Dynamic Changes in Triglyceride Glucose‒Waist‒to‒Height Ratio and the Risk of Major Adverse Cardiovascular Events: Role of Concurrent Mean Arterial Pressure Change

It remains unclear whether a fixed-period increase in the triglyceride glucose‒waist height ratio (TyG‒WHtR) index, an indicator of short-term metabolic worsening, is associated with future cardiovascular disease (CVD) risk. To investigate this, we conducted a prospective cohort study in a Beijing community-based population in China, enrolling participants without a history of stroke or myocardial infarction (MI). The primary outcome was major adverse cardiovascular events (MACEs), defined as a composite of MI, stroke, and cardiovascular death. We employed Cox proportional hazards models with landmark analysis to evaluate the association. Among 3466 individuals followed for a median of 7.52 years since 2014, 270 MACE events occurred. Our analysis suggested a potential threshold effect, with CVD risk increasing more markedly when the TyG-WHtR increase exceeded approximately 0.400. Using this cutoff, individuals with a higher two-year increase in TyG-WHtR had a 30% higher risk of MACE (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.00-1.69) compared to those with lower increase. Landmark analysis revealed no significant association during the first 2 years; however, beyond this period, the association emerged, with an HR of 1.41 (95% CI 1.06-1.89). Further mediation analysis revealed that concurrent changes in mean arterial pressure (MAP) explained 30.4% of the association between changes in TyG-WHtR and MACEs. In conclusion, an increase in TyG-WHtR reflecting short-term metabolic worsening, is associated with an increased MACE risk, and this relationship appears to be partly mediated by changes in MAP.