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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

Multivariable-adjusted hazard ratio (HR) and 95% confidence interval for 15-year all-cause mortality (n = 547) in participants dichotomized by OPG levels and eGFR.Multivariable-adjustments were baseline age, body mass index, smoking history, history of hormone replacement therapy, treatment code (calcium or placebo) and comorbidity score.
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pone.0134266.g002: Multivariable-adjusted hazard ratio (HR) and 95% confidence interval for 15-year all-cause mortality (n = 547) in participants dichotomized by OPG levels and eGFR.Multivariable-adjustments were baseline age, body mass index, smoking history, history of hormone replacement therapy, treatment code (calcium or placebo) and comorbidity score.

Mentions: Participants with above-median OPG levels and eGFR ≥60mL/min/1.73m2 had significantly higher incidence of 15-year all-cause mortality (44.0%) in unadjusted models (HR 1.35, 95%CI 1.09–1.66, P = 0.006) and that became non-significant after multivariable adjustment (Fig 2). Compared to participants with below-median OPG levels and eGFR ≥60mL/min/1.73m2, participants with elevated OPG above the median and an eGFR <60mL/min/1.73m2 had the highest incidence of all-cause mortality (56.6%) before adjustment (HR 1.97, 95%CI 1.56–2.48, P < 0.001) that remained significant after adjustment (Fig 2). Participants with below the median OPG levels and eGFR ≥60mL/min/1.73m2 were not at a higher risk in before adjustment (HR 1.13, 95%CI 0.85–1.48, P = 0.401) or after multivariate-adjusted analyses (Fig 2).


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)

Multivariable-adjusted hazard ratio (HR) and 95% confidence interval for 15-year all-cause mortality (n = 547) in participants dichotomized by OPG levels and eGFR.Multivariable-adjustments were baseline age, body mass index, smoking history, history of hormone replacement therapy, treatment code (calcium or placebo) and comorbidity score.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0134266.g002: Multivariable-adjusted hazard ratio (HR) and 95% confidence interval for 15-year all-cause mortality (n = 547) in participants dichotomized by OPG levels and eGFR.Multivariable-adjustments were baseline age, body mass index, smoking history, history of hormone replacement therapy, treatment code (calcium or placebo) and comorbidity score.
Mentions: Participants with above-median OPG levels and eGFR ≥60mL/min/1.73m2 had significantly higher incidence of 15-year all-cause mortality (44.0%) in unadjusted models (HR 1.35, 95%CI 1.09–1.66, P = 0.006) and that became non-significant after multivariable adjustment (Fig 2). Compared to participants with below-median OPG levels and eGFR ≥60mL/min/1.73m2, participants with elevated OPG above the median and an eGFR <60mL/min/1.73m2 had the highest incidence of all-cause mortality (56.6%) before adjustment (HR 1.97, 95%CI 1.56–2.48, P < 0.001) that remained significant after adjustment (Fig 2). Participants with below the median OPG levels and eGFR ≥60mL/min/1.73m2 were not at a higher risk in before adjustment (HR 1.13, 95%CI 0.85–1.48, P = 0.401) or after multivariate-adjusted analyses (Fig 2).

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