Association of insulin resistance-related indicators with cardiovascular disease and cardiovascular disease mortality in individuals with MASLD: a population-based study.

内容摘要

Limited studies have explored the relationship between surrogate markers of insulin resistance (IR) with both cardiovascular disease (CVD) risk and CVD mortality in individuals with metabolic dysfunction-associated fatty liver disease (MASLD). This study aimed to assess the associations of various IR surrogates with CVD risk and mortality and to identify effective predictors of cardiovascular outcomes in this population. This study constituted a population-based cross-sectional investigation, utilizing data derived from six cycles of the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2016. The data were linked to the NHANES public-use linked mortality files up to December 31, 2019, to facilitate follow-up on CVD mortality. Following predefined exclusion criteria, participants diagnosed with MASLD were identified and incorporated into the study. The research assessed the associations between surrogate markers of IR and both the prevalence of CVD and CVD mortality. The primary outcome of this study was the incidence of CVD in individuals with MASLD, and the secondary outcome was CVD mortality. Weighted multivariate logistic regression was utilized to examine the relationship between surrogate markers of IR with total CVD and other subtypes. Weighted multivariate Cox regression and Kaplan-Meier analysis were used to examine the relationship between surrogate markers of IR and CVD mortality. Restricted cubic spline (RCS) was used to explore potential nonlinear relationships. Receiver operating characteristics (ROC) and calibration curves were plotted to evaluate the discriminability and accuracy of IR surrogate markers in predicting CVD risk. Furthermore, mediation analysis was conducted to determine whether surrogate markers of liver fibrosis play a mediating role in the association of surrogate markers of IR with the risk of total CVD and other subtypes. This study suggests that in the fully adjusted model, estimated glucose disposal rate (eGDR) was significantly negatively correlated with total CVD, congestive heart failure (CHF), heart attack (HA), and CVD mortality. Metabolic score for IR and triglyceride-glucose-body mass index were significantly positively correlated with CVD mortality, total CVD, and CHF. eGDR was best correlated with total CVD (odds ratio (OR) = 0.40, 95% confidence interval (CI): 0.25, 0.63), CHF (OR = 0.15, 95% CI: 0.06, 0.38), and HA (OR = 0.40, 95% CI: 0.22, 0.71). Weighted multivariate Cox regression indicated that for each unit increase in eGDR, the risk of CVD mortality decreased by 27%. RCS analysis showed that all surrogate markers of IR were linearly related to CVD and CVD mortality (P-nonlinear relationship >0.05). In addition, the ROC curve showed that eGDR had a more robust diagnostic efficacy than other IR markers, and eGDR had a higher accuracy in predicting long-term CVD mortality. Adding eGDR to the base model improved the C statistic, net reclassification improvement, and composite discrimination improvement for most outcome variables. In mediation analysis, Metabolic Dysfunction Associated Fibrosis 5 mediated part of the association between eGDR and total CVD, coronary heart disease, HA, and stroke. In conclusion, eGDR outperformed other IR surrogates in predicting both CVD risk and CVD mortality in MASLD. Incorporating eGDR into prediction models may enhance risk stratification and facilitate early identification of high-risk individuals in this population. Further studies are warranted to validate these findings in external cohorts. IR surrogates and CVD risk in MASLD What we wanted to know For people with metabolic dysfunction-associated fatty liver disease (MASLD), which simple blood-based markers of insulin resistance best flag a higher risk of heart and blood-vessel problems–and which one does the best job of predicting future deaths from these conditions? What we did We analyzed data from 3919 U.S. adults with MASLD who took part in the NHANES surveys (2005–2016). We compared several common markers of insulin resistance, including the estimated glucose disposal rate (eGDR)–a calculation where higher values mean better insulin sensitivity–as well as METS-IR and TyG-BMI. We looked at who had cardiovascular disease (CVD) such as heart failure, heart attack, or stroke, and who later died from CVD. We also tested how well each marker could sort people into higher- vs lower-risk groups. What we found What it means People with higher eGDR had lower chances of having CVD, including heart failure and heart attack, and were also less likely to die from CVD over time. METS-IR and TyG-BMI were linked to some CVD outcomes (like overall CVD and heart failure) but did not predict CVD death as well. Overall, eGDR outperformed the other markers in identifying who was at risk. When we added eGDR to a basic risk model, its ability to tell apart high- and low-risk patients improved. We also found that signs of liver scarring (fibrosis) may partly explain how eGDR relates to heart problems. What it means For people with MASLD, eGDR is a strong, easy-to-use signal of heart risk and future CVD death. Including eGDR in routine assessments could help clinicians spot high-risk patients earlier and act sooner. These results should be confirmed in other groups to make sure they apply widely.