title: Association between plasma PCSK9 levels and 10-year progression of carotid atherosclerosis beyond LDL-C: A cohort study.
abstract: BACKGROUND
  To evaluate the association of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels with the progression of carotid atherosclerosis and identify additional PCSK9-lipoprotein-atherosclerosis pathway beyond low-density lipoprotein cholesterol (LDL-C).
  
  
  METHODS
  Among 643 participants (aged from 45 to 74years) free of cardiovascular disease at baseline, carotid ultrasound examinations were performed in 2002 (baseline) and 2012 (follow-up). None of the participants were taking lipid-lowering drugs or had detectable carotid plaques at baseline. Carotid plaque formation and total plaque area (TPA) were used to reflect 10-year progression of atherosclerosis.
  
  
  RESULTS
  Baseline plasma PCSK9 levels have a wide variation, ranged from 64.60-532.20ng/mL (median: 192.57ng/mL). PCSK9 levels were significantly associated with new plaque formation after adjusting for LDL-C levels and other risk factors (relative risk for per quartile increase=1.09, 95% confidence interval: 1.03-1.15). PCSK9 levels were also linearly associated with TPA after multivariate adjustment including LDL-C (P=0.008). Among participants with the lowest or second tertile of LDL-C, PCSK9 quartiles were linearly associated with TPA (P=0.021), but the association lost significance after additional adjustment for very low-density lipoprotein cholesterol (VLDL-C) tertiles (P=0.072). Further stepwise linear regression (entry, 0.05; removal, 0.05) indicated that VLDL-C tertiles could be entered into the model but PCSK9 quartiles could not.
  
  
  CONCLUSIONS
  Plasma PCSK9 levels are associated with 10-year progression of atherosclerosis. The LDL-independent association of PCSK9 levels may through its ability to regulate VLDL-C levels. Further research is needed to systematically investigate the role of PCSK9 for the pathogenesis of atherosclerosis, beyond LDL-C metabolism.
authors.affiliation: Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Wuxiang
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China. Electronic address: deezhao@vip.sina.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhao
mesh_terms: D000368:Aged; D002339:Carotid Arteries / Q000000981:diagnostic imaging* / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000378:metabolism; D002681:China / Q000453:epidemiology; D008078:Cholesterol, LDL / Q000097:blood*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9 / Q000097:blood*
chemical_list: D008078:Cholesterol, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: Atherosclerosis; Carotid ultrasound; Low-density lipoprotein cholesterol; Proprotein convertase subtilisin/kexin type 9; Very low-density lipoprotein cholesterol