Abstract
Introduction: Increased systemic inflammation is one of the key triggers in the initiation and progression of atherosclerosis. We investigated interleukin 18 binding protein (IL-18BP), a new inflammatory marker of the IL-1 cytokine family, on its predictive value for cardiovascular disease in subjects under investigation for stenotic atherosclerotic disease. Methods: We performed a prospective, single-center, investigator-initiated, observational cohort study in 927 subjects who underwent coronary and/or peripheral angiography. The cohort was randomly split into a discovery (n=627) and a validation set (n =267). Predictive value for incident cardiovascular events (composite of cardiovascular death, myocardial infarction and stroke), cardiovascular mortality and all-cause mortality was investigated using Cox proportional hazard models, including concordance index analyses and assessment of net reclassification for 10-year cardiovascular risk categories using Weibull modelling. Results: An one standard deviation increase in log-transformed IL-18BP was strongly associated with cardiovascular events (HR 1.96, 95% CI 1.54-2.51), cardiovascular mortality (HR 1.59, 95% CI 1.04-2.44) and all-cause mortality (HR 1.72, 95 CI 1.43-2.07), independent of the traditional cardiovascular risk factors, including body mass index. C-index of a clinical model for prediction of cardiovascular events improved from 0.69 (95% CI to 0.62-0.75) to 0.73 (95% CI 0.67-0.79) with inclusion of IL-18BP in the model; in doing so, a reclassification of 35.9% (p < 0.001) for events was demonstrated. Conclusions: Among a population of patient undergoing coronary angiography, results of IL18-BP measurement improved cardiovascular risk prediction beyond the traditional risk factors. Kaplan-Meier survival curves for CV events during one-year follow up comparing tertiles IL-18BP (discovery set)
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