The relationship between Type D personality with atherosclerotic plaque and cardiovascular events: The mediation effect of inflammation and kynurenine/tryptophan metabolism

PURPOSE: Cardiovascular events and coronary plaque vulnerability are linked to Type D personality. However, the fundamental mechanism has not been clarified. Our study determined to illustrate whether inflammatory status in plasma, in combination with kynurenine pathway activity in Type D individuals, is associated with plaque vulnerability and cardiovascular events in patients with coronary artery disease (CAD). MATERIALS AND METHODS: The Type D personality of 177 CAD patients were evaluated. Plasma biomarkers of inflammation (TNF-α, IL-6, and hs-CRP) were measured and pooled into standardized sumscores. Tryptophan and kynurenine metabolites were measured, and the kynurenine/tryptophan ratio (KTR) was calculated. Plaque vulnerability was measured in vivo by optical coherence tomography. All patients had a follow up of 2 years in which cardiovascular adverse events were recorded. RESULTS: Type D individuals exhibited elevated TNF-α (p = 0.007), IL-6 (p = 0.049), inflammation sumscores (p = 0.002), kynurenine (p = 0.008), and KTR (p = 0.005) than non-Type D group. The serial-multiple mediation showed that the Type D personality with a direct, favorable impact on plaque vulnerability, including thin cap fibroatheroma (TCFA) (point estimate = 0.81; 95% CI = 0.09–1.53), macrophages (point estimate = 0.79; 95% CI = 0.05–1.51), and major adverse cardiac events (MACE) (point estimate = 0.88, 95% CI = 0.08–1.70). In addition, the standardized inflammation sumscores and KTR were mediators of the Type D personality associations with TCFA, macrophages and MACE. CONCLUSION: These results demonstrated that the connection between Type D personality and poor cardiovascular outcomes in CAD patients can be mediated by pro-inflammatory biomarkers and KTR.