Research

JAMA Oncology | Original Investigation

Body Composition and Cardiovascular Events

in Patients With Colorectal Cancer
A Population-Based Retrospective Cohort Study
Justin C. Brown, PhD; Bette J. Caan, DrPH; Carla M. Prado, PhD; Erin Weltzien, BA; Jingjie Xiao, PhD;
Elizabeth M. Cespedes Feliciano, ScD; Candyce H. Kroenke, ScD; Jeffrey A. Meyerhardt, MD

Invited Commentary
IMPORTANCE Patients with colorectal cancer (CRC) are up to 4-fold more likely than Supplemental content
individuals without a history of cancer to develop cardiovascular disease. Clinical care
guidelines recommend that physicians counsel patients with CRC regarding the association
between obesity (defined using body mass index [BMI] calculated as weight in kilograms
divided by height in meters squared) and cardiovascular disease risk; however, this
recommendation is based on expert opinion.

OBJECTIVE To determine which measures of body composition are associated with major
adverse cardiovascular events (MACEs) in patients with CRC.

DESIGN, SETTING, AND PARTICIPANTS Population-based retrospective cohort study of 2839

patients with stage I to III CRC diagnosed between January 2006 and December 2011 at an
integrated health care system in North America.

EXPOSURES The primary exposures were BMI and computed tomography–derived body
composition measurements (eg, adipose tissue compartments and muscle characteristics)
obtained at the diagnosis of CRC.

MAIN OUTCOMES AND MEASURES The primary outcome was time to the first occurrence of
MACE after diagnosis of CRC, including myocardial infarction, stroke, and cardiovascular
death.

RESULTS In this population-based cohort study of 2839 participants with CRC (1384 men and
1455 women), the average age (SD) was 61.9 (11.5) years (range, 19-80 years). A substantial
number of patients were former (1127; 40%) or current smokers (340; 12%), with
hypertension (1150; 55%), hyperlipidemia (1389; 49%), and type 2 diabetes (573; 20%).
The cumulative incidence of MACE 10 years after diagnosis of CRC was 19.1%. Body mass
index was positively correlated with some computed tomography-derived measures of body
composition. However, BMI was not associated with MACE; contrasting BMI categories of
greater than or equal to 35 vs 18.5 to 24.9, the hazard ratio (HR) was 1.23 (95% CI, 0.85-1.77;
P = .50 for trend). Visceral adipose tissue area was associated with MACE; contrasting the
highest vs lowest quintile, the HR was 1.54 (95% CI, 1.02-2.31; P = .04 for trend).
Subcutaneous adipose tissue area was not associated with MACE; contrasting the highest vs Author Affiliations: Pennington
Biomedical Research Center, Baton
lowest quintile, the HR was 1.15 (95% CI, 0.78-1.69; P = .65 for trend). Muscle mass was not Rouge, Louisiana (Brown); Stanley S.
associated with MACE; contrasting the highest vs lowest quintile, the HR was 0.96 (95% CI, Scott Cancer Center, Louisiana State
0.57-1.61; P = .92 for trend). Muscle radiodensity was associated with MACE; contrasting the University Health Sciences Center,
New Orleans (Brown); Kaiser
highest (ie, less lipid stored in the muscle) vs lowest quintile, the HR was 0.67 (95% CI,
Permanente Northern California,
0.44-1.03; P = .02 for trend). Oakland (Caan, Weltzien, Cespedes
Feliciano, Kroenke); University of
CONCLUSIONS AND RELEVANCE Visceral adiposity and muscle radiodensity appear to be risk Alberta, Edmonton, Alberta, Canada
(Prado, Xiao); Dana-Farber Cancer
factors for MACE. Body mass index may have limited use for determining cardiovascular risk Institute, Boston, Massachusetts
in this patient population. (Meyerhardt).
Corresponding Author: Justin C.
Brown, PhD, Pennington Biomedical
Research Center, 6400 Perkins Rd,
JAMA Oncol. doi:10.1001/jamaoncol.2019.0695 Baton Rouge, LA 70808 (justin.
Published online May 16, 2019. brown@pbrc.edu).

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 Research Original Investigation
C
olorectal cancer (CRC) is the fourth most common ma-
lignant neoplasm in the United States.1 Five-year sur-
vival for patients with CRC has increased by 33% over
the past 4 decades.2 Patients with CRC are now more suscep-
tible to competing causes of morbidity and mortality, such as
those from cardiovascular disease (CVD).3,4 Patients with CRC
are 2-fold to 4-fold more likely than individuals without a his-
tory of cancer to develop CVD.5 Given the high risk of CVD in
patients with CRC, evidence is necessary to inform cardiovas-
cular management in this susceptible population.
The American Cancer Society’s CRC survivorship care
guidelines recommend that physicians counsel patients with
CRC regarding the association between obesity (defined using
body mass index [BMI], which is calculated as weight in kilo-
grams divided by height in meters squared) and CVD risk, a rec-
ommendation based exclusively on expert opinion.6 More-
over, uncertainty exists regarding the use of BMI for optimal
cardiovascular risk management.7-9 At CRC diagnosis, pa-
tients undergo radiologic imaging with computed tomogra-
phy (CT) to characterize the disease stage. Using commer-
cially available automated analysis methods, CT images can
be used to quantify body composition, including visceral and
subcutaneous adiposity and muscle mass and radiodensity
(a measure of lipid deposition into skeletal muscle).10 Quan-
tification of body composition may improve prognostication
of overall and cancer-specific survival11; however, the incre-
mental utility to guide CVD risk management is unknown.
This study aimed to achieve 3 objectives using a popula-
tion-based retrospective cohort of 2839 patients with CRC who
were treated with curative intent. The first objective was to
quantify the incidence of cardiovascular events up to 10 years
after diagnosis of CRC. The second objective was to quantify
the correlation between BMI and other measures of body com-
position. The third objective was to determine if specific BMI
categories and CT-derived measures of body composition are
risk factors for cardiovascular events independent of tradi-
tional risk factors, including smoking, hypertension, hyper-
lipidemia, and type 2 diabetes.
Methods
Study Population and Design
The Colorectal, Sarcopenia, Cancer And Near-term Survival
(C-SCANS) cohort was derived from the Kaiser Permanente
Northern California (KPNC) cancer registry, with ascertain-
ment of all patients aged 18 to 80 years who were diagnosed
with stage I to III invasive CRC from 2006 to 2011 and under-
went surgical resection for CRC (n = 4465). We excluded 693
patients without abdominal or pelvic CT images, 411 patients
without valid measures of body mass, 99 patients whose CT
images were unreadable owing to poor image quality, and 423
patients who had a history of myocardial infarction or stroke
documented in the electronic medical record (EMR) prior to
CRC diagnosis. The final analytic sample included 2839 pa-
tients. A waiver of written patient informed consent was ob-
tained by the study investigators, and this study was ap-
proved by the KPNC and University of Alberta institutional
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Body Composition and Cardiovascular Events in Patients With Colorectal Cancer
Key Points
Question Which measures of body composition are associated
with major adverse cardiovascular events in patients with
colorectal cancer (CRC)?
Findings In this population-based cohort study of 2839 patients
with CRC, body composition measured by visceral adiposity and
muscle radiodensity was associated with major adverse
cardiovascular events, whereas body composition measured by
body mass index was not associated with these events.
Meaning Body composition measures collected using routine
computed tomographic images, including visceral adiposity and
muscle radiodensity, can be used to assess cardiac risk in patients
with CRC; however, body mass index may have limited use for
assessing cardiovascular risk in this patient population.
review boards. Data analyses were performed from March 2018
to September 2018.
Measures of Body Composition
Height in meters and weight in kilograms were measured by
medical assistants at the time of diagnosis. Body mass index
was calculated as weight in kilograms divided by height in me-
ters squared and categorized using the World Health Organi-
zation classifications.12 Body composition was measured using
a single-slice transverse CT image of the third lumbar verte-
b r a a n d a n a l yze d w it h s l i c e O m at i c s o f t w a re V 5 .0
(TomoVision).13 Tissues were demarcated with a semiauto-
mated procedure using Hounsfield unit thresholds of −29 to
150 for muscle, −150 to −50 for visceral adipose tissue, and −190
to −30 for subcutaneous adipose tissue. Muscle radiodensity
quantifies the average radiation attenuation rate (in Houn-
sfield units) and is a radiologic measure of lipid deposition into
skeletal muscle.14 A randomly selected subsample of 50 CT im-
ages were analyzed by 2 research staff members blinded to out-
come (eFigure 1 in the Supplement), and the remaining CT im-
ages were analyzed by a single trained research staff member
blinded to outcome.
Covariates
The KPNC EMR was used to obtain baseline information on age,
sex, self-reported race and ethnicity, and CVD risk factors, in-
cluding smoking history, hypertension, hyperlipidemia, and
type 2 diabetes.15 Cardiovascular disease risk factors were ob-
tained using a 36-month lookback period from the time of CRC
diagnosis in the EMR. The KPNC cancer registry provided in-
formation on the anatomical site of cancer, cancer stage, and
the administration of chemotherapy and radiation. Covariate
data was 99.9% complete (2 missing observations for self-
reported race and ethnicity and 3 missing observations for
smoking history).
Study Outcomes
The primary end point was defined as the time from cancer
diagnosis to the first occurrence of any component of the com-
posite major adverse cardiovascular event (MACE) outcome,
including death from cardiovascular causes, nonfatal myocar-
dial infarction, or nonfatal stroke (3-component MACE). The
jamaoncology.com
 Body Composition and Cardiovascular Events in Patients With Colorectal Cancer Original Investigation Research

3-component MACE is recommended by the US Food and Drug

Table 1. Baseline Characteristics of the Study Population
Administration for use in cardiovascular safety studies.16
Deaths were identified from the California State death regis- No. (%)a
Characteristic (n = 2839)
try, the National Death Index (using Social Security Adminis- Age, mean (SD), y 61.9 (11.5)
tration data), and KPNC electronic mortality files. Deaths were Sex
classified as cardiovascular specific if a cardiovascular cause
Male 1384 (49)
was documented as an underlying or contributing cause of
Female 1455 (51)
death on the death certificate through January 31, 2015. Vali-
Race/ethnicity
dated International Classification of Diseases codes were used
White 1828 (64)
to identify nonfatal myocardial infarction and nonfatal stroke
Black 201 (7)
in the EMR. 17,18 The end point event database was con-
Hispanic 320 (11)
structed by investigators blinded to BMI and body composi-
Asian and Pacific Islander 468 (17)
tion values.
Other 22 (1)
Cancer site
Statistical Analysis
Two time-to-event regression models were used to estimate Colon 1992 (70)

hazard ratios (HRs) and 95% CIs for each body composition Rectal 847 (30)
variable. The first regression model estimated the cause- Cancer stage
specific hazard using a Cox proportional hazards regression I 859 (30)
model. The cause-specific hazard is interpreted as the mag- II 891 (31)
nitude of the relative change in the instantaneous rate of the III 1089 (39)
occurrence of MACE in patients who are event free.19 The sec- Cancer treatment
ond regression model estimated the subdistribution hazard Chemotherapy 1501 (53)
using a Fine-Gray competing risk model.20 The subdistribu- Radiation 454 (16)
tion hazard is interpreted as the magnitude of relative change Smoking history
in the instantaneous rate of the occurrence of MACE in pa- Never 1389 (48)
tients who are event free or who have experienced a compet- Former 1127 (40)
ing event (eg, death from noncardiovascular causes, such as Current 340 (12)
CRC, which we previously reported is associated with body Cardiovascular risk factors
composition).21,22 Detailed comparisons of these 2 regres-
Hypertension 1150 (55)
sion models are described elsewhere.23,24 Contrasts were es-
Hyperlipidemia 1389 (49)
timated to test for trends across categories.
Type 2 diabetes 573 (20)
Covariates were chosen a priori and included age, sex, race,
Body composition measures, mean (SD)
ethnicity, cancer site, cancer stage, cancer treatment, smok-
Body mass, kg 80.8 (20.5)
ing history, hypertension, hyperlipidemia, and type 2 diabe-
Height, m 1.7 (0.1)
tes; analyses of CT-derived measures of body composition were
BMI 28.1 (6.0)
adjusted for patient height.25 One subgroup was specified a
Visceral adipose tissue area, cm2 151.7 (108.2)
priori, to test if sex modified any associations between BMI and
body composition with the risk of MACE. Effect modification Subcutaneous adipose tissue area, cm2 213.3 (121.2)

was examined by adding a statistical interaction term to the Muscle mass, cm2 140.5 (38.3)

regression model. Correlations between BMI and measures of Muscle radiodensity, HU 39.6 (9.8)
body composition were quantified using the Pearson correla- Abbreviations: BMI, body mass index (calculated as weight in kilograms divided
tion coefficient with 95% CI. by height in meters squared); HU, Hounsfield units.
a
Unless otherwise indicated, the number in parentheses is the percentage
of patients.

Results
Characteristics of the Study Cohort
Of 2839 participants, 1384 were men and 1455 were women
with an average (SD) age of 61.9 (11.5) years (range, 19-80 years).
Many participants were former (n = 1127, 40%) or current smok-
ers (n = 340, 12%) and had hypertension (n = 1150, 55%), hy-
perlipidemia (n = 1389, 49%), and type 2 diabetes (n = 573,
20%) (Table 1).
Computed tomographic images were obtained at a
median of 6 days (interquartile range [IQR], 0-13) after results
of a biopsy confirmed diagnosis of CRC. By a median fol-
low-up of 6.8 years (IQR, 5.2- 8.3), MACE had occurred in 366
participants (12.9%). The cumulative incidence of MACE at 1,
3, and 10 years after diagnosis was 3.4%, 5.9%, 19.1%, respec-
tively (Figure).
Correlation Between BMI and Body Composition
Body mass index was positively correlated with visceral adi-
pose tissue area (r = 0.61; 95% CI, 0.59-0.63), subcutaneous
adipose tissue area (r = 0.83; 95% CI, 0.82-0.85), and muscle
mass (r = 0.41; 95% CI, 0.38-0.44). Body mass index was nega-
tively correlated with muscle radiodensity (r = −0.33; 95% CI,
−0.37 to −0.30).

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 Research Original Investigation
Figure. Cumulative Incidence Estimates of the Proportion of Participants
Experiencing a Major Adverse Cardiovascular Event
0.25
Cumulative Incidence of MACE
0.20
0.15
0.10
0.05
0
0 1 2 3 4 5 6 7
Time, y
The solid line denotes the cumulative incidence function estimate accounting
for competing risk. Shading around the line denotes the 95% CI. MACE
indicates major adverse cardiovascular event.
BMI, Body Composition, and Major Adverse
Cardiovascular Events
Body mass index was not associated with risk of MACE. For
BMI categories greater than 35 vs 18.5 to 24.9, the HR was 1.23
(95% CI, 0.85-1.77; P = .50 for trend) (Table 2). Contrasting the
highest to lowest quintile of visceral adipose tissue area, the
multivariable-adjusted cause-specific HR for MACE was 1.54
(95% CI, 1.02-2.31; P = .04 for trend) (eFigure 2 in the Supple-
ment). Conversely, subcutaneous adipose tissue area was not
associated with risk of MACE. Contrasting the highest vs the
lowest quintile, the HR for MACE was 1.15 (95% CI, 0.78-1.69;
P = .65 for trend). Muscle mass was not associated with risk
of MACE; comparing the highest vs lowest quintile, the HR for
MACE was 0.96 (95% CI, 0.57-1.61; P = .92 for trend). Contrast-
ing the highest (eg, less lipid stored in the muscle) to lowest
quintile of muscle radiodensity, the multivariable-adjusted
cause-specific HR for MACE was 0.67 (95% CI, 0.44-1.03;
P = .02 for trend). Sex did not modify the association be-
tween any body composition measure and risk of MACE
(results not shown). Effect estimates did not meaningfully dif-
fer when body composition measures were analyzed in their
continuous form (eTable 1 and eFigure 3 in the Supplement),
when body composition measures were additionally
adjusted for BMI (eTable 2 in the Supplement), or in a variety
of sensitivity analyses (eTables 3-6 and eFigure 4 in the
Supplement).
Discussion
In this population-based cohort, 1 of 5 patients experienced
MACE within 10 years after CRC diagnosis. Visceral adipos-
ity but not subcutaneous adiposity was statistically signifi-
cantly associated with the risk of MACE. To our knowledge,
we are among the first to study muscle mass and muscle
radiodensity in relation to MACE in CRC; of these muscle
characteristics, muscle radiodensity was statistically signifi-
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Body Composition and Cardiovascular Events in Patients With Colorectal Cancer
cantly associated with the risk of MACE whereas muscle
mass was not. These associations were independent of
other established cardiovascular risk factors, including
smoking, hypertension, hyperlipidemia, and type 2 diabe-
tes. Surprisingly, BMI was not associated with the risk of
MACE in this cohort.
Incident CRC and CVD share many risk factors, includ-
ing excess adiposity.26 Improvements in early cancer detec-
tion and chemotherapy efficacy have reduced the risk of
disease recurrence and cancer-specific mortality in CRC
survivors.27 However, the increasing burden of CVD in this
population may compromise improvements in overall
survival.28 Among 1966 Australian patients with CRC, the
3-year cumulative incidence of CVD after diagnosis of CRC
8 9 10 11 was 16%.29 Among 72 408 Medicare beneficiaries with CRC,
the 10-year cumulative incidence of CVD after diagnosis of
CRC was 57%.5 Physicians should be aware that patients
diagnosed with CRC are not only at risk for cancer recur-
rence but are at high risk of developing CVD at some point
during their survivorship trajectory. Furthermore, this CVD
risk is not described by BMI alone, and other body composi-
tion measures should be considered to identify patients
most in need of preventive cardiovascular care.
Visceral adipose tissue area and muscle radiodensity were
identified as risk factors for MACE. The risk of MACE was higher
among patients in the highest quintile of visceral adiposity,
compared with those in the lowest quintile. These data are con-
sistent with observations that waist circumference (an anthro-
pometric proxy measure for visceral adipose tissue area) is in-
dependently associated with CVD.30 A meta-analysis of 15
studies with 258 114 participants demonstrated that each 1-cm
increase in waist circumference increased the risk of a CVD
event by 2%.31
The risk of MACE was lower among patients in the high-
est quintile of muscle radiodensity (ie, less lipid stored in the
skeletal muscle), compared with those in the lowest quintile.
The exact mechanisms linking muscle radiodensity to MACE
are not clear. Muscle is an ectopic adiposity depot, and the ac-
cumulation of adiposity within skeletal muscle alters whole-
body metabolism, manifesting in insulin resistance,14 im-
paired glucose tolerance, and type 2 diabetes.32 In addition,
intermuscular adiposity is positively associated with a vari-
ety of proinflammatory mediators that are associated with CVD
risk, such as C-reactive protein, interleukin-6, and tumor ne-
crosis factor.33 Further research is necessary to better under-
stand the mechanisms linking muscle radiodensity to MACE.
In CRC survivors, we found no association between BMI
and the risk of MACE. Uncertainty exists regarding the use of
BMI as the optimal measure for c ardiovascular risk
stratification.34 In a nationally representative sample of 13 601
adults, obesity defined as a BMI category of 30 or more had a
high sensitivity (≥95%) but poor specificity (36%-49%) in iden-
tification of obesity defined using percent body fat with bio-
electric impedance analysis.9 A meta-analysis of 10 studies
demonstrated that anthropometric measures of visceral adi-
posity are superior to BMI in identifying cardiovascular risk fac-
tors, including hyperlipidemia, hypertension, and type 2
diabetes.8
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 Body Composition and Cardiovascular Events in Patients With Colorectal Cancer Original Investigation Research

Table 2. Association Between Categorical Measures of Body Composition and Major Adverse Cardiovascular Events
P Value
for
Measure Body Composition Measurement Category Trend
BMI <18.5 18.5-24.9 25.0-29.9 30.0-34.9 ≥35.0
Mean (SD), kg/m2 17.3 (1.0) 22.5 (1.7) 27.3 (1.4) 32.2 (1.4) 40.0 (4.3)
No. events/No. at risk 4/52 114/888 133/1,016 68/551 47/332
Cause-specific hazard model,a 0.64 (0.23-1.74) 1 [Reference] 0.98 (0.76-1.27) 0.89 (0.65-1.22) 1.23 (0.85-1.77) .50
HR (95% CI)
Subdistribution hazard model,a 0.53 (0.19-1.53) 1 [Reference] 1.01 (0.78-1.31) 0.90 (0.65-1.24) 1.18 (0.81-1.71) .54
HR (95% CI)
Visceral Adipose Tissue Area, cm2 <53.9 53.9-106.2 106.3-163.6 163.7-238.0 ≥238.1
Mean (SD), cm2 26.0 (15.5) 79.2 (15.4) 135.0 (16.4) 199.1 (20.8) 319.7 (74.5)
No. events/No. at risk 41/568 62/570 72/566 83/568 108/567
Cause-specific hazard model,a 1 [Reference] 1.25 (0.84-1.86) 1.42 (0.96-2.10) 1.50 (1.01-2.23) 1.54 (1.02-2.31) .04
HR (95% CI)
Subdistribution hazard model,a 1 [Reference] 1.30 (0.87-1.94) 1.48 (1.00-2.21) 1.57 (1.05-2.35) 1.59 (1.06-2.40) .02
HR (95% CI)
Subcutaneous Adipose Tissue <117.3 117.4-163.0 163.1-214.1 214.2-294.9 ≥295.0
Area, cm2
Mean (SD), cm2 82.7 (26.9) 141.1 (13.1) 186.2 (14.9) 250.4 (23.8) 406.6 (101.1)
No. events/No. at risk 65/568 85/568 81/568 73/569 62/566
Cause-specific hazard model,a 1 [Reference] 1.21 (0.87-1.68) 1.20 (0.86-1.68) 1.12 (0.79-1.58) 1.15 (0.78-1.69) .65
HR (95% CI)
Subdistribution hazard model,a 1 [Reference] 1.28 (0.92-1.78) 1.26 (0.90-1.78) 1.16 (0.81-1.65) 1.16 (0.78-1.73) .65
HR (95% CI)
Muscle Mass, cm2 <105.3 105.4-123.9 124.0-147.8 147.9-174.6 ≥174.7
Mean (SD), cm2 93.6 (8.8) 114.1 (5.3) 135.3 (7.0) 161.1 (7.4) 198.8 (20.1)
No. events/No. at risk 79/570 63/566 71/568 80/571 73/564
Cause-specific hazard model,a 1 [Reference] 0.88 (0.63-1.25) 0.81 (0.54-1.20) 0.85 (0.53-1.35) 0.96 (0.57-1.61) .92
HR (95% CI)
Subdistribution hazard model,a 1 [Reference] 0.90 (0.63-1.27) 0.88 (0.60-1.30) 0.89 (0.56-1.43) 1.03 (0.62-1.73) .88
HR (95% CI)
Muscle Radiodensity, HU <31.5 31.5-37.5 37.6-42.5 42.6-48.0 ≥48.1
Mean (SD), HU 25.4 (4.9) 34.6 (1.7) 40.1 (1.5) 45.1 (1.6) 52.8 (4.3)
No. events/No. at risk 130/569 84/568 62/567 54/568 36/567
Cause-specific hazard model,a 1 [Reference] 0.68 (0.51-0.90) 0.58 (0.42-0.80) 0.68 (0.48-0.97) 0.67 (0.44-1.03) .02
HR (95% CI)
Subdistribution hazard model,a 1 [Reference] 0.71 (0.54-0.95) 0.61 (0.44-0.85) 0.72 (0.51-1.02) 0.70 (0.45-1.08) .04
HR (95% CI)
Abbreviations: BMI, body mass index (calculated as weight in kilograms divided radiation, smoking history, hyperlipidemia, hypertension, type 2 diabetes, and
by height in meters squared); HR, hazard ratio; HU, Hounsfield units. height (the analysis of body mass index did not include height as a covariate).
a
Models are adjusted for age, sex, race/ethnicity, cancer stage, chemotherapy,

Limitations sue volume or changes in this volume are associated with

The main limitation of this study is the observational
design, which precludes our ability to rule out residual con-
founding. The data used in our analysis were collected for
clinical care purposes. The reliance of this study on admin-
istrative codes within the EMR precluded our ability to
obtain information on patient behaviors such as physical
activity, dietary patterns, and other behaviors or health con-
ditions that may influence body composition and the risk of
MACE. The measurement of physical activity was adopted
across the KPNC health care system beginning in October
2009. 35 Consequently, only 230 (8%) of our cohort had
physical activity measures available at the time of CRC diag-
nosis. Moreover, using administrative codes for the identifi-
cation of CVD risk factors has high specificity (>0.95), but
low sensitivity (<0.76) compared with manual medical rec-
ord review.36 Measures of body composition were obtained
at the third lumbar vertebrae at a solitary time point.
Although this anatomical region is correlated with whole-
body tissue volumes,13 it is not known how whole-body tis-
cardiovascular risk.
Conclusions
Because patients with CRC are at a higher risk of developing CVD
than the general population, physicians may wish to refine car-
diovascular risk management by integrating quantitative mea-
sures of body composition that can be derived automatically from
CT scans that are routinely obtained during CRC diagnosis. This
precision prevention approach to cardiovascular risk manage-
ment may help to cost-effectively allocate limited resources such
as dietary and physical activity counseling to patients who may
be most likely to benefit from lifestyle counseling. Our findings
suggest that body composition measures that are collected using
routine CT images, including visceral adiposity and muscle ra-
diodensity, can be used to assess risk for MACEs in patients with
CRC, whereas BMI may have limited use for determining cardio-
vascular risk in this patient population.

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 Research Original Investigation
ARTICLE INFORMATION
Accepted for Publication: February 11, 2019.
Published Online: May 16, 2019.
doi:10.1001/jamaoncol.2019.0695
Author Contributions: Drs Brown and Weltzien had
full access to all the data in the study and take respon-
sibility for the integrity of the data and accuracy of the
data analysis.
Study concept and design: Brown, Caan, Prado,
Cespedes Feliciano, Kroenke.
Acquisition, analysis, or interpretation of data:
All authors.
Drafting of the manuscript: Brown, Cespedes
Feliciano, Kroenke, Meyerhardt.
Critical revision of the manuscript for important
intellectual content: All authors.
Statistical analysis: Brown, Weltzien, Cespedes
Feliciano, Kroenke.
Obtained funding: Brown, Caan, Prado.
Administrative, technical, or material support:
Brown, Caan, Cespedes Feliciano.
Study supervision: Brown, Caan, Prado,
Meyerhardt.
Conflict of Interest Disclosures: Dr Brown reports
grants from the National Cancer Institute (paid to his
institution). Dr Prado reports personal fees from Ab-
bott Nutrition outside the submitted work.
Dr Cespedes Feliciano reports grants from National
Cancer Institute (K01-CA226155, R01CA175011)
during the conduct of the study. No other disclosures
were reported.
Funding/Support: Research reported in this publica-
tion was supported by the National Cancer Institute of
the National Institutes of Health under award
numbers K99-CA218603, R01-CA175011, and R25-
CA203650.
Role of the Funder/Sponsor: The funder had no
role in the design and conduct of the study; collection,
management, analysis, and interpretation of the data;
preparation, review, or approval of the manuscript;
and decision to submit the manuscript for publication.
Disclaimer: The content is solely the responsibility of
the authors and does not necessarily represent the
official views of the National Institutes of Health.
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