Abstract
BACKGROUND: A direct comparison between glycemic-based and lipid-based insulin sensitivity indices (ISIs) for ECG findings and all-cause and cardiovascular mortality is lacking. METHODS: 963 community-dwelling older adults, examined as part of the third phase of the Glucose intolerance, Obesity, and Hypertension study between 1999 and 2008, were followed until December 2016 and December 2019 for cardiovascular and all-cause mortality, respectively. Eleven different ISIs were calculated and evaluated against ECG findings, all-cause, and cardiovascular mortality with multivariable regression models. The area under the receiver operating curve (AUC) and net reclassification improvement (NRI) analysis were implemented to compare ISIs performance. RESULTS: Mean age was 72.3 ± 7 years and 471 (49%) were females. Ischemic ECG changes were observed in 107 (11.2%) individuals. Upper quartile (Q(4)) of triglyceride-glucose waist-to-height ratio (TyG-WTHR) was associated with 220% greater odds for ischemic changes on ECG compared with lower quartiles (Q(1-3)) (95%CI:1.3-3.7, p = 0.004), an association that was not observed with other ISIs. During a median follow-up of 13 [IQR-8] and 11 [IQR-6] years for all-cause and CV mortality, respectively, 466 (48.4%) participants died, of them, 179 (38.4%) were attributed to cardiovascular causes. TyG-WTHR was the only ISI that was associated with both all-cause (HR = 1.3, 95%CI:1.0-1.6, p = 0.04) and cardiovascular (HR = 1.7, 95%CI:1.2-2.4, p = 0.004) mortality. Lipid based and glycemic ISIs showed similar predicative ability with slightly better predictive performance for TyG-WTHR for all-cause mortality (AUC = 0.46, 95%CI:0.4-0.5, p = 0.02). The NRI analysis revealed better reclassification ability for triglyceride-high-density-lipoprotein ratio (95%CI: 0.02-0.27, p = 0.03) and TyG-WTHR (95%CI: 0.0004-0.01, p = 0.03) for all-cause mortality while TyG-WTHR-based model correctly reclassified 19% of participants (95%CI: 0.02-0.36, p = 0.03) for cardiovascular mortality compared with model unadjusted for any ISIs and correctly reclassified 3% (95%CI:0.003-0.05, p = 0.02) compared with QUICKI based-model for all-cause mortality. CONCLUSIONS: TyG-WTHR was the only ISI associated with ischemic changes on ECG and all-cause and cardiovascular mortality and significantly improved the predictive performance for all-cause cardiovascular mortality. While most glycemic-based and lipid-based ISIs showed similar predictive ability, TyG-WTHR stands as the preferred ISI and should be considered for screening at-risk individuals for cardiovascular morbidity and mortality.