Zhimin Chen1,2, Abdul Rashid Qureshi2, Paolo Parini3,4, Eva Hurt-Camejo5, Jonaz Ripsweden6,7, Torkel B Brismar6,7, Peter Barany2, Armand M Jaminon8, Leon J Schurgers8, Olof Heimbürger2, Bengt Lindholm2, Peter Stenvinkel2. 1. Kidney Disease Center, First Affiliated Hospital College of Medicine, Zhejiang University, Hangzhou, China. 2. Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. 3. Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. 4. Metabolism Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. 5. Translational Science, CVMD iMed, AstraZeneca R&D, Gothenburg, Sweden. 6. Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden. 7. Department of Radiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden. 8. Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
Abstract
BACKGROUND: In end-stage renal disease (ESRD), coronary artery calcification (CAC) and inflammation contribute to cardiovascular disease (CVD). Statins do not improve survival in patients with ESRD, and their effect on vascular calcification is unclear. We explored associations between CAC, inflammatory biomarkers, statins and mortality in ESRD. MATERIALS AND METHODS: In 240 patients with ESRD (63% males; median age 56 years) from cohorts including 86 recipients of living donor kidney transplant (LD-Rtx), 96 incident dialysis patients and 58 prevalent peritoneal dialysis patients, associations of CAC score (Agatston Units, AUs), interleukin-6 (IL-6) with high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor (TNF), use of statins and all-cause mortality were analysed. Cardiac CT was repeated in 35 patients after 1·5 years of renal replacement therapy. In vitro, human vascular smooth muscle cells (hVSMCs) were used to measure vitamin K metabolism. RESULTS: Among 240 patients, 129 (53%) had a CAC score > 100 AUs. Multivariate analysis revealed that independent predictors of 1-SD higher CAC score were age, male gender, diabetes and use of statins. The association between CAC score and mortality remained significant after adjustment for age, gender, diabetes, CVD, use of statins, protein-energy wasting and inflammation. Repeated CAC imaging in 35 patients showed that statin therapy was associated with greater progression of CAC. In vitro synthesis of menaquinone-4 by hVSMCs was significantly impaired by statins. CONCLUSION: Elevated CAC score is a mortality risk factor in ESRD independent of inflammation. Future studies should resolve if statins promote vascular calcification and inhibition of vitamin K synthesis in the uremic milieu.
BACKGROUND: In end-stage renal disease (ESRD), coronary artery calcification (CAC) and inflammation contribute to cardiovascular disease (CVD). Statins do not improve survival in patients with ESRD, and their effect on vascular calcification is unclear. We explored associations between CAC, inflammatory biomarkers, statins and mortality in ESRD. MATERIALS AND METHODS: In 240 patients with ESRD (63% males; median age 56 years) from cohorts including 86 recipients of living donor kidney transplant (LD-Rtx), 96 incident dialysis patients and 58 prevalent peritoneal dialysis patients, associations of CAC score (Agatston Units, AUs), interleukin-6 (IL-6) with high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor (TNF), use of statins and all-cause mortality were analysed. Cardiac CT was repeated in 35 patients after 1·5 years of renal replacement therapy. In vitro, human vascular smooth muscle cells (hVSMCs) were used to measure vitamin K metabolism. RESULTS: Among 240 patients, 129 (53%) had a CAC score > 100 AUs. Multivariate analysis revealed that independent predictors of 1-SD higher CAC score were age, male gender, diabetes and use of statins. The association between CAC score and mortality remained significant after adjustment for age, gender, diabetes, CVD, use of statins, protein-energy wasting and inflammation. Repeated CAC imaging in 35 patients showed that statin therapy was associated with greater progression of CAC. In vitro synthesis of menaquinone-4 by hVSMCs was significantly impaired by statins. CONCLUSION: Elevated CAC score is a mortality risk factor in ESRD independent of inflammation. Future studies should resolve if statins promote vascular calcification and inhibition of vitamin K synthesis in the uremic milieu.
Authors: Stephanie G Harshman; M Kyla Shea; Xueyan Fu; Michael A Grusak; Donald Smith; Stefania Lamon-Fava; Athan Kuliopulos; Andrew Greenberg; Sarah L Booth Journal: J Nutr Date: 2019-03-01 Impact factor: 4.798
Authors: Julie Ann Kemp; Livia Alvarenga; Ludmila F M F Cardozo; Lu Dai; Peter Stenvinkel; Paul G Shiels; Tilman M Hackeng; Leon J Schurgers; Denise Mafra Journal: Curr Nutr Rep Date: 2022-09-23
Authors: Karen J Rees-Milton; Patrick Norman; Corinne Babiolakis; Maggie Hulbert; Mandy E Turner; Claudie Berger; Tassos P Anastassiades; Wilma M Hopman; Michael A Adams; Wendy L Powley; Rachel M Holden Journal: J Endocr Soc Date: 2020-05-15