title: Elevated Circulating Osteoprotegerin and Renal Dysfunction Predict 15-Year Cardiovascular and All-Cause Mortality: A Prospective Study of Elderly Women.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Western Australia School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, Perth, Australia; Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Lewis
authors.affiliation: University of Western Australia School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, Perth, Australia; Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Wai H
authors.initials: WH
authors.lastname: Lim
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.affiliation: Centre for Kidney Research, Children's Hospital at Westmead School of Public Health, Sydney Medical School, The University of Sydney, Sydney, Australia.
authors.forename: Germaine
authors.initials: G
authors.lastname: Wong
authors.affiliation: University of Western Australia School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, Perth, Australia; Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, Australia; PathWest, Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Ee M
authors.initials: EM
authors.lastname: Lim
authors.affiliation: Section of Specialised Endocrinology, Department of Endocrinology, Oslo University Hospital, Rikshospitalet, and University of Oslo, Oslo, Norway.
authors.forename: Jens
authors.initials: J
authors.lastname: Bollerslev
authors.affiliation: University of Western Australia School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, Perth, Australia; Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Prince
mesh_terms: D000368:Aged; D001315:Australia; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality*; D002319:Cardiovascular System / Q000378:metabolism / Q000473:pathology; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D053244:Osteoprotegerin / Q000097:blood*; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000097:blood / Q000401:mortality; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000401:mortality*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; D003404:Creatinine