Elevated Circulating Osteoprotegerin and Renal Dysfunction Predict 15-Year Cardiovascular and All-Cause Mortality: A Prospective Study of Elderly Women

PLoS One. 2015 Jul 29;10(7):e0134266. doi: 10.1371/journal.pone.0134266. eCollection 2015.

Abstract

Background: Data on the predictive role of estimated glomerular filtration rate (eGFR) and osteoprotegerin (OPG) for cardiovascular (CVD) and all-cause mortality risk have been presented by our group and others. We now present data on the interactions between OPG with stage I to III chronic kidney disease (CKD) for all-cause and CVD mortality.

Methods and results: The setting was a 15-year study of 1,292 women over 70 years of age initially randomized to a 5-year controlled trial of 1.2 g of calcium daily. Serum OPG and creatinine levels with complete mortality records obtained from the Western Australian Data Linkage System were available. Interactions were detected between OPG levels and eGFR for both CVD and all-cause mortality (P < 0.05). Compared to participants with eGFR ≥60 ml/min/1.73 m2 and low OPG, participants with eGFR of <60 ml/min/1.73 m2 and elevated OPG had a 61% and 75% increased risk of all-cause and CVD mortality respectively (multivariate-adjusted HR, 1.61; 95% CI, 1.27-2.05; P < 0.001 and HR, 1.75; 95% CI, 1.22-2.55; P = 0.003). This relationship with mortality was independent of decline in renal function (P<0.05). Specific causes of death in individuals with elevated OPG and stage III CKD highlighted an excess of coronary heart disease, renal failure and chronic obstructive pulmonary disease deaths (P < 0.05).

Conclusion: The association between elevated OPG levels with CVD and all-cause mortality was more evident in elderly women with poorer renal function. Assessment of OPG in the context of renal function may be important in studies investigating its relationship with all-cause and CVD mortality.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Australia
  • Biomarkers / blood
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality*
  • Cardiovascular System / metabolism
  • Cardiovascular System / pathology
  • Creatinine / blood
  • Female
  • Glomerular Filtration Rate / physiology
  • Humans
  • Osteoprotegerin / blood*
  • Prospective Studies
  • Renal Insufficiency / blood
  • Renal Insufficiency / mortality
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / mortality*
  • Risk Factors

Substances

  • Biomarkers
  • Osteoprotegerin
  • Creatinine

Grants and funding

The study was supported by Kidney Health Australia grant S07 10, Healthway Health Promotion Foundation of Western Australia, Sir Charles Gairdner Hospital Research Advisory Committee Grant and by project grants 254627, 303169 and 572604 from the National Health and Medical Research Council of Australia. The salary of Dr. Lewis is supported by a Raine Medical Research Foundation Priming Grant. None of the funding agencies had any role in the conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.