Abstract 12474: Amyloid-β 1-40 as an Independent Cardiovascular Risk Factor: First Evidence in Patients With Cardiovascular Disease
Aims: Amyloid-β 1-40 (Aβ40) has been reported to cause endothelial cell and monocyte/macrophage activation contributing to vascular inflammation in vivo. The aims of the present translational study were: 1) to define the levels of plasma Aβ40 in two independent cohorts of total 908 patients with cardiovascular (CV) disease, and 2) to define the prognostic value of Aβ40 in predicting arterial stiffness progression and cardiovascular mortality after a 5- and 3.5-year follow-up period, respectively.
Methods and Results: Mean Aβ40 plasma levels progressively increased across quartiles of Framingham risk score (FRS; n=908; F=130.8, P≤0.001). Plasma levels of Aβ40 were associated with incident CAD in two independent cohorts after adjustment for cardiovascular risk factors. After multivariable adjustment, Aβ40 was also associated with the extent of subclinical atherosclerosis (intima media thickness and number of atherosclerotic plaques in carotid and femoral arteries; n=394, P≤0.001 for all). Aβ40 levels also conferred incremental value over FRS in identifying high CV risk. In a subcohort of our study (n=110), we evaluated the predictive value of Aβ40 in detecting the progression of arterial stiffness as assessed by pulse wave velocity during a 5-year follow-up period. By linear mixed model analysis, changes in plasma Aβ40 from baseline to follow-up were positively associated with changes in arterial stiffness (P=0.003) independent of mean blood pressure alterations. Moreover, Aβ40 plasma levels at baseline were positively associated with changes in Framingham risk score (F=9.8, P=0.002) from baseline to follow-up. Finally, low Aβ40 levels were associated with a lower CV mortality rate in high CV risk patients (n=198) after a median follow-up period of 3.5 years.
Conclusion: This study demonstrates for the first time that Aβ40 may be an independent cardiovascular risk factor reflecting the extent of human atherosclerosis. Alterations in Aβ40 plasma levels are independently accompanied by development of arterial stiffness after a 5-year follow-up period. Further prospective studies are required to elucidate the potential value of Aβ40 as a useful atherosclerosis biomarker or a novel therapeutic target.
- © 2013 by American Heart Association, Inc.