HDL oxidation increases early during weight gain and may represent a functional marker linking adiposity-related inflammation and oxidative stress to cardiovascular vulnerability.
Key Findings
Results
HDLox levels were significantly higher in overweight and obese individuals compared with normal-weight participants.
Study included 1227 consecutive patients undergoing elective coronary angiography
Participants were stratified into five predefined BMI categories
HDLox was significantly higher in overweight individuals compared to normal-weight (p = 0.002)
HDLox was significantly higher in obese individuals compared to normal-weight (p < 0.001)
HDLox was quantified using a validated fluorometric assay assessing HDL lipid peroxide content
Results
HDLox showed a non-linear relationship with BMI, increasing from normal weight to obesity class I and plateauing at higher BMI levels.
HDLox increased from normal weight to obesity class I (BMI 30–34.9 kg/m²)
HDLox plateaued at BMI levels above obesity class I
This pattern indicates a non-linear relationship between BMI and HDLox
The plateau suggests a ceiling effect at higher BMI categories
Results
BMI showed a weak but significant association with HDLox in the overall cohort.
In the overall cohort, β = 0.064, p = 0.024 in univariable linear regression
Within a restricted BMI interval of 15–35 kg/m², the association was more pronounced (β = 0.158, p < 0.001)
The stronger association in the restricted interval suggests that the BMI–HDLox relationship is most detectable in the lower-to-moderate BMI range
Associations were analyzed using both univariable and multivariable linear regression
Results
BMI, high-sensitivity C-reactive protein (hsCRP), and male sex remained independently associated with HDLox in multivariable models.
Traditional cardiovascular risk factors were not independently associated with HDLox in multivariable models
BMI remained an independent predictor of HDLox after multivariable adjustment
hsCRP, a marker of systemic inflammation, was independently associated with HDLox
Male sex was independently associated with HDLox
These findings suggest that inflammation and adiposity, rather than traditional risk factors, drive HDL oxidation
Discussion
HDL oxidation appears to emerge early during weight gain, potentially serving as a functional cardiovascular risk marker before overt obesity.
The association between BMI and HDLox was more pronounced in the restricted BMI interval of 15–35 kg/m²
This suggests HDL oxidative modification begins at lower BMI levels, not exclusively in severely obese individuals
Authors conclude that HDLox 'increases early during weight gain'
HDLox may represent 'a functional marker linking adiposity-related inflammation and oxidative stress to cardiovascular vulnerability'
Traditional cardiovascular risk factors did not independently predict HDLox, highlighting HDLox as a potentially distinct pathway
Methods
The study population consisted of 1227 consecutive patients undergoing elective coronary angiography, representing a coronary-suspected cohort.
All participants were undergoing elective coronary angiography
The cohort was described as a 'Coronary-Suspected Cohort'
Participants were stratified into five predefined BMI categories
The study design was a cross-sectional analysis using univariable and multivariable linear regression
What This Means
This research examined how body weight, measured by body mass index (BMI), relates to the oxidation (chemical damage) of high-density lipoprotein (HDL), often called 'good cholesterol.' The study analyzed 1,227 patients who were being evaluated for possible coronary artery disease. The researchers found that people who were overweight or obese had significantly higher levels of oxidized HDL compared to normal-weight individuals. Importantly, the increase in HDL oxidation appeared early in the weight gain process — rising from normal weight to the first category of obesity — and then leveling off at higher BMI levels, rather than continuing to climb with more severe obesity.
The study also found that BMI, a marker of inflammation called high-sensitivity C-reactive protein (hsCRP), and male sex were independently linked to oxidized HDL, while traditional cardiovascular risk factors like high blood pressure or high cholesterol were not. This suggests that weight-related inflammation, rather than standard risk factors, may be the key driver of HDL damage. The association between BMI and HDL oxidation was particularly strong when looking at people with BMI values between 15 and 35 kg/m², reinforcing the idea that HDL oxidation begins relatively early in the course of weight gain.
This research suggests that oxidized HDL may be an important early marker of cardiovascular risk that appears with modest increases in body weight, even before severe obesity develops. If confirmed in future studies, measuring oxidized HDL could potentially help identify people who are gaining weight and developing hidden cardiovascular vulnerability before traditional risk factors become apparent. The findings highlight that inflammation associated with excess body weight may damage HDL function in ways that standard cholesterol tests would not detect.
Sasko B, Shi T, Christ M, Ritter O, Kostin S, Sultana I, et al.. (2026). Early Emergence of HDL Oxidation Across the Body Mass Index Spectrum in Patients with Suspected Coronary Artery Disease.. International journal of molecular sciences. https://doi.org/10.3390/ijms27177570