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

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.

LDL Cholesterol Variability Impacts the Prognosis of Patients with Chronic Ischemic Heart Disease: A Real-World Italian Experience

“…In the context of comorbidities increasing ASCVD risk, type 2 diabetes mellitus can not be overlooked. Indeed, estimates from epidemiological studies report that up to twothirds of individuals with type 2 diabetes mellitus develop ASCVD in their lifetime, with many events attributable to ischemic heart disease [41]. This was consistent with our study reporting a 26% increase in the risk of hard outcomes in people diagnosed with type 2 diabetes mellitus.…”

Prognostic Value of PCSK9 Levels in Premenopausal Women at Risk of Breast Cancer—Evidence from a 17-Year Follow-Up Study

“…Thirdly, although no gold-standard assays are recognized for the evaluation of circulating PCSK9, the intra-assay and interassay coefficients of variability of the assay we used showed good reproducibility. This has been demonstrated by running this assay in our lab with approximately 8500 samples over the last few years [52,53]. Furthermore, the mean values we found in these women are in line with those we detected in women in early pregnancy [20].…”

Maternal Obesity Modulates Cord Blood Concentrations of Proprotein Convertase Subtilisin/Kexin-type 9 Levels

“…In addition, we do not have data on maternal lipid profiles, circulating PCSK9 concentrations, or markers of glucose metabolism. Although in previous studies, PCSK9 levels have been correlated with markers of blood glucose homeostasis in patients with type 2 diabetes [ 48 ], in our retrospective study, we used stored samples that were of limited quantity and were not appropriately processed for lipid analysis, inflammation markers, or markers of glucose metabolism. Future longitudinal studies would be important in further delineating the relationship between maternal obesity or diabetes and infant PCSK9 levels.…”