Amyloid-β (1-40) and Mortality in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: A Cohort Study
Kimon Stamatelopoulos1, Matthias Mueller-Hennessen2, Georgios Georgiopoulos1
1Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece (K.S., G.G., F.A.).
Insights
Circulating Amyloid-β (1-40) predicts mortality in non-ST-segment elevation acute coronary syndrome (NSTE-ACS). This biomarker improves risk stratification beyond the GRACE score, suggesting potential for enhanced patient management.
Area of Science:
- Cardiovascular Medicine
- Biomarker Discovery
- Acute Coronary Syndromes
Background:
- Amyloid-β (1-40) (Aβ40) is linked to plaque destabilization and adverse outcomes in stable coronary artery disease.
- Existing risk stratification for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) relies on scores like GRACE.
Purpose of the Study:
- To evaluate the prognostic and reclassification value of baseline circulating Aβ40 levels in NSTE-ACS patients.
- To assess if Aβ40 improves risk stratification when added to the GRACE score.
Main Methods:
- Retrospective cohort study involving two independent prospective cohorts: Heidelberg (n=1145) and APACE (n=734).
- Patients with NSTE-ACS were followed for mortality, with Aβ40 levels measured at baseline.
- Multivariate regression analyses were performed, adjusting for clinical factors and the GRACE score.
Main Results:
- Elevated circulating Aβ40 levels were significantly associated with all-cause mortality in both cohorts, even after adjusting for clinical variables and the GRACE score.
- Aβ40 demonstrated significant risk reclassification value over the GRACE score, with net reclassification indices of 33.4% (Heidelberg) and 47.1% (APACE).
- Hazard ratios for mortality associated with Aβ40 differed at low concentrations between cohorts, potentially due to variations in blood preparation methods.
Conclusions:
- Circulating Aβ40 is an independent predictor of mortality in patients with NSTE-ACS.
- Aβ40 improves risk stratification beyond the current GRACE score recommendations.
- Further validation is warranted to explore the clinical application of Aβ40 as a novel biomarker in NSTE-ACS.
Background:
Amyloid-β (1-40) (Aβ40) is implicated in mechanisms related to plaque destabilization and correlates with adverse outcomes in stable coronary artery disease.
Objective:
To determine the prognostic and reclassification value of baseline circulating levels of Aβ40 after adjustment for the Global Registry of Acute Coronary Events (GRACE) score, which is widely recommended for risk stratification in non-ST-segment elevation acute coronary syndrome (NSTE-ACS).
Design:
Retrospective cohort study using data from 2 independent prospective cohorts, the Heidelberg study (n = 1145) and the validation multicenter international APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation) study (n = 734).
Setting:
Academic hospitals in 7 European countries.
Participants:
Patients with adjudicated NSTE-ACS followed for a median of 21.9 and 24.9 months in the Heidelberg and APACE studies, respectively.
Measurements:
All-cause mortality was the primary end point.
Results:
Amyloid-β (1-40) was associated with mortality after multivariate adjustment for age, sex, diabetes mellitus, high-sensitivity cardiac troponin T and C-reactive protein, revascularization, and ACS type (Heidelberg cohort hazard ratio [HR] for 80th vs. 20th percentiles, 1.66 [95% CI, 1.06 to 2.61; P = 0.026]; APACE cohort HR, 1.50 [CI, 1.15 to 1.96; P = 0.003]). It was also associated with mortality after adjustment for the GRACE score (Heidelberg cohort HR for 80th vs. 20th percentiles, 1.11 [CI, 1.04 to 1.18; P = 0.001]; APACE cohort HR, 1.39 [CI, 1.02 to 1.88; P = 0.036]). Amyloid-β (1-40) correctly reclassified risk for death over the GRACE score (net reclassification index, 33.4% and 47.1% for the Heidelberg and APACE cohorts, respectively) (P < 0.05).
Limitation:
At low concentrations of Aβ40, dose-response associations with mortality differed between cohorts, possibly because of varying blood preparations used to measure Aβ40.
Conclusion:
Circulating Aβ40 is a predictor of mortality and improves risk stratification of patients with NSTE-ACS over the GRACE score recommended by clinical guidelines. The clinical application of Aβ40 as a novel biomarker in NSTE-ACS should be further explored and validated.
Primary Funding Source:
German Cardiac Society.
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