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Updated: Jun 24, 2025
Isolation and Analysis of Plasma Lipoproteins by Ultracentrifugation
Published on: January 28, 2021
Excess Apolipoprotein B and Cardiovascular Risk in Women and Men
Camilla Ditlev Lindhardt Johannesen1, Anne Langsted1, Børge Grønne Nordestgaard1
1Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev Gentofte, Copenhagen, Denmark; The Copenhagen General Population Study, Copenhagen University Hospital-Herlev Gentofte, Copenhagen, Denmark; The Copenhagen City Heart Study, Copenhagen University Hospital-Bispebjerg Frederiksberg, Copenhagen, Denmark; Institute of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.
Insights
Excess apolipoprotein B (apoB) is linked to higher risks of heart attack and atherosclerotic cardiovascular disease in both men and women. This indicates apoB offers significant predictive value beyond LDL cholesterol alone.
Area of Science:
- Cardiology
- Lipid Metabolism
- Preventive Medicine
Background:
- Low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) are key markers for atherogenic lipoproteins.
- Apolipoprotein B is a structural protein of LDL particles.
Purpose of the Study:
- To investigate the association between excess apoB and the risk of myocardial infarction (MI), atherosclerotic cardiovascular disease (ASCVD), and all-cause mortality.
- To determine if apoB provides predictive value beyond LDL-C for cardiovascular events.
Main Methods:
- A large cohort study (53,484 women, 41,624 men) from the Copenhagen General Population Study.
- Cox proportional hazards regressions were used to estimate associations.
- Excess apoB was defined as measured apoB minus expected apoB based on LDL-C levels.
Main Results:
- A dose-dependent association was observed between excess apoB and increased risk of MI and ASCVD in both sexes.
- Excess apoB was also associated with all-cause mortality in women.
- Hazard ratios for ASCVD increased significantly with higher levels of excess apoB in both women and men.
Conclusions:
- Elevated apoB levels, beyond those explained by LDL-C, are dose-dependently associated with increased risks of MI and ASCVD.
- ApoB offers significant predictive value for cardiovascular events that is independent of LDL-C levels.
Background:
Low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) are highly correlated measures of atherogenic lipoproteins.
Objectives:
The study investigators hypothesized that excess apoB is associated with an increased risk of myocardial infarction (MI), atherosclerotic cardiovascular disease (ASCVD), and all-cause mortality.
Methods:
The study included 53,484 women and 41,624 men not taking statins from the Copenhagen General Population Study. Associations of excess apoB with the risk of MI, ASCVD, and all-cause mortality were estimated by Cox proportional hazards regressions with 95% CIs. Excess apoB was defined as measured levels of apoB minus expected levels of apoB from LDL-C alone; expected levels were defined by linear regressions of LDL-C levels vs apoB levels in individuals with triglycerides ≤1 mmol/L (89 mg/dL).
Results:
During a median follow-up of 9.6 years, 2,048 MIs, 4,282 ASCVD events, and 8,873 deaths occurred. There was a dose-dependent association between excess apoB and the risk of MI and ASCVD in both women and men, as well as an association with the risk of all-cause mortality in women. For ASCVD in women compared with those with excess apoB <11 mg/dL, the multivariable adjusted HR was 1.08 (95% CI: 0.97-1.21) for excess apoB 11 to 25 mg/dL, 1.30 (95% CI: 1.14-1.48) for 26 to 45 mg/dL, 1.34 (95% CI: 1.14-1.58) for 46 to 100 mg/dL, and 1.75 (95% CI: 1.08-2.83) for excess apoB >100 mg/dL. Corresponding HRs in men were 1.14 (95% CI: 1.02-1.26), 1.41 (95% CI: 1.26-1.57), 1.41 (95% CI: 1.25-1.60), and 1.52 (95% CI: 1.13-2.05), respectively. Results were robust across the entire LDL-C spectrum.
Conclusions:
Excess apoB (ie, the value of apoB above that contributed by LDL-C levels alone) is associated dose-dependently with an increased risk of MI and ASCVD in women and men. This finding demonstrates that apoB provides important predictive value beyond LDL-C across the entire LDL-C spectrum.
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