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

Lewis JR, Lim WH, Ueland T, Wong G, Zhu K, Lim EM, Bollerslev J, Prince RL - PLoS ONE (2015)

Bottom Line: This relationship with mortality was independent of decline in renal function (P<0.05).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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Relationship between quartiles of circulating OPG dichotomized by eGFR categories (≥ 60ml/min/1.73m2 and < 60ml/min/1.73m2) for all-cause mortality (top left, n = 547) and cardiovascular mortality (top right, n = 210) and relationship between quartiles of estimated glomerular filtration rate by the CKD-EPI equation (CKD-EPI eGFR) dichotomized by circulating OPG levels (< median and ≥ median) for all-cause mortality (bottom left) and cardiovascular mortality (bottom right).
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pone.0134266.g001: Relationship between quartiles of circulating OPG dichotomized by eGFR categories (≥ 60ml/min/1.73m2 and < 60ml/min/1.73m2) for all-cause mortality (top left, n = 547) and cardiovascular mortality (top right, n = 210) and relationship between quartiles of estimated glomerular filtration rate by the CKD-EPI equation (CKD-EPI eGFR) dichotomized by circulating OPG levels (< median and ≥ median) for all-cause mortality (bottom left) and cardiovascular mortality (bottom right).

Mentions: As we sought to determine whether eGFR modified or accounted for the previously observed relationship between OPG and mortality, interaction tests between OPG and eGFR were undertaken. Using both variables as continuous (log transformed OPG and eGFR ml/min/1.73m2) there was an interaction observed between OPG and eGFR for all-cause mortality (P = 0.044) and CVD mortality (P = 0.028). Similarly when eGFR was dichotomized into above or below stage 3 CKD (eGFR < 60 ml/min/1.73m2) there was a significant interaction with log transformed OPG and stage of CKD for all-cause mortality (P = 0.043) and CVD mortality (P = 0.016) or when dichotomizing by median OPG levels with eGFR (ml/min/1.73m2) the interaction term remained significant for all-cause (P = 0.021) and CVD mortality (P = 0.047). Accordingly the participants were stratified into 4 groups according to median OPG levels (<2.2 ng/mL and ≥2.2 ng/mL) and eGFR dichotomised by the presence or absence of stage III CKD (< and ≥60mL/min/1.73m2). Graphical representation of these interactions are presented in Fig 1.


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

Lewis JR, Lim WH, Ueland T, Wong G, Zhu K, Lim EM, Bollerslev J, Prince RL - PLoS ONE (2015)

Relationship between quartiles of circulating OPG dichotomized by eGFR categories (≥ 60ml/min/1.73m2 and < 60ml/min/1.73m2) for all-cause mortality (top left, n = 547) and cardiovascular mortality (top right, n = 210) and relationship between quartiles of estimated glomerular filtration rate by the CKD-EPI equation (CKD-EPI eGFR) dichotomized by circulating OPG levels (< median and ≥ median) for all-cause mortality (bottom left) and cardiovascular mortality (bottom right).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4519299&req=5

pone.0134266.g001: Relationship between quartiles of circulating OPG dichotomized by eGFR categories (≥ 60ml/min/1.73m2 and < 60ml/min/1.73m2) for all-cause mortality (top left, n = 547) and cardiovascular mortality (top right, n = 210) and relationship between quartiles of estimated glomerular filtration rate by the CKD-EPI equation (CKD-EPI eGFR) dichotomized by circulating OPG levels (< median and ≥ median) for all-cause mortality (bottom left) and cardiovascular mortality (bottom right).
Mentions: As we sought to determine whether eGFR modified or accounted for the previously observed relationship between OPG and mortality, interaction tests between OPG and eGFR were undertaken. Using both variables as continuous (log transformed OPG and eGFR ml/min/1.73m2) there was an interaction observed between OPG and eGFR for all-cause mortality (P = 0.044) and CVD mortality (P = 0.028). Similarly when eGFR was dichotomized into above or below stage 3 CKD (eGFR < 60 ml/min/1.73m2) there was a significant interaction with log transformed OPG and stage of CKD for all-cause mortality (P = 0.043) and CVD mortality (P = 0.016) or when dichotomizing by median OPG levels with eGFR (ml/min/1.73m2) the interaction term remained significant for all-cause (P = 0.021) and CVD mortality (P = 0.047). Accordingly the participants were stratified into 4 groups according to median OPG levels (<2.2 ng/mL and ≥2.2 ng/mL) and eGFR dichotomised by the presence or absence of stage III CKD (< and ≥60mL/min/1.73m2). Graphical representation of these interactions are presented in Fig 1.

Bottom Line: This relationship with mortality was independent of decline in renal function (P<0.05).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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus