Fig. 2.

Middle-age serum sodium and risk to develop age-related chronic diseases. a) Age dependence of chronic diseases. Cumulative incidence curves (CIFs) accounting for competing mortality for eight age-dependent chronic diseases in ARIC study participants (N = 11,255). Right panel shows how diseases are combined into two sets containing four and seven diseases for following analysis of chronic diseases burden. b-d) Analysis of chronic diseases burden in 5168 ARIC study participants aged 70–90 years who attended visit 5 at the end of 25 years follow-up. b) Distribution of the study participants based on number of diseases from Set 1 (blue) and Set 2 (orange) that they are diagnosed with. c, d) Analysis of association between middle-age serum sodium and risk to develop chronic diseases from Set 1. c) Splitting study participants into four groups using classification and regression trees (CART) algorithm based on average serum sodium measured at visits 1 and 2. Percent of people diagnosed with at least one out of four diseases from Set 1 by the end of follow-up was used as outcome variable for the splitting algorithm. d) Assessment of relative risk to develop at least one disease from Set 1 in four sodium groups. Participants are divided into 2 groups: 0 – disease-free at the end of follow-up; 1 – have at least one disease. Left panel: Time-to-event analysis: Cox proportional hazards model. Right panel: Retrospective case–control analysis: multivariable logistic regression. Participants with serum sodium 138-140 mmol/l have lowest risk to develop chronic diseases. Both lower and higher sodium concentrations are associated with increased risk. See also Fig. S3 for analysis of Set 2 diseases.