Epidemiology

Body Fat Distribution and Risk of Coronary Heart

Disease in Men and Women in the European Prospective
Investigation Into Cancer and Nutrition in Norfolk Cohort
A Population-Based Prospective Study
Dexter Canoy, MPhil, MD, PhD; S. Matthijs Boekholdt, MD, PhD; Nicholas Wareham, MBBS, FRCP;
Robert Luben, BSc; Ailsa Welch, PhD; Sheila Bingham, PhD; Iain Buchan, MD, FFPH;
Nicholas Day, PhD, FRS; Kay-Tee Khaw, MBBChir, FRCP

Background—Body fat distribution has been cross-sectionally associated with atherosclerotic disease risk factors, but the
prospective relation with coronary heart disease remains uncertain.
Methods and Results—We examined the prospective relation between fat distribution indices and coronary heart disease
among 24 508 men and women 45 to 79 years of age using proportional hazards regression. During a mean 9.1 years
of follow-up, 1708 men and 892 women developed coronary heart disease. The risk for developing subsequent coronary
heart disease increased continuously across the range of waist-hip ratio. Hazard ratios (95% CI) of the top versus bottom
fifth of waist-hip ratio were 1.55 (1.28 to 1.73) in men and 1.91 (1.44 to 2.54) in women after adjustment for body mass
index and other coronary heart disease risk factors. Hazard ratios increased with waist circumference, but risk estimates
for waist circumference without hip circumference adjustment were lower by 10% to 18%. After adjustment for waist
circumference, body mass index, and coronary heart disease risk factors, hazard ratios for 1-SD increase in hip
circumference were 0.80 (95% CI, 0.74 to 0.87) in men and 0.80 (95% CI, 0.69 to 0.93) in women. Hazard ratios for
body mass index were greatly attenuated when we adjusted for waist-hip ratio or waist circumference and other
covariates.
Conclusions—Indices of abdominal obesity were more consistently and strongly predictive of coronary heart disease than
body mass index. These simple and inexpensive measurements could be used to assess obesity-related coronary heart
Downloaded from http://ahajournals.org by on April 11, 2023

disease risk in relatively healthy men and women. (Circulation. 2007;116:2933-2943.)

Key Words: coronary disease 䡲 myocardial infarction 䡲 obesity

V isceral fat accumulation may underlie the adverse met-

abolic profile associated with obesity.1 Indeed, waist
circumference and waist-hip ratio, as indicators of abdominal
adiposity,2 have been shown to be better than body mass
index, an indicator of total adiposity, for identifying individ-
uals at higher risk of developing atherosclerotic diseases.3 It
is plausible that body mass index may be less sensitive than
waist circumference or waist-hip ratio at capturing the under-
lying and disparate metabolic effects of fat depots. A case-
control study involving populations worldwide recently re-
ported that waist-hip ratio was associated with acute
myocardial infarction independently of, and more strongly
than, body mass index.4 However, the prospective relation
between fat distribution and coronary heart disease is less
clear because findings have been inconsistent.5–20 Many
prospective studies reported fewer coronary heart disease
events, whereas others relied on self-reported anthropometry.
Comparison of risks between sexes is limited because many
studies involved only women or men.
Clinical Perspective p 2943
Furthermore, waist and hip circumferences have been
shown to have separate and opposite cross-sectional associ-
ations with metabolic factors.21–27 The prognostic relevance
of these separate associations for future coronary heart
disease events is less clear.16,19 We examined the prospective

Received November 1, 2006; accepted October 16, 2007.

From the Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK (D.C., A.W., R.L., S.B., N.D., K.K.); Northwest
Institute for Bio-Health Informatics, University of Manchester, Manchester, UK (D.C., I.B.); Department of Cardiology, Academic Medical Center,
Amsterdam, Netherlands (S.M.B.); MRC Epidemiology Unit, Cambridge, UK (N.W.); MRC Centre for Nutritional Epidemiology in Cancer Prevention
and Survival, Cambridge, UK (S.B.); and MRC Dunn Human Nutrition Unit, Cambridge, UK (S.B.).
The online-only Data Supplement, consisting of tables, is available with this article at http://circ.ahajournals.org/cgi/content/full/CIRCULATIONAHA.
106.673756/DC1.
Correspondence to Dexter Canoy, MPhil, MD, PhD, Northwest Institute for Bio-Health Informatics, The University of Manchester, University Place
(1st Floor), Oxford Rd, Manchester M13 9PL, UK. E-mail dexter.canoy@manchester.ac.uk
© 2007 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.106.673756

2933
 2934 Circulation December 18/25, 2007
relation between indices of fat distribution and future coro-
nary heart disease among men and women in the general
population and determined whether this association is inde-
pendent of body mass index and other conventional coronary
heart disease risk factors. We also explored the contribution
of hip girth in predicting future coronary heart disease.
Methods
The European Prospective Investigation Into Cancer and Nutrition in
Norfolk (EPIC-Norfolk) is a prospective population study of men
and women 45 to 79 years of age living in Norfolk, UK, who were
recruited from general practice registers during 1993–1997.28 The
study was approved by the Norfolk Health District Ethics Commit-
tee, and participants signed an informed consent. At the clinic visit,
trained research nurses took anthropometric measurements on indi-
viduals in light clothing without shoes using a standard protocol.29
Height was measured to the nearest 0.1 cm with a free-standing
stadiometer. Weight was measured to the nearest 100 g with digital
scales (Salter, UK). We used a D-loop nonstretch fiberglass tape to
measure waist circumference (measured at the smallest circumfer-
ence between the ribs and iliac crest) and hip circumference
(measured at the maximum circumference between the iliac crest and
the crotch) to the nearest 0.1 cm. We calculated body mass index as
weight/height2 (kg/m2) and waist-hip ratio as waist circumference/
hip circumference. Body mass index was correlated with waist-hip
ratio (men⫽0.56, women⫽0.40) and waist circumference (men and
women⫽0.85). Both body mass index and waist circumference were
correlated with hip circumference in men and women (all coeffi-
cients⫽0.80). After adjustment for age and sex, the correlations of
body mass index with waist, hip, and waist-hip ratio were 0.85, 0.86,
and 0.46, respectively, and the correlation of waist to hip was 0.80.
We obtained blood pressure readings and measured serum lipid
concentration from nonfasting blood samples.21,22,28 Participants
Downloaded from http://ahajournals.org by on April 11, 2023
completed a health and lifestyle questionnaire indicating any family
history of heart disease or physician-diagnosed prevalent diseases
such as heart attack or myocardial infarction, stroke, and diabetes
mellitus. We also assessed cigarette smoking habit (never, former,
and current),30 physical activity level (I [sedentary] to IV [most
active]),31 and alcohol intake. We further divided current smokers
into the categories of 10, 10 to 19, and ⱖ20 pack-years of smoking
(20 cigarettes per day for 365 days⫽1 smoking pack-year).
All participants were flagged for death certification at the Office
of National Statistics, and vital status was obtained for the whole
cohort. Trained nosologists coded all death certificates. Participants
admitted to a hospital were identified by their unique National Health
Service number, which a local health authority in Norfolk linked to
the Hospital Episode Statistics (a database of all hospital contacts
throughout the country). We defined coronary heart disease accord-
ing to the International Classification of Diseases, Ninth Revision
codes 410 to 414 or International Statistical Classification of
Diseases, 10th Revision codes I20 to I25. Case ascertainment
validation has been described previously.32 A case was considered if
a participant had a hospital diagnosis and/or died of coronary heart
disease during the follow-up, which ended either on the date of first
disease event (diagnosis or death) or on March 31, 2005, for the
remaining cohort. We also identified those who only developed fatal
or nonfatal acute myocardial infarction (International Classification
of Diseases, Ninth Revision code 410 or International Statistical
Classification of Diseases, 10th Revision code I21 to I22).
Statistical Analysis
Of those 25 623 who attended the baseline health check, we analyzed
data of 24 508 participants who completed the health and lifestyle
questionnaire and had complete anthropometric data. For categorical
analyses, we divided participants into sex-specific quintiles of their
baseline anthropometry. Using Cox proportional hazards regression,
we quantified the risk for developing subsequent coronary heart
disease after baseline clinical examination by calculating hazard
ratios with and without adjustments for various confounding and
mediating biological factors. Different regression models were used
because these models could help to assess the usefulness of adiposity
indices in predicting coronary heart disease events in general
populations (age-adjusted models) as well as for better understanding
of disease etiology (multivariable-adjusted models). We chose to
take into account factors known to be classic coronary heart disease
risk factors that are by themselves modifiable (hypertension, hyper-
cholesterolemia, and smoking) as well as potential confounders
because these factors are known to influence adiposity33,34 and
independently predict coronary heart disease events.20,35 Our sex-
specific multivariable models consisted of the following covariates:
age, systolic blood pressure, total cholesterol, cigarette smoking,
physical activity, and alcohol intake. We calculated hazard ratios by
fifths of adiposity indices (using the bottom fifth as the reference
category) and examined risk trends across categories by using
adiposity indices as continuous variables (per 1-quintile change) in
the regression model. We also calculated hazard ratio for every 1-SD
change in adiposity index as well as for every 1-unit change in the
adiposity measurement (waist-hip ratio⫽0.05, waist circumfer-
ence⫽5 cm, and body mass index⫽1 kg/m2) to allow us to compare
magnitude of risk estimates, particularly between men and women.
To determine the separate associations for waist and hip circumfer-
ence, we computed the age-adjusted coronary heart disease rates by
thirds of waist stratified by hip category (ⱕ102 or ⬎102 cm), which
was based on median hip circumference (men⫽102 cm, wom-
en⫽102.3 cm). We standardized disease rates on the basis of the
sex-specific age distribution of the whole cohort. We estimated
hazard ratios for waist and hip circumference with and without
adjustments for each other as well as for body mass index and other
covariates.
We also assessed discrimination (the capacity of the model to
predict true-positives as opposed to false-positives for a given
outcome) by calculating Harrell’s c statistic for the area under the
receiver operating characteristic curve of the Cox regression model
of age, age2, sex, systolic blood pressure, total cholesterol, and
cigarette smoking when added to an adiposity parameter (body mass
index, waist circumference, waist and hip circumference, or waist-
hip ratio). To assess calibration (correspondence between the prob-
ability to develop the disease as predicted by a model and the actual
disease event), we calculated the estimated risk score for each
participant on the basis of the relevant Cox regression model.36
Participants were then categorized into decile of risk scores, and a
comparison of the predicted and observed disease event was made
for each risk category by calculating the Z score (dividing the
difference by the square root of the predicted cases). We also
assessed the global goodness of fit of the model by comparing the
model with and without the indicator variable for the risk score
categories using the likelihood ratio test.37 A better calibration is
reflected by a higher probability value, whereas P⬍0.05 suggests
poorer calibration. Furthermore, we assessed the risk estimates for
excess adiposity using clinically useful categories of waist-hip ratio
(men: ⬍0.95 and ⱖ0.95; women: ⬍0.80 and ⱖ0.80) and body mass
index (⬍25, 25 to 29.9, ⱖ30 kg/m2).38 Age, systolic blood pressure,
total cholesterol, and alcohol intake were analyzed as continuous
variables, whereas cigarette smoking and physical activity were
analyzed as categorical variables in all models. We present disease
rates and risk estimates with their 95% CIs and considered P⬍0.05
significant. We conducted the analyses using Stata 9.2 (StataCorp,
College Station, Tex) statistical software.
The authors had full access to and take full responsibility for the
integrity of the data. All authors have read and agreed to the
manuscript as written.
Results
Baseline characteristics are shown in Table 1. Men and
women were ⬇60 years of age and were slightly overweight.
Higher fifths of waist-hip ratio, waist circumference, and
body mass index were related to increasing age, systolic
blood pressure, and total cholesterol (all P⬍0.001). The
proportion of current smokers increased with higher waist-hip
 Canoy et al Fat Distribution and Coronary Heart Disease 2935

Table 1. Baseline Characteristics of Men and Women in the and other covariates in men (Figure 1). In women, the linear
EPIC-Norfolk Cohort Recruited Between 1993 and 1997 association persisted despite slight attenuation after adjust-
Characteristics Men (n⫽11 117) Women (n⫽13 391) ment for covariates and exclusion of current smokers and
those with prevalent disease (Figure 2). Furthermore, risk
Age, y 60.3 (8.8) 59.6 (8.8)
estimates for waist circumference in women were almost
Systolic blood 137.8 (17.8) 134.5 (18.9) comparable to the estimates for waist-hip ratio except when
pressure, mm Hg
analyses were limited to nonsmokers without prevalent dis-
Total 6.05 (1.09) 6.35 (1.21)
ease (Table II in the online-only Data Supplement). There
cholesterol, mmol/L
was no increasing risk with higher waist circumference in
Body mass index,* 26.6 (3.3) 26.3 (4.3)
men and women with prevalent disease (P for trend ⬎0.05).
kg/m2
The age- and covariate-adjusted hazard ratios also in-
Waist circumference, 95.9 (9.8) 82.4 (10.8)
creased with increasing fifths of body mass index (Table III
cm
in the online-only Data Supplement) in both men and women
Hip circumference, cm 102.8 (6.4) 103.5 (9.2)
(body mass index⫻sex interaction: P⬎0.05). However, the
Waist-hip ratio 0.932 (0.060) 0.795 (0.063) graded relation was no longer demonstrable with further
Alcohol intake, U/wk 10.1 (11.8) 4.3 (5.7) adjustments for waist-hip ratio and when the analyses were
Cigarette smoking limited to those without prevalent disease and nonsmokers
habit, % (n) (Figures 1 and 2). Among those with prevalent disease, the
Current smokers 12.2 (1341) 11.2 (1490) linear increase in the hazard ratios with higher body mass
Former smokers 55.3 (6101) 32.5 (4301) index was noted in women (P for trend⫽0.046) but not in
Never smokers 32.6 (3598) 56.3 (7463) men (P⬎0.05).
Sedentary lifestyle† 29.6 (3299) 29.4 (3935)
We also explored the role of other lipids as potential
biological mediating factors. With adjustment for covariates
Prevalent disease‡ 9.6 (1063) 3.8 (508)
as well as high-density lipoprotein cholesterol, nonfasting
Parental history of 30.3 (3364) 32.3 (4332)
triglycerides, and body mass index, the linear increase in risk
heart attack
across waist-hip ratio fifths was attenuated but remained
Data are presented as mean (SD) for continuous variables or proportions for significant in men (P for trend ⬍0.001) and women (P for
categorical variables; proportions may not add up to 100% because of some
trend⫽0.003) even after exclusion of those with prevalent
missing variables.
*Weight/height2. disease (P for trend: men, P⬍0.001; women, P⫽0.023); the
Downloaded from http://ahajournals.org by on April 11, 2023

†Physical activity index I.
‡Self-reported physician-diagnosed heart disease, stroke, or diabetes
mellitus at baseline.
ratio fifths (P⬍0.001) but not with higher fifths of waist
circumference or body mass index (both P⬎0.05).
After a mean follow-up of 9.1 years (222 701 person-
years), we observed 2600 coronary heart disease events (662
fatal and 1938 nonfatal) with 1708 events in men (27.6%
fatal) and 892 events in women (21.4% fatal). When catego-
rized into fifths, an increasing risk for coronary heart disease
was observed across the whole range of waist-hip ratio with
no apparent threshold in both men and women (Table I in the
online-only Data Supplement). The graded linear association
was attenuated but persisted after adjustment for various
covariates. Figures 1 (men) and 2 (women) show an increas-
ing risk trend with higher waist-hip ratio after adjustment for
body mass index and other coronary heart disease risk factors
(waist-hip ratio⫻sex interaction: P⬎0.05). The association
remained significant even when we limited our analysis to
nonsmokers and those without prevalent disease. There was
no increased risk with higher waist-hip ratio for those with
prevalent disease (P for trend ⬎0.05).
Higher waist circumference fifths were associated with
higher risks for coronary heart disease, but the strength of the
association varied with adjustments for various covariates
(Table II in the online-only Data Supplement) and between
men and women (waist circumference⫻sex interaction:
P⫽0.046). In men, a monotonic linear increase was not
clearly demonstrated when we adjusted for body mass index
increasing risks across waist circumference categories was
observed for all women (P for trend⫽0.035), including
women without prevalent disease (P for trend⫽0.041), but
not in men (P for trend ⬎0.05). Across fifths of body mass
index, increasing risks were observed in men (P for
trend⫽0.007) and weakly for women (P for trend⫽0.097).
We did not observe significant trends among those without
prevalent disease or after substituting waist-hip ratio for waist
circumference in the multivariable models (all P for trend
⬎0.05).
When the risk was assessed in various subgroups, as
shown in Table 2, we found increased risks for higher
waist-hip ratio in all subgroups except in men with
parental history of myocardial infarction or who had early
coronary heart disease (occurring within 5 years of follow-
up) and among men and women with prevalent disease.
Statistical interactions were significant in men for waist-
hip ratio with prevalent disease (P⫽0.040), family history of
myocardial infarction (P⫽0.002), and early coronary heart
disease events (P⫽0.001) and in women for waist-hip ratio
with early coronary heart disease events (P⫽0.001). Waist
circumference was also associated with increased risk among
women for all subgroups except for those with prevalent
disease (P for interaction⫽0.020). However, the risk esti-
mates for waist circumference in men were smaller in
magnitude and had wider CIs.
When separate associations for waist and hip circumfer-
ence were assessed, higher waist circumference was associ-
ated with higher age-adjusted coronary heart disease rates,
but at any given waist circumference, those with bigger hips
 2936 Circulation December 18/25, 2007

Figure 1. Hazard ratios for coronary heart disease among 11 117 men (1708 cases) 45 to 79 years of age by quintiles of adiposity
indices (Q1 through Q5; lowest quintile as reference category). CVD indicates cardiovascular disease; prevalent CVD or diabetes
refers to physician-diagnosed heart disease, stroke, or diabetes mellitus at baseline. Hazard ratios were adjusted for age, systolic
blood pressure, total cholesterol, cigarette smoking, physical activity, and alcohol intake; models for waist-hip ratio and waist cir-
cumference were additionally adjusted for body mass index; models for body mass index were additionally adjusted for waist-hip
ratio. P for trend for all men: waist-hip ratio ⬍0.001, waist⫽0.027, body mass index ⬍0.001; P for trend for men without prevalent
CVD or diabetes: waist-hip ratio ⬍0.001, waist⫽0.040, body mass index⫽0.018; P for trend for men who were nonsmokers and
without prevalent CVD or diabetes: waist-hip ratio ⬍0.001, waist⫽0.055, body mass index⫽0.015. In subgroup analyses, for no
prevalent CVD or diabetes, n⫽9386 (1101 cases); for nonsmokers and no prevalent CVD or diabetes, n⫽8309 (937 cases).

had lower disease rates than those with smaller hips (Figure prevalent disease heart disease, stroke, or diabetes (both
Downloaded from http://ahajournals.org by on April 11, 2023

3). Table 3 shows the risk estimates for waist and hip
circumference; their simultaneous adjustment showed that
these indices were related to coronary heart disease, even
after adjustment for each other, and in opposite directions, ie,
increasing risk with bigger waist circumference but decreas-
ing risk with bigger hip circumference (model 3). Findings
were consistent even when we excluded those with prevalent
disease. With the use of a similar covariate-adjusted model,
Figure 4 shows the hazard ratio by waist and hip circumfer-
ence quintiles with simultaneous adjustment for each other as
well as for body mass index and other risk factors. When
those with prevalent disease were excluded, the opposite
trends remained significant for waist and hip girth in men
(P⬍0.001) and waist girth in women (P⫽0.001) but weakly
for hip girth (P⫽0.099).
When acute myocardial infarction occurring after baseline
recruitment was used as the end point (855 events), the body
mass index– and covariate-adjusted hazard ratios per 0.05
increase in waist-hip ratio were 1.13 (95% CI, 1.05 to1.23) in
men and 1.25 (95% CI, 1.13 to 1.39) in women, and per 5-cm
increase in waist circumference the risks were 1.10 (95% CI,
1.02 to 1.19) in men and 1.24 (95% CI, 1.12 to 1.38) in
women. Exclusion of those with prevalent disease showed
comparable risk estimates. The covariate-adjusted hazard
ratios per 1-kg/m2 increase in body mass index were 1.03
(95% CI, 1.01 to1.06) in men and 1.05 (95% CI, 1.02 to 1.08)
in women. These risk estimates were attenuated in both men
and women when waist-hip ratio or waist circumference was
added to the model and when we excluded those with
P⬎0.05).
We assessed how adiposity measures improved the
prediction of coronary heart disease among those without
prevalent disease. The area under the receiver operating
characteristic curve increased modestly when an adiposity
term was added to the baseline model of age, sex, and
standard coronary heart disease risk factors (Table 4). The
probability values were ⬍0.05 for all models, suggesting
poor overall goodness of fit for the models. However,
when the calibration in each stratum of risk was examined,
divergence of the observed from the predicted number of
disease events was observed mainly in the lowest 2 risk
strata for most models, with the risk models predicting up
to twice the number of observed disease events. When we
limited our analyses to noncurrent smokers, calibration for
the models improved, particularly for models with terms
for waist and hip or waist-hip ratio (Table IV in the
online-only Data Supplement). Finally, when we estimated
risks by clinical cut points for body mass index and
waist-hip ratio, highest risks were associated with higher
body mass index and waist-hip ratio (Table V in the
online-only Data Supplement). Even among lean individ-
uals (body mass index ⬍25 kg/m2), those with higher
waist-hip ratio had ⬇50% higher risk than those with
lower waist-hip ratio. These risks were not explained by
conventional risk factors.
Discussion
We observed a continuous and graded relation between
waist-hip ratio and subsequent coronary heart disease event,
 Canoy et al Fat Distribution and Coronary Heart Disease 2937

Figure 2. Hazard ratios for coronary heart disease among 13 391 women (892 cases) 45 to 79 years of age by quintiles of adipos-
ity indices (Q1 through Q5; lowest quintile as reference category). CVD indicates cardiovascular disease; prevalent CVD or diabe-
tes refers to physician-diagnosed heart disease, stroke, or diabetes mellitus at baseline. Hazard ratios were adjusted for age, sys-
tolic blood pressure, total cholesterol, cigarette smoking, physical activity, and alcohol intake; models for waist-hip ratio and
waist circumference were additionally adjusted for body mass index; models for body mass index were additionally adjusted for
waist-hip ratio. P for trend for all women: waist-hip ratio ⬍0.001, waist ⱕ0.001, body mass index⫽0.001; P for trend for women
without prevalent CVD or diabetes: waist-hip ratio ⬍0.001, waist ⱕ0.001, body mass index⫽0.006; P for trend for women who
were nonsmokers and without prevalent CVD or diabetes: waist-hip ratio⫽0.002, waist⫽0.009, body mass index⫽0.008. In sub-
group analyses, for no prevalent CVD or diabetes, n⫽11 787 (653 cases); for nonsmokers and no prevalent CVD or diabetes,
n⫽10 569 (564 cases).
Downloaded from http://ahajournals.org by on April 11, 2023

particularly among men and women who were relatively
healthy at baseline recruitment. The association persisted
even after body mass index and conventional coronary heart
disease risk factors were taken into account and could reflect
the separate and opposite associations of waist and hip
circumference with coronary heart disease. Waist-hip ratio,
waist circumference, and body mass index were directly
related to development of coronary heart disease, but the
magnitude and shape of the associations were influenced by
adjustments for possible mediating biological factors and
potential confounders. Describing the nature of the associa-
tion between adiposity and coronary heart disease with the
use of different models could be useful for different purposes,
such as in assessing coronary heart disease risk in the general
population (age-adjusted models) and understanding the bio-
logical pathways underlying the observed associations (mul-
tivariable models). However, regardless of the model used,
waist-hip ratio was independently and more consistently
predictive of coronary heart disease than waist circumference
or body mass index in both men and women.
Body mass index remained predictive of coronary heart
disease, but risk estimates were greatly attenuated when fat
distribution, biological mediating factors, and prevalent
disease were considered. Because it is simple to use, waist
circumference alone may be used because it has been
shown to be cross-sectionally associated with coronary
heart disease risk factors3 and may predict future disease
events.12,14,18 In our cohort, waist circumference predicted
future coronary heart disease events, but the magnitude of
its effect was lower than that of waist-hip ratio, particu-
larly in men. The effect modification by hip circumference
suggests that coronary heart disease risk may be underes-
timated when waist circumference alone is used. Because
waist circumference is highly correlated with hip circum-
ference and body mass index, the adverse metabolic effect
of abdominal fat deposition may not be captured when
waist circumference is used without the separate effects of
body mass index or hip girth being taken into account.
Similarly, the risks associated when hip circumference
alone is used may reflect the effect of total adiposity; lower
risks associated with higher hip girth may not be observed
without total body size being taken into account. Indeed,
other studies have similarly observed that the inverse
association between hip circumference and disease event
was contingent on adjustment for total body size such as
body mass index.4,16 On the other hand, waist-hip ratio
could be a simple but more consistent indicator of the
combined risk estimates for central and peripheral adipos-
ity in both men and women.
A number of studies addressed the prospective relation of
waist circumference or waist-hip ratio with coronary heart
disease with body mass index taken into account, but results
have been inconsistent.5–20 Associations for abdominal adi-
posity independent of body mass index and other covariates
were shown in some studies6,9,11,17 but not in others.5,15,16
Others report an independent association for waist-hip ratio
only in men,9 women,6,12,14 or older participants.10 The
prediction for coronary heart disease could also differ be-
 2938 Circulation December 18/25, 2007

Table 2. Risk for Coronary Heart Disease per 1-Unit Change in Fat Distribution Measure, Stratified by Covariates, in Men and
Women 45 to 79 Years of Age
Men (n⫽11 117) Women (n⫽13 391)

Hazard Ratio (95% CI) Hazard Ratio (95% CI)

Variables Person-Years Cases (n) WHR (per 0.05) Waist (per 5 cm) Person-Years Cases (n) WHR (per 0.05) Waist (per 5 cm)
Body mass index*
⬍25 kg/m2 331 880 452 1.12 (1.02 to 1.23) 1.04 (0.96 to 1.13) 54 354 270 1.25 (1.12 to 1.40) 1.18 (1.06 to 1.31)
ⱖ25 kg/m2 66 606 1256 1.11 (1.06 to 1.17) 1.08 (1.04 to 1.11) 69 553 622 1.11 (1.04 to 1.19) 1.09 (1.04 to 1.14)
Current smokers
No 87 053 1481 1.08 (1.03 to 1.14) 1.02 (0.97 to 1.08) 110 239 776 1.11 (1.05 to 1.18) 1.08 (1.02 to 1.15)
Yes 11 742 227 1.11 (0.97 to 1.27) 1.05 (0.92 to 1.20) 13 668 116 1.32 (1.13 to 1.55) 1.33 (1.13 to 1.56)
Age
⬍65 y 66 124 743 1.13 (1.07 to 1.20) 1.10 (1.03 to 1.17) 85 518 305 1.14 (1.02 to 1.26) 1.12 (1.01 to 1.24)
ⱖ65 y 33 670 965 1.06 (1.00 to 1.13) 0.99 (0.93 to 1.06) 38 389 587 1.17 (1.09 to 1.25) 1.14 (1.05 to 1.22)
Prevalent disease†
No 91 105 1183 1.12 (1.05 to 1.19) 1.05 (0.99 to 1.12) 119 798 723 1.17 (1.10 to 1.25) 1.14 (1.07 to 1.22)
Yes 7689 525 1.01 (0.93 to 1.09) 0.95 (0.87 to 1.03) 4109 169 1.02 (0.90 to 1.16) 0.98 (0.86 to 1.13)
Parental history of
heart attack
No 69 454 1125 1.14 (1.07 to 1.21) 1.05 (0.99 to 1.11) 84 343 541 1.13 (1.05 to 1.22) 1.11 (1.03 to 1.19)
Yes 29 235 581 1.01 (0.94 to 1.09) 0.97 (0.89 to 1.05) 39 474 348 1.15 (1.05 to 1.26) 1.12 (1.01 to 1.24)
Early CHD cases‡
No 96 726 1005 1.11 (1.04 to 1.18) 1.02 (0.96 to 1.09) 122 991 585 1.09 (1.01 to 1.17) 1.07 (1.00 to 1.16)
Yes 2068 702 0.96 (0.89 to 1.04) 0.96 (0.89 to 1.03) 916 305 1.09 (0.98 to 1.21) 1.10 (1.00 to 1.21)
Downloaded from http://ahajournals.org by on April 11, 2023

WHR indicates waist-hip ratio; CHD, coronary heart disease. All values were adjusted for all listed variables (but not early CHD cases) and for systolic blood pressure,
total cholesterol, physical activity, and alcohol intake except when used for stratification. In men, all P for interaction between fat distribution measure and covariate
⬎0.10 except for WHR and prevalent disease (P⫽0.036), WHR and parental history of heart attack (P⫽0.002), WHR and early CHD cases (P⬍0.001), waist
circumference and age (P⫽0.051), waist circumference and prevalent disease (P⫽0.060), and waist circumference and early CHD cases (P⫽0.001). In women, all
P for interaction between fat distribution measure and covariate ⬎0.10 except for WHR and early CHD cases (P⬍0.001), waist circumference and being overweight
(P⫽0.069), waist circumference and cigarette smoking (P⫽0.099), and waist circumference and early CHD cases (P⫽0.009).
*Weight/height2.
†Physician-diagnosed heart disease, stroke, or diabetes mellitus at baseline.
‡CHD occurring within 5 years of follow-up.

tween waist-hip ratio and waist circumference within a
cohort.14,18 Errors associated with self-reported measures
might obscure true relations,10,12,14 and lack of power (involv-
ing ⬇20 to ⬇500 cases5,6,8,10 –19) could provide unreliable risk
estimates. Comparisons between sexes within the same co-
hort were only possible in some studies,7,11,17,19 and any
sex-related differences in associations were not reported
adequately. Inconsistencies in the results could also be due to
differences in adjustments for confounding and mediating
factors, although a number of studies reported that the
associations between fat distribution and coronary heart
disease remained significant after adjustment for conven-
tional risk factors.6,8,12,14,17 Factors such as blood pressure or
lipids are not usually adjusted for because they may form part
of the causal pathway. However, taking these factors into
account could help toward understanding their role as medi-
ating factors. Despite the observed separate and opposing
associations between central and peripheral adiposity with
various metabolic factors, few studies investigated the prog-
nostic relevance of these cross-sectional associations. Greater
hip or thigh circumference has been associated with reduced
type 2 diabetes incidence,39 aortic calcification progression in
women,27 and coronary heart disease events in women16,19 but
not in men.19 In our cohort, the top hip circumference fifth
was related to a risk reduction of up to 44% in men and 33%
in women after waist circumference, body mass index, and
other conventional risk factors were taken into account.
Moreover, adjustment for hip circumference increased the
risk prediction afforded by using waist circumference alone
by ⬇10% to ⬇18% in men and women (risk difference
between models 3 and 1, Table 2).
Our results are comparable to the findings in INTER-
HEART, a case-control study involving populations across 52
countries4 that reported waist-hip ratio to be more strongly
associated with acute myocardial infarction than body mass
index. They estimated an increased risk of 37% per 0.085
change in waist-hip ratio (after adjustment for age, sex,
region, and body mass index), which is close to our estimate
of 39% increase in risk (based on a comparable regression
model with acute myocardial infarction used as the disease
outcome). Each 12.08-cm change in waist circumference and
10.96-cm change in hip circumference in their study was
 Canoy et al Fat Distribution and Coronary Heart Disease 2939

40
Hip circumference (cm):

102 >102
35
Age-adjusted CHD rate (cases/1000 person-years)

30

25

20

15

10

N=3262 N=467 N=1795 N=1945 N=396 N=3252 N=4069 N=637 N=2085 N=2137 N=544 N=3919
0
<77.1 77.1 to 85.6 >85.6 <91.7 91.7 to 93.4 >93.4

WOMEN (892 cases & 123 907 person-years) MEN (1708 cases & 98 794 person-years)

Waist circumference (cm)

Figure 3. Age-standardized rate (95% CI) for coronary heart disease (CHD) by waist and hip circumference categories in men and
women 45 to 79 years of age. Stratification is based on sex-specific waist circumference tertile distribution and median value of hip
circumference (median⫽102 cm in men and 102.3 cm in women).
Downloaded from http://ahajournals.org by on April 11, 2023

associated with a 25% increase and 13% decrease in risk, subcutaneous portion of the abdominal fat is unlikely to
respectively, after adjustment for age, sex, region, and body contribute to disease risk. On the contrary, subcutaneous fat,
mass index. Using a comparable model, we report a 66% which comprises 85% of total body fat,44 may help to regulate
increased risk for waist circumference and 21% reduced risk metabolism by buffering the elevated postprandial fatty acid
for hip circumference. Our results also show a significant 9% and lipid fluxes.45 Peripheral body fat, which is mainly stored
increased risk for every 4.15-kg/m2 change in body mass subcutaneously in femoral, gluteal, and thigh regions, has
index after adjustment for age, sex, and waist-hip ratio lower lipolytic activity than abdominal body fat.1 It is
compared with only 2% in INTERHEART. The magnitude of plausible that peripheral adipose tissue serves as a “metabolic
the association for each anthropometry differed slightly, sink” by taking up excess circulating fatty acids and even
perhaps reflecting variation in body fat and lean mass preventing ectopic fat accumulation, a morphological feature
according to ethnicity or medical condition during recruit- of insulin resistance.46 Indeed, absence of subcutaneous fat
ment. Unlike participants in INTERHEART, our cohort such as in lipodystrophy is associated with insulin resistance,
involved mainly white subjects who were not recruited on the dyslipidemia, and fatty liver.47 In animals, improvements in
basis of disease status. Nevertheless, the consistency in the insulin sensitivity and lipid profile have been observed in
results for waist-hip ratio for men and women in both studies transgenic lipoatrophic mice after transplantation of adipose
suggests that it could be a useful measure for assessing tissue subcutaneously.48 In humans, relatively greater periph-
obesity-related risk for atherosclerotic disease within and eral adiposity has been associated with lower blood pres-
between populations. sure,21 healthier lipid profile,22–24 and better glucose ho-
Variation in risks by the anatomic location of fat could meostasis and insulin sensitivity.23,24,26,39 The associations
reflect differences in metabolic characteristics between ab- for waist-hip ratio that we observed could reflect the
dominal and peripheral body fat. Increased abdominal obesity separate and opposite metabolic effects of central and
could indicate increased visceral fat accumulation, which is peripheral adiposity, as indicated by waist and hip circum-
associated with elevated lipolysis and portal fatty acid efflux, ference, respectively.
thereby promoting an atherogenic lipid profile, decreasing Sex hormones, growth hormones, corticosteroids, and ge-
hepatic clearance of insulin, and increasing peripheral hyper- netic factors contribute to fat patterning.49 –51 However, little
insulinemia.1 Regional variations in adipokine secretions is known about modifiable factors that influence fat distribu-
have also been observed.40,41 Because the adverse metabolic tion. Studies suggest that not smoking, physical activity, and
profile of obese individuals improved with omentectomy42 a healthy diet could contribute to healthier fat distribu-
but not with abdominal subcutaneous fat liposuction,43 the tion.30,34,52 Targeting different fat depots separately to achieve
 2940 Circulation December 18/25, 2007

Table 3. Risk for Coronary Heart Disease per 1-SD Increase in Waist and Hip Circumference in Men and Women 45 to
79 Years of Age
All
Without Prevalent Disease
Regression Model* (1 SD) Age-Adjusted Covariate-Adjusted†‡ (Covariate-Adjusted)
Men n⫽11 117 (1708 cases, 98 794 person-years) n⫽10 054 (1183 cases, 91 105 person-years)
Model 1: Waist circumference (9.8 cm) 1.23 (1.18 to 1.29) 1.20 (1.14 to 1.26) 1.18 (1.11 to 1.25)
Model 2: Hip circumference (6.4 cm) 1.10 (1.05 to 1.15) 1.09 (1.31 to 1.14) 1.08 (1.02 to 1.14)
Model 3: Waist circumference (9.8 cm) 1.40 (1.30 to 1.50) 1.34 (1.24 to 1.45) 1.32 (1.19 to 1.45)
Hip circumference (6.4 cm) 0.85 (0.79 to 0.92) 0.90 (0.83 to 0.97) 0.87 (0.79 to 0.96)
Model 4: Waist circumference (9.8 cm) 1.21 (1.10 to 1.33) 1.17 (1.06 to 1.29) 1.20 (1.06 to 1.35)
Hip circumference (6.4 cm) 0.78 (0.72 to 0.84) 0.80 (0.74 to 0.87) 0.83 (0.75 to 0.92)
Body mass index (3.3 kg/m2) 1.29 (1.18 to 1.42) 1.27 (1.15 to 1.40) 1.17 (1.04 to 1.07)
Women n⫽13 391 (892 cases, 907 person-years) n⫽12 883 (723 cases, 119 798 person-years)
Model 1: Waist circumference (10.8 cm) 1.35 (1.27 to 1.44) 1.29 (1.20 to 1.38) 1.26 (1.17 to 1.36)
Model 2: Hip circumference (9.2 cm) 1.20 (1.12 to 1.27) 1.16 (1.08 to 1.24) 1.14 (1.05 to 1.22)
Model 3: Waist circumference (10.8 cm) 1.55 (1.39 to 1.72) 1.45 (1.30 to 1.63) 1.42 (1.25 to 1.62)
Hip circumference (9.2 cm) 0.85 (0.77 to 0.94) 0.90 (0.80 to 1.00) 0.86 (0.76 to 0.98)
Model 4: Waist circumference (10.8 cm) 1.41 (1.25 to 1.59) 1.38 (1.21 to 1.57) 1.38 (1.19 to 1.59)
Hip circumference (9.2 cm) 0.74 (0.64 to 0.85) 0.80 (0.69 to 0.93) 0.82 (0.69 to 0.97)
Body mass index (4.3 kg/m2) 1.27 (1.09 to 1.48) 1.14 (0.96 to 1.34) 1.09 (0.91 to 1.31)
Values are hazard ratio (95% CI). Prevalent disease refers to reported physician-diagnosed heart disease, stroke, or diabetes mellitus at baseline.
*Waist and hip circumference used separately (models 1 and 2), together (model 3), or with additional adjustment for body mass index (model 4)
in the Cox regression model.
†Covariates were age, systolic blood pressure, total cholesterol, cigarette smoking, physical activity, and alcohol intake.
‡Because of missing values, numbers were lower in covariate-adjusted models for all (10 364 men 关1583 cases兴 and 12 230 women 关798 cases兴)
and for those without prevalent disease (10 364 men 关1583 cases兴 and 12 230 women 关798 cases兴).
Downloaded from http://ahajournals.org by on April 11, 2023

an ideal adiposity phenotype is unlikely to be feasible,
although a randomized controlled trial suggested that
exercise led to reduction in fat mass, including waist and
hip girths.34 Because waist and hip girths are highly
correlated, those with bigger hips are likely to have bigger
waist circumference and should therefore benefit from
reducing excess fat. Our findings suggested that reducing
weight by 1 kg (for a given height) could translate to
reducing coronary heart disease risk by 2% in both men
and women. Alternatively, reducing waist circumference

Figure 4. Hazard ratios for coronary heart disease by waist and hip circumference quintiles in men and women 45 to 79 years of age.
Estimates were obtained by simultaneously adding the categorical terms for waist and hip circumference quintiles in a sex-specific Cox
regression model with adjustment for body mass index, age, systolic blood pressure, total cholesterol, cigarette smoking, physical
activity, and alcohol intake.
 Canoy et al Fat Distribution and Coronary Heart Disease 2941

Table 4. Discrimination and Calibration in the Coronary Heart Disease Risk Prediction of Adiposity Indices in Relatively Healthy*
Men and Women 45 to 79 Years of Age
Decile of Risk Scores (n⫽22 937 Persons; 1906 Cases)

1st 2nd 3rd 4th 5th 6th 7th 8th 9th 10th
Model: Age⫹sex⫹CHD risk factors (area under ROC⫽0.739); ␹2⫽37.2, P⬍0.001†
Observed 12 30 56 92 117 154 198 253 343 499
Predicted 25.1 42.9 63.3 84.7 113.1 145.1 185.2 239.8 326.5 528.3
Z score ⫺2.608 ⫺1.965 ⫺0.922 0.790 0.365 0.742 0.940 0.850 0.915 ⫺1.276
Model: Age⫹sex⫹CHD risk factors⫹body mass index (area under ROC ⫽0.743); ␹2⫽29.0, P⫽0.001†
Observed 11 27 57 93 113 153 199 257 344 500
Predicted 23.3 41.2 61.6 83.1 111.1 143.8 186.0 238.2 327.9 537.8
Z score ⫺2.553 ⫺2.208 ⫺0.588 1.085 0.176 0.77 0.95 1.22 0.892 ⫺1.629
Model: Age⫹sex⫹CHD risk factors⫹waist circumference (area under ROC ⫽0.745); ␹2⫽34.2, P⬍0.001†
Observed 12 25 58 87 119 153 181 274 351 494
Predicted 23.3 40.9 61.6 83.1 110.3 143.5 185.7 236.4 327.5 542.0
Z score ⫺2.342 ⫺2.489 ⫺0.464 0.433 0.827 0.704 ⫺0.346 2.467 1.301 ⫺2.062
Model: Age⫹sex⫹CHD risk factors⫹waist⫹hip (area under ROC⫽0.746); ␹2⫽37.9, P⬍0.001†
Observed 13 26 54 79 125 144 187 278 350 498
Predicted 23.3 40.7 61.1 82.8 109.7 143.5 184.1 237.4 327.4 544.0
Z score ⫺2.131 ⫺2.306 ⫺0.908 ⫺0.419 1.457 0.046 0.216 0.2632 1.25 ⫺1.972
Model: Age⫹sex⫹CHD Risk factors⫹waist-hip ratio (area under ROC⫽0.746); ␹2⫽30.5, P⬍0.001†
Observed 13 30 52 80 123 148 187 270 346 505
Predicted 23.4 40.6 61.3 82.9 109.7 143.4 184.1 239.3 327.5 541.8
Z score ⫺2.153 ⫺1.667 ⫺1.188 ⫺0.317 1.27 0.388 0.211 1.983 1.024 ⫺1.58
CHD indicates coronary heart disease; ROC, receiver operating characteristics. First tenth is the lowest risk. Discrimination of the Cox regression model was
assessed by calculating the area under the ROC as estimated by Harrell’s c statistic; calibration of the Cox regression model was assessed by difference between
Downloaded from http://ahajournals.org by on April 11, 2023

the predicted and observed disease event in each stratum of risk score decile. A quadratic term for age was fitted in all models. CHD risk factors were systolic blood
pressure, cholesterol, and cigarette smoking.
*Without prevalent heart disease, stroke, or diabetes mellitus.
†Goodness-of-fit statistics for the Cox proportional hazards model when adding the decile risk score variable into the model.

by 5 cm could lower risk by 11% in men and 15% in
women. Such magnitudes of reduction in weight or waist
circumference are achievable with dietary restriction and
low-intensity walking 3 times per week.34,53
We used only surrogate indicators of body composition
and could not delineate separate associations for different fat
depots. More accurate measures of fat distribution may be
needed to improve risk assessment in specific subgroups in
the population. Further studies are needed to assess to what
extent central adiposity measurement can improve disease
prediction with the use of existing coronary heart disease risk
models. Reduced hip circumference could reflect muscle
atrophy observed in insulin resistance or diabetes,54 which is
related to increased risk for coronary heart disease.55 Al-
though we accounted for prevalent illness in our analyses, we
did not assess insulin sensitivity directly. However, we used
a prospective study design, showed data for both men and
women, and had sufficient power to examine in more detail
the nature of the association between adiposity and coronary
heart disease, particularly the separate associations for waist
and hip girths.
The population-attributable risk estimates based on body
mass index might be grossly underestimated up to 3-fold.4
Because our results suggested that waist-hip ratio was more
consistently associated with coronary heart disease than body
mass index in both men and women, this simple and inex-
pensive measure could be useful not only for improving
coronary heart disease risk assessment but also for estimating
the burden of obesity-related coronary heart disease in the
general population. Peripheral adiposity, which is often ne-
glected when the health risks of excess fat are studied, should
be taken into account for better prediction of coronary heart
disease by waist circumference. Nevertheless, regardless of
how adiposity is distributed, the challenge remains the same:
to reduce the prevalence of obesity and prevent weight gain
due to excess fat in the general population.
Acknowledgments
The authors extend their appreciation to EPIC-Norfolk Study partic-
ipants, staff members, and collaborating general practices and
hospitals.
Sources of Funding
The EPIC-Norfolk Study is supported by program grants from
Cancer Research UK and the Medical Research Council with
additional grants from the Stroke Association, British Heart Foun-
dation, Department of Health, Europe Against Cancer Programme
Commission of the European Union, Food Standards Agency, and
Wellcome Trust. Dr Canoy was supported by Cambridge Common-
wealth Trust/Cambridge Overseas Trust and Christ’s College.
 2942 Circulation December 18/25, 2007
Disclosures
None.
References
1. Bjorntorp P. “Portal” adipose tissue as a generator of risk factors for
cardiovascular disease and diabetes. Arteriosclerosis. 1990;10:493– 496.
2. Despres JP, Prud’homme D, Pouliot MC, Tremblay A, Bouchard C.
Estimation of deep abdominal adipose-tissue accumulation from simple
anthropometric measurements in men. Am J Clin Nutr. 1991;54:471– 477.
3. Han TS, van Leer EM, Seidell JC, Lean ME. Waist circumference action
levels in the identification of cardiovascular risk factors: prevalence study
in a random sample. BMJ. 1995;311:1401–1405.
4. Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P,
Lang CC, Rumboldt Z, Onen CL, Lisheng L, Tanomsup S, Wangai P Jr,
Razak F, Sharma AM, Anand SS. Obesity and the risk of myocardial
infarction in 27,000 participants from 52 countries: a case-control study.
Lancet. 2005;366:1640 –1649.
5. Larsson B, Svardsudd K, Welin L, Wilhelmsen L, Bjorntorp P, Tibblin G.
Abdominal adipose tissue distribution, obesity, and risk of cardiovascular
disease and death: 13 year follow up of participants in the study of men
born in 1913. BMJ (Clin Res Ed). 1984;288:1401–1404.
6. Lapidus L, Bengtsson C, Larsson B, Pennert K, Rybo E, Sjostrom L.
Distribution of adipose tissue and risk of cardiovascular disease and
death: a 12 year follow up of participants in the population study of
women in Gothenburg, Sweden. BMJ (Clin Res Ed). 1984;289:
1257–1261.
7. Higgins M, Kannel W, Garrison R, Pinsky J, Stokes J 3rd. Hazards of
obesity: the Framingham experience. Acta Med Scand Suppl. 1988;723:
23–36.
8. Stevens J, Keil JE, Rust PF, Verdugo RR, Davis CE, Tyroler HA, Gazes
PC. Body mass index and body girths as predictors of mortality in black
and white men. Am J Epidemiol. 1992;135:1137–1146.
9. Terry RB, Page WF, Haskell WL. Waist/hip ratio, body mass index and
premature cardiovascular disease mortality in US Army veterans during a
twenty-three year follow-up study. Int J Obes Relat Metab Disord. 1992;
Downloaded from http://ahajournals.org by on April 11, 2023
16:417– 423.
10. Rimm EB, Stampfer MJ, Giovannucci E, Ascherio A, Spiegelman D,
Colditz GA, Willett WC. Body size and fat distribution as predictors of
coronary heart disease among middle-aged and older US men. Am J
Epidemiol. 1995;141:1117–1127.
11. Folsom AR, Stevens J, Schreiner PJ, McGovern PG; Atherosclerosis Risk
in Communities Study Investigators. Body mass index, waist/hip ratio,
and coronary heart disease incidence in African Americans and whites.
Am J Epidemiol. 1998;148:1187–1194.
12. Rexrode KM, Carey VJ, Hennekens CH, Walters EE, Colditz GA,
Stampfer MJ, Willett WC, Manson JE. Abdominal adiposity and coronary
heart disease in women. JAMA. 1998;280:1843–1848.
13. Fujimoto WY, Bergstrom RW, Boyko EJ, Chen KW, Leonetti DL,
Newell-Morris L, Shofer JB, Wahl PW. Visceral adiposity and incident
coronary heart disease in Japanese-American men: the 10-year follow-up
results of the Seattle Japanese-American Community Diabetes Study.
Diabetes Care. 1999;22:1808 –1812.
14. Folsom AR, Kushi LH, Anderson KE, Mink PJ, Olson JE, Hong CP,
Sellers TA, Lazovich D, Prineas RJ. Associations of general and
abdominal obesity with multiple health outcomes in older women: the
Iowa Women’s Health Study. Arch Intern Med. 2000;160:2117–2128.
15. Rexrode KM, Buring JE, Manson JE. Abdominal and total adiposity and
risk of coronary heart disease in men. Int J Obes Relat Metab Disord.
2001;25:1047–1056.
16. Lissner L, Bjorkelund C, Heitmann BL, Seidell JC, Bengtsson C. Larger
hip circumference independently predicts health and longevity in a
Swedish female cohort. Obes Res. 2001;9:644 – 646.
17. Welborn TA, Dhaliwal SS, Bennett SA. Waist-hip ratio is the dominant
risk factor predicting cardiovascular death in Australia. Med J Aust.
2003;179:580 –585.
18. Lakka HM, Lakka TA, Tuomilehto J, Salonen JT. Abdominal obesity is
associated with increased risk of acute coronary events in men. Eur
Heart J. 2002;23:706 –713.
19. Heitmann BL, Frederiksen P, Lissner L. Hip circumference and cardio-
vascular morbidity and mortality in men and women. Obes Res. 2004;
12:482– 487.
20. Li TY, Rana JS, Manson JE, Willett WC, Stampfer MJ, Colditz GA,
Rexrode KM, Hu FB. Obesity as compared with physical activity in
predicting risk of coronary heart disease in women. Circulation. 2006;
113:499 –506.
21. Canoy D, Luben R, Welch A, Bingham S, Wareham N, Day N, Khaw KT.
Fat distribution, body mass index and blood pressure in 22 090 men and
women in the Norfolk cohort of the European Prospective Investigation
into Cancer and Nutrition (EPIC-Norfolk) study. J Hypertens. 2004;22:
2067–2074.
22. Canoy D, Wareham N, Luben R, Welch A, Bingham S, Day N, Khaw KT.
Serum lipid concentration in relation to anthropometric indices of central
and peripheral fat distribution in 20,021 British men and women: results
from the EPIC-Norfolk population-based cohort study. Atherosclerosis.
2006;189:420 – 427.
23. Seidell JC, Perusse L, Despres JP, Bouchard C. Waist and hip cir-
cumferences have independent and opposite effects on cardiovascular
disease risk factors: the Quebec Family Study. Am J Clin Nutr.
2001;74:315–321.
24. Tanko LB, Bagger YZ, Alexandersen P, Larsen PJ, Christiansen C.
Peripheral adiposity exhibits an independent dominant antiatherogenic
effect in elderly women. Circulation. 2003;107:1626 –1631.
25. Snijder MB, Dekker JM, Visser M, Yudkin JS, Stehouwer CD, Bouter
LM, Heine RJ, Nijpels G, Seidell JC. Larger thigh and hip circumferences
are associated with better glucose tolerance: the Hoorn study. Obes Res.
2003;11:104 –111.
26. Tanko LB, Bruun JM, Alexandersen P, Bagger YZ, Richelsen B,
Christiansen C, Larsen PJ. Novel associations between bioavailable
estradiol and adipokines in elderly women with different phenotypes
of obesity: implications for atherogenesis. Circulation. 2004;110:
2246 –2252.
27. Tanko LB, Bagger YZ, Alexandersen P, Larsen PJ, Christiansen C.
Central and peripheral fat mass have contrasting effect on the progression
of aortic calcification in postmenopausal women. Eur Heart J. 2003;24:
1531–1537.
28. Day N, Oakes S, Luben R, Khaw KT, Bingham S, Welch A, Wareham N.
EPIC-Norfolk: study design and characteristics of the cohort: European
Prospective Investigation of Cancer. Br J Cancer. 1999;80(suppl 1):
95–103.
29. Lohman T, Roche A, Martorell R. Anthropometric Standardization
Reference Manual. Champaign, Ill: Human Kinetics Books; 1991.
30. Canoy D, Wareham N, Luben R, Welch A, Bingham S, Day N, Khaw KT.
Cigarette smoking and fat distribution in 21,828 British men and women:
a population-based study. Obes Res. 2005;13:1466 –1475.
31. Wareham NJ, Jakes RW, Rennie KL, Mitchell J, Hennings S, Day NE.
Validity and repeatability of the EPIC-Norfolk Physical Activity Ques-
tionnaire. Int J Epidemiol. 2002;31:168 –174.
32. Boekholdt SM, Peters RJ, Day NE, Luben R, Bingham SA, Wareham NJ,
Hack CE, Reitsma PH, Khaw KT. Macrophage migration inhibitory
factor and the risk of myocardial infarction or death due to coronary
artery disease in adults without prior myocardial infarction or stroke: the
EPIC-Norfolk prospective population study. Am J Med. 2004;117:
390 –397.
33. Caan B, Armstrong MA, Selby JV, Sadler M, Folsom AR, Jacobs D,
Slattery ML, Hilner JE, Roseman J. Changes in measurements of body fat
distribution accompanying weight change. Int J Obes Relat Metab
Disord. 1994;18:397– 404.
34. Slentz CA, Duscha BD, Johnson JL, Ketchum K, Aiken LB, Samsa GP,
Houmard JA, Bales CW, Kraus WE. Effects of the amount of exercise on
body weight, body composition, and measures of central obesity:
STRRIDE: a randomized controlled study. Arch Intern Med. 2004;164:
31–39.
35. Miller GJ, Beckles GL, Maude GH, Carson DC. Alcohol consumption:
protection against coronary heart disease and risks to health. Int J
Epidemiol. 1990;19:923–930.
36. Hosmer DW, Lemeshow S. Applied Survival Analysis. New York, NY:
John Wiley & Sons Inc; 1999.
37. May S, Hosmer DW. A simplified method of calculating an overall
goodness-of-fit test for the Cox proportional hazards model. Lifetime
Data Anal. 1998;4:109 –120.
38. World Health Organization. Obesity: Preventing and Managing the
Global Epidemic. Geneva, Switzerland: World Health Organization;
2000.
39. Snijder MB, Dekker JM, Visser M, Bouter LM, Stehouwer CD, Kostense
PJ, Yudkin JS, Heine RJ, Nijpels G, Seidell JC. Associations of hip and
thigh circumferences independent of waist circumference with the
incidence of type 2 diabetes: the Hoorn Study. Am J Clin Nutr. 2003;77:
1192–1197.
 Canoy et al Fat Distribution and Coronary Heart Disease 2943

40. Hube F, Lietz U, Igel M, Jensen PB, Tornqvist H, Joost HG, Hauner H.
Difference in leptin mRNA levels between omental and subcutaneous
abdominal adipose tissue from obese humans. Horm Metab Res. 1996;
28:690 – 693.
41. Eriksson P, Van Harmelen V, Hoffstedt J, Lundquist P, Vidal H, Stemme
V, Hamsten A, Arner P, Reynisdottir S. Regional variation in plasmino-
gen activator inhibitor-1 expression in adipose tissue from obese indi-
viduals. Thromb Haemost. 2000;83:545–548.
42. Thorne A, Lonnqvist F, Apelman J, Hellers G, Arner P. A pilot study of
long-term effects of a novel obesity treatment: omentectomy in con-
nection with adjustable gastric banding. Int J Obes Relat Metab Disord.
2002;26:193–199.
43. Klein S, Fontana L, Young VL, Coggan AR, Kilo C, Patterson BW,
Mohammed BS. Absence of an effect of liposuction on insulin action and
risk factors for coronary heart disease. N Engl J Med. 2004;350:
2549 –2557.
44. Thomas EL, Saeed N, Hajnal JV, Brynes A, Goldstone AP, Frost G, Bell
JD. Magnetic resonance imaging of total body fat. J Appl Physiol. 1998;
85:1778 –1785.
45. Frayn KN. Adipose tissue as a buffer for daily lipid flux. Diabetologia.
2002;45:1201–1210.
46. Kelley DE. Skeletal muscle triglycerides: an aspect of regional adiposity
and insulin resistance. Ann N Y Acad Sci. 2002;967:135–145.
47. Garg A. Lipodystrophies. Am J Med. 2000;108:143–152.
48. Gavrilova O, Marcus-Samuels B, Graham D, Kim JK, Shulman GI,
Castle AL, Vinson C, Eckhaus M, Reitman ML. Surgical implantation of
adipose tissue reverses diabetes in lipoatrophic mice. J Clin Invest.
2000;105:271–278.
49. Bjorntorp P. The regulation of adipose tissue distribution in humans. Int
J Obes Relat Metab Disord. 1996;20:291–302.
50. Bouchard C, Despres JP, Mauriege P. Genetic and nongenetic deter-
minants of regional fat distribution. Endocr Rev. 1993;14:72–93.
51. Jbilo O, Ravinet-Trillou C, Arnone M, Buisson I, Bribes E, Peleraux A,
Penarier G, Soubrie P, Le FG, Galiegue S, Casellas P. The CB1 receptor
antagonist rimonabant reverses the diet-induced obesity phenotype
through the regulation of lipolysis and energy balance. FASEB J. 2005;
19:1567–1569.
52. Kahn HS, Tatham LM, Heath CW Jr. Contrasting factors associated with
abdominal and peripheral weight gain among adult women. Int J Obes
Relat Metab Disord. 1997;21:903–911.
53. Ryan AS, Nicklas BJ, Berman DM, Dennis KE. Dietary restriction and
walking reduce fat deposition in the midthigh in obese older women.
Am J Clin Nutr. 2000;72:708 –713.
54. Seidell JC, Han TS, Feskens EJ, Lean ME. Narrow hips and broad waist
circumferences independently contribute to increased risk of non-insulin-
dependent diabetes mellitus. J Intern Med. 1997;242:401– 406.
55. Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heart
disease associated with diabetes in men and women: meta-analysis of 37
prospective cohort studies. BMJ. 2006;332:73–78.

CLINICAL PERSPECTIVE
The obesity-associated increased risk for developing coronary heart disease (CHD) could be due to the adverse metabolic
profile associated with increased visceral fat accumulation rather than to subcutaneous fat, which comprises ⬎85% of total
body fat. However, using more sophisticated instruments, such as magnetic resonance imaging, to accurately quantify fat
in specific depots is impractical for use in a clinical setting. Simple anthropometric measures, which are known to correlate
with fat distribution, would therefore be preferred. Body mass index, which is weight/height2, is a measure used to define
overweight and obesity, but this measure does not provide enough information on fat distribution. Alternatively, waist
Downloaded from http://ahajournals.org by on April 11, 2023

circumference could be measured and is simple enough for use in assessing abdominal obesity over time. However, waist
girth is correlated with hip circumference, a measure that showed an independent and seemingly “protective” effect on
CHD. Without hip girth being taken into account, the use of waist circumference alone may underestimate true CHD risk.
Waist-hip ratio could be an alternative measure to use because it is strongly predictive of CHD in both men and women.
Even among lean individuals (body mass index ⬍25 kg/m2), an increased waist-hip ratio was associated with higher CHD
risk, suggesting that the impact of excess visceral fat can be observed even without gaining so much weight as to be
considered overweight or obese. However, despite the need to reduce excess weight in healthy individuals, the role of
excess weight reduction in patients with known history of cardiovascular disease or diabetes needs further investigation.