Mailing address: Daniela Reis Elbert Farias •Rua Aureliano Coutinho, 88/303 - 25625-000 - Centro - Petrópolis, RJ - BrazilE-mail: elbert@compuland.com.brManuscript received on October 09, 2008; revised manuscript received February 02, 2008; accepted April 30, 2008.

Key wordsMetabolic syndrome; coronary artery disease; vascular

diseases; meta-analysis.

AbstractNowadays, the metabolic syndrome (MS) is highly prevalent

and is associated with risk factors for non-transmissible chronic diseases, such as type 2 diabetes mellitus, and coronary atherosclerotic disease. The objective of this systematic review is to describe the results of studies that investigated the association of MS with coronary artery disease and occlusive vascular diseases. We conducted a systematic review of data from original studies published between 1999 and 2008, written in English or Portuguese, using the databases Medline, Pubmed, Science Direct and HighWire Press. We included articles in which the diagnosis of MS was made by the criteria of the National Cholesterol Education Program - Adult Treatment Panel III (NCEP ATP III, 2001). We excluded studies with animals, supplementation studies, and those with oral or intravenous administration of any substance, as well as those of low methodological quality and those which had a heterogeneous initial sample. Despite the heterogeneity among studies, we observed that individuals with MS had a higher probability (risk = 2.13) of developing occlusive vascular diseases, coronary disease, diabetes and stroke. Lifestyle changes such as healthy eating habits, regular physical activity and cessation of smoking should be encouraged by health professionals to minimize the complications and morbidity associated with MS.

IntroductionThe metabolic syndrome (MS) is characterized by

metabolic changes related to abdominal obesity and insulin resistance. According to the NCEP ATP III1 the diagnosis is made when there is occurrence of three or more of the following conditions: abdominal obesity (waist circumference above 102 cm in men and 88 cm in women), hypertriglyceridemia (greater than or equal to 150mg/dl); low concentrations of HDL cholesterol (less than 40mg/dl in males and less than 50mg/dl in females); systolic blood pressure above or equal to 130 mmHg, and diastolic blood

Metabolic Syndrome in Coronary Artery and Occlusive Vascular Diseases: A Systematic ReviewDaniela Reis Elbert Farias, Avany Fernandes Pereira, Glorimar Rosa Instituto de Nutrição Josué de Castro - Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil

pressure above 85 mmHg; and fasting hyperglycemia (greater than or equal to 110mg/dl).

There are other proposed criteria for this diagnosis, such as: the World Health Organization2 (WHO) criteria, which use microalbuminuria and insulin resistance values; the European Group for the Study of Insulin Resistance3 (EGIR) criteria, which consider insulin resistance as a mandatory risk factor associated with two or more risk factors; the American Heart Association/National Heart, Lung and Blood Institute4 (AHA/NHLBI) criteria, which require the presence of three or more risk factors associated with coronary artery disease (CAD); and the International Diabetes Federation5 (IDF) criteria, which use different values for waist circumference according to ethnicity. Despite the many similarities among the criteria, it is observed that the NCEP ATP III1 criteria are the most used in the literature4.

The global prevalence of MS is high—between 20% and 25%—and varies according to the diagnostic criteria used6-9. Regardless of the diagnostic criteria used, its prevalence is high in individuals with cardiovascular diseases (CVDs)10. There are no epidemiological studies to define its prevalence among Brazilians. However, in a regional study with 530 Japanese-Brazilians, a prevalence of 21%11 was observed, and in a study conducted among the Spanish population of migrants and their descendants in Brazil, a prevalence of 35.6%12 was observed.

MS is considered a risk factor as important as smoking habit for the development of occlusive vascular diseases and atherosclerotic diseases1,9,13. Therefore, the diagnosis and treatment of MS are extremely important because its prevalence is increasing worldwide.

ObjectiveTo describe the results of clinical studies that investigated

the impact of MS, diagnosed by the NCEP ATP III criteria1, on the occurrence of CAD and occlusive vascular disease in individuals aged over 18 years.

MethodsThe bibliographic research was conducted in 2008, and

the following electronic databases were reviewed: Medline, Scielo, Pubmed, Science Direct and HighWire Press. A retrospective search was limited to indexed original scientific articles, such as clinical, randomized and non-randomized, transversal, prospective, cohort and population-based studies, involving humans aged 18 years or over, published between 2004 and 2008, written in English or Portuguese, with a combination of the following keywords: metabolic syndrome and coronary artery disease, metabolic syndrome and vascular

Review Article

diseases. Another strategy we used was the manual selection of references in the articles found.

The articles, originally identified by three different researchers, were selected by the initial search strategy using the following eligibility criteria: (1) articles published in the last four years; (2) articles written in English or Portuguese; (3) Clinical observational studies; (4) randomized or non-randomized studies; (5) studies with adult or elderly human subjects with MS; (6) clinical diagnosis of coronary artery disease and/or occlusive vascular diseases; and (7) studies showing as the main outcome the association of metabolic syndrome abnormalities with these diseases. We included articles that used the NCEP ATP III1 criteria for the diagnosis of MS and those which used the NCEP ATP III2 with another criteria for the diagnosis of MS, such as the WHO2, the EGIR3, the AHA/NHLBI4, the IDF5, or the American College of Endocrinology (ACE)14 criteria. According to a criterion defined before the search, we excluded studies with animals, supplementation studies, studies with oral or intravenous administration of any substance, studies of low methodological quality and with heterogeneous sample, as well as studies whose information was available in more recent articles.

The selected studies had as the primary outcome the association of metabolic abnormalities of individuals with MS in the presence of coronary artery disease and/or occlusive vascular diseases15. The methodological quality of the studies was evaluated considering several aspects: specification of the inclusion and exclusion criteria for the study; random allocation of participants in the study; similarities between the study groups and control groups in the initial phase of the study; and statistical analysis report. Finally, these articles were reviewed to avoid inclusion of duplicated data.

Data Analysis We used the program RevMan version 5.0 (The Cochrane

Collaboration, Copenhagen) to analyze the data16. To assess the heterogeneity among studies, we used the Chi2 test, with n - 1 degrees of freedom, in which “n” is the number of studies. We calculated the significant heterogeneity using the fixed-effects model. The inconsistency (I2) was calculated so as to verify the differences between studies that included groups of subjects with and without MS who had CAD or occlusive vascular disease, and an inconsistency rate of 25% was considered low, 50% was considered moderate, and greater than 75% was considered high17.

ResultsA total of 42 studies have been identified, of which

30 used the NCEP ATP III criterion (2001)1 as the sole diagnostic criteron for MS, and 12 articles used other criteria for the diagnosis of MS besides the NCEP ATP III1. A total of 42 articles have been selected, as follows: 14 cohort studies13,15-27, 12 cross-sectional studies10,30-40, 8 prospective cohort studies41-48, 2 observational studies49,50, 2 prospective studies51,52, 1 prospective observational study53, 1 cross-sectional and population cohort study54, 1 case-control study55, and 1 longitudinal community-based study56.

The largest number of publications were from the United States (n = 17), of which only 12 articles used the NCEP ATP III criterion (2001), followed by Italy (n = 6) and Holland (n = 3). Two articles were selected from each of the following countries: England, Greece, France, Canada, Finland, Turkey. From Japan, Argentina, Norway and Austria, only 1 article was selected from each.

The methodological characteristics, year of publication, country of origin, study population, study group, sample age range, criterion used for diagnosis of MS, type, duration and main results of these studies are presented in table 1.

Time duration of some studies was not mentioned. Among the studies in which these data were obtained we observed that no less than 6 months duration28, was the largest follow-up time of 20 years53.

The form of recruitment of participants was specified in all studies. The sample size ranged from 83 to 15,922 individuals; of the 42 studies selected, only 2 had lower total sample of 100 individuals; 83 and 87 individuals respectively32,37.

Most studies included individuals of both genders (n = 36), with the exception of 5 studies that included only women28,34,37,48,50, and 1 study that included only men in its sample43. Of the studies selected, 50% did not mention the sample age range, but 31 (73.8%) selected articles mentioned the mean age and the standard deviation of the study groups. Of the articles which did not mention the standard deviation of the study groups’ age, 3 reported only the mean age of the groups, 3 mentioned only the age range of the groups, and 5 mentioned the mean age and the age range of the groups.

Discussion MS stands out due to its high prevalence and because

it represents an important set of cardiovascular risk factors, often associated with central fat deposition and insulin resistance57. From the epidemiological point of view, MS is responsible for an estimated increase in overall mortality by 1.5 times, and in mortality from CAD and occlusive vascular disease by 2.5 times58. Despite its relevance, in Brazil there is still a lack of data on its characteristics and no epidemiological studies to assess its relationship with increased morbidity from occlusive vascular disease and CAD. The study of MS has also been hampered by the lack of consensus on the criterion for its diagnosis and the cut-off points for its risk factors, with important implications in clinical practice and public health measures. In this review, we selected articles that used the NCEP ATP III1 criterion for the diagnosis of MS, not only because this is a criterion that has easy applicability in clinical practice, but it is also widely used in scientific publications.

Individually, the components of MS are independent risk factors for the development of atherosclerotic cardiovascular disease10,13,20,23,24,40,42. The different criteria used for the diagnosis of MS are based on the principle that its risk factors may interact synergistically, or may increase the risk for CAD and atherosclerotic disease. Some studies have shown that the higher the number of components of MS in an individual,

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

87

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Carm

initi e

t al.,

(200

8)30

.

Italy

Total

(n =

286)

187

men

99wo

men

1- w

ith M

S

2- w

ithou

t MS

Total NM

66.2 ±

10.6

anos

grou

p 1:

67 ±

7 ye

ars

grou

p 2:

66 ±

8.6 y

ears

NCEP

ATP

III (2

001)

Cros

s-sec

tiona

l

6 mon

ths

The p

reva

lence

of M

S in

the st

udy w

as 48

%, w

ith no

sign

ifican

t diffe

renc

e in

prev

alenc

e betw

een g

ende

rs.

Patie

nts w

ith M

S sh

owed

sign

ifican

t diffe

renc

es in

BMI

, whic

h was

gr

eater

in th

e gro

up w

ith M

S, an

d a re

ducti

on in

the c

once

ntrati

on of

HD

L-c a

nd in

exer

cise t

ime m

easu

red i

n minu

tes, w

hich w

ere m

ore

pron

ounc

ed w

hen c

ompa

red t

o tho

se of

the g

roup

with

out M

S.

Patie

nts w

ith C

AD an

d with

out M

S ac

hieve

d a hi

gher

rate

of wo

rk du

ring

traini

ng, w

hen c

ompa

red t

o pati

ents

with

MS. P

atien

ts wi

th CA

D an

d MS

had l

ower

func

tiona

l reco

very

and l

ower

reco

very

hear

t rate

whe

n co

mpar

ed to

thos

e with

out M

S.

The m

axim

um ex

ercis

e cap

acity

achie

ved d

uring

the t

est e

ffort

was

signifi

cantl

y low

er in

the g

roup

with

MS

when

comp

ared

to th

e gro

up

witho

ut MS

(7.6 ±

1.8 vs

. 9.3 ±

1.2).

MS w

as an

inde

pend

ent p

redic

tor of

a d

ecre

ase i

n fun

ction

al re

cove

ry on

ly in

female

patie

nts w

ith C

AD an

d MS

(OR

1.31,

95%

CI 1

.20 to

1.62

).

Hamb

urg e

t al.,

(200

8)15

.

Unite

d Stat

es

Total

(n =

2123

)

917

men

1206

wome

n

1- w

ith M

S (n

= 76

2)

2 with

out M

S (n

= 13

61)

NM Total

59

± 9

year

s

grou

p 1:

61 ±

9 ye

ars

grou

p 2:

58 ±

9 ye

ars

NCEP

ATP

III (2

001)

Coho

rt

NM

The p

reva

lence

of M

S wa

s high

er th

an 33

% an

d sho

wed a

ssoc

iation

with

inc

reas

ed th

ickne

ss of

the b

rach

ial ar

tery a

nd hy

pere

mia.

A re

lation

ship

betw

een M

S an

d vas

odila

tor dy

sfunc

tion w

as ob

serve

d. Th

e HOM

A ind

ex w

as si

gnific

antly

high

er in

the M

S gr

oup w

hen c

ompa

red t

o the

gr

oup w

ithou

t MS

(p <

0.000

1), in

simi

larity

with

the p

reva

lence

of in

sulin

re

sistan

ce, c

lassifi

ed in

the h

ighes

t qua

rtile o

f the H

OMA

index

, was

51%

an

d 10%

in th

e gro

ups w

ith an

d with

out M

S, re

spec

tively

. Th

e high

er th

e num

ber o

f risk

facto

rs tha

t cha

racte

rize M

S, th

e gre

ater

the va

sodil

ator d

ysfun

ction

in pa

tients

with

MS

(p <

0.000

1). T

hese

fin

dings

corro

bora

te the

hypo

thesis

that

MS an

d ins

ulin r

esist

ance

act

upon

the v

ascu

lar fu

nctio

n in o

rder

to in

fluen

ce th

e risk

facto

rs tha

t ch

arac

terize

MS.

Tabl

e 1 -

Char

acte

ristic

s of s

tudi

es w

hich

had

met

abol

ic sy

ndro

me,

vasc

ular

occ

lusiv

e dise

ase a

nd co

rona

ry ar

tery

dise

ase a

s the

main

varia

bles

.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

88

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Holvo

et et

al.,

(200

8)53

.

Unite

d Stat

es

Total

(n =

1889

)

1058

wom

en

831

men

5 quin

tiles

acco

rding

to

oxidi

zed L

DL-c

(U/L)

and L

DL-c

(mg/d

L)

1: (<

55.4

U/L e

< 86

mg/d

L)

2: (5

5.4 –

69.1

U/L

e 86

-101

mg/d

L)

3: (6

9.2-8

1.2 U

/L e

102 -

118 m

g/dL)

4: (8

1.3-9

7.3 U

/L e

119-

138m

g/dL)

5: (≥

97.4U

L e ≥

13

9mg/d

L )

Total

: NM

grou

p 1:

1º qu

intil L

DL-

oxida

da:

40.l y

ears

(NM)

1º qu

intil L

DL-c:

40

.2 ye

ars (

NM)

grou

p 2:

2º qu

intil L

DL-

oxida

da:

40.2

year

s (NM

)- 2

º quin

til LD

L-c:

40 ye

ars (

NM)

grou

p 3:

3º qu

intil L

DL-

oxida

da:

40.2

year

s (NM

)- 3

º quin

til LD

L-c:

40.3

year

s (NM

)gr

oup 4

:4º

quint

il LDL

- ox

idada

: 40

.2 ye

ars (

NM)

4º qu

intil L

DL-c:

40

.1 ye

ars (

NM)

grou

p 5:

5º qu

intil L

DL-

oxida

da:

40.4

year

s (NM

)5º

quint

il LDL

-c:

40.5

year

s (NM

)

NCEP

ATP

III (2

001)

Popu

lation

base

d pr

ospe

ctive

ob

serva

tiona

l

20-ye

ar fo

llow-

up

by C

ARDI

A

MS w

as di

agno

sed i

n a 20

-year

follo

w-up

in 12

.9% of

the p

artic

ipants

. Am

ong t

he st

udy p

artic

ipants

, oxid

ized L

DL w

as po

sitive

ly as

socia

ted

with

male

gend

er, bl

ack e

thnici

ty, hi

gher

BMI

and o

besit

y, C-

reac

tive

prote

in, an

d MS

comp

onen

ts.

The O

R for

the d

ichoto

mous

effec

t of th

e risk

facto

rs tha

t cha

racte

rize M

S of

the la

rges

t quin

tile ve

rsus t

he lo

west

quint

ile of

oxidi

zed L

DL w

ere 2

.1 (9

5% C

I, 1.2-

3.6) f

or ab

domi

nal o

besit

y; 2.4

( 95

% C

I, 1.5-

3.8) f

or fa

sting

hy

perg

lycem

ia; an

d 2.1

(95%

CI, 1

.1-4.0

) for

hype

rtrigl

ycer

idemi

a. Th

is stu

dy sh

ows t

hat a

n imp

ortan

t mar

ker o

f oxid

ative

stre

ss, m

easu

red

by th

e high

est q

uintile

of ox

idize

d LDL

, was

sign

ifican

tly as

socia

ted w

ith

the in

ciden

ce of

MS,

as w

ell as

abdo

mina

l obe

sity,

hype

rglyc

emia

and

hype

rtrigl

ycer

idemi

a. Ho

weve

r, oxid

ized L

DL sh

owed

no as

socia

tion w

ith

BP an

d HDL

-c inc

reas

e.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

89

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Kasa

i et a

l., (2

008)

31.

Japa

n

Total

(n =

656)

496

men

160

wome

n

1- M

en

2- W

omen

Total

NM

64.8 ±

10.6

year

s

grou

p 1:

63.9 ±

10.1

year

s

grou

p 2:

67.6 ±

11.5

year

s

NCEP

ATP

III (2

001)

IDF

(200

6)

AHA/

NHLB

I (20

05)

Cros

s-sec

tiona

l

1 yea

r

The p

reva

lence

of M

S ac

cord

ing to

NCE

P AT

P III

(200

1) w

as 25

.5%.

Ther

e was

no di

ffere

nce i

n the

prev

alenc

e of M

S be

twee

n male

s and

fem

ales.

The G

ensin

i sco

re w

as us

ed to

asse

ss th

e exte

nt of

coro

nary

ather

oscle

rosis

, and

a hig

her s

core

was

obse

rved o

nly in

patie

nts w

ith

MS di

agno

sed b

y the

AHA

/NHL

BI (2

005)

crite

rion.

Ther

e was

no el

evati

on

of the

Gen

sini s

core

in pa

tients

with

MS

diagn

osed

by th

e NCE

P AT

P III

(200

1) an

d the

IDF

(200

6) cr

iterio

n; ho

weve

r, fem

ale pa

tients

with

MS

show

ed si

gnific

ant in

creas

e in t

he ex

tent o

f CAD

by al

l crite

ria fo

r the

diag

nosis

of M

S. W

hen a

sses

sing t

he ris

k of C

AD pr

ogre

ssion

, the

asso

ciatio

n betw

een M

S an

d inc

reas

ed ris

k CAD

prog

ress

ion w

as

obse

rved i

n both

gend

ers (

OR 1.

39, 9

5% C

I 0.93

to 2.

09, p

= 0.

111 i

n me

n and

OR

2.32,

95%

CI 1

.11 to

4.86

, p =

0.02

56 in

wom

en) a

ccor

ding

to the

NCE

P AT

P III

(200

1) cr

iterio

n. Am

ong t

he in

dividu

al co

mpon

ents

of MS

, incre

ased

BP,

redu

ced c

once

ntrati

on of

HDL

-c, an

d fas

ting

hype

rglyc

aemi

a sho

wed a

ssoc

iation

with

CAD

prog

ress

ion in

male

s. Th

e gre

ater t

he nu

mber

of ris

k fac

tors o

f MS

in an

indiv

idual,

the g

reate

r the

risk o

f CAD

prog

ress

ion ac

cord

ing to

coro

nary

angio

grap

hy.

Noto

et al.

, (2

008)

41.

Italy

Total

(n =

685)

307

men

378

wome

n

1- w

ith M

S (n

= 15

7)

2- w

ithou

t MS

(n =

528)

Total

35 a

75 ye

ars N

M

57

± 11

ye

ars

grou

p 1:

59 ±

10ye

ars

grou

p 2:

56 ±

11 ye

ars

NCEP

ATP

III (2

001)

IDF

(200

6)

Pros

pecti

ve

Coho

rt

15-ye

ar fo

llow-

up

by D

CV

MS w

as si

gnific

antly

mor

e pre

valen

t in w

omen

(p <

0.000

01) (

31.5%

) tha

n in

men (

12.4%

). Th

e clin

ical a

nd bi

oche

mica

l data

of th

e stud

y gro

ups h

ave s

hown

that

patie

nts w

ith M

S ha

d high

er co

ncen

tratio

ns of

trigl

ycer

ides,

gluco

se, u

ric

acid,

fibrin

ogen

; lowe

r con

centr

ation

of H

DL-c;

and h

igher

BMI

and W

C.

As fo

r lifes

tyle,

we o

bser

ved t

hat a

lcoho

l con

sump

tion w

as si

gnific

antly

hig

her in

the M

S gr

oup w

hen c

ompa

red t

o the

grou

p with

out M

S. T

here

we

re no

diffe

renc

es be

twee

n gro

ups a

s to s

mokin

g hab

it. MS

incre

ased

the r

isk fo

r car

diova

scula

r eve

nts by

up to

1.9 (

95%

CI,

1.46-

2.46)

. Th

e risk

rate

for ca

rdiov

ascu

lar ev

ents

amon

g pati

ents

with

and w

ithou

t MS

was

high

er in

patie

nts w

ith M

S dia

gnos

ed by

the N

CEP

ATP

III (2

001)

cri

terion

, whe

n com

pare

d to t

he ID

F (2

006)

crite

rion.

Acco

rding

to th

e Cox

mod

el for

risk a

sses

smen

t, the

survi

val c

urve

s of

patie

nts w

ith M

S wi

thout

gluco

se in

toler

ance

wer

e not

statis

ticall

y dif

feren

t from

thos

e with

DM

and g

lucos

e into

leran

ce.

MS w

as a

pred

ictive

facto

r for

card

iovas

cular

even

ts, in

depe

nden

tly of

the

pres

ence

of gl

ucos

e into

leran

ce.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

90

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Gome

z Ros

so et

al.

, (20

08)32

.

Arge

ntina

Total

(n =

87)

men

(NM)

wome

n(N

M)

1- co

ntrol

witho

ut MS

(n

= 56

)

2- w

ith M

S (n

= 31

)

Total

: NM

grou

p 1:

43 ±

13 ye

ars

grou

p 2:

48 ±

9 ye

ars

NCEP

ATP

III (2

001)

Cros

s-sec

tiona

l

NM

Patie

nts w

ith M

S sh

owed

hypo

adipo

necti

nemi

a, inc

reas

ed ac

tivity

of ce

ll ad

hesio

n mole

cules

(CE

TP),

ather

ogen

ic lip

opro

tein a

nd lip

id pr

ofile,

inc

reas

ed B

MI, h

igher

conc

entra

tions

of in

sulin

and h

igher

HOM

A ind

ex

when

comp

ared

to in

dividu

als in

the c

ontro

l gro

up.

An im

porta

nt fin

ding o

f this

study

was

the o

bser

vatio

n of h

igher

mole

cular

leu

kocy

te an

d end

otheli

al ad

here

nce i

n pati

ents

with

MS. T

he in

creas

e in

CETP

in pa

tients

with

MS,

whic

h is c

rucia

l for t

he in

terac

tion o

f leuk

ocyte

s wi

th the

endo

theliu

m, w

ith su

bseq

uent

migr

ation

of ce

lls in

the a

rtery

wall.

Thes

e infl

amma

tory c

hang

es ar

e ass

ociat

ed w

ith hy

poad

ipone

ctine

mia,

ather

ogen

ic lip

id an

d lipo

prote

in pr

ofiles

and c

hemi

cal c

hang

es in

the

comp

ositio

n of H

DL-C

, acc

ompa

nied b

y high

conc

entra

tions

of

chole

stero

l and

trigl

ycer

ides —

meta

bolic

cond

itions

pres

ent in

patie

nts

with

MS.

Thes

e res

ults i

ndica

te tha

t the a

thero

scler

otic p

laque

form

ation

is

stimu

lated

and t

he ca

rdiov

ascu

lar ris

k is i

ncre

ased

in pa

tients

with

MS.

Ryan

et al

., (2

008)

33.

Unite

d Stat

es

Total

(n =

402 a

nces

tors

of Eu

rope

ans)

227

men

175

wome

n

1 - w

ith ab

domi

nal

obes

ity

2- no

n obe

se (b

y W

C)

Total

: NM

grou

p 1:

52 ±

9 ye

ars

grou

p 2:

50 ±

9 ye

ars

NCEP

ATP

III (2

001)

IDF

(200

6)

Cros

s-sec

tiona

l

NM

The r

esult

s hav

e sho

wn a

signifi

cant

corre

lation

betw

een W

C an

d BMI

(p

<0.0

01).

The p

reva

lence

of M

S wa

s sim

ilar r

egar

dless

of th

e WC

class

ificati

on us

ed by

the I

DF cr

iterio

n (20

06) a

nd th

e NCE

P AT

P III

(200

1) cr

iterio

n. Ac

cord

ing to

the N

CEP

ATP

III (2

001)

crite

rion,

the

prev

alenc

e of M

S wa

s 40%

in th

e gen

eral

popu

lation

, with

24%

in

indivi

duals

aged

over

50 ye

ars,

and 1

5% in

thos

e age

d belo

w 50

year

s. Th

e risk

facto

r for

CVD

s stat

us w

as no

t sign

ifican

t whe

n the

volun

teers

were

divid

ed ac

cord

ing to

BMI

and W

C. T

he pr

evale

nce o

f MS

or ris

k fac

tors f

or C

VDs d

id no

t var

y acc

ordin

g to t

he cr

iteria

used

. How

ever,

BMI

an

d WC

effec

tively

iden

tified

indiv

iduals

at ris

k for

CVD

s.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

91

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Wier

zbick

i, et a

l., (2

008)

18.

Engla

nd

Total

(n

= 40

0 ind

ividu

als fr

om

Pakis

tan)

Men a

nd W

omen

fro

m Pa

kistan

(NM)

1 - W

ith C

AD

defin

ed by

50

% st

enos

is in

one o

r mor

e co

rona

ry ar

tery b

y an

giogr

aphy

2 - C

ontro

l: the

pr

esen

ce of

sy

mptom

s sim

ilar

to gr

oup 1

but

witho

ut ev

idenc

e of

CAD

by

angio

grap

hy.

Total

: NM

grou

p 1:

51.2 ±

9.5 ye

ars

grou

p 2:

48.2 ±

9.5 ye

ars

NCEP

ATP

III (2

001)

IDF

(200

6)

Coho

rt

With

recru

itmen

t fro

m 19

98 to

20

01.

The p

rese

nce o

f MS

as de

fined

by th

e NCE

P AT

P III

(200

1) cr

iterio

n was

44

%.

The i

ncide

nce o

f CAD

(65%

vs. 3

4%, O

R: 1.

88, p

<0.0

01) d

iffere

d sig

nifica

ntly b

etwee

n the

grou

ps w

ith an

d with

out M

S ac

cord

ing to

the I

DF

(200

6) cr

iterio

n, wh

erea

s littl

e diffe

renc

e was

obse

rved w

hen u

sing t

he

diagn

ostic

crite

rion o

f the N

CEP

ATP

III (2

001)

for t

he in

ciden

ce of

CAD

(5

3 vs.

48%

, p =

0.31

). Ac

cord

ing to

this

criter

ion th

ere w

as no

relat

ionsh

ip be

twee

n MS

and

ather

omato

us pl

aque

. In

contr

ast, t

he pr

esen

ce of

MS,

by th

e IDF

(200

6) cr

iteria

, was

as

socia

ted w

ith C

AD an

d occ

lusive

vasc

ular

disea

se.

Athy

ros e

t al.,

(200

7)10

Gree

ce

Total

(n =

9669

)

4738

me

n

4931

wom

en

1- w

ith M

S by

NC

EP AT

P III

criter

ion

2- w

ith M

S by

IDF

criter

ion

3- w

ith M

S by

AH

A/NH

LBI

criter

ion

Total

: Ov

er 18

year

sNM To

tal

46 ±

18 ye

ars

grou

p 1:

57 ±

13 ye

ars

grou

p 2:

56 ±

12 ye

ars

grou

p 3:

54 ±

16 ye

ars

NCEP

ATP

III (2

001)

IDF

(200

6)

AHA/

NHLB

I (20

05)

Cros

s-sec

tiona

l

1 yea

r

Ther

e was

a hig

h pre

valen

ce of

CVD

s in s

ubjec

ts wi

th MS

, reg

ardle

ss

of the

diag

nosti

c crite

rion u

sed.

Howe

ver, t

his in

creas

e was

pron

ounc

ed

when

the N

CEP

ATP

III cri

terion

and t

he A

HA/N

HLBI

crite

rion w

ere

appli

ed. T

he di

agno

sis of

MS

and i

ts tre

atmen

t, eith

er by

LC or

drug

s, ar

e vit

al to

redu

ce m

ortal

ity fr

om C

VDs i

n the

se in

dividu

als.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

92

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Bellia

et al

., (2

007)

49.

Italy

Total

(n

= 18

1)

men e

wom

en

NM

1 - w

ith C

VDs

acco

rding

to

angio

grap

hy (5

0%

steno

sis in

at 1.

2 or

3 co

rona

ry ar

teries

) (6

0 men

and

66 w

omen

)

2 - he

althy

su

bjects

Total

: NM

grou

p 1:

men a

ged

34 to

72 ye

ars

wome

n age

d36

to 70

year

s

grou

p 2: N

M

NCEP

ATP

III (2

001)

Obse

rvatio

nal

NM

In mo

st pa

tients

with

hear

t dise

ase t

he pr

esen

ce of

MS

and H

hcy h

as

been

obse

rved.

The p

reva

lence

of M

S an

d Hhc

y was

17.4%

and 2

5.4%

re

spec

tively

. MS

and H

hcy w

ere p

rese

nt in

67.2%

of pa

tients

. Hh

cy an

d MS

show

ed an

asso

ciatio

n with

CVD

s (OR

2:53

, 95%

CI, 1

.95-

12.43

and O

R 5.7

4, 95

% C

I, 2.67

-12.3

4, re

spec

tively

). Ac

cord

ing to

data

on pr

evale

nce,

when

Hhc

y and

MS

were

pres

ent in

the

same

indiv

idual,

ther

e was

an in

creas

ed ris

k for

the d

evelo

pmen

t of C

VDs

(13.1

1 CI 9

5% 5.

27-3

2.06)

. Th

ese r

esult

s sug

gest

that H

hcy a

nd M

S ma

y act

syne

rgist

ically

in

incre

asing

the r

isk fo

r CVD

s. Th

e stud

y also

sugg

ests

that M

S an

d Hhc

y wo

rk tog

ether

in in

creas

ing th

e risk

for C

VDs m

ore t

han t

he pr

esen

ce of

tw

o meta

bolic

cond

itions

that

char

acter

ize M

S.

The s

tudy a

lso su

gges

ts tha

t a lif

estyl

e cha

nge w

ith em

phas

is on

re

ducin

g bod

y weig

ht sh

ould

be th

e the

rapy

of ch

oice f

or M

S.

Empa

na et

al.,

(200

7)42

.

Fran

ce

Total

(n

= 55

85)

witho

ut DM

2.

2124

men

3461

wome

n

1 - w

ith M

S (n

= 67

4)

2 - w

ithou

t MS

(n =

4911

)

Total

: 65

a 85

year

s 73

.5 ±

4.9 ye

ars

grou

p 1:

73.9 ±

4.9 ye

ars

grou

p 2:

73.5 ±

4.9 ye

ars

NCEP

ATP

III (2

001)

Pros

pecti

ve co

hort

3 yea

rs

The p

reva

lence

of M

S wa

s 12.1

% am

ong s

tudy p

artic

ipants

. The

mos

t co

mmon

comp

onen

ts of

MS in

the s

tudy p

opula

tion w

ere t

he el

evati

on of

BP

(87%

), inc

reas

ed W

C (2

6.8%

), hy

pertr

iglyc

eride

mia (

16%

), re

duce

d HD

L-c (

10.3%

), an

d fas

ting h

yper

glyce

mia (

3.8%

). Pa

tients

with

MS

had h

igher

risk f

or pl

aque

s in t

he ca

rotid

(33%

), inc

reas

ed co

mmon

caro

tid ar

tery i

ntima

-med

ia thi

ckne

ss (4

6%),

and

incre

ased

thick

ness

of th

e lum

en, (

62%

) eve

n afte

r adju

stmen

t for

age,

study

cente

r, gen

der, s

mokin

g hab

it, tre

atmen

t for r

educ

tion o

f ath

erog

enic

lipid

profi

le an

d hist

ory o

f CVD

s. Ind

ividu

als w

ith M

S ha

d high

er fr

eque

ncy o

f car

otid a

thero

matou

s pla

ques

(OR

1.30,

95%

CI, 1

.09 to

1.55

), hig

her c

ommo

n car

otid a

rtery

intim

a-me

dia th

ickne

ss (O

R 1.8

1, 95

% C

I, 1.37

to 2.

41),

and i

ncre

ased

thi

ckne

ss of

the l

umen

(OR

2.17,

95%

CI, 1

.61 to

2.94

) (top

quint

ile) a

fter

adjus

tmen

t for o

ther c

ardio

vasc

ular r

isk fa

ctors.

This

asso

ciatio

n was

ob

serve

d in b

oth ge

nder

s and

in su

bjects

with

out p

reva

lent C

VDs.

The

eleva

tion o

f BP

was t

he m

ain de

termi

nant

of re

lation

ship

betw

een M

S an

d the

para

meter

s mea

sure

d in t

he ca

rotid

, esp

ecial

ly the

thick

ness

of

the lu

men.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

93

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Hajer

et al

., (2

007)

19.

Norw

ay

Total

(n

= 21

69)

1692

men 477

wome

n

1- F

irst T

ertile

of

hcy

(9.8 ±

1.3 μ

mol/L

)

2- S

econ

d Ter

tile

of hc

y(1

3.3 ±

1.0

μmol/

L)

3- T

hird T

ertile

of

hcy

(20.4

± 8.

5 μm

ol/L)

Total

: NM

grou

p 1:

56.8 ±

9.8 ye

ars

grou

p 2:

59.3 ±

9.8 ye

ars

grou

p 3:

62.8 ±

10.4

year

s

NCEP

ATP

III (2

001)

Coho

rt

2.8-ye

ar fo

llow-

up

of pa

tients

with

va

scula

r dise

ases

After

adjus

tmen

t for a

ge, g

ende

r and

crea

tinine

clea

ranc

e, the

co

ncen

tratio

n of p

lasma

Hcy

was

sign

ifican

tly hi

gher

in th

e gro

up w

ith M

S (1

4.9 m

mol/l,

95%

CI, 1

4.5 -

15.3

mmol/

l v 14

.1 mm

ol/l, 9

5% C

I: 13.8

to

14.5

mmol/

l, p =

0.00

2).

Its co

ncen

tratio

n inc

reas

ed ac

cord

ing to

the n

umbe

r of r

isk fa

ctors

for

MS. F

rom

0 to 5

risk f

actor

s for

MS,

the c

once

ntrati

on of

plas

ma H

cy

incre

ased

from

12.7

to 15

.9 mm

ol/L,

p = 0.

001)

. In

the st

udy g

ener

al po

pulat

ion, it

was

obse

rved t

hat p

atien

ts wi

th pla

sma

conc

entra

tions

of H

cy in

the h

ighes

t tertil

e sho

wed a

40%

incre

ase i

n ris

k of n

ew ca

rdiov

ascu

lar ev

ents

when

comp

ared

to th

ose i

n the

lowe

st co

ncen

tratio

ns of

Hcy

tertil

e (OR

1.4,

95%

CI, 0

.9 - 2

.2). F

or pa

tients

in

the in

terme

diate

tertile

, the i

ncre

ased

risk w

as 10

% (O

R 1.1

, 95%

CI, 0

.7 to

1.7).

Altho

ugh w

e obs

erve

d tha

t indiv

iduals

with

MS

had h

igh co

ncen

tratio

ns of

pla

sma H

cy, th

ese c

once

ntrati

ons s

howe

d no a

ssoc

iation

with

incre

ased

ris

k for

the d

evelo

pmen

t of n

ew ca

rdiov

ascu

lar ev

ents.

In co

ntras

t, Hhc

y wa

s ass

ociat

ed w

ith in

creas

ed ris

k for

the d

evelo

pmen

t of C

VDs

in pa

tients

with

out M

S.

Lapo

inte e

t al.,

(200

7)34

.

Cana

da

Total

(n

= 12

4 po

stmen

opau

sal

wome

n)

1 - w

ithou

t MS

(n =

78)

2- w

ith M

S (n

= 37

)

Total

: 46

to 68

year

sNM

grou

p 1:

56.4 ±

4.5 y

ears

grou

p 2:

57.6 ±

4.0 ye

ars

NCEP

ATP

III (2

001)

Cros

s-sec

tiona

l

NM

The c

once

ntrati

on of

circu

lating

oxidi

zed L

DL ha

d a si

gnific

ant a

ssoc

iation

wi

th so

me ris

k fac

tors t

hat c

hara

cteriz

e MS,

such

as hy

pertr

iglyc

eride

mia

(r =

0.48,

p <0.0

001)

, low

conc

entra

tion o

f HDL

-c (r

= -0

.34, p

= 0.

0001

). an

d fas

ting h

yper

glyce

mia (

r = 0.

21, p

= 0.

02).

The d

urati

on of

men

opau

se w

as al

so po

sitive

ly as

socia

ted w

ith th

e co

ncen

tratio

n of o

xidize

d LDL

. Th

e con

centr

ation

s of L

DL-c,

trigl

ycer

ides a

nd ap

olipo

prote

in B

show

ed

a pos

itive a

ssoc

iation

with

oxidi

zed L

DL, w

here

as th

ere w

as a

nega

tive

asso

ciatio

n with

the c

once

ntrati

on of

HDL

-c. T

he co

ncen

tratio

ns of

LD

L-ap

olipo

prote

in B

(p <

0.000

1) an

d trig

lycer

ides (

p = 0.

0006

) are

the

stron

gest

pred

ictor

s of th

e con

centr

ation

of ox

idize

d LDL

after

mult

ivaria

te an

alysis

. The

se pr

edict

ors a

re si

gnific

antly

high

er in

wom

en w

ith M

S.

Wom

en w

ith M

S ha

d sign

ifican

tly in

creas

ed co

ncen

tratio

ns of

circu

lating

ox

idize

d LDL

(79.5

± 28

.3 U

/ L) w

hen c

ompa

red t

o wom

en w

ithou

t DM

(64.2

± 19

.9 U

/ L). A

s for

the n

umbe

r of M

S co

mpon

ents,

wom

en

who h

ad 5

MS co

mpon

ents

had s

ignific

antly

incre

ased

conc

entra

tions

of

oxidi

zed L

DL (9

9.5 ±

31.3)

whe

n com

pare

d to w

omen

with

3 MS

co

mpon

ents(

72.9 ±

28 , 1

) (p =

0.00

4).

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

94

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Lore

nzo e

t al.,

(200

7)20

.

Unite

d Stat

es

Total

(n

= 25

59)

1088

men

1471

wome

n

1- no

n Hisp

anic

white

men

2- M

exica

n-Am

erica

n men

3- no

n Hisp

anic

white

wom

en

4 - M

exica

n-Am

erica

n wom

en

Total

: 25

to 64

year

s NM

grou

p 1:

44 ±

11 ye

ars

grou

p 2:

43 ±

12 ye

ars

grou

p 3:

44 ±

11ye

ars

grou

p 4:

43 ±

11ye

ars

IDF

(200

6)

NCEP

ATP

III (2

001)

WHO

(199

9)

Popu

lation

base

d co

hort

7.4-ye

ar fo

llow-

up

The p

reva

lence

of M

S wa

s high

er by

the I

DF (2

006)

crite

rion,

follow

ed

by th

e NCE

P AT

P III

criter

ion (2

001)

, and

the W

HO (1

999)

crite

rion,

resp

ectiv

ely. A

ccor

ding t

o the

NCE

P AT

P III

(200

1) cr

iterio

n, the

pr

evale

nce o

f MS

was

24%

(fro

m 20

.2 to

28.4%

) and

29.6%

(26.6

-32.8

%) in

non-

Hisp

anic

men

and i

n Mex

ican-

Amer

ican w

hites

, res

pecti

vely,

and 1

6.8%

(13

.8 - 2

0, 4%

) an

d 30.9

% (2

8.3 -

33.6%

) in no

n-Hi

span

ic wh

ite w

omen

and i

n Mex

ican-

Amer

ican w

omen

, res

pecti

vely.

In

men a

nd w

omen

aged

45 or

55 ye

ars,

resp

ectiv

ely, M

S ha

d a hi

gher

pr

edict

ive va

lue fo

r CVD

s. Th

e risk

for D

M 2 i

n pati

ents

with

MS w

as

high (

OR 6.

90, 9

5% C

I, 4.97

to 9.

58).

In me

n age

d 45 y

ears

or ov

er th

e ris

k of C

VDs f

rom

MS w

as co

mpar

able

to th

e mult

iple r

isk fa

ctor (

two o

r mo

re) in

10 ye

ars o

f CAD

(10 t

o 20%

) in w

omen

. MS

show

ed in

creas

ed

risk f

or C

VDs,

indep

ende

ntly o

f age

, gen

der, e

thnici

ty, hi

story

of CV

Ds

and r

elativ

es w

ith ca

rdiov

ascu

lar ev

ents,

DM

2, no

n-HD

L cho

lester

ol an

d sm

oking

habit

(OR

2.00,

95%

CI, 1

.33 to

3.01

). Ho

weve

r, MS

incre

ases

the

CVD

risk i

n ind

ividu

als w

ho do

not h

ave d

iabete

s 2 an

d CVD

s.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

95

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Skou

mas e

t al.,

(200

7)54

.

Gree

ce

Total

(n

= 70

6 Ca

ucas

ian

subje

cts w

ith

familia

l com

bined

hy

perlip

idemi

a)

463

men

24

3 wo

men

+ 22

82 V

olunte

ers

of At

tica,

a Gre

ek

popu

lation

-bas

ed

study

cons

isting

of:

11

28

men

1154

wo

men

1- w

ith M

S

2- w

ith D

M 2 (

gly/

cemi

a hig

her t

han

125m

g/dL)

3- w

ithou

t MS

Total

: Ov

er 20

year

s NM

grou

p 1:

50.3 ±

10.9

year

s

grou

p 2:

52.2 ±

10.8

year

s

grou

p 3:

46.6 ±

9.2 ye

ars

Partic

ipants

in th

e At

tica s

tudy

NM

NCEP

ATP

III (2

001)

Cros

s-sec

tiona

l an

d Pop

ulatio

n ba

sed c

ohor

t

NM

MS ha

d a hi

gher

prev

alenc

e in t

he gr

oup w

ith fa

milia

l com

bined

hy

perlip

idemi

a (41

.8% —

63%

in m

en an

d 37%

in w

omen

) whe

n co

mpar

ed to

volun

teers

in the

Attic

a stud

y (1

9.8%

— 62

.69%

in m

en an

d 37

.3% in

wom

en).

A pr

evale

nce o

f CAD

was

obse

rved a

s foll

ows:

15.2%

in th

e gro

up w

ith

MS, 1

1.1%

in th

e gro

up w

ithou

t DM,

and 2

6.5%

in th

e gro

up w

ith D

M 2.

We f

ound

high

er co

ncen

tratio

ns of

apoli

popr

otein

B, th

e main

comp

onen

t of

the LD

L-c p

artic

le, in

the g

roup

with

MS

(178

mg/dL

) whe

n com

pare

d to

the gr

oup w

ithou

t MS

(170

.8 mg

/dL);

and l

ower

conc

entra

tions

of

apoli

popr

otein

A, th

e main

prote

in co

mpon

ent o

f the H

DL-c

partic

le, in

the

grou

p with

MS

(139

.8 mg

/dL) w

hen c

ompa

red t

o the

grou

p with

out M

S (1

46 m

g/dL)

. How

ever,

we o

nly fo

und a

n ass

ociat

ion of

CAD

with

DM

2.

Stein

et al

., (2

007)

21.

Unite

d Stat

es

Total

(n

= 18

5)

61

men

124

wome

n

Non d

iabeti

c Af

rican

Ame

rican

s

1- M

en

2- W

omen

Total

: 28

to 51

year

s

Total

:39

.8 ±

3.7 ye

ars

grou

p 1:

39.7 ±

3.9 y

ears

grou

p 2:

39.8 ±

3.6 y

ears

NCEP

ATP

III (2

001)

Coho

rt

5.3 ye

ars

The p

reva

lence

of M

S wa

s 19%

. Of a

ll volu

nteer

s in t

he st

udy,

55%

wer

e ob

ese,

and 3

8% ha

d high

BP.

Men a

nd w

omen

had s

imila

r mea

n gen

eral

char

acter

istics

, exc

ept B

MI an

d bod

y fat

perce

ntage

, whic

h wer

e high

er

in wo

men.

Even

with

high

er B

MI, th

e mea

n con

centr

ation

s of tr

iglyc

eride

s an

d HDL

-c we

re si

milar

betw

een g

roup

s. Al

thoug

h the

re w

ere n

o sta

tistic

al dif

feren

ces b

etwee

n the

grou

ps, in

sulin

sens

itivity

was

lowe

r in

wome

n. Th

ere w

ere s

ignific

ant a

ssoc

iation

s of th

ese c

once

ntrati

ons w

ith

all ot

her M

S co

mpon

ents,

as w

ell as

a po

sitive

corre

lation

of H

DL-c

with

insuli

n sen

sitivi

ty.

The d

iagno

sis of

MS

may b

e clin

ically

usefu

l to de

tect p

atien

ts wi

th pr

obab

le ins

ulin r

esist

ance

and r

educ

tion o

f risk

s for

CVD

s.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

96

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Wan

g et a

l., (2

007)

51.

Finlan

d

Total

(n

= 10

25 no

n dia

betic

Finn

ish

subje

ctswi

th MS

)

Divid

ed ac

cord

ing

to 6 d

iffere

nt cri

teria

for th

e dia

gnos

is of

MS

Total

: 65

to 74

year

s

NM

IDF

(200

6)

AHA/

NHLB

I (20

05)

ACE

(200

3)

NCEP

ATP

III (2

001)

WHO

(199

9)

EGIR

(199

9)

Popu

lation

base

d pr

ospe

ctive

13 ye

ars

The p

reva

lence

of M

S is

highly

varia

ble ac

cord

ing to

diffe

rent

criter

ia,

rang

ing fr

om 22

.5% by

the E

GIR

(199

9) cr

iterio

n, to

66.4%

by th

e ACE

(2

003)

crite

rion.

Acco

rding

to th

e NCE

P AT

P III

(200

1) cr

iterio

n, the

pr

evale

nce o

f MS

was 4

2.7%

, and

it wa

s a pr

edict

ive fa

ctor f

or m

ortal

ity

from

CVDs

. The

MS

risk r

ate fo

r CVD

s was

1.43

, 95%

CI: 1

.12-1

.84.

After

using

the C

ox m

odel

for m

ultiva

riate

analy

sis, m

ale ge

nder,

olde

r ag

e, pr

eviou

s AMI

, cur

rent

smok

ing ha

bit, p

hysic

al ina

ctivit

y, HB

P, an

d the

ur

inary

album

in to

creati

nine r

atio s

howe

d ass

ociat

ion w

ith C

AD, C

VDs

and a

ll cau

ses o

f mor

tality

. The

hype

rchole

stero

lemia

was a

ssoc

iated

wi

th mo

rtality

from

CAD

, and

fasti

ng in

sulin

was

asso

ciated

with

mor

tality

fro

m CV

Ds.

None

of th

e meth

ods f

or th

e diag

nosis

of M

S us

ed in

the s

tudy w

as ab

le to

pred

ict th

e ove

rall m

ortal

ity af

ter ad

justm

ent fo

r con

found

ing fa

ctors,

ho

weve

r, MS

shou

ld be

cons

idere

d a m

arke

r for

CVD

risk,

but n

o high

er

than i

ts co

mpon

ents

evalu

ated i

ndivi

duall

y.

Brev

etti e

t al.,

(200

6)35

.

Italy

Total

(n

= 15

4)

115

men

39wo

men

1- w

ith M

S (n

= 79

)

2- w

ithou

t MS

(n =

75)

Total

: NM

grou

p 1:

67.1 ±

9.0 ye

ars

grou

p 2:

67.5 ±

10.0

year

s

NCEP

ATP

III (2

001)

Cros

s-sec

tiona

l

1.3 ye

ars

The p

reva

lence

of M

S wa

s 51.9

% —

42.7%

in m

en, a

nd 74

.3% in

wom

en

(p <

0.01)

. Indiv

iduals

with

med

ian an

kle/br

achia

l inde

x low

er th

an of

0.64

we

re m

ore s

usce

ptible

to M

S wh

en co

mpar

ed to

thos

e with

less

seve

re

PAD

(63.9

% ve

rsus 4

2.8%

, p <

0.02)

. The

asso

ciatio

n betw

een l

ow an

kle/

brac

hial in

dex w

as m

aintai

ned a

fter a

djustm

ent fo

r age

and g

ende

r (OR

2.1

9, 95

% C

I, 1.03

to 4.

68).

Whe

n pati

ents

with

PAD

with

and w

ithou

t MS

were

comp

ared

we f

ound

a h

igher

BMI

in su

bjects

with

MS

(28.2

[25.6

to 29

.8 kg

/m2]

versu

s 26.1

[24

.2 to

27.7

kg / m

2], p

<0.01

) and

high

er co

ncen

tratio

ns of

C-re

activ

e pr

otein

(3.9

[1.6 t

o 7.6]

mg /

L ve

rsus 2

.0 [1.

1 to 3

.7] m

g / L,

p <0

.02).

The

occu

rrenc

e of a

n AMI

was

docu

mente

d in 5

8.2%

of pa

tients

with

MS

and

in 37

.5% of

patie

nts w

ithou

t MS

(p <

0.01)

. In m

ultiva

riate

analy

sis, M

S wa

s sign

ifican

tly as

socia

ted w

ith an

terior

AMI

as w

ell as

with

the a

nkle/

brac

hial in

dex (

OR 2.

15, 9

5% C

I, 1.06

to 4.

38).

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

97

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Eber

ly et

al.,

(200

6)22

.

Unite

d Stat

es

Total

(n

= 10

950)

4588

men

with

MS

6362

men

with

out

MS

1- w

ith M

S

2- w

ithou

t MS

Total

: 35

to 57

year

s (re

cruitm

ent)

NM

grou

p 1:

53 ±

5.9 y

ears

(6th

annu

al vis

it)

grou

p 2:

53 ±

5.9 y

ears

(6th

annu

al vis

it)

NCEP

ATP

III (2

001)

Popu

lation

base

d co

hort

18.4-

year

follo

w-up

of pa

tients

wi

th CV

Ds.

The p

reva

lence

of M

S wa

s 41.8

% am

ong t

he s

tudy p

artic

ipants

. In th

e gr

oup w

ith M

S 57

.9% ha

d 3 cr

iteria

for d

iagno

sis of

MS,

32.3%

had 4

cri

teria,

and 9

.9% ha

d all 5

crite

ria.

The m

ost fr

eque

nt MS

comp

onen

ts we

re hi

gh B

P, hy

pertr

iglyc

eride

mia,

and l

ow H

DL-c

conc

entra

tion.

In the

MS

grou

p hyp

ergly

caem

ia an

d low

er co

ncen

tratio

n of H

DL-c

were

pr

edict

ive of

CVD

mor

tality

, follo

wed b

y inc

reas

ed B

MI, in

creas

ed B

P an

d hy

pertr

iglyc

eride

mia.

In co

ntras

t, HDL

-c wa

s not

a pre

dictiv

e fac

tor in

men

with

out M

S.

The r

isk of

CVD

mor

tality

was

thre

e tim

es hi

gher

in in

dividu

als w

ho ha

d all

5 ris

k fac

tors f

or th

e diag

nosis

of M

S wh

en co

mpar

ed to

indiv

iduals

wh

o did

not h

ave a

ny of

the c

ompo

nents

for t

he di

agno

sis of

MS.

Iribar

ren e

t al.,

(200

6)55

.

Unite

d Stat

es

Total

(n

= 78

6)

308

men

478

wome

n

1 - w

ith C

AD (A

MI,

angin

a with

≥ 50

%

steno

sis

of the

arter

y or

coro

nary

reva

scula

rizati

on)

2 - w

ithou

t CA

D

Total

:NM

Men a

ged o

ver 4

6 ye

ars

Wom

en ag

ed ov

er

56 ye

ars

grou

p 1:

45.8 ±

6.5 ye

ars

Grou

p 2:

45.2 ±

5.6 ye

ars

NCEP

ATP

III (2

001)

AHA/

NHLB

I (20

05)

Contr

ol ca

se

4-ye

ar pe

riod

of dia

gnos

tic

verifi

catio

n.

In the

grou

p with

CAD

, 59%

had a

AMI

, 26%

unde

rwen

t a

reva

scula

rizati

on pr

oced

ure,

and 1

6% w

ere d

iagno

sed w

ith an

gina.

The p

rese

nce o

f MS

was s

ignific

antly

high

er in

patie

nts w

ith C

AD.

Acco

rding

to th

e NCE

P AT

P III

(200

1) cr

iterio

n, the

prev

alenc

e of M

S in

the gr

oup w

ith C

AD an

d with

out D

M 2 w

as 32

%, a

nd in

thos

e with

DM

2 it w

as 26

%.

The C

AD pa

tients

had g

reate

r elev

ation

of S

BP, h

igher

prev

alenc

e of

hype

rtens

ion, h

yper

triglyc

eride

mia,

hype

rglyc

emia,

hype

rinsu

linem

ia,

incre

ased

C-re

activ

e pro

tein a

nd H

OMA

index

. MS

resu

lted i

n high

risk o

f ear

ly on

set o

f CAD

, but

the pr

ogno

sis w

as no

t dif

feren

t whe

n the

patie

nt ha

d MS

or on

e or m

ore o

f its r

isk

factor

s.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

98

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Kurl e

t al.,

(200

6)43

.

Finlan

d

Total

(n

= 11

31 m

en

with

no hi

story

of DM

2 an

d CVD

s at

base

line)

1- w

ith M

S (n

= 11

4)

2- w

ithou

t MS

(n =

1017

)

Total

: NM

grou

p 1:

51.8 ±

5.8 ye

ars

grou

p 2:

51.6 ±

5.8 ye

ars

NCEP

ATP

III (2

001)

WHO

(199

9)

Popu

lation

base

d pr

ospe

ctive

coho

rt

14.3-

year

follo

w-up

At th

e beg

inning

of th

e mon

itorin

g only

9% of

men

had M

S ac

cord

ing to

the

NCE

P AT

P III

(200

1) cr

iterio

n. MS

was

asso

ciated

with

all ty

pes o

f stro

ke (O

R 2.0

5, 95

% C

I, 1.03

to

4.11,

p = 0.

042)

, and

65 st

roke

s occ

urre

d dur

ing m

onito

ring,

of wh

ich 47

we

re is

chem

ic.

It was

obse

rved t

hat M

S wa

s ass

ociat

ed w

ith in

creas

ed ris

k of is

chem

ic typ

e of s

troke

(OR

2.39,

95%

CI, 1

.17 to

4.89

, p =

0.01

6) ad

justed

for

chan

ges i

n the

test

effor

t, LDL

-c, fib

rinog

en, in

take o

f satu

rated

fatty

acids

an

d whit

e bloo

d cell

s.

Lang

enbe

rg et

al.

, (20

06)44

.

Unite

d Stat

es

Total

(n =

2118

)

977

men

1141

wome

n

1- m

en

2- w

omen

Total

: 40

to 94

year

s

grou

p 1:

71.1

year

s NM

grou

p 2:

70 ye

ars

NM

NCEP

ATP

III (2

001)

Pros

pecti

ve co

hort

4 yea

rs

The p

reva

lence

of M

S wa

s app

roxim

ately

17%

in m

en an

d 15%

in

wome

n. Th

e gen

der a

nd ag

e adju

sted r

isk ra

te for

CAD

and M

S wa

s 1.65

(1.25

-2.1

8), 9

5%, p

<0.0

01, a

nd th

is as

socia

tion w

as no

t alte

red s

ignific

antly

aft

er ad

justm

ent fo

r gen

der, a

ge or

DM

2 for

each

of th

e inte

racti

ons.

The a

djustm

ents

for ad

ipone

ctin,

leptin

, and

ghre

lin ex

erted

little

influ

ence

on

the a

ssoc

iation

betw

een M

S an

d CVD

mor

tality

; the m

axim

um ch

ange

in

the ra

te of

risk w

as fo

r adip

onec

tin, th

at infl

uenc

ed th

is as

socia

tion b

y 15

.4%.

The a

ssoc

iation

of C

AD an

d MS

was r

educ

ed by

25%

after

adjus

tmen

t for

inter

leukin

6, an

d by 3

5% af

ter ad

justm

ent fo

r C-re

activ

e pro

tein.

The

CVD

morta

lity in

creas

ed lin

early

with

high

er co

ncen

tratio

ns of

inter

leukin

6 a

nd C

-reac

tive p

rotei

n. W

e fou

nd no

evide

nce o

f the i

nflue

nce o

f MS

acco

rding

to di

ffere

nt co

ncen

tratio

ns of

horm

ones

that

are i

nvolv

ed w

ith fa

t or in

flamm

atory

marke

rs. H

owev

er, IL

6 an

d C-re

activ

e pro

tein s

howe

d a si

gnific

ant li

near

re

lation

ship

with

CVD

morta

lity af

ter an

alysis

adjus

ted fo

r age

and g

ende

r (p

<0.0

01 fo

r both

).

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

99

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Meigs

et al

., (2

006)

56.

Unite

d Stat

es

Total

(n =

2902

)

1302

men

1600

wome

n

By B

MI an

d with

or

with

out M

S:

1 - ≤

25 kg

/m2

2 - 25

to 29

.9 kg

/m2

3 - ≥

30 kg

/m2

Total

: NM

grou

p 1:

with

MS: 5

9 yea

rs (N

M)

witho

ut MS

: 52

year

s (NM

)

grou

p 2:

with

MS: 5

7 yea

rs (N

M)

witho

ut MS

: 53

year

s (NM

)

grou

p 3:

with

MS: 5

6 yea

rs (N

M)

witho

ut MS

: 52

year

s (NM

)

NCEP

ATP

III (2

001)

Comm

unity

base

d lon

gitud

inal

11-ye

ar fo

llow-

up

The p

reva

lence

of M

S in

norm

al ind

ividu

als w

as 7%

and t

he re

lative

risk

for D

M 2 w

as O

R 3.9

7 (95

% C

I, 1,35

-11,6)

, and

for C

VDs i

t was

3.01

(C

I 95 %

1.68

-5.41

). In

obes

e sub

jects

the pr

evale

nce o

f MS

was 6

3%,

and t

he re

lative

risk f

or D

M 2 i

ncre

ased

sign

ifican

tly: 1

0.3 (9

5% C

I, 5.44

-1

9.5);

and f

or C

VDs b

y 2.13

(95%

CI, 1

.43-3

.18).

The r

esult

s wer

e sim

ilar in

the a

nalys

is of

the B

MI an

d the

categ

ories

of in

sulin

resis

tance

. Th

e set

of ris

k fac

tors f

or M

S an

d ins

ulin r

esist

ance

resu

lted i

n a hi

gh ris

k for

DM

2 and

CVD

s ass

ociat

ed m

ainly

with

BMI in

creas

e.

Najar

ian et

al.,

(200

6)45

.

Unite

d Stat

es

Total

(n =

2097

)

1059

men

1038

wome

n

1- m

en

2- w

omen

Total

: 50

to 81

year

s;

59.1 ±

6.1 ye

ars

grou

p 1:

59.1 ±

6.2 ye

ars

grou

p 2:

59.1 ±

6.0 ye

ars

NCEP

ATP

III (2

001)

Pros

pecti

ve co

hort

14 ye

ars

The p

reva

lence

of M

S wa

s 30.3

% in

men

and 2

4.7%

of w

omen

. Afte

r a 1

4-ye

ar fo

llow-

up, 7

5 men

and 5

5 wom

en su

ffere

d the

first

strok

e. Th

e rela

tive r

isk of

stro

ke in

indiv

iduals

with

DM

2 and

MS

was h

igh

(3.28

, 95%

CI, 1

.82 to

5.92

), hig

her t

han t

hat o

f any

othe

r MS

risk f

actor

ev

aluate

d ind

ividu

ally.

In thi

s stud

y, MS

had a

high

prev

alenc

e and

was

cons

idere

d an

indep

ende

nt ris

k fac

tor fo

r stro

ke in

indiv

iduals

with

out d

iabete

s. Ho

weve

r, pre

venti

on an

d con

trol o

f MS

and i

ts ris

k fac

tors m

ay he

lp in

redu

cing t

he in

ciden

ce of

stro

ke.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

100

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Polle

x et a

l., (2

006)

23.

Cana

da

Total

(n =

166)

66 men

100

wome

n

1- w

ith M

S (n

= 73

)

2- w

ithou

t MS

(n =

93)

Total

: NM

grou

p 1:

42.2 ±

1.6ye

ars

grou

p 2:

34.8 ±

1.6ye

ars

NCEP

ATP

III (2

001)

Coho

rt NM

The p

reva

lence

of M

S in

the st

udy p

opula

tion w

as 44

%. T

he gr

oup w

ith

MS sh

owed

sign

ifican

tly in

creas

ed co

ncen

tratio

ns of

total

chole

stero

l and

BM

I whe

n com

pare

d to t

he gr

oup w

ithou

t MS

(p <

0.000

1).

In thi

s stud

y, the

caro

tid in

tima-

media

laye

r thic

knes

s and

the t

otal v

olume

of

platel

ets w

ere e

valua

ted in

volun

teers

with

and w

ithou

t MS.

Only

after

ad

justm

ent fo

r age

and g

ende

r, stat

istica

l diffe

renc

es in

the c

aroti

d arte

ry int

ima-

media

laye

r thic

knes

s wer

e obs

erve

d betw

een t

he gr

oups

with

and

witho

ut MS

, 81

8 ± 18

μm an

d 746

± 20

μm, r

espe

ctive

ly (p

= 0.

039)

. The

grea

ter th

e nu

mber

of ris

k fac

tors t

hat c

hara

cteriz

e MS

the gr

eater

the i

ncre

ase i

n the

ca

rotid

intim

a-me

dia la

yer t

hickn

ess.

Tavil

et al

., (2

006)

36.

Turke

y

Total

(n =

345)

143

men

202

wome

n

1- w

ith M

S (n

= 20

5)

2- w

ithou

t MS

(n =

140)

Total

: NM

grou

p 1:

53 ±

7 ye

ars

grou

p 2:

52 ±

6 ye

ars

NCEP

ATP

III (2

001)

Cros

s-sec

tiona

l

NM

Patie

nts w

ith M

S sh

owed

a sig

nifica

nt inc

reas

e in t

he va

lues o

f the m

ean

platel

et vo

lume,

an in

dicato

r of th

e path

ophy

siolog

ical p

roce

ss of

CAD

, wh

en co

mpar

ed to

the c

ontro

l gro

up.

MS w

as as

socia

ted w

ith m

ean p

latele

t volu

me in

depe

nden

tly of

WC,

fas

ting h

yper

glyce

mia a

nd nu

mber

of M

S co

mpon

ents.

In ad

dition

, the

value

s of m

ean p

latele

t volu

me w

ere s

ignific

antly

diffe

rent

in ind

ividu

als

with

MS an

d with

DAC

. W

hen p

atien

ts wi

th MS

wer

e divi

ded i

nto 3

subg

roup

s, ac

cord

ing to

the

seve

rity of

CAD

, a pr

ogre

ssive

incre

ase i

n the

mea

n plat

elet v

olume

was

ob

serve

d fro

m the

first

to the

last

grou

p. Ho

weve

r, whe

n the

grou

ps w

ith an

d with

out M

S we

re ev

aluate

d, no

sig

nifica

nt dif

feren

ce w

as ob

serve

d whe

n the

seve

rity of

CAD

was

co

nside

red.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

101

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Dekk

er et

al.,

(200

5)13

.

Nethe

rland

Total

(n =

1364

)

615

men

749

wome

n

1 - w

omen

with

MS

acco

rding

to

NCEP

ATP

III (2

001)

2 -

wom

en w

ith

MS ac

cord

ing to

oth

er cr

iteria

than

the

NCE

P 3 -

men

with

MS

acco

rding

to

criter

ia of

NCEP

AT

P III

(200

1)

4 - m

en w

ith M

S ac

cord

ing to

othe

r cri

teria

than t

he

NCEP

ATP

III (2

001)

.

Total

: 50

to 75

year

s;NM

grou

p 1:

62.8 ±

7.6 ye

ars;

grou

p 2:

60.3 ±

7.2 ye

ars;

grou

p 3:

62.2 ±

7.2 ye

ars;

grou

p 4:

60.4 ±

7.1 ye

ars.

ACE

(200

3)

NCEP

ATP

III (2

001)

WHO

(199

9)

EGIR

(199

9)

Popu

lation

base

d co

hort

10-ye

ar fo

llow-

up

of pa

tients

with

mo

rbity

and

morta

lity fr

om

DCVs

(Hoo

rn

study

).

Acco

rding

to th

e NCE

P AT

P III

(200

1) cr

iterio

n, MS

had a

prev

alenc

e of

19%

in m

en, a

nd 26

% in

wom

en, in

this

study

, and

it wa

s ass

ociat

ed

with

incre

ased

risk o

f mor

bidity

and m

ortal

ity fr

om C

VDs (

twice

mor

e).

Rega

rdles

s of th

e meth

od us

ed fo

r the

diag

nosis

of M

S, th

is stu

dy

show

ed in

creas

ed ris

k for

fatal

and n

onfat

al CV

Ds. T

he pr

esen

ce of

only

1 or 2

risk f

actor

s was

also

asso

ciated

with

CVD

s, pa

rticula

rly in

wom

en.

Whe

n the

numb

er of

risk f

actor

s was

inclu

ded a

s a lin

ear v

ariab

le, th

e ra

te of

fatal

and n

onfat

al ris

k for

CVD

s ros

e fro

m 1.2

9 and

1.11

to 1.

50 fo

r ea

ch ris

k fac

tor pr

esen

t in bo

th ge

nder

s.

Dursu

noglu

et al

., (2

005)

37.

Turke

y

83 w

omen

1- w

omen

with

MS

(n =

53)

2- he

althy

wom

en

(n =

30)

Total

: NM

grou

p 1:

53.1 ±

6.9 ye

ars

grou

p 2:

52.8 ±

6.3 ye

ars

NCEP

ATP

III (2

001)

Cros

s-sec

tiona

l

NM

Wom

en w

ith M

S ha

d mild

left v

entric

ular d

iastol

ic dy

sfunc

tion i

n co

mpar

ison t

o hea

lthy w

omen

. MS

was

asso

ciated

with

grea

ter le

ft ven

tricula

r dys

functi

on an

d dia

stolic

dysfu

nctio

n with

an in

creas

e in t

he ov

erall

inde

x of m

yoca

rdial

pe

rform

ance

. The

pres

ence

of gl

obal

dysfu

nctio

n in p

atien

ts wi

th MS

ca

n lea

d to t

he de

velop

ment

of he

art fa

ilure

. The

se fin

dings

sugg

est a

n as

socia

tion o

f MS

with

CVDs

.

Girm

an et

al.,

(200

5)24

.

Nethe

rland

Total

(n =

1391

)

631

men

760

wome

n

1- m

en

2- w

omen

Total

: NM

grou

p 1:

60.8 ±

7.1 ye

ars

grou

p 2:

60.9 ±

7.3 ye

ars

NCEP

ATP

III (2

001)

Popu

lation

base

d co

hort

11-ye

ar fo

llow-

up

of mo

rbity

and

morta

lity fr

om

CVDs

MS ha

d a po

sitive

asso

ciatio

n with

CVD

s; ho

weve

r, the

high

er th

e nu

mber

of M

S ris

k fac

tors i

n the

se in

dividu

als, th

e high

er w

as th

e risk

for

CVD

s. In

men,

the ris

k was

grea

ter in

the p

rese

nce o

f 3 or

mor

e MS

comp

onen

ts, w

here

as in

wom

en th

e pre

senc

e of 2

or m

ore M

S co

mpon

ents

incre

ased

the r

isk fo

r CVD

s. Af

ter a

binar

y re

gres

sion

analy

sis of

the c

ross

-secti

onal

data,

this

study

sugg

ests

that M

S co

mpon

ents

can n

ot be

equa

lly w

eighte

d, an

d it a

lso su

gges

ts tha

t am

ong t

he co

mpon

ents

of MS

, the c

once

ntrati

ons o

f trigl

ycer

ides a

nd

HDL-

c are

the M

S co

mpon

ents

with

the gr

eates

t indiv

idual

weigh

t for

CVDs

, by t

he N

CEP

ATP

III cri

terion

(200

1).

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

102

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Iglse

der e

t al.,

(200

5)46

.

Austr

ia

Total

(n =

1588

)

1001

men

587

wome

n

1- co

ntrol

(men

/ wo

men)

2- w

ith M

S (m

en / w

omen

)

Total

: NM

men:

40 to

55 ye

ars

wome

n: 50

to 65

year

s

grou

p 1:

men:

49

.1 ±

5.4 ye

ars

wome

n: 56

.4 ±

4.2ye

ars

grou

p 2:

men:

50.5 ±

5.2ye

ars

wome

n: 57

.1± 4.

7ye

ars

NCEP

ATP

III (2

001)

Pros

pecti

ve co

hort

NM

The e

xtent

of ath

eros

clero

tic pl

aque

s in t

he ar

tery a

nd th

e car

otid i

ntima

-me

dia la

yer t

hickn

ess s

howe

d sign

ifican

t elev

ation

in vo

luntee

rs wi

th MS

. In

logist

ic re

gres

sion,

after

adjus

tmen

t for a

ge, B

MI, s

mokin

g hab

it and

LD

L-c,

the od

ds ra

tio fo

r gre

ater c

aroti

d inti

ma-m

edia

layer

thick

ness

re

maine

d sign

ifican

t in w

omen

(OR,

2.26

, 95%

CI, 1

.31 to

3.89

, p =

0.0

03),

but n

ot in

men (

OR, 1

.16, 9

5% C

I, 0.77

to 1.

15).

The d

evelo

pmen

t of a

thero

scler

osis

was m

ore p

rono

unce

d in w

omen

wh

en co

mpar

ed to

that

obse

rved i

n men

. Am

ong t

he ris

k fac

tors t

hat c

hara

cteriz

e MS,

HDL

-c wa

s the

facto

r with

the

grea

ter im

pact

on th

e mea

n car

otid i

ntima

l laye

r thic

knes

s in m

en,

wher

eas b

lood g

lucos

e had

grea

ter im

pact

in wo

men.

Monta

lcini

et al.

, (2

005)

50.

Italy

Total

(n =

265

meno

paus

al wo

men)

1- w

omen

with

MS

(n =

55)

2- w

omen

with

out

MS

(n =

210)

Total

: 45

to 75

year

s NM

grou

p 1:

58.6 ±

7.5 ye

ars

grou

p 2:

56.4 ±

7.6 ye

ars

NCEP

ATP

III (2

001)

Obse

rvatio

nal

MS w

as st

rong

ly as

socia

ted w

ith at

hero

scler

osis

in the

extra

crania

l ca

rotid

arter

y, a m

arke

r of C

VDs i

n the

stud

y pop

ulatio

n. In

wome

n with

no

rmal

conc

entra

tions

of LD

L-c o

r with

bord

erlin

e valu

es, th

e inc

idenc

e of

ather

oscle

rosis

was

sign

ifican

tly lo

wer w

hen c

ompa

red t

o wom

en

with

eleva

ted LD

L-c.

The h

igh pl

asma

conc

entra

tion o

f LDL

-C w

as

indep

ende

ntly a

ssoc

iated

with

athe

rosc

leros

is in

the ex

tracra

nial c

aroti

d ar

tery (

p = 0.

026)

amon

g wom

en w

ith M

S.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

103

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Rutte

r et a

l., (2

005)

25.

Engla

nd

Total

(n =

2898

)

1302

men

1596

wome

n

1- m

en

2- w

omen

Total

: 26

to 82

year

s 54

year

s (NM

)

grou

p 1NM

grou

p 2NM

NCEP

ATP

III (2

001)

Popu

lation

base

d co

hort

7 yea

rs

MS an

d ins

ulin r

esist

ance

have

been

indiv

iduall

y rela

ted to

CVD

s, an

d age

and g

ende

r-adju

sted r

isk ra

tes w

ere 2

.0 (9

5% C

I, 1.5

to 2.6

, p =

0.00

01) f

or M

S; an

d 1.9

(95%

CI, 1

.2 to

2.9, p

= 0.

003)

for in

sulin

re

sistan

ce, a

ccor

ding t

o the

HOM

A ind

ex. In

this

study

, MS

was

cons

idere

d as a

n ind

epen

dent

pred

ictor

for C

VDs.

Wils

on et

al.,

(200

5)26

.

Unite

d Stat

es

Total

(n =

3323

)

1524

men

1774

wome

n

1-

men

with

MS

2- m

en w

ithou

t MS

3- w

omen

with

MS

4- w

omen

with

out

MS

Total

: 22

to 81

year

sNM

grou

p 1:

53 ±

9 ye

ars;

grou

p 2:

49 ±

10 ye

ars;

grou

p 3:

55 ±

9 ye

ars

grou

p 4:

50 ±

10 ye

ars

NCEP

ATP

III (2

001)

Coho

rt

8 yea

rs

The p

reva

lence

of M

S wa

s 26.8

% in

men

and 1

6.6%

in w

omen

. In m

en,

the re

lative

risk o

f MS

adjus

ted fo

r age

and f

or C

VDs w

as 2.

88 (9

5% C

I, 1.9

9 to 4

.16);

for C

AD it

was 2

.54 (9

5% C

I, 1.62

to 3,

98);

and f

or D

M 2

it was

6.92

(95%

CI, 4

.47 to

10.81

). In

wom

en, r

isk ra

tes w

ere l

ower

for

CVDs

(2.25

, 95%

CI, 1

.31 to

3.88

) and

CAD

(1.54

, 95%

CI, 0

.68 to

3.53

), an

d sim

ilar f

or D

M 2 (

6.90,

95%

CI, 4

.34 to

10.94

). Th

e esti

mated

risk o

f MS

asso

ciated

with

CVD

s, CA

D an

d DM

2 wer

e 34

%, 2

9% an

d 62%

in m

en, a

nd 16

%, 8

%, 4

7% in

wom

en, r

espe

ctive

ly.

MS sh

owed

asso

ciatio

n with

CVD

s and

DM

2 in b

oth ge

nder

s.

Zelle

r et a

l., (2

005)

52.

Fran

ce

Total

(n

= 63

3)

475

men

158

wome

n

1- w

ith M

S (n

= 29

0)

2- w

ithou

t MS

(n =

343)

Total

: NM

grou

p 1:

57 to

70 ye

ars

70 ye

ars

NM

grou

p 2:

52 to

74 ye

ars

63 ye

ars

NM

NCEP

ATP

III (2

001)

Pros

pecti

ve

NM

The p

reva

lence

of M

S wa

s 46%

, and

it wa

s mor

e pre

valen

t in w

omen

. Th

e rate

of in

-hos

pital

morta

lity w

as hi

gher

in pa

tients

with

MS,

and a

lso

the in

ciden

ce of

seve

re he

art fa

ilure

with

out h

ospit

al de

ath. A

mong

the

risk f

actor

s tha

t cha

racte

rize M

S, hy

pertr

iglyc

erida

emia

was t

he m

ost

critic

al in

seve

re he

art fa

ilure

.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

104

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

China

li et a

l., (2

004)

27.

Unite

d Stat

es

Total

(n

= 14

34)

598

men

838

wome

n

1- m

en w

ith M

S

(n =

197)

2- m

en w

ithou

t MS

(n

= 40

1)

3- w

omen

with

MS

(n =

415)

4- w

omen

with

out

MS

(n =

423)

Total

: 45

to 74

year

s NM

grou

p 1:

59 ±

5.1

year

s;

grou

p 2:

58 ±

4.4

year

s;

grou

p 3:

60.2 ±

7.9 ye

ars

grou

p 4:

58.6 ±

8.0 ye

ars

NCEP

ATP

III (2

001)

Coho

rt

NM

Patie

nts w

ith M

S ha

d a la

rger

left v

entric

le an

d gre

ater v

esse

l wall

thi

ckne

ss, le

ft atria

l diam

eter (

all w

ith p ≤

0.01)

and h

igher

prev

alenc

e of

left v

entric

ular h

yper

troph

y (p <

0.001

). In

the m

ultipl

e reg

ress

ion m

odel,

on

ly inc

reas

ed B

P an

d WC

show

ed as

socia

tion w

ith th

e lar

ger d

iamete

r of

the le

ft ven

tricle,

and o

nly in

creas

ed B

P sh

owed

asso

ciatio

n with

hig

her le

ft ven

tricula

r mas

s and

left v

entric

ular h

yper

troph

y (p <

0.001

for

both)

.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

105

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Gorte

r et a

l., (2

004)

38.

Nethe

rland

Total

(n

= 11

17)

883

men

234

wome

n

1 - w

ith C

AD

(n =

527)

2 - w

ith C

VDs

(n =

258)

3 - w

ith P

AD

(n =

232)

4 - w

ith A

AA

(n =

100)

Total

: 18

a 80

year

s60

± 10

year

s

grou

p 1:

men:

(n =

434;

57 ±

9 ye

ars)

wome

n: (n

= 93

; 61

± 9

year

s)

grou

p 2:

men:

(n =

192;

61 ±

11 ye

ars)

wome

n: (n

= 66

; 60

± 11

year

s)

grou

p 3:

men:

(n =

163;

58 ±

10 ye

ars)

wome

n: (n

= 69

; 59

± 11

year

s)

grou

p 4:

men:

(n =

94;

69 ±

6 ye

ars)

wome

n: (n

= 6;

66

± 10

year

s)

NCEP

ATP

III (2

001)

Cros

s-sec

tiona

l

NM

The p

reva

lence

of M

S in

the st

udy w

as 46

% co

mpar

ed w

ith 58

% in

pa

tients

with

PAD

, 41%

in th

ose w

ith C

AD, 4

3% in

patie

nts w

ith C

VDs

and 4

7% in

thos

e with

AAA

. In

gene

ral, w

omen

had a

high

er pr

evale

nce o

f MS,

56%

, whe

n com

pare

d to

men,

43%

. Th

e inc

reas

ed B

P co

mpon

ent o

f MS

was m

ore f

requ

ently

obse

rved i

n vo

luntee

rs, es

pecia

lly in

wom

en (7

8%).

Ther

e was

a hig

h pre

valen

ce of

MS

in pa

tients

with

man

ifesta

tions

of at

hero

scler

otic v

ascu

lar di

seas

e. Pa

tients

with

MS

had m

ore o

ften a

med

ical h

istor

y of v

ascu

lar di

seas

e, pa

rticula

rly pa

tients

with

CVD

s and

PAD

.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

106

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Kip e

t al.,

(200

4)28

.

Unite

d Stat

es

Total

(n

= 78

0 wom

en

with

coro

nary

angio

grap

hy

to ev

aluate

su

spec

ted

myoc

ardia

l isc

hemi

a)

Acco

rding

To

BMI

.

1 - eu

troph

ic (B

MI

<24.9

kg/m

2, n

= 18

4)

2 - ov

erwe

ight

(BMI

≥ 25

and

≤ 29

.9 kg

/m2,

n =

269)

3 - ob

ese (

BMI

≥ 30

kg/m

2, n

= 32

7)

Acco

rding

to th

e pr

esen

ce of

MS

a - w

ith M

S (n

= 45

1)

b-MS

with

out

(n =

329)

Total

: 21

to 86

year

sNM

grou

p 1:

59 ±

13 ye

ars

grou

p 2:

58 ±

11 ye

ars

grou

p 3:

57 ±

11 ye

ars

a - N

M

b - N

M

NCEP

ATP

III (2

001)

Coho

rt

3 yea

rs

The p

reva

lence

of C

AD (s

tenos

is ≥

50%

) and

the 3

-year

risk f

or C

VD

were

evalu

ated a

nd co

mpar

ed w

ith B

MI an

d MS.

MS

and B

MI w

ere

stron

gly as

socia

ted, b

ut on

ly MS

had a

sign

ifican

t ass

ociat

ion w

ith C

AD.

MS in

creas

ed th

e risk

of m

ortal

ity by

2.01

, 95%

CI, 1

.26 to

3.20

and

incre

ased

the r

isk of

nonfa

tal M

I, stro

ke, a

nd C

HF by

1.88

(95%

CI,

1.38 t

o 2.57

). Co

ncen

tratio

ns of

C-re

activ

e pro

tein w

ere m

ore s

trong

ly as

socia

ted w

ith M

S tha

n BMI

, but

were

not in

depe

nden

tly as

socia

ted w

ith

risk o

f mor

tality

after

3 ye

ars.

Howe

ver, M

S ca

n pre

dict fu

ture r

isk of

CVD

in

wome

n.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

107

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Mali

k et a

l., (2

004)

47.

Unite

d Stat

es

Total

(n

= 62

55)

2852

men

3403

wome

n

1 - 28

72 pa

tients

wi

thout

MS,

witho

ut DM

2 an

d wi

thout

CVDs

.

2- 16

98 pa

tients

wi

th MS

3- 11

78 pa

tients

wi

th MS

and

wi

thout

DM 2

4- 52

0 pati

ents

with

DM 2

5- 16

79 pa

tients

wi

th CV

Ds

6 - 13

98 pa

tients

wi

th pr

e- ex

isting

CV

Ds

7 - 28

1 pati

ents

with

DM 2

and

CVDs

Total

: 30 t

o 74

year

s49

.7 ye

ars

NM

grou

p 1: 4

5.6

year

sNM

grou

p 2: 5

1.4

year

sNM

grou

p 3: 5

0.0

year

sNM

grou

p 4: 5

5.4

year

sNM

grou

p 5: 5

0.6

year

sNM

grou

p 6: 5

0.8

year

sNM

grou

p 7: 6

1.7

year

sNM

NCEP

ATP

III (2

001)

Pros

pecti

ve co

hort

Mean

follo

w-up

pe

riod o

f 13-

year

s by

NHA

NES

III

The p

rese

nce o

f DM

2 was

pred

ictive

for a

ll-cau

se m

ortal

ity. T

hose

ind

ividu

als w

ith on

e or t

wo m

etabo

lic ab

norm

alitie

s of M

S ha

d an

incre

ased

risk f

or C

AD an

d CVD

mor

tality

. Ab

ove a

ll, MS

was

a str

ong p

redic

tor fo

r CAD

, CVD

, and

all-c

ause

mo

rtality

whe

n com

pare

d to i

ts ind

ividu

al co

mpon

ents.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

108

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Marro

quin

et al.

, (2

004)

48.

Unite

d Stat

es

Total

(n

= 75

5 wom

en)

1 - w

ith M

S 2 -

with

out M

S 3 -

with

DM

2

Total

: NM

grou

p 1:

60 ye

ars

NM

grou

p 2:

57 ye

ars

NM

grou

p 3:

59 ye

ars

NM

NCEP

ATP

III (2

001)

Pros

pecti

ve co

hort

4 yea

rs

Whe

n wom

en w

ith M

S we

re co

mpar

ed to

wom

en w

ithou

t MS,

a low

er

survi

val ra

te wa

s obs

erve

d afte

r 4 ye

ars,

in the

grou

p with

MS.

A 4-

year

ab

senc

e of e

vents

(non

fatal

MI, s

troke

or C

HF) w

as 87

.8% in

the g

roup

wi

th DM

and 9

3.5%

in th

e gro

up w

ithou

t MS

(p =

0.00

3). W

omen

with

MS

and w

ith an

giogr

aphic

ally s

ignific

ant C

AD ha

d a hi

gher

risk o

f dev

elopin

g ca

rdiov

ascu

lar ev

ents

when

comp

ared

to w

omen

with

out M

S (O

R 4.9

3, 95

% C

I, 1.02

to 23

.76, p

= 0.

05).

Nino

miya

et al

., (2

004)

29.

Unite

d Stat

es

Total

(n

= 15

922)

men a

nd w

omen

NM

1 - M

S wi

th an

d with

out

card

iovas

cular

ev

ent

(n =

14,82

4)

2 - w

ith M

S wi

th AM

I/stro

ke

(n =

1098

)

3 - w

ith M

S an

d AM

I (n

= 75

2)

4 - w

ith M

S an

d str

oke

(n =

464)

Total

: 20

a 89

year

s NM

grou

p 1:

46.7

year

sNM

grou

p 2:

68.5

year

s NM

grou

p 3:

68.2

year

sNM

grou

p 4:

43.5

year

sNM

NCEP

ATP

III (2

001)

“Full

Syn

drom

e”:

patie

nts w

ith at

lea

st 3 o

f thes

e fiv

e con

dition

s: ins

ulin r

esist

ance

, ab

domi

nal

obes

ity (b

y WC)

hy

pertr

iglice

ridem

ia,

low

HDL-

c and

HBP

.

Coho

rt

6-ye

ar fo

llow-

up

by N

HANE

S III

After

mult

ivaria

te an

alysis

, MS

show

ed a

signifi

cant

relat

ionsh

ip wi

th AM

I (O

R, 2.

01, 9

5% C

I, 1.53

to 2.

64),

strok

e (OR

, 2.16

; 95%

CI, 1

.48 to

3.16

) an

d MI/s

troke

(OR,

2.05

, 95%

CI, 1

.64 to

2.57

). Am

ong t

he ris

k fac

tors f

or M

S, in

sulin

resis

tance

(OR,

1.30

, 95%

CI, 1

.03

to 1.6

6), lo

w HD

L-c (

OR, 1

.35; 9

5% C

I, 1.05

to 1.

74),

HBP

(OR,

1.44

, 95

% C

I, 1.00

to 2.

08) a

nd hy

pertr

iglyc

eride

mia (

OR, 1

.66; 9

5% C

I 1.20

to

2.30)

show

ed in

depe

nden

t and

sign

ifican

t rela

tions

hip w

ith M

I/stro

ke.

The r

esult

s ind

icate

stron

g and

cons

isten

t ass

ociat

ion of

MS

with

the

prev

alenc

e of A

MI an

d stro

ke.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

109

Review Article

Bibl

iogr

aphi

cal

Refe

renc

e/ (

Coun

try)

Popu

latio

n /

Gend

erSt

udy G

roup

sAg

e Ran

ge

(yea

rs) /

Mea

n an

d SD

(yea

rs)

Crite

ria u

sed

for

the d

iagno

sis

of M

S

Type

of S

tudy

/ Du

ratio

nMa

in R

esul

ts

Reilly

et al

., (2

004)

39.

Unite

d Stat

es

Total

(n

= 84

0)

443

men

397

wome

n

1 - M

en

2 - W

omen

Both

grou

ps w

ere

comp

osed

of no

n-dia

betic

subje

cts

with

family

histo

ry of

prem

ature

CV

Ds an

d risk

s as

socia

ted w

ith

coro

nary

arter

y ca

lcific

ation

.

Total

: 40

to 57

year

sNM

grou

p 1:

40 to

51 ye

ars

NM

grou

p 2:

44 to

57 ye

ars

NCEP

ATP

III (2

001)

WHO

(199

9)

Cros

s-sec

tiona

l

NM

MS, B

P inc

reas

e, W

C an

d the

HOM

A ind

ex sh

owed

an as

socia

tion

with

coro

nary

arter

y calc

ificati

on in

age-

adjus

ted an

alysis

. MS

was a

n im

porta

nt ma

rker o

f sub

clinic

al co

rona

ry ath

eros

clero

sis in

non-

diabe

tic

subje

cts w

ith fa

mily

histor

y of p

rema

ture C

VDs.

Scute

ri et a

l. (2

004)

40.

Italy

Total

(n

= 47

1)

200

men

271

wome

n

1 - w

ith M

S (n

= 95

)

2 - w

ithou

t MS

(n =

376)

Total

: NM

59 ±

16 ye

ars

grou

p 1:

62 ±

15 ye

ars

grou

p 2:

57 ±

17 ye

ars

NCEP

ATP

III (2

001)

Cros

s-sec

tiona

l

NM

MS re

sulte

d in i

ncre

ased

thick

ness

by m

ore t

han 1

6% an

d inc

reas

ed

stiffn

ess b

y mor

e tha

n 32%

in th

e car

otid i

ntima

med

ia lay

er (p

<0.0

001

for bo

th) w

hen c

ompa

red t

o ind

ividu

als in

the c

ontro

l gro

up.

The m

ultipl

e reg

ress

ion m

odel

that in

clude

d age

, gen

der, s

mokin

g ha

bit, L

DL-c,

and M

S ris

k fac

tors s

howe

d MS

as an

inde

pend

ent fa

ctor

for in

creas

ing th

e thic

knes

s (p =

0.00

2) an

d stiff

ness

(p =

0.01

2) of

the

caro

tid in

tima m

edia

layer.

MS

comp

onen

ts ma

y syn

ergis

ticall

y inte

ract

to ha

ve an

impa

ct on

the v

ascu

lar th

ickne

ss an

d stiff

ness

of th

e cor

onar

y ar

tery.

MS

- met

aboli

c sy

ndro

me;

NCE

P AT

P III

- Na

tiona

l Cho

leste

rol E

duca

tion

Prog

ram

Adu

lt Tre

atm

ent P

anel

III (2

001)

; WHO

- W

orld

Healt

h Or

ganiz

ation

(199

9); E

GIR

- Eur

opea

n Gr

oup

for t

he S

tudy

of I

nsuli

n Re

sista

nce

(199

9);

ACE

- Am

erica

n Coll

ege o

f End

ocrin

ology

(200

3); ID

F - I

nter

natio

nal D

iabet

es F

eder

ation

(200

6); A

HA/N

HLBI

- Am

erica

n Hea

rt Ass

ociat

ion/N

ation

al He

art, L

ung a

nd B

lood I

nstitu

te (2

005)

; NM

- no

t men

tione

d; C

VDs -

card

iovas

cular

dis

ease

s; CA

D - c

oron

ary a

rtery

dise

ase;

PAD

- pe

riphe

ral a

rteria

l dise

ase;

AAA

- ab

dom

inal a

ortic

ane

urys

m; B

P - b

lood

pres

sure

; SBP

- sy

stolic

bloo

d pr

essu

re; H

BP -

high

blood

pre

ssur

e; A

MI -

acu

te m

yoca

rdial

infa

rctio

n; C

VA

- stro

ke; W

C - w

aist c

ircum

fere

nce;

DM

2 -

diabe

tes m

ellitu

s Typ

e 2;

CHF

- co

nges

tive

hear

t fail

ure;

LC

- life

style

chan

ge; H

cy -

hom

ocys

teine

; Hhc

y - h

yper

hom

ocys

teine

mia;

OR

- odd

s rat

io; C

I - co

nfide

nce

inter

val; S

D - s

tand

ard

devia

tion;

n -

num

ber o

f indiv

iduals

.

Arq Bras Cardiol 2010;94(6) : e86-e114

Farias et alMetabolic Syndrome and Occlusive Vascular Diseases

110

Review Article

Fig. 1 - Heterogeneity and risk for development of vascular occlusive or coronary disease or stroke: comparison between the groups with and without MS.

Study or SubgroupAthyros 2007Brevetti 2006Carminit 2008Eberly 2006Empana2007Hajer 2007Iribarren 2006Kasai 2008Kip 2004Langenberg 2006Malik 2004Marroquin 2004Meigs 2006Montalcini 2005Najarian 2006Noto 2008Reilly 2004Scuteri 2004Skoumas 2007Wierzbicki 2008Wilson l 2005Zeller 2005

Total (95% CI)Total eventsHeterogeneity: Chi² = 993.73, df = 21 (P < 0.00001); I² = 98%Test for overall effect: Z = 45.45 (P < 0.00001)

Events1279

2798

153284

19520998

20965

33614212344

1562760384593

103114

5077

Total2369

79137

4588674886267167259337

169843080455

57715720895

295176613290

15161

Events1041

1595

143138317218423281

22813285

13584764419

11346

10591

152

4944

Total7300

75149

636249111174519489329

17814557325

2098210

1520528632376411224

2710343

37023

Weight16.2%0.5%2.9%

38.2%2.9%4.7%4.0%3.8%2.3%2.3%2.3%3.1%2.4%1.1%1.3%0.6%0.3%1.5%1.2%2.9%1.1%4.4%

100.0%

M-H, Fixed, 95% CI3.79 [3.54, 4.05]1.71 [0.99, 2.95]1.12 [0.96, 1.32]1.48 [1.40, 1.58]1.60 [1.28, 2.00]1.50 [1.25, 1.81]2.21 [1.93, 2.52]1.24 [1.06, 1.45]3.28 [2.69, 4.00]1.51 [1.17, 1.93]6.83 [5.63, 8.29]1.26 [1.01, 1.58]2.38 [1.89, 2.99]2.00 [1.62, 2.47]5.41 [4.18, 6.99]2.06 [1.32, 3.22]

9.60 [5.87, 15.69]1.33 [1.00, 1.78]1.36 [0.93, 2.00]1.13 [0.93, 1.37]5.00 [3.83, 6.54]0.89 [0.74, 1.07]

2.13 [2.06, 2.20]

Positivo Negativo Risk Ratio Risk RatioM-H, Fixed, 95% CI

0.001 0.1 1 10 1000Favours experimental Favours control

the greater the risk for or the severity of the MS-related disease15,23,24,31.

The studies selected in this systematic review have shown an association of MS with the development of or mortality from CVD10,13,20,24,25,29,41,47,49,51, CAD22,28,31,44,47,55, diabetes mellitus 2 (DM 2)20,26,56, and stroke (CVA)29,43,45. Some studies also suggest that individuals with MS have higher mortality from CVDs20,41 and higher prevalence of CVA43, regardless of the presence of glucose intolerance or DM 220,41,45.

Among the selected articles, 4 assessed the mean carotid intima-media thickness23, 40,42,46, showing an association of MS with the atherothrombotic process; increased blood pressure42, decreased concentration of HDL-C in men, and fasting hyperglycemia in women46 were the most important components of MS in this association. It was reported that the higher the number of risk factors that characterize MS the greater the increase in the mean carotid intima-media thickness23.

Some studies report the association of MS with higher body mass index (BMI)28,30,56. It has been also highlighted that individuals with MS have higher BMI and higher risk of DM 2 and CVDs56. Other studies showed the association

of MS with increased cell adhesion molecular activity, hypoadiponectinemia32, and increased concentrations of oxidized LDL34,53 and C-reactive protein35,55. One study reports that there has been an increase of CVD mortality in patients with MS and increased concentration of C-reactive protein44.

Studies that evaluated the concentration of circulating oxidized LDL showed that among the risk factors that characterize MS, those with a higher association with the oxidation of the lipoprotein are fasting hyperglycemia, hypertriglyceridemia, low concentration of HDL-C, and abdominal obesity34,53. The adjusted odds ratio for the dichotomous effect of risk factors that characterize MS, versus the fifth quintile of oxidized LDL were 2.1 (95% CI, 1.2 to 3.6) for abdominal obesity; 2.4 (95% CI, 1.5 to 3.8) for fasting hyperglycemia; and 2.1 (95% CI, 1.1 to 4.0) for hypertriglyceridemia53.

Although hyperhomocysteinemia (Hhcy) is a known marker of occlusive vascular diseases, there are still few studies that assess its association with MS. Among the studies selected in this systematic review, only two assessed the association of Hhcy with MS and its risk factors19,49. A recent study showed that plasma homocysteine (Hcy) was higher in subjects with

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MS when compared to those without MS. Its concentration also increased according to the number of risk factors that characterize MS. When individuals without MS were compared with those who had all five risk factors for MS, the plasma concentration of Hcy increased significantly (from 12.7 mmol/L to 15.9 mmol/L)19. These findings suggest that MS and Hhcy have synergistic effect in increasing the risk for occlusive vascular diseases.

Of the studies selected in this review, one showed no association of MS with CAD54, and another showed no association of MS with atheromatous plaque formation18. However, most studies showed the association of MS and some of its components with higher risk of general morbidity and mortality and of CVD. Therefore, we must highlight the importance of taking measures for the prevention and control of MS and its associated risk factors, in order to reduce CVDs, the main cause of mortality worldwide.

The heterogeneity among the selected studies is shown in Figure 1, and probably is a result of the different markers used for the diagnosis of vascular disease or coronary occlusion. An increased probability (risk = 2.13) of individuals with MS to develop vascular or coronary disease has also been demonstrated. But the results remain contradictory and require further research to obtain more consistent results.

The adoption, preferably from childhood and by the entire population, of healthy lifestyles, such as a balanced diet and the regular practice of physical activity is a basic component of MS prevention. The benefits of the regular practice of physical exercise on the reduction of CVD morbidity have been shown in scientific literature as part of a lifestyle change (LC), along with a reduction in body fat deposition, especially in the abdominal region, which represents an important risk factor for the diagnosis of MS. The success of the intervention in the control and treatment of MS is closely related to the LC, and non-drug therapy is the treatment of choice, with a food plan for reducing body weight associated with physical activity57, besides cessation of smoking and excessive alcohol consumption and reduction of stress. These behavioral changes may improve the quality of life and life expectancy of individuals with MS11.

Although LC is essential for the prevention and treatment of MS, only one study revealed in its conclusion the importance of LC for the reduction of CVD and occlusive vascular disease morbidity and mortality in patients with MS10. Another study showed only the importance of the prevention of MS and its risk factors for the reduction in the incidence of stroke29.

Therefore, in order to achieve the remission of MS and reduce the prevalence of CAD and occlusive vascular

diseases, health professionals should encourage healthy eating habits, such as reducing the consumption of saturated and hydrogenated fats, increasing the consumption of fruits, vegetables, fiber, and whole grains, and lifestyle changes such as cessation of smoking, which is fundamental and a priority measure in preventing the individual components of MS. Moreover, the practice of aerobic physical exercise promotes a reduction in plasma triglycerides and an increase in HDL-c concentration58, which are important risk factors that characterize MS.

A balanced diet combined with a regular practice of physical activity can promote body weight reduction and improve the clinical condition of patients with MS, with a reduction in the risks and the morbidity and mortality from CVD and vascular occlusive disease.

ConclusionThe aggregat ion of MS components and the

pathophysiological mechanisms that trigger it are not yet fully understood. But despite controversial literature reports and heterogeneity among studies, the impact of MS on the occurrence of CAD and occlusive vascular diseases has been observed in this review.

Therefore, it is critical that randomized studies be conducted, using more reliable markers for the diagnosis of CAD and occlusive vascular diseases, and thus generating more consistent results.

AcknowledgmentsWe would like to thank the support of the National Council

for Scientific and Technological Development (CNPq) and the Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ).

Potential Conflict of InterestNo potential conflict of interest relevant to this article was

reported.

Sources of FundingThis study was funded by CNPq and FAPERJ.

Study AssociationThis study is not associated with any post-graduation

program.

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