levels in patients with coronary multi-vessel disease (MVD) remains controversial. Given the complex pathophysiology of MVD, further evidence is needed to clarify the relationship between PCSK9 levels, disease severity, and long-term outcomes.
Aims: To investigate the association between circulating PCSK9 levels and long-term cardiovascular outcomes and coronary lesion severity in MVD patients.
Methods: This secondary analysis utilized data from a large, prospective, multicenter observational cohort involving 18,701 patients with coronary artery disease (CAD). A total of 1,060 MVD patients who underwent percutaneous coronary intervention were included. The primary endpoint was 2-year major adverse cardiovascular events (MACE, including all-cause death, myocardial infarction, and unplanned revascularization). The secondary endpoints were unplanned revascularization and coronary lesion severity, assessed using the SYNTAX score (≥22 indicating intermediate-high severity). Cox and logistic regression analyses were used to evaluate associations between PCSK9 levels and outcomes.
Results: The mean age of patients was 62.5 ± 10.7 years, with 75.8% being male. The median PCSK9 concentration was 114.93 ng/mL (IQR: 81.55–165.30). For the primary endpoint, multivariable Cox regression analysis demonstrated that patients in the highest PCSK9 tertile (Q3) had a significantly higher risk of MACE compared to those in the lowest tertile (Q1) (HR: 1.751; 95% CI: 1.035–2.961; p = 0.037), even after adjusting for LDL-C and apolipoprotein B (Table 1). No significant interaction was observed between PCSK9 and LDL-C levels. Furthermore, elevated PCSK9 levels were independently associated with a higher risk of unplanned revascularization (HR: 2.150; 95% CI: 1.118–4.135; p = 0.022) (Table 2). In addition, higher PCSK9 levels were significantly associated with intermediate-to-high coronary lesion severity, as defined by a SYNTAX score ≥22 (OR: 1.458; 95% CI: 1.014–2.097) (Table 3).
Conclusion: Elevated circulating PCSK9 levels are significantly associated with worse clinical outcomes and greater coronary lesion severity in patients with MVD, highlighting the potential of PCSK9 as a prognostic biomarker and therapeutic target beyond traditional lipid parameters in high-risk CAD populations.