Joint association of TyG index and LDL-C with all-cause and cardiovascular mortality among patients with cardio-renal-metabolic disease

Background: Both the triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, and low-density lipoprotein cholesterol (LDL-C) are independent risk factors for long-term prognosis among patients with cardio-renal-metabolic (CRM) disease. However, the co-exposures of TyG index and LDL-C to all-cause and cardiovascular death among patients with CRM remain unknown. Methods: Patients with CRM from the National Health and Nutrition Examination Survey (NHANES) database (1999–2018) were included. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Multivariable Cox and restricted cubic spline (RCS) regression models were used to estimate the individual and joint association of TyG index and LDL-C with the risk of all-cause and cardiovascular mortality. The interaction between the TyG index and LDL-C to mortality was also evaluated. Results: During a median follow-up of 7.6 years, there were 1608 (22.8%) and 609 (8.4%) patients who died from all-cause and cardiovascular mortality, respectively. In patients with LDL-C<2.6 mmol/L, no significant differences were observed in all-cause and cardiovascular mortality when comparing higher TyG index to the lowest tertile (T1). Specifically, the hazard ratios (HRs) for all-cause mortality in the second (T2) and third tertiles (T3) were 0.81 (95%CI: 0.59–1.09) and 0.87 (95%CI: 0.62–1.22), respectively, with a P for trend of 0.468. For cardiovascular mortality, the HRs for T2 and T3 compared to T1 were 0.80 (95%CI: 0.48–1.32) and 0.72 (95%CI: 0.45–1.15), respectively, with a P for trend of 0.173. However, elevated TyG index was related to markedly increased risk of all-cause and cardiovascular mortality in patients with LDL-C≥2.6 mmol/L. Specifically, for all-cause mortality, HRs for T2 and T3 compared to T1 were 1.01 (95%CI: 0.79–1.28) and 1.38 (95%CI: 1.07–1.79), respectively, with a P for trend of 0.009. For cardiovascular mortality, the HRs were 1.09 (95% CI: 0.72–1.65) for T2 and 1.80 (95% CI: 1.18–2.75) for T3, with a P for trend of 0.005. Similar results were found in RCS and sensitivity analyses. Interactive analysis also demonstrated that a significant association of TyG index and LDL-C with the risk of all-cause (P for interaction=0.011) and cardiovascular (P for interaction=0.050) mortality was observed. Conclusions: Our research demonstrated the co-exposure effects between the TyG index and LDL-C on all-cause and cardiovascular mortality. Elevated TyG index can significantly increase the risk of all-cause and cardiovascular mortality only among CRM patients with LDL-C ≥ 2.6 mmol/L, but not among patients with LDL-C < 2.6 mmol/L.