Epicardial,pericardial and total cardiac fat and cardiovascular disease in type 2 diabetic patients with elevated urinary albumin excretion rate

Abstract

Background

We evaluated the association of cardiac adipose tissue including epicardial adipose tissue and pericardial adipose tissue with incident cardiovascular disease and mortality, coronary artery calcium, carotid intima media thickness and inflammatory markers.

Design

A prospective study of 200 patients with type 2 diabetes and elevated urinary albumin excretion rate (UAER).

Methods

Cardiac adipose tissue was measured from baseline echocardiography. The composite endpoint comprised incident cardiovascular disease and all-cause mortality. Coronary artery calcium, carotid intima media thickness and inflammatory markers were measured at baseline. Cardiac adipose tissue was investigated as continuous and binary variable. Analyses were performed unadjusted (model 1), and adjusted for age, sex (model 2), body mass index, low-density lipoprotein cholesterol, smoking, glycated haemoglobin, and systolic blood pressure (model 3).

Results

Patients were followed-up after 6.1 years for non-fatal cardiovascular disease (n = 29) or mortality (n = 23). Cardiac adipose tissue (p = 0.049) and epicardial adipose tissue (p = 0.029) were associated with cardiovascular disease and mortality in model 1. When split by the median, patients with high cardiac adipose tissue had a higher risk of cardiovascular disease and mortality than patients with low cardiac adipose tissue in unadjusted (hazard ratio 1.9, confidence interval: 1.1; 3.4, p = 0.027) and adjusted (hazard ratio 2.0, confidence interval: 1.1; 3.7, p = 0.017) models. Cardiac adipose tissue (p = 0.033) was associated with baseline coronary artery calcium (model 1) and interleukin-8 (models 1–3, all p < 0.039).

Conclusions

In type 2 diabetes patients without coronary artery disease, high cardiac adipose tissue levels were associated with increased risk of incident cardiovascular disease or all-cause mortality even after accounting for traditional cardiovascular disease risk factors. High cardiac adipose tissue amounts were associated with subclinical atherosclerosis (coronary artery calcium) and with the pro-atherogenic inflammatory marker interleukin-8.

Keywords

Type 2 diabetes epicardial fat pericardial fat cardiovascular disease coronary artery calcium

Get full access to this article

View all access options for this article.

References

Cavender

Steg

Smith

et al.

Impact of diabetes mellitus on hospitalization for heart failure, cardiovascular events, and death: Outcomes at 4 years from the Reduction of Atherothrombosis for Continued Health (REACH) registry. Circulation 2015; 132: 923–931.

Yang

F-S

Yun

C-H

T-H

et al.

High pericardial and peri-aortic adipose tissue burden in pre-diabetic and diabetic subjects. BMC Cardiovasc Disord 2013; 13: 98–98.

Chatterjee

Stoll

Denning

et al.

Pro-inflammatory phenotype of perivascular adipocytes: Influence of high fat feeding. Circ Res 2009; 104: 541–549.

Mazurek

Zhang

Zalewski

et al.

Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 2003; 108: 2460–2466.

Zakynthinos

Pappa

. Inflammatory biomarkers in coronary artery disease. J Cardiol 2009; 53: 317–333.

Bos

Shahzad

Walsum

et al.

Epicardial fat volume is related to atherosclerotic calcification in multiple vessel beds. Eur Heart J Cardiovasc Imaging 2015; 16: 1264–1269.

Sengul

Cevik

Ozveren

et al.

Echocardiographic epicardial fat thickness is associated with carotid intima-media thickness in patients with metabolic syndrome. Echocardiography 2011; 28: 853–858.

Ding

Hsu

F-C

Harris

et al.

The association of pericardial fat with incident coronary heart disease: The Multi-Ethnic Study of Atherosclerosis (MESA) 1–3. Am J Clin Nutr 2009; 90: 499–504.

Cheng

Dey

Tamarappoo

et al.

Pericardial fat burden on ECG-Gated noncontrast CT in asymptomatic patients who subsequently experience adverse cardiovascular events. JACC Cardiovasc Imaging 2010; 3: 352–360.

10.

Reinhard

Hansen

Persson

et al.

Elevated NT-proBNP and coronary calcium score in relation to coronary artery disease in asymptomatic type 2 diabetic patients with elevated urinary albumin excretion rate. Nephrol Dial Transplant 2011; 26: 3242–3249.

11.

Iacobellis

Willens

. Echocardiographic epicardial fat: A review of research and clinical applications. J Am Soc Echocardiogr 2009; 22: 1311–1319.

12.

Davidovich

Gastaldelli

Sicari

. Imaging cardiac fat. Eur Heart J Cardiovasc Imaging 2013; 14: 625–630.

13.

Reinhard

Wiinberg

Hansen

et al.

NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: Peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis. Cardiovasc Diabetol 2011; 10: 71–71.

14.

Von Scholten

Reinhard

Hansen

et al.

Markers of inflammation and endothelial dysfunction are associated with incident cardiovascular disease, all-cause mortality, and progression of coronary calcification in type 2 diabetic patients with microalbuminuria. J Diabetes Complications 2016; 30: 248–255.

15.

Iacobellis

Willens

Barbaro

et al.

Threshold values of high-risk echocardiographic epicardial fat thickness. Obesity (Silver Spring) 2008; 16: 887–892.

16.

Sacks

Fain

Bahouth

et al.

Adult epicardial fat exhibits beige features. J Clin Endocrinol Metab 2013; 98: 1448–1455.

17.

Marchington

Mattacks

Pond

. Adipose tissue in the mammalian heart and pericardium; structure, fetal development and biochemical properties. Comp Biochem Physiol 1989; 94: 225–232.

18.

Sacks

Fain

. Human epicardial fat: What is new and what is missing? Clin Exp Pharmacol Physiol 2011; 38: 879–887.

19.

Iacobellis

. Epicardial and pericardial fat: Close, but very different. Obesity 2009; 17: 625–625.

20.

Gerszten

Garcia-Zepeda

Lim

Y-C

et al.

MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature 1999; 398: 718–723.

21.

Iacobellis

Assael

Ribaudo

et al.

Epicardial fat from echocardiography: A new method for visceral adipose tissue prediction. Obes Res 2003; 11: 304–310.

22.

Franssens

Nathoe

Leiner

et al.

Relation between cardiovascular disease risk factors and epicardial adipose tissue density on cardiac computed tomography in patients at high risk of cardiovascular events. Eur J Prev Cardiol 2017; 24: 660–670.

23.

Dutour

. Looking beyond ectopic fat amount: A SMART method to quantify epicardial adipose tissue density. Eur J Prev Cardiol 2017; 24: 657–659.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.06 MB