Abstract
BACKGROUND: Insulin resistance (IR) is a key driver of cardiovascular disease. The triglyceride-glucose (TyG) index, derived from fasting triglyceride and glucose levels, has been proposed as a surrogate marker of IR. However, its effect on lipid control in patients with coronary artery disease (CAD) receiving lipid-lowering therapy (LLT) remains unclear. METHODS: In this prospective cohort study, biochemical parameters of 1393 CAD patients were measured and followed over a median of one year. Participants received either low-/moderate-intensity LLT or high-intensity LLT. Linear regression models, logistic regression analyses, and change-to-change analyses were conducted to comprehensively assess the associations between baseline levels, longitudinal changes, and status transitions of the TyG index and lipid parameters. RESULTS: Lipid levels differed significantly across TyG index tertiles, with the highest tertile showing more adverse profiles at baseline and follow-up. Higher baseline TyG levels were independently associated with increased follow-up atherogenic lipid parameters and failure to achieve targets of non-high-density lipoprotein cholesterol (Non-HDL-C, OR = 1.23, 95% CI 1.01-1.51) and remnant cholesterol (RC, OR = 1.38, 95% CI 1.09-1.76). Participants in the highest tertile had the highest odds of not achieving targets for LDL-C, Non-HDL-C, and RC. Each 1% increase in the index was associated with percent increases in lipids including LDL-C (β = 1.10), Non-HDL-C (β = 1.81), and RC (β = 4.92, all P < 0.001). Patients transitioning from the lowest to the highest TyG tertile showed significant lipid worsening, while improvement from the highest to the lowest tertile was associated with reductions in RC and Non-HDL-C. High-intensity LLT led to greater reductions in TyG and lipid levels, mitigating the adverse lipid effects of TyG elevation. The adverse effects were also more evident in women and in those with obesity or prior revascularization. CONCLUSIONS: Higher TyG levels were positively associated with atherogenic lipid profiles and failure to achieve lipid goals. In addition, upward changes in TyG over time were related to worsened atherogenic lipid status, particularly among patients receiving low-/moderate-intensity LLT. These findings support the routine monitoring of TyG to identify patients at risk of poor lipid control who may require high-intensity LLT.