The circulating furin-cleaved/mature PCSK9 ratio has a potential prognostic significance in statin-naïve patients with acute ST elevation myocardial infarction.

Background and aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulates as mature and furin-cleaved forms, but their biological functions are uncertain. We investigated whether their levels associate with prognosis in patients with acute ST elevation myocardial infarction (STEMI). Methods: We enrolled 160 statin-naïve patients with acute STEMI and followed for 3 years. PCSK9 subtype levels were determined by an enzyme-linked immunosorbent assay before and at five timepoints up to 48 h after emergent coronary intervention. The occurrence of coronary and cardiac events was compared between subjects stratified by the PCSK9 level. Results: One hundred and twenty-six patients completed 3 years of follow-up. In the acute phase, both PCSK9 subtype levels decreased, and thereafter increased from 6 to 48 h (mature: from 198 ± 67 to 334 ± 116 ng/mL, furin-cleaved: from 20 ± 7 to 39 ± 16 ng/mL, both p < 0.01). Major cardiac events occurred in 46 patients. The furin-cleaved/mature PCSK9 ratio at 48 h after coronary intervention predicted the likelihood of experiencing of events; patients in the third tertile had lower event-free survival than those in the first and second tetiles in Kaplan-Meier analysis (p = 0.004). Multivariate Cox regression analysis revealed that this ratio had a greater impact (HR: 1.92; 95% CI: 1.06-3.45, p = 0.03) on events than other known atherosclerosis risk factors. Conclusions: The furin-cleaved/mature PCSK9 ratio was associated with 3-year cardiovascular events in statin-naïve patients with acute STEMI, suggesting a potential link between furin cleavage process of PCSK9 and its effect on prognosis. (249 words).