Relationship of 5-year changes in inflammatory, metabolic and oxidative biomarkers with cardiovascular diseases incidence at 10-years

Abstract

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Carlos III Health Institute and the European Regional Development Fund Government of Catalonia through the Agency for Management of University and Research Grants Background Early stratification of cardiovascular (CV) risk saves thousands of lives every year. There is a debate about the value of determining genetic or plasma biochemical biomarkers, related to atherosclerosis process, to improve the prediction of an incident CV disease. While, single measurements of some of these biomarkers have been associated with an increased risk of CV disease, the change of the levels of these biomarkers over time could also improve the prediction of CV events and drive the identification of new biological pathways and therapeutic targets. Purpose This study aimed to examine the relationship between 5-year change in the levels of biomarkers of inflammation (TNF-α, IL-10, IL-6, MCP-1, and CRP), glucidic metabolism (adiponectin, leptin, and insulin) and oxidation (GHS-Px), and the incidence of CV events at 10 years in a population without previous CV disease. Methods This was a cohort study nested in a large population cohort. Participants were randomly selected from the REGICOR cohort (North-Eastern Spain) recruited in 2005 (6.352 participants). Biomarkers were measured at baseline and in a re-examination in 2010. Participants were followed until 2020 for a composite CV disease endpoint including fatal and non-fatal first occurrence of coronary artery disease, stroke and peripheral artery disease. Baseline characteristics were compared between participants with and without CV events with standard parametric and non-parametric methods, as required. We used Cox regression to analyse the effect of the 5-year change of the biomarker levels on the occurrence of the composite endpoint adjusted for age, sex, baseline levels of each biomarker and classical CV risk factors. Results We included 419 individuals aged 35 to 74 years. Overall, 6.2% developed an incident CV disease within the 10-year follow-up. Characteristics of participants, who had or not a CV event, are compared in Table 1. Cases had a more adverse CV and anthropometric risk profile. Compared to individuals with sustained IL-6 and insulin levels, those with increased IL-6 or insulin after five years were at higher independent risk of CV disease at ten years. After adjusting for potential confounders, an increased IL-6 and insulin at the 5-year follow-up were independently associated with CV disease at 10-years (Table 2). Each rise of IL-6 or insulin in 1pg/mL or 10pg/mL, respectively, increased 32% (IL-6) and 2% (insulin) the risk of developing a CV event at 10-years. Conclusions Increasing IL-6 and insulin levels over five years indicates a higher risk of CV disease ten years thereafter, independently of classical risk factors.