Imbalance Between Interleukin-1β and Interleukin-1 Receptor Antagonist in Epicardial Adipose Tissue Is Associated With Non ST-Segment Elevation Acute Coronary Syndrome

Abstract Background ST segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). We analyzed the effect of recombinant interleukin-1 receptor antagonist (anakinra) 100 mg subcutaneous injection given once or twice daily for 14 days on the occurrence of HF in a pooled analysis of 3 clinical trials. Methods Enrollment criteria and study procedures were the same across the three studies. High-sensitivity C-reactive protein (CRP) was measured at baseline, 72 hours, and 14 days to construct an area under the curve (AUC0–14). Clinical events up to 1 year were adjudicated by an independent committee blinded to treatment allocation. Data for anakinra once daily and anakinra twice daily were pooled into a single anakinra group. CRP data are presented as median and interquartile range to allow for deviation from Gaussian distribution and non-parametric tests were used to evaluate differences between groups. Kaplan-Meier survival analyses were conducted and the intervention groups were compared using a log-rank test. Results Between 2008 and 2017, 139 patients with STEMI were enrolled. 84 patients were randomized to anakinra and 55 patients were randomized to placebo. Anakinra significantly reduced the CRP AUC0–14 (76 [42–147] vs 222 [117–339] mg*day/L; P<0.001), the composite of death or HF hospitalization (Chi2=7.167; P=0.007), and the composite of death or new onset HF (Chi2=9.43; P=0.002) compared with placebo. Treatment with anakinra had no effect on ischemic events (composite of death, myocardial infarction, and unstable angina; (Chi2=0.574; P=0.45) or the composite of death, myocardial infarction and cerebrovascular accident (Chi2=0.065; P=0.80). Patients receiving anakinra had increased injection site reactions (20.2% vs 3.6%; P=0.005) but no change in infections (14.3% vs 9.1%, P=0.435) versus placebo. Conclusions Treatment with anakinra for 14 days following STEMI blunts the inflammatory response and appears to reduce the occurrence of HF events at 1 year. These results support the hypothesis that early and targeted modification of the inflammatory response in STEMI may be a viable strategy to improve patient outcomes. Adjudicated events at 1 year Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Heart Lung and Blood Institute (USA), American Heart Association (USA)

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Pre‐percutaneous Coronary Intervention Pericoronary Adipose Tissue Attenuation Evaluated by Computed Tomography Predicts Global Coronary Flow Reserve After Urgent Revascularization in Patients With Non–ST‐Segment–Elevation Acute Coronary Syndrome

Journal of the American Heart Association ◽

10.1161/jaha.120.016504 ◽

2020 ◽

Vol 9 (17) ◽

Author(s):

Yoshihisa Kanaji ◽

Hidenori Hirano ◽

Tomoyo Sugiyama ◽

Masahiro Hoshino ◽

Tomoki Horie ◽

...

Keyword(s):

Computed Tomography ◽

Percutaneous Coronary Intervention ◽

Acute Coronary Syndrome ◽

Adipose Tissue ◽

Coronary Intervention ◽

St Segment Elevation ◽

Coronary Syndrome ◽

St Segment ◽

Percutaneous Coronary ◽

Elevation Acute Coronary Syndrome

Background Impaired global coronary flow reserve (g‐CFR) is related to worse outcomes. Inflammation has been postulated to play a role in atherosclerosis. This study aimed to evaluate the relationship between pre‐procedural pericoronary adipose tissue inflammation and g‐CFR after the urgent percutaneous coronary intervention in patients with first non–ST‐segment–elevation acute coronary syndrome. Methods and Results Phase‐contrast cine‐magnetic resonance imaging was performed to obtain g‐CFR by quantifying coronary sinus flow at 1 month after percutaneous coronary intervention in a total of 116 first non–ST‐segment–elevation acute coronary syndrome patients who underwent pre‐percutaneous coronary intervention computed tomography angiography. On proximal 40‐mm segments of 3 major coronary vessels on computed tomography angiography, pericoronary adipose tissue attenuation was assessed by the crude analysis of mean computed tomography attenuation value. The patients were divided into 2 groups with and without impaired g‐CFR divided by the g‐CFR value of 1.8. There were significant differences in age, culprit lesion location, N‐terminal pro‐B‐type natriuretic peptide levels, high‐sensitivity C‐reactive protein (hs‐CRP) levels, mean pericoronary adipose tissue attenuation between patients with impaired g‐CFR and those without (g‐CFR, 1.47 [1.16, 1.68] versus 2.66 [2.22, 3.28]; P <0.001). Multivariable logistic regression analysis revealed that age (odds ratio [OR], 1.060; 95% CI, 1.012–1.111, P =0.015) and mean pericoronary adipose tissue attenuation (OR, 1.108; 95% CI, 1.026–1.197, P =0.009) were independent predictors of impaired g‐CFR (g‐CFR <1.8). Conclusions Mean pericoronary adipose tissue attenuation, a marker of perivascular inflammation, obtained by computed tomography angiography performed before urgent percutaneous coronary intervention, but not hs‐CRP, a marker of systemic inflammation was significantly associated with g‐CFR at 1‐month after revascularization. Our results may suggest the pathophysiological mechanisms linking perivascular inflammation and g‐CFR in patients with non–ST‐segment–elevation acute coronary syndrome.

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