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Peak Caspase‐1 p20 Levels During Acute Myocardial Infarction Correlate with Pre‐Existing Hypertension, Age and Post‐Infarction Cardiac Dysfunction
Author(s) -
Greenwood Matthew,
Morgan Andrew,
Na Sam,
Gold Courtney,
Liang Brannen,
Shapior Linda,
Liang Bruce
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb558
Subject(s) - medicine , myocardial infarction , cardiology , inflammasome , inflammation , diabetes mellitus , caspase 1 , cardiac function curve , infarction , heart failure , endocrinology
Background Increased inflammation contributes to the development of myocardial infarction (MI) and adversely impacts infarct healing. Caspase‐1 is an end effector of inflammasome activation and is an important mediator of systemic inflammation. Caspase‐1 is cleaved to produce a 20 kDa (p20) peptide upon activation. Activated Caspase‐1 activates downstream cytokines IL‐1β and IL‐18. Previous work demonstrated that the p20 is elevated in patient serum during and after acute MI. Objective The aim of this study was to further elucidate the relationship of Caspase‐1 p20 and risk factors for MI. Between 12/10/2007 and 3/28/2016, 170 eligible patients with acute MI were enrolled that had complete information on p20 levels. Method Using a solid phase enzyme‐linked immunosorbent assay, the 20 kDa peptide was detected in serum during ST elevation (STEMI) and non‐ST elevation (NSTEMI) MI as well as after MI. Cardiac function post‐MI was evaluated via standard‐of‐care echocardiography. Results There is a positive correlation between age and peak p20 level during acute MI (P=0.01, linear regression, n=170). In STEMI but not in NSTEMI subjects, pre‐existing hypertension (HTN) was associated with a 50.3% higher average circulating peak p20 level during acute MI than those without HTN (P=0.0056, Wilcoxon, n=31 for both groups‐those with HTN and without HTN), suggesting a greater degree of inflammasome activation in HTN patients during STEMI. In these STEMI subjects, the existence of diabetes mellitus or smoking was not associated with a higher peak p20 level during acute MI. There is a trend for all acute MI patients to have a reduced post‐MI cardiac function as quantified by LV fractional shortening in echocardiography (P=0.05, Spearman correlation, r=−0.35, n=31). Conclusion Older subjects had more elevated peak p20 levels during acute MI, consistent with the concept of a larger inflammasome response to MI as age increases. Inflammasome activation is more pronounced in HTN patients during STEMI, implying a greater degree of inflammatory response in the presence of HTN. A greater extent of inflammasome activation during STEMI may be associated with a worse LV function subsequently. Support or Funding Information The study is supported by the Pat and Jim Calhoun Cardiology Endowment Fund.