Plasma amyloid-β40 in relation to subclinical atherosclerosis and cardiovascular disease: A population-based study

Background and aims: We aimed to determine associations of plasma amyloid-beta 40 (A beta 40) with subclinical atherosclerosis and risk of atherosclerotic cardiovascular disease (ASCVD) in the general population.Methods: Between 2002 and 2005, plasma A beta 40 was measured by single molecule array (SiMoA (R)) in 3879 participants of the population-based Rotterdam Study (mean age: 71 years, 61% female). Subclinical atherosclerosis was quantified as computed tomography-assessed calcification volumes. We determined the association of A beta 40 with calcification volumes and clinical ASCVD event risk, and repeated the analyses for ASCVD in a replication cohort of 1467 individuals.Results: Higher levels of A beta 40 were associated with increased volumes of calcification in the coronary arteries and to a lesser extent extracranial carotid arteries, independent of traditional cardiovascular risk factors. Of all 3879 participants, 748 developed ASCVD during a median 9.7 years of follow-up. In age-and sex-adjusted models, higher A beta 40 predisposed to a minor increase in ASCVD risk (HR [95%CI]: 1.11[1.02-1.21] per 1-SD increase in A beta 40), driven by coronary heart disease (HR: 1.17[1.05-1.29]) rather than stroke (HR: 1.04 [0.93-1.16]). However, excess risk of clinical outcomes was largely explained by baseline differences in cardiovascular risk factors and attenuated after further adjustment (for ASCVD- HR: 1.05[0.96-1.15] and for CHD- HR: 1.08[0.96-1.20]). Results were similar in the replication cohort, with highest risk estimates for CHD (HR: 1.24[1.04-1.48]) in age-and sex-adjusted models, attenuated after adjustment for cardiovascular risk factors (HR: 1.15[0.96-1.39]).Conclusions: In this population-based study, higher plasma amyloid-beta 40 is associated with subclinical atherosclerosis, but not risk of first-ever ASCVD after accounting for traditional cardiovascular risk factors.

Automated summary

This population-based study found that higher levels of plasma amyloid-beta 40 are associated with subclinical atherosclerosis, but not with the risk of first-ever atherosclerotic cardiovascular disease after considering traditional cardiovascular risk factors.