Does statins promote vascular calcification in chronic kidney disease?

• Published in: European journal of clinical investigation 2017-02, Vol.47 (2), p.137-148
• Main Authors: Chen, Zhimin, Qureshi, Abdul Rashid, Parini, Paolo, Hurt‐Camejo, Eva, Ripsweden, Jonaz, Brismar, Torkel B., Barany, Peter, Jaminon, Armand M., Schurgers, Leon J., Heimbürger, Olof, Lindholm, Bengt, Stenvinkel, Peter
• Format: Article
• Language: English
• Subjects: Adult; Age; Aged; Biomarkers; Biomarkers - metabolism; C-reactive protein; Calcification; Calcification (ectopic); Cardiovascular diseases; Chronic kidney disease; Computed tomography; Coronary artery; Coronary Artery Disease - chemically induced; Coronary Artery Disease - mortality; Diabetes; Diabetes mellitus; Dialysis; End-stage renal disease; Energy consumption; Female; Heart diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; In vitro methods and tests; Inflammation; Inhibition; Interleukin 6; Kaplan-Meier Estimate; Kidney diseases; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - mortality; Kidney transplantation; Male; Males; Medicin och hälsovetenskap; Metabolism; Middle Aged; Mortality; Multivariate analysis; Muscle, Smooth, Vascular - metabolism; Patients; Peritoneal dialysis; Peritoneum; Risk factors; Smooth muscle; statin; Statins; Synthesis; Therapy; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumors; vascular calcification; Vascular Calcification - chemically induced; Vascular Calcification - mortality; Vitamin K; Vitamin K - metabolism
• ISSN: 0014-2972; 1365-2362; 1365-2362
• DOI: 10.1111/eci.12718

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.