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

Frank J. Wolters*, Saima Hilal, Maarten J.G. Leening, Maryam Kavousi, Mohsen Ghanbari, the Heart Brain Connection Consortium, Oscar H. Franco, Albert Hofman, Peter J. Koudstaal, Meike W. Vernooij, M. Kamran Ikram, Daniel Bos, M. Arfan Ikram

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
15 Downloads (Pure)


Background and aims: 

We aimed to determine associations of plasma amyloid-β40 (Aβ40) with subclinical atherosclerosis and risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. 


Between 2002 and 2005, plasma Aβ40 was measured by single molecule array (SiMoA®) 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 Aβ40 with calcification volumes and clinical ASCVD event risk, and repeated the analyses for ASCVD in a replication cohort of 1467 individuals. 


Higher levels of Aβ40 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 Aβ40 predisposed to a minor increase in ASCVD risk (HR [95%CI]: 1.11[1.02–1.21] per 1-SD increase in Aβ40), 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]). 


In this population-based study, higher plasma amyloid-β40 is associated with subclinical atherosclerosis, but not risk of first-ever ASCVD after accounting for traditional cardiovascular risk factors.

Original languageEnglish
Pages (from-to)44-50
Number of pages7
Publication statusPublished - May 2022


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