Prospective study of IL-18 and risk of MI and stroke in men and women aged 60-79 years: a nested case-control study.

Abstract

AIM:

IL-18 is hypothesized to destabilise atherosclerotic plaques, leading to thrombotic events and epidemiologic studies suggest that IL-18 may increase risk of CHD or CVD. We examined prospective associations between levels of serum IL-18 and new CHD and stroke events in older men and women from a general population.

METHODS:

A case-control study was nested within a prospective cohort of men and women aged 60-79 years recruited from general practices in 25 British towns in 1998-2000 and followed-up for 7.5 years for fatal and non-fatal MI and stroke. Baseline IL-18 was measured in stored serum samples of incident cases of MI (n=364) or stroke (n=300) and two controls per case.

RESULTS:

Geometric mean IL-18 levels were higher among the 364 MI cases than the 706 controls; 417.84 pg/mL (IQR 316.25, 537.44) compared to 386.90 pg/mL (IQR 296.54, 482.33), p(difference)=0.002. IL-18 was positively associated with adverse lipid and inflammatory profiles. Men and women in the top third of baseline IL-18 levels had an age and sex-adjusted odds ratio (OR) for MI of 1.31 (95%CI 0.92, 1.85) compared with those in the lowest third; this attenuated to 1.05 (95%CI 0.72, 1.53) after additional adjustment for established vascular and inflammatory risk factors. Each doubling of IL-18 level was associated with an increased OR for MI 1.34 (95%CI 1.04, 1.72), which was attenuated on adjustment for established vascular and inflammatory risk factors; 1.09 (95%CI 0.83, 1.44). Geometric mean IL-18 levels did not differ between stroke cases and controls. The OR for stroke associated with the highest compared to the lowest tertile of IL-18 was 1.24 (95%CI 0.84, 1.84). Results for MI and stroke did not differ by presence of pre-existing CVD, gender or age.

CONCLUSIONS:

Circulating IL-18 levels were strongly associated with a range of established and novel risk factors but were not independently associated with risk of MI or stroke in our study.

• Authors: Barbara J Jefferis, Peter H Whincup, Paul Welsh, S Goya Wannamethee, Ann Rumley, Shah Ebrahim, Debbie A Lawlor, Gordon D O Lowe
• Journal: Cytokine (Cytokine) Vol. 61 Issue 2 Pg. 513-20 (Feb 2013) ISSN: 1096-0023 [Electronic] England
• PMID: 23207179 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Interleukin-18

Topics

• Aged
• Case-Control Studies
• Female
• Humans
• Interleukin-18 (blood)
• Male
• Middle Aged
• Myocardial Infarction (blood, complications)
• Odds Ratio
• Prospective Studies
• Regression Analysis
• Risk Factors
• Stroke (blood, complications)