Abstract 17312: Amyloid-β (1-40) and the Risk of Death from Cardiovascular Causes in Patients with Coronary Heart Disease

Abstract

Introduction: Investigation of the clinical value of biologic pathways that are involved in pathogenesis of atherosclerotic disease is essential for identification of novel therapeutic targets and improvement of cardiovascular risk stratification. Hypothesis: To determine the clinical value of amyloid-β 1-40 (Aβ40) measurement in predicting cardiovascular (CV) mortality in patients with coronary heart disease (CHD) and arterial stiffness progression in young healthy subjects. Methods: Aβ40 was retrospectively measured in blood samples collected from three independent prospective cohorts and two case-control cohorts (total n=1464). Major adverse CV events (MACE) were assessed in the two prospective cohorts (n=877) followed for a median of 4.4 years. Arterial stiffness was evaluated at baseline and after a 5-year follow-up period (n=107) in young healthy subjects. The primary endpoint was the predictive value of Aβ40 for CV mortality and outcomes in patients with CHD. Further, the associations of Aβ40 levels with arterial stiffness progression, incident subclinical atherosclerosis and incident CHD were addressed. Results: In Cox proportional-hazards models adjusted for age, gender, glomerular filtration rate, left ventricular ejection fraction, high-sensitivity C-reactive protein and high-sensitivity troponin-T, Aβ40 was an independent predictor of CV death and MACE in patients with CHD (P<0.05 for all). After multivariate adjustment, Aβ40 levels conferred a substantial enhancement of net reclassification index (continuous NRI value and 95% confidence interval: 36.7%, 12.5-60.7, P=0.001) and integrated discrimination improvement (IDI value±SE: 1.92±0.62, P<0.001) of individuals at risk in the total combined CHD cohort over the best predictive model. Further cohort-based analysis revealed that Aβ40 levels were significantly and independently associated with arterial stiffness progression, incident subclinical atherosclerosis and incident CHD. Conclusions: Measuring blood levels of Aβ40 identifies patients at high risk for cardiovascular death.