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Discordance between LDL-C and Apolipoprotein B Levels and Its Association with Renal Dysfunction: Insights from a
Mohsen Mazidi1,2, Richard J Webb3, Gregory Y H Lip4,5
1Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Oxford OX3 7LF, UK.
Insights
Apolipoprotein B (ApoB) is a superior predictor of atherosclerotic cardiovascular disease when discordant with low-density lipoprotein cholesterol (LDL-C). High ApoB levels, even with low LDL-C, are independently linked to a higher likelihood of chronic kidney disease (CKD).
Area of Science:
- Cardiology
- Nephrology
- Metabolic Disorders
Background:
- Low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB) are key biomarkers for atherosclerotic cardiovascular disease (ASCVD).
- The independent role of atherogenic lipoproteins in chronic kidney disease (CKD) remains debated.
- Discordance between LDL-C and ApoB levels suggests ApoB is a more accurate predictor of ASCVD risk.
Purpose of the Study:
- To investigate the independent association between discordant lipid profiles (LDL-C and ApoB) and the prevalence of chronic kidney disease (CKD).
- To determine if ApoB is a superior predictor of CKD compared to LDL-C, particularly when levels are discordant.
- To explore the relationship between atherogenic lipoproteins and metabolic dysfunction in the context of CKD.
Main Methods:
- Participants were categorized into four groups based on high and low levels of LDL-C (>160 mg/dL) and ApoB (>130 mg/dL).
- Continuous and categorical variables, including markers of CKD, were compared across these groups.
- Logistic regression analysis was employed to assess the association between the defined groups and CKD.
Main Results:
- Individuals with low LDL-C and high ApoB exhibited significantly higher body mass index, waist circumference, fasting glucose, insulin, and insulin resistance.
- This same group also presented with elevated urine albumin, log albumin-creatinine ratio, serum uric acid, and a lower estimated glomerular filtration rate (eGFR).
- Logistic regression revealed that low LDL-C with high ApoB showed the strongest association with CKD (OR 1.12, 95% CI 1.08-1.16) compared to the low LDL-C/low ApoB reference group.
Conclusions:
- Discordantly high levels of Apolipoprotein B are independently associated with an increased likelihood of developing chronic kidney disease.
- ApoB demonstrates a persistent association with metabolic dysfunction, irrespective of LDL-C levels.
- These findings highlight ApoB as a critical marker for assessing cardiovascular and kidney disease risk, especially in cases of lipid profile discordance.
Abstract:
Low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB) are established markers of atherosclerotic cardiovascular disease (ASCVD), but when concentrations are discordant ApoB is the superior predictor. Chronic kidney disease (CKD) is associated with ASCVD, yet the independent role of atherogenic lipoproteins is contentious. Four groups were created based upon high and low levels of ApoB and LDL-C. Continuous and categorical variables were compared across groups, as were adjusted markers of CKD. Logistic regression analysis assessed association(s) with CKD based on the groups. Subjects were categorised by LDL-C and ApoB, using cut-off values of >160 mg/dL and >130 mg/dL, respectively. Those with low LDL-C and high ApoB, compared to those with high LDL-C and high ApoB, had significantly higher body mass index (30.7 vs. 30.1 kg/m2) and waist circumference (106.1 vs. 102.7 cm) and the highest fasting blood glucose (117.5 vs. 112.7 mg/dL), insulin (16.6 vs. 13.1 μU/mL) and homeostatic model assessment of insulin resistance (5.3 vs. 3.7) profiles (all p < 0.001). This group, compared to those with high LDL-C and high ApoB, also had the highest levels of urine albumin (2.3 vs. 2.2 mg/L), log albumin-creatinine ratio (2.2 vs. 2.1 mg/g) and serum uric acid (6.1 vs. 5.6 mg/dL) and the lowest estimated glomerular filtration rate (81.3 vs. 88.4 mL/min/1.73 m2) (all p < 0.001). In expanded logistic regression models, using the low LDL-C and low ApoB group as a reference, those with low LDL-C and high ApoB had the strongest association with CKD, odds ratio (95% CI) 1.12 (1.08-1.16). Discordantly high levels of ApoB are independently associated with increased likelihood of CKD. ApoB remains associated with metabolic dysfunction, regardless of LDL-C.
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