Article Text

Original research article
High levels of cathepsin D and cystatin B are associated with increased risk of coronary events
  1. Isabel Gonçalves1,2,
  2. Karin Hultman1,
  3. Pontus Dunér1,
  4. Andreas Edsfeldt1,2,
  5. Bo Hedblad3,
  6. Gunilla Nordin Fredrikson1,
  7. Harry Björkbacka1,
  8. Jan Nilsson1 and
  9. Eva Bengtsson1
  1. 1Experimental Cardiovascular Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden
  2. 2Department of Cardiology, Skåne University Hospital, Malmö, Sweden
  3. 3Department of Clinical Sciences, Lund University, Malmö, Sweden
  1. Correspondence to Eva Bengtsson; eva.bengtsson{at}med.lu.se

Abstract

Objective The majority of acute coronary syndromes are caused by plaque ruptures. Proteases secreted by macrophages play an important role in plaque ruptures by degrading extracellular matrix proteins in the fibrous cap. Matrix metalloproteinases have been shown to be markers for cardiovascular disease whereas the members of the cathepsin protease family are less studied.

Methods Cathepsin D, cathepsin L and cystatin B were measured in plasma at baseline from 384 individuals who developed coronary events (CEs), and from 409 age-matched and sex-matched controls from the Malmö Diet and Cancer cardiovascular cohort.

Results Cathepsin D (180 (142–238) vs 163 (128–210), p<0.001), cathepsin L (55 (44–73) vs 52 (43–67), p<0.05) and cystatin B levels (45 (36–57) vs 42 (33–52), p<0.001) were significantly increased in CE cases compared to controls. In addition, increased cathepsin D (220 (165–313) vs 167 (133–211), p<0.001), cathepsin L (61 (46–80) vs 53 (43–68), p<0.05) and cystatin B (46 (38–58) vs 43 (34–54), p<0.05) were associated with prevalent diabetes. Furthermore, cathepsin D and cystatin B were increased in smokers. The HRs for incident CE comparing the highest to the lowest tertile(s) of cathepsin D and cystatin B were 1.34 (95% CI 1.02 to 1.75) and 1.26 (95% CI 1.01 to 1.57), respectively, after adjusting for age, sex, low-density lipoprotein/high-density lipoprotein ratio, triglycerides, body mass index, hypertension and glucose, but these associations did not remain significant after further addition of smoking to the model. In addition, cathepsin D was increased in incident CE cases among smokers after adjusting for cardiovascular risk factors.

Conclusions The associations of cathepsin D and cystatin B with future CE provide clinical support for a role of these factors in cardiovascular disease, which for cathepsin D may be of particular importance for smokers.

  • cathepsin D
  • cystatin B
  • diabetes
  • coronary events

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Statistics from Altmetric.com

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.