Plasma PCSK9 predicts microvascular function but not arterial stiffness in African-Americans with well controlled type 2 diabetes

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) genetic variants are associated with increased risk of type 2 diabetes mellitus (T2DM). Contradictory outcomes have been reported for the relationship between PCSK9 and increased diabetes risk. Furthermore, the relationship between PCSK9 levels, glycemic status, and vascular function among different ethnic groups is still not fully understood. African-Americans suffer disproportionately from many chronic diseases including T2DM due to many factors including environmental, socioeconomic and genetics factors. Thus, we aimed in this study is to examine the association between plasma PCSK9 and vascular dysfunction in African-Americans with T2DM. PCSK9 and total nitric oxide (NO) levels were measured by enzyme-linked immunosorbent assays (ELISA). Microvascular function was assessed by the vascular reactivity index (VRI) and large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). A total of 146 participants with T2DM were enrolled in this study. Mean patients’ age was 60 ± 8 years. Eighty percent (80%) had hypertension, 90% had dyslipidemia and 15% had chronic kidney disease. Total population was categorized into two groups based on HbA1c median value (7.5%). PCSK9 levels negatively correlated with VRI but not PWV in the total population and in well controlled patients with HbA1c ≤7.5% (r=-0.175, p=0.036 and r=-0.293, p=0.010; respectively). PCSK9 levels positively correlated with total NO levels in total population and in well controlled patients (r=0.186, p=0.0024 and r=0.256, p=0.023; respectively). Univariate analysis exhibited that PCSK9 levels were associated with VRI, but not PWV, in total population and in well controlled patients ( β =-0.175, p=0.036 and β =-0.293, p=0.010; respectively). Multivariable-adjusted regression analysis revealed that PCSK9 levels predicted VRI in well controlled patients ( β =-0.384, p=0.033) but not in poorly controlled patients. Furthermore, changes in total NO availability did not impact the PCSK9-VRI association in well controlled diabetic patients. Larger studies are needed to confirm the association of circulating PCSK9 with subclinical microvascular changes in T2DM, particularly in patients with good glycemic control.