Epicardial adipose tissue characteristics, obesity and clinical outcomes in COVID-19: A post-hoc analysis of a prospective cohort study

Abstract

Background and aims: Obesity-related cardiometabolic risk factors associate with COVID-19 severity and outcomes. Epicardial adipose tissue (EAT) is associated with cardiometabolic disturbances, is a source of proinflammatory cytokines and a marker of visceral adiposity. We investigated the relation between EAT characteristics and outcomes in COVID-19 patients.

Methods and results: This post-hoc analysis of a large prospective investigation included all adult patients (≥18 years) admitted to San Raffaele University Hospital in Milan, Italy, from February 25th to April 19th, 2020 with confirmed SARS-CoV-2 infection who underwent a chest computed tomography (CT) scan for COVID-19 pneumonia and had anthropometric data available for analyses. EAT volume and attenuation (EAT-At, a marker of EAT inflammation) were measured on CT scan. Primary outcome was critical illness, defined as admission to intensive care unit (ICU), invasive ventilation or death. Cox regression and regression tree analyses were used to assess the relationship between clinical variables, EAT characteristics and critical illness. One-hundred and ninety-two patients were included (median [25th-75th percentile] age 60 years [53-70], 76% men). Co-morbidities included overweight/obesity (70%), arterial hypertension (40%), and diabetes (16%). At multivariable Cox regression analysis, EAT-At (HR 1.12 [1.04-1.21]) independently predicted critical illness, while increasing PaO₂/FiO₂ was protective (HR 0.996 [95% CI 0.993; 1.00]). CRP, plasma glucose on admission, EAT-At and PaO₂/FiO₂ identified five risk groups that significantly differed with respect to time to death or admission to ICU (log-rank p < 0.0001).

Conclusion: Increased EAT attenuation, a marker of EAT inflammation, but not obesity or EAT volume, predicts critical COVID-19.

Trial registration: NCT04318366.

Keywords: COVID-19; Cardiac injury; Epicardial adipose tissue; Inflammation; SARS-CoV-2; Visceral fat.

Graphical abstract

Figure 1

Time to death or ICU admission according to BMI category (NW, normal weight; OW, overweight; OB, obesity).

Figure 2

The structured risk tree for prediction of critical illness developed by regression tree analysis using age, sex, BMI, EAT attenuation (EAT-At), PaO₂/FiO₂ (data available for 177 patients), plasma glucose (PG), neutrophil and lymphocyte counts, LDH, eGFR and CRP on admission, history of hypertension, diabetes mellitus, dyslipidaemia, ischaemic heart disease, and malignancy. Risk Groups identified by the regression tree analysis are as follows: Group 1 (lowest risk, 5% probability of critical illness): CRP < 217 mg/dL and PG < 128 mg/dL and EAT-At < −96.3 HU; Group 2 (18% probability of critical illness): CRP < 217 mg/dL and PG < 128 mg/dL and EAT-At ≥ −96.3 HU and PaO₂/FiO₂ ≥ 260; Group 3 (46% probability of critical illness): CRP < 217 mg/dL and PG ≥ 128 mg/dL; Group 4 (48% probability of critical illness): CRP < 217 mg/dL and PG < 128 mg/dL and EAT-At ≥ −96.3 HU and PaO₂/FiO₂ < 260; Group 5 (highest risk, 87% probability of critical illness): CRP ≥ 217 mg/dL.

Figure 3

Colorimetric map of epicardial fat attenuation of (A) a 63-year old man with low EAT attenuation (<96.3 HU) and (B) a 71-year old man with high EAT attenuation (>96.3 HU).

Figure 4

Body mass index (A) and epicardial adipose tissue (EAT) volume (B) across the five risk groups identified by classification and regression tree analysis.

Figure 5

Event-free survival across the five risk groups identified by classification and regression tree analysis.

figs1

Supplemental Figure 1. Study flow-chart.

figs2

Supplemental Figure 2. Receiver operating characteristic (ROC) curve for the model obtained by classification and regresstion tree (CART) analysis.

figs3

Supplemental Figure 3. Proportion of patients with myocardial injury, as defined by high-sensitivity troponin T levels above the upper limit of normal (14 ng/L) across risk groups. ∗ p<0.001 vs. Group 5; ^# p<0.05 vs. Group 5; † p<0.05 vs. Group 3; ‡ p<0.05 vs. Group 4.

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Supplemental Figure 4. Epicardial adipose tissue attenuation (EAT-At) across risk groups. More negative values indicate less inflamed EAT. ∗ p<0.001 vs. Group 1; ^# p<0.05 vs. Group 3.

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Supplemental Figure 5. Correlation between epicardial adipose tissue attenuation (EAT-At) and high-sensitivity troponin T (Spearman’s rho 0.19, p=0.049). More negative values indicate less inflamed EAT.