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.

Background/Objectives: Despite significant progress, cardiovascular disease remains the primary global cause of disability-adjusted life years. Atherosclerosis, an early form of vascular disorder, is driven by low-grade chronic inflammation and lipid accumulation. Obesity exacerbates atherosclerosis through insulin resistance, adipokine imbalance, and sustained inflammation, leading to endothelial dysfunction. Given this intricate involve-ment, understanding the effect of weight loss on derived indices associated with athero-sclerosis progression is crucial for developing effective strategies against this pervasive health challenge. Methods: 73 overweight or obese adults completed a six-month die-tary-based weight loss intervention. A 15% caloric deficit target was set, excluding poten-tially influencing pharmacotherapy, and limiting physical activity to daily walking. Sta-tistical analysis focused on anthropometric measures, lipid panel parameters and derived atherosclerosis indices, the latter stratified by gender and weight drop magnitude to as-sess robustness. Results: The intervention returned a median weight loss of 11.8 (IQR: 8 – 19) kg. Before-After analysis showed statistically significant improvement in anthropo-metric indices and most lipid profile components. Castelli Risk Index (CRI)-2 significantly improved (p < 0.05) from 3.28 (IQR: 2.57 – 4) to 3.22 (IQR: 2.55 – 3.71), Lipid Accumulation Product (LAP) decreased from 62.6 to 40.3 (p< 0.001). 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 ob-tained AUC values allowed to clearly highlight the superior discrimination performance of ACLI regarding the inflammatory markers hs-CRP and IL-6 in obese or overweight pa-tients involved in dietary interventions for weight loss. The AUC values for ACLI were significantly higher than those corresponding to the other atherogenic indices evaluated (AIP, CRI-1 and CRI-2) for both evaluation times (before intervention and after interven-tion. Conclusions. This study demonstrates that a calculated dietary deficit alone is suffi-cient to significantly improve critical surrogate markers of atherosclerosis and visceral adiposity, specifically AIP, CRI-2, LAP and the proposed central atherogenic load index (ACLI). Our results highlighted the superior potential of the ACLI index for predicting en-dothelial dysfunction with reference to the inflammatory markers hs-CRP and IL-6, com-pared to traditional derived indices associated with atherosclerosis progression (AIP, CRI-1 and CRI-2). These findings suggest physically demanding exercise regimens are not mandatory to mitigate CVD risk. Dietary-focused interventions offer an effective strategy for improving cardiovascular health in selected obese populations without requiring in-tensive physical training.