Serum proprotein convertase subtilisin/Kexin type 9 and vascular disease in type 2 diabetic patients

Abstract

Background Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) levels have been suggested as novel atherosclerotic biomarker. PCSK9 plays important roles in the pathogenesis of atherosclerosis by regulating the degradation of low‐density lipoprotein receptor as well as different inflammatory pathways. Considering the important prognostic role of arterial stiffness in cardiovascular disease (CVD), the aim of the study is to investigate the correlation between PCSK9 levels and arterial stiffness in a cohort of diabetic patients, without previous CV events. Methods This cross‐sectional analysis enrolled 401 Caucasian patients with type II diabetes mellitus (T2DM). PCSK9 levels were measured by ELISA test, arterial stiffness was estimated by measuring carotid‐femoral pulse wave velocity (PWV). Results Patients were divided in three tertiles according to increasing value of PCSK9. From the I to the III tertiles, there was a significant increase in high sensitivity C‐reactive protein (hs‐CRP), fibrinogen and white blood cells (WBC) and a reduction in estimated glomerular filtration rate (e‐GFR). Patients with higher levels of PCSK9 presented increased systolic, diastolic blood pressure, pulse pressure and PWV. PWV was significantly and directly correlated with PCSK9, fibrinogen, age, BMI and PP, and indirectly correlated with diet, lifestyle and e‐GFR. Serum PCSK9 was the major predictor of PWV, justifying a 16.9% of its variation. Conclusion Our study demonstrates a close association between circulating PCSK9 levels and PWV in T2DM subjects without previous CV events even after adjusting for well‐known CV risk factor and pharmacological medications. Serum PCSK9 could be a useful biomarker for CV risk stratification in diabetic subjects.

Association between serum PCSK9 and coronary heart disease in patients with type 2 diabetes mellitus

“…In our study, in a group of Chinese Han T2DM patients, the plasma level of PCSK9 was positively correlated with the severity of coronary heart disease, as shown by the linear correlation results (diseased vessels: r = 0.35, p < 0.001; GS: r = 0.46, p < 0.001, significantly). To date, only Armentaro et al have reported similar results in Caucasian populations [20]. It is important to emphasize how the genetic background affects clinical outcomes.…”

“…To explore the relationship between PCSK9 and CHD severity, we divided the patients in the CHD group into four subgroups based on the quartile of PCSK9 levels (Supplementary Table 1). We observed that the percentage of patients with three-vessel disease (17.30% vs. 31.01% vs. 50.45% vs. 66.52%, p < 0.001) and GS [23 (21) vs. 30 (21) vs. 36 (24) vs. 46 (20), p < 0.001] increased in the high PCSK9 group, whereas the percentage of patients with one-vessel disease decreased (p < 0.001), indicating that PCSK9 levels may be associated with CHD severity. Furthermore, Spearman's correlation analysis showed that serum PCSK9 levels were significantly and positively associated with diseased vessels and GS (r = 0.35, p < 0.001; r = 0.46, p < 0.001, respectively) (Fig.…”

“…Several studies have shown that plasma PCSK9 levels are significantly higher in patients with CHD than in healthy individuals [ 20 , 44 , 45 ]. Existing epidemiological and clinical research results have shown that PCSK9 levels are high in patients with diabetes.…”

“…Most importantly, circulating PCSK9 has been recognized as an adverse cardiovascular risk factor in patients with CAD [18,19]. Owing to the close relationship between lipid and glucose metabolism, an increasing number of studies have found a close relationship between PCSK9 and diabetes [20,21]. However, the pathogenicity of PCSK9 in T2DM patients and T2DM patients with CHD has not been completely established.…”