Plasma levels of amyloid beta 1-40 are associated with ultrasonographic morphological characteristics related with carotid plaque vulnerability in individuals without cardiovascular disease

Abstract

Abstract Background Amyloid-beta (1-40) (Αb40), a proinflammatory and pro-atherosclerotic peptide, is associated with concurrent subclinical atherosclerotic cardiovascular disease (ASCVD) and with major adverse cardiac events in both primary and secondary prevention settings conferring additive and reclassification value over traditional risk factors and risk scores. This evidence supports the hypothesis that Ab40 could be a biomarker of ASCVD. However, mechanistic data on the association of Αb40 with in vivo morphological characteristics of atherosclerosis related with plaque vulnerability are not available. Purpose To examine the association of Ab40 levels with characteristics of the carotid artery wall in the general population. Methods In the settings of the Athens Vascular registry, subjects without clinically overt ASCVD were consecutively recruited (n=301). Subclinical carotid atherosclerosis was assessed by ultrasonography and the images were subsequently analyzed using a dedicated software (AMS v3.03). The sum and maximal area of atherosclerotic plaques (PLQ) and the minimum echogenicity using grey scale median (GSM) of intima-media thickness (IMT, IMT_GSM) and atherosclerotic plaques (PLQ_GSM) were used as the main endpoints of the analysis. Αb40 was measured in plasma samples. Results Subjects with Ab40 levels in the highest tertile had higher prevalence of male sex, presence of carotid plaque atherosclerosis, higher sum and maximal PLQ are and lower GFR HDL-C levels and lower PLQ_GSM (p<0.05 for all). Ab40 in the highest vs. lower tertile was associated with higher sum and maximal plaque area (b-coefficient= 22.9 95% CI: 0.72, 45.1, p=0.43 and b-coefficient= 10.5 95% CI: 1.77, 19.3, p=0.019, for sum and maximal plaque area, respectively) after adjustment for traditional cardiovascular risk factors and GFR (core model). Moreover, Ab40 in the highest tertile was associated with decreased GSM of both IMT and PLQ in the carotid arteries (b-coefficient= -6.0 95% CI: -9.6, -2.36, p=0.001, for IMT and b-coefficient= -8.66 95% CI: -16.5, -0.79, p=0.31, for PLQ) after adjustment for the core model. Conclusion In individuals without clinically overt ASCVD, higher levels of Ab40 are associated with the larger atherosclerotic burden and with ultrasonographic characteristics related to higher plaque vulnerability. These findings suggest a mechanistic background for the established association of Ab40 with major adverse cardiovascular events.