Proprotein convertase subtilisin/kexin type 9 in rheumatoid arthritis.
OBJECTIVE
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation and that has been linked with cardiovascular risk. The purpose of the present study was to examine whether PCSK9 levels are related to both abnormalities in the lipid profile and the severe atherosclerosis that occur in rheumatoid arthritis (RA) patients.


METHODS
Cross-sectional study that encompassed 520 individuals; 326 patients with RA and 194 age- and sex-matched controls. PCSK9 and lipoproteins serum concentrations, standard lipid profile and carotid intima-media thickness (cIMT) and carotid plaques were assessed in patients and controls. A multivariable analysis, adjusted for standard cardiovascular risk factors, was performed to evaluate the influence of PCSK9 on RA related dyslipidaemia and subclinical carotid atherosclerosis.


RESULTS
After adjusting for classical cardiovascular risk factors, lipid profile and statins, RA patients showed lower PCSK9 serum concentrations than controls (beta coefficient -45 95%CI [-53, -38] ng/ml, p=0.00). PCSK9 was associated with both cIMT and the presence of carotid plaques in RA patients. However, this association was lost after adjusting for classical cardiovascular risk factors.


CONCLUSIONS
PCSK9 is down-regulated in patients with RA.
Division of Rheumatology, Hospital Universitario de Canarias, Tenerife, Spain.
Ivan
I
Ferraz-Amaro
Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.
Raquel
R
López-Mejías
Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.
Begoña
B
Ubilla
Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.
Fernanda
F
Genre
Division of Rheumatology, Hospital Universitario de Canarias, Tenerife, Spain.
Beatriz
B
Tejera-Segura
Central Laboratory Division. Hospital Universitario de Canarias, Tenerife, Spain.
Antonia M
AM
de Vera-González
Central Laboratory Division. Hospital Universitario de Canarias, Tenerife, Spain.
Agustín F
AF
González-Rivero
Division of Internal Medicine, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, RETICEF, Santander, Spain.
Jose M
JM
Olmos
Division of Internal Medicine, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, RETICEF, Santander, Spain.
Jose L
JL
Hernández
Division of Epidemiology and Computational Biology, School of Medicine, IDIVAL, University of Cantabria, Santander; and CIBER Epidemiología y Salud Pública (CIBERESP), Santander, Spain.
Javier
J
Llorca
Dept.Rheumatology, Complejo Hosp.Univ. Santiago de Compostela, Spain; School of Medicine, Univ.Cantabria, Santander, Spain; Cardiovascular Pathophysiology & Genomics Res.Unit, School Physiology, Health Sciences, Univ. Witwatersran, Johannesburg, S.Africa.
Miguel A
MA
González-Gay
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D059168:Carotid Intima-Media Thickness; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D000071449:Proprotein Convertase 9 / Q000097:blood*; D015854:Up-Regulation
D008055:Lipids; D008074:Lipoproteins; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9