Abstract Background Low-density lipoprotein cholesterol (LDL-C) plays a central role in the pathogenesis of acute myocardial infarction (AMI). However, major adverse cardiovascular events (MACE) still occur despite achieving guideline-recommended LDL-C levels. Inflammation and atherogenic lipoproteins beyond LDL-C, notably remnant cholesterol (RC), may underlie this residual risk. Purpose To assess the association between one-year change in a Remnant Lipid-Inflammatory Index (ReLI) and long-term outcomes among AMI survivors with well-controlled LDL-C. Methods We performed a retrospective 12-month landmark analysis using the KAMIR-NIH-LIPID registry (Korean Acute Myocardial Infarction Registry – National Institutes of Health – LIPID). Patients achieving LDL-C control at 12 months (≤70 mg/dL or ≥50% reduction from baseline) were included (n=1,978). ReLI was defined as the mean of z-scores for RC, high-sensitivity C-reactive protein (hsCRP), and white blood cell count (WBC). The one-year change (ΔReLI = 12-month − baseline) was categorized by ±1 SD: Improved (≤−1 SD), Stable (−1 to +1 SD), and Worsened (≥+1 SD). The primary endpoint was post-landmark MACE through 4 years. Kaplan–Meier analyses and multivariable Cox regression adjusting for clinical covariates were performed. Results Four-year MACE-free survival differed significantly across ΔReLI categories (log-rank p=0.019), with separation driven by excess events in the Worsened group. In multivariable Cox models landmarked at 12 months and adjusted for demographics, comorbidities, index MI characteristics, and evidence-based therapies, the Worsened group had a higher risk of MACE versus Stable (HR 1.58, 95% CI 1.11–2.25), whereas Improved did not differ from Stable (HR 0.97, 95% CI 0.63–1.48). The corresponding Kaplan–Meier curves and 4-year cumulative incidence estimates were concordant, showing overlapping risks for Improved and Stable and the highest risk in Worsened. Conclusions Among AMI survivors achieving LDL-C targets at 12 months, deterioration of ReLI during the first year independently identifies patients at elevated long-term risk. The remnant lipo-inflammatory axis may represent an actionable residual risk component beyond LDL-C control and warrants prospective validation.
Lee et al. (Fri,) studied this question.