Sedentary behaviour and cerebrovascular disease: molecular mechanisms and the impact of bout duration. : A multicentre cohort study

Abstract Background: Sedentary behaviour is associated with vascular disease, and being sedentary for long periods at a time is believed to be associated with the highest risk. The molecular mechanisms are presumed to follow metabolic and inflammatory pathways. Details about these pathways or the length of a clinical significant sedentary bout is not known. Aims: The primary aim of this study was to investigate the association between sedentary behaviour and novel blood biomarkers with potential predictive and explanatory properties. The secondary aim was to investigate the impact of sedentary behaviour bout length on these biomarkers. Materials and methods: Patients admitted to hospital for acute stroke were included in the multicentre cohort study entitled the Norwegian Cognitive Impairment After Stroke (Nor-COAST) study (n=815). At the three-month assessment (n=700), sedentary behaviour was measured using the body-worn sensor ActivPAL. Blood samples were drawn for analyses at the local laboratory directly, and biobank samples were stored and later analysed for inflammatory biomarkers at two research laboratories. The long-term outcomes, ischemic stroke recurrence and mortality was identified using national registries. Results: Glycated haemoglobin A (HbA1c) was positively associated with sedentary behaviour accumulated through bouts of 90 minutes or more. Total sedentary time was associated with higher levels of the inflammatory biomarkers C-reactive protein (CRP), interleukin-6 (IL-6), the pyridoxic acid ratio-index (PAr-index), and neopterin, and lower levels of kynurenic acid (KA). The study did not have enough power for investigating the impact of bout length on these biomarkers. There were no associations between the biomarkers and ischemic stroke recurrence. Mortality was associated with higher levels of CRP. When added to the same model, neopterin and KA showed positive and negative associations to mortality, respectively. Conclusion and implications: The results support that the impact of sedentary behaviour on disease progression is mediated through known vascular risk factors and novel biomarkers can be useful for future intervention studies.