Elevated osteoprotegerin is associated with inflammation, malnutrition and new onset cardiovascular events in peritoneal dialysis patients

Atherosclerosis. 2011 Dec;219(2):925-30. doi: 10.1016/j.atherosclerosis.2011.09.025. Epub 2011 Sep 21.

Abstract

Backgrounds: Osteoprotegerin (OPG) is known to regulate bone mineral metabolism and to be also associated with inflammation, cardiovascular disease (CVD) and mortality. Malnutrition-inflammation-atherosclerosis (MIA) syndrome is commonly found and closely linked to mortality in dialysis patients. The aim of this study was to investigate the associations between OPG and MIA syndrome in prevalent peritoneal dialysis (PD) patients.

Methods: Prevalent PD patients for more than 6 months were prospectively followed up from March 2005 to May 2010. At baseline, OPG, hs-CRP, albumin, and %lean body mass (LBM) by creatinine kinetics were checked, and subjective global assessment (SGA) was performed. New-onset cardiovascular events were evaluated during the study period. Based on the median level of OPG, patients were classified as lower OPG (LO) group (n = 88) and higher OPG (HO) group (n = 88).

Results: A total of 176 patients (age 52.0 ± 11.8 years, male 50.6%, duration of PD 105.3 ± 67.2 months) were recruited and followed. In HO group, age, hs-CRP level and Charlson's comorbidity indices were higher, whereas serum albumin level, %LBM and SGA score were significantly lower than LO group. OPG levels were positively correlated with inflammatory markers, whereas negatively correlated with nutritional status. Cardiovascular events occurred in 51 patients during the study period. Newly developed cardiovascular events were significantly common in HO group (n = 36, 40.9%) than LO group (n = 15, 17%, p = 0.002). Cox regression analysis revealed that higher OPG level (per 1-SD increase in OPG, HR: 1.44; 95% CI: 1.03-2.00; p = 0.034) was a significant risk factor for cardiovascular events even after adjustments for demographic and biochemical parameters.

Conclusion: OPG was significantly correlated with markers of systemic inflammation and malnutrition and was a significant predictor of CVD in PD patients. These findings suggest OPG might be a prognostic indicator of MIA syndrome in prevalent PD patients.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Body Composition
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / mortality
  • Comorbidity
  • Creatinine / blood
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / etiology*
  • Inflammation / mortality
  • Inflammation Mediators / blood
  • Kaplan-Meier Estimate
  • Male
  • Malnutrition / blood
  • Malnutrition / etiology*
  • Malnutrition / mortality
  • Middle Aged
  • Osteoprotegerin / blood*
  • Peritoneal Dialysis / adverse effects*
  • Peritoneal Dialysis / mortality
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Republic of Korea / epidemiology
  • Risk Assessment
  • Risk Factors
  • Serum Albumin / metabolism
  • Time Factors
  • Up-Regulation

Substances

  • Biomarkers
  • Inflammation Mediators
  • Osteoprotegerin
  • Serum Albumin
  • TNFRSF11B protein, human
  • C-Reactive Protein
  • Creatinine