Does interleukin-18 or tumour necrosis factor-α have an independent association with the risk of coronary heart disease? Results from a prospective study in New Zealand

Background: The pro-inflammatory cytokines, interleukin (IL)-18 and tumour necrosis factor-α (TNFα) may play a role in coronary heart disease (CHD). We aimed to extend data on their relationships to the risk of CHD in generally healthy populations. Methods: During 5.5 years follow-up in the Fletcher Challenge general population cohort there were 256 CHD cases, and 615 controls were matched for age and sex. Baseline plasma levels of IL-18 and TNFα were related to CHD risk in available samples (77%). Results: Plasma levels of IL-18 (11% increase in mean, p = 0.01) and TNFα (10% increase in mean p = 0.024) were significantly elevated in CHD cases versus controls. In univariable models IL-18 was associated with CHD risk (odds ratio [OR] upper third to lower third, 1.63; 95% CI 1.08, 2.46), but TNFα was not (OR 1.33; 95% CI 0.87, 2.02).After adjusting for major CHD risk factors and CRP, the association of IL-18 with CHD risk was attenuated (OR 1.69; 95% CI 0.94, 3.03). Conclusions: IL-18, but not TNFα, had a non-negligible association with CHD risk, although the association of IL-18 with risk was weak after full adjustment. These cytokines may play a role in CHD pathology, but may not be robust risk biomarkers.