RT Journal Article
SR Electronic
T1 High levels of cathepsin D and cystatin B are associated with increased risk of coronary events
JF Open Heart
JO Open Heart
FD British Cardiovascular Society
SP e000353
DO 10.1136/openhrt-2015-000353
VO 3
IS 1
A1 Isabel Gonçalves
A1 Karin Hultman
A1 Pontus Dunér
A1 Andreas Edsfeldt
A1 Bo Hedblad
A1 Gunilla Nordin Fredrikson
A1 Harry Björkbacka
A1 Jan Nilsson
A1 Eva Bengtsson
YR 2016
UL http://openheart.bmj.com/content/3/1/e000353.abstract
AB 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.