Systemic inflammation is associated with incident stroke and heart disease in East Asians

Mohd A Karim; Christiana Kartsonaki; Derrick A Bennett; Iona Y Millwood; Michael R Hill; Daniel Avery; Zheng Bian; Huaidong Du; Yu Guo; Yijian Qian; Chan Qu; Iain Turnbull; Dan Schmidt-Valle; Chunmei Wang; Canqing Yu; Jun Lv; Junshi Chen; Robert Clarke; Liming Li; Zhengming Chen; Michael V Holmes; Robin G Walters; China Kadoorie Biobank (CKB) collaborative group

doi:10.1038/s41598-020-62391-3

Systemic inflammation is associated with incident stroke and heart disease in East Asians

Mohd A Karim, Christiana Kartsonaki, Derrick A Bennett, Iona Y Millwood, Michael R Hill, Daniel Avery, Zheng Bian, Huaidong Du, Yu Guo, Yijian Qian, Chan Qu, Iain Turnbull, Dan Schmidt-Valle, Chunmei Wang, Canqing Yu, Jun Lv, Junshi Chen, Robert Clarke, Liming Li, Zhengming ChenMichael V Holmes, Robin G Walters, China Kadoorie Biobank (CKB) collaborative group

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Abstract

Systemic inflammation, reflected by increased plasma concentrations of C-reactive protein (CRP) and fibrinogen, is associated with increased risk of coronary heart disease, but its relevance for stroke types remains unclear. Moreover, evidence is limited in non-European populations. We investigated associations of CRP and fibrinogen with risks of incident major coronary events (MCE), ischemic stroke (IS) and intracerebral hemorrhage (ICH) in a cohort of Chinese adults. A nested case-control study within the prospective China Kadoorie Biobank included 1,508 incident MCE cases, 5,418 IS cases, 4,476 ICH cases, and 5,285 common controls, aged 30-79 years. High-sensitivity CRP and low-density lipoprotein cholesterol (LDL-C) were measured in baseline plasma samples from all participants, and fibrinogen in a subset (n = 9,380). Logistic regression yielded adjusted odds ratios (ORs) per SD higher usual levels of log-transformed CRP and fibrinogen. The overall mean (SD) baseline LDL-C was 91.6 mg/dL (24.0) and geometric mean (95% CI) CRP and fibrinogen were 0.90 mg/L (0.87-0.93) and 3.01 g/L (2.98-3.03), respectively. There were approximately log-linear positive associations of CRP with each outcome, which persisted after adjustment for LDL-C and other risk factors, with adjusted ORs (95% CI) per SD higher CRP of 1.67 (1.44-1.94) for MCE and 1.22 (1.10-1.36) for both IS and ICH. No associations of fibrinogen with MCE, IS, or ICH were identified. Adding CRP to prediction models based on established risk factors improved model fit for each of MCE, IS, and ICH, with small improvements in C-statistic and correct reclassification of controls to lower risk groups. Among Chinese adults, who have low mean LDL-C, CRP, but not fibrinogen, was independently associated with increased risks of MCE and stroke.

Original language	English
Article number	5605
Number of pages	11
Journal	Scientific Reports
Volume	10
Issue number	1
Early online date	27 Mar 2020
DOIs	https://doi.org/10.1038/s41598-020-62391-3
Publication status	Published - 1 Dec 2020

Bibliographical note

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

A Publisher Correction to this article was published on 12 May 2020

Funding

The chief acknowledgement is to the collaborators and participants of China Kadoorie Biobank, to the project staff at Beijing, Oxford, and the 10 regional CKB centers, and to the China National Centre for Disease Control and Prevention (CDC) and its regional offices for assisting with the fieldwork. The baseline survey was supported by the Kadoorie Charitable Foundation, Hong Kong. Long-term follow-up and the second resurvey were supported by grants 088158/Z/09/Z and 104085/Z/14/Z from the UK Wellcome Trust, grant 2011BAI09B01 (2012\u20132014) from the Chinese Ministry of Science and Technology, and grant 81390541 from the Chinese National Natural Science Foundation. The British Heart Foundation, UK Medical Research Council, and Cancer Research UK provided core funding to the Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford. Dr Karim is supported by the Nuffield Department of Population Health (NDPH) Studentship for his DPhil. Dr Holmes is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/18/23/33512) and the National Institute for Health Research Oxford Biomedical Research Centre.

Funders	Funder number
Medical Research Council
Kadoorie Charitable Foundation
University of Oxford
Cancer Research UK
British Heart Foundation
Oxford NIHR Biomedical Research Centre
National Natural Science Foundation of China
Wellcome Trust Centre for Mitochondrial Research	088158/Z/09/Z, 104085/Z/14/Z
University of Oxford	FS/18/23/33512
Wellcome Trust	088158
National Natural Science Foundation of China-Yunnan Joint Fund	81390541
Chinese Ministry of Science and Technology	2011BAI09B01

Keywords

Myocardial infarction
Predictive markers
Stroke

ASJC Scopus subject areas

General

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10.1038/s41598-020-62391-3Licence: CC BY

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Karim, M. A., Kartsonaki, C., Bennett, D. A., Millwood, I. Y., Hill, M. R., Avery, D., Bian, Z., Du, H., Guo, Y., Qian, Y., Qu, C., Turnbull, I., Schmidt-Valle, D., Wang, C., Yu, C., Lv, J., Chen, J., Clarke, R., Li, L., ... China Kadoorie Biobank (CKB) collaborative group (2020). Systemic inflammation is associated with incident stroke and heart disease in East Asians. Scientific Reports, 10(1), Article 5605. https://doi.org/10.1038/s41598-020-62391-3

Karim, MA, Kartsonaki, C, Bennett, DA, Millwood, IY, Hill, MR, Avery, D, Bian, Z, Du, H, Guo, Y, Qian, Y, Qu, C, Turnbull, I, Schmidt-Valle, D, Wang, C, Yu, C, Lv, J, Chen, J, Clarke, R, Li, L, Chen, Z, Holmes, MV, Walters, RG & China Kadoorie Biobank (CKB) collaborative group 2020, 'Systemic inflammation is associated with incident stroke and heart disease in East Asians', Scientific Reports, vol. 10, no. 1, 5605. https://doi.org/10.1038/s41598-020-62391-3

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abstract = "Systemic inflammation, reflected by increased plasma concentrations of C-reactive protein (CRP) and fibrinogen, is associated with increased risk of coronary heart disease, but its relevance for stroke types remains unclear. Moreover, evidence is limited in non-European populations. We investigated associations of CRP and fibrinogen with risks of incident major coronary events (MCE), ischemic stroke (IS) and intracerebral hemorrhage (ICH) in a cohort of Chinese adults. A nested case-control study within the prospective China Kadoorie Biobank included 1,508 incident MCE cases, 5,418 IS cases, 4,476 ICH cases, and 5,285 common controls, aged 30-79 years. High-sensitivity CRP and low-density lipoprotein cholesterol (LDL-C) were measured in baseline plasma samples from all participants, and fibrinogen in a subset (n = 9,380). Logistic regression yielded adjusted odds ratios (ORs) per SD higher usual levels of log-transformed CRP and fibrinogen. The overall mean (SD) baseline LDL-C was 91.6 mg/dL (24.0) and geometric mean (95% CI) CRP and fibrinogen were 0.90 mg/L (0.87-0.93) and 3.01 g/L (2.98-3.03), respectively. There were approximately log-linear positive associations of CRP with each outcome, which persisted after adjustment for LDL-C and other risk factors, with adjusted ORs (95% CI) per SD higher CRP of 1.67 (1.44-1.94) for MCE and 1.22 (1.10-1.36) for both IS and ICH. No associations of fibrinogen with MCE, IS, or ICH were identified. Adding CRP to prediction models based on established risk factors improved model fit for each of MCE, IS, and ICH, with small improvements in C-statistic and correct reclassification of controls to lower risk groups. Among Chinese adults, who have low mean LDL-C, CRP, but not fibrinogen, was independently associated with increased risks of MCE and stroke.",

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Systemic inflammation is associated with incident stroke and heart disease in East Asians

Abstract

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