title: Prognostic impact of circulating soluble LR11 on long-term clinical outcomes in patients with coronary artery disease.
abstract: BACKGROUND
  LR11, a member of LDL receptor family, is a novel marker of the proliferation of intimal smooth muscle cells (SMCs). LR11 is released in soluble form (sLR11) by proteolytic shedding and has biological activity toward SMC migration. We previously showed that circulating sLR11 positively correlates with carotid intima-medial thickness (IMT) independently of classical atherosclerotic risk factors and that it significantly associates with the severity of CAD. However, the association between sLR11 and long-term clinical outcomes remain uncertain.
  
  
  RESULTS
  This study included 438 consecutive patients (mean age, 65.8 ± 9.6 y; male, 82.4%) who underwent coronary intervention between March 2003 and December 2004 at our institution. The patients were assigned to quartiles according to pre-procedural sLR11 values. The primary endpoints were composite cardiovascular disease (CVD) endpoints including cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke. During median follow-up of 2876 days, composite CVD endpoints occurred 97 (22.1%) patients including 41 (9.4%) with cardiovascular disease (CVD)-related death, 36 (8.2%) non-fatal ACS and 20 (4.6%) non-fatal strokes. The hazard ratio (HR) for composite CVD endpoints significantly and dose-dependently increased with sLR11 levels (p for trend = 0.0077). A higher logarithm-transformed sLR11 value was associated with a greater risk of composite CVD endpoints, and the increased number of adverse long-term clinical outcomes persisted even after adjustment for other independent variables (HR 1.87 95%CI 1.02-3.31, p = 0.0435).
  
  
  CONCLUSIONS
  Elevated sLR11 levels were significantly associated with higher long-term adverse cardiac events in patients with CAD. Further extensive studies are expected to elucidate the mechanistic role of sLR11 and its clinical value as a prognostic marker in the development of atherosclerosis.
authors.affiliation: Department of Cardiovascular Medicine, Juntendo University Shizuoka Hospital, Japan. Electronic address: m-ogita@sa2.so-net.ne.jp.
authors.forename: Manabu
authors.initials: M
authors.lastname: Ogita
authors.affiliation: Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Miyauchi
authors.affiliation: Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Kasai
authors.affiliation: Department of Cardiovascular Medicine, Juntendo University Shizuoka Hospital, Japan.
authors.forename: Shuta
authors.initials: S
authors.lastname: Tsuboi
authors.affiliation: Department of Cardiovascular Medicine, Juntendo University Shizuoka Hospital, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Wada
authors.affiliation: Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Naito
authors.affiliation: Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Konishi
authors.affiliation: Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Japan.
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Dohi
authors.affiliation: Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamura
authors.affiliation: Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Okazaki
authors.affiliation: Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Japan.
authors.forename: Naotake
authors.initials: N
authors.lastname: Yanagisawa
authors.affiliation: Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Cardiovascular Medicine, Juntendo University Shizuoka Hospital, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Suwa
authors.affiliation: Department of Clinical-laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Japan.
authors.forename: Meizi
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Clinical-laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Bujo
authors.affiliation: Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Daida
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000453:epidemiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan / Q000453:epidemiology; D026502:LDL-Receptor Related Proteins / Q000097:blood*; D008297:Male; D026901:Membrane Transport Proteins / Q000097:blood*; D008875:Middle Aged; D009017:Morbidity / Q000639:trends; D009419:Nerve Tissue Proteins; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013997:Time Factors
chemical_list: D015415:Biomarkers; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C102582:SORL1 protein, human
keywords: Biomarker; Coronary artery disease; Long-term outcomes; Smooth muscle cell