Discordance between serum cholesterol concentration and atherogenic lipoprotein particle number in people with metabolic disease: A systematic review

Abstract This systematic review examines the discordance between low‐density lipoprotein cholesterol (LDL‐C), non‐high‐density lipoprotein cholesterol (non‐HDL‐C), and apolipoprotein B‐100 (apoB) in individuals with metabolic diseases, such as metabolic syndrome and type 2 diabetes, and evaluates the implications for atherosclerotic cardiovascular disease (ASCVD) risk assessment. A systematic literature search was conducted using Academic Search Complete, CINAHL Complete, and MEDLINE databases from 10 January 2024 to 28 May 2024. Studies were selected based on pre‐defined inclusion and exclusion criteria, focusing on observational studies that compared LDL‐C, non‐HDL‐C, and apoB levels in individuals with metabolic disease. Studies were included if they assessed fasted blood samples and reported lipid measurements, excluding those involving drug therapies or dietary interventions. Nine studies met the inclusion criteria, revealing significant discordance between LDL‐C and apoB levels in individuals with metabolic syndrome or type 2 diabetes. These individuals often achieve optimal LDL‐C levels while exhibiting elevated apoB and non‐HDL‐C concentrations, highlighting the limitations of LDL‐C as the sole marker for ASCVD risk. The discordance is largely attributed to differences in LDL particle size and density, with metabolic disease contributing to a higher proportion of small, dense, atherogenic LDL particles. Elevated triglyceride‐rich lipoproteins (TRLs), such as very low‐density lipoproteins (VLDL), were also identified as contributing to ASCVD risk underestimation by traditional LDL‐C measurements. While LDL‐C remains a central marker for ASCVD, apoB quantification provides a more accurate assessment of ASCVD risk, particularly in individuals with metabolic diseases. Incorporating apoB levels into therapeutic strategies for lipid reduction is recommended to improve cardiovascular risk management in this population.