Abstract
BACKGROUND: The dose-response relationship and independent prognostic value of free fatty acids (FFA) for major adverse cardiovascular events (MACE) in patients with premature myocardial infarction are not well established. This study aimed to evaluate the impact of FFA levels on long-term outcomes and their combined effects with inflammatory markers, obesity, and insulin resistance. METHODS: This prospective cohort study enrolled 1168 consecutive patients with premature myocardial infarction admitted to the coronary care unit ward of Tianjin Chest Hospital from March 2017 to December 2024. Participants were categorized into 4 groups (Q1-Q4) by baseline FFA quartiles. Over a median follow-up of 2.83 years (interquartile range, 2.58-3.10), the primary end point was MACE. Cox proportional hazards models and restricted cubic splines were used to assess associations and nonlinear relationships between FFA levels and MACE risk. RESULTS: FFA levels showed a U-shaped association with long-term prognosis in patients with premature myocardial infarction. Using Q2 (0.43-0.61 mmol/L) as reference, adjusted hazards for MACE were significantly higher in Q1 (hazard ratio [HR], 1.89 [95% CI, 1.11-2.96], P=0.009), Q3 (HR, 2.47 [95% CI, 1.55-3.93], P<0.001), and Q4 (HR, 2.94 [95% CI, 1.86-4.65], P<0.001). Joint analyses indicated synergistic risks increased when abnormal FFA coexisted with hs-CRP (high-sensitivity C-reactive protein) >5 mg/L, body mass index >28 kg/m(2), or triglyceride-glucose index >9.21 mmol/L. CONCLUSIONS: Both elevated and decreased FFA levels independently increase MACE risk in patients with premature myocardial infarction. Abnormal FFA levels combined with high inflammation, obesity, and insulin resistance significantly increase the risk of MACE, highlighting their combined value in the long-term poor prognosis.