Interactive Role of Surrogate Liver Fibrosis Assessment and Insulin Resistance on the Incidence of Major Cardiovascular Events

Abstract

Introduction: The combination of easy-to-obtain validated biomarkers is interesting in the prognostic evaluation of patients at cardiovascular risk in a precision medicine scenario. The evaluation of the effect modification of insulin resistance and liver fibrosis with the Triglyceride-Glucose index (TyG) and Fibrosis-4 index (FIB4) might provide prognostic information in patients at cardiovascular risk. Patients and methods: A retrospective cohort study was performed with 2055 patients recruited in the Vascular Metabolic CUN cohort. The studied outcome was the incidence rate of major cardiovascular events (MACE). The Systematic Coronary Risk Evaluation (SCORE), FIB4 and TyG indexes were calculated according to validated formulas. Results: FIB4 and TyG showed a synergistic interaction using validated cut-offs for both indexes in the prediction of MACE (Hazard ratio (HR) 1.05 CI95% 1.01–1.08) which remained after adjustment by age, sex, SCORE subgroup, presence of diabetes, or previous MACE using standardized cut-off (HR 2.29 CI95% 1.33–3.94). Finally, a subgroup with significant TyG and FIB4 showed a higher cardiovascular risk in the study population (adjusted HR 3.34 CI 95% 1.94–5.77). Conclusion: The combined interpretation of TyG and FIB4 indexes might have a potential predictive value of major cardiovascular events.

Bridging Metabolic-Associated Steatotic Liver Disease and Cardiovascular Risk: A Potential Role for Ketogenesis

“…Thus, hepatic steatosis may be considered a surrogate metric for metabolic risk when evaluated through non-invasive techniques such as ultrasound, MRI, and transient elastography [ 45 , 46 ] and even validated serologic indices [ 47 ]. Several epidemiological studies have explored the association between non-invasively assessed SLD and metabolic and cardiovascular risk regarding quality of life [ 48 ], as well as the impact of lifestyle modification [ 49 ], incidence of T2DM [ 50 ], and incidence of cardiovascular events [ 51 ]. Various prospective cohort analyses and meta-analyses, grounded in liver biopsy results [ 42 ] and non-invasive biomarkers [ 52 , 53 ], have buttressed this hypothesis and precipitated a specific AHA statement on this subject [ 27 ] ( Table 1 ).…”

Health associations of liver enzymes and inflammatory scores with urinary citrus flavonoid metabolites

“…24,64 Also, citrus flavanones showed a great capacity to decrease the free radical scavenging activity, increase the expression of peroxisome proliferator-activated receptor α genes, and mitigate the activation of inflammatory pathways, avoiding liver damage, which are crucial approaches for NAFLD prevention. 24,30,64,65 Despite the noteworthy results of experimental studies of citrus flavanone effects on the liver, randomized control trials (RCT) in humans that established safe and tolerable dosage ranges are lacking. A randomized cross-over trial evaluated the effect of 600 ml d −1 orange juice intake on twenty-nine men over 50 years with hypercholesterolemia for 4 weeks.…”