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 Gonçalves, Isabel A1 Hultman, Karin A1 Dunér, Pontus A1 Edsfeldt, Andreas A1 Hedblad, Bo A1 Fredrikson, Gunilla Nordin A1 Björkbacka, Harry A1 Nilsson, Jan A1 Bengtsson, Eva 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.