Journal Article

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

Bonfigli, Anna Rita, Olivieri, Fabiola, Sabbatinelli, Jacopo, Macchi, Chiara, Carugo, Stefano, Ruscica, Massimiliano, Corsini, Alberto, Sbriscia, Matilde, Rizzuto, Alessandra Stefania, Giuliani, Angelica, Ramini, Deborah

2023

Overview

Background Atherosclerotic 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. Methods Taking 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. Results Median 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). Conclusions Considering 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.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: All-cause mortality / Angiology / Arteriosclerosis / Atherosclerosis / Biomarkers / Body mass index / Cardiology / 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 / Medicine / Medicine & Public Health / Morbidity / Mortality / Proprotein Convertase Subtilisin/kexin type 9 / Proprotein convertases / Risk assessment / Sex differences / Software / Subtilisin / Type 2 diabetes mellitus / Variables / Variance analysis