Association of T3/T4 ratio with inflammatory indicators and all-cause mortality in stroke survivors.

Abstract

Background: Abnormal thyroid hormone levels may occur in critical illness, which may have an interactive relationship with inflammatory reaction. At present, the relationship between triiodothyronine (T3)/thyroxine (T4) ratio and inflammatory indicators and all-cause mortality of stroke survivors is still unclear.

Methods: We obtained the relevant data of the respondents from 2007 to 2012 through the National Health and Nutrition Examination Survey (NHANES) database for statistical analysis. The ratio of T3/T4, a continuous variable, is transformed into three groups of classified variables, namely Q1, Q2 and Q3. The relationship between T3/T4 ratio and mortality was analyzed by Log-Rank test and K-M survival curve. Pearson correlation analysis was used to analyze the correlation between T3/T4 ratio and white blood cell (WBC), Neutrophil-to-Lymphocyte Ratio (NLR), systemic immune-inflammation index (SII) and neutrophil percentage-to-albumin ratio (NPAR). Cox univariate and multivariate analysis was used to identify independent risk factors for all-cause mortality in stroke survivors and a nomogram was drawn. Restricted cubic spline (RCS) curve was drawn to determine whether there was a linear relationship between T3/T4 ratio and mortality and the best cut-off value. Subgroup analysis showed the difference between the T3/T4 ratio and all-cause mortality among subgroups and a forest plot was drawn. The mediation effect analysis was used to analyze whether the ratio of T3/T4 could mediate the survival time through inflammatory indicators.

Results: According to the inclusion and exclusion criteria, a total of 267 people were included in the study, with a mortality rate of 49.06% (131/267), an average survival time of 111.22 ± 3.19 months, and a median survival time of 130 ± 11.27 months. The Log-Rank test and K-M survival curve showed that there were statistical differences among the Q1, Q2, and Q3 groups of the T3/T4 ratio (x ² = 16.32, p<0.001), and the lower the T3/T4 level, the shorter the survival time. Pearson correlation analysis showed that the T3/T4 ratio had a linear relationship with NLR, SII, and NPAR, and only had a weak correlation with NPAR (r = -0.31, p<0.001). Cox univariate analysis showed that age, marital status, race, cancer, T3/T4 ratio, NPAR and all-cause mortality were related. Multivariate regression analysis showed that age ≥ 60 years, race of non-Hispanic black, low T3/T4 ratio (p = 0.014, HR = 0.92, 95% CI = 0.87~0.98) and high NPAR (p = 0.009, HR = 2.50, 95% CI = 1.26~4.99) were independent risk factors for all-cause mortality. The RCS curve shows that the ratio of T3/T4 is linearly correlated with mortality, and the optimal cutoff value of T3/T4 is 12.97. Subgroup analysis showed that T3/T4 ratio is more likely to affect the survival of stroke survivors with BMI 18.5~28. Mediation effect analysis showed that there was a mediation effect between T3/T4 ratio, NPAR and survival time. The effect size of T3/T4 directly affecting survival time is 78.45%, and the effect size of T3/T4 indirectly affecting survival time through NPAR is 21.55%.

Conclusions: T3/T4 ratio is an independent risk factor for all-cause mortality in stroke survivors, especially in the people with BMI 18.5~28. T3/T4 ratio may mediate the survival time through NPAR level. Therefore, monitoring thyroid function is beneficial to the management of stroke survivors.