The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis.

Abstract

We sought to conduct a systematic review and meta-analysis of the cardiovascular risk associated with the metabolic syndrome as defined by the 2001 National Cholesterol Education Program (NCEP) and 2004 revised National Cholesterol Education Program (rNCEP) definitions.
Numerous studies have investigated the cardiovascular risk associated with the NCEP and rNCEP definitions of the metabolic syndrome. There is debate regarding the prognostic significance of the metabolic syndrome for cardiovascular outcomes.
We searched the Cochrane Library, EMBASE, and Medline databases through June 2009 for prospective observational studies investigating the cardiovascular effects of the metabolic syndrome. Two reviewers extracted data, which were aggregated using random-effects models.
We identified 87 studies, which included 951,083 patients (NCEP: 63 studies, 497,651 patients; rNCEP: 33 studies, 453,432 patients). There was little variation between the cardiovascular risk associated with NCEP and rNCEP definitions. When both definitions were pooled, the metabolic syndrome was associated with an increased risk of cardiovascular disease (CVD) (relative risk [RR]: 2.35; 95% confidence interval [CI]: 2.02 to 2.73), CVD mortality (RR: 2.40; 95% CI: 1.87 to 3.08), all-cause mortality (RR: 1.58; 95% CI: 1.39 to 1.78), myocardial infarction (RR: 1.99; 95% CI: 1.61 to 2.46), and stroke (RR: 2.27; 95% CI: 1.80 to 2.85). Patients with the metabolic syndrome, but without diabetes, maintained a high cardiovascular risk.
The metabolic syndrome is associated with a 2-fold increase in cardiovascular outcomes and a 1.5-fold increase in all-cause mortality. Studies are needed to investigate whether or not the prognostic significance of the metabolic syndrome exceeds the risk associated with the sum of its individual components. Furthermore, studies are needed to elucidate the mechanisms by which the metabolic syndrome increases cardiovascular risk.

Full text

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doi:10.1016/j.jacc.2010.05.034
2010;56;1113-1132
J. Am. Coll. Cardiol.
Pilote, Paul Poirier, Stéphane Rinfret, Ernesto L. Schiffrin, and Mark J. Eisenberg
Salvatore Mottillo, Kristian B. Filion, Jacques Genest, Lawrence Joseph, Louise

Meta-Analysis
The Metabolic Syndrome and Cardiovascular Risk: A Systematic Review and
This information is current as of October 13, 2011
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QUARTERLY FOCUS ISSUE: PREVENTION/OUTCOMES
Metabolic Syndrome
The Metabolic Syndrome and Cardiovascular Risk
A Systematic Review and Meta-Analysis
Salvatore Mottillo, BSC,*† Kristian B. Filion, PHD,*‡§ Jacques Genest, MD,? Lawrence Joseph, PHD,‡§
Louise Pilote, MD, MPH, PHD,‡§¶ Paul Poirier, MD, PHD,†† Stéphane Rinfret, MD, MSC,‡‡
Ernesto L. Schiffrin, MD, PHD,** Mark J. Eisenberg, MD, MPH*‡
Montreal and Sainte-Foy, Quebec, Canada
Objectives
We sought to conduct a systematic review and meta-analysis of the cardiovascular risk associated with the met-
abolic syndrome as defined by the 2001 National Cholesterol Education Program (NCEP) and 2004 revised Na-
tional Cholesterol Education Program (rNCEP) definitions.
Background
Numerous studies have investigated the cardiovascular risk associated with the NCEP and rNCEP definitions of
the metabolic syndrome. There is debate regarding the prognostic significance of the metabolic syndrome for
cardiovascular outcomes.
Methods
We searched the Cochrane Library, EMBASE, and Medline databases through June 2009 for prospective observa-
tional studies investigating the cardiovascular effects of the metabolic syndrome. Two reviewers extracted data,
which were aggregated using random-effects models.
Results
We identified 87 studies, which included 951,083 patients (NCEP: 63 studies, 497,651 patients; rNCEP: 33
studies, 453,432 patients). There was little variation between the cardiovascular risk associated with NCEP and
rNCEP definitions. When both definitions were pooled, the metabolic syndrome was associated with an in-
creased risk of cardiovascular disease (CVD) (relative risk [RR]: 2.35; 95% confidence interval [CI]: 2.02 to 2.73),
CVD mortality (RR: 2.40; 95% CI: 1.87 to 3.08), all-cause mortality (RR: 1.58; 95% CI: 1.39 to 1.78), myocardial
infarction (RR: 1.99; 95% CI: 1.61 to 2.46), and stroke (RR: 2.27; 95% CI: 1.80 to 2.85). Patients with the meta-
bolic syndrome, but without diabetes, maintained a high cardiovascular risk.
Conclusions
The metabolic syndrome is associated with a 2-fold increase in cardiovascular outcomes and a 1.5-fold increase
in all-cause mortality. Studies are needed to investigate whether or not the prognostic significance of the meta-
bolic syndrome exceeds the risk associated with the sum of its individual components. Furthermore, studies are
needed to elucidate the mechanisms by which the metabolic syndrome increases cardiovascular risk.
Coll Cardiol 2010;56:1113–32) © 2010 by the American College of Cardiology Foundation
(J Am
The metabolic syndrome affects approximately one-quarter
of North Americans and has become a leading health
concern due to its link to cardiovascular disease (1). Ever
since the metabolic syndrome was described by Reaven in
1988 (2), a number of definitions have been published by
organizations including the National Cholesterol Education
Program (NCEP) (3), the International Diabetes Federa-
tion (4), and the World Health Organization (5), among
others. Of these, the 2001 Third Report of the NCEP’s
Adult Treatment Panel has emerged as the most widely
used definition, primarily because it provides a relatively
simple approach for diagnosing the metabolic syndrome by
From the *Divisions of Cardiology and Clinical Epidemiology, Jewish General
Hospital/McGill University, Montreal, Quebec, Canada; †Faculty of Medicine,
University of Montreal, Montreal, Quebec, Canada; ‡Department of Epidemiology,
Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Can-
ada; §Division of Clinical Epidemiology, McGill University Health Center, Mon-
treal, Quebec, Canada; ?Division of Cardiology, McGill University Health Center,
Montreal, Quebec, Canada; ¶Division of Internal Medicine, McGill University
Health Center, Montreal, Quebec, Canada; **Division of Internal Medicine, Jewish
General Hospital, Montreal, Quebec, Canada; ††Faculty of Pharmacy, Laval Hos-
pital, Quebec Heart and Lung Institute, Sainte-Foy, Quebec, Canada; and the
‡‡Clinical and Interventional Cardiology, Multidisciplinary Cardiology Department,
Laval Hospital, Quebec Heart and Lung Institute, Sainte-Foy, Quebec, Canada. This
work is supported by the Canadian Institutes of Health Research (CIHR grant
number 82918). Mr. Mottillo is supported by a Canadian Cardiovascular Outcomes
Research Team (CCORT) summer studentship funded through a CIHR Team
Grant in Cardiovascular Outcomes Research. Dr. Genest is on the Speakers’ Bureau
for Merck and AstraZeneca. Dr. Joseph is a Chercheur-National of the Fonds de la
Recherche en Santé du Québec (FRSQ). Dr. Pilote is a Chercheur-National of the
FRSQ. Dr. Poirier is a Senior Physician-Scientist of the FRSQ. Dr. Rinfret is a
Junior Physician-Scientist of the FRSQ. Dr. Schiffrin holds a Canada Research Chair
in Vascular and Hypertension Research. Dr. Eisenberg is a Chercheur-National of the
FRSQ. All other authors have reported that they have no relationships to disclose.
Manuscript received February 11, 2010; revised manuscript received May 10, 2010,
accepted May 13, 2010.
Journal of the American College of Cardiology
© 2010 by the American College of Cardiology Foundation
Published by Elsevier Inc.
Vol. 56, No. 14, 2010
ISSN 0735-1097/$36.00
doi:10.1016/j.jacc.2010.05.034
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employing easily measurable risk
factors (3,6). Specifically, the
NCEP defines the metabolic
syndrome as having 3 or more of
the following 5 cardiovascular
risk factors: 1) central obesity
(waist circumference: men ?102
cm; women ?88 cm); 2) elevated
triglycerides (?150 mg/dl); 3)
diminished high-density lipo-
protein (HDL) cholesterol (men
?40 mg/dl; women ?50 mg/dl);
4) systemic hypertension (?130/
?85 mm Hg); and 5) elevated
fasting glucose (?110 mg/dl). In
2004, this NCEP definition was
revised (rNCEP) by lowering the
threshold for fasting glucose to
?100 mg/dl in concordance with
American Diabetes Association
criteria for impaired fasting glu-
cose (7). Also, thresholds for central obesity were lowered
from strictly ?102 cm in men and 88 cm in women to
greater than or equal to these values. Finally, the rNCEP
definition includes patients being treated for dyslipidemia,
hyperglycemia, or systemic hypertension.
The value of the metabolic syndrome as a predictor of
cardiovascular risk has been met with much debate. In 2005,
the American Diabetes Association and the European
Association for the Study of Diabetes issued a joint state-
ment summarizing the issues surrounding the metabolic
syndrome (8). In this statement, they underscore the need to
identify the cardiovascular risk associated with the metabolic
syndrome. A large number of observational studies have
been carried out to investigate this risk, and there is a need
to synthesize the results of these studies. Two previous
meta-analyses investigating the metabolic syndrome only
included studies published prior to 2005 and did not
investigate the rNCEP definition (9,10). Since then, 71
studies have been published that used the NCEP and
rNCEP definitions to investigate the cardiovascular effects
of the metabolic syndrome. Thus, our objective was to carry
out a systematic review and meta-analysis to estimate the
cardiovascular risk associated with the metabolic syndrome
according to the NCEP and rNCEP definitions in the
general population and the subpopulations of men, women,
and patients without type 2 diabetes mellitus.
Methods
Data sources and searches. We systematically searched
the Cochrane Library, EMBASE, and Medline databases
through June 2009 using the following key words: all-cause
mortality, cardiovascular risk, cardiovascular disease, cardio-
vascular mortality, fatal myocardial infarction (MI), meta-
bolic syndrome, National Cholesterol Education Program
Adult Treatment Panel III, nonfatal MI, revised National
Cholesterol Education Program Adult Treatment Panel III,
stroke, and syndrome X. References from published pro-
spective studies, relevant reviews, and previous meta-
analyses were hand searched for additional studies not
identified in the database search.
Study selection. Eligible studies: 1) were prospective, ob-
servational studies; 2) stratified patients based on the pres-
ence or absence of the metabolic syndrome using the NCEP
or rNCEP definitions; 3) reported cardiovascular outcomes
and/or all-cause mortality; 4) reported outcomes as count
data, or as relative risk (RR) or hazard ratio (HR) with a
corresponding measure of variance; and 5) were published in
the English language. Studies investigating more than 1
cardiovascular outcome or more than 1 definition of the
metabolic syndrome were also eligible for inclusion. Studies
not meeting these criteria were excluded.
Data extraction. Two reviewers independently extracted
data using standardized data extraction forms. Disagree-
ments were resolved by consensus or, when necessary, by a
third reviewer. Reviewers extracted information on study
design, including the duration of follow-up, the setting, and
the number of participants with and without the metabolic
syndrome according to each definition. Extracted baseline
participant characteristics included age, sex, mean blood
pressure, body mass index (BMI), cholesterol, triglycerides,
waist circumference, and the prevalence of cardiovascular
disease (CVD), type 2 diabetes mellitus, systemic hyperten-
sion, obesity, and smoking. Reviewers extracted the follow-
ing outcomes: all-cause mortality, CVD, CVD mortality,
MI, and stroke. Outcomes data presented as count data,
nonadjusted risk estimates (RR or HR) with corresponding
measures of variance, or multivariable adjusted risk esti-
mates were extracted for participants with and without the
metabolic syndrome. The variables included in the multi-
variable models were also extracted. In addition, when
available, outcomes were extracted for different subpopula-
tions, which included men, women, and patients without
type 2 diabetes mellitus.
Data synthesis and analysis. We synthesized the results of
included studies using random-effects meta-analyses, and
synthesized results are presented as RRs with corresponding
95% confidence intervals (CIs). Heterogeneity was assessed
using I2statistics. We only conducted these meta-analyses
for studies that reported outcomes as count data; studies that
reported outcomes as risk estimates only (HR and RR) were
excluded from these analyses. In the general population, we
estimated the cardiovascular risk associated with the NCEP,
modified NCEP, the rNCEP, and modified rNCEP defini-
tions of the metabolic syndrome separately. The modified
NCEP and modified rNCEP definitions typically used mea-
surements of BMI (typically, BMI ?30 kg/m2or BMI
ranging from ?25 to 27 kg/m2for Asian populations) instead
of waist circumference to define central obesity.
We also assessed the cardiovascular risk when all definitions
were pooled. With the pooled definitions, we determined the
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Abbreviations
and Acronyms
BMI ? body mass index
CI ? confidence interval
CVD ? cardiovascular
disease
HDL ? high-density
lipoprotein
HR ? hazard ratio
LDL ? low-density
lipoprotein
MI ? myocardial infarction
NCEP ? National
Cholesterol Education
Program
rNCEP ? revised National
Cholesterol Education
Program
RR ? relative risk
1114Mottillo et al.
The Metabolic Syndrome and Cardiovascular Risk
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risk in the general population, in men, in women, and in
patients without type 2 diabetes mellitus. Pooled analyses were
conducted for the following 5 outcomes: 1) all-cause mortality;
2) CVD; 3) CVD mortality; 4) MI; and 5) stroke. For each
outcome, a meta-analysis was performed to summarize the
overall effects across all relevant studies.
We reported risk estimates (HR and RR) in tables as part
of our systematic review. We classified nonadjusted risk
estimates and risk estimates adjusting exclusively for age
and/or sex as “least adjusted.” In contrast, risk estimates
adjusting for any cardiovascular risk factor (i.e., smoking
status, low-density lipoprotein [LDL] cholesterol, and
physical activity) were classified as “most adjusted.” The
length of follow-up varied considerably between studies.
Therefore, we conducted a sensitivity analysis in which we
stratified studies using the median length of follow-up. In
addition, funnel plots were constructed and visually assessed
for the possible presence of publication bias. All analyses
were conducted using MIX software version 1.7 (11,12).
Results
Search results and study inclusion. A total of 3,162
potentially relevant studies were identified in our initial
literature search (Fig. 1). After screening the abstracts of
these studies, the full-length papers of 189 studies were
retrieved and assessed for eligibility. Of the retrieved stud-
ies, a total of 87 met our inclusion criteria and were included
in our systematic review (Tables 1 to 5). The remaining 102
studies were excluded either because they did not use the
NCEP or rNCEP definitions of the metabolic syndrome to
stratify patients (n ? 68), they used a cross-sectional study
design (n ? 31), or they did not report any cardiovascular
outcomes (n ? 3). No additional studies were identified
through our hand search of references from published
studies, relevant reviews, and previous meta-analyses.
All included studies were published since 2002, had
sample sizes ranging from 76 to 124,513 patients, and had
follow-up durations ranging from 1.0 to 32.7 years (Online
Tables 1 to 4). The prevalence of the metabolic syndrome in
these studies ranged from 1% in a study of women without
type 2 diabetes mellitus (13) and 78% in a study of patients
with type 2 diabetes mellitus (14). There were also varia-
tions in the mean values for each of the 5 components of the
metabolic syndrome: 1) BMI ranged from 22 to 33 kg/m2;
2) fasting glucose ranged from 82 to 196 mg/dl; 3) HDL
cholesterol ranged from 37 to 64 mg/dl; 4) triglycerides ranged
from 88 to 199 mg/dl; and 5) systolic blood pressure ranged
from 117 to 174 mm Hg. Many studies followed specific
subpopulations, accounting for much of the variability. In
particular, several studies reported outcomes for men (28
studies; n ? 172,548), women (24 studies; n ? 164,768), and
participants without diabetes (17 studies; n ? 172,367).
Of the 87 studies (n ? 951,083) included in our system-
atic review, 43 reported all-cause mortality data (n ?
536,864) (Table 1), 19 reported CVD (n ? 116,202)
(Table 2), 38 reported CVD mortality (n ? 407,350)
(Table 3), 12 reported MI (n ? 29,470) (Table 4), and 26
reported stroke (n ? 126,633) (Table 5). A total of 38
studies investigated the NCEP definition (n ? 345,560)
(Online Table 1), and 26 studies investigated the rNCEP
definition (n ? 433,808) (Online Table 2). In addition, 25
studies investigated the modified NCEP definition (n ?
152,091) (Online Table 3), and 7 studies investigated the
modified rNCEP definition (n ? 19,624) (Online Table 4).
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Figure 1Flow Diagram of Studies Included in the Systematic Review
NCEP ? National Cholesterol Education Program; rNCEP ? revised National Cholesterol Education Program.
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MetS Studies Reporting the Incidence of All-Cause Mortality
Table 1MetS Studies Reporting the Incidence of All-Cause Mortality
First Author, Year (Ref. #)*Population n MetS (%)
Follow-Up
(yrs)
Effect
Measure
Risk of All-Cause Mortality†
(95% CI)
All-Cause
Mortality (%)
Least Adjusted Most Adjusted
MetS
Group
Non-MetS
Group
NCEP definition‡
Benetos et al., 2008 (33)
Butler et al., 2006 (14)
Pts without CVD
General population
Men
Women
Pts with T2DM
Pts without T2DM
Men
Women
General population
Elderly women with no T2DM
Pts with atherosclerosis
Men with atherosclerosis
Women with atherosclerosis
General population
Subjects with CVD
Nonobese men
Overweight men
Obese men
Men
Middle-aged men
General population
Men
Women
General population
Women with CAD
Women without CAD
Women with T2DM without CAD
Pts with T2DM
Normotensive pts
Hypertensive pts
Pts with moderate CKD
70-year-old men
Pts with AMI
Elderly without T2DM
Elderly men without T2DM
Elderly women without T2DM
Pts with CV risk factor
Elderly
Elderly men
Elderly women
84,730
3,035
1,473
1,562
461
2,562
615
749
60,754
921
14,699
6,389
8,310
2,107
1,947
7,505
9,048
2,620
20,789
707
2,118
977
1,141
2,013
147
362
340
1,716
34,577
26,447
710
1,221
461
1,025
—
—
3,196
2,910
1,174
1,736
9.6
38.5
—
—
77.9
31.6
19.0
25.8
10.3
27.1
—
32.4
29.1
9.4
—
4.7
19.8
61.1
19.7
15.0
—
16.9
15.1
16.2
42.2
34.5
30.3
67.1
4.5
17.7
48.9
24.1
37.3
42.7
—
—
42.6
39.0
25.6
48.1
4.7§
6.0?
6.0?
6.0?
6.0?
6.0?
11.0?
11.0?
3.6§
12.2§
9.0§
9.0§
9.0§
12.7§
12.7§
10.0§
10.2§
10.2§
11.0§
12.0¶
20.0?
20.0?
20.0?
12.3?
3.5¶
3.5¶
3.5¶
4.7§
4.7§
4.7§
9.0?
32.7?
1.5¶
13.5¶
13.5¶
13.5¶
3.2¶
4.4§
4.4§
4.4§
HR
RR
RR
RR
RR
RR
HR
HR
HR
HR
RR
RR
RR
HR
HR
RR
RR
RR
RR
RR
HR
HR
HR
HR
HR
HR
RR
HR
HR
HR
HR
HR
HR
HR
HR
HR
HR
HR
HR
HR
—1.63 (1.38–1.93)
—
—
—
—
—
—
—
1.79 (1.35–2.38)
1.30 (1.00–1.70)
1.39 (1.22–1.58)
1.57 (1.31–1.89)
1.22 (1.02–1.47)
—
—
0.92 (0.53–1.60)
—
—
1.36 (1.14–1.62)
1.67 (0.91–3.08)
1.43 (1.24–1.65)
1.44 (1.18–1.76)
1.46 (1.19–1.80)
1.37 (1.02–1.84)
4.93 (1.02–23.76)
1.41 (0.32–6.32)
—
—
1.09 (0.68–1.75)
1.40 (1.13–1.74)
1.40 (1.01–1.94)
1.26 (0.95–1.66)
1.27 (0.54–3.04)
1.08 (0.89–1.31)
1.08 (0.82–1.42)
1.08 (0.83–1.40)
1.43 (1.14–1.78)
—
—
—
——
1.02 (0.85–1.22)
—
—
0.71 (0.48–1.06)
0.95 (0.76–1.17)
1.98 (1.28–3.05)
1.18 (0.72–1.94)
—
—
—
—
—
1.47 (1.13–1.92)
1.06 (0.71–1.58)
—
—
—
1.46 (1.23–1.74)
1.67 (0.95–2.92)
—
—
—
2.39 (1.79–3.18)
—
—
2.20 (0.60–8.04)
1.36 (1.10–1.69)
—
—
—
1.58 (1.24–2.01)
—
1.13 (0.93–1.37)
—
—
1.45 (1.17–1.80)
1.30 (1.11–1.54)
1.26 (0.99–1.60)
1.33 (1.06–1.68)
14.5
15.9
13.4
18.1
12.9
—
—
—
—
9.6
10.2
9.2
—
—
3.98
3.52
3.44
4.5
—
71.5
74.5
68.6
20.2
14.5
3.2
7.8
—
—
—
—
—
—
—
—
—
—
—
—
—
14.2
19.0
9.0
25.5
13.6
—
—
—
—
5.9
8.0
4.3
—
—
2.24
2.21
2.45
2.7
—
58.8
65.8
53.0
9.2
2.11
3.5
3.5
—
—
—
—
—
—
—
—
—
—
—
—
—
Dekker et al., 2005 (34)
Guize et al., 2007 (35)
Hillier et al., 2005 (36)
Hong et al., 2007 (37)
Hunt et al., 2004 (28)
Katzmarzyk et al., 2005 (38)
Katzmarzyk et al., 2006 (39)
Lakka et al., 2002 (40)
Langenberg et al., 2006 (41)
Mancia et al., 2007 (42)
Marroquin et al., 2004 (43)
Monami et al., 2008 (44)
Pannier et al., 2008 (45)
Ramkumar et al., 2007 (46)
Sundstrom et al., 2006 (47)
Takeno et al., 2008 (48)
Wang et al., 2007 (49)
Wassink et al., 2008 (50)
Zambon et al., 2009 (51)
Modified NCEP definition#
Chen et al., 2006 (52)
Feinberg et al., 2007 (53)
Kasai et al., 2006 (54)
Levantesi et al., 2005 (55)
Malik et al., 2004 (56)
Pts with renal disease and ACS
Pts with ACS, without T2DM
Pts who underwent PCI
Pts post-MI
General population
Subjects with T2DM
General population
50-year-old-men
70-year-old-men
General population
7676.3
33.9
42.5
37.0
37.1
29.0
13.5
17.4
23.1
17.5
18.1§
1.0?
12.0§
3.5?
13.3§
13.3§
12.6§
32.7?
32.7?
8.5§
RR
HR
HR
RR
HR
HR
HR
HR
HR
RR
2.82 (0.72–11.09)
—
—
1.15 (0.99–1.33)
—
—
1.23 (1.16–1.29)
1.67 (1.45–1.93)
1.52 (1.19–1.94)
3.03 (2.00–4.59)
—31.4
8.9
13.5
8.5
—
—
—
—
—
7.0
11.1
4.6
10.5
7.4
—
—
—
—
—
2.3
1,060
748
8,245
4,576
4,056
24,358
2,322
1,221
2,863
1.96 (1.18–3.24)
1.34 (0.88–2.05)
1.29 (1.10–1.51)
1.40 (1.19–1.66)
1.17 (0.96–1.42)
1.21 (1.14–1.29)
1.36 (1.17–1.58)
1.20 (0.90–1.59)
—
Nigam et al., 2006 (57)
Sundstrom et al., 2006 (47)
Thomas et al., 2007 (58)
Revised NCEP definition**
Benetos et al., 2008 (33)
Davis et al., 2007 (59)
Guize et al., 2007 (35)
Hildrum et al., 2009 (60)
Pts without CVD
Subjects with type 1 diabetes
General population
Age 40–59 yrs
Age 60–74 yrs
Age 75–89 yrs
Men
Women
Pts without T2DM without CVD
Pts with T2DM who underwent CABG
Pts without T2DM who underwent CABG
Men
Men
Women
84,730
127
60,754
3,789
1,973
986
58,771
65,742
117,045
16.5
41.7
17.7
28.0
47.0
57.0
—
—
—
65.3
40.9
26.9
24.3
21.4
4.7§
11.0§
3.6§
7.9§
7.9§
7.9§
8.0?
8.0?
8.0?
10.5§
10.5§
11.0§
14.1§
14.1§
HR
HR
HR
HR
HR
HR
RR
RR
RR
HR
HR
RR
HR
HR
—
—
—
1.32 (1.13–1.53)
0.74 (0.32–1.74)
1.46 (1.14–1.88)
2.14 (1.40–3.29)
1.14 (0.92–1.41)
1.05 (0.87–1.26)
1.21 (1.09–1.34)
1.30 (1.12–1.49)
1.04 (0.94–1.15)
—
—
1.31 (1.11–1.54)
1.40 (1.10–1.80)
1.80 (1.30–2.60)
—
—
—
—
—
—
4.7
4.4
3.1
—
—
4.2
16.8
11.7
—
—
—
—
—
—
2.3
4.1
1.4
—
—
2.6
6.3
2.7
2.06 (1.35–3.13)
1.10 (0.90–1.36)
1.05 (0.88–1.25)
2.09 (1.90–2.30)
4.33 (3.85–4.88)
—
0.84 (0.56–1.27)
1.34 (1.03–1.74)
1.41 (1.21–1.67)
3.20 (2.50–4.10)
5.00 (3.50–6.90)
Huang et al., 2008 (61)
Kajimoto et al., 2008 (62)274
909
Katzmarzyk et al., 2006 (39)
Lee et al., 2008 (63)
20,789
2,787
2,912
(continued on next page)
1116Mottillo et al.
The Metabolic Syndrome and Cardiovascular Risk
JACC Vol. 56, No. 14, 2010
September 28, 2010:1113–32
by on October 13, 2011 content.onlinejacc.orgDownloaded from