Interleukin-18 is a strong predictor of cardiovascular events in elderly men with the metabolic syndrome. Synergistic effect of inflammation and hyperglycemia

Abstract

Objective. To investigate the role of inflammatory markers as potential predictors of cardiovascular events in subjects with and without the metabolic syndrome (MetS).

Research design and Methods. This was a post hoc analysis from the Diet and Omega-3 Intervention Trial (DOIT), comprising 563 elderly men with (n=221) and without (n=342) MetS. Circulating inflammatory markers were measured.

Results. During 3 years, 68 cardiovascular events were recorded. In the total population, C-reactive protein (CRP) (p<0.001), interleukin-18 (IL-18) (p=0.008) and IL-6 (p=0.003) were elevated in subjects with events. In subjects with MetS, IL-18 was the strongest predictor (adjusted OR 2.9 [1.1, 7.8]). In subjects without MetS, only CRP appeared an independent predictor (adjusted OR 3.3 [1.5, 7.3]). There was a significant interaction between fasting glucose and IL-18 (p=0.008) and IL-6 (p=0.024), but not CRP. Elevated fasting glucose (>6.2 mmol/L) markedly increased the predictive power of inflammatory markers (IL-18: adjusted OR 5.5 [1.4, 21.1], IL-6: adjusted OR 3.5 [1.0, 11.8], CRP: adjusted OR 3.5 [1.0, 11.9]). For IL-18, there was a stepwise increase in event rate by quartiles of fasting glucose.

Conclusions. IL-18 was an independent predictor of cardiovascular events in subjects with Mets, and even more in the presence of elevated fasting glucose. Our findings suggest a mutually potentiating effect of hyperglycemia and inflammation in cardiovascular risk prediction.