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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

VOL. 68, NO. 14, 2016

PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN COLLEGE OF

ISSN 0735-1097/$36.00

CARDIOLOGY FOUNDATION

http://dx.doi.org/10.1016/j.jacc.2016.06.067

Association of Changes in Abdominal


Fat Quantity and Quality With Incident
Cardiovascular Disease Risk Factors
Jane J. Lee, PHD,a Alison Pedley, PHD,a Udo Hoffmann, MD, MPH,b Joseph M. Massaro, PHD,c
Caroline S. Fox, MD, MPHa,d

ABSTRACT
BACKGROUND Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) are associated with adverse
cardiometabolic risk proles.
OBJECTIVES This study explored the degree to which changes in abdominal fat quantity and quality are associated
with changes in cardiovascular disease (CVD) risk factors.
METHODS Study participants (n 1,106; 44.1% women; mean baseline age 45.1 years) were drawn from the
Framingham Heart Study Third Generation cohort who participated in the computed tomography (CT) substudy Exams 1
and 2. Participants were followed for 6.1 years on average. Abdominal adipose tissue volume in cm3 and attenuation in
Hounseld units (HU) were determined by CT-acquired abdominal scans.
RESULTS The mean fat volume change was an increase of 602 cm3 for SAT and an increase of 703 cm3 for VAT; the
mean fat attenuation change was a decrease of 5.5 HU for SAT and an increase of 0.07 HU for VAT. An increase in fat
volume and decrease in fat attenuation were associated with adverse changes in CVD risk factors. An additional 500 cm3
increase in fat volume was associated with incident hypertension (odds ratio [OR]: 1.21 for SAT; OR: 1.30 for VAT),
hypertriglyceridemia (OR: 1.15 for SAT; OR: 1.56 for VAT), and metabolic syndrome (OR: 1.43 for SAT; OR: 1.82 for VAT; all
p < 0.05). Similar trends were observed for each additional 5 HU decrease in abdominal adipose tissue attenuation. Most
associations remained signicant even after further accounting for body mass index change, waist circumference change,
or respective abdominal adipose tissue volumes.
CONCLUSIONS Increasing accumulation of fat quantity and decreasing fat attenuation are associated with worsening
of CVD risk factors beyond the associations with generalized adiposity, central adiposity, or respective adipose
tissue volumes. (J Am Coll Cardiol 2016;68:150921) Published by Elsevier on behalf of the American College of
Cardiology Foundation.

C
Listen to this manuscripts

ardiovascular disease (CVD), one of the lead-

closely associated with a cluster of cardiometabolic

ing causes of morbidity and mortality in the

abnormalities (3). Computed tomography (CT) en-

United States (1), substantially increases the

ables the indirect assessment of both adipose tissue

economic burden among individuals, families, and

quantity in cubic centimeters and quality in Houns-

the health care system (2). Abdominal subcutaneous

eld units (HU) via CT threshold attenuation (4).

adipose tissue (SAT) and visceral adipose tissue

Numerous studies have shown that greater accumula-

(VAT) are 2 major fat compartments that are

tion of abdominal SAT and VAT is associated with a

From the aNational Heart, Lung, and Blood Institutes Division of Intramural Research, the Framingham Heart Study, and the

audio summary by

Population Studies Branch, Framingham, Massachusetts; bDepartment of Radiology, Massachusetts General Hospital, Boston,

JACC Editor-in-Chief

Massachusetts; cDepartment of Biostatistics, Boston University, Boston, Massachusetts; and the dDivision of Endocrinology,

Dr. Valentin Fuster.

Brigham and Womens Hospital and Harvard Medical School, Boston, Massachusetts. This work was supported by the National
Heart, Lung and Blood Institutes Framingham Heart Study (contract N01-HC-25195). The views expressed in this manuscript are
those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; National Institutes of Health; or the U.S. Department of Health and Human Services. Drs. Pedley and Fox are employees of Merck & Company,
Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Manuscript received December 11, 2015; revised manuscript received June 22, 2016, accepted June 28, 2016.

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Abdominal Fat and Cardiometabolic Risk Factors

OCTOBER 4, 2016:150921

ABBREVIATIONS

higher prevalence of diabetes (5), hyperten-

vs. 20.2%; p < 0.0001). The institutional review

AND ACRONYMS

sion (6), and hypertriglyceridemia (7). In

boards of the Boston University Medical Center and

addition, we have shown that greater abdom-

Massachusetts General Hospital approved the study.

inal fat volume and lower (i.e., more nega-

All participants provided written informed consent.

BMI = body mass index


CT = computed tomography
CVD = cardiovascular disease

tive) abdominal fat attenuation assessed by


CT are cross-sectionally associated with

HDL = high-density lipoprotein

adverse levels of CVD risk factors (3,8) and

HU = Hounseld units

longitudinally associated with higher inci-

MDCT = multidetector

dence of CVD risk factors (9). However,

computed tomography

limited studies have explored the longitudi-

SAT = subcutaneous adipose

nal associations between quantitative and

tissue

qualitative changes in abdominal adipose tis-

VAT = visceral adipose tissue

sue with incidence and changes in CVD risk

factors over time.


Therefore, the primary purpose of this study was
to explore the longitudinal associations between
changes in abdominal fat volume and attenuation
with incidence and changes in a broad array of CVD
risk factors during an average of 6.1 years of follow-up.
SEE PAGE 1522

METHODS
The Framingham Heart Study is a long-term prospective study that has collected information on
participants medical history, physical examinations,
and laboratory tests since 1948. In addition, the Framingham Heart Study has monitored participants for
the development of CVD to identify major CVD risk

ABDOMINAL SAT AND VAT VOLUME AND ATTENUATION.

The participants underwent abdominal scans via an


8-slice MDCT while lying in the supine position
(LightSpeed Ultra, General Electric, Milwaukee, Wisconsin) (4). Starting from the upper edge of the S1
vertebrae, 5-mm thickness of 25 consecutive CT slices
were acquired with a tube voltage of 120 kVp, and
effective radiation exposure dosage of 2.7 mSv (4). A
3-dimensional Workstation tool was utilized to assess
abdominal adipose tissue volume and attenuation
(Aquarius 3D Workstation, TeraRecon Inc., San
Mateo, California). The readers outlined the abdominal muscular wall to differentiate the abdominal SAT
and VAT area and the average cubic centimeters and
HU of SAT and VAT were recorded based on the
radiographic pixel threshold between 195 and 45
HU with center attenuation of 120 HU. Detailed information regarding the MDCT scan protocol and the
reproducibility of these 2 abdominal fat compartments were reported previously with inter-reader and
intra-reader reliability of 0.997 for SAT and 0.992 for
VAT (4). Due to the CT imaging technique involved
with the adipose tissue measurement, fat quality was
referred to as fat attenuation and denoted in HU.

factors (10). Participants for this study were drawn

CVD RISK FACTORS. CVD risk factor proles were

from the Third Generation cohort who participated in

assessed and analyzed on site in the laboratory at each

the multidetector CT (MDCT) substudy Exam 1 from

examination by study physicians and clinic techni-

2002 to 2005 (baseline) and Exam 2 from 2008 to 2011

cians. BMI was computed as weight in kilograms

(follow-up). The design and selection criteria of the

divided by the square of height in meters. Obesity was

Third Generation cohort of the Framingham Heart

dened as BMI $30 kg/m 2. Blood pressure including

Study has been described previously (11). Among the

systolic blood pressure and diastolic blood pressure

sample of 1,994 Third Generation participants who

was assessed twice with participants seated after a 5-

attended the MDCT substudy Exam 1, we excluded

min rest. Hypertension was dened as systolic blood

participants in the following order: 1) who did not

pressure $140 mm Hg, diastolic blood pressure $90

participate in the Third Generation Exam 2 (n 229),

mm Hg, or the use of hypertensive medication. Blood

2) missing fat measures (weight, abdominal SAT and

samples were collected in the morning from partici-

VAT volume and attenuation) because participants

pants who had fasted for $8 h prior to the blood draw.

did not attend the MDCT substudy Exam 2 (n 609);

Fasting plasma glucose, total cholesterol, high-density

3) missing outcomes (n 5); 4) missing covariates

lipoprotein (HDL) cholesterol, and triglycerides were

(n 28); and 5) a history of CVD diagnosis on or

assessed from the blood samples. Impaired fasting

before Exam 2 (n 17), resulting in a total of 1,106

glucose was dened as fasting plasma glucose 100 to

participants. Compared with participants excluded

125 mg/dl and not on insulin or hypoglycemic medi-

from the analysis (n 888), participants included in

cation. Diabetes mellitus was dened as plasma

the analysis (n 1,106) had lower weight (80.5 kg vs.

fasting glucose $126 mg/dl or current use of insulin or

82.1 kg; p 0.04), body mass index (BMI) (27.2 kg/m2

oral hypoglycemic medication. Hypercholesterolemia

vs. 27.8 kg/m 2; p 0.02), SAT volume (2,732 cm 3 vs.

was dened as total cholesterol $240 mg/dl or

2,872 cm 3; p 0.03), and VAT volume (1,571 cm 3 vs.

lipid-lowering treatment. Low HDL cholesterol was

1,659 cm3 , p 0.04), and were less likely to be dia-

dened as HDL cholesterol <50 mg/dl for women

betic (2.8% vs. 5.4%; p 0.004) and smokers (10.4%

and <40 mg/dl for men. Hypertriglyceridemia was

Lee et al.

JACC VOL. 68, NO. 14, 2016


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Abdominal Fat and Cardiometabolic Risk Factors

dened as triglycerides $150 mg/dl or lipid treatment.

for the following models: baseline systolic blood

Metabolic

according

pressure and diastolic blood pressure for the hyper-

to the denition of Modied National Cholesterol

tension model; baseline glucose fasting plasma for

Education Program Adult Treatment Panel III guide-

the impaired fasting glucose and diabetes mellitus

lines (12).

models; baseline total cholesterol for the hypercho-

syndrome

was

determined

MEASUREMENT OF COVARIATES. All of the cova-

riates were measured at the baseline examination


cycle. Weight and height were assessed to the closest
pound and 0.25 inch, respectively. Waist circumference was measured at the horizontal level of the
umbilicus to the nearest 0.25 inch. Information
regarding

smoking

status,

alcohol

use,

post-

menopausal status, and current use of hormone


replacement therapy was documented during the
physician-administered medical and physical history
interview. Participants were classied as a current
smoker if they smoked >1 cigarette in the year preceding the examination. Moderate to heavy drinking
was dened as >7 drinks per week for women and
>14 drinks for men. Participants completed the
technician-administered questionnaire to estimate
the physical activity index score that assessed the
participants physical activity level (13).

lesterolemia model; baseline HDL cholesterol for the


low HDL cholesterol model; and baseline triglycerides
for the hypertriglyceridemia model. Participants
who were taking antihypertensive medication at
baseline were excluded from the systolic blood pressure and diastolic blood pressure models. If participants were in use of antihypertensive medication at
the follow-up examination, 10 mm Hg were added to
the follow-up systolic blood pressure and 5 mm Hg
were added to the follow up diastolic blood pressure
to reect the effect of the antihypertensive medications to their blood pressure (9,16,17).
Generalized adiposity (BMI) change, abdominal
adiposity (waist circumference) change, or respective
fat volumes (SAT volume for SAT attenuation model
and VAT volume for VAT attenuation model) was
additionally included in the multivariable-adjusted
model as a second-level adjustment. The tests for
interactions with sex were conducted based on the

STATISTICAL ANALYSIS. For the continuous CVD

multivariable-adjusted model.

risk factors, age-adjusted Pearson correlation co-

Additionally, we stratied the participants into

efcients were examined to explore the correlations

groups according to tertiles of abdominal adipose

between changes in abdominal fat volume and

tissue volume and attenuation change and examined

attenuation with changes in CVD risk factors during

CVD risk factor incidence across the groups. A 2-tailed

follow-up. Multivariable-adjusted linear regression

p value <0.05 was considered statistically signicant.

analyses were performed to predict changes in CVD

The primary purpose of this research was hypothesis

risk factors from changes in abdominal fat volume

generating (i.e., to explore the associations between

and

natural-

changes in fat quantity and quality with changes in

logarithmically transformed to normalize its dis-

CVD risk factors), thus we conducted exploratory data

tribution. For the dichotomous CVD risk factors,

analyses without adjustments for multiple compari-

multivariable-adjusted logistic regression models

sons. Statistical analyses were conducted via SAS

were constructed with changes in abdominal fat

software, version 9.2 (SAS Institute, Cary, North

volume and attenuation as independent variables

Carolina).

attenuation.

Triglycerides

were

and incident CVD risk factors as dependent variables.


The odds ratios from the logistic regression models
and b-coefcients from the linear regression models
were based on a 500 cm 3 increase in abdominal adipose tissue volume and a 5 HU decrease in abdominal
adipose tissue attenuation for consistency with our
previous adipose tissue studies (14,15).
The multivariable adjustments for the regression
models included baseline abdominal adipose tissue,
baseline CVD risk factors, age, sex, current smoking,
alcohol intake, physical activity, postmenopausal
status (women only), and hormone replacement
therapy (women only). For the logistic regression

RESULTS
DESCRIPTIVE CHARACTERISTICS. Table 1 summa-

rizes the baseline characteristics of the overall


participants (44.1% women). During 6.1 years of
follow-up, weight, BMI, and waist circumference
increased by 2.4 kg, 1.1 kg/m 2, and 3.7 cm, respectively.
The participants gained an average of 602 cm 3 of
SAT volume and 703 cm 3 of VAT volume. The average
fat attenuation decreased by 5.5 HU for SAT and
increased by 0.07 HU for VAT attenuation.
CORRELATIONS BETWEEN CHANGES IN ABDOMINAL

analysis, model-specic adjustments for baseline

FAT AND CHANGES IN CVD RISK FACTORS. Age- and

levels of CVD risk factors were additionally applied.

sex-adjusted Pearson correlation coefcients are

More specically, additional adjustments were made

shown in Table 2. In general, increases in fat volume

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Abdominal Fat and Cardiometabolic Risk Factors

CHANGES IN ABDOMINAL FAT VOLUME AND ATTENUATION

T A B L E 1 Baseline Characteristics of the Participants

WITH INCIDENT CVD RISK FACTORS. Tables 3 and 4 pre-

Overall Participants (n 1,106)

sent the associations between changes in abdominal

Baseline

Follow-Up

fat volume and attenuation with incident CVD

Age, yrs

45.1  6.2

51.3  6.2

risk factors. For each additional 500 cm 3 increase in

Weight, kg

80.5  17.2

82.9  18.1

Body mass index, kg/m2

27.2  5.0

28.3  5.3

SAT and VAT volume from baseline to follow-up,

Waist circumference, cm

95.1  14.0

98.8  14.0

Characteristics

the odds of incident CVD risk factors generally


increased, with the exception of SAT volume change

2,732  1,387

3,334  1,632

VAT volume, cm3

1,571  890

2,274  1,403

SAT attenuation, HU

100.8  5.2

106.3  4.3

low HDL cholesterol; and VAT volume change with

VAT attenuation, HU

93.9  4.7

93.9  7.0

impaired fasting glucose and diabetes mellitus.

Systolic blood pressure, mm Hg

119.3  14.4

118.6  13.2

The additional adjustment of change in BMI or

Diastolic blood pressure, mm Hg

76.7  9.0

75.3  8.7

waist circumference did not materially change the

Fasting plasma glucose, mg/dl

97.0  18.8

98.8  20.4

Total cholesterol, mg/dl

194.6  34.4

191.6  34.8

HDL cholesterol, mg/dl

53.9  17.0

59.4  18.6

Triglycerides, mg/dl

SAT volume, cm

with diabetes mellitus, hypercholesterolemia, and

direction or the signicance of these associations


(Table 3).
Similarly, each additional 5 HU decrease in the

97 (67145)

96.0 (71138)

Obesity

24.1 (266)

31.5 (348)

change in SAT and VAT attenuation was associated

Hypertension

20.3 (225)

26.7 (295)

with increased odds of incident CVD risk factor pro-

2.8 (31)

6.0 (66)

les (p < 0.05), except for impaired fasting glucose

Hypercholesterolemia

18.6 (206)

29.2 (323)

and diabetes mellitus (Table 4). Sex-specic regres-

Low HDL cholesterol

27.1 (300)

16.3 (180)

sion models for changes in abdominal fat volume and

Hypertriglyceridemia

29.7 (329)

36.2 (400)

Metabolic syndrome

24.9 (275)

28.8 (319)

Diabetes mellitus

Current smoking*

10.4 (115)

7.3 (81)

Moderate to heavy alcohol use

15.4 (170)

15.6 (172)

Physical activity index

37.4  8.0

38.2  9.0

attenuation with incident CVD risk factor proles are


provided in Online Tables 1 and 2.
We further tested for the sex interactions between
changes in abdominal fat volume and attenuation
with

incident

CVD

risk

factors

based

on

the

Values are mean  SD, % (n), or median (25th, 75th percentile) (due to the skewed
distribution). *Dened as $1 cigarette/day within the previous year. Dened as
>7 drinks/week for women and >14 drinks/week for men.

multivariable-adjusted model. Most of the sex in-

HDL high-density lipoprotein; HU Hounseld units; SAT subcutaneous


adipose tissue; VAT visceral adipose tissue.

ume change with hypertension (p 0.03), impaired

teractions were not signicant, except for VAT volfasting glucose (p 0.001), and metabolic syndrome
(p 0.02); SAT attenuation change with hypertriglyceridemia (p 0.047); and VAT attenuation

and decreases in fat attenuation were correlated


with adverse changes in CVD risk factor proles.
The partial Pearson correlation coefcients ranged

change with impaired fasting glucose (p 0.02) and


metabolic syndrome (p 0.04) (Tables 3 and 4). All
other p values were $0.07.

from 0.29 to 0.31, suggesting weak to moderate

CHANGES

correlations between changes in abdominal fat vol-

ATTENUATION

ume and attenuation with changes in CVD risk

FACTORS. The associations between changes in CVD

factors.

risk factors with changes in fat volume and changes

IN

ABDOMINAL
WITH

FAT

CHANGES

VOLUME

AND

IN

RISK

CVD

T A B L E 2 Age- and Sex-Adjusted Pearson Correlation Coefcients Between Changes in Abdominal Fat Volume and Attenuation With

Changes in Cardiovascular Disease Risk Factors


Overall Participants

Parameters

D in SAT volume
D in VAT volume
D in SAT attenuation
D in VAT attenuation

D in Systolic

D in Diastolic

D in Fasting

Blood Pressure

Blood Pressure

Plasma Glucose

D in HDL
Cholesterol

D in Log
Triglycerides

0.19

0.16

0.07*

0.12

0.16

0.20

0.22

0.15

0.08

0.07*

0.29

0.18

0.12

0.14

0.03

0.11

0.09

0.19

0.17

0.17

0.05

0.00

0.31

0.20

*Signicant at 0.05 level. Signicant at 0.01 level. Signicant at 0.001 level.


Abbreviations as in Table 1.

D in Total
Cholesterol

Lee et al.

JACC VOL. 68, NO. 14, 2016


OCTOBER 4, 2016:150921

Abdominal Fat and Cardiometabolic Risk Factors

T A B L E 3 Multivariable-Adjusted Logistic Regression Models for Changes in Abdominal Fat Volume With Incident

Cardiovascular Disease Risk Factors


Overall Participants
Parameters

Hypertension

Model

1.21 (1.031.41)

0.02

1.30 (1.101.55)

0.002

1.21 (1.031.41)

0.02

1.30 (1.101.55)

0.003

MV WC

1.21 (1.031.41)

0.02

1.32 (1.111.57)

0.002

0.65

Incident*
MV

1.25 (1.081.45)

0.003

1.10 (0.941.29)

0.23

1.24 (1.061.44)

0.006

1.08 (0.921.26)

0.37

MV WC

1.24 (1.071.45)

0.004

1.09 (0.931.27)

0.08

MV

1.00 (0.811.24)

0.99

1.13 (0.891.43)

0.31

MV BMI

1.00 (0.811.24)

0.99

1.15 (0.911.45)

0.25

MV WC

1.00 (0.801.24)

0.98

1.13 (0.901.43)

0.30

0.18

0.75

Incident*

0.001

36/1,075 (3.3)

Incident*

150/900 (16.7)

MV

1.10 (0.961.26)

0.18

1.37 (1.181.60)

<0.0001

MV BMI

1.10 (0.961.26)

0.17

1.38 (1.181.61)

<0.0001

MV WC

1.10 (0.961.26)

0.18

1.40 (1.201.63)

<0.0001

0.16

Incident*

0.12

31/806 (3.8)

MV

1.20 (0.931.54)

0.16

1.48 (1.121.97)

0.007

MV BMI

1.22 (0.941.57)

0.13

1.46 (1.101.95)

0.01

MV WC

1.20 (0.931.54)

0.16

1.44 (1.081.92)

0.01

0.43

0.86

MV

1.15 (1.011.30)

0.04

1.56 (1.331.83)

<0.0001

MV BMI

1.15 (1.011.31)

0.03

1.58 (1.341.85)

<0.0001

MV WC

1.14 (1.001.30)

0.047

1.59 (1.351.87)

<0.0001

0.09

Incident*

Sex interaction
Metabolic syndrome

0.31

Sex interaction
Hypertriglyceridemia

0.03

130/788 (16.5)

MV BMI

Sex interaction
Low HDL cholesterol

p Value

MV

Sex interaction
Hypercholesterolemia

D in VAT Volume

115/881 (13.1)

MV BMI

Sex interaction
Diabetes mellitus

p Value

Incident*

Sex interaction
Impaired fasting glucose

D in SAT Volume

141/777 (18.1)

Incident*

0.57

109/831 (13.1)

MV

1.43 (1.231.68)

<0.0001

1.82 (1.512.19)

MV BMI

1.41 (1.201.65)

<0.0001

1.76 (1.462.11)

<0.0001

MV WC

1.42 (1.211.66)

<0.0001

1.77 (1.472.13)

<0.0001

0.48

0.02

Sex interaction

<0.0001

Values are n/n (%) or odds ratio (95% condence interval). The results show the odds of cardiovascular disease risk factor for each additional 500 cm3 increase in the change in
abdominal fat volume. *The number of new cases of a cardiovascular disease risk factor at follow-up divided by the number of persons at risk for the risk factor. Multivariable
(MV) model was adjusted for baseline fat volume, baseline cardiovascular disease risk factors, age, sex, current smoking, alcohol intake, physical activity, postmenopausal status
(women only), and hormone replacement therapy (women only). MV body mass index (BMI) model was additionally adjusted for BMI change. MV waist circumference (WC)
model was additionally adjusted for waist circumference change. Sex interaction was examined based on the multivariable-adjusted model.

in fat attenuation are shown in Tables 5 and 6,

for BMI change, waist circumference change, or

respectively. The longitudinal changes in abdominal

respective fat volume (all p # 0.001); except for

fat volume during the follow-up were associated with

changes in SAT volume and fasting plasma glucose

adverse changes in CVD risk factor proles over time

(all p 0.06). Sex-specic regression models for

(all p # 0.0005) (Table 5). Associations remained sig-

changes in abdominal fat and changes in CVD risk

nicant even after further adjustment for change in

factor proles are provided in Online Tables 3 and 4.

BMI or waist circumference (all p # 0.0006) (Table 5).

Tests for sex interactions between changes in

Similar patterns were observed between changes in

abdominal fat volume with changes in CVD risk factor

abdominal fat attenuation with changes in CVD risk

proles were signicant for most of the CVD risk

factor proles (all p < 0.05) (Table 6). These associa-

outcomes (Table 5). In general, these associations

tions persisted even after additional adjustment

were stronger in women, as compared to men

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JACC VOL. 68, NO. 14, 2016


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Abdominal Fat and Cardiometabolic Risk Factors

T A B L E 4 Multivariable-Adjusted Logistic Regression Models for Changes in Abdominal Fat Attenuation With Incident Cardiovascular

Disease Risk Factors


Overall Participants
Parameters

Hypertension

Model

2.92 (1.794.79)

<0.0001

1.56 (1.172.08)

0.002

2.73 (1.674.49)

<0.0001

1.52 (1.132.05)

0.005

MV WC

2.74 (1.674.51)

<0.0001

1.58 (1.172.14)

0.003

MV fat volume

2.89 (1.615.19)

0.0004

0.75

MV

1.44 (0.972.13)

0.07

1.28 (1.001.64)

0.05

MV BMI

1.30 (0.871.93)

0.20

1.15 (0.891.49)

0.27

MV WC

1.31 (0.881.94)

0.18

1.19 (0.921.54)

0.18

0.91 (0.561.48)

0.71

1.31 (0.881.95)

0.19

0.07

0.02

Incident*

130/788 (16.5)

Incident*

36/1,075 (3.3)

MV

0.91 (0.531.56)

0.74

1.29 (0.822.01)

0.27

MV BMI

0.97 (0.571.66)

0.91

1.28 (0.821.99)

0.28

MV WC

0.91 (0.541.56)

0.74

1.25 (0.801.95)

0.33

MV fat volume

0.83 (0.391.75)

0.62

1.21 (0.562.60)

0.63

0.20

0.42

Incident*

150/900 (16.7)

MV

1.73 (1.162.59)

0.007

1.69 (1.322.15)

<0.0001

MV BMI

1.71 (1.152.55)

0.009

1.71 (1.332.21)

<0.0001
<0.0001

MV WC

1.72 (1.152.57)

0.008

1.78 (1.372.32)

MV fat volume

1.82 (1.112.98)

0.02

1.29 (0.881.90)

0.19

0.16

0.08
0.002

Incident*

31/806 (3.8)

MV

2.73 (1.226.12)

0.01

2.15 (1.313.52)

MV BMI

2.62 (1.185.86)

0.02

2.16 (1.283.65)

0.004

MV WC

2.53 (1.145.60)

0.02

2.00 (1.193.36)

0.009

MV fat volume

2.69 (1.037.06)

0.04

1.91 (0.894.11)

0.10

0.11

0.99

Sex interaction
Incident*

141/777 (18.1)

MV

1.84 (1.262.68)

0.002

1.93 (1.522.45)

<0.0001

MV BMI

1.82 (1.252.65)

0.002

1.99 (1.552.56)

<0.0001

MV WC

1.82 (1.252.66)

0.002

2.04 (1.582.63)

<0.0001

MV fat volume

1.87 (1.153.06)

0.012

1.32 (0.891.96)

0.17

0.047

0.21

Sex interaction
Metabolic syndrome

0.34

0.72

Sex interaction

Hypertriglyceridemia

1.23 (0.801.88)

Sex interaction

Low HDL cholesterol

p Value

MV BMI

Sex interaction

Hypercholesterolemia

D in VAT Attenuation

115/881 (13.1)

MV

MV fat volume
Diabetes mellitus

p Value

Incident*

Sex interaction
Impaired fasting glucose

D in SAT Attenuation

Incident*

109/831 (13.1)

MV

2.60 (1.644.14)

<0.0001

3.58 (2.574.97)

<0.0001

MV BMI

2.24 (1.403.59)

0.0008

3.06 (2.184.30)

<0.0001

MV WC

2.15 (1.353.42)

0.001

3.05 (2.164.29)

<0.0001

MV fat volume

1.31 (0.752.29)

0.45

2.49 (1.524.08)

0.0003

0.34

Sex interaction

0.04

Values are n/n (%) or odds ratio (95% condence interval). The results show the odds of cardiovascular disease risk factor for each additional 5 HU decrease in the change in
abdominal fat attenuation. *The number of new cases of a cardiovascular disease risk factor at follow-up divided by the number of persons at risk for the risk factor. MV model,
adjusted for baseline fat attenuation, baseline cardiovascular disease risk factors, age, sex, current smoking, alcohol intake, physical activity, postmenopausal status (women
only), and hormone replacement therapy (women only). MV BMI model was additionally adjusted for BMI change. MV WC model was additionally adjusted for waist
circumference change. MV Fat Volume model was additionally adjusted for respective fat volume (SAT volume for SAT attenuation and VAT volume for VAT attenuation).
Sex interaction was examined based on the multivariable-adjusted model.
Abbreviations as in Tables 1 and 3.

(Online Table 3). Conversely, the majority of the sex

SECONDARY ANALYSES. We further explored the

interactions between changes in abdominal fat atten-

associations between incident CVD risk factors with

uation with changes in CVD risk factors were not sig-

SAT and VAT volumes and attenuation change over

nicant (Table 6).

time by examining the proportion of participants with

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Abdominal Fat and Cardiometabolic Risk Factors

T A B L E 5 Multivariable-Adjusted Linear Regression Models for Changes in Abdominal Fat Volume With Changes in

Cardiovascular Disease Risk Factors


Overall Participants
Parameters

D in Systolic blood pressure

Model

1.49 (1.04 to 1.94)

<0.0001

1.90 (1.38 to 2.41)

<0.0001

MV BMI*

1.48 (1.03 to 1.94)

<0.0001

1.90 (1.38 to 2.42)

<0.0001

MV WC*

1.49 (1.03 to 1.94)

<0.0001

1.91 (1.40 to 2.43)

<0.0001

0.01

<0.0001

Sample size
0.87 (0.56 to 1.18)

<0.0001

1.34 (0.99 to 1.70)

<0.0001

MV BMI*

0.87 (0.56 to 1.18)

<0.0001

1.34 (0.99 to 1.69)

<0.0001

MV WC*

0.87 (0.56 to 1.18)

<0.0001

1.35 (0.99 to 1.70)

<0.0001

0.009

0.002

1,084

MV*

0.96 (0.42 to 1.50)

0.0005

1.14 (0.52 to 1.75)

MV BMI*

0.96 (0.42 to 1.50)

0.0005

1.13 (0.52 to 1.75)

0.0003

MV WC*

0.96 (0.41 to 1.50)

0.0006

1.13 (0.51 to 1.75)

0.0003

0.0003

0.49

Sample size

0.04

998

MV*

2.30 (1.18 to 3.42)

<0.0001

2.54 (1.23 to 3.85)

0.0002

MV BMI*

2.34 (1.23 to 3.45)

<0.0001

2.63 (1.32 to 3.94)

<0.0001

MV WC*

2.39 (1.27 to 3.50)

<0.0001

2.63 (1.32 to 3.95)

<0.0001

0.62

0.06

Sample size

998

MV*

1.15 (1.57 to 0.73)

<0.0001

2.26 (2.75 to 1.78)

<0.0001

MV BMI*

1.15 (1.57 to 0.73)

<0.0001

2.25 (2.74 to 1.76)

<0.0001

MV WC*

1.13 (1.56 to 0.71)

<0.0001

2.22 (2.71 to 1.74)

<0.0001

0.02

Sex interaction

D in Log triglycerides

Sample size

Sex interaction

D in HDL cholesterol

988

MV*

Sex interaction

D in Total cholesterol

p Value

988

MV*

Sex interaction

D in Fasting plasma glucose

D in VAT Volume

p Value

Sample size

Sex interaction

D in Diastolic blood pressure

D in SAT Volume

0.13

Sample size

998

MV*

0.05 (0.04 to 0.07)

<0.0001

0.10 (0.08 to 0.11)

<0.0001

MV BMI*

0.05 (0.04 to 0.07)

<0.0001

0.10 (0.08 to 0.11)

<0.0001

MV WC*

0.05 (0.04 to 0.07)

<0.0001

0.10 (0.08 to 0.11)

<0.0001

0.01

0.046

Sex interaction

Values are estimated b (95% condence interval). The results show the association of changes in cardiovascular disease risk factor for each additional 500 cm3 increase in the
change in abdominal fat volume. *MV model, adjusted for baseline fat volume, baseline cardiovascular disease risk factors, age, sex, current smoking, alcohol intake, physical
activity, postmenopausal status (women only), and hormone replacement therapy (women only). MV BMI model was additionally adjusted for BMI change. MV WC model
was additionally adjusted for waist circumference change. Sex interaction was tested based on multivariable-adjusted model.
Abbreviations as in Tables 1 and 3.

incident CVD risk factors across tertiles of fat volume

with incidence and changes in CVD risk factor proles

and attenuation. The incidence rate of CVD risk fac-

during a 6-year interval. Our principal ndings are

tors were stratied by tertiles of changes in SAT and

3-fold. First, an increase in the change in abdominal

VAT volume (Central Illustration) and attenuation

SAT and VAT volume are associated with an increased

(Figure 1) during follow-up. In general, higher tertiles

incidence of CVD risk factors and more adverse

of abdominal fat volume (i.e., increase in the change

changes in CVD risk factors over time. Second, a

in fat volume) and attenuation (i.e., decrease in the

decrease in the change in SAT and VAT attenuation

change in fat attenuation) change were associated

was associated with an increased incidence of CVD

with a relatively higher incidence of CVD risk factors,

risk factors, as well as more adverse changes in CVD

as compared to the lower tertile groups.

risk factors. Finally, the majority of these associations


remained signicant even after further accounting for

DISCUSSION

BMI change, waist circumference change, or respective

abdominal

adipose

tissue

volumes.

Taken

In this large community-based observational study,

together, these ndings suggest that adverse changes

we examined longitudinal associations between

in fat quantity and attenuation are associated with

changes in abdominal fat volume and attenuation

changes in CVD risk factors above and beyond the

1515

1516

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Abdominal Fat and Cardiometabolic Risk Factors

T A B L E 6 Multivariable-Adjusted Linear Regression Models for Changes in Abdominal Fat Attenuation With Changes in Cardiovascular

Disease Risk Factors


Overall Participants
Parameters

Model

D in Systolic blood pressure

D in SAT Attenuation

Sample size
MV*

2.89 (1.86 to 3.93)

<0.0001

2.55 (1.85 to 3.24)

<0.0001

MV BMI*

2.81 (1.77 to 3.84)

<0.0001

2.57 (1.84 to 3.30)

<0.0001

MV WC*

2.80 (1.77 to 3.84)

<0.0001

2.62 (1.88 to 3.36)

<0.0001

MV fat volume*

2.82 (1.78 to 3.85)

<0.0001

2.60 (1.84 to 3.36)

<0.0001

MV*

2.24 (1.54 to 2.94)

<0.0001

2.01 (1.53 to 2.48)

<0.0001

MV BMI*

2.20 (1.50 to 2.90)

<0.0001

2.01 (1.51 to 2.51)

<0.0001

MV WC*

2.21 (1.50 to 2.91)

<0.0001

2.05 (1.55 to 2.56)

<0.0001

MV fat volume*

2.21 (1.50 to 2.91)

<0.0001

2.06 (1.54 to 2.58)

<0.0001

0.26

Sample size

0.07

MV*

1.29 (0.03 to 2.55)

0.04

1.57 (0.71 to 2.43)

MV BMI*

1.23 (0.02 to 2.49)

0.06

1.55 (0.65 to 2.44)

0.0007

MV WC*

1.20 (0.06 to 2.45)

0.06

1.53 (0.62 to 2.44)

0.001

MV fat volume*

1.19 (0.07 to 2.45)

0.06

1.61 (0.68 to 2.54)

0.11

Sample size

0.0004

0.0007
0.13

988

MV*

5.01 (2.40 to 7.62)

0.0002

2.87 (1.06 to 4.68)

0.002

MV BMI*

5.20 (2.63 to 7.78)

<0.0001

4.40 (2.53 to 6.27)

<0.0001

MV WC*

5.35 (2.76 to 7.93)

<0.0001

4.47 (2.57 to 6.37)

<0.0001

MV fat volume*

5.31 (2.72 to 7.90)

<0.0001

4.97 (3.04 to 6.90)

<0.0001

0.58

Sex interaction
Sample size

0.18

988

MV*

3.25 (4.21 to 2.29)

<0.0001

3.64 (4.29 to 2.99)

<0.0001

MV BMI*

3.23 (4.20 to 2.27)

<0.0001

3.70 (4.38 to 3.02)

<0.0001

MV WC*

3.21 (4.17 to 2.25)

<0.0001

3.66 (4.35 to 2.96)

<0.0001

MV fat volume*

3.23 (4.19 to 2.27)

<0.0001

3.93 (4.64 to 3.23)

<0.0001

0.64

Sex interaction

D in Log triglycerides

1,084

Sex interaction

D in HDL cholesterol

0.01

988

Sex interaction

D in Total cholesterol

0.23

Sample size

D in Fasting plasma glucose

p Value

988

Sex interaction

D in Diastolic blood pressure

D in VAT Attenuation

p Value

0.0005

Sample size

988

MV*

0.11 (0.07 to 0.15)

<0.0001

0.11 (0.09 to 0.14)

<0.0001

MV BMI*

0.11 (0.07 to 0.15)

<0.0001

0.13 (0.10 to 0.15)

<0.0001

MV WC*

0.11 (0.07 to 0.15)

<0.0001

0.13 (0.10 to 0.16)

<0.0001

MV fat volume*

0.11 (0.07 to 0.15)

<0.0001

0.14 (0.11 to 0.16)

<0.0001

0.03

Sex interaction

0.15

Values are estimated b (95% condence interval). The results show the association of changes in cardiovascular disease risk factor for each additional 5 HU decrease in the
change in abdominal fat attenuation. *MV model, adjusted for baseline fat attenuation, baseline cardiovascular disease risk factors, age, sex, current smoking, alcohol intake,
physical activity, postmenopausal status (women only), and hormone replacement therapy (women only). MV BMI model was additionally adjusted for BMI change. MV WC
model was additionally adjusted for waist circumference change. MV fat volume model was additionally adjusted for respective fat volume (SAT volume for SAT attenuation
and VAT volume for VAT attenuation). Sex interaction was examined based on the multivariable-adjusted model.
Abbreviations as in Tables 1 and 3.

contribution

of

generalized

adiposity,

central

adiposity, or absolute levels of respective fat volume.

metabolic risk factors, including hyperglycemia, high


triglycerides, and low HDL cholesterol (18). Two
prospective studies reported that increase in the

CONTEXT

LITERATURE. Our

change in abdominal VAT volume was associated

research builds on previous investigations that have

OF

THE

CURRENT

with incident diabetes even after adjusting for

reported consistent ndings with our study results

weight change (19); and with incident hypertension

regarding abdominal fat volume and attenuation with

after further adjusting for abdominal SAT volume

CVD risk factor proles (8,9,1823). For example, in-

change (20). Implementing radiographic imaging

dividuals with greater increase in abdominal VAT

techniques to assess adipose tissue attenuation as a

volume showed substantial increase in incident

proxy of fat quality is a relatively newer measure

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Abdominal Fat and Cardiometabolic Risk Factors

C ENTR AL I LL U STRA T I O N Abdominal Fat Volume and Cardiovascular Disease Risk Factors

Lee, J.J. et al. J Am Coll Cardiol. 2016;68(14):150921.

Incidence of cardiovascular disease risk factors according to the tertiles of changes in (Top) subcutaneous adipose tissue (SAT) and (Bottom) visceral adipose tissue
(VAT) volumes in overall participants. Tertile 3 corresponds to a larger increase in the change in adipose tissue volumes, as compared with tertile 1. The linear trend for
each cardiovascular disease risk factor model is shown as a single p value. HDL high-density lipoprotein cholesterol; SAT subcutaneous adipose tissue;
VAT visceral adipose tissue.

(8,15,24,25). We have previously demonstrated the

factors prole (26,27). Two large cohort studies

cross-sectional associations between lower attenua-

documented that SAT and VAT are both associated

tion of abdominal fat with adverse CVD risk factors

with CVD risk factors. Yet, VAT was more closely

(8), as well as longitudinal associations between

associated with CVD risk factors, as opposed to SAT in

baseline

levels

of

abdominal

fat

quantity

and

both African-American (28) and white participants

quality with incidence and changes in CVD risk

(3). Of interest, we have previously underscored the

factors (9).

protective role of SAT by reporting lower levels of

In addition to our primary nding, we identied an

triglycerides with increasing SAT volume among

interesting signal in our study results, in which

participants with the highest VAT volume tertile

several CVD risk factors, including hypercholester-

(26). Collectively, our ndings add to the growing

olemia and low HDL cholesterol, were associated only

body of literature by reporting the intriguing pat-

with VAT volume change, but not with SAT volume

terns between VAT, but not SAT, with CVD risk

change. These ndings correspond to the previous

factors that are associated with lipid metabolism.

ndings that higher VAT is detrimental, whereas

This study may further support the prominent role

higher SAT is protective of the cardiometabolic risk

of VAT that is intrinsically different than SAT in the

1517

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Abdominal Fat and Cardiometabolic Risk Factors

F I G U R E 1 Incidence of Cardiovascular Disease Risk Factors According to the Tertiles of Changes in (A) SAT and (B) VAT Attenuation

in Overall Participants

Changes in Subcutaneous Adipose Tissue Attenuation


Overall Participants

25
p = 0.26

p = 0.05

p = 0.09

p = 0.77

p = 0.39

Incidence (%)

20

1st SAT HU Tertile


2nd SAT HU Tertile
3rd SAT HU Tertile
p = 0.46

15
10
5
0
Hypertension

Diabetes

Hypercholesterolemia

Low HDL

Hypertriglyceridemia Metabolic Syndrome

Cardiovascular Disease Risk Factors

B Changes in Visceral Adipose Tissue Attenuation

1st VAT HU Tertile


2nd VAT HU Tertile
3rd VAT HU Tertile

Overall Participants

35
30

Incidence (%)

1518

p < 0.0001

p = 0.004

p < 0.0001

p = 0.02

p < 0.0001

p < 0.0001

25
20
15
10
5
0
Hypertension

Diabetes

Hypercholesterolemia

Low HDL

Hypertriglyceridemia Metabolic Syndrome

Cardiovascular Disease Risk Factors

Tertile 3 corresponds to more decrease (i.e., more negative) in the change in adipose tissue attenuation, as compared to tertile 1. The linear
trend for each cardiovascular disease risk factor model is shown as a single p value. HDL high-density lipoprotein cholesterol; HU
Hounseld units; SAT subcutaneous adipose tissue; VAT visceral adipose tissue.

manifestation of cardiometabolic disease. However,

attenuation is a dynamic aspect of the fat deposition.

it should be noted that impaired fasting glucose was

In particular, we have previously shown that the

only associated with SAT volume change, but not

mean VAT attenuation increased in weight stable

with VAT volume change, which adds complexity to

and weight loss groups; whereas VAT attenuation

the pathogenic properties of abdominal adiposity

decreased in weight gain group only (29). In contrast,

tissue.

regardless of the type of weight change group, SAT

In conjunction with this investigation, we have

attenuation decreased over time (29). In this present

recently published a study that examined associa-

study, SAT attenuation was more likely to decrease

tions between changes in body weight and changes in

than VAT attenuation, as shown by the decrease in

abdominal fat volume and attenuation during 6.1

mean SAT attenuation and increase in mean VAT

years of follow-up (29). That study documented that

attenuation during the follow-up. These data suggest

increases in body weight were associated with de-

that there is potential variability in the dynamic of

creases in both abdominal SAT and VAT attenuation,

fat attenuation between different types of abdominal

even after further adjusting for fat volume change.

adipose tissue. Further research is needed to explore

In the current study, we demonstrated that de-

the dynamic of CT fat attenuation as a measure of fat

creases in fat attenuation were associated with

quality.

changes in CVD risk factors. Collectively, a decrease

Overall, we extend the existing literature in

in fat attenuation may reect adverse changes in

several different ways. First, we expanded the study

fat quality, supported by the association with the

sample to encompass large numbers of women and

increases in weight, as well as adverse changes in

men in a community-based setting. Second, our

CVD risk factors. It should be recognized that fat

study incorporated a broader prole of CVD risk

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Abdominal Fat and Cardiometabolic Risk Factors

factors as clinical outcomes at baseline and follow-

array of traditional CVD risk proles, with increased

up for a more precise assessment. Third, a novel

CVD risk observed with an increase in fat volume and

fat measurement assessed by CT attenuation was

decrease in fat attenuation.

used to examine the long-term associations of the

Our study makes signicant advances to the cur-

qualitative changes in abdominal adipose tissue with

rent literature by extending the understanding of the

cardiometabolic risk.

association between abdominal adiposity and meta-

POTENTIAL PHYSIOLOGICAL MECHANISMS. There

are several potential mechanisms that may explain


our ndings regarding the quantitative and qualitative changes in abdominal adipose tissue with
changes in CVD risk factors. First, the worsening fat
quality along with the simultaneous increase in fat
mass

may

manifest

the

development

of

car-

diometabolic disease. Fat quantity and attenuation


are closely linked, as the most distinctive changes in

bolic risk factors. We have demonstrated that


concomitant changes in both abdominal fat volume
and attenuation are associated with concurrent incidence and changes in traditional CVD risk factors.
Further studies are warranted to elucidate the histologic mechanisms that lie underneath the associations between concomitant changes of abdominal fat
volume and attenuation with incident CVD risk factor
proles.

the state of positive energy balance are an expansion

STUDY STRENGTHS AND LIMITATIONS. There are

of the ectopic fat storage reservoir (i.e., adipocyte

several strengths of this study. First, this study

hyperplasia) along with the enlargement of the size of

incorporated

the individual adipose tissue cell (i.e., adipocyte

abdominal adipose tissue volume and attenuation

hypertrophy) (30). Simultaneously, the adipose tissue

assessed by MDCT to subsequently explore incidence

remodeling

process

accompanies

highly

reproducible

measures

of

dysfunctional

and changes in CVD risk proles. Next, a compre-

modication in the fat properties, such as abnormal

hensive list of CVD risk factors was incorporated in

excretion of anti- and proinammatory adipokines

this study. Finally, the baseline and follow-up mea-

(31,32), alteration in free fatty acid metabolism (33),

surements of CT-derived abdominal fat and CVD risk

poor vascularity (34), and cellular hypoxia (35). In the

factors in between a mean interval of 6 years apart

context of adipose tissue cellularity, a more negative

enable the assessment of longitudinal associations

attenuation of adipose tissue may correspond to

over time. Some limitations warrant mention. First,

higher lipid content (36), decreased lipolytic activity

our design was observational, which limits causal

(37,38), poor vascularity (34), cellular hypoxia (35),

inference of our ndings. Second, abdominal CT fat

and a larger adipocyte size (36). Thus, more negative

attenuation was utilized as a proxy of fat quality.

attenuation of CT fat observed in this study may

Thus, the signicance of fat attenuation requires

reect worsening fat quality, which may concur with

further research to understand its biological mecha-

adipocyte hyperplasia and hypertrophy, and eventu-

nism. Third, the study sample was comprised pri-

ally leads to a higher risk of developing car-

marily of white individuals, thus generalization to

diometabolic disease (39).

other individuals with different racial or ethnic

Next, weight loss studies may provide insights into

backgrounds cannot be made. Next, we did not

our results. These weight loss intervention studies

perform interscan reproducibility, thus the values of

have demonstrated that reduction in abdominal fat

the CT fat change during follow-up may have been

volume was associated with improvement in CVD risk

affected by the interscan variability. Although a ma-

factors (4043), as well as improvement in fat quality,

jority of our study results were statistically signi-

such as reduced adipocyte size (44,45). A reduction in

cant, the magnitude of the associations assessed via

subcutaneous fat cell diameter achieved after bariat-

age- and sex-adjusted Pearson correlations indicate

ric

with

that the associations between the changes in fat and

improved insulin sensitivity, as compared to the

changes in CVD risk factors were relatively weak to

decrease in fat mass (46). Taken together, these

modest. We observed differences in the characteris-

reversible associations of adipose tissue and CVD risk

tics of participants who were included and excluded

may support that both quantity and quality of the

from the study. This may have introduced an

adipose tissue constitutes a major contributor for the

inherent bias in our study design.

surgery

showed

stronger

associations

development or prevention of CVD risk factor


proles.

CONCLUSIONS

IMPLICATIONS. The current study highlights the

importance of quantitative and qualitative changes in

In a large community- and population-based cohort,

adipose tissue over time for the changes in a broad

greater accumulation of abdominal fat volume and

1519

1520

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Abdominal Fat and Cardiometabolic Risk Factors

more negative changes in fat attention during


follow-up were associated with increased incidence
and adverse changes in CVD risk factors above and
beyond generalized adiposity, central adiposity, and
respective fat volumes. Our ndings highlight the
importance of quantitative and qualitative aspects of
adipose tissue for a better understanding of CVD
risk.

PERSPECTIVES
COMPETENCY IN MEDICAL KNOWLEDGE:
Increasing abdominal fat volume and decreasing fat
attenuation (a measure of fat quality), as determined
by MDCT scans, are associated with worsening CVD
risk factors beyond associations with generalized or
central adiposity.

REPRINT REQUESTS AND CORRESPONDENCE: Dr.

Caroline S. Fox, Framingham Heart Study, National


Heart, Lung, and Blood Institute, 73 Mount Wayte
Avenue, Suite 2, Framingham, Massachusetts 01702.

TRANSLATIONAL OUTLOOK: Further studies are


warranted to clarify the mechanisms that underlie
these associations.

E-mail: foxca@nhlbi.nih.gov.

REFERENCES
1. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart
disease and stroke statistics-2015 update: a report
from the American Heart Association. Circulation
2015;131:e29322.
2. Mathers CD, Loncar D. Projections of global
mortality and burden of disease from 2002 to
2030. PLoS Med 2006;3:e442.
3. Fox CS, Massaro JM, Hoffmann U, et al.
Abdominal visceral and subcutaneous adipose
tissue compartments: association with metabolic
risk factors in the Framingham Heart Study. Circulation 2007;116:3948.

design, recruitment, and initial examination. Am J


Epidemiol 2007;165:132835.
12. Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults.
Executive Summary of The Third Report of The
National Cholesterol Education Program (NCEP)
Expert Panel on Detection, Evaluation, And
Treatment of High Blood Cholesterol In Adults
(Adult Treatment Panel III). JAMA 2001;285:
248697.

in metabolic risk factors in Japanese men: the


Hitachi Health Study. Diabetes Care 2012;35:
113943.
22. Rheaume C, Arsenault BJ, Dumas MP, et al.
Contributions of cardiorespiratory tness and
visceral adiposity to six-year changes in cardiometabolic risk markers in apparently healthy
men and women. J Clin Endocrinol Metab 2011;96:
14628.

13. Kannel WB, Sorlie P. Some health benets of


physical activity. The Framingham Study. Arch
Intern Med 1979;139:85761.

23. Shah RV, Murthy VL, Abbasi SA, et al. Visceral


adiposity and the risk of metabolic syndrome
across body mass index: the MESA Study. J Am
Coll Cardiol Img 2014;7:122135.

14. Lee JJ, Britton KA, Pedley A, et al. Adipose


tissue depots and their cross-sectional associa-

24. Rosenquist KJ, Massaro JM, Pedley A, et al.


Fat quality and incident cardiovascular disease,

tions with circulating biomarkers of metabolic


regulation. J Am Heart Assoc 2016;5:e002936.

all-cause mortality, and cancer mortality. J Clin


Endocrinol Metab 2015;100:22734.

15. Lee JJ, Pedley A, Hoffmann U, et al. Crosssectional associations of computed tomography
(CT)-derived adipose tissue density and adipokines: the Framingham Heart Study. J Am Heart
Assoc 2016;5:e002545.

25. Yeoh AJ, Pedley A, Rosenquist KJ,


Hoffmann U, Fox CS. The association between
subcutaneous fat density and the propensity to
store fat viscerally. J Clin Endocrinol Metab 2015;
100:E105664.

16. Levy D, Ehret GB, Rice K, et al. Genome-wide


association study of blood pressure and hypertension. Nat Genet 2009;41:67787.

26. Porter SA, Massaro JM, Hoffmann U, et al.


Abdominal subcutaneous adipose tissue: a protective fat depot? Diabetes Care 2009;32:

4. Maurovich-Horvat P, Massaro J, Fox CS, et al.


Comparison of anthropometric, area- and volumebased assessment of abdominal subcutaneous and
visceral adipose tissue volumes using multidetector computed tomography. Int J Obes
(Lond) 2007;31:5006.
5. Smith JD, Borel AL, Nazare JA, et al. Visceral
adipose tissue indicates the severity of cardiometabolic risk in patients with and without type
2 diabetes: results from the INSPIRE ME IAA study.
J Clin Endocrinol Metab 2012;97:151725.
6. Kurukulasuriya LR, Stas S, Lastra G, et al. Hypertension in obesity. Med Clin North Am 2011;95:
90317.
7. Ibrahim MM. Subcutaneous and visceral adipose
tissue: structural and functional differences. Obes
Rev 2010;11:118.
8. Rosenquist KJ, Pedley A, Massaro JM, et al.
Visceral and subcutaneous fat quality and cardiometabolic risk. J Am Coll Cardiol Img 2013;6:
76271.
9. Abraham TM, Pedley A, Massaro JM, et al. Association between visceral and subcutaneous adipose depots and incident cardiovascular disease
risk factors. Circulation 2015;132:163947.

17. Cui JS, Hopper JL, Harrap SB. Antihypertensive


treatments obscure familial contributions to blood
pressure variation. Hypertension 2003;41:20710.
18. Matsushita Y, Nakagawa T, Yamamoto S, et al.
Effect of longitudinal changes in visceral fat area
on incidence of metabolic risk factors: the Hitachi
health study. Obesity (Silver Spring) 2013;21:
21269.
19. Wander PL, Boyko EJ, Leonetti DL, et al.
Change in visceral adiposity independently predicts a greater risk of developing type 2 diabetes
over 10 years in Japanese Americans. Diabetes
Care 2013;36:28993.

10. Dawber TR, Kannel WB, Lyell LP. An approach


to longitudinal studies in a community: the Framingham Study. Ann N Y Acad Sci 1963;107:
53956.

20. Sullivan CA, Kahn SE, Fujimoto WY, et al.


Change in intra-abdominal fat predicts the risk of
hypertension in Japanese Americans. Hypertension 2015;66:13440.

11. Splansky GL, Corey D, Yang Q, et al. The Third


Generation Cohort of the National Heart, Lung,
and Blood Institutes Framingham Heart Study:

21. Matsushita Y, Nakagawa T, Yamamoto S, et al.


Effect of longitudinal changes in visceral fat area
and other anthropometric indices to the changes

106875.
27. McLaughlin T, Lamendola C, Liu A, Abbasi F.
Preferential fat deposition in subcutaneous versus
visceral depots is associated with insulin sensitivity. J Clin Endocrinol Metab 2011;96:E175660.
28. Liu J, Fox CS, Hickson DA, et al. Impact of
abdominal visceral and subcutaneous adipose tissue on cardiometabolic risk factors: the Jackson
Heart Study. J Clin Endocrinol Metab 2010;95:
541926.
29. Therkelsen KE, Pedley A, Rosenquist KJ, et al.
Adipose tissue attenuation as a marker of adipose
tissue quality: Associations with six-year changes
in body weight. Obesity 2015;24:499505.
30. Sun K, Kusminski CM, Scherer PE. Adipose
tissue remodeling and obesity. J Clin Invest 2011;
121:2094101.
31. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inammation and metabolic disease. Nat
Rev Immunol 2011;11:8597.

Lee et al.

JACC VOL. 68, NO. 14, 2016


OCTOBER 4, 2016:150921

Abdominal Fat and Cardiometabolic Risk Factors

32. Makki K, Froguel P, Wolowczuk I. Adipose


tissue in obesity-related inammation and insulin
resistance: cells, cytokines, and chemokines. ISRN
inamm 2013;2013:139239.

metabolically active and inactive adipose tissues:


preliminary ndings. J Comput Assist 2011;35:
6571.

33. Despres JP, Lemieux I. Abdominal obesity and


metabolic syndrome. Nature 2006;444:8817.

Abdominal obesity and the metabolic syndrome:


contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol 2008;28:103949.

34. Furlan A, Fakhran S, Federle MP. Spontaneous


abdominal hemorrhage: causes, CT ndings, and
clinical implications. AJR Am J Roentgenol 2009;
193:107787.
35. Trayhurn P. Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev 2013;
93:121.
36. Murphy RA, Register TC, Shively CA, et al.
Adipose tissue density, a novel biomarker predicting mortality risk in older adults. J Gerontol A
Biol Sci Med Sci 2014;69:10917.
37. Baba S, Jacene HA, Engles JM, et al. CT
Hounseld units of brown adipose tissue increase

39. Despres JP, Lemieux I, Bergeron J, et al.

40. Fujioka S, Matsuzawa Y, Tokunaga K, et al.


Improvement of glucose and lipid metabolism
associated with selective reduction of intraabdominal visceral fat in premenopausal women
with visceral fat obesity. Int J Obes 1991;15:8539.
41. Leenen R, van der Kooy K, Droop A, et al.
Visceral fat loss measured by magnetic resonance
imaging in relation to changes in serum lipid levels
of obese men and women. Arterioscler Thromb
1993;13:48794.
42. Kanai H, Tokunaga K, Fujioka S, et al. Decrease

with activation: preclinical and clinical studies.


J Nucl Med 2010;51:24650.

in intra-abdominal visceral fat may reduce blood


pressure in obese hypertensive women. Hypertension 1996;27:1259.

38. Hu HH, Chung SA, Nayak KS, et al. Differential computed tomographic attenuation of

43. Okauchi Y, Nishizawa H, Funahashi T, et al.


Reduction of visceral fat is associated with

decrease in the number of metabolic risk factors in


Japanese men. Diabetes Care 2007;30:23924.
44. Albu JB, Heilbronn LK, Kelley DE, et al.
Metabolic changes following a 1-year diet and
exercise intervention in patients with type 2 diabetes. Diabetes 2010;59:62733.
45. Schaefer EJ, Woo R, Kibata M, et al. Mobilization of triglyceride but not cholesterol or
tocopherol from human adipocytes during weight
reduction. Am J Clin Nutr 1983;37:74954.
46. Andersson DP, Eriksson Hogling D, Thorell A,
et al. Changes in subcutaneous fat cell volume and
insulin sensitivity after weight loss. Diabetes Care
2014;37:18316.

KEY WORDS cardiovascular disease,


computed tomography, epidemiology, fat
attenuation, subcutaneous adipose tissue,
visceral adipose tissue

A PP END IX For supplemental tables, please


see the online version of this article.

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