Lipid peroxidation mediates the relationship between cardiopulmonary fitness and depressive symptoms in people with coronary artery disease

Abstract

AbstractBackgroundEmerging evidence suggests that poor cardiorespiratory fitness levels are related to greater depressive symptoms. In those with coronary artery disease (CAD) depressive symptoms are common and are associated with an increased risk of mortality. Exercise intervention is suggested to have positive effects on depressive symptoms and counteract oxidative stress (OS) in the body. However, a mechanistic link between cardiorespiratory fitness (CRF) and depressive symptoms has not been identified in CAD individuals. We aim to investigate if OS explains the relationship between poor cardiorespiratory fitness and higher depressive symptoms in CAD individuals.MethodCAD participants were recruited and OS was measured via serum lipid peroxidation marker 8‐isoprostane (8‐ISO), lipid hydroperoxides (LPH), and 4‐hydroxyneoneal (4‐HNE). CRF was assessed by peak oxygen uptake (VO2peak) and depressive symptoms measured via Center for Epidemiological Studies‐Depression (CES‐D) scale. Analyses were controlled for age, hypertension, hypercholesterolemia, and antidepressant use. Mediation effects of OS markers on the relationship between CRF and depressive symptoms were tested. A bias‐corrected inferential bootstrapping with 10,000 permutations was used to obtain a 95% confidence interval (CI) for the indirect effect.ResultAmong CAD individuals (n=224), lower VO2peak was associated with higher 8‐ISO (β=0.31, p<0.001) and greater depressive symptoms (β=‐0.143, p=0.038). LPH (B=‐0.172 p=0.017) was associated with greater CES‐D score, but not VO2peak levels (B=‐0.122, p=0.109), when controlling for the same covariates. 4‐HNE was not a significant predictor of CES‐D scores (B=0.059, p=0.372) or VO2peak levels (B=‐0.052, p=0.440). 8‐ISO mediated the relationship between VO2peak (β=0.02, p=0.01) and CES‐D (β=7.13, p=0.001), and LPH did not (‐0.0098, 95% CI [‐0.0314, 0.0042]). Bootstrapping produced a significant unstandardized indirect effect for 8‐ISO (β=‐0.20, SE=0.05, 95% CI=‐0.32, ‐0.01).ConclusionIn those with CAD, poor CRF and greater OS levels were associated with higher depressive symptoms, and this relationship was mediated by 8‐ISO, but not LPH or 4‐HNE. These findings provide greater understanding of the mechanistic reasoning for the link between poor CRF and depressive symptoms.