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Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD.
Clin J Am Soc Nephrol. 2016 07 07; 11(7):1163-72.CJ

Abstract

BACKGROUND AND OBJECTIVES

The high risk of cardiovascular disease (CVD) and premature death in patients with CKD associates with a plethora of elevated circulating biomarkers that may reflect distinct signaling pathways or simply, are epiphenomena of CKD. We compared the predictive strength of 12 biomarkers analyzed concomitantly in patients with stage 5 CKD.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS

From 1994 to 2014, 543 patients with stage 5 CKD (median age =56 years old; 63% men; 199 patients had CVD) took part in our study on malnutrition, inflammation, and CVD in incident dialysis patients. Circulating levels of albumin, ferritin, high-sensitivity C-reactive protein (hsCRP), IGF-1, IL-6, orosomucoid, troponin T (TnT), TNF, soluble intracellular adhesion molecule, soluble vascular cellular adhesion molecule 1 (sVCAM-1), and platelet and white blood cell (WBC) counts were analyzed as predictors of the presence of clinically overt CVD at baseline, protein-energy wasting (PEW), and subsequent all-cause mortality. During follow-up for a median of 28 months, there were 149 deaths, 81 of which were caused by CVD.

RESULTS

Most biomarkers were elevated compared with reference values and--except for albumin, ferritin, and IGF-1-higher in patients with CVD. In receiver operating characteristic analysis, age, IL-6, TnT, hsCRP, and IGF-1 were classifiers of baseline CVD and predictors of all-cause mortality. In addition to age, diabetes mellitus, smoking (for CVD), and PEW, only IL-6, relative risk (RR) 1.10 and 95% confidence interval ([95% CI], 1.02 to 1.19), sVCAM-1 RR 1.09 (95% CI, 1.01 to 1.17), and serum albumin RR 0.89 (95% CI, 0.83 to 0.95) associated with baseline CVD, and only WBC, hazard ratio (HR) 1.94 (95% CI, 1.34 to 2.82), IL-6 HR 1.79 (95% CI, 1.20 to 2.67), and TNF HR 0.65 (95% CI, 0.44 to 0.97) predicted all-cause mortality.

CONCLUSIONS

In addition to age and comorbidities, only IL-6, sVCAM-1, and albumin could-independently of other biomarkers-classify clinical CVD, and only IL-6, WBC, and TNF could-independently of other biomarkers-predict all-cause mortality risk. These data underscore the robustness of IL-6 as a classifier of clinically overt CVD and predictor of all-cause mortality in patients with stage 5 CKD.

Authors+Show Affiliations

Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology and.Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology and.Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology and.Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology and.Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology and.Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology and.Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology and.Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology and tony.qureshi@ki.se.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27281698

Citation

Sun, Jia, et al. "Biomarkers of Cardiovascular Disease and Mortality Risk in Patients With Advanced CKD." Clinical Journal of the American Society of Nephrology : CJASN, vol. 11, no. 7, 2016, pp. 1163-72.
Sun J, Axelsson J, Machowska A, et al. Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD. Clin J Am Soc Nephrol. 2016;11(7):1163-72.
Sun, J., Axelsson, J., Machowska, A., Heimbürger, O., Bárány, P., Lindholm, B., Lindström, K., Stenvinkel, P., & Qureshi, A. R. (2016). Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD. Clinical Journal of the American Society of Nephrology : CJASN, 11(7), 1163-72. https://doi.org/10.2215/CJN.10441015
Sun J, et al. Biomarkers of Cardiovascular Disease and Mortality Risk in Patients With Advanced CKD. Clin J Am Soc Nephrol. 2016 07 7;11(7):1163-72. PubMed PMID: 27281698.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD. AU - Sun,Jia, AU - Axelsson,Jonas, AU - Machowska,Anna, AU - Heimbürger,Olof, AU - Bárány,Peter, AU - Lindholm,Bengt, AU - Lindström,Karin, AU - Stenvinkel,Peter, AU - Qureshi,Abdul Rashid, Y1 - 2016/06/08/ PY - 2015/10/02/received PY - 2016/03/12/accepted PY - 2016/6/10/entrez PY - 2016/6/10/pubmed PY - 2017/12/13/medline KW - Biomarkers KW - C-Reactive Protein KW - Follow-Up Studies KW - Humans KW - Inflammation KW - Interleukin-6 KW - Renal Insufficiency, Chronic KW - cardiovascular disease KW - chronic kidney disease KW - mortality SP - 1163 EP - 72 JF - Clinical journal of the American Society of Nephrology : CJASN JO - Clin J Am Soc Nephrol VL - 11 IS - 7 N2 - BACKGROUND AND OBJECTIVES: The high risk of cardiovascular disease (CVD) and premature death in patients with CKD associates with a plethora of elevated circulating biomarkers that may reflect distinct signaling pathways or simply, are epiphenomena of CKD. We compared the predictive strength of 12 biomarkers analyzed concomitantly in patients with stage 5 CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From 1994 to 2014, 543 patients with stage 5 CKD (median age =56 years old; 63% men; 199 patients had CVD) took part in our study on malnutrition, inflammation, and CVD in incident dialysis patients. Circulating levels of albumin, ferritin, high-sensitivity C-reactive protein (hsCRP), IGF-1, IL-6, orosomucoid, troponin T (TnT), TNF, soluble intracellular adhesion molecule, soluble vascular cellular adhesion molecule 1 (sVCAM-1), and platelet and white blood cell (WBC) counts were analyzed as predictors of the presence of clinically overt CVD at baseline, protein-energy wasting (PEW), and subsequent all-cause mortality. During follow-up for a median of 28 months, there were 149 deaths, 81 of which were caused by CVD. RESULTS: Most biomarkers were elevated compared with reference values and--except for albumin, ferritin, and IGF-1-higher in patients with CVD. In receiver operating characteristic analysis, age, IL-6, TnT, hsCRP, and IGF-1 were classifiers of baseline CVD and predictors of all-cause mortality. In addition to age, diabetes mellitus, smoking (for CVD), and PEW, only IL-6, relative risk (RR) 1.10 and 95% confidence interval ([95% CI], 1.02 to 1.19), sVCAM-1 RR 1.09 (95% CI, 1.01 to 1.17), and serum albumin RR 0.89 (95% CI, 0.83 to 0.95) associated with baseline CVD, and only WBC, hazard ratio (HR) 1.94 (95% CI, 1.34 to 2.82), IL-6 HR 1.79 (95% CI, 1.20 to 2.67), and TNF HR 0.65 (95% CI, 0.44 to 0.97) predicted all-cause mortality. CONCLUSIONS: In addition to age and comorbidities, only IL-6, sVCAM-1, and albumin could-independently of other biomarkers-classify clinical CVD, and only IL-6, WBC, and TNF could-independently of other biomarkers-predict all-cause mortality risk. These data underscore the robustness of IL-6 as a classifier of clinically overt CVD and predictor of all-cause mortality in patients with stage 5 CKD. SN - 1555-905X UR - https://www.unboundmedicine.com/medline/citation/27281698/Biomarkers_of_Cardiovascular_Disease_and_Mortality_Risk_in_Patients_with_Advanced_CKD_ L2 - https://cjasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=27281698 DB - PRIME DP - Unbound Medicine ER -