Serum osteoprotegerin as a long-term predictor for patients with stable coronary artery disease and its association with diabetes and statin treatment: A CLARICOR trial 10-year follow-up substudy

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  • Mette Bjerre
  • Jørgen Hilden, University of Copenhagen
  • ,
  • Per Winkel, University of Copenhagen
  • ,
  • Gorm Boje Jensen, University of Copenhagen
  • ,
  • Erik Kjøller, Copenhagen University Hospital - Rigshospitalet, University of Copenhagen
  • ,
  • Ahmad Sajadieh, University of Copenhagen
  • ,
  • Jens Kastrup, University of Copenhagen
  • ,
  • Hans Jørn Kolmos, Odense University Hospital
  • ,
  • Anders Larsson, Uppsala University
  • ,
  • Johan Ärnlöv, Karolinska Institute, Dalarna University
  • ,
  • Janus Christian Jakobsen, Copenhagen University Hospital - Rigshospitalet, Holbæk Hospital, University of Southern Denmark
  • ,
  • Christian Gluud, Copenhagen University Hospital - Rigshospitalet

BACKGROUND AND AIMS: Elevated circulating levels of osteoprotegerin (OPG) are known to add to the prediction of cardiovascular mortality. Our objective was to clarify the long-term risk associated with serum OPG and the possible influence of diabetes and statins on OPG levels in patients with stable coronary artery disease (CAD).

METHODS: We assessed the placebo-treated group (n = 1998) from the CLARICOR trial (NCT00121550), a cohort with stable CAD. At entry, 15% of the participants had diabetes and 41% received statins. Serum OPG levels were measured in blood drawn at randomization. Participants were followed through public registers for 10 years.

RESULTS: OPG levels correlated positively with diabetes status, age, CRP and female sex, but negatively with the use of statins. CAD participants with diabetes had significantly elevated serum OPG levels compared to participants without diabetes, p < 0.0001. The participants without diabetes treated with statins presented with significantly lower serum OPG levels than the corresponding non-statin-users (p < 0.0001). However, statin use showed no association with OPG levels in the participants with diabetes. High OPG levels at entry showed long-term associations with all-cause mortality and cardiovascular events (hazard ratio associated with factor 10 OPG increase 15.9 (95% CI 11.0-22.9) and 6.38 (4.60-8.90), p = 0.0001, even after adjustment for standard predictors (3.16 (1.90-5.25) and 2.29 (1.53-3.44), p < 0.0001).

CONCLUSIONS: Circulating OPG holds long-term independent predictive ability for all-cause mortality and cardiovascular events in CAD participants. OPG levels were associated with diabetes, age, and female sex and statin treatment was associated with lower OPG levels in the absence of diabetes.

Original languageEnglish
JournalAtherosclerosis
Volume301
Pages (from-to)8-14
Number of pages7
ISSN0021-9150
DOIs
Publication statusPublished - May 2020

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