Abstract: Objective To investigate the association between serum free fatty acid (FFA) level measured at admission and 90-day mortality in elderly patients with spontaneous intracerebral hemorrhage (sICH). Methods A retrospective study was conducted on 564 patients aged >60 years with sICH. Baseline data, including sex, age, smoking history, alcohol consumption history, blood pressure, comorbidities, National Institutes of Health Stroke Scale (NIHSS) score, FFA, blood lipid profile, blood routine index, hematoma volume, and activated partial thromboplastin time (APTT), were collected from all enrolled patients. Patients were divided into a low FFA group (FFA≤0.40 mmol/L, n=293) and a high FFA group (FFA>0.40 mmol/L, n=271) based on median serum FFA level. All patients were followed up for 90 days following discharge, with the outcome defined as all-cause mortality. Univariate and multivariate Cox proportional hazards regression models were employed to analyze the association between serum FFA level and the risk of 90-day all-cause mortality in elderly patients with sICH. Pearson correlation analysis was performed to examine the relationship between FFA level and hematoma volume. Mediation analysis was conducted via the bootstrap method, with FFA as the independent variable, hematoma volume as the mediator, and 90-day mortality as the dependent variable. Results Significant differences were observed in systolic blood pressure, hematoma volume, high-density lipoprotein cholesterol, lipoprotein(a), apolipoprotein B, and mortality rate between elderly sICH patients with different FFA levels (P<0.05). The log-rank test demonstrated that elderly sICH patients with different FFA levels exhibited significant differences in 90-day mortality risk (P<0.05). Univariate Cox proportional hazards regression analysis indicated that age, FFA, hematoma volume, NIHSS score, white blood cell count, hypertension, smoking, and APTT might be associated with 90-day all-cause mortality in elderly sICH patients (P<0.05). In the multivariate Cox proportional hazards regression model, after adjusting for hematoma volume, NIHSS score, APTT, white blood cell count, age, and diastolic blood pressure, FFA remained an independent influencing factor for 90-day all-cause mortality in elderly patients with sICH (HR=2.803, 95%CI: 1.032-7.611). Pearson correlation analysis indicated a positive correlation between FFA level and hematoma volume (r=0.161, P<0.001). Mediation analysis revealed that the indirect effect of FFA on 90-day mortality through hematoma volume was 0.351 (95%CI: 0.123-0.663). Conclusions FFA level at admission is significantly associated with the 90-day mortality risk in elderly sICH patients, and it may influence the 90-day mortality through hematoma volume.

Key words: free fatty acids, spontaneous intracerebral hemorrhage, aged, risk factor, all-cause mortality