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Published on: January 28, 2020
Risk-weighted apoB: a novel summary metric outperforming traditional lipid biomarkers in predicting coronary heart
Michaela B Rehman1, Elias Björnson2, Martin Adiels2
1Cardiology Department, Ramsay Santé, Médipôle Lyon-Villeurbanne, Villeurbanne, France.
Insights
A new metric, risk-weighted apolipoprotein B (RW-apoB), improves coronary heart disease (CHD) risk prediction by accounting for triglyceride-rich lipoproteins (TRL) and lipoprotein(a) [Lp(a)]. This advanced measure offers better risk stratification than traditional apoB alone.
Area of Science:
- Cardiovascular Medicine
- Lipid Metabolism
- Biomarkers
Background:
- Standard lipid markers like LDL-C and non-HDL-C do not fully assess coronary heart disease (CHD) risk from all atherogenic lipoproteins.
- Apolipoprotein B (apoB) indicates total atherogenic particle number but may underestimate risk when triglyceride-rich lipoproteins (TRL/remnants) and lipoprotein(a) [Lp(a)] are high.
Purpose of the Study:
- To develop a novel metric, risk-weighted apoB (RW-apoB), to integrate risk from LDL, TRL/remnants, and Lp(a) into a single value.
- To enhance the accuracy of cardiovascular risk prediction beyond current apoB measurements.
Main Methods:
- The RW-apoB metric was formulated using UK Biobank data based on established relative atherogenicity estimates.
- The formula is: RW-apoB = 11.65×TG(mmol/L) + 0.215×lipoprotein(a)(nmol/L) + 0.736×apoB(mg/dL).
Main Results:
- RW-apoB significantly reclassified individuals' CHD risk status compared to measured apoB, with 52% changing rank by ≥10 percentiles.
- Individuals in the top RW-apoB quintile with elevated TRL and Lp(a) showed a 5.4% CHD event rate, often misclassified as lower risk by apoB alone.
- RW-apoB demonstrated superior risk prediction, significantly improving Harrell's C-index (P < .0001) and outperforming apoB in Cox models across multiple cohorts.
Conclusions:
- RW-apoB accounts for both atherogenic particle number and the increased atherogenicity of TRL and Lp(a).
- This new metric offers clinically significant improvements in CHD risk stratification, particularly for residual risk in statin-treated patients.
Background And Aims:
LDL-C and non-HDL-C do not fully capture coronary heart disease (CHD) risk attributed to all apoB-containing lipoproteins. Use of apolipoprotein B (apoB) as a marker of total atherogenic particle number improves risk prediction, but risk may still be underestimated when triglyceride-rich lipoproteins (TRL/remnants) and lipoprotein(a) [Lp(a)] are elevated. The aim was to formulate a new metric-risk-weighted apoB (RW-apoB)-designed to capture risk from LDL, TRL/remnants, and Lp(a) in a single number.
Methods:
Based on previously published estimates of the relative atherogenicity of LDL, TRL/remnant, and Lp(a) particles, RW-apoB was developed (using UK Biobank data) as an atherogenicity-weighted apoB-sum calculated as: RW-apoB = 11.65×TG(mmol/L) + 0.215×lipoprotein(a)(nmol/L) + 0.736×apoB(mg/dL).
Results:
Assigning RW-apoB to individuals substantially reclassified their risk status. Compared with ranking by measured apoB, 52% of individuals were up- or down-ranked by ≥10 percentiles. About one-third of those in the top RW-apoB quintile-with elevated TRL and Lp(a) and a CHD event rate of 5.4%-were misclassified as lower risk by apoB. Conversely, individuals in the top measured apoB quintile but with low TRL and Lp(a) had a lower event rate (3.9%) and were correctly down-ranked. RW-apoB improved risk prediction, significantly increasing Harrell's C-index relative to apoB (P < .0001). In statin-treated subjects, RW-apoB was potentially a better index of residual risk. RW-apoB consistently outperformed apoB as a risk predictor in Cox models across the UK Biobank and three other large population cohorts.
Conclusions:
RW-apoB represents not only particle number but also accounts for the higher atherogenicity of TRL and Lp(a). It offers clinically meaningful improvements in CHD risk stratification.
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