Objective: N-Acetylserotonin and serotonin, both important neurotransmitters implicated in sleep rhythm regulation. This study aimed to investigate the association between the N-Acetylserotonin-to-serotonin ratio (NSR) and the incidence of atherosclerotic cardiovascular disease (ASCVD) in a community-based Chinese population. Design and method: We included 2,633 participants from a prospective community-based cohort in Suzhou, Jiangsu, China. Participants were categorized into low, medium, and high NSR groups based on baseline levels at the 50th and 90th percentiles. Follow-up continued until December 31, 2022. Using enzyme-linked immunosorbent assay (ELISA, Cayman Chemical, Ann Arbor, MI), we assessed plasma levels of five key specialized pro-resolving mediators: resolvin D1, resolvin D2, resolvin E1, lipoxin A4, and maresin-1. Cox proportional hazards models were used to assess the relationship between NSR and ASCVD incidence, with adjustment for age, sex, physical activity, smoking, and alcohol consumption. Nonlinear trends were evaluated using restricted cubic spline (RCS) regression. Mediation analysis was performed to estimate the percentage of the association mediated by SPMs. Results: Among the 2,633 participants (1,028 men and 1,605 women; mean age 50.10 ± 6.07 years), 284 incident ASCVD cases were recorded over a median follow-up of 7 years. After full adjustment, compared with the low NSR group, the hazard ratios (95% CIs) for ASCVD were 0.77 (0.45–0.98) in the medium group and 0.66 (0.50–0.86) in the high group. The association between NSR and ASCVD risk followed an inverted L-shaped curve, with no significant nonlinear pattern detected. Adding NSR to conventional risk models significantly improved ASCVD risk reclassification (net reclassification improvement: 19.35%, P=0.019; integrated discrimination index: 1.88%, P=0.003). Mediation analysis indicated that lipoxin A4 and maresin-1 accounted for 13.18% and 8.87%, respectively, of the association between NSR and ASCVD. Conclusions: The present findings indicate that the NSR is an independent protective factor for ASCVD, with its beneficial effect partially mediated by the pro-resolving mediators lipoxin A4 and maresin-1.
Dong et al. (Fri,) studied this question.