Article Text
Abstract
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-γ), tumour necrosis factor-alpha (TNF-α) 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-γ, respectively. However, neither TNF-α, 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.
- cytokines
- coronary heart disease
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Footnotes
Contributors RC, JCH, MF, AH and HW designed the study. EV-M and JCH conducted the statistical analyses. MH and JG conducted the laboratory analyses. RC and JCH drafted the manuscript. All other authors contributed to the revisions of the manuscript and approved the final version.
Funding The PROCARDIS study was supported by the European Community Sixth Framework Program (LSHM-CT-2007–037273), AstraZeneca, the British Heart Foundation, the University of Oxford British Heart Foundation Centre of Research Excellence, the Wellcome Trust (075491/Z/04), the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung Foundation, the Torsten and Ragnar Söderberg Foundation, the Strategic Cardiovascular Program of Karolinska Institutet and Stockholm County Council, the Foundation for Strategic Research and the Stockholm County Council (560283). JCH acknowledges personal funding from the British Heart Foundation (FS/14/55/30806).
Competing interests None declared.
Patient consent Obtained.
Ethics approval MREC (South East England).
Provenance and peer review Not commissioned; internally peer reviewed.
Data sharing statement Data from this study will be made available to bona fide researchers for collaborative studies on cytokines and risk of coronary heart disease.