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Background  Proprotein convertase subtilisin/kexin type 9 ( PCSK 9) is involved in cholesterol homeostasis, inflammation, and oxidative stress. This study investigated the association of plasma  PCSK 9 levels with the presence and severity of peripheral artery disease ( PAD ) and with parameters of endothelial homeostasis.    Methods and Results  A post hoc analysis of 2 randomized trials (115 patients, 44 with  PAD  and 71 without atherosclerotic disease) was conducted. Patients with  PAD  had significantly higher plasma  PCSK 9 levels than those without (471.6±29.6 versus 302.4±16.1 ng/mL,  P <0.001). Parameters for glucose homeostasis, endothelial progenitor cell functions, apoptotic circulating endothelial cell counts, and plasma levels of vascular endothelial growth factor–A165 and oxidized low‐density lipoprotein were correlated with  PCSK 9 concentration. By multivariable linear regression analysis, presence of  PAD , plasma glucose or hemoglobin A1c levels, apoptotic  circulating endothelial cell  counts, and vascular endothelial growth factor–A165 concentration were found to be associated with  PCSK 9 levels after multivariable adjustment. Patients with extensive involvement of  PAD  or with severe  PAD  had significantly higher  PCSK 9 levels than those without PAD. Computed tomographic angiography showed that the numbers of chronic total occlusion sites and vessels involved were positively associated with  PCSK 9 levels in patients with  PAD  ( r =0.40,  P =0.01, and  r =0.36,  P =0.02, respectively).    Conclusion   PCSK 9 levels were significantly higher in patients with  PAD , especially those with advanced  PAD . Further large‐scale studies examining the effect of  PCSK 9‐targeting therapies or the modification of  PCSK 9 levels on cardiovascular outcomes in this clinical setting are warranted.    Clinical Trial Registration  Cohort 1: URL: ClinicalTrials.gov. Unique identifier: NCT01952756; cohort 2: URL: ClinicalTrials.gov. Unique identifier: NCT02194686.

journal of the american heart association

Plasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 Are Elevated in Patients With Peripheral Artery Disease and Associated With Metabolic Disorders and Dysfunction in Circulating Progenitor Cells