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}


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

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