Lipoprotein Combine Index as a Better Marker for NAFLD Identification Than Traditional Lipid Parameters.

Purpose: The association between traditional lipid parameters and non-alcoholic fatty liver disease (NAFLD) has been extensively discussed. This study aims to evaluate and compare the lipoprotein combine index (LCI) and traditional lipid parameters [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] to identify NAFLD. Patients and Methods: The analysis included 14,251 participants from the NAfld in the Gifu Area, Longitudinal Analysis (NAGALA). Logistic regression models were employed to calculate standardized odds ratios (ORs) and 95% confidence intervals (CIs) for assessing and comparing the association of LCI and traditional lipid parameters with NAFLD. Additionally, receiver operating characteristic (ROC) curves were used to calculate the area under the curve (AUC) for LCI and traditional lipid parameters in identifying NAFLD. Results: After adjusting for various confounders, we found that LCI was positively associated with NAFLD (OR=2.25, 95% CI 1.92-2.63), and this association was stronger than that of traditional lipid parameters [OR: TC1.23, TG1.73 LDL-C1.10]. Further subgroup analyses revealed that the association of LCI with NAFLD was stronger than other traditional lipid parameters in all subgroups, including men and women, overweight/obese [body mass index (BMI)≥25 kg/m2] and non-obese (BMI<25 kg/m2), and older (age≥45 years) and younger (age<45 years) participants. Additionally, ROC analysis indicated that LCI (AUC=0.8118) had significantly higher accuracy (All DeLong P<0.05) in identifying NAFLD compared to traditional lipid parameters (AUC: TC0.6309; TG0.7969; LDL-C0.6941); HDL-C0.7587). Sensitivity analysis further confirmed the robustness of the study findings. Conclusion: This study revealed for the first time a positive correlation between LCI and NAFLD. Compared to traditional lipid parameters, LCI has a higher correlation with NAFLD. Additionally, further ROC analysis demonstrated that LCI had higher accuracy in identifying NAFLD compared to traditional lipid parameters, suggesting that LCI may be a better marker for NAFLD identification than traditional lipid parameters.

Evaluating the prognostic value of systemic immune-inflammatory index in patients with acute decompensated heart failure.

AIMS: The value of the systemic immune-inflammatory index (SII) in assessing adverse outcomes in various cardiovascular diseases has been extensively discussed. This study aims to evaluate the predictive value and risk stratification ability of SII for 30 day mortality in patients with acute decompensated heart failure (ADHF). METHODS: This analysis included 1452 patients hospitalized for ADHF, all the participants being part of the China Jiangxi-acute decompensated heart failure1 project. The risk stratification capability of the SII in patients with ADHF, as well as its correlation with the 30 day mortality risk among ADHF patients, was evaluated utilizing Kaplan-Meier survival analysis and multivariable Cox regression models. A restricted cubic spline was employed to model the dose-response relationship between the two, and the receiver operating characteristic curve was utilized to assess the predictive ability of SII for 30 day mortality. RESULTS: The Kaplan-Meier analysis revealed that the risk of mortality in the high SII group (SII ≥ 980 × 109/L) was significantly greater than that in the low SII group (SII < 980 × 109/L, log-rank P < 0.001). After adjusting for various confounding factors, a higher SII was associated with an increased risk of 30 day mortality in ADHF patients [hazard ratio (HR) = 2.03, 95% confidence interval (CI): 1.34-3.08]. Further restricted cubic spline analysis revealed a non-linear dose-response relationship between the two (P for non-linear = 0.006). Receiver operating characteristic analysis demonstrated that SII had a high accuracy in predicting 30 day mortality events in ADHF patients (AUC = 0.7479), and the optimal predictive threshold was calculated to be 980 × 109/L, a sensitivity of 0.7547 and a specificity of 0.7234. CONCLUSIONS: This study found a significant positive association between SII and 30 day all-cause mortality in ADHF patients. We determined the SII cut-off point for predicting 30 day all-cause mortality in patients with ADHF to be 980 × 109/L.

Atherogenic index of plasma: a new indicator for assessing the short-term mortality of patients with acute decompensated heart failure.

Objective: Arteriosclerosis is a primary causative factor in cardiovascular diseases. This study aims to explore the correlation between the atherogenic index of plasma (AIP) and the 30-day mortality rate in patients with acute decompensated heart failure (ADHF). Methods: A total of 1,248 ADHF patients recruited from the Jiangxi-Acute Decompensated Heart Failure1 (JX-ADHF1) cohort between 2019 and 2022 were selected for this study. The primary outcome was the 30-day mortality rate. Multivariable Cox regression, restricted cubic splines (RCS), and stratified analyses were utilized to assess the relationship between AIP and the 30-day mortality rate in ADHF patients. Mediation models were employed for exploratory analysis of the roles of inflammation, oxidative stress, and nutrition in the association between AIP and the 30-day mortality rate in ADHF patients. Results: During the 30-day follow-up, 42 (3.37%) of the ADHF patients died. The mortality rates corresponding to the quartiles of AIP were as follows: Q1: 1.28%, Q2: 2.88%, Q3: 2.88%, Q4: 6.41%. The multivariable Cox regression revealed a positive correlation between high AIP and the 30-day mortality rate in ADHF patients [Hazard ratio (HR) 3.94, 95% confidence interval (CI): 1.08-14.28], independent of age, gender, heart failure type, cardiac function classification, and comorbidities. It is important to note that there was a U-shaped curve association between AIP (<0.24) and the 30-day mortality rate before the fourth quartile, with the lowest 30-day mortality risk in ADHF patients around an AIP of -0.1. Furthermore, mediation analysis suggested significant mediating effects of inflammation and nutrition on the 30-day mortality rate in ADHF patients related to AIP, with inflammation accounting for approximately 24.29% and nutrition for about 8.16% of the mediation effect. Conclusion: This retrospective cohort analysis reveals for the first time the association between AIP and the 30-day mortality rate in ADHF patients. According to our findings, maintaining an AIP around -0.1 in ADHF patients could be crucial for improving poor prognoses from a medical perspective. Additionally, for ADHF patients with high AIP, it is important to assess and, if necessary, enhance nutritional support and anti-inflammatory treatment.

Lipids as potential mediators linking body mass index to diabetes: evidence from a mediation analysis based on the NAGALA cohort.

BACKGROUND: Body mass index (BMI) and lipid disorders are both known to be strongly associated with the development of diabetes, however, the indirect effect of lipid parameters in the BMI-related diabetes risk is currently unknown. This study aimed to investigate the mediating role of lipid parameters in the association of BMI with diabetes risk. METHODS: We assessed the association of diabetes risk with BMI, as well as lipid parameters including high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-CF and LDL-CS), triglycerides(TG), total cholesterol(TC), remnant cholesterol(RC), non-HDL-C, and combined indices of lipid parameters with HDL-C (RC/HDL-C ratio, TG/HDL-C ratio, TC/HDL-C ratio, non-HDL/HDL-C ratio, LDL/HDL-C ratio) using data from 15,453 subjects in the NAGALA project. Mediation models were used to explore the mediating role of lipid parameters in the association of BMI with diabetes risk, and mediation percentages were calculated for quantifying the strength of the indirect effects. Finally, receiver operating characteristic curve (ROC) analysis was used to compare the accuracy of BMI and BMI combined with lipid parameters in predicting incident diabetes. RESULTS: Multivariate regression models, adjusted for confounding factors, demonstrated robust associations of lipid parameters, BMI, with diabetes risk, with the exception of TC, LDL-CF, LDL-CS, and non-HDL-C. Mediation analysis showed that lipid parameters except TC, LDL-CF, LDL-CS, and Non-HDL-C were involved in and mediated the association of BMI with diabetes risk, with the largest mediation percentage being the RC/HDL-C ratio, which was as high as 40%; it is worth mentioning that HDL-C and HDL-C-related lipid ratio parameters also play an important mediating role in the association between BMI and diabetes, with the mediator proportion being greater than 30%. Finally, based on the ROC results, we found that the prediction performance of all lipid parameters in the current study except TC was significantly improved when combined with BMI. CONCLUSION: Our fresh findings suggested that lipid parameters partially mediated the association of BMI with diabetes risk; this result indicated that in the context of diabetes risk screening and disease management, it is important to not only monitor BMI but also pay attention to lipid parameters, particularly HDL-C and HDL-C-related lipid ratio parameters.

Prognostic value of geriatric nutritional risk index in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Malnutrition increases the risk of poor prognosis in patients with cardiovascular disease, and our current research was designed to assess the predictive performance of the Geriatric Nutrition Risk Index (GNRI) for the occurrence of poor prognosis after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (SCAD) and to explore possible thresholds for nutritional intervention. METHODS: This study retrospectively enrolled newly diagnosed SCAD patients treated with elective PCI from 2014 to 2017 at Shinonoi General Hospital, with all-cause death as the main follow-up endpoint. Cox regression analysis and restricted cubic spline (RCS) regression analysis were used to explore the association of GNRI with all-cause death risk and its shape. Receiver operating characteristic curve (ROC) analysis and piecewise linear regression analysis were used to evaluate the predictive performance of GNRI level at admission on all-cause death in SCAD patients after PCI and to explore possible nutritional intervention threshold points. RESULTS: The incidence of all-cause death was 40.47/1000 person-years after a mean follow-up of 2.18 years for 204 subjects. Kaplan-Meier curves revealed that subjects at risk of malnutrition had a higher all-cause death risk. In multivariate Cox regression analysis, each unit increase in GNRI reduced the all-cause death risk by 14% (HR 0.86, 95% CI 0.77, 0.95), and subjects in the GNRI > 98 group had a significantly lower risk of death compared to those in the GNRI < 98 group (HR 0.04, 95% CI 0.00, 0.89). ROC analysis showed that the baseline GNRI had a very high predictive performance for all-cause death (AUC = 0.8844), and the predictive threshold was 98.62; additionally, in the RCS regression analysis and piecewise linear regression analysis we found that the threshold point for the GNRI-related all-cause death risk was 98.28 and the risk will be significantly reduced when the subjects' baseline GNRI was greater than 98.28. CONCLUSIONS: GNRI level at admission was an independent predictor of all-cause death in SCAD patients after PCI, and GNRI equal to 98.28 may be a useful threshold for nutritional intervention in SCAD patients treated with PCI.

Evaluating the relative importance of different blood pressure indices in screening for NAFLD: a survey report based on a health examination population.

Objective: While hypertension is a well-recognized risk factor for non-alcoholic fatty liver disease (NAFLD), the specific roles of various common blood pressure measurements [diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), mean arterial pressure (MAP)] in detecting NAFLD and evaluating the associated risk in adults remain unclear. Methods: A retrospective analysis was conducted on 14,251 adult participants undergoing health screenings in the NAfld in the Gifu Area, Longitudinal Analysis project (NAGALA). Following the Z-transformation of the independent variables, we evaluated the relationships between the four blood pressure indices and NAFLD through multivariable logistic regression models. This analysis documented the odds ratio (OR) and 95% confidence interval (CI) for each standard deviation (SD) increase. Additionally, the effectiveness of these indices in identifying NAFLD was comparatively analyzed using receiver operating characteristic (ROC) curves. Results: After adequately adjusting for confounders, all blood pressure indices except PP showed a positive correlation with NAFLD. For each SD increment, MAP had the strongest association with NAFLD compared to SBP and DBP. This finding was confirmed in populations without exercise habits, under 60 years of age, with normal blood pressure, and in non-obese groups. Furthermore, based on ROC analysis, MAP was found to have the highest accuracy in identifying NAFLD compared to the other three blood pressure indices. Conclusion: Among the four blood pressure indices evaluated, MAP demonstrates the greatest efficacy in identifying NAFLD and assessing its associated risk. These findings underscore the potential of MAP as the most promising blood pressure index for screening NAFLD.

Predictive value of insulin resistance surrogates for the development of diabetes in individuals with baseline normoglycemia: findings from two independent cohort studies in China and Japan.

BACKGROUND: Insulin resistance (IR) plays a crucial role in the occurrence and progression of diabetes. This study aimed to evaluate and compare the predictive value of four IR surrogates, including the triglycerides glucose (TyG) index, TyG and body mass index (TyG-BMI), triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) ratio, and the metabolic score for IR (MetS-IR) for diabetes in two large cohorts. METHODS: A total of 116,661 adult participants from the China Rich Healthcare Group and 15,464 adult participants from the Japanese NAGALA cohort were included in the study. Multivariable Cox proportional hazards models were used to assess the standardized hazard ratio (HR) of the TyG index, TyG-BMI, TG/HDL-C ratio, and MetS-IR directly associated with diabetes. Receiver operating characteristic (ROC) curve and time-dependent ROC curve analysis were performed to evaluate and compare the predictive value of the four IR surrogates for diabetes. RESULTS: In the two independent cohorts, the average follow-up time was 3.1 years in the China cohort, with 2681(2.30%) incident cases of diabetes recorded, and 6.13 years in the Japan cohort, with 373 incident cases (2.41%) of diabetes recorded. After adjusting for potential confounding factors, we found that among the four IR surrogates, TyG-BMI and MetS-IR showed stronger associations with diabetes. The stronger associations persisted even after further stratification by age, sex, hypertension, and obese subgroups. In terms of diabetes prediction, based on ROC analysis, TyG-BMI demonstrated the highest predictive accuracy for diabetes in the Chinese population, while both TyG-BMI and MetS-IR showed the highest predictive accuracy in the Japanese population. The results of further subgroup ROC analysis confirmed the robustness of these findings. Furthermore, the time-dependent ROC results indicated that among the four IR surrogates, MetS-IR exhibited the highest accuracy in predicting future diabetes at various time intervals in the Japanese population. CONCLUSION: Our findings suggest that evaluating TyG-BMI and MetS-IR as IR surrogates may be the most useful for predicting diabetes events and assessing the risk of developing diabetes in East Asian populations.

Sex-specific associations between haemoglobin glycation index and the risk of cardiovascular and all-cause mortality in individuals with pre-diabetes and diabetes: A large prospective cohort study.

AIM: The aim of this study was to investigate the relationship between the haemoglobin glycation index (HGI), and cardiovascular disease (CVD) and all-cause mortality in adults with pre-diabetes and diabetes. METHODS: This study included 10 267 adults with pre-diabetes and diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Sex-differentiated relationships between HGI and mortality were elucidated using multivariate Cox proportional hazards models, restricted cubic splines and a two-piecewise Cox proportional hazards model. RESULTS: During the median follow-up time of 103.5 months, a total of 535 CVD deaths and 1918 all-cause deaths were recorded. After multivariate adjustment, in males with pre-diabetes and diabetes, there was a U-shaped relationship between HGI and CVD mortality and all-cause mortality, with threshold points of -0.68 and -0.63, respectively. Before the threshold point, HGI was negatively associated with CVD mortality [hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.41, 0.89] and all-cause mortality (HR 0.56; 95% CI 0.43, 0.74), and after the threshold point, HGI was positively associated with CVD mortality (HR 1.46; 95% CI 1.23, 1.73) and all-cause mortality (HR 1.40; 95% CI 1.23, 1.59). In contrast, HGI had an L-shaped relationship with all-cause mortality and no significant association with CVD mortality in females. To the left of the threshold points, the risk of all-cause mortality decreased (HR 0.50; 95% CI 0.35, 0.71) progressively with increasing HGI. CONCLUSIONS: In the cohort study, HGI in pre-diabetic and diabetic populations was found to have a U-shaped association with CVD mortality and all-cause mortality in males and an L-shaped association with all-cause mortality only in females. Further prospective and mechanistic studies are warranted.

Relative importance of triglyceride glucose index combined with body mass index in predicting recovery from prediabetic state to normal fasting glucose: a cohort analysis based on a Chinese physical examination population.

BACKGROUND: Prediabetes is a high-risk state for diabetes, and numerous studies have shown that the body mass index (BMI) and triglyceride-glucose (TyG) index play significant roles in risk prediction for blood glucose metabolism. This study aims to evaluate the relative importance of BMI combination with TyG index (TyG-BMI) in predicting the recovery from prediabetic status to normal blood glucose levels. METHODS: A total of 25,397 prediabetic subjects recruited from 32 regions across China. Normal fasting glucose (NFG), prediabetes, and diabetes were defined referring to the American Diabetes Association (ADA) criteria. After normalizing the independent variables, the impact of TyG-BMI on the recovery or progression of prediabetes was analyzed through the Cox regression models. Receiver Operating Characteristic (ROC) curve analysis was utilized to visualize and compare the predictive value of TyG-BMI and its constituent components in prediabetes recovery/progression. RESULTS: During the average observation period of 2.96 years, 10,305 individuals (40.58%) remained in the prediabetic state, 11,278 individuals (44.41%) recovered to NFG, and 3,814 individuals (15.02%) progressed to diabetes. The results of multivariate Cox regression analysis demonstrated that TyG-BMI was negatively associated with recovery from prediabetes to NFG and positively associated with progression from prediabetes to diabetes. Further ROC analysis revealed that TyG-BMI had higher impact and predictive value in predicting prediabetes recovering to NFG or progressing to diabetes in comparison to the TyG index and BMI. Specifically, the TyG-BMI threshold for predicting prediabetes recovery was 214.68, while the threshold for predicting prediabetes progression was 220.27. Additionally, there were significant differences in the relationship of TyG-BMI with prediabetes recovering to NFG or progressing to diabetes within age subgroups. In summary, TyG-BMI is more suitable for assessing prediabetes recovery or progression in younger populations (< 45 years old). CONCLUSIONS: This study, for the first time, has revealed the significant impact and predictive value of the TyG index in combination with BMI on the recovery from prediabetic status to normal blood glucose levels. From the perspective of prediabetes intervention, maintaining TyG-BMI within the threshold of 214.68 holds crucial significance.

Association between weight-adjusted waist index and non-alcoholic fatty liver disease: a population-based study.

BACKGROUND: Obesity is the most important driver of non-alcoholic fatty liver disease (NAFLD); nevertheless, the relationship of weight-adjusted waist index (WWI), a new obesity index, with NAFLD is unclear. METHODS: This retrospective study used data from the NAGALA project from 1994 to 2016. WWI values were calculated using waist circumference (WC) and weight measurements of the participants. Three stepwise adjusted logistic regression models were developed to assess the relationship of WWI with NAFLD in the whole population and in both sexes. Additionally, we also conducted a series of exploratory analysis to test the potential impact of body mass index (BMI), age, smoking status and exercise habits on the association of WWI with NAFLD. Receiver operating characteristic (ROC) curves were used to estimate cut-off points for identifying NAFLD in the entire population and in both sexes. RESULTS: The current study included a population of 11,805 individuals who participated in health screenings, including 6,451 men and 5,354 women. After adjusting for all non-collinear variables in the multivariable logistic regression model, we found a significant positive correlation of WWI with NAFLD. For each unit increase in WWI, the risk of NAFLD increased by 72% in the entire population, by 84% in men, and by 63% in women. Furthermore, subgroup analyses revealed no significant discrepancies in the correlation of WWI with NAFLD across individuals with varying ages, exercise habits, and smoking status (all P-interaction > 0.05), except for different BMI groups (P-interaction < 0.05). Specifically, compared to the overweight/obese group, the relationship of WWI with NAFLD was significantly stronger in the non-obese group, especially in non-obese men. Finally, based on the results of ROC analysis, we determined that the WWI cut-off point used to identify NAFLD was 9.7675 in men and 9.9987 in women. CONCLUSIONS: This study is the first to establish a positive correlation between WWI and NAFLD. Moreover, assessing the influence of WWI on NAFLD in individuals without obesity may yield more valuable insights compared to those who are overweight or obese.

Evaluation of the role of atherogenic index of plasma in the reversion from Prediabetes to normoglycemia or progression to Diabetes: a multi-center retrospective cohort study.

BACKGROUND: Atherosclerosis is closely linked with glucose metabolism. We aimed to investigate the role of the atherogenic index of plasma (AIP) in the reversal of prediabetes to normal blood glucose levels or its progression to diabetes. METHODS: This multi-center retrospective cohort study included 15,421 prediabetic participants from 32 regions across 11 cities in China, under the aegis of the Rich Healthcare Group's affiliated medical examination institutions. Throughout the follow-up period, we monitored changes in the glycemic status of these participants, including reversal to normal fasting glucose (NFG), persistence in the prediabetic state, or progression to diabetes. Segmented regression, stratified analysis, and restricted cubic spline (RCS) were performed based on the multivariable Cox regression model to evaluate the association between AIP and the reversal of prediabetes to NFG or progression to diabetes. RESULTS: During a median follow-up period of 2.9 years, we recorded 6,481 individuals (42.03%) reverting from prediabetes to NFG, and 2,424 individuals (15.72%) progressing to diabetes. After adjusting for confounders, AIP showed a positive correlation with the progression from prediabetes to diabetes [(Hazard ratio (HR) 1.42, 95% confidence interval (CI):1.24-1.64)] and a negative correlation with the reversion from prediabetes to NFG (HR 0.89, 95%CI:0.81-0.98); further RCS demonstrated a nonlinear relationship between AIP and the reversion from prediabetes to NFG/progression to diabetes, identifying a turning point of 0.04 for reversion to NFG and 0.17 for progression to diabetes. In addition, we observed significant differences in the association between AIP and reversion from prediabetes to NFG/progression to diabetes across age subgroups, specifically indicating that the risk associated with AIP for progression from prediabetes to diabetes was relatively higher in younger populations; likewise, a younger age within the adult group favored the reversion from prediabetes to NFG in relation to AIP. CONCLUSION: Our study, for the first time, reveals a negative correlation between AIP and the reversion from prediabetes to normoglycemia and validates the crucial role of AIP in the risk assessment of prediabetes progression. Based on threshold analysis, therapeutically, keeping the AIP below 0.04 was of paramount importance for individuals with prediabetes aiming for reversion to NFG; preventatively, maintaining AIP below 0.17 was vital to reduce the risk of diabetes onset for those with prediabetes.

Alanine aminotransferase to high- density lipoprotein cholesterol ratio is positively correlated with the occurrence of diabetes in the Chinese population: a population-based cohort study.

Objective: Both alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDL-C) are closely related to glucose homeostasis in the body, and the main objective of this study was to investigate the association between ALT to HDL-C ratio (ALT/HDL-C ratio) and the risk of diabetes in a Chinese population. Methods: The current study included 116,251 participants who underwent a healthy physical examination, and the study endpoint was defined as a diagnosis of new-onset diabetes. Multivariate Cox regression models and receiver operator characteristic curves were used to assess the association of the ALT/HDL-C ratio with diabetes onset. Results: During the average observation period of 3.10 years, a total of 2,674 (2.3%) participants were diagnosed with new-onset diabetes, including 1,883 (1.62%) males and 791 (0.68%) females. After fully adjusting for confounding factors, we found a significant positive association between the ALT/HDL-C ratio and the risk of diabetes [Hazard ratios 1.06, 95% confidence intervals: 1.05, 1.06], and this association was significantly higher in males, obese individuals [body mass index ≥ 28 kg/m2] and individuals aged < 60 years (All P interaction < 0.05). In addition, the ALT/HDL-C ratio was significantly better than its components ALT and HDL-C in predicting diabetes in the Chinese population. Conclusion: There was a positive relationship between ALT/HDL-C ratio and diabetes risk in the Chinese population, and this relationship was significantly stronger in males, obese individuals, and individuals younger than 60 years old.

The newly proposed Metabolic Score for Visceral Fat is a reliable tool for identifying non-alcoholic fatty liver disease, requiring attention to age-specific effects in both sexes.

Objective: The newly proposed Metabolic Visceral Fat Score (METS-VF) is considered a more effective measure for visceral adipose tissue (VAT) than other obesity indicators. This study aimed to reveal the association between METS-VF and non-alcoholic fatty liver disease (NAFLD), and its variations across age groups within both sexes. Methods: Data from 14,251 medical examiners in the NAGALA project were employed in this study. 3D fitted surface plots were constructed based on multivariate logistic regression models to visualize the isolated and combined effects of aging and METS-VF on NAFLD. Receiver operating characteristic curve (ROC) analysis was conducted to compare the diagnostic performance of METS-VF with other VAT surrogate markers in predicting NAFLD. Results: The results of multivariate logistic regression analysis showed that each unit increase in METS-VF was independently associated with a 333% and 312% increase in the odds of NAFLD in males and females, respectively. Additionally, the 3D fitted surface plot showed that age significantly influenced the association between METS-VF and the odds of NAFLD in both sexes, as follows: (i) In males, when METS-VF was less than 6.2, the METS-VF-related odds of NAFLD increased gradually with age in the 20-45 age group, reached a plateau in the 45-65 age group, and then decreased in the group above 65 years old; however, when male METS-VF exceeded 6.2, aging and METS-VF combined to further increase the odds of NAFLD in all age groups, particularly in the 45-65 age group. (ii) In females, aging seemed to reduce METS-VF-related odds of NAFLD in the 18-40 age group, but significantly increased it in the 40-60 age group, particularly for those with higher METS-VF levels. Further ROC analysis revealed that compared to other VAT surrogate markers, METS-VF showed the highest diagnostic accuracy for NAFLD in females, especially in those under 45 years of age [area under the curve (AUC) = 0.9256]. Conclusions: This study firstly revealed a significant positive correlation between METS-VF and the odds of NAFLD, with METS-VF surpassing other VAT surrogate markers in NAFLD diagnosis. Moreover, age significantly influenced the METS-VF-related odds of NAFLD and METS-VF's diagnostic efficacy for NAFLD in both sexes.

Gender perspective on the association between liver enzyme markers and non-alcoholic fatty liver disease: insights from the general population.

Objective: Every distinct liver enzyme biomarker exhibits a strong correlation with non-alcoholic fatty liver disease (NAFLD). This study aims to comprehensively analyze and compare the associations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) with NAFLD from a gender perspective. Methods: This study was conducted on 6,840 females and 7,411 males from the NAGALA cohort. Multivariable logistic regression analysis was used to compare the associations between liver enzyme markers and NAFLD in both genders, recording the corresponding adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of individual liver enzyme markers and different combinations of them in identifying NAFLD. Results: Liver enzyme markers ALT, AST, and GGT were all independently associated with NAFLD and exhibited significant gender differences (All P-interaction<0.05). In both genders, ALT exhibited the most significant association with NAFLD, with adjusted standardized ORs of 2.19 (95% CI: 2.01-2.39) in males and 1.60 (95% CI: 1.35-1.89) in females. Additionally, ROC analysis showed that ALT had significantly higher accuracy in identifying NAFLD than AST and GGT in both genders (Delong P-value < 0.05), and the accuracy of ALT in identifying NAFLD in males was higher than that in females [Area under the ROC curve (AUC): male 0.79, female 0.77]. Furthermore, out of the various combinations of liver enzymes, ALT+GGT showed the highest accuracy in identifying NAFLD in both genders, with AUCs of 0.77 (95% CI: 0.75-0.79) in females and 0.79 (95% CI: 0.78-0.81) in males. Conclusion: Our study revealed significant gender differences in the associations of the three commonly used liver enzyme markers with NAFLD. In both genders, the use of ALT alone may be the simplest and most effective tool for screening NAFLD, especially in males.

Association of mean arterial pressure with non-alcoholic fatty liver disease: results from the NAGALA study.

Objective: Several recent reports have suggested the use of mean arterial blood pressure (MAP) to assess/predict the risk of developing atherosclerosis, chronic kidney disease, diabetes, metabolic syndrome, and poor prognosis in a variety of cardiovascular and cerebrovascular diseases. The current study aimed to investigate the association of MAP with non-alcoholic fatty liver disease (NAFLD) and to explore the differences in this association across populations. Methods: This study used data from the NAGALA study from 1994 to 2016. MAP was calculated as 1/3 systolic blood pressure (SBP) + 2/3 diastolic blood pressure (DBP). Restricted cubic spline (RCS) and logistic regression models were used to examine the correlation of MAP with NAFLD. Results: The study population was 14,251 general people undergoing health screening, with a median (interquartile range) age of 42 (36-50) years; among them, 48% were women, and 2,507 (17.59%) were diagnosed with NAFLD. After fully controlling for confounders in the current dataset, MAP was positively and non-linearly associated with NAFLD [(odds ratios (ORs): 1.39, 95% confidence intervals (CIs): 1.15, 1.68); P for non-linearity = 0.024]; the dose-response curve showed that there was a transient saturation effect interval when MAP was between 85 and 95 mmHg, where the risk of NAFLD was neither increased nor decreased. The results of the stratified analysis showed that the risk of NAFLD associated with MAP appeared to be influenced only by age (P-interaction = 0.002), but not by sex, body mass index (BMI), habits of exercise, drinking status, or smoking status (P-interaction > 0.05); further age-stratified RCS analysis showed that the non-linear association between MAP and NAFLD in the young and middle-aged and the middle-aged and elderly populations was consistent with the results of the whole population, whereas, in the elderly population, a U-shaped curve association between MAP and NAFLD was observed, with both low and high MAP increasing the risk of NAFLD. Conclusion: In the general population, MAP was positively and non-linearly associated with NAFLD, and this association only differed significantly by age, but not by sex, BMI, habits of exercise, drinking status, and smoking status.

The predictive significance of lipid accumulation products for future diabetes in a non-diabetic population from a gender perspective: an analysis using time-dependent receiver operating characteristics.

Objective: The increasing prevalence of diabetes is strongly associated with visceral adipose tissue (VAT), and gender differences in VAT remarkably affect the risk of developing diabetes. This study aimed to assess the predictive significance of lipid accumulation products (LAP) for the future onset of diabetes from a gender perspective. Methods: A total of 8,430 male and 7,034 female non-diabetic participants in the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) program were included. The ability of LAP to assess the risk of future new-onset diabetes in both genders was analyzed using multivariate Cox regression. Subgroup analysis was conducted to explore the impact of potential modifiers on the association between LAP and diabetes. Additionally, time-dependent receiver operator characteristics (ROC) curves were used to assess the predictive power of LAP in both genders for new-onset diabetes over the next 2-12 years. Results: Over an average follow-up of 6.13 years (maximum 13.14 years), 373 participants developed diabetes. Multivariate Cox regression analysis showed a significant gender difference in the association between LAP and future diabetes risk (P-interaction<0.05): the risk of diabetes associated with LAP was greater in females than males [hazard ratios (HRs) per standard deviation (SD) increase: male 1.20 (1.10, 1.30) vs female 1.35 (1.11, 1.64)]. Subgroup analysis revealed no significant modifying effect of factors such as age, body mass index (BMI), smoking history, drinking history, exercise habits, and fatty liver on the risk of diabetes associated with LAP (All P-interaction <0.05). Time-dependent ROC analysis showed that LAP had greater accuracy in predicting diabetes events occurring within the next 2-12 years in females than males with more consistent predictive thresholds in females. Conclusions: This study highlighted a significant gender difference in the association between LAP and future diabetes risk. The risk of diabetes associated with LAP was greater in females than in males. Furthermore, LAP showed superior predictive ability for diabetes at different time points in the future in females and had more consistent and stable predictive thresholds in females, particularly in the medium and long term.

The newly proposed alanine aminotransferase to high-density lipoprotein cholesterol ratio has shown effectiveness in identifying non-alcoholic fatty liver disease.

Objective: Alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDL-C) are important predictive factors for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to analyze the association between the ALT/HDL-C ratio and NAFLD. Methods: We conducted a retrospective analysis of data from 14,251 individuals participating in the NAGALA project's health screening program. The presence of NAFLD was diagnosed based on the participants' alcohol consumption status and liver ultrasonography images. Multivariable logistic regression models were used to assess the association between the ALT/HDL-C ratio and NAFLD. Receiver operating characteristic (ROC) analysis was performed to determine and compare the effectiveness of ALT, HDL-C, the aspartate aminotransferase to HDL-C (AST/HDL-C) ratio, the gamma-glutamyl transferase to HDL-C (GGT/HDL-C) ratio and the ALT/HDL-C ratio in identifying NAFLD. Results: We observed a significant positive association between the ALT/HDL-C ratio and the prevalence of NAFLD. For each standard deviation (SD) increase in the ALT/HDL-C ratio, the adjusted odds ratio (OR) for NAFLD among the participants was 3.05 [95% confidence interval (CI): 2.63, 3.53], with the highest quartile of ALT/HDL-C ratio having a 9.96-fold increased risk compared to the lowest quartile. In further subgroup analyses stratified by gender, age, and waist circumference (WC), we observed a significantly higher risk of NAFLD associated with the ALT/HDL-C ratio among individuals aged ≥45 years, males, and those who were abdominal obesity. Furthermore, based on the results of ROC analysis, we found that the ALT/HDL-C ratio [area under the curves (AUC): 0.8553] was significantly superior to ALT, HDL-C, AST/HDL-C ratio and GGT/HDL-C ratio in identifying NAFLD (All Delong P<0.05); the threshold of suggested ALT/HDL-C ratio for identifying NAFLD was 15.97. Conclusion: This population-based study demonstrates a positive association between the ALT/HDL-C ratio and NAFLD. The ALT/HDL-C ratio can effectively identify individuals with NAFLD.

M6A regulator methylation patterns and characteristics of immunity in acute ST-segment elevation myocardial infarction.

M6A methylation is the most prevalent and abundant RNA modification in mammals. Although there are many studies on the regulatory role of m6A methylation in the immune response, the m6A regulators in the pathogenesis of acute ST-segment elevation myocardial infarction (STEMI) remain unclear. We comprehensively analysed the role of m6A regulators in STEMI and built a predictive model, revealing the relationship between m6A methylations and the immune microenvironment. Differential analysis revealed that 18 of 24 m6A regulators were significantly differentially expressed, and there were substantial interactions between the m6A regulator. Then, we established a classifier and nomogram model based on 6 m6A regulators, which can easily distinguish the STEMI and control samples. Finally, two distinct m6A subtypes were obtained and significantly differentially expressed in terms of infiltrating immunocyte abundance, immune reaction activity and human leukocyte antigen genes. Three hub m6A phenotype related genes (RAC2, RELA, and WAS) in the midnightblue module were identified by weighted gene coexpression network analysis, and were associated with immunity. These findings suggest that m6A modification and the immune microenvironment play a key role in the pathogenesis of STEMI.

Assessing the usefulness of a newly proposed metabolic score for visceral fat in predicting future diabetes: results from the NAGALA cohort study.

Objective: Visceral adipose tissue assessment holds significant importance in diabetes prevention. This study aimed to explore the association between the newly proposed Metabolic Score for Visceral Fat (METS-VF) and diabetes risk and to further assess the predictive power of the baseline METS-VF for the occurrence of diabetes in different future periods. Methods: This longitudinal cohort study included 15,464 subjects who underwent health screenings. The METS-VF, calculated using the formula developed by Bello-Chavolla et al., served as a surrogate marker for visceral fat obesity. The primary outcome of interest was the occurrence of diabetes during the follow-up period. Established multivariate Cox regression models and restricted cubic spline (RCS) regression models to assess the association between METS-VF and diabetes risk and its shape. Receiver operating characteristic (ROC) curves were used to compare the predictive power of METS-VF with body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and visceral adiposity index (VAI) for diabetes, and time-dependent ROC analysis was conducted to assess the predictive capability of METS-VF for the occurrence of diabetes in various future periods. Results: During a maximum follow-up period of 13 years, with a mean of 6.13 years, we observed that the cumulative risk of developing diabetes increased with increasing METS-VF quintiles. Multivariable-adjusted Cox regression analysis showed that each unit increase in METS-VF would increase the risk of diabetes by 68% (HR 1.68, 95% CI 1.13, 2.50), and further RCS regression analysis revealed a possible non-linear association between METS-VF and diabetes risk (P for non-linearity=0.002). In addition, after comparison by ROC analysis, we found that METS-VF had significantly higher predictive power for diabetes than other general/visceral adiposity indicators, and in time-dependent ROC analysis, we further considered the time-dependence of diabetes status and METS-VF and found that METS-VF had the highest predictive value for predicting medium- and long-term (6-10 years) diabetes risk. Conclusion: METS-VF, a novel indicator for assessing visceral adiposity, showed a significantly positive correlation with diabetes risk. It proved to be a superior risk marker in predicting the future onset of diabetes compared to other general/visceral adiposity indicators, particularly in forecasting medium- and long-term diabetes risk.

Association of predicted fat mass and lean body mass with diabetes: a longitudinal cohort study in an Asian population.

Objective: The relationship between body composition fat mass (FM) and lean body mass (LBM) and diabetes risk is currently debated, and the purpose of this study was to examine the association of predicted FM and LBM with diabetes in both sexes. Methods: The current study was a secondary analysis of data from the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) cohort study of 15,463 baseline normoglycemic participants. Predicted LBM and FM were calculated for each participant using anthropometric prediction equations developed and validated for different sexes based on the National Health and Nutrition Examination Survey (NHANES) database, and the outcome of interest was diabetes (types not distinguished) onset. Multivariate Cox regression analyses were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of predicted FM and LBM with diabetes risk and further visualized their associations using a restricted cubic spline function. Results: The incidence density of diabetes was 3.93/1000 person-years over a mean observation period of 6.13 years. In women, predicted LBM and FM were linearly associated with diabetes risk, with each kilogram increase in predicted LBM reducing the diabetes risk by 65% (HR 0.35, 95%CI 0.17, 0.71; P < 0.05), whereas each kilogram increase in predicted FM increased the diabetes risk by 84% (HR 1.84, 95%CI 1.26, 2.69; P < 0.05). In contrast, predicted LBM and FM were non-linearly associated with diabetes risk in men (all P for non-linearity < 0.05), with an L-shaped association between predicted LBM and diabetes risk and a saturation point that minimized the risk of diabetes was 45.4 kg, while predicted FM was associated with diabetes risk in a U-shape pattern and a threshold point with the lowest predicted FM-related diabetes risk was 13.76 kg. Conclusion: In this Asian population cohort, we found that high LBM and low FM were associated with lower diabetes risk according to anthropometric equations. Based on the results of the non-linear analysis, we believed that it may be appropriate for Asian men to keep their LBM above 45.4 kg and their FM around 13.76 kg.