Circulating PCSK9 as a prognostic biomarker of cardiovascular events in individuals with type 2 diabetes: evidence from a 16.8-year follow-up study

• Published in: Cardiovascular diabetology 2023-08, Vol.22 (1), p.1-222, Article 222
• Main Authors: Ruscica, Massimiliano, Macchi, Chiara, Giuliani, Angelica, Rizzuto, Alessandra Stefania, Ramini, Deborah, Sbriscia, Matilde, Carugo, Stefano, Bonfigli, Anna Rita, Corsini, Alberto, Olivieri, Fabiola, Sabbatinelli, Jacopo
• Format: Article
• Language: English
• Subjects: All-cause mortality; Arteriosclerosis; Atherosclerosis; Biomarkers; Body mass index; Cardiovascular disease; Cardiovascular diseases; Cardiovascular risk; Cholesterol; Collaboration; Creatinine; Diabetes; Diabetes mellitus (non-insulin dependent); Epidemiology; Fasting; Glucose; Heart attacks; High density lipoprotein; Homeostasis; Hypotheses; Inflammation; Ischemia; Kexin; Kidney diseases; Life expectancy; Major adverse cardiovascular events; Morbidity; Mortality; Proprotein Convertase Subtilisin/kexin type 9; Proprotein convertases; Risk assessment; Sex differences; Software; Subtilisin; Type 2 diabetes mellitus; Variables; Variance analysis
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-023-01948-8

BackgroundAtherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality, being twofold to fourfold more common in patients with type 2 diabetes mellitus (T2DM) than in individuals without diabetes. However, despite this decade-old knowledge, the identification of a specific prognostic risk biomarker remains particularly challenging.MethodsTaking advantage of a large sample of Caucasian patients (n = 529) with a diagnosis of T2DM followed for a median of 16.8 years, the present study was aimed at testing the hypothesis that fasting serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels could be prognostic for major adverse cardiovascular events (MACE) and all-cause mortality.ResultsMedian levels of PCSK9 were 259.8 ng/mL, being higher in women compared to men and increasing even more in the presence of a complication (e.g., diabetic kidney disease). PCSK9 positively correlated with markers of blood glucose homeostasis (e.g., HbA1c, fasting insulin and HOMA-IR) and the atherogenic lipid profile (e.g., non-HDL-C, apoB and remnant cholesterol). Serum PCSK9 predicted new-onset of MACE, either fatal or non-fatal, only in women (Odds Ratio: 2.26, 95% CI 1.12–4.58) and all-cause mortality only in men (Hazard Ratio: 1.79, 95% CI 1.13–2.82).ConclusionsConsidering that up to two-thirds of individuals with T2DM develop ASCVD in their lifetime, the assessment of circulating PCSK9 levels can be envisioned within the context of a biomarker-based strategy of risk stratification. However, the sex difference found highlights an urgent need to develop sex-specific risk assessment strategies.Trial registration: It is a retrospective study.