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. 2009 Mar;32(3):486-92.
doi: 10.2337/dc08-1710. Epub 2008 Dec 17.

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

Marius Trøseid  1 , Ingebjørg Seljeflot, Elsa M Hjerkinn, Harald Arnesen
Affiliations

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

Marius Trøseid et al. Diabetes Care. 2009 Mar.

Abstract

Objective: The aim of this study was to investigate the role of inflammatory markers as potential predictors of cardiovascular events in subjects with and without the metabolic syndrome.

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) metabolic syndrome. 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 metabolic syndrome, IL-18 was the strongest predictor (adjusted odds ratio 2.9 [95% CI 1.1-7.8]). In subjects without metabolic syndrome, only CRP seemed to be an independent predictor (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: 5.5 [1.4-21.1], IL-6: 3.5 [1.0-11.8], and CRP: 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 metabolic syndrome and even more so in the presence of elevated fasting glucose. Our findings suggest a mutually potentiating effect of hyperglycemia and inflammation in cardiovascular risk prediction.

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Figures

Figure 1
Figure 1
Number of cardiovascular events by quartiles of IL-18, IL-6, and CRP in subjects with (▪, n = 221) and without (□, n = 342) the metabolic syndrome. P values refer to trend analysis. MetS+, with metabolic syndrome; MetS−, without metabolic syndrome; n.s., not significant.
Figure 2
Figure 2
Number of cardiovascular events by quartiles of IL-18, IL-6, and CRP in subjects with (▪, n = 139) and without (□, n = 424) elevated fasting glucose (>6.2 mmol/l). P values refer to trend analysis. n.s., not significant.
See this image and copyright information in PMC

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