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Plasma cytokines and risk of coronary heart disease in the PROCARDIS study
Robert Clarke1, Elsa Valdes-Marquez1, Michael Hill1
1Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Insights
Interleukin-6 (IL-6) and Interleukin-5 (IL-5) show significant associations with coronary heart disease (CHD) risk. This study highlights IL-6 as a key cytokine and suggests IL-5 warrants further investigation for its role in CHD.
Area of Science:
- Cardiovascular Disease Research
- Immunology and Inflammation
- Biomarker Discovery
Background:
- Coronary heart disease (CHD) remains a leading cause of mortality worldwide.
- Understanding the role of inflammatory markers, such as cytokines, is crucial for risk assessment.
- Previous research has suggested links between inflammation and cardiovascular events.
Purpose of the Study:
- To investigate the association between plasma levels of five cytokines (interleukin-6, IL-5, interferon-gamma, tumor necrosis factor-alpha, IL-6 receptor) and C-reactive protein (CRP) with the risk of CHD.
- To determine the independent contribution of these biomarkers to CHD risk.
- To explore these associations in specific subgroups, such as non-statin and non-aspirin users.
Main Methods:
- A case-control study design was employed, including 931 CHD cases and 974 controls.
- Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for CHD.
- Adjustments were made for established cardiovascular risk factors, and sensitivity analyses were performed.
Main Results:
- Plasma levels of C-reactive protein (CRP) showed moderate correlation with IL-6 but weak correlations with other cytokines.
- After risk factor adjustment, IL-6 (OR 2.53), IL-5 (OR 1.46), and IFN-γ (OR 1.46) were significantly associated with CHD risk.
- Tumor necrosis factor-alpha (TNF-α), IL-6 receptor (IL-6R), and CRP were not significantly associated with CHD. IL-5 and IL-6 remained significant after further adjustment for other cytokines.
Conclusions:
- Interleukin-6 (IL-6) is confirmed as a strongly associated cytokine with coronary heart disease (CHD) risk.
- Novel and independent associations of Interleukin-5 (IL-5) with CHD risk were identified, suggesting its potential importance.
- Further research with larger cytokine panels is recommended to elucidate the role of IL-5 in CHD pathogenesis.
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.
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