Journal
OPEN HEART
Volume 5, Issue 1, Pages -Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/openhrt-2018-000807
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Funding
- European Community [LSHM-CT-2007-037273]
- AstraZeneca
- British Heart Foundation
- University of Oxford British Heart Foundation Centre of Research Excellence
- Wellcome Trust [075491/Z/04]
- Swedish Research Council
- Knut and Alice Wallenberg Foundation
- Swedish Heart-Lung Foundation
- Torsten and Ragnar Soderberg Foundation
- Strategic Cardiovascular Program of Karolinska Institutet
- Stockholm County Council [560283]
- Foundation for Strategic Research
- British Heart Foundation [FS/14/55/30806]
- MRC [MC_U137686855] Funding Source: UKRI
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Objective The aims of the study were to examine the associations of plasma levels of five cytokines (interleukin (IL)-6, IL-5, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-6 receptor (IL-6R)) and C reactive protein (CRP) with risk of coronary heart disease (CHD). Methods In a case-control study of 931 CHD cases and 974 controls, logistic regression was used to estimate the OR and 95% CI of CHD for extreme thirds of biomarkers after adjustment for established risk factors. Sensitivity analyses were conducted in non-statin and in non-aspirin users. Results Plasma levels of CRP were moderately correlated with IL-6 (r=0.45) in controls, but more weakly correlated with other cytokines. Likewise, all other cytokines were only weakly correlated with each other. After adjustment for established risk factors, the ORs (95% CI) for CHD comparing extreme thirds of cytokine levels (defined in controls) were 2.53 (1.86 to 3.43) for IL-6, 1.46 (1.11 to 1.93) for IL-5 and 1.46 (1.09 to 1.95) for IFN-gamma, respectively. However, neither TNF-alpha, IL-6R nor CRP was significantly associated with CHD. After further adjustment for the associated cytokines, only IL-5 (1.34; 1.00 to 1.80) and IL-6 (2.39; 1.73 to 3.30) remained significantly associated with CHD. The risk associations of cytokines in non-users of statins or aspirin were comparable with the overall population. Conclusions This study confirmed the importance of IL-6 as the most strongly associated cytokine with CHD risk, but also demonstrated novel and independent associations of IL-5 with CHD that warrant further investigation using larger panels of cytokines.
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