Transforming Primary Healthcare (PHC) for Adiposity-Based Chronic Disease (ABCD) and Cardiovascular-Kidney-Metabolic (CKM) Syndrome: Integrating Endothelin-1 (ET-1) and TG/HDL-C Ratio for Subclinical Cardiovascular Risk Stratification

ABSTRACT Objective To fill the gaps in primary healthcare (PHC) service delivery strategies focused on adiposity-based chronic disease and chronic kidney metabolic syndrome in the non-communicable diseases (NCD) context, focus on healthcare transformation and practice redesign. Design an experimental analytics study in tertiary care hospitals with a study population of adults aged 30-65 years with ABCD (BMI ≥ 25 kg/m 2 ) or stage 1 CKM syndrome (defined by coexisting overweight and/or obesity conditions). The study is designed to address locally relevant health priorities, specifically, the rising burden of cardiovascular-renal-metabolic (CKM) diseases and the need for early, affordable risk stratification tools such as ET-1 and the TG/HDL-C ratio. The research aims to generate evidence that can directly inform local clinical practice and health policy, thereby benefiting both study participants and the broader community. The collected data were then analyzed statistically; the quantification method used body mass index (BMI), then examination of ET-1 levels was carried out using the ELISA method, and lipid fractions using the enzymatic method. Setting The study is designed to address locally relevant health priorities, specifically, the rising burden of cardiovascular-renal-metabolic (CKM) diseases and the need for early, affordable risk stratification tools such as ET-1 and the TG/HDL-C ratio. The research aims to generate evidence that can directly inform local clinical practice and health policy, thereby benefiting both study participants and the broader community. The study included adults aged 30 to 65 years, consistent with common age ranges for cardiovascular risk studies in LMICs, diagnosed with ABCD or stage I CKM syndrome, including obesity (BMI ≥ 25 kg/m 2 ), and 97 participants met the inclusion criteria, with the rest of the subjects excluded. Participants The study included adults aged 30 to 65 years, consistent with common age ranges for cardiovascular risk studies in LMICs, diagnosed with ABCD or stage I CKM syndrome, including obesity (BMI ≥ 25 kg/m 2 ), and 97 participants met the inclusion criteria, with the rest of the subjects excluded. Results The collected data were then analyzed statistically with distribution tests, difference tests, correlation tests, and multivariate analysis. The difference test of ET-1 levels and TG/HDL-C ratios to the degree of obesity using the one-way ANOVA test found significant differences in ET-1 levels and TG/HDL-C ratios to the degree of obesity (p-value < 0.001). and (p-value < 0.001). Where based on the least significant difference in the non-obese sub-population against obesity (p-value 0.051) and significantly different from the obesity II population (p-value < 0.001), then the LSD test of the TG/HDL-C ratio against the degree of obesity was significantly different in the non-obese population against obesity I (p-value 0.002) and non-obese against obesity II (p-value < 0.001). From the multivariate analysis, there were statistically significant differences in the mean values of the ET-1 variable between the obese II sub-population and the non-obese sub-population OR: 216.29 (95% CI: 91.25 to 341.33; p-value 0.000), as well as between obesity II and obesity I OR: 119.49 (95% CI: 60.68 to 178.29; p-value 0.000). Meanwhile, the TG/HDL-C ratio variable had a statistically significant effect on the non-obese, obesity I, and obesity II populations OR: 3.16 (95% CI: 0.71 to 5.52; p-value < 0.001). From this study, all subjects were indicated to have endothelial dysfunction, where, based on the TG/HDL-C ratio, all subjects could be classified as having insulin resistance, and, based on the atherogenic index of plasma (AIP) algorithm, the study population was stratified into moderate risk for first-time incidence of atherosclerotic cardiovascular disease (n=10) and high risk for first-time incidence of atherosclerotic cardiovascular disease (n=87). Conclusion Integrating plasma endothelin-1 (ET-1) levels and the triglyceride-to-HDL cholesterol (TG/HDL-C) ratio into cardiovascular risk assessment frameworks offers a promising strategy to enhance early detection and management of adiposity-based chronic disease (ABCD) and cardiovascular-kidney-metabolic (CKM) syndrome, particularly in low- and middle-income countries (LMICs). These biomarkers reflect key pathophysiological processes, endothelial dysfunction and atherogenic dyslipidemia, that underpin subclinical cardiovascular and renal injury. Their combined application in primary healthcare settings can bridge critical gaps in current non-communicable disease (NCD) care by enabling precision risk stratification, guiding timely interventions, and ultimately reducing morbidity and mortality. Future large-scale, longitudinal studies are warranted to validate these findings and support guideline incorporation, thereby advancing healthcare transformation aligned with national health security (NHS) and sustainable development goals (SDGs).