Vascular injury biomarkers and stroke risk: A population-based study

Laura Pletsch-Borba; Mirja Grafetstätter; Anika Hüsing; Theron Johnson; Sandra González Maldonado; Marie-Luise Groß; Manja Kloss; Michael Hoffmeister; Peter Bugert; Rudolf Kaaks; Tilman Kühn

doi:10.1212/WNL.0000000000009391

Vascular injury biomarkers and stroke risk: A population-based study

Laura Pletsch-Borba, Mirja Grafetstätter, Anika Hüsing, Theron Johnson, Sandra González Maldonado, Marie-Luise Groß, Manja Kloss, Michael Hoffmeister, Peter Bugert, Rudolf Kaaks, Tilman Kühn

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

OBJECTIVE: Because little is known about associations between biomarkers of vascular injury and stroke risk, we evaluated associations between plasma concentrations of 6 novel biomarkers of vascular injury and stroke risk in a population-based study.

METHODS: A case-cohort subset of EPIC-Heidelberg (European Prospective Investigation for Cancer and Nutrition-Heidelberg) including incident stroke cases (n = 335) and a random subcohort (n = 2,418) was selected. Concentrations of intercellular adhesion molecule 3 (ICAM3), soluble E-selectin and P-selectin, soluble thrombomodulin (sTM), thrombopoietin, and glycoprotein IIb/IIIa were measured in baseline plasma samples. Weighted Cox regression analyses were used to assess associations between biomarker levels and stroke risk.

RESULTS: Median follow-up in the subcohort and among cases was 9.8 (range, 0.1-12.5) years and 6.2 (range, 0.01-12.1) years, respectively. ICAM3 levels were associated with increased risk of incident stroke after multivariable adjustment (hazard ratio, highest vs lowest quartile: 1.64 [95% confidence interval, 1.15-2.32]; plinear trend < 0.001). This association was more apparent for ischemic (1.65 [1.12-2.45]; plinear trend < 0.01) than for hemorrhagic stroke (1.29 [0.60-2.78]; plinear trend = 0.3). We further observed a borderline significant trend for a positive association between sTM and overall stroke risk (1.47 [0.99-2.19]; plinear trend = 0.05).

CONCLUSIONS: In this population-based study, circulating levels of ICAM3, an adhesion molecule shed by leukocytes, were associated with increased risk of incident stroke. Further mechanistic studies are needed to elucidate the pathophysiology underlying this association.

CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that plasma levels of ICAM3 are associated with increased stroke risk.

Original language	English
Journal	Neurology
Early online date	05 May 2020
DOIs	https://doi.org/10.1212/WNL.0000000000009391
Publication status	Early online date - 05 May 2020
Externally published	Yes

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@article{b25c89fd57184f048f9b10d025ec7ef3,

title = "Vascular injury biomarkers and stroke risk: A population-based study",

abstract = "OBJECTIVE: Because little is known about associations between biomarkers of vascular injury and stroke risk, we evaluated associations between plasma concentrations of 6 novel biomarkers of vascular injury and stroke risk in a population-based study.METHODS: A case-cohort subset of EPIC-Heidelberg (European Prospective Investigation for Cancer and Nutrition-Heidelberg) including incident stroke cases (n = 335) and a random subcohort (n = 2,418) was selected. Concentrations of intercellular adhesion molecule 3 (ICAM3), soluble E-selectin and P-selectin, soluble thrombomodulin (sTM), thrombopoietin, and glycoprotein IIb/IIIa were measured in baseline plasma samples. Weighted Cox regression analyses were used to assess associations between biomarker levels and stroke risk.RESULTS: Median follow-up in the subcohort and among cases was 9.8 (range, 0.1-12.5) years and 6.2 (range, 0.01-12.1) years, respectively. ICAM3 levels were associated with increased risk of incident stroke after multivariable adjustment (hazard ratio, highest vs lowest quartile: 1.64 [95% confidence interval, 1.15-2.32]; plinear trend < 0.001). This association was more apparent for ischemic (1.65 [1.12-2.45]; plinear trend < 0.01) than for hemorrhagic stroke (1.29 [0.60-2.78]; plinear trend = 0.3). We further observed a borderline significant trend for a positive association between sTM and overall stroke risk (1.47 [0.99-2.19]; plinear trend = 0.05).CONCLUSIONS: In this population-based study, circulating levels of ICAM3, an adhesion molecule shed by leukocytes, were associated with increased risk of incident stroke. Further mechanistic studies are needed to elucidate the pathophysiology underlying this association.CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that plasma levels of ICAM3 are associated with increased stroke risk.",

author = "Laura Pletsch-Borba and Mirja Grafetst{\"a}tter and Anika H{\"u}sing and Theron Johnson and {Gonz{\'a}lez Maldonado}, Sandra and Marie-Luise Gro{\ss} and Manja Kloss and Michael Hoffmeister and Peter Bugert and Rudolf Kaaks and Tilman K{\"u}hn",

note = "{\textcopyright} 2020 American Academy of Neurology.",

year = "2020",

month = may,

day = "5",

doi = "10.1212/WNL.0000000000009391",

language = "English",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams & Wilkins",

}

TY - JOUR

T1 - Vascular injury biomarkers and stroke risk: A population-based study

AU - Pletsch-Borba, Laura

AU - Grafetstätter, Mirja

AU - Hüsing, Anika

AU - Johnson, Theron

AU - González Maldonado, Sandra

AU - Groß, Marie-Luise

AU - Kloss, Manja

AU - Hoffmeister, Michael

AU - Bugert, Peter

AU - Kaaks, Rudolf

AU - Kühn, Tilman

PY - 2020/5/5

Y1 - 2020/5/5

N2 - OBJECTIVE: Because little is known about associations between biomarkers of vascular injury and stroke risk, we evaluated associations between plasma concentrations of 6 novel biomarkers of vascular injury and stroke risk in a population-based study.METHODS: A case-cohort subset of EPIC-Heidelberg (European Prospective Investigation for Cancer and Nutrition-Heidelberg) including incident stroke cases (n = 335) and a random subcohort (n = 2,418) was selected. Concentrations of intercellular adhesion molecule 3 (ICAM3), soluble E-selectin and P-selectin, soluble thrombomodulin (sTM), thrombopoietin, and glycoprotein IIb/IIIa were measured in baseline plasma samples. Weighted Cox regression analyses were used to assess associations between biomarker levels and stroke risk.RESULTS: Median follow-up in the subcohort and among cases was 9.8 (range, 0.1-12.5) years and 6.2 (range, 0.01-12.1) years, respectively. ICAM3 levels were associated with increased risk of incident stroke after multivariable adjustment (hazard ratio, highest vs lowest quartile: 1.64 [95% confidence interval, 1.15-2.32]; plinear trend < 0.001). This association was more apparent for ischemic (1.65 [1.12-2.45]; plinear trend < 0.01) than for hemorrhagic stroke (1.29 [0.60-2.78]; plinear trend = 0.3). We further observed a borderline significant trend for a positive association between sTM and overall stroke risk (1.47 [0.99-2.19]; plinear trend = 0.05).CONCLUSIONS: In this population-based study, circulating levels of ICAM3, an adhesion molecule shed by leukocytes, were associated with increased risk of incident stroke. Further mechanistic studies are needed to elucidate the pathophysiology underlying this association.CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that plasma levels of ICAM3 are associated with increased stroke risk.

AB - OBJECTIVE: Because little is known about associations between biomarkers of vascular injury and stroke risk, we evaluated associations between plasma concentrations of 6 novel biomarkers of vascular injury and stroke risk in a population-based study.METHODS: A case-cohort subset of EPIC-Heidelberg (European Prospective Investigation for Cancer and Nutrition-Heidelberg) including incident stroke cases (n = 335) and a random subcohort (n = 2,418) was selected. Concentrations of intercellular adhesion molecule 3 (ICAM3), soluble E-selectin and P-selectin, soluble thrombomodulin (sTM), thrombopoietin, and glycoprotein IIb/IIIa were measured in baseline plasma samples. Weighted Cox regression analyses were used to assess associations between biomarker levels and stroke risk.RESULTS: Median follow-up in the subcohort and among cases was 9.8 (range, 0.1-12.5) years and 6.2 (range, 0.01-12.1) years, respectively. ICAM3 levels were associated with increased risk of incident stroke after multivariable adjustment (hazard ratio, highest vs lowest quartile: 1.64 [95% confidence interval, 1.15-2.32]; plinear trend < 0.001). This association was more apparent for ischemic (1.65 [1.12-2.45]; plinear trend < 0.01) than for hemorrhagic stroke (1.29 [0.60-2.78]; plinear trend = 0.3). We further observed a borderline significant trend for a positive association between sTM and overall stroke risk (1.47 [0.99-2.19]; plinear trend = 0.05).CONCLUSIONS: In this population-based study, circulating levels of ICAM3, an adhesion molecule shed by leukocytes, were associated with increased risk of incident stroke. Further mechanistic studies are needed to elucidate the pathophysiology underlying this association.CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that plasma levels of ICAM3 are associated with increased stroke risk.

U2 - 10.1212/WNL.0000000000009391

DO - 10.1212/WNL.0000000000009391

M3 - Article

C2 - 32371447

SN - 0028-3878

JO - Neurology

JF - Neurology

ER -

Vascular injury biomarkers and stroke risk: A population-based study

Abstract

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