Interleukin-18 in patients with acute coronary syndromes.

Abstract

BACKGROUND:

We aimed to assess associations between circulating IL-18 concentrations and cardiovascular outcomes in patients with acute coronary syndromes (ACS).

HYPOTHESIS AND METHODS:

Plasma IL-18 concentrations were measured at admission, discharge, 1 month, and 6 months in patients with ACS in the PLATelet inhibition and patient Outcomes (PLATO) trial. Associations with outcomes were evaluated with Cox regression models on the composite of CV death, spontaneous myocardial infarction (sMI), or stroke; and on CV death or sMI separately, including adjustment for clinical risk factors and biomarkers (cTnT-hs, NT-proBNP, cystatin C, CRP-hs, and GDF-15).

RESULTS:

Median IL-18 concentrations at baseline, discharge, 1 month, and 6 months were 237, 283, 305, and 320 ng/L (n = 16 636). Male sex, obesity, diabetes, and plasma levels of cystatin C, GDF-15, and CRP-hs were independently associated with higher IL-18 levels. Higher baseline IL-18 levels were associated with the composite endpoint and with CV death (hazard ratio [HR] 1.05, 95% confidence interval [95% CI] 1.02-1.07 and HR 1.10, 95% CI 1.06-1.14, respectively, per 25% increase of IL-18 levels). Associations remained significant after adjustment for clinical variables but became non-significant after adjustment for all biomarkers (HR 1.01, 95% CI 0.98-1.04 and HR 1.04, 95% CI 1.00-1.08, respectively). There were no associations with sMI.

CONCLUSIONS:

In ACS patients, IL-18 concentrations increased after the acute event and remained increased for 6 months. Baseline IL-18 levels were significantly associated with CV mortality, independent of clinical characteristics and indicators of renal/cardiac dysfunction but this association was attenuated after adjustment for multiple biomarkers.

• Authors: Axel Åkerblom, Stefan K James, Tatevik G Lakic, Richard C Becker, Christopher P Cannon, Philippe G Steg, Anders Himmelmann, Hugo A Katus, Robert F Storey, Lars Wallentin, W Douglas Weaver, Agneta Siegbahn, PLATO Investigators
• Journal: Clinical cardiology (Clin Cardiol) Vol. 42 Issue 12 Pg. 1202-1209 (Dec 2019) ISSN: 1932-8737 [Electronic] United States
• PMID: 31596518 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.

Chemical References

• Biomarkers
• IL18 protein, human
• Interleukin-18
• Platelet Aggregation Inhibitors

Topics

• Acute Coronary Syndrome (blood, drug therapy, mortality)
• Aged
• Biomarkers (blood)
• Female
• Humans
• Interleukin-18 (blood)
• Male
• Middle Aged
• Platelet Aggregation Inhibitors (therapeutic use)
• Survival Rate
• Time Factors