Impact of Chronic Inflammation, Assessed by hs-CRP, on the Association between Red Cell Distribution Width and Arterial Cardiovascular Disease: The Tromsø Study

Jostein Lappegård; Trygve S Ellingsen; Kristian Hindberg; Ellisiv B Mathiesen; Inger Njølstad; Tom Wilsgaard; Maja-Lisa Løchen; Sigrid K Brækkan; John-Bjarne Hansen

doi:10.1055/s-0038-1651523

Impact of Chronic Inflammation, Assessed by hs-CRP, on the Association between Red Cell Distribution Width and Arterial Cardiovascular Disease: The Tromsø Study

TH Open. 2018 May 16;2(2):e182-e189. doi: 10.1055/s-0038-1651523. eCollection 2018 Apr.

Authors

Jostein Lappegård¹, Trygve S Ellingsen¹, Kristian Hindberg¹, Ellisiv B Mathiesen^{1

2

3}, Inger Njølstad^{1

4}, Tom Wilsgaard⁴, Maja-Lisa Løchen⁴, Sigrid K Brækkan^{1

5}, John-Bjarne Hansen^{1

5}

Affiliations

¹ K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
² Brain and Circulation Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
³ Department of Neurology and Neurophysiology, University Hospital of North Norway, Tromsø, Norway.
⁴ Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
⁵ Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.

Abstract

Red cell distribution width (RDW), a measure of variability in size of circulating erythrocytes, is associated with arterial cardiovascular disease (CVD), but the underlying mechanism remains unclear. We aimed to investigate the impact of chronic inflammation as measured by high-sensitivity C-reactive protein (hs-CRP) on this relationship, and explore whether RDW could be a mediator in the causal pathway between inflammation and arterial CVD. Baseline characteristics, including RDW and hs-CRP, were obtained from 5,765 individuals attending a population-based cohort study. We followed up participants from inclusion in the fourth survey of the Tromsø Study (1994/1995) until December 31, 2012. Multivariable Cox-regression models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for incident myocardial infarction (MI) and ischemic stroke across quintiles of hs-CRP and RDW. Subjects with hs-CRP in the highest quintile had 44% higher risk of MI (HR: 1.44, 95% CI: 1.14-1.80), and 64% higher risk of ischemic stroke (HR: 1.64, 95% CI: 1.20-2.24) compared with subjects in the lowest quintile. RDW mediated 7.2% (95% CI: 4.0-30.8%) of the association between hs-CRP and ischemic stroke. Subjects with RDW in the highest quintile had 22% higher risk of MI (HR: 1.22, 95% CI: 0.98-1.54) and 44% higher risk of ischemic stroke (HR: 1.44, 95% CI: 1.06-1.97) compared with subjects in the lowest quintile. These risk estimates were slightly attenuated after adjustments for hs-CRP. Our findings suggest that chronic inflammation is not a primary mechanism underlying the relationship between RDW and arterial CVD.

Keywords: blood cells; epidemiology; myocardial infarction; risk factors; stroke.

Grants and funding

Funding K.G. Jebsen Thrombosis Research and Expertise Centre (TREC) is supported by an independent grant from Stiftelsen Kristian Gerhard Jebsen. S.K.B. and J-B.H. have received research grants from the Northern Norway Regional Health Authority (URL: http://www.helse-nord.no/ ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.