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

Abstract

Abstract 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, particularly challenging remains the identification of a specific prognostic risk biomarker. Methods. Taking advantage of a large sample of Caucasian patients (n = 568) 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 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 (Odd Ratio: 2.26, 95% CI 1.12–4.58) and all-cause mortality only in men (Hazard Ratio: 1.79 [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 we found highlight an urgent need to develop sex-specific risk assessment strategies. Trial registration It is a retrospective study