Low-density lipoprotein quantity versus quality: Discordance between equation-based low-density lipoprotein cholesterol estimations and oxidized low-density lipoprotein as a determinant of residual cardiovascular risk in coronary artery disease

Background: Premature coronary artery disease (CAD), defined as onset at or before 45 years of age, has a disproportionately higher prevalence among South Asians compared to Western populations, with Indian individuals particularly affected. Traditional lipid metrics primarily quantify low-density lipoprotein cholesterol (LDL-C) but often fail to reflect qualitative changes, such as LDL oxidation, which may contribute to residual cardiovascular risk. Objective: This study aimed to assess the concordance among three LDL-C estimation methods (Friedewald, Martin–Hopkins, and NIH Equation-2) and their relationship with oxidized LDL (ox-LDL) levels in young Indian adults with premature CAD. Methods: This case–control study enrolled 150 participants, including 100 patients with CAD and 50 age-matched controls. Standard lipid parameters were measured, and LDL-C levels were calculated using Friedewald, Martin–Hopkins, and NIH Equation 2 methods while ox-LDL levels were quantified using sandwich enzyme-linked immunosorbent assay. Intergroup differences were evaluated using Mann–Whitney U -test. Associations among LDL-C estimates, conventional lipid fractions, and ox-LDL were examined using Spearman’s rho correlation analysis. Results: LDL-C estimation by all three methods demonstrated strong concordance. However, ox-LDL showed no significant correlation with any of the LDL-C estimation methods. This indicates that ox-LDL “quality” reflects a distinct atherogenic dimension independent of LDL-C “quantity.” Conclusions: Although LDL-C equations provide reliable estimates of LDL cholesterol levels, they do not capture oxidative modifications that contribute to residual cardiovascular risk. Integrating ox-LDL assessment into routine screening may strengthen early detection and enable targeted prevention, addressing the escalating public health burden of premature CAD among young Indians.