Impact of a Hypocaloric Diet on Prognostic Biomarkers of Endothelial Dysfunction: A Prospective Study

Background/Objectives: To assess the impact of weight loss on the atherogenic profile of patients with obesity, we proposed the Atherogenic Central Load Index (ACLI). The aim of the study was to validate ACLI as a novel lipid biomarker reflecting the balance between atherogenic and antiatherogenic lipoproteins, the overall atherogenic burden, and its association with inflammatory markers. Methods: A prospective study was conducted from January 2024 to July 2024. A total of 73 adults with overweight or obesity completed a six-month dietary-based weight loss intervention. A 15% caloric deficit target was set, excluding the potential influence of pharmacotherapy, and limiting physical activity to daily walking. Statistical analysis focused on anthropometric measures, lipid panel parameters and derived atherosclerosis indices. Results: The intervention returned a median weight loss of 11.8 (IQR: 8–19) kg. Before–after analysis showed a statistically significant improvement in anthropometric indices and most lipid profile components. To assess the effect of weight loss on the atherogenic profile of patients, we proposed an atherogenic load index (Atherogenic Central Load Index (ACLI)). ACLI decreased significantly following the hypocaloric diet and showed a significant correlation with the inflammatory markers hs-CRP and IL-6. ACLI showed a strong, inversely significant correlation (p < 0.05) with AIP, hs-CRP and IL-6, at the time of intervention initiation and after 6 months. The evaluation of the obtained AUC values allowed to clearly highlight the superior discrimination performance of ACLI regarding the inflammatory markers hs-CRP and IL-6 in patients with overweight and obesity involved in dietary interventions for weight loss. Conclusions. The proposed index (ACLI) showed strong and significant associations with key inflammatory markers, including hs-CRP and IL-6. Moreover, ACLI demonstrated superior discriminatory performance for elevated inflammatory status in overweight and individuals with obesity undergoing dietary weight-loss interventions, outperforming traditional atherogenic indices related to atherosclerosis progression (AIP, CRI–1, and CRI–2). These findings support the potential clinical utility of ACLI as an integrative marker of atherogenic burden and cardiometabolic risk.