Circulating amyloid-β (1-40), or Aβ40, predicts mortality risk better than the currently recommended Global Registry of Acute Coronary Events (GRACE) score in patients with broader non–ST-segment elevation acute coronary syndrome (NSTE-ACS), according to a recent study published in the Annals of Internal Medicine.

“We recently observed that increased circulating levels of Aβ40 are associated with increased risk for cardiovascular mortality and a composite of death or ACS in patients with stable CAD [coronary artery disease],” wrote the authors, led in part by Konstantinos Stellos, MD, Cardiovascular Research Centre, Institute of Genetic Medicine, Newcastle upon Tyne, United Kingdom. The researchers suggest that these findings indicate that Aβ40 plays a role in the precipitation and clinical outcome of ACS.

Aβ40 is a derivative of the amyloid precursor protein and has proinflammatory and prothrombotic properties. It likely contributes to mechanisms linked to plaque destabilization and is positively associated with clinical outcomes in stable CAD. Consequently, Dr. Stellos and colleagues hypothesized that Aβ40 blood levels may be correlated with ACS clinical risk profiles and outcomes.

To date, no inflammatory markers have been included as a contributor to GRACE scores, which is a well-validated metric for patient triage and management that is recommended in guidelines by the American College of Cardiology, American Heart Association, and the European Society of Cardiology.

GRACE scores are calculated using a formula that includes the main predictors of adverse events in ACS: age, systolic blood pressure, heart rate, serum creatinine concentration, Killip class, existence of ST-segment deviation, cardiac arrest, and increased markers of cardiac injuries. Nevertheless, GRACE scores have limited discriminative ability in certain clinical studies—particularly those in elderly patients or patients with early percutaneous coronary intervention.

“Identification of a blood-based inflammatory biomarker with significant reclassification ability,” the authors wrote, “could contribute substantially to correct risk stratification of NSTE-ACS.”

In the current retrospective cohort study, the researchers mined two distinct prospective cohorts—the Heidelberg study and the validation multicenter international APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation) study—for patients with NSTE-ACS. The team followed 1,145 subjects in the Heidelberg study for a median of 21.9 months and 734 subjects in the APACE study for a median of 24.9 months.

The primary endpoint for the study was all-cause mortality, and the secondary endpoint was the composite of death or nonfatal acute MI. The team employed Cox proportional hazards models to analyze the statistical link between levels of Aβ40 and the endpoints of the study. Furthermore, the investigators adjusted dose-response curves in the two cohorts for covariates, including age (≥ 66 years), sex, diabetes mellitus, levels of high sensitivity cardiac troponin T, levels of high-sensitivity C-reactive protein (hsCRP), index diagnosis of ACS, and revascularizations. They also utilized Aβ40 prediction models to determine the prognostic value after adjusting for the established GRACE score.

“Taken together,” the authors wrote, “these results suggest that Aβ40 may be pivotal in the CAD continuum, from its subclinical to chronic and acute clinical phenotypes. Thus, given that these findings were confirmed in an independent validation cohort, whether this peptide is a suitable early therapeutic target during development of atherosclerosis to prevent ACS triggering and improve post-ACS outcomes should be further explored.”

The authors concede that this study had limitations, in addition to being a retrospective study. For instance, the endpoints contained no distinct cardiovascular outcomes. Additionally, although Aβ40 can be measured for clinical practice, its levels can be affected by antibodies used in ELISA and conditions of storage and preparation.

This study was funded by the German Cardiac Society.