Associations of long-term cumulative C-reactive protein and glycoprotein acetyls concentrations in childhood, adolescence and adulthood with adulthood retinal microvascular structure

Oskari Repo; Markus Juonala; Harri Niinikoski; Suvi Rovio; Juha Mykkänen; Carol Y Cheung; Mika Ala-Korpela; Hanna Vaahtoranta-Lehtonen; Jaakko Nevalainen; Antti Jula; Mika Kähönen; Terho Lehtimäki; Tomi P Laitinen; Tapani Rönnemaa; Jorma Viikari; Olli Raitakari; Robyn Tapp; Katja Pahkala

doi:10.1016/j.atherosclerosis.2025.120595

Associations of long-term cumulative C-reactive protein and glycoprotein acetyls concentrations in childhood, adolescence and adulthood with adulthood retinal microvascular structure

Oskari Repo, Markus Juonala, Harri Niinikoski, Suvi Rovio, Juha Mykkänen, Carol Y Cheung, Mika Ala-Korpela, Hanna Vaahtoranta-Lehtonen, Jaakko Nevalainen, Antti Jula, Mika Kähönen, Terho Lehtimäki, Tomi P Laitinen, Tapani Rönnemaa, Jorma Viikari, Olli Raitakari, Robyn Tapp, Katja Pahkala

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Abstract

BACKGROUNG AND AIMS: Inflammation is associated with cardiovascular disease development and microvascular dysfunction. The aim of the present study is to test the hypothesis that long-term exposure to chronic inflammation in childhood and adulthood is associated with adverse retinal microvascular structure in young and mid-adulthood.

METHODS: We analyzed data derived from the Special Turku Coronary Risk Factor Intervention Project (STRIP) and longitudinal Cardiovascular Risk in Young Finns Study (YFS). In STRIP, fundus photos were taken in young adulthood (aged 26 years), and in YFS in mid-adulthood (aged 34-49 years). Retinal microvascular measures were derived in both cohorts (arteriolar and venular diameters and tortuosity; additionally, fractal dimensions in STRIP). Cumulative exposure as the area under the curve for high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls (GlycA), and other conventional cardiovascular risk factors was determined over a 15- and 17-year period in STRIP, and a 10-year period in YFS. Overall, retinal microvascular and cumulative hsCRP and/or GlycA were available for 344 STRIP and 1211 YFS participants, thus forming the cohort of the present study.

RESULTS: In both cohorts, cumulative hsCRP was associated with wider venules when adjusted for sex (and age in YFS), and further for related cardiovascular risk factors. In young adulthood (STRIP), higher exposure to cumulative hsCRP was associated with decreased venular tortuosity, whereas in mid-adulthood (YFS), the association was inverse. Cumulative hsCRP was not associated with arteriolar measures whereas cumulative GlycA showed no significant association with any retinal microvascular measures.

CONCLUSIONS: Long-term cumulative hsCRP exposure was associated with wider venules in young and mid-adulthood, whereas the associations with venular tortuosity were inconsistent. Wider retinal venules might act as a marker for cumulative inflammatory burden.

Original language	English
Article number	120595
Number of pages	9
Journal	Atherosclerosis
Volume	412
Early online date	20 Nov 2025
DOIs	https://doi.org/10.1016/j.atherosclerosis.2025.120595
Publication status	Published - Jan 2026

Bibliographical note

© 2025 The Authors. Published by Elsevier B.V
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Funding

The STRIP study has been supported by the Academy of Finland (grants 206374, 294834, 251360, 275595, 307996 and 322112), the Juho Vainio Foundation, the Finnish Foundation for Cardiovascular Research, the Finnish Ministry of Education and Culture, the Finnish Cultural Foundation, the Sigrid Jusélius Foundation, Special Governmental grants for Health Sciences Research (Turku University Hospital), the Yrjö Jahnsson Foundation, the Finnish Medical Foundation, and the Turku University Foundation. The YFS has been financially supported by the Academy of Finland: grants 356,405, 322,098, 286,284, 134,309 (Eye), 126,925, 121,584, 124,282, 129,378 (Salve), 117,797 (Gendi), and 141,071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848,146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; Finnish Society of Clinical Chemistry; the Cancer Foundation Finland; pBETTER4U_EU (Preventing obesity through Biologically and bEhaviorally Tailored inTERventions for you; project number: 101080117); CVDLink (EU grant nro. 101137278) and the Jane and Aatos Erkko Foundation. K.P. is supported by Academy of Finland research fellowship (322,112). M.A.-K. was supported by a research grant from the Sigrid Jusélius Foundation, the Finnish Foundation for Cardiovascular Research, and the Research Council of Finland (grant no. 357183). The YFS has been financially supported by the Academy of Finland : grants 356,405, 322,098, 286,284, 134,309 (Eye), 126,925, 121,584, 124,282, 129,378 (Salve), 117,797 (Gendi), and 141,071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association ; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848,146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; Finnish Society of Clinical Chemistry; the Cancer Foundation Finland; pBETTER4U_EU (Preventing obesity through Biologically and bEhaviorally Tailored inTERventions for you; project number: 101080117); CVDLink (EU grant nro. 101137278) and the Jane and Aatos Erkko Foundation . K.P. is supported by Academy of Finland research fellowship (322,112). M.A.-K. was supported by a research grant from the Sigrid Jusélius Foundation , the Finnish Foundation for Cardiovascular Research , and the Research Council of Finland (grant no. 357183). The STRIP study has been supported by the Academy of Finland (grants 206374 , 294834 , 251360 , 275595 , 307996 and 322112 ), the Juho Vainio Foundation , the Finnish Foundation for Cardiovascular Research , the Finnish Ministry of Education and Culture , the Finnish Cultural Foundation , the Sigrid Jusélius Foundation, Special Governmental grants for Health Sciences Research (Turku University Hospital) , the Yrjö Jahnsson Foundation, the Finnish Medical Foundation , and the Turku University Foundation .

Funders	Funder number
Tampereen Tuberkuloosisäätiö
Signe and Ane Gyllenberg Foundation
Paavo Nurmen Säätiö
Paavo Nurmi Foundation
Jane ja Aatos Erkon Säätiö
Turku University Foundation
Signe ja Ane Gyllenbergin Säätiö
Suomen Kulttuurirahasto
Sigrid Juselius Foundation
Turku University Hospital
Research Council of Finland	294834, 286,284, 124,282, 134,309, 206374, 117,797, 251360, 322,098, 275595, 126,925, 141,071, 307996, 357183, 322,112, 356,405, 121,584
Tampereen Tuberkuloosisäätiö
Cancer Foundation Finland
Suomen kliinisen kemian yhdistys
Juho Vainion Säätiö
Emil Aaltosen Säätiö
Suomen kliinisen kemian yhdistys
Tampere University Hospital Supporting Foundation
Diabetes Research Foundation
Diabetestutkimussäätiö
Cancer Foundation Finland
Sydäntutkimussäätiö
Finnish Medical Foundation
Opetus- ja Kulttuuriministeriö
Horizon Europe
European Research Council	742927
Yrjö Jahnssonin Säätiö
Sigrid Juselius Foundation
Emil Aaltonen Foundation
Horizon Europe	848,146, 755320
Turku University Hospitals	X51001

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Tapp202052VoRFinal published version, 1.09 MBLicence: CC BY

Cite this

Repo, O., Juonala, M., Niinikoski, H., Rovio, S., Mykkänen, J., Cheung, C. Y., Ala-Korpela, M., Vaahtoranta-Lehtonen, H., Nevalainen, J., Jula, A., Kähönen, M., Lehtimäki, T., Laitinen, T. P., Rönnemaa, T., Viikari, J., Raitakari, O., Tapp, R., & Pahkala, K. (2026). Associations of long-term cumulative C-reactive protein and glycoprotein acetyls concentrations in childhood, adolescence and adulthood with adulthood retinal microvascular structure. Atherosclerosis, 412, Article 120595. https://doi.org/10.1016/j.atherosclerosis.2025.120595

Repo, O, Juonala, M, Niinikoski, H, Rovio, S, Mykkänen, J, Cheung, CY, Ala-Korpela, M, Vaahtoranta-Lehtonen, H, Nevalainen, J, Jula, A, Kähönen, M, Lehtimäki, T, Laitinen, TP, Rönnemaa, T, Viikari, J, Raitakari, O, Tapp, R & Pahkala, K 2026, 'Associations of long-term cumulative C-reactive protein and glycoprotein acetyls concentrations in childhood, adolescence and adulthood with adulthood retinal microvascular structure', Atherosclerosis, vol. 412, 120595. https://doi.org/10.1016/j.atherosclerosis.2025.120595

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title = "Associations of long-term cumulative C-reactive protein and glycoprotein acetyls concentrations in childhood, adolescence and adulthood with adulthood retinal microvascular structure",

abstract = "BACKGROUNG AND AIMS: Inflammation is associated with cardiovascular disease development and microvascular dysfunction. The aim of the present study is to test the hypothesis that long-term exposure to chronic inflammation in childhood and adulthood is associated with adverse retinal microvascular structure in young and mid-adulthood.METHODS: We analyzed data derived from the Special Turku Coronary Risk Factor Intervention Project (STRIP) and longitudinal Cardiovascular Risk in Young Finns Study (YFS). In STRIP, fundus photos were taken in young adulthood (aged 26 years), and in YFS in mid-adulthood (aged 34-49 years). Retinal microvascular measures were derived in both cohorts (arteriolar and venular diameters and tortuosity; additionally, fractal dimensions in STRIP). Cumulative exposure as the area under the curve for high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls (GlycA), and other conventional cardiovascular risk factors was determined over a 15- and 17-year period in STRIP, and a 10-year period in YFS. Overall, retinal microvascular and cumulative hsCRP and/or GlycA were available for 344 STRIP and 1211 YFS participants, thus forming the cohort of the present study.RESULTS: In both cohorts, cumulative hsCRP was associated with wider venules when adjusted for sex (and age in YFS), and further for related cardiovascular risk factors. In young adulthood (STRIP), higher exposure to cumulative hsCRP was associated with decreased venular tortuosity, whereas in mid-adulthood (YFS), the association was inverse. Cumulative hsCRP was not associated with arteriolar measures whereas cumulative GlycA showed no significant association with any retinal microvascular measures.CONCLUSIONS: Long-term cumulative hsCRP exposure was associated with wider venules in young and mid-adulthood, whereas the associations with venular tortuosity were inconsistent. Wider retinal venules might act as a marker for cumulative inflammatory burden.",

author = "Oskari Repo and Markus Juonala and Harri Niinikoski and Suvi Rovio and Juha Mykk{\"a}nen and Cheung, \{Carol Y\} and Mika Ala-Korpela and Hanna Vaahtoranta-Lehtonen and Jaakko Nevalainen and Antti Jula and Mika K{\"a}h{\"o}nen and Terho Lehtim{\"a}ki and Laitinen, \{Tomi P\} and Tapani R{\"o}nnemaa and Jorma Viikari and Olli Raitakari and Robyn Tapp and Katja Pahkala",

note = "{\textcopyright} 2025 The Authors. Published by Elsevier B.V This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)",

year = "2026",

month = jan,

doi = "10.1016/j.atherosclerosis.2025.120595",

language = "English",

volume = "412",

journal = "Atherosclerosis",

issn = "0021-9150",

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T1 - Associations of long-term cumulative C-reactive protein and glycoprotein acetyls concentrations in childhood, adolescence and adulthood with adulthood retinal microvascular structure

AU - Repo, Oskari

AU - Juonala, Markus

AU - Niinikoski, Harri

AU - Rovio, Suvi

AU - Mykkänen, Juha

AU - Cheung, Carol Y

AU - Ala-Korpela, Mika

AU - Vaahtoranta-Lehtonen, Hanna

AU - Nevalainen, Jaakko

AU - Jula, Antti

AU - Kähönen, Mika

AU - Lehtimäki, Terho

AU - Laitinen, Tomi P

AU - Rönnemaa, Tapani

AU - Viikari, Jorma

AU - Raitakari, Olli

AU - Tapp, Robyn

AU - Pahkala, Katja

PY - 2026/1

Y1 - 2026/1

N2 - BACKGROUNG AND AIMS: Inflammation is associated with cardiovascular disease development and microvascular dysfunction. The aim of the present study is to test the hypothesis that long-term exposure to chronic inflammation in childhood and adulthood is associated with adverse retinal microvascular structure in young and mid-adulthood.METHODS: We analyzed data derived from the Special Turku Coronary Risk Factor Intervention Project (STRIP) and longitudinal Cardiovascular Risk in Young Finns Study (YFS). In STRIP, fundus photos were taken in young adulthood (aged 26 years), and in YFS in mid-adulthood (aged 34-49 years). Retinal microvascular measures were derived in both cohorts (arteriolar and venular diameters and tortuosity; additionally, fractal dimensions in STRIP). Cumulative exposure as the area under the curve for high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls (GlycA), and other conventional cardiovascular risk factors was determined over a 15- and 17-year period in STRIP, and a 10-year period in YFS. Overall, retinal microvascular and cumulative hsCRP and/or GlycA were available for 344 STRIP and 1211 YFS participants, thus forming the cohort of the present study.RESULTS: In both cohorts, cumulative hsCRP was associated with wider venules when adjusted for sex (and age in YFS), and further for related cardiovascular risk factors. In young adulthood (STRIP), higher exposure to cumulative hsCRP was associated with decreased venular tortuosity, whereas in mid-adulthood (YFS), the association was inverse. Cumulative hsCRP was not associated with arteriolar measures whereas cumulative GlycA showed no significant association with any retinal microvascular measures.CONCLUSIONS: Long-term cumulative hsCRP exposure was associated with wider venules in young and mid-adulthood, whereas the associations with venular tortuosity were inconsistent. Wider retinal venules might act as a marker for cumulative inflammatory burden.

AB - BACKGROUNG AND AIMS: Inflammation is associated with cardiovascular disease development and microvascular dysfunction. The aim of the present study is to test the hypothesis that long-term exposure to chronic inflammation in childhood and adulthood is associated with adverse retinal microvascular structure in young and mid-adulthood.METHODS: We analyzed data derived from the Special Turku Coronary Risk Factor Intervention Project (STRIP) and longitudinal Cardiovascular Risk in Young Finns Study (YFS). In STRIP, fundus photos were taken in young adulthood (aged 26 years), and in YFS in mid-adulthood (aged 34-49 years). Retinal microvascular measures were derived in both cohorts (arteriolar and venular diameters and tortuosity; additionally, fractal dimensions in STRIP). Cumulative exposure as the area under the curve for high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls (GlycA), and other conventional cardiovascular risk factors was determined over a 15- and 17-year period in STRIP, and a 10-year period in YFS. Overall, retinal microvascular and cumulative hsCRP and/or GlycA were available for 344 STRIP and 1211 YFS participants, thus forming the cohort of the present study.RESULTS: In both cohorts, cumulative hsCRP was associated with wider venules when adjusted for sex (and age in YFS), and further for related cardiovascular risk factors. In young adulthood (STRIP), higher exposure to cumulative hsCRP was associated with decreased venular tortuosity, whereas in mid-adulthood (YFS), the association was inverse. Cumulative hsCRP was not associated with arteriolar measures whereas cumulative GlycA showed no significant association with any retinal microvascular measures.CONCLUSIONS: Long-term cumulative hsCRP exposure was associated with wider venules in young and mid-adulthood, whereas the associations with venular tortuosity were inconsistent. Wider retinal venules might act as a marker for cumulative inflammatory burden.

UR - https://www.scopus.com/pages/publications/105022794824

U2 - 10.1016/j.atherosclerosis.2025.120595

DO - 10.1016/j.atherosclerosis.2025.120595

M3 - Article

C2 - 41275596

SN - 0021-9150

VL - 412

JO - Atherosclerosis

JF - Atherosclerosis

M1 - 120595

ER -

Associations of long-term cumulative C-reactive protein and glycoprotein acetyls concentrations in childhood, adolescence and adulthood with adulthood retinal microvascular structure

Abstract

Bibliographical note

Funding

UN SDGs

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