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

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

doi:10.1016/j.atherosclerosis.2022.03.025

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

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

^*Corresponding author for this work

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Abstract

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. Methods: 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. Results: 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]). Conclusions: 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 language	English
Pages (from-to)	44-50
Number of pages	7
Journal	Atherosclerosis
Volume	348
DOIs	https://doi.org/10.1016/j.atherosclerosis.2022.03.025
Publication status	Published - May 2022

Bibliographical note

Financial support
This work is part of the Heart-Brain Connection crossroads (HBCx)
consortium of the Dutch CardioVascular Alliance (DCVA), which
received funding from the Dutch Heart Foundation under grant agree-
ments 2018-28 and 2012-06. It was partly performed in the context of
the Netherlands consortium of Dementia Cohorts, which receives
funding within the Deltaplan Dementie framework from ZonMw Mem-
orabel (project 73305095005) and Alzheimer Nederland. The Rotter-
dam Study is supported by the Erasmus MC and Erasmus University
Rotterdam, The Netherlands Organisation for Scientific Research
(NWO), The Netherlands Organisation for Health Research and Devel-
opment (ZonMw), the Research Institute for Diseases in the Elderly
(RIDE), the Netherlands Genomics Initiative, the Ministry of Education,
Culture and Science, the Ministry of Health, Welfare and Sports, the
European Commission (DG XII), and the Municipality of Rotterdam. This
study is further funded by the European Union’s Horizon 2020 research
and innovation programme as part of the Common mechanisms and
pathways in Stroke and Alzheimer’s disease (CoSTREAM) project (www.
costream.eu, grant agreement no. 667375). None of the funding orga-
nisations or sponsors were involved in study design, in collection,
analysis, and interpretation of data, in writing of the report, or in the
decision to submit the article for publication.

Publisher Copyright: © 2022 The Authors

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Wolters, F. J., Hilal, S., the Heart Brain Connection Consortium, Leening, M. J. G., Kavousi, M., Ghanbari, M., Franco, O. H., Hofman, A., Koudstaal, P. J., Vernooij, M. W., Ikram, M. K., Bos, D., & Ikram, M. A. (2022). Plasma amyloid-β40 in relation to subclinical atherosclerosis and cardiovascular disease: A population-based study. Atherosclerosis, 348, 44-50. https://doi.org/10.1016/j.atherosclerosis.2022.03.025

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

abstract = "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. Methods: Between 2002 and 2005, plasma Aβ40 was measured by single molecule array (SiMoA{\textregistered}) 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. Results: 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]). Conclusions: 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.",

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

note = "Financial support This work is part of the Heart-Brain Connection crossroads (HBCx) consortium of the Dutch CardioVascular Alliance (DCVA), which received funding from the Dutch Heart Foundation under grant agree- ments 2018-28 and 2012-06. It was partly performed in the context of the Netherlands consortium of Dementia Cohorts, which receives funding within the Deltaplan Dementie framework from ZonMw Mem- orabel (project 73305095005) and Alzheimer Nederland. The Rotter- dam Study is supported by the Erasmus MC and Erasmus University Rotterdam, The Netherlands Organisation for Scientific Research (NWO), The Netherlands Organisation for Health Research and Devel- opment (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. This study is further funded by the European Union{\textquoteright}s Horizon 2020 research and innovation programme as part of the Common mechanisms and pathways in Stroke and Alzheimer{\textquoteright}s disease (CoSTREAM) project (www. costream.eu, grant agreement no. 667375). None of the funding orga- nisations or sponsors were involved in study design, in collection, analysis, and interpretation of data, in writing of the report, or in the decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = may,

doi = "10.1016/j.atherosclerosis.2022.03.025",

language = "English",

volume = "348",

pages = "44--50",

journal = "Atherosclerosis",

issn = "0021-9150",

publisher = "Elsevier Ireland Ltd",

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Wolters, FJ, Hilal, S, the Heart Brain Connection Consortium, Leening, MJG , Kavousi, M , Ghanbari, M, Franco, OH, Hofman, A, Koudstaal, PJ , Vernooij, MW , Ikram, MK , Bos, D & Ikram, MA 2022, 'Plasma amyloid-β40 in relation to subclinical atherosclerosis and cardiovascular disease: A population-based study', Atherosclerosis, vol. 348, pp. 44-50. https://doi.org/10.1016/j.atherosclerosis.2022.03.025

TY - JOUR

T1 - Plasma amyloid-β40 in relation to subclinical atherosclerosis and cardiovascular disease

T2 - A population-based study

AU - Wolters, Frank J.

AU - Hilal, Saima

AU - the Heart Brain Connection Consortium

AU - Leening, Maarten J.G.

AU - Kavousi, Maryam

AU - Ghanbari, Mohsen

AU - Franco, Oscar H.

AU - Hofman, Albert

AU - Koudstaal, Peter J.

AU - Vernooij, Meike W.

AU - Ikram, M. Kamran

AU - Bos, Daniel

AU - Ikram, M. Arfan

N1 - Financial support This work is part of the Heart-Brain Connection crossroads (HBCx) consortium of the Dutch CardioVascular Alliance (DCVA), which received funding from the Dutch Heart Foundation under grant agree- ments 2018-28 and 2012-06. It was partly performed in the context of the Netherlands consortium of Dementia Cohorts, which receives funding within the Deltaplan Dementie framework from ZonMw Mem- orabel (project 73305095005) and Alzheimer Nederland. The Rotter- dam Study is supported by the Erasmus MC and Erasmus University Rotterdam, The Netherlands Organisation for Scientific Research (NWO), The Netherlands Organisation for Health Research and Devel- opment (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. This study is further funded by the European Union’s Horizon 2020 research and innovation programme as part of the Common mechanisms and pathways in Stroke and Alzheimer’s disease (CoSTREAM) project (www. costream.eu, grant agreement no. 667375). None of the funding orga- nisations or sponsors were involved in study design, in collection, analysis, and interpretation of data, in writing of the report, or in the decision to submit the article for publication. Publisher Copyright: © 2022 The Authors

PY - 2022/5

Y1 - 2022/5

N2 - 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. Methods: 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. Results: 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]). Conclusions: 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.

AB - 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. Methods: 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. Results: 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]). Conclusions: 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.

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DO - 10.1016/j.atherosclerosis.2022.03.025

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SN - 0021-9150

VL - 348

SP - 44

EP - 50

JO - Atherosclerosis

JF - Atherosclerosis

ER -

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

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