Low-grade inflammation and endothelial dysfunction predict four-year risk and course of depressive symptoms: The Maastricht study

•LGI and ED were both associated with incident depressive symptoms.•The association of ED was substantially mediated by LGI.•ED was associated with a persistent course of depressive symptoms.•LGI was not associated with a persistent course of depressive symptoms.•This suggests a temporal, vascular contribution of LGI and ED to the etiology and chronicity of depressive symptoms. Low-grade inflammation (LGI) and endothelial dysfunction (ED) might play a key role in the development of depression. We investigated the associations and mediation of LGI and ED with four-year incidence and course of depressive symptoms (remitted, recurrent or persistent). In this prospective cohort study (mean age 59.6 ± 8.2 years, 48.9% women, 26.6% diabetes by design), Cox and multinomial regression analyses, adjusted for age, sex, educational level and diabetes status were used to investigate the associations of LGI and ED with onset and course of depressive symptoms as assessed by the PHQ-9 questionnaire. During 10,847 person-years of follow-up, 264 participants developed incident depression. Higher levels of LGI (OR [95%CI] per SD 1.32[1.16–1.49], p