Cor Vasa 2026, 68(1):51-60 | DOI: 10.33678/cor.2025.085

Pilot Evaluation of Endothelin-1 and TG/HDL-C Ratio for Early Cardiovascular Risk Stratification in Adiposity-Based and Cardiovascular-Kidney-Metabolic Syndromes

Aldian Arie Pratama^a-c, Agustin Iskandar^c, Singgih Pudjo Wahono^c

^a Indonesian National Army Health Center, Jakarta, Indonesia

^b Ministry of Defense of the Republic of Indonesia, Jakarta, Indonesia

^c Department of Clinical Pathology, Faculty of Medicine, Brawijaya University, Malang, Indonesia

Adiposity-related chronic diseases and cardiovascular-kidney-metabolic (CKM) syndrome significantly contribute to the burden of non-communicable diseases (NCDs), especially in low- and middle-income countries (LMICs), where early risk stratification is still inadequate. This study evaluated the efficacy of endothelin-1 (ET-1) and the triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio as early, cost-efficient biomarkers for cardiovascular risk assessment in persons with adiposity-based chronic disease (ABCD) and early-stage CKM syndrome. An analytical experimental investigation was performed on persons aged 30 to 65 years with ABCD (body mass index >25 kg/m²) or stage 1 CKM syndrome. 97 participants met the inclusion criteria. Plasma ET-1 concentrations and lipid profiles were assessed, and individuals were classified based on the severity of obesity. Statistical analyses comprised one-way analysis of variance, post hoc testing, and multivariate regression. The one-way ANOVA test revealed significant differences in ET-1 levels and TG/HDL-C ratios relative to the degree of obesity, with p-values <0.001 for="" both="" measurements="" the="" least="" significant="" difference="" lsd="" in="" non-obesity="" sub-population="" compared="" to="" obesity="" i="">p-value = 0.051) was significantly distinct from the obesity II population (p-value <0.001). Consequently, the LSD test of the TG/HDL-C ratio revealed significant differences in the non-obesity population compared to obesity I (p-value = 0.002) and non-obesity versus obesity II (p-value <0.001). The multivariate analysis revealed statistically significant differences in the mean values of the ET-1 variable between the obesity II sub-population and the non-obesity sub-population, with an odds ratio of 216.29 (95% CI: 91.25-341.33; p-value = 0.000), as well as between obesity II and obesity I, with an odds ratio of 119.49 (95% CI: 60.68-178.29; p-value = 0.000). The TG/HDL-C ratio exhibited a statistically significant impact on the non-obesity, obesity I, and obesity II populations, with an odds ratio of 3.16 (95% CI: 0.71-5.52; p-value <0.001). The findings demonstrated that all participants displayed endothelial dysfunction. All participants were characterized as exhibiting insulin resistance based on the TG/HDL-C ratio. The study population was classified into moderate risk (n = 10) and high risk (n = 87) for the initial incidence of atherosclerotic cardiovascular disease using the atherogenic index of plasma (AIP) method. The atherogenic index of plasma indicated that most individuals were classified as having a high risk for an initial atherosclerotic cardiovascular event. Incorporating ET-1 and TG/HDL-C ratio into cardiovascular risk assessment models may improve the early identification and management of ABCD and CKM syndrome, facilitating effective non-communicable disease prevention aligned with sustainable development goals.

Keywords: Adiposity-based chronic disease, Atherogenic index of plasma, Cardiovascular risk assessment, Cardiovascular-kidney-metabolic syndrome, Endothelin-1, Triglyceride-to-HDL cholesterol ratio

Received: June 29, 2025; Revised: July 25, 2025; Accepted: August 1, 2025; Prepublished online: June 2, 2012; Published: March 15, 2026  Show citation