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


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.
Trøseid
Marius
M
Center for Clinical Heart Research, Department of Cardiology, University of Oslo, Oslo, Norway. troseid@hotmail.com
Seljeflot
Ingebjørg
I
Hjerkinn
Elsa M
EM
Arnesen
Harald
H
D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology*; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000150:complications* / Q000503:physiopathology; D008875:Middle Aged
D020382:Interleukin-18