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Multiplex Apolipoprotein Panel Improves Cardiovascular Event Prediction and Cardiovascular Outcome by Identifying
Esther Reijnders1, Patrick Bossuyt2, J Wouter Jukema3,4
1Department of Clinical Chemistry and Laboratory Medicine (E.R., L.R.R., F. P.H.T.M.R., C.M.C.), Leiden University Medical Center, the Netherlands.
Insights
A novel apolipoprotein panel improves prediction of cardiovascular events and death in patients with acute coronary syndrome. This panel also predicts treatment benefits from alirocumab, a PCSK9 inhibitor, enabling precision medicine.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Precision Medicine
Background:
- Residual cardiovascular risk persists despite statin therapy and optimal lipid levels.
- Traditional risk scores are insufficient for predicting outcomes in acute coronary syndrome (ACS) patients.
- Apolipoproteins offer potential for enhanced risk stratification and personalized treatment strategies.
Purpose of the Study:
- To evaluate the prognostic utility of a 9-plex apolipoprotein panel in ACS patients on statins.
- To assess the panel's ability to predict treatment benefit from alirocumab, a PCSK9 inhibitor.
- To enable precision medicine approaches for cardiovascular risk management.
Main Methods:
- Analysis of baseline serum samples from 11,843 ODYSSEY OUTCOMES trial participants using mass spectrometry.
- Measurement of nine key apolipoproteins (Apo(a), ApoA-I, ApoA-II, ApoA-IV, ApoB, ApoC-I, ApoC-II, ApoC-III, ApoE).
- Logistic regression models used to estimate major adverse cardiovascular events (MACE) and all-cause death, comparing apolipoprotein, lipid, and combined panels.
Main Results:
- The apolipoprotein panel demonstrated superior prognostic performance for MACE (AUC 0.648) and all-cause death (AUC 0.699) compared to the lipid panel (AUC 0.579 and 0.599, respectively).
- Adding the apolipoprotein panel significantly improved the predictive accuracy of the conventional lipid panel (P<0.0001).
- Higher MACE risk predicted by the apolipoprotein panel correlated with greater treatment benefit from alirocumab.
Conclusions:
- A multiplex apolipoprotein panel significantly enhances prediction of MACE and all-cause death in post-ACS patients on statins, outperforming traditional lipid panels.
- The apolipoprotein panel can predict treatment response to alirocumab, supporting its role in precision cardiovascular medicine.
- Further validation is required, but this approach holds promise for improved disease prediction and patient management.
Background:
Residual cardiovascular risk remains, despite achieving low-density lipoprotein cholesterol targets with high-intensity statins. Traditional risk scores are suboptimal. This study evaluated the prognostic utility of a 9-plex apolipoprotein panel in recent patients with acute coronary syndrome on statins and its role in predicting treatment benefit by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, enabling precision medicine.
Methods:
Baseline serum samples from 11 843 participants in the ODYSSEY OUTCOMES trial (https://www.clinicaltrials.gov; Unique identifier: NCT01663402) were analyzed using mass spectrometry to measure Apo(a), ApoA-I, ApoA-II, ApoA-IV, ApoB, ApoC-I, ApoC-II, ApoC-III, and ApoE. Using logistic regression, probabilities of major adverse cardiovascular events (MACE) and all-cause death over a median follow-up of 2.9 years were estimated based on baseline apolipoproteins and lipid concentrations. Clinical performance was assessed by comparing the area under the curve (AUC) of 3 models: the apolipoprotein panel, the lipid panel (total cholesterol, high-density lipoprotein cholesterol, and triglycerides), and a combination. In addition, prediction models estimating the treatment benefit of alirocumab by the apolipoprotein panel were developed.
Results:
The prognostic performance of the apolipoprotein panel for MACE showed an AUC (95% CI) of 0.648 (0.626-0.670), compared with 0.579 (0.557-0.602) for the lipid panel. For all-cause death, the apolipoprotein panel had an AUC of 0.699 (0.664-0.733), while the lipid panel had an AUC of 0.599 (0.564-0.635). Adding the apolipoprotein panel significantly improved the performance of the conventional lipid panel (P<0.0001): AUC, 0.659 (0.637-0.681) for MACE and 0.724 (0.691-0.756) for all-cause death. Higher risk for MACE based on the baseline apolipoprotein panel was found to predict greater treatment benefit with alirocumab.
Conclusions:
A multiplex apolipoprotein panel led to better prediction of MACE and all-cause death, beyond lipids, in patients with postacute coronary syndrome on optimized statin therapy. The panel also predicts the treatment benefit of alirocumab. Further validation of this approach is now needed, and if confirmed and improved, it could lead to better disease prediction and management in the future.
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