Establishing serum proprotein convertase Subtilisin/Kexin type 9 (PCSK9) reference intervals

Abstract

Background and aims Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is a key regulator of lipid metabolism and a therapeutic target in cardiovascular disease. Despite its growing clinical relevance, reference intervals (RIs) for circulating PCSK9 are not established, limiting its interpretative utility in clinical and research settings. In this study, we established serum PCSK9 RIs in a healthy adult population, accounting for key demographic and biological variables such as age, sex, and lipid profile. Methods We enrolled 132 healthy adult blood donors (88 men, 44 women) aged 18–65 years with normal lipid profiles and no history of cardiovascular, autoimmune, or metabolic disorders. Serum PCSK9 concentrations were measured using a validated ELISA assay. Statistical analyses included assessment of distribution, sex- and age-based stratification, and calculation of RIs using both parametric and robust methods, following CLSI guidelines. Results The mean serum PCSK9 level was 428 ± 119 ng/mL. PCSK9 values were significantly higher in women compared to men and showed a moderate positive correlation with age ( r = 0.36, p < 0.001). RIs for the overall population ranged from 201 to 659 ng/mL (parametric method). Stratified RIs demonstrated notable sex- and age-related differences, reinforcing the need for subgroup-specific interpretation. Conclusion This study provides the first rigorously derived RIs for serum PCSK9 in a healthy Caucasian population. The observed sex- and age-related variations underscore the importance of personalized reference values.