Mehdi Rambod1, Gunnar H Heine2, Sarah Seiler2, Elizabeth A Dominic3, Kyrill S Rogacev2, Rama Dwivedi4, Ali Ramezani5, Maria R Wing5, Richard L Amdur6, Danilo Fliser2, Dominic S Raj7. 1. Department of Internal Medicine, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, TX, USA. 2. Saarland University Medical Center and Saarland University Faculty of Medicine, Internal Medicine IV - Nephrology and Hypertension, Homburg, Saar, Germany. 3. The George Washington University, Washington, DC, USA. 4. Division of Renal Diseases and Hypertension, The George Washington University School of Medicine, Washington, DC, USA; Division of Cardiovascular and Renal Products, Office of New Drugs, US Food and Drug Administration, Silver Spring, MD, USA. 5. Division of Renal Diseases and Hypertension, The George Washington University School of Medicine, Washington, DC, USA. 6. Biostatistics Core, The George Washington University, USA. 7. Division of Renal Diseases and Hypertension, The George Washington University School of Medicine, Washington, DC, USA. Electronic address: draj@mfa.gwu.edu.
Abstract
BACKGROUND: Angiogenic cytokines fms-like tyrosine kinase-1(sFlt-1) and placental growth factor (PlGF) are associated with increased risk for cardiovascular disease (CVD) in the general population. In this study we examine the association between these vascular endothelial factors and atherosclerosis, cardiovascular outcome, and mortality in chronic kidney disease (CKD) patients. METHODS: Serum level of PlGF and sFlt-1 were measured in 301 patients with CKD, who were followed for up to 4 years. Primary outcomes were CV events and all-cause mortality. Carotid-intima media thickness (CIMT) was used as marker of atherosclerosis. Kaplan-Meier survival curves and the Cox proportional hazard model were used to assess the association of biomarkers and clinical outcomes. RESULTS: Mean (SD) PlGF and sFlt-1 were 5.45 ng/ml (3.76) and 68.6 (28.0) pg/ml, respectively. During the follow up time, 60 patients (19.9%) experienced CV events and 22 patients (7.3%) died. Compared with low PlGF, patients with PlGF above median level had higher CV events (12.7% vs. 27.2%, p = 0.002) and mortality (2.0% vs. 12.6%, p < 0.001). The associations of PlGF and sFlt-1 with CV events were not statistically significant in the fully adjusted model. Higher PlGF was associated with greater death risk (HR = 5.22, 95% CI: 1.49-18.33, p = 0.01), which was robust to adjustment for sFlt-1 and other risk factors. Elevated sFlt-1 level was also an independent predictor of mortality (HR 3.41, 95% CI: 1.49-9.51, p = 0.019). CONCLUSION: In CKD patients not yet on dialysis, higher serum level of PlGF and sFlt-1 are associated with increased mortality, but not CV events.
BACKGROUND: Angiogenic cytokines fms-like tyrosine kinase-1(sFlt-1) and placental growth factor (PlGF) are associated with increased risk for cardiovascular disease (CVD) in the general population. In this study we examine the association between these vascular endothelial factors and atherosclerosis, cardiovascular outcome, and mortality in chronic kidney disease (CKD) patients. METHODS: Serum level of PlGF and sFlt-1 were measured in 301 patients with CKD, who were followed for up to 4 years. Primary outcomes were CV events and all-cause mortality. Carotid-intima media thickness (CIMT) was used as marker of atherosclerosis. Kaplan-Meier survival curves and the Cox proportional hazard model were used to assess the association of biomarkers and clinical outcomes. RESULTS: Mean (SD) PlGF and sFlt-1 were 5.45 ng/ml (3.76) and 68.6 (28.0) pg/ml, respectively. During the follow up time, 60 patients (19.9%) experienced CV events and 22 patients (7.3%) died. Compared with low PlGF, patients with PlGF above median level had higher CV events (12.7% vs. 27.2%, p = 0.002) and mortality (2.0% vs. 12.6%, p < 0.001). The associations of PlGF and sFlt-1 with CV events were not statistically significant in the fully adjusted model. Higher PlGF was associated with greater death risk (HR = 5.22, 95% CI: 1.49-18.33, p = 0.01), which was robust to adjustment for sFlt-1 and other risk factors. Elevated sFlt-1 level was also an independent predictor of mortality (HR 3.41, 95% CI: 1.49-9.51, p = 0.019). CONCLUSION: In CKDpatients not yet on dialysis, higher serum level of PlGF and sFlt-1 are associated with increased mortality, but not CV events.
Authors: Sharon E Maynard; Jiang-Yong Min; Jaime Merchan; Kee-Hak Lim; Jianyi Li; Susanta Mondal; Towia A Libermann; James P Morgan; Frank W Sellke; Isaac E Stillman; Franklin H Epstein; Vikas P Sukhatme; S Ananth Karumanchi Journal: J Clin Invest Date: 2003-03 Impact factor: 14.808
Authors: Theresa M Wewers; Annika Schulz; Ingo Nolte; Hermann Pavenstädt; Marcus Brand; Giovana S Di Marco Journal: J Am Soc Nephrol Date: 2021-06-21 Impact factor: 14.978
Authors: Markus Sällman Almén; Jonas Björk; Ulf Nyman; Veronica Lindström; Magnus Jonsson; Magnus Abrahamson; AnnaLotta Schiller Vestergren; Örjan Lindhe; Gary Franklin; Anders Christensson; Anders Grubb Journal: Kidney Int Rep Date: 2018-09-13