Pericardial Fat and CVD

JACC: CARDIOVASCULAR IMAGING

VOL.

ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

-, NO. -, 2017

ISSN 1936-878X/$36.00

PUBLISHED BY ELSEVIER

http://dx.doi.org/10.1016/j.jcmg.2016.11.018

EDITORIAL COMMENT

Pericardial Fat and CVD Is All Fat Created Equally?* Carl J. Lavie, MD,a Ahmet Afs¸in Oktay, MD,a Ambarish Pandey, MDb

A

diposity and its regional distribution play a

The significant association between PAT volume

significant role in the development of cardio-

and CVD usually, but not always, persists when other

vascular disease (CVD). Although it was once

traditional CVD risk factors and variables of visceral

considered as a nonspecific component of visceral ad-

adiposity are considered. Several mechanisms un-

ipose tissue (VAT) or an insignificant incidental imag-

derlie the direct pathophysiological link between

ing finding, adiposity surrounding the heart is now

increased PAT and alterations in cardiac structure and

recognized as an independent, quantifiable risk factor

function and subsequent CVD risk, including fatty

for CVD morbidity and mortality. Because of lack of a standard taxonomy, there exist

infiltration of the myocardium, increased fibrosis, endothelial dysfunction, and the paracrine and

a significant heterogeneity and inconsistency in the

proinflammatory effects of adipokines secreted from

terminology used to define the VAT depots around

pericardial fat and oxidative stress induced by reac-

the heart. In general, epicardial adipose tissue (EAT)

tive oxygen species released from adipocytes (1,2).

is defined as the adipose tissue between the

In this issue of the iJACC, the seminal paper

myocardium and visceral pericardium, and para-

authored by Shah et al. (3) explores the relationship of

cardial fat is defined as the adipose tissue surround-

PAT with alterations in cardiac structure and function

ing the parietal pericardium. Pericardial adipose

and CVD using the data from MESA (Multi-Ethnic

tissue (PAT) often refers to all adipose tissue internal

Study of Atherosclerosis), a multiracial/multi-ethnic

to the parietal pericardium plus paracardial fat (1).

population-based

longitudinal

study

from

the

We use the term PAT to refer to VAT depots sur-

United States. The major findings of this well-

rounding the heart, because this term is more inclu-

designed study are consistent with prior reports

sive. However, it should be noted that EAT is more

with regard to confirming the significant association

relevant from a biological standpoint due to its

between increased PAT, but not hepatic fat, and

embryological origin and anatomic contiguity to

adverse CVD outcomes, even after adjustment for

the myocardium and major coronary arteries, and

other risk factors. In fact, in the regression model, 1-

EAT is believed to carry several physiological func-

standard deviation increment in PAT, was associated

tions, such as lipid storage for myocardial energy,

with a 22% higher risk of hard atherosclerotic CVD

prevention of lipotoxicity (via buffering), thermo-

events (p ¼ 0.0001). Similarly, a prior report from

regulation and mechanical protection of coronary

MESA revealed that the excess risk of coronary heart

arteries, autonomic ganglia, and nervous system of

disease due to each standard deviation increase in

the heart (1,2).

PAT is approximately equivalent to 18 pack-years increment in cigarette smoking (4). To our knowledge, the study by Shah et al. (3) had

*Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology. From the aDepartment of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, Louisiana; and the

one of the highest numbers of participants (n ¼ 4,232) and the longest follow-up duration (median: 12.2 years) compared with other studies investigating the role of PAT in CVD morbidity and mortality. It is novel that this study has demonstrated for the first time a

b

Division of Cardiology, Department of Internal Medicine, University of

significant correlation between increased PAT and all-

Texas Southwestern Medical Center, Dallas, Texas. Dr. Lavie is the

cause mortality, incident heart failure (HF), and

author of The Obesity Paradox. All other authors have reported that they have no relationships relevant to the contents of the paper to disclose.

stroke. A prior report from the Framingham Heart Study showed a significant association between PAT

2

Lavie et al.

JACC: CARDIOVASCULAR IMAGING, VOL.

-, NO. -, 2017 - 2017:-–-

Editorial Comment

and all-cause mortality in the age- and sex-adjusted

subcutaneous adipose tissue, which could be car-

model; however, the association became nonsignifi-

dioprotective from a metabolic standpoint. Certainly,

cant in the multivariable model, which included

many studies from the Dallas Heart Study have

several additional CVD risk factors as covariates (5).

demonstrated the importance of VAT as a risk factor

Shah et al. (3) demonstrated that PAT results in

for CVD (10–12) and cardiac structure and function

favorable risk reclassification of all outcomes even

(13). Further studies are needed to determine if PAT is

when other clinical parameters and Coronary Artery

associated with CVD independent of other VAT

Calcium Score are taken into account. Similar findings

depots.

were reported from Heinz Nixdorf Recall Study, a

Previous studies have demonstrated an inverse

prospective, population-based cohort study con-

association of PAT and cardiorespiratory fitness (CRF)

ducted in Germany, which demonstrated that PAT

(14). It is plausible that PAT may influence CVD and

volume predicted coronary heart disease events even

HF risk through limiting the favorable remodeling

after adjustment of CVD risk factors and Coronary

(more eccentric) in response to higher CRF. We have

Artery Calcium Score (6). These findings point to the

also previously demonstrated that CRF is a major

fact that PAT is associated with not only presence of

predictor of HF and other CVD, and associated with

calcified coronary plaques but also noncalcified cor-

measures of cardiac structure and function (15–20),

onary plaques and high-risk coronary artery lesion

which is a major determinant of CVD prognosis.

morphology (2).

Therefore, it would be interesting to know if CRF may

The study by Shah et al. (3) has several additional

mediate the observed relationship between PAT and

strengths (1). The study population was multiracial/

CVD risk and if interventions aimed at improving CRF

multi-ethnic, making it more applicable to the gen-

can alter this relationship.

eral population (2). To our knowledge, MESA is the

In summary, the current report from MESA (3)

only major cohort study that used multimodality im-

offers important insights into the emerging role of

aging, including computed tomography and cardiac

PAT in the development and prognosis of CVD. The

magnetic resonance imaging for the quantification of

study also reminds us about the knowledge gaps in

PAT, the latter usually considered as the “gold stan-

this field, the most basic of which are standardized

dard” imaging modality for fat tissue. Additionally,

definitions, quantification algorithms, and upper

cardiac magnetic resonance imaging is the only im-

limits of normality for PAT. In terms of future di-

aging modality validated for quantification of PAT

rections, it would also be interesting to know if

ex vivo, and it is considered to have better image

intervention aimed at reducing adiposity, such as

resolution and accuracy compared with computed

intentional weight loss with or without exercise

tomography (2,7). It is also a strength that the left

training, may modify PAT amount and its association

ventricular mass and geometry was assessed with

with cardiac structure and function (21). Addition-

cardiac magnetic resonance imaging, which could also

ally, future research could assess the role of PAT

be superior to echocardiography in this regard (8).

in the prognosis of patients with established CVD

A common limitation for the studies on PAT is the difficulty of differentiating true EAT, the pathophy-

and if it impacts the obesity paradox in HF and other CVD (22,23).

siologically more relevant part, from the rest of the PAT. The study by Shah et al. (3) did not quantify and

ADDRESS FOR CORRESPONDENCE: Dr. Carl J. Lavie,

report the volume of EAT rather than PAT. A major

Department

limitation is that their study did not include the

Ochsner

quantity of other VAT depots as a covariate, which

Clinical School-the UQ School of Medicine, 1516 Jef-

was shown to alter the impact of PAT on CVD in

ferson Hwy., New Orleans, Louisiana 70121. E-mail:

prior reports (9), nor did it assess and quantify

[email protected].

of

Heart

Cardiovascular and

Vascular

Diseases,

Institute,

John

Ochsner

REFERENCES 1. Wong CX, Ganesan AN, Selvanayagam JB.

3. Shah RV, Anderson A, Ding J, et al. Pericar-

heart

Epicardial fat and atrial fibrillation: current evidence, potential mechanisms, clinical implications, and future directions. Eur Heart J 2016:1–11.

dial, but not hepatic, fat by computed tomography is associated with cardiovascular outcomes and structure: the Multi-Ethnic Study of Atherosclerosis (MESA). J Am Coll Cardiol Img 2016;10:XXX–XXX.

Atherosclerosis (MESA) 1–3. Am J Clin Nutr 2009;90:499–504.

2. Talman AH, Psaltis PJ, Cameron JD, Meredith IT, Seneviratne SK, Wong DTL. Epicardial adipose tissue: far more than a fat depot. Cardiovasc Diagn Ther 2014;4:416–29.

4. Ding J, Hsu F-C, Harris TB, et al. The association of pericardial fat with incident coronary

disease:

the

Multi-Ethnic

Study

of

5. Britton KA, Massaro JM, Murabito JM, Kreger BE, Hoffmann U, Fox CS. Body fat distribution, incident cardiovascular disease, cancer, and all-cause mortality. J Am Coll Cardiol 2013;62: 921–5.

JACC: CARDIOVASCULAR IMAGING, VOL.

-, NO. -, 2017

Lavie et al.

- 2017:-–-

6. Mahabadi AA, Berg MH, Lehmann N, et al. Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf recall study. J Am Coll Cardiol 2013;61:1388–95. 7. Nelson AJ, Worthley MI, Psaltis PJ, et al. Validation of cardiovascular magnetic resonance assessment of pericardial adipose tissue volume. J Cardiovasc Magn Reson 2009;11:15. 8. Oktay AA, Lavie CJ, Milani RV, et al. Current perspectives on left ventricular geometry in systemic hypertension. Prog Cardiovasc Dis 2016;59: 235–46. 9. Fox CS, Gona P, Hoffmann U, et al. Pericardial fat, intrathoracic fat, and measures of left ventricular structure and function. Circulation 2009; 119:1586–91. 10. Chandra A, Neeland IJ, Berry JD, et al. The relationship of body mass and fat distribution with incident hypertension: Observations from the dallas heart study. J Am Coll Cardiol 2014;64: 997–1002. 11. Neeland IJ, Turer AT, Ayers CR, et al. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA 2012; 308:1150–9.

Editorial Comment

12. Neeland IJ, Turer AT, Ayers CR, et al. Body fat distribution and incident cardiovascular disease in obese adults. J Am Coll Cardiol 2015;65:2150–1. 13. Neeland IJ, Gupta S, Ayers CR, et al. Relation of regional fat distribution to left ventricular structure and function. Circ Cardiovasc Imaging 2013;6: 800–7. 14. Kim MK, Tanaka K, Kim MJ, et al. Epicardial fat tissue: Relationship with cardiorespiratory fitness in men. Med Sci Sports Exerc 2010;42:463–9. 15. Lavie CJ, Arena R, Swift DL, et al. Exercise and the cardiovascular system: Clinical science and cardiovascular outcomes. Circ Res 2015;117: 207–19.

of stroke: The Cooper Center Longitudinal Study. Stroke 2016;47:1720–6. 19. Brinker SK, Pandey A, Ayers CR, et al. Association of cardiorespiratory fitness with left ventricular remodeling and diastolic function: The Cooper Center Longitudinal Study. J Am Coll Cardiol HF 2014;2:238–46. 20. Lavie CJ, Ventura HO, Milani RV, Arena R. Critical impact of fitness in the prevention and treatment of heart failure. Am Heart J 2015;169: 194–6. 21. Pandey A, Berry JD, Lavie CJ. Cardiometabolic disease leading to heart failure: better fat and fit than lean and lazy. Curr Heart Fail Rep 2015;12: 302–8.

16. Berry JD, Pandey A, Gao A, et al. Physical fitness and risk for heart failure and coronary artery disease. Circ Hear Fail 2013;6:627–34.

22. Lavie CJ, Sharma A, Alpert MA, et al. Update on obesity and obesity paradox in heart failure.

17. Pandey A, Patel M, Gao A, et al. Changes in mid-life fitness predicts heart failure risk at a later

23. Lavie CJ, De Schutter A, Parto P, et al. Obesity

age independent of interval development of cardiac and noncardiac risk factors: The Cooper Center Longitudinal Study. Am Heart J 2015;169: 290–7.e1. 18. Pandey A, Patel MR, Willis B, et al. Association between midlife cardiorespiratory fitness and risk

Prog Cardiovasc Dis 2016;58:393–400.

and prevalence of cardiovascular diseases and prognosis-the obesity paradox updated. Prog Cardiovasc Dis 2016;58:537–47.

KEY WORDS adiposity, cardiac MRI, metabolic syndrome, obesity

3