Impact of metabolic syndrome definitions on prevalence estimates: a study in a Portuguese community.

Abstract

This study compared the prevalence of metabolic syndrome (MS) according to World Health Organization (WHO), National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATP III), International Diabetes Federation (IDF) and American Heart Association/ National Heart, Lung and Blood Institute (AHA/NHLBI) definitions, to evaluate how well the different classifications agreed. The study also compared their 10-year predicted risk of coronary heart disease (CHD) with the Framingham risk score (FRS). Some 886 women and 547 men aged 18-92 years were included in the study. Demographic and personal medical history data were obtained at interview. Four operational definitions of MS were used (those of the WHO, NCEP-ATP III, AHA/NHLBI and IDF). The prevalence of metabolic syndrome was found to be 26.4% (WHO criteria), 24.0% (NCEP-ATP III criteria), 41.9% (IDF criteria) and 37.2% (AHA/NHLBI criteria). According to the definition used, central obesity ranged from 41.9% to 75.1% and high blood pressure from 52.9% to 65.8%. Agreement between classifications ranged from 75.2% (kappa=0.47) to 90.4% (kappa=0.80) and was lower in males. The 10-year predicted risk of CHD by FRS was similar between the different definitions. IDF and AHA/NHLBI definitions resulted in a higher prevalence of MS than the NCEP-ATP III or WHO definition. Overall, however, good agreement was found between definitions, and the predicted 10-year of CHD risk was similar.

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Diabetes and Vascular Disease Research
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DOI: 10.3132/dvdr.2007.059
2007 4: 320Diabetes and Vascular Disease Research
Ana-Cristina Santos and Henrique Barros
Impact of metabolic syndrome definitions on prevalence estimates: a study in a Portuguese community


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Abstract
T
Third Adult Treatment Panel (NCEP-ATP III), International
Diabetes Federation (IDF) and American Heart Association/
National Heart, Lung and Blood Institute (AHA/NHLBI) def-
initions, to evaluate how well the different classifications
agreed. The study also compared their 10-year predicted
risk of coronary heart disease (CHD) with the Framingham
risk score (FRS).
Some 886 women and 547 men aged 18–92 years were
included in the study. Demographic and personal medical
history data were obtained at interview. Four operational
definitions of MS were used (those of the WHO, NCEP-ATP
III, AHA/NHLBI and IDF).
The prevalence of metabolic syndrome was found to be
26.4% (WHO criteria), 24.0% (NCEP-ATP III criteria), 41.9%
(IDF criteria) and 37.2% (AHA/NHLBI criteria). According to
the definition used, central obesity ranged from 41.9% to
75.1% and high blood pressure from 52.9% to 65.8%.
Agreement between classifications ranged from 75.2%
(κ=0.47) to 90.4% (κ=0.80) and was lower in males. The
10-year predicted risk of CHD by FRS was similar between
the different definitions.
IDF and AHA/NHLBI definitions resulted in a higher
prevalence of MS than the NCEP-ATP III or WHO definition.
Overall, however, good agreement was found between def-
initions, and the predicted 10-year of CHD risk was similar.
Diabetes Vasc Dis Res 2007;4:320–7
doi:10.3132/dvdr.2007.059
his study compared the prevalence of metabolic syn-
drome (MS) according to World Health Organization
(WHO), National Cholesterol Education Program
Key words: definitions, epidemiology, metabolic
syndrome, prevalence.
Introduction
The cluster of metabolic and haemodynamic disturbances
known as metabolic syndrome is increasingly attracting the
attention of international research institutions and scientific
societies, as a major modifiable determinant of cardiovascu-
lar disease and type 2 diabetes.1-4
Since its initial description, this condition has had sever-
al definitions and sets of classification criteria,5,6especially
concerning its two major aetiological categories, obesity and
insulin resistance. All the proposed definitions agreed on the
syndrome core components, namely central obesity, insulin
resistance, dyslipidaemia and high blood pressure.
No definitive agreement has been reached on the defin-
ition of metabolic syndrome. Currently, the definitions most
often used are those of the World Health Organization
(WHO) in 1998,4the National Cholesterol Education
Program – Third Adult Treatment Panel (NCEP-ATP III) in
20011and the International Diabetes Federation (IDF) in
2005.7An additional operating definition was published in
2005 by the American Heart Association and the National
Heart, Lung, and Blood Institute (AHA/NHLBI).8
There is generally a strong age and gender dependence
in prevalence of the metabolic syndrome but a wide geo-
graphical variation in its frequency.9This variation relates
more to differences in case definition than true differences
among populations. However, the effect of case definition
on estimates of the syndrome’s frequency and classification
agreement remains to be established.
The metabolic syndrome is associated with a more than
two-fold increase in the risk of cardiovascular events10,11
though it remains controversial whether the risk associated
with metabolic syndrome is greater than the sum of the risk
resulting from its component features.12Metabolic syndrome
is helpful in predicting the occurrence of type 2 diabetes
mellitus but is less effective than the Framingham risk score
algorithm in predicting coronary heart disease.13However,
almost all published prospective research on the occurrence
of cardiovascular events has used the NCEP-ATP III to define
metabolic syndrome; it will be essential to evaluate the per-
formance of the other syndrome definitions in predicting risk
using the same longitudinal approach. Meanwhile, using a
cross-sectional sample and different case definitions for the
same set of subjects can be used as a proxy approach to esti-
mate the predictive ability of those different criteria sets to
measure cardiovascular risk against the traditional
Framingham risk score.
ORIGINAL ARTICLE
Impact of metabolic syndrome definitions
on prevalence estimates: a study in a
Portuguese community
ANA-CRISTINA SANTOS, HENRIQUE BARROS
Department of Hygiene and Epidemiology, University of Porto Medical
School, 4200-319 Porto, Portugal.
Ana-Cristina Santos, Lecturer of Epidemiology and Researcher
Henrique Barros, Professor of Epidemiology
Correspondence to: Dr Ana-Cristina Santos
Department of Hygiene and Epidemiology, University of Porto Medical
School, 4200-319 Porto, Portugal.
Tel: + 351 225513652; Fax: + 351 225513653
E-mail: acsantos@med.up.pt
DIABETES AND VASCULAR DISEASE RESEARCH
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In a representative sample of Portuguese urban adults,
we compared the prevalence of metabolic syndrome using
four case definitions – the modified WHO definition, the
NCEP-ATP III, the IDF and the AHA/NHLBI – and measured
classification agreement. Also, we aimed to compare the
predicted 10-year risk of coronary heart disease associated
with metabolic syndrome cases according to the various def-
initions.
Methods
A detailed description of participants and methods have
been published previously.14Briefly, non-institutionalised
inhabitants of Porto, Portugal, were selected using random
digit dialling. After identification of a household, permanent
adult residents were characterised according to age and gen-
der, and one adult was selected by simple random sampling
and invited to visit our department for interview and exam-
ination. The participation rate at cohort assembly was 70%,15
and a total of 2,488 participants were evaluated. For 1,433
participants (886 women and 547 men), data were available
on the different features that can combine to define meta-
bolic syndrome. This subsample of participants was similar
to the total cohort regarding age, sex, education and ciga-
rette consumption (data not shown). The local institutional
ethics committee approved the study and all participants
gave their written informed consent.
Participants were invited to visit our department for an
interview and information was collected by trained inter-
viewers, using a structured questionnaire. Data on social,
demographic, past personal and family medical conditions
and behavioural characteristics (regarding smoking; partici-
pants who smoked during the previous 12 months were clas-
sified as smokers) were self-reported.
All participants were asked to bring their current med-
ication, and this was recorded by a trained pharmacist, who
classified all the medications according to the WHO
Anatomical Therapeutic Chemical (ATC) classification sys-
tem.16
Anthropometric data were obtained after a 12-hour
fast, with the subject in light clothing and barefoot. Body
weight was measured to the nearest 0.1 kg using a digital
scale, and height to the nearest centimetre in the standing
position using a wall stadiometer. Body mass index (BMI)
was calculated as weight in kilograms divided by the height
in metres, squared. Waist and hip circumference were
measured to the nearest centimetre, with the subject
standing, using a flexible and non-distensible tape and
avoiding exertion of pressure on the tissues. The waist cir-
cumference (WC) was measured midway between the
lower limit of the rib cage and the iliac crest. The hip cir-
cumference was considered as the maximal circumference
over the femoral trochanters. Waist-to-hip circumference
ratio was calculated (WHR). Blood pressure was measured
on a single occasion using a standard mercury sphygmo-
manometer with the cuff on the right upper arm. Two
blood pressure readings were taken after the participant
had rested for 10 minutes, and the mean of the two read-
ings was calculated. When the difference between the two
measures was larger than 5 mmHg for systolic or diastolic
blood pressure, a third measurement was taken and the
mean of the two closest values was registered.
A venous blood sample was drawn after a 12-hour
overnight fast. All the samples were analyzed at the central
laboratory of the university hospital. Serum glucose, choles-
terol and triglycerides were determined using automatic
standard routine enzymatic methods.17,18High-density
lipoprotein (HDL)-cholesterol was determined after precipi-
tation of apolipoprotein B-containing lipoproteins. Serum
insulin was measured using a 125I-labelled insulin radioim-
munoassay method, and insulin resistance was estimated
according to the homeostatic model assessment (HOMA), as
the product of fasting glucose (mmol/L) and insulin (µUI/mL)
divided by a constant 22.5.19High-sensitivity C-reactive pro-
tein (hs-CRP) levels were determined by means of particle-
enhanced immunonephelometry using a BNTTMII neph-
elometer (Dade Bhering).
Four operational definitions of metabolic syndrome were
used: the WHO definition as modified by the European
Group for the Study of Insulin Resistance, for application in
epidemiological studies,20NCEP-ATP III,1IDF7and the
AHA/NHLBI.8Metabolic syndrome was considered present
by the modified WHO definition if the subject had fasting
glucose > 6.1 mmol/L or was in the highest quartile of
HOMA or had previously diagnosed diabetes and at least
two of the following: blood pressure > 149/90 mmHg;
triglycerides > 1.7 mmol/L or HDL cholesterol < 1.0 mmol/L
in women and < 0.9 mmol/L in men; BMI > 30.0 kg/m2or
WHR > 0.85 in women and > 0.90 in men. They were con-
sidered to have metabolic syndrome defined by NCEP-ATP
III, if at least three (of any) of the following characteristics
were present: fasting glucose > 6.1 mmol/L; blood pressure
> 130/85 mmHg; triglycerides > 1.7 mmol/L; HDL choles-
terol < 1.29 mmol/L in women and < 1.03 mmol/L in men;
WC > 88 cm in women and > 102 cm in men. The IDF def-
inition was WC > 80 cm in women and > 94 cm in men,
and at least two of the following: fasting glucose
> 5.6 mmol/L or previously diagnosed type 2 diabetes;
blood pressure > 130/85 mmHg or antihypertensive med-
ication; triglycerides > 1.7 mmol/L or specific treatment for
this lipid abnormality; HDL cholesterol < 1.29 mmol/L in
women and < 1.03 mmol/L in men or specific treatment for
this lipid abnormality. Finally, the AHA/NHLBI defined meta-
bolic syndrome as at least three (of any) of the following: fast-
ing glucose > 5.6 mmol/L or antidiabetic treatment; blood
pressure > 130/85 mmHg or antihypertensive medication;
triglycerides > 1.7 mmol/L or specific treatment for this lipid
abnormality; HDL cholesterol < 1.29 mmol/L in women and
< 1.03 mmol/L in men or specific treatment for this lipid
abnormality; WC > 80 cm in women and > 102 cm in men.
Participants who self-reported a clinical diagnosis of dia-
betes by answering yes to the question “Has a doctor ever
diagnosed you with diabetes?”, were additionally consid-
ered as having this feature in the IDF metabolic syndrome
definition.
The predicted 10-year risk of coronary heart disease was
calculated for participants aged less than 75 years and with-
out a diagnosis of coronary heart disease, using the
Framingham Heart Study risk prediction score.21Models
ORIGINAL ARTICLE
VOLUME 4 ISSUE 4 .DECEMBER 2007
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based on low-density lipoprotein (LDL)-cholesterol rather
than total cholesterol were used.
Statistical analysis
Statistical analysis was performed with STATA version 9 sta-
tistical software.
Data were described as mean values and their respective
95% confidence intervals (95% CI), or as median values and
corresponding 25th and 75th centiles for non-normally dis-
tributed variables. Counts and proportions were reported for
categorical variables. Proportions were compared using the
chi-squared test or Fisher’s exact test, whenever appropriate.
The kappa coefficient was used to analyze statistical
agreement between WHO, NCEP-ATP III, IDF and
AHA/NHLBI definitions of the metabolic syndrome.
Results
Table 1 presents the clinical and biological characteristics of
the 1,433 participants in the present evaluation. The medi-
an age was 59 years and 62% were women. Men had a sig-
nificantly higher median number of years of schooling (nine
versus seven, p<0.05) and were more likely to be smokers
(28% vs. 14%, p<0.05).
The prevalence of metabolic syndrome varied from
24.0% (95% CI 21.8–26.4%) when considering the NCEP-
ATP III definition to 41.9% (95% CI 39.3–44.5%) considering
the IDF definition, with intermediate values of 26.4% (95%
CI 24.0–28.8%) considering the WHO proposal and 37.2%
(95% CI 34.6–39.8%) by the AHA/NHLBI definition. Results
regarding the prevalence of each individual feature, accord-
ing to gender and the four definitions, are presented in fig-
ures 1–3. The most common feature of metabolic syndrome
ORIGINAL ARTICLE
Table 1. Clinical and biological characteristics of the sample
Women Men
N
Age (years)
Education (years)
Smokers (n [%])
Antihypertensive medication (n [%]) 333 (38)
Antidiabetic medication (n [%])
BMI (kg/m2)
Waist-to-hip ratio
Waist circumference (cm)
Total cholesterol (mg/dL)
HDL cholesterol (mg/dL)
Triglycerides (mg/dL)
Systolic blood pressure (mmHg)
Diastolic blood pressure (mmHg)
Fasting glucose levels (mg/dL)
Insulin (µUI/mL)
C-reactive protein (mg/L)
Framingham CHD risk score
886 547
59 (49–68)
7 (4–13)
120 (14)
59 (50–70)
9 (4–9)
152 (28)
168 (31)
33 (6)
26 (24–28)
1.0 (0.9–1.0)
95 (88–101)
2.1 (1.8–2.4)
0.5 (0.4–0.6)
1.2 (0.9–1.7)
80 (9)
27 (24–31)
0.9 (0.8–0.9)
89 (82–89)
2.2 (1.9–2.4)
0.6 (0.5–0.7)
1.1 (0.8–1.5)
130 (116–142)131 (120–144)
80 (71–88)
0.9 (0.9–1.0)
4.7 (2.8–7.5)
1.9 (0.9–3.8)
6 (3–9)
81 (75–88)
1.0 (0.9–1.1)
4.7 (2.6–7.6)
1.3 (0.7–3.0)
9 (6–14)
Data are presented as median (25th and 75th centiles), unless otherwise
indicated.
Key: BMI = body mass index; HDL = high-density lipoprotein;
CHD = coronary heart disease
DIABETES AND VASCULAR DISEASE RESEARCH
Figure 1. Prevalence of metabolic syndrome and its
individual components according to four definitions
80
70
60
50
40
30
20
10
0
WHO-definition
of obesity
29.2
52.8
33.3
75.1
WHO-definition
of insulin
resistance
WHO-definition
of dyslipidemia
WHO-definition
of high
blood pressure
WHO-definition
of metabolic
syndrome
26.4
90
80
70
60
50
40
30
20
10
0
ATP III-
definition
of obesity
28.1
19.1
12.8
41.8
24.0
64.6
ATP III-
definition
of low HDL
cholesterol
ATP III-
definition
of high
triglycerides
ATP III-
definition
of high
fasting glucose
ATP III-
definition
of high blood
pressure
ATP III-
definition
of metabolic
syndrome
90
80
70
60
50
40
30
20
10
0
AHA/NHLBI-
definition
of obesity
29.8
36.7
30.4
43.2
37.2
64.6
AHA/NHLBI-
definition
of low HDL
cholesterol
AHA/NHLBI-
definition
of high
triglycerides
AHA/NHLBI-
definition
of high
fasting glucose
AHA/NHLBI-
definition
of high blood
pressure
AHA/NHLBI-
definition
of metabolic
syndrome
90
80
70
60
50
40
30
20
10
0
IDF-
definition
of obesity
29.8
37.2
30.4
70.1
41.9
64.6
IDF-
definition
of low HDL
cholesterol
IDF-
definition
of high
triglycerides
IDF-
definition
of high
fasting glucose
IDF-
definition
of high blood
pressure
IDF-
definition
of metabolic
syndrome
%
%
%
%
Key: WHO = World Health Organization; ATP = (National
Cholesterol Education Program) Adult Treatment Panel;
AHA/NHLBI = American Heart Association/National Heart, Lung
and Blood Institute; IDF = International Diabetes Federation
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varied according to the definition used. With the WHO and
the IDF definitions the most common feature was obesity,
followed by high blood pressure. The prevalence of obesity
was 75.1% (95% CI 72.7–77.3%) by the WHO definition and
70.0% (95% CI 67.5–73.4%) by the IDF classification. High
blood pressure was present in 52.8% (95% CI 50.3–55.5%)
and 64.6% (95% CI 63.2–68.2%) of the participants consid-
ering the WHO and IDF definitions, respectively.
ORIGINAL ARTICLE
VOLUME 4 ISSUE 4 .DECEMBER 2007
Figure 2. Prevalence of metabolic syndrome and its
individual components according to four definitions in men
90
80
70
60
50
40
30
20
10
0
WHO-definition
of obesity
36.9
53.6
33.1
84.5
WHO-definition
of insulin
resistance
WHO-definition
of dyslipidemia
WHO-definition
of high
blood pressure
WHO-definition
of metabolic
syndrome
29.8
90
80
70
60
50
40
30
20
10
0
ATP III-
definition
of obesity
31.9
22.2
8.8
21.9
18.7
68.6
ATP III-
definition
of low HDL
cholesterol
ATP III-
definition
of high
triglycerides
ATP III-
definition
of high
fasting glucose
ATP III-
definition
of high blood
pressure
ATP III-
definition
of metabolic
syndrome
90
80
70
60
50
40
30
20
10
0
AHA/NHLBI-
definition
of obesity
33.3
42.3
34.2
23
32.4
68.6
AHA/NHLBI-
definition
of low HDL
cholesterol
AHA/NHLBI-
definition
of high
triglycerides
AHA/NHLBI-
definition
of high
fasting glucose
AHA/NHLBI-
definition
of high blood
pressure
AHA/NHLBI-
definition
of metabolic
syndrome
90
80
70
60
50
40
30
20
10
0
IDF-
definition
of obesity
33.3
42.3
34.2
54.9
37.8
68.6
IDF-
definition
of low HDL
cholesterol
IDF-
definition
of high
triglycerides
IDF-
definition
of high
fasting glucose
IDF-
definition
of high blood
pressure
IDF-
definition
of metabolic
syndrome
%
%
%
%
Figure 3. Prevalence of metabolic syndrome and its
individual components according to four definitions in
women
90
80
70
60
50
40
30
20
10
0
WHO-definition
of obesity
31.1
52.4
26.7
69.3
WHO-definition
of insulin
resistance
WHO-definition
of dyslipidemia
WHO-definition
of high
blood pressure
WHO-definition
of metabolic
syndrome
24.2
90
80
70
60
50
40
30
20
10
0
ATP III-
definition
of obesity
25.7
17.2
15.3
54.1
27.2
62.2
ATP III-
definition
of low HDL
cholesterol
ATP III-
definition
of high
triglycerides
ATP III-
definition
of high
fasting glucose
ATP III-
definition
of high blood
pressure
ATP III-
definition
of metabolic
syndrome
90
80
70
60
50
40
30
20
10
0
AHA/NHLBI-
definition
of obesity
26.6
33.3
28.9
55.6
40.1
62.2
AHA/NHLBI-
definition
of low HDL
cholesterol
AHA/NHLBI-
definition
of high
triglycerides
AHA/NHLBI-
definition
of high
fasting glucose
AHA/NHLBI-
definition
of high blood
pressure
AHA/NHLBI-
definition
of metabolic
syndrome
90
80
70
60
50
40
30
20
10
0
IDF-
definition
of obesity
26.6
34.2
28.9
79.3
44.4
62.2
IDF-
definition
of low HDL
cholesterol
IDF-
definition
of high
triglycerides
IDF-
definition
of high
fasting glucose
IDF-
definition
of high blood
pressure
IDF-
definition
of metabolic
syndrome
%
%
%
%
Key: WHO = World Health Organization; ATP = (National
Cholesterol Education Program) Adult Treatment Panel;
AHA/NHLBI = American Heart Association/National Heart, Lung
and Blood Institute; IDF = International Diabetes Federation
Key: WHO = World Health Organization; ATP = (National
Cholesterol Education Program) Adult Treatment Panel;
AHA/NHLBI = American Heart Association/National Heart, Lung
and Blood Institute; IDF = International Diabetes Federation
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