Early Emergence of HDL Oxidation Across the Body Mass Index Spectrum in Patients with Suspected Coronary Artery Disease

Background: Obesity, commonly defined by body mass index (BMI), promotes cardiovascular disease through chronic inflammation and oxidative stress, which impair high-density lipoprotein (HDL) function and favor oxidative modification. Oxidized HDL (HDLox) may link adiposity to cardiovascular risk. However, the association between BMI and HDLox across the adiposity spectrum remains unclear. We therefore examined this relationship in a Coronary-Suspected Cohort. Methods: This study included 1,227 consecutive patients undergoing elective coronary angiography. Participants were stratified into five predefined BMI categories. HDLox was quantified using a validated fluorometric assay assessing HDL lipid peroxide content. Associations between BMI and HDLox were analyzed using univariable and multivariable linear regression across the full BMI range and within a restricted BMI interval (15–35 kg/m²). Results: HDLox levels were significantly higher in overweight and obese individuals compared with normal-weight participants (p = 0.002 and p < 0.001). HDLox increased from normal weight to obesity class I (BMI 30–34.9 kg/m²) and plateaued at higher BMI levels, indicating a non-linear relationship. In the overall cohort, BMI showed a weak but significant association with HDLox (β = 0.064, p = 0.024). Within the restricted BMI interval, the association was more pronounced (β = 0.158, p < 0.001). In multivariable models, BMI, high-sensitivity C-reactive protein, and male sex remained independently associated with HDLox, whereas traditional cardiovascular risk factors were not. Conclusions: HDL oxidation increases early during weight gain and may represent a functional marker linking adiposity-related inflammation and oxidative stress to cardiovascular vulnerability.