Objective:To explore the correlation of cumulative atherogenic index of plasma (cumAIP) and cumulative atherosclerosis index (cumAI) with new-onset non-alcoholic fatty liver disease (NAFLD).Methods:From January 2017 to December 2023, 2 472 subjects who underwent health checkups at the Second Affiliated Hospital of Dalian Medical University for 3 consecutive years were enrolled. Triglyceride, total cholesterol, high density lipoprotein cholesterol and their measurement time intervals were used to calculate cumAIP and cumAI. The subjects were divided into Q1, Q2, Q3 and Q4 groups with the threshold values of 25th percentile, median and 75th percentile of the baseline atherogenic index of plasma (AIP) and atherosclerotic index (AI) subjects. Cox regression model was used to analyze the effects of cumAIP and cumAI on the new-onset NAFLD, restricted cubic spline was performed to analyze the nonlinear association between cumAIP and cumAI and new-onset NAFLD, and the clinical decision curve was used to compare the decision value of different indicators for NAFLD. Results:The risk of NAFLD gradually increased along with the increasing of cumAIP and cumAI. In the quartile groups of cumAIP, the incidence of Q1 to Q4 groups was 6.15%, 8.74%, 15.05%, and 25.08%, respectively. In the quartile groups of cumAI, the incidence of Q1 to Q4 groups was 5.99%, 11.17%, 15.21%, and 22.65%, respectively. After adjusting the confounding factors, the risk of new-onset NAFLD in the high-level group ( Q4) was higher than that in the low-level cumAIP group ( Q1) ( HR=3.15, 95% confidence interval (95% CI): 2.15 to 4.63, P<0.001) and the high-level cumAI group ( Q4) ( HR=2.74, 95% CI: 1.82 to 4.10, P<0.001). cumAIP and cumAI showed a significant nonlinear association with new-onset NAFLD ( χ2=119.15, 94.53; both P<0.001). The cumAIP had higher predictive value for NAFLD than the other cumulative lipid metrics and baseline AIP or AI. Conclusion:CumAIP and cumAI can be served as new predictive indicators of NAFLD, with a particular focus on the dynamic cumulative changes of AIP, which can achieve effective early screening for NAFLD.

Objective:Investigating the association of the systemic immune-inflammation index and the pan-inflammation index with incident non-alcoholic fatty liver disease (NAFLD).Methods:This retrospective cohort study included 42 891 participants who underwent at least two health examinations at the Second Affiliated Hospital of Dalian Medical University between 2014 and 2023. Based on their levels of the systemic immune inflammation index (SII) and the pan immune inflammation value (PIV), participants were respectively divided into four quartile groups (Q1 to Q4). Cox proportional hazards models were employed to analyze the association of different SII and PIV levels, as well as their quartile groups, with new onset NAFLD in the total population and across various subgroups. Restricted cubic splines were used to examine the dose response relationship between these inflammatory indices and incident NAFLD. Additionally, sensitivity analyses were conducted to confirm the robustness of the findings.Results:After adjusting for confounding factors, the natural logarithm-transformed lnSII ( HR=1.247, 95% CI: 1.184-1.314, P<0.001) and lnPIV ( HR=1.192, 95% CI: 1.148-1.238, P<0.001) were significantly positively associated with the risk of NAFLD. When the subjects were grouped by SII quartiles (Q1-Q4), compared with those in Q1, participants in Q2, Q3, and Q4 exhibited progressively higher risks of incident NAFLD:11.9% ( HR=1.119, 95% CI: 1.051-1.192, P<0.001), 17.1% ( HR=1.171, 95% CI: 1.100-1.248, P<0.001), and 29.1% ( HR=1.291, 95% CI: 1.211-1.377, P<0.001), respectively. Quartile analysis of PIV yielded similar trends: the risk of incident NAFLD increased for 10.4% ( HR=1.104, 95% CI: 1.034-1.179, P=0.003), 18.7% ( HR=1.187, 95% CI: 1.112-1.266, P<0.001), and 30.5% ( HR=1.305, 95% CI: 1.223-1.393, P<0.001) in Q2, Q3, and Q4 group respectively when compared to that in Q1 group. Subgroup analysis confirmed consistent associations of SII and PIV with elevated NAFLD risk across all subgroups. Conclusion:Elevated levels of SII and PIV are significantly associated with increased risk of NAFLD.

Objective:To investigate transition pattern of health status among middle-aged and elderly population in China based on frailty index.Methods:In this retrospective cohort study, middle-aged and elderly people were selected from the China Health and Retirement Longitudinal Study (CHARLS) in 2011; and 1 434 subjects were followed up to 2015. The frailty index was calculated from the prevalence of chronic diseases, daily activity ability and blood biomarkers, and the frailty state was divided by quartiles of the frailty index. Markov models were constructed to determine the transition probabilities of different frailty states.Results:The mean age of the 1 434 subjects was (59.0±9.4) years and the mean frailty index was 0.11±0.05. In the healthy individuals, 63.0% remained healthy after a four-year follow-up; during the same follow-up period, 40.9% of the mildly frail individuals and 23.0% of the moderately frail individuals remained in their baseline frailty status. Increasing age leaded to a gradual increase in the probability of the population shifting to a severely frailty state. Women were more likely to shift to severe frailty status than men (0.029 vs 0.019, Z=3.03, P=0.002). Conclusion:Among middle-aged and elderly population in China, the transition of health states follows a pattern where higher frailty levels are associated with lower stability. Advanced age and female gender are identified as risk factors for progression to severe frailty.

Objective:To explore the relationship between thyroid hormone sensitivity and metabolic dysfunction-associated steatotic liver disease(MASLD) in a population with normal thyroid function, with a particular focus on sex-specific differences.Methods:This retrospective study included 41 355 euthyroid cases who underwent routine health examinations at the Health Management Centre of the Second Affiliated Hospital of Dalian Medical University from January 2014 to December 2023 were included. The free triiodothyronine(FT 3) to free thyroxine(FT 4) ratio(FT 3/FT 4) was calculated in order to reflect the peripheral sensitivity of the thyroid gland. Similarly, thyroid feedback quantile-based index(TFQI), thyrotrophic thyroxine resistance index(TT 4RI), and the FT 3-based TFQI-derived index(TFQI-FT 3) were calculated in order to reflect the central sensitivity of the thyroid gland. A Logistic regression was employed to analyse the effect of sex-specific thyroid hormone sensitivity indices on the prevalence of MASLD. The restricted cubic spline was used to analyse the non-linear relationship between the thyroid sensitivity hormone indices and MASLD. Furthermore, the correlation between the thyroid hormone sensitivity indices and MASLD in different subgroups was also analysed. Results:The prevalence of MASLD in the study population was 28.8%. After adjusting the model for confounders, the risk of MASLD increased by 7%, 3%, 10%, and 5% for each standard deviation increase in FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI in the total population, respectively. The risk of MASLD increased by 6% and 5% for each standard deviation increase in FT 3/FT 4 and TFQI-FT 3 in men, respectively. For each standard deviation increase in FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI in women, the risk of MASLD increased by 6%, 5%, 11%, and 5%, respectively. Higher FT 3/FT 4 and TFQI-FT 3 were positively associated with the risk of developing MASLD in men, and higher FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI were positively associated with the risk of developing MASLD in women. There was a non-linear, inverted U-shaped relationship between TFQI and risk of MASLD in women. Subgroup analyses showed positive associations between FT 3/FT 4, TFQI, TFQI-FT 3, and MASLD. Conclusions:The thyroid hormone sensitivity indices may provide a basis for clinical prevention and management of MASLD in individuals with normal thyroid function. Additionally, FT 3/FT 4 and TFQI-FT 3 may indicate the risk of MASLD in the general population, while TFQI and TT 4RI are more suitable for assessing the risk of MASLD in women.

Objective:Investigating the association of the systemic immune-inflammation index and the pan-inflammation index with incident non-alcoholic fatty liver disease (NAFLD).Methods:This retrospective cohort study included 42 891 participants who underwent at least two health examinations at the Second Affiliated Hospital of Dalian Medical University between 2014 and 2023. Based on their levels of the systemic immune inflammation index (SII) and the pan immune inflammation value (PIV), participants were respectively divided into four quartile groups (Q1 to Q4). Cox proportional hazards models were employed to analyze the association of different SII and PIV levels, as well as their quartile groups, with new onset NAFLD in the total population and across various subgroups. Restricted cubic splines were used to examine the dose response relationship between these inflammatory indices and incident NAFLD. Additionally, sensitivity analyses were conducted to confirm the robustness of the findings.Results:After adjusting for confounding factors, the natural logarithm-transformed lnSII ( HR=1.247, 95% CI: 1.184-1.314, P<0.001) and lnPIV ( HR=1.192, 95% CI: 1.148-1.238, P<0.001) were significantly positively associated with the risk of NAFLD. When the subjects were grouped by SII quartiles (Q1-Q4), compared with those in Q1, participants in Q2, Q3, and Q4 exhibited progressively higher risks of incident NAFLD:11.9% ( HR=1.119, 95% CI: 1.051-1.192, P<0.001), 17.1% ( HR=1.171, 95% CI: 1.100-1.248, P<0.001), and 29.1% ( HR=1.291, 95% CI: 1.211-1.377, P<0.001), respectively. Quartile analysis of PIV yielded similar trends: the risk of incident NAFLD increased for 10.4% ( HR=1.104, 95% CI: 1.034-1.179, P=0.003), 18.7% ( HR=1.187, 95% CI: 1.112-1.266, P<0.001), and 30.5% ( HR=1.305, 95% CI: 1.223-1.393, P<0.001) in Q2, Q3, and Q4 group respectively when compared to that in Q1 group. Subgroup analysis confirmed consistent associations of SII and PIV with elevated NAFLD risk across all subgroups. Conclusion:Elevated levels of SII and PIV are significantly associated with increased risk of NAFLD.

Objective:To investigate transition pattern of health status among middle-aged and elderly population in China based on frailty index.Methods:In this retrospective cohort study, middle-aged and elderly people were selected from the China Health and Retirement Longitudinal Study (CHARLS) in 2011; and 1 434 subjects were followed up to 2015. The frailty index was calculated from the prevalence of chronic diseases, daily activity ability and blood biomarkers, and the frailty state was divided by quartiles of the frailty index. Markov models were constructed to determine the transition probabilities of different frailty states.Results:The mean age of the 1 434 subjects was (59.0±9.4) years and the mean frailty index was 0.11±0.05. In the healthy individuals, 63.0% remained healthy after a four-year follow-up; during the same follow-up period, 40.9% of the mildly frail individuals and 23.0% of the moderately frail individuals remained in their baseline frailty status. Increasing age leaded to a gradual increase in the probability of the population shifting to a severely frailty state. Women were more likely to shift to severe frailty status than men (0.029 vs 0.019, Z=3.03, P=0.002). Conclusion:Among middle-aged and elderly population in China, the transition of health states follows a pattern where higher frailty levels are associated with lower stability. Advanced age and female gender are identified as risk factors for progression to severe frailty.

Objective:To explore the relationship between thyroid hormone sensitivity and metabolic dysfunction-associated steatotic liver disease(MASLD) in a population with normal thyroid function, with a particular focus on sex-specific differences.Methods:This retrospective study included 41 355 euthyroid cases who underwent routine health examinations at the Health Management Centre of the Second Affiliated Hospital of Dalian Medical University from January 2014 to December 2023 were included. The free triiodothyronine(FT 3) to free thyroxine(FT 4) ratio(FT 3/FT 4) was calculated in order to reflect the peripheral sensitivity of the thyroid gland. Similarly, thyroid feedback quantile-based index(TFQI), thyrotrophic thyroxine resistance index(TT 4RI), and the FT 3-based TFQI-derived index(TFQI-FT 3) were calculated in order to reflect the central sensitivity of the thyroid gland. A Logistic regression was employed to analyse the effect of sex-specific thyroid hormone sensitivity indices on the prevalence of MASLD. The restricted cubic spline was used to analyse the non-linear relationship between the thyroid sensitivity hormone indices and MASLD. Furthermore, the correlation between the thyroid hormone sensitivity indices and MASLD in different subgroups was also analysed. Results:The prevalence of MASLD in the study population was 28.8%. After adjusting the model for confounders, the risk of MASLD increased by 7%, 3%, 10%, and 5% for each standard deviation increase in FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI in the total population, respectively. The risk of MASLD increased by 6% and 5% for each standard deviation increase in FT 3/FT 4 and TFQI-FT 3 in men, respectively. For each standard deviation increase in FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI in women, the risk of MASLD increased by 6%, 5%, 11%, and 5%, respectively. Higher FT 3/FT 4 and TFQI-FT 3 were positively associated with the risk of developing MASLD in men, and higher FT 3/FT 4, TFQI, TFQI-FT 3, and TT 4RI were positively associated with the risk of developing MASLD in women. There was a non-linear, inverted U-shaped relationship between TFQI and risk of MASLD in women. Subgroup analyses showed positive associations between FT 3/FT 4, TFQI, TFQI-FT 3, and MASLD. Conclusions:The thyroid hormone sensitivity indices may provide a basis for clinical prevention and management of MASLD in individuals with normal thyroid function. Additionally, FT 3/FT 4 and TFQI-FT 3 may indicate the risk of MASLD in the general population, while TFQI and TT 4RI are more suitable for assessing the risk of MASLD in women.

Objective:To explore the correlation of cumulative atherogenic index of plasma (cumAIP) and cumulative atherosclerosis index (cumAI) with new-onset non-alcoholic fatty liver disease (NAFLD).Methods:From January 2017 to December 2023, 2 472 subjects who underwent health checkups at the Second Affiliated Hospital of Dalian Medical University for 3 consecutive years were enrolled. Triglyceride, total cholesterol, high density lipoprotein cholesterol and their measurement time intervals were used to calculate cumAIP and cumAI. The subjects were divided into Q1, Q2, Q3 and Q4 groups with the threshold values of 25th percentile, median and 75th percentile of the baseline atherogenic index of plasma (AIP) and atherosclerotic index (AI) subjects. Cox regression model was used to analyze the effects of cumAIP and cumAI on the new-onset NAFLD, restricted cubic spline was performed to analyze the nonlinear association between cumAIP and cumAI and new-onset NAFLD, and the clinical decision curve was used to compare the decision value of different indicators for NAFLD. Results:The risk of NAFLD gradually increased along with the increasing of cumAIP and cumAI. In the quartile groups of cumAIP, the incidence of Q1 to Q4 groups was 6.15%, 8.74%, 15.05%, and 25.08%, respectively. In the quartile groups of cumAI, the incidence of Q1 to Q4 groups was 5.99%, 11.17%, 15.21%, and 22.65%, respectively. After adjusting the confounding factors, the risk of new-onset NAFLD in the high-level group ( Q4) was higher than that in the low-level cumAIP group ( Q1) ( HR=3.15, 95% confidence interval (95% CI): 2.15 to 4.63, P<0.001) and the high-level cumAI group ( Q4) ( HR=2.74, 95% CI: 1.82 to 4.10, P<0.001). cumAIP and cumAI showed a significant nonlinear association with new-onset NAFLD ( χ2=119.15, 94.53; both P<0.001). The cumAIP had higher predictive value for NAFLD than the other cumulative lipid metrics and baseline AIP or AI. Conclusion:CumAIP and cumAI can be served as new predictive indicators of NAFLD, with a particular focus on the dynamic cumulative changes of AIP, which can achieve effective early screening for NAFLD.