Correlation of plasma insulin-like factor 6 level with risk of acute aortic syndrome and adverse prognosis

Objective‍ ‍To analyze the clinical value of plasma insulin-like factor 6 (INSL6) in predicting the risk of acute aortic syndromes (AAS) and adverse outcomes. Methods‍ ‍A retrospective case-control trial was conducted on 194 AAS patients admitted to Department of Cardiovascular Diseases of Second Affiliated Hospital of Army Medical University between April 2021 and June 2023. Another 194 sex-, age- and BMI-matched individuals without aortic diseases were recruited from the health examination center between December 2021 and January 2024. Their plasma INSL6 level was measured with ELISA, and the general clinical data and results of some laboratory tests were collected and compared between the 2 groups. Spearman correlation analysis was used to assess the relationship between plasma INSL6 and other variables, receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficacy of INSL6 for AAS occurrence, multivariate conditional logistic regression model was utilized to analyze the association between plasma INSL6 and AAS onset, and Kaplan-Meier survival curve and multivariate Cox proportional hazards regression model was applied to analyze the relationship between acute-phase plasma INSL6 level and adverse prognosis in AAS patients. Results‍ ‍The plasma INSL6 level was significantly higher in AAS patients at acute phase than the control individuals [704.40 (481.32~1 152.62) vs 141.24 (107.60~163.72) pg/mL, P<0.001], but no statistical difference was observed in the level among the patients with different AAS subtypes (aortic dissection, intramural hematoma, and penetrating aortic ulcer). Spearman correlation analysis showed that the plasma INSL6 level was positively correlated with platelet count (r=0.325, P<0.001) and hemoglobin concentration (r=0.186, P=0.009), and negatively with IL-6 (r=-0.182, P=0.011), INF-γ (r=-0.283, P<0.001), and D-dimer levels (r=-0.195, P=0.006). Multivariate conditional logistic regression analysis revealed that plasma INSL6 level was independently associated with the occurrence of AAS (OR=28.634, 95%CI: 7.267~112.820, P<0.001). ROC curve analysis further confirmed that the optimal cutoff value of plasma INSL6 in predicting AAS was 259.425 pg/mL, with a sensitivity of 95.9% and a specificity of 98.5% at this threshold. Kaplan-Meier curve analysis demonstrated that AAS patients with low INSL6 level had significantly lower cumulative survival rates (P=0.020) and event-free survival rates (P=0.004) than those with high INSL6 level (P<0.05). Multivariate COX regression analysis revealed that, after adjusting for sex, age, systolic blood pressure, ST classification, and surgical treatment, acute-phase INSL6 level was independently associated with all-cause mortality (HR: 0.999, 95%CI: 0.999~1.000, P=0.023), AAS-related mortality (HR: 0.999, 95%CI: 0.998~1.000, P=0.012), and composite endpoint events (HR: 0.999, 95%CI: 0.999~1.000, P=0.026) in AAS patients during follow-up. Conclusion‍ ‍Plasma INSL6 level is closely associated with the occurrence and adverse prognosis of AAS, and the indicator is expected to be an effective biomarker for diagnosing AAS and predicting its prognosis.