#673 Predictive value of insulin resistance and GFR-adjusted uricemia on all-cause mortality: the URRAH study
Authors: Russo Elisa , Viazzi Francesca , Pontremoli Roberto , Casiglia Edoardo , Grassi Guido , Muiesan Maria Lorenza , Virdis Agostino , Borghi Claudio ,   Working Group on Uricacid and Cardiovascular Risk of the Italian Society of Hypertension (Siia)
Published: May 2024

Abstract

Background and Aims
Uric acid (UA) and insulin resistance (IR) are interlinked: UA contributes to adversely affects the insulin signaling pathway, while IR predicts the development of hyperuricemia. Both UA and IR are related to metabolic syndrome, which is nowadays one of the most prevalent risk factors for mortality. In the clinical scenario, the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been proved to have a high correlation with IR. Lipoprotein-based markers of IR are at least as strongly associated with subclinical atherosclerosis and with newly developing atherosclerotic manifestations than Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The aim of the research was to explore the extent of interaction between IR and GFR-adjusted uricemia in determining mortality risk in a large population cohort study.

Method
data from 18,694 subjects were included from Uric acid Right foR heArt Healt (URRAH) database. Differences between TG/HDL-C ratio quintiles were evaluated by t-test or chi-square test. We evaluated the association between TG/HDL-C ratio and GFR-adjusted uricemia, and the development of outcomes during the follow-up study period. The primary endpoint was all-cause mortality. The Kaplan-Meier method was used to calculate the cumulative survival rate. Cox proportional hazard regression models were used to analyze the prognosis associated with IR.

Results
after a mean follow-up of 124 ± 64 months, there were 2,665 (14.2%) deaths for all causes. The incidence of fatal, non-fatal cardiovascular events, and all-cause mortality increased in parallel with the increase of TG/HDL-C quintiles. In both diabetic and non-diabetic patients, TG/HDL-C ratio showed a positive association with increasing of GFR-adjusted uricemia (UA/GFR ratio). TG/HDL-C ratio and GFR-adjusted uricemia significantly interact in determining all-cause mortality, even in non-diabetic patients (P &lt; 0.0001). Subjects with higher TG/HDL-C ratio quintile had a statistically significantly higher rate of mortality than patients with lower quintiles (Fig. 1, log rank test P &lt; 0.0001), independently by uricemia, GFR, the presence of diabetes and body mass index (BMI). Multivariate analysis showed that the TG/HDL-C ratio increase the mortality risk even after adjustment for potential confounding factors included age, diabetes, UA/GFR, BMI and statins treatment (Table 1).

Conclusion
For practical purposes, the easily obtainable TG/HDL-C ratio may suffice to determine the impact of insulin resistance as a risk factor. TG/HDL-C ratio interacts with GFR-adjusted uricemia in predicting mortality, even in non-diabetic patients. In conclusion, Both IR and GFR-adjusted UA levels seems to have an important predictive role on all-cause mortality, independently of age, gender, diabetes, hypertension and statins.