Influence of bone-associated and cardiovascular biomarkers on vascular events and mortality in relation to renal dysfunction

Sammanfattning: Biomarkers can help physicians identify subjects with an increased cardiovascular risk. Apart from the clinical factors, some biomarkers have been recognized as important predictors and risk factors for cardiovascular disease in renal disease. The applicability of biomarkers may be limited in patients with kidney disease due to the complex etiology of cardiovascular disease, which warrants separate evaluations, including established and novel biomarkers. The overall aim of the thesis was to investigate the association between bone-associated markers and cardiovascular proteins on death and vascular events in the elderly male population and patients with kidney disease.Study I included 3,014 participants in Swedish multicenter prospective Osteoporotic Fractures in Men (MrOS) cohort and investigated the associations between Klotho single-nucleotide polymorphism and mortality. Two potentially damaging single-nucleotide polymorphisms (rs9536314 and rs9527025) in the Klotho gene were not associated with mortality.Study II investigated the association between mineral bone markers and all-cause mortality / cardiovascular mortality. The composite evaluation of elevated fibroblast growth factor-23 levels, vitamin D deficiency, and renal impairment was associated with mortality.Study III evaluated the bone-associated proteins and mortality/composite vascular events in the 331 Demark hemodialysis patients. Osteoprotegerin, as one of the most promising bone-related proteins, was associated with composite vascular events independent of cytokine.Study IV investigated the association between 92 proteins measured by proximity extension assay and mortality/composite vascular events in hemodialysis patients. A higher level of Interleukin-8, T-cell immunoglobulin and mucin domain 1, C-C motif chemokine 20, and lower level of stem cell factor and galanin peptides were associated with poor outcomes.This thesis addressed the issue of bone-vascular axis and cardiovascular disease. We evaluated from gene levels to circulating protein levels and from the general population to patients with kidney disease. Based on our research findings, more evidence was linked between bone and vascular complications. We also identified several cardiovascular proteins considered potentially important predictors for cardiovascular disease in patients with renal failure, especially hemodialysis patients.