Pericardial, But Not Hepatic, Fat by CT Is Associated With CV Outcomes and Structure: The Multi-Ethnic Study of Atherosclerosis

Abstract

Objectives: The study sought to determine the associations between local (pericardial) fat and incident cardiovascular disease (CVD) events and cardiac remodeling independent of markers of overall adiposity.

Background: The impact of pericardial fat-a local fat depot encasing the heart-on myocardial function and long-term CV prognosis independent of systemic consequences of adiposity or hepatic fat is an area of active debate.

Methods: We studied 4,234 participants enrolled in the MESA (Multi-Ethnic Study of Atherosclerosis) study with concomitant cardiac magnetic resonance imaging and computed tomography (CT) measurements for pericardial fat volume and hepatic attenuation (a measure of liver fat). Poisson and Cox regression were used to estimate the annualized risk of incident hard atherosclerotic CVD (ASCVD), all-cause death, heart failure, all-cause CVD, hard coronary heart disease, and stroke as a function of pericardial and hepatic fat. Generalized additive models were used to assess the association between cardiac magnetic resonance indices of left ventricular (LV) structure and function and pericardial fat. Models were adjusted for relevant clinical, demographic, and cardiometabolic covariates.

Results: MESA study participants with higher pericardial and hepatic fat were more likely to be older, were more frequently men, and had a higher prevalence of cardiometabolic risk factors (including dysglycemia, dyslipidemia, hypertension), as well as adiposity-associated inflammation. Over a median 12.2-year follow-up (interquartile range: 11.6 to 12.8 years), pericardial fat was associated with a higher rate of incident hard ASCVD (standardized hazard ratio: 1.22; 95% confidence interval: 1.10 to 1.35; p = 0.0001). Hepatic fat by CT was not significantly associated with hard ASCVD (standardized hazard ratio: 0.96; 95% confidence interval: 0.86 to 1.08; p = 0.52). Higher pericardial fat was associated with greater indexed LV mass (37.8 g/m^2.7 vs. 33.9 g/m^2.7, highest quartile vs. lowest quartile; p < 0.01), LV mass-to-volume ratio (1.2 vs. 1.1, highest quartile vs. lowest quartile; p < 0.01). In adjusted models, a higher pericardial fat volume was associated with greater LV mass (p < 0.0001) and concentricity (p < 0.0001).

Conclusions: Pericardial fat is associated with poorer CVD prognosis and LV remodeling, independent of insulin resistance, inflammation, and CT measures of hepatic fat.

Keywords: cardiac magnetic resonance imaging; hepatic fat; obesity; pericardial fat; remodeling.

Figure 1. Associations between pericardial and hepatic fat and cardiovascular events

Event rate regression for association between pericardial (panel A) or hepatic (panel B) fat and annualized rates of all-cause death (red), hard cardiovascular (CVD) events (cyan), hard coronary heart disease (CHD) events (green) and heart failure (purple). Fully adjusted p-values are presented.

Figure 2. Relationships between pericardial fat and left ventricular geometry and function

Associations for LV mass (panel A), LV mass-to-volume ratio (panel C) and ejection fraction were curvilinear (panel D), with significant quadratic terms (Table 4). There was no significant relationship noted between pericardial fat and LV volume (panel B). Graphs and p-values are derived from fully adjusted generalized additive spline models with grey bands represent 95% confidence intervals.

Figure 3. Modification of relationships between pericardial fat and left ventricular geometry and function by sex, race and diabetes

Plots in top row (A-D) evaluate effect modification by sex (male=red, female=cyan) while the middle row (E-H) evaluate effect modification by race (white=red, Chinese=green, black=blue, Hispanic=purple) and the lower row (I-L) evaluate effect modification by diabetes (non-diabetic=red, diabetic=cyan).