Abstract
BACKGROUND: Future risk of cardiovascular disease (CVD) and mortality is associated with cumulative amount TyG index (cumTyG) exposure, while whether time course of TyG accumulation modulates the risk remains unclear. This study sought to examine the associations of cumTyG index accumulation time course with the risk of CVD and all-cause mortality. METHODS: We enrolled 51,734 participants free of CVD and underwent three examinations at year 2006, 2008, and 2010. CumTyG from baseline to the third examination was calculated. Time course of cumTyG accumulation was calculated as the slope of TyG versus time from 2006 to 2010, or as splinting the overall TyG index accumulation into early (cumTyG(06 - 08)) and late accumulation (cumTyG(08 - 10)). Participants were categorized by the combination of cumTyG < or ≥ median (34.44 × years) and a negative or positive TyG slope. RESULTS: During a median follow-up of 9.04 years, we identified 3,602 incident CVD cases and 3,165 deaths. The risk of CVD and all-cause mortality increased with decreased TyG slope, the corresponding adjusted hazard ratio (aHR) with 95% confidence interval (CI) was 1.11 (1.04-1.19) and 1.18 (1.10-1.26) for patients with a negative TyG slope, respectively. Consistently, a later accumulation of TyG index was not associated with the risk of CVD and all-cause mortality after adjustment for an early accumulation. When considering the combination of cumTyG index and time course, participants with a cumTyG ≥ median and a negative TyG slope had elevated risk of CVD (aHR, 1.37; 95% CI, 1.24-1.51) and all-cause mortality (aHR, 1.28; 95% CI, 1.15-1.43). Additionally, the association was more prominent in young adults. CONCLUSION: Early TyG index accumulation resulted in a greater risk of CVD and all-cause mortality than later TyG later accumulation with the same overall cumulative exposure, emphasizing the importance of optimal TyG index control earlier in life.