Wuxiang Xie1, Jing Liu1, Wei Wang1, Miao Wang1, Yue Qi1, Fan Zhao1, Jiayi Sun1, Jun Liu1, Yan Li1, Dong Zhao2. 1. Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China. 2. 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.
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.
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: José Tuñón; Lina Badimón; Marie-Luce Bochaton-Piallat; Bertrand Cariou; Mat J Daemen; Jesus Egido; Paul C Evans; Imo E Hoefer; Daniel F J Ketelhuth; Esther Lutgens; Christian M Matter; Claudia Monaco; Sabine Steffens; Erik Stroes; Cécile Vindis; Christian Weber; Magnus Bäck Journal: Cardiovasc Res Date: 2019-01-01 Impact factor: 10.787
Authors: Lars Lind; Bruna Gigante; Yan Borné; Tobias Feldreich; Jerzy Leppert; Pär Hedberg; Carl Johan Östgren; Fredrik H Nyström; Johan Sundström; Johan Ärnlöv; Damiano Baldassarre; Elena Tremoli; Fabrizio Veglia; Anders Hamsten; Christopher J O'Donnell; Nora Franceschini; Marju Orho-Melander; Jan Nilsson; Olle Melander; Gunnar Engström; Anders Mälarstig Journal: Arterioscler Thromb Vasc Biol Date: 2021-03-04 Impact factor: 8.311