Metabolic Syndrome Student

8/13/2019 Metabolic Syndrome Student

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MODULE

PATHOLOGY OF

CARDIOVASCULAR SYSTEM

Cardiometabolic Sydrome

!For St"det#

FACULTY OF MEDICI$E

U$IVERSITAS %RA&I'AYA


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( ) * +

STUDE$T GUIDA$CE

Co"r,e Period - . t/ Seme,ter

Co"r,e Cotet - Pat/olo0y o1 Cardio2a,c"lar ,y,tem

Mod"le - Cardiometabolic ,ydrome

*3 Cotrib"tor!,#

Cholid Tri Tjahjono, Heny Martini

(3 Com4etecy Area

This module is a part of the elaboration of the area of competence 3 of the Indonesian Doctor

Competencies i.e. The Scientific-ase of Medical Sciences .

+3 Com4etecy Com4oet

To introduce the cardio!ascular diseases in terms of their basic pathophysiolo"ic mechanisms# to

discuss cardiometabolic syndrome and other clinical features of the conte$t of this diseases# to

incorporate pertinent laboratory tests and ancillary studies into clinical problem sol!in"# and to

pro!ide a solid bac%"round and understandin" of the pharmacolo"ic a"ents and non-

pharmacolo"ic inter!entions used to mana"e cariometabolic syndrome.

53 Cliical Com4etece

e able to reco"ni&e and place the clinical pictures of cardiometabolic syndrome.

.3 Leari0 Ob6ecti2e,


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't the end of the Teachin" learnin" (rocess of this Module, the) Students should be able to)

* +e!ie the normal anatomy and physiolo"y of the heart and cardio!ascular system.

* 'ssess the si"ns and symptoms associated ith metabolic syndrome..

* Incorporate laboratory data into the assessment of a patient ith metabolic syndrome

* * Characteri&e the classic patholo"ic features of the cardio!ascular disorders discussed in

this module.

* Discuss the "oals of therapy based on the underlyin" pathophysiolo"ical condition.

* $plain ho the mechanisms of action of the cardio!ascular dru"s lead to their therapeutic

effect.

* Identify the most common side effects and to$icities of each class of cardio!ascular dru"s.

73 Lect"re De,cri4tio

This module is a part of Module on Cardio!ascular system inte"ratedly desi"ned for medical student of

the th semester throu"h Teachin"-/earnin" (rocess in the loc both in /ecture and Small 0roup

Discussion. This part of Module ill facilitate the student a basic understandin" of the cardio!ascular

disease.

83 O2er2ie9

1.. Introduction

The term 2Metabolic Syndrome is "enerally used to indicate a clinical entity of substantial

hetero"eneity, represented by the co-occurrence of hypertension, impaired "lucose tolerance, athero"enic

dyslipidemia, central fat accumulation, insulin resistance, as ell as prothrombotic and inflammatory

states. This multiple metabolic and cardio!ascular disorders clusters to"ether in the same indi!idual more

often than mi"ht be e$pected by chance, leadin" to an increased probability of sufferin" from

cardio!ascular disease and type 4 diabetes mellitus.

5otithstandin" the contro!ersial concept, data from lar"e prospecti!e population-based studies, such as

the 6ramin"ham offsprin" study, the otnia study, the 7uopio Ischemic heart Disease study, the Italian

study, and the 'therosclerosis +is% in Communities 8'+IC9 study, confirmed that the presence of the

metabolic syndrome as si"nificantly associated ith an increased ris% of cardio!ascular disease

morbidity and mortality, thus pro!idin" substantial support for the metabolic syndrome hypothesis.


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syndrome, and its introduction as a clinically easy-measurable entity. This second hallmar% put the

abdominal obesity on the front line to dia"nose the metabolic syndrome.

+3 Debated :ey 4oit,

'fter a plethora of international publications, the metabolic syndrome concept is still ill-defined

ith many unansered Auestions. So far, e!idence-based outcomes concernin" the components and cut-

off !alues are limited and based principally on e$pert consensus.

+3* Di2er,ity o1 de1iitio,

Durin" the last decade, se!eral definitions of the metabolic syndrome ere su""ested by a

number of e$pert "roups. 'lthou"h these definitions ere similar in their focus on basic

criteria as obesity, dyslipidemia, hyper"lycemia, and hypertension, substantial differences

remained concernin" the insulin resistance.

+3*3* &HO de1iitio

In an attempt to pro!ide a tool for clinicians and researchers, the 2EH: Eor%in" 0roup on

Diabetes proposed a set of criteria to define the metabolic syndrome. The consensus as

published on the EH: ebsite in 1===, but reported clearly that the definition ould be modified as ne

information became a!ailable about the components and their predicti!e poer. The EH: definition,

stated that diabetes type 4 or impaired "lucose tolerance 8I0T9, to"ether ith at least 4 of ? other factors

8hypertension, hyperlipidemia, obesity and microalbuminuria9 define the metabolic syndrome. In case of

normal "lucose tolerance, the e!idence of insulin resistance is needed# this is defined as the loest

Auartile of measures of insulin sensiti!ity. The definition of obesity is based either on o!erall obesity

assessed by body mass inde$ 8MI9, or on central obesity assessed by aist-to-hip ratio 8EH+9 8Table

19.

Table 1. EH: definition of the metabolic syndrome 1===

&HO de1iitio o1 t/e metabolic ,ydrome *;;;

0lucose intolerance, Impaired 0lucose Tolerance 8I0T9 or Diabetes mellitus andFor insulin

resistance to"ether ith to or more of the folloin" criteria listed belo)

1. :besity) MI G 3; %"Fm4 and F or Eaist-to-hip ratio G =; cm in men or G


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?. Hypertension) lood pressure 1?;F=; mmH"

The potential disad!anta"e of the EH: criteria is that special testin" of "lucose status, beyond routine

clinical assessment, is necessary to dia"nose the metabolic syndrome, for e$ample) oral "lucose tolerance

test 8:0TT9 and insulin resistance measurement by hyperinsulinemic eu"lycemic clamp. Since insulin

clamp e!aluation as impractical, most epidemiolo"ical studies used hyperinsulinemia as a surro"ate for

insulin resistance. 'nother ea% point as related to the non-reliable measurement of obesity by the

MI, especially in the elderly, due to the chan"es in hei"ht ith ad!ancin" a"e compared to youn"er

adults. In addition, for any "i!en MI tertile, subjects in the top aist tertile had a orse ris% factor

profile than indi!iduals ith the same MI but ith loer aist circumference measures, meanin" that

the MI and aist circumference did not predict the ris% of metabolic disturbances eAually. The "reater

truncal adipose tissue as distin"uished as the real ris% factor for the metabolic syndrome . Moreo!er,

the freAuency of microalbuminuria in non-diabetic indi!iduals is !ery lo and, therefore, this criterion

as rele!ant only in the presence of diabetes.

+3*3( EGIR de1iitio

In 1===, the uropean 0roup for the Study of Insulin +esistance 80I+9 proposed an alternati!e

definition, hich as called the insulin resistance syndrome. Ehile the EH: definition reAuired an

e!aluation of insulin resistance under eu"lycemic hyperinsulinemic conditions and as applied ali%e to

diabetic and non-diabetic subjects, the 0I+ definition e$cluded the diabetic population and relied on

fastin" insulin as a surro"ate mar%er of insulin resistance. The 0I+ definition retained insulin resistance,

as an essential component and major etiolo"ical determinant of the metabolic syndrome. Hoe!er, aist

circumference as used as surro"ate for obesity measured by the MI# this represented a major de!iation

in the conceptual de!elopment of the metabolic syndrome. In addition, the impaired "lucose tolerance

as not necessary for the reco"nition of the metabolic syndrome 8Table 49

Table 4. 0I+ definition of the metabolic syndrome1===

EGIR de1iitio o1 t/e metabolic ,ydrome*;;;

Hyperinsulinaemia defined as fastin" insulin concentration abo!e the upper Auartile for the non-diabetic

subjectsL 8a"e and se$es combined9 in addition to to or more of the folloin" components)

1. Central obesity) aist circumference =? cm in men or


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L The 0I+ insulin resistance syndrome as defined only for non-diabetic subjects.

+3*3+ $CEP


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Table ?. +e!ised 'T(III definition of the metabolic syndrome 4;;

Re2i,ed ATPIII de1iitio o1 t/e metabolic ,ydrome ()).

'ny 3 of criteria listed belo constitute the dia"nosis of metabolic syndrome

1. le!ated aist circumference 1;4 cm in men or


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dia"nosed hypertension

?. le!ated fastin" plasma "lucose 1;; m"Fd/ or pre!iously dia"nosed type 4 diabetes.

If 6astin" plasma "lucose as abo!e 1;; m"Fd/, oral "lucose tolerance test 8:0TT9 as stron"ly

recommended but as not necessary to define the presence of the metabolic syndrome.

The underlyin" principle behind the ethnic-specific thresholds as that for a "i!en aist circumference,

'sians, lac%s, Caucasians shoed different le!els of intra-abdominal adiposity, puttin" the subjects at

different ris% le!els of cardio!ascular disease and diabetes.

Table B. thnic specific !alues for aist circumference

CountryFthnic "roup Eaist

circumference

Eaist circumference

uropids

In the JS', the 'T( III !alues

81;4 cm male#


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ere essentially identical to those pro!ided by the +-'T( III and ID6. The presence of 3 components out

of establishes the dia"nosis of metabolic syndrome 8Table @9.

This ne definition reco"ni&es that the ris% associated ith a particular aist measurement !aries in

different populations and ethnic "roups. The EH: identified 4 le!els of abdominal obesity in uropean

population dependin" on ris% for metabolic complications. 'n increased ris% occurs at aist

circumferences of =? cm in men or


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The lon"-standin" debate about ho to define this syndrome led to the appearance of to distinct schools

of thou"ht) the insulin resistance-based and the ectopic fat deposition-based hypothesis. So far, both

su""ested mechanisms remain eAui!ocal and debated.

The basic scientists and endocrinolo"ists support the point of !ie that the insulin resistance and

compensatory hyperinsulinemia are sAuarely responsible for the metabolic syndrome . 'ccordin" to this

"roup, obesity is thou"ht to e$acerbate insulin resistance and thus increase the li%elihood of an associated

ad!erse clinical condition.

Hoe!er, the obesity is not considered as a fundamental component of the syndrome, as the clusterin" of

ris% factors can occur in insulin resistant indi!iduals of normal ei"ht. The primary "oal of this

pathophysiolo"ical approach is to alert physicians to the idea that patients ith insulin resistance are not

only at ris% for cardio!ascular disease, but also to other multiple ad!erse clinical conditions such as

polycystic o!arian syndrome, nonalcoholic fatty li!er disease, breast cancer, sleep apnoea. Cardio!ascular

disease is just one of these important conditions. This "roup of researchers do not see% strict clinical

definition for the metabolic syndrome.

In opposition, the other "roup consists of cardiolo"ists and clinical epidemiolo"ists. This "roup support

the term 2metabolic syndrome and see% to assemble a set of related metabolic ris% factors for

cardio!ascular pre!ention perspecti!es. In line ith this !iepoint, obesity is considered as a core

component of the metabolic syndrome rather than a modulator of the effects of insulin resistance. The

primary clinical "oal of this school of thou"ht is to su""est an operational tool to be used for lon"-term

ris% stratification of atherosclerosis patients . This "roup supports the idea that the abdominal obesity is

the predominant dri!in" force behind the metabolic syndrome and is a particularly detrimental factor in

persons ho ha!e concomitant metabolic susceptibility from other causes.

Chronolo"ically, the pathophysiolo"ical 2Insulin +esistance Syndrome transmuted into clinical

2Metabolic Syndrome in the 1==;s. This shift happened to help the scientists to translate science into

practice in an area of major medical and public health concern. 's insulin resistance as difficult to be

measured by the "lucose clamp techniAue, at the population le!el, fastin" plasma insulin le!els as used

as a pro$y to prompt the research for cheap, easy surro"ates of insulin resistance. Hoe!er, this

introduced a confusion because of the partial difference in the physiolo"y of hyperinsulinemia and insulin

resistance, as ell as a lac% of measurement standardi&ation across studies.


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Thereafter, anthropometric measures ere su""ested to replace insulin resistance in ne definitions of the

metabolic syndrome. The 5C(-'T(III and particularly the ID6, too% the position that obesity

8especially abdominal obesity9 is a dominant factor behind the multiplication of ris% factors. 'ccordin" to

the 5C(, the onset of obesity elicits a clusterin" of ris% factors in persons ho are metabolically

susceptible.

In sum, the metabolic susceptibility has many contributin" factors, includin" "enetic forms of insulin

resistance, increased abdominal fat, ethnic and racial influences, physical inacti!ity, ad!ancin" a"e,

endocrine dysfunction, and "enetic di!ersity. Hoe!er, the rele!ance of this application has not yet

e$clusi!ely been established by the research.

+3+ Ucertai cliical "tility

'lthou"h the su""ested definitions pro!ided some uniformity to researchers, a considerable confusion

about the precise clinical utility of the 2metabolic syndrome e$ists and remains contro!ersial. The major

polemic emer"ed in 4;; hen a joint committee of the 'merican Diabetes 'ssociation 8'D'9 and from

the uropean 'ssociation for the Study of Diabetes 8'SD9 published a critical appraisal of the

metabolic syndrome concept, and of its dia"nostic utility in clinical practice. This "roup of researchers

opposed e$tendin" the concept of the metabolic syndrome to clinical practice and objected to

characteri&e the metabolic syndrome as a ris% factor for heart disease or diabetes. The claim as that the

primary clinical emphasis should remain on treatin" the indi!idual ris% factors and that a""re"atin" them

into a syndrome has little clinical utility.

Moreo!er, creatin" a dia"nostic cate"ory of the metabolic syndrome as critici&ed by +ea!en himself

ho as a pioneer in systemi&in" the concept of a ris% factor syndrome. +ea!en belie!ed that this effort

had little clinical or peda"o"ic utility and if necessary the EH: approach as the most rational one. In

this line, the EH: $pert Consultation, ho edited the first definition 1; years earlier, released in 4;;= a

(osition Statement, pertainin" to e!aluate the rele!ance and the clinical utility of the metabolic syndrome

concept. The statement critically concluded that thou"h the metabolic syndrome may be considered useful

as an educational concept, it has limited practical utility as a dia"nostic or mana"ement tool.

The counter ar"uments, represented principally by the ID6 and 'H', ad!ocated that the dia"nosis of the

metabolic syndrome helps physicians to disco!er persons at increased lifetime ris% for cardio!ascular

disease . They belie!e that the metabolic syndrome is a simple useful tool to call attention to patients ho

are at hi"h lifetime ris% for both atherosclerotic cardio!ascular disease and diabetes# such persons deser!e

increased attention in clinical mana"ement and monitorin". 0rundy as the scientist ho most


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thorou"hly ad!ocated the clinical utility of the metabolic syndrome, by lin%in" the importance of clinical

metabolic syndrome reco"nition to an 2iceber" phenomenon. He e$plained that identifyin" the metabolic

syndrome pro!ides a simple means of reco"nisin" the ris%, submer"ed in a tan"le of metabolic

deran"ement. 'ccordin" to 0rundy, seein" the tip of the iceber" can be lifesa!in" because most of the

dan"er lies belo. The same is true in case of findin" a""re"ated metabolic si"ns such as hi"h T0, lo

HD/-C, impaired fastin" plasma "lucose, and mildly ele!ated ( in a patient ith an increased aist

circumference .

'lthou"h the metabolic syndrome seemed to pro!ide little ad!anta"e o!er the a!ailable ris%s scores

86ramin"ham or uropean SC:+9, se!eral clinicians belie!e that the clinical dia"nosis is useful because

it determines the therapeutic strate"y in patients at hi"her ris%. Moreo!er, the application of the a!ailable

cardio!ascular disease ris% scores is still cumbersome and not routinely used in clinical practice. The

metabolic syndrome may thus represent a simple con!enient alternati!e tool to identify indi!iduals at

increased ris% of atherosclerotic cardio!ascular disease or type 4 diabetes mellitus. eyond ris%

assessment, the presence of the metabolic syndrome can alert clinicians to the li%elihood of related

patholo"ical conditions, e.". obstructi!e sleep apnoea, fatty li!er, cholesterol "allstones, and polycystic

o!arian disease. In addition, it helps to reco"ni&e that patients ith a clusterin" of measured ris% factors

usually ha!e se!eral hidden metabolic ris% factors, e.", a prothrombotic state, a proinflammatory state,

and multiple lipoprotein abnormalities.

+35 Debated t/era4e"tic ,trate0ie,

0lobally, there are to !iepoints about the best therapeutic strate"y for patients ith the metabolic

syndrome. :ne con!entional approach holds that each of the metabolic ris% factors should be sin"led out

and treated separately. Hoe!er, the concern about this prescription is that it may lead to an a""ressi!e

use of medications at the e$pense of lifestyle therapies, particularly, ei"ht reduction and increased

e$ercise. 'lternati!ely, the other !ie emphasi&es the "lobal approach that aims to implement lifestyle

therapies to reduce all ris% factors simultaneously. It tar"ets multiple ris% factors to"ether by stri%in" at

the underlyin" causes. Treatin" the underlyin" causes does not rule out the mana"ement of indi!idual ris%

factors, but it may reinforce the control of multiple ris% factors. In practice, there is a tendency to sitch

from a !ertical approach 8by speciality9 to a multidisciplinary hori&ontal approach, hich enables early

detection of the combination of ris% factors, sometimes ithout ob!ious illness, as measure of effecti!e

pre!ention. So far, there is no proof that the lifestyle # modification inter!entions tar"etin" the metabolic

syndrome are superior to those tar"etin" the indi!idual components.


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+ecently, a ne study published in 4;1; analy&ed data from the I5T+H'+T study, a case-control

study of incident acute myocardial infarction that in!ol!ed 14 4=@ cases and 1? B;B controls from 4

countries. The results su""ested that patients ith metabolic syndrome are not at hi"her ris% of future

myocardial infarction than those ith diabetes or hypertension alone. The results stron"ly su""ested that

treatin" the indi!idual ris% factors is rather better than focusin" on the metabolic syndrome, supportin"

therefore, the indi!idual ris%-factor approach.

+3. Predictability o1 t/e metabolic ,ydrome to cardio2a,c"lar ri,:

:ne of the most important criticisms addressed to the concept of the metabolic syndrome as its

efficiency to properly e!aluate the "lobal cardio!ascular disease ris% in clinical practice. The plethora of

epidemiolo"ical, metabolic and clinical studies, published o!er the last 4 decades, ha!e demonstrated that

the different definitions of the metabolic syndrome ere able to identify sub"roups of patients at "reater

ris% of type 4 diabetes and at increased relati!e ris% of coronary heart disease. 5e!ertheless, none of these

definitions can properly assess "lobal cardio!ascular disease ris%.

Many prospecti!e studies documented the relation of metabolic syndrome to cardio!ascular ris%,

particularly to cardio!ascular morbidity, mortality as ell as all-cause mortality. In the 7uopio Ischemic

Heart Disease +is% 6actor Study, a population-based, prospecti!e cohort study of 14;= 6innish men a"ed

?4 to B; years, the 1;-year cardio!ascular disease ris% as increased 4.1- and 4.-fold ith the 'T( III

and EH: definitions, respecti!ely. The same study found that the ris% of death from cardio!ascular

disease as increased by 4.BO3 times, and the ris% of all-cause mortality as increased 1.=O4.1 times ith

the presence of metabolic syndrome. The DC:D project, based on 11 prospecti!e uropean cohort

studies, comprisin" B1B men and 3B omen, a"ed from 3; to


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In sum, the use of different definitions of the metabolic syndrome led to inconsistent results on its

association ith the ris% of cardio!ascular disease . Systematic research re!ies shoed that the

cardio!ascular ris%, conferred by the different definitions, !aried beteen populations# in most studies, it

as loer ith the ID6 definition as compared to other alternati!es. In addition, to recent meta-analyses

of lon"itudinal studies, shoed that the relati!e ris% of cardio!ascular disease associated ith the

metabolic syndrome as hi"her in omen compared to men, and hi"her in studies that used the EH:

definition compared to studies that used the 5C(-'T( III definition.

+37 Predictability o1 t/e metabolic ,ydrome to ty4e ( diabete,

The most important clinical dimension of the metabolic syndrome is its association ith the ris% of

de!elopment of type 4 diabetes. Se!eral prospecti!e studies indicated that the metabolic syndrome

predicts type 4 diabetesR. (eople ith the syndrome ere o!er ? times as li%ely to de!elop type 4 diabetes

compared ith subjects ho did not ha!e it, althou"h ithout e$cludin" the diabetic subjects, this mi"ht

not be surprisin", since impaired fastin" "lucose 8I609 and impaired "lucose tolerance 8I0T9 are

components of the EH: definition. In addition, neither the 'T( III nor the ID6 criteria e$cluded

hyper"lycaemia as 1 of the criteria for the dia"nosis of the metabolic syndrome. y these

criteria, most patients ith type 4 diabetes mellitus ha!e the metabolic syndrome. In the San 'ntonio

Heart Study, the 5C( definition of the metabolic syndrome predicted diabetes better than the EH:

definition, independently of other factors. It as su""ested therefore to loer the fastin" "lucose cut-off

points to impro!e the diabetes prediction .

Despite the abo!e data, there is an on"oin" contro!ersy as to hether the metabolic syndrome is

associated ith increased cardio!ascular and diabetes ris% or is simply a sum of the ris% of the associated

components) "lucose tolerance, ele!ated blood pressure, dyslipidemia, and abdominal obesity. 'ccordin"

to a recent research re!ie, aimed to e$amine the ability of the metabolic syndrome to predict !ascular

e!ents and incident diabetes, the number of e$istin" studies appeared limited to dra definite conclusions

and the metabolic syndrome predicts diabetes much more efficiently in non-diabetic indi!iduals.

53 E2ol"tio to9ard a e9 0lobal =cardiometabolic ri,:> coce4t

The traditional ris% assessment al"orithms 86ramin"ham, (+:C'M or uropean SC:+, etc.9 ta%e into

account classical ris% factors such as a"e, se$, family history, blood pressure, smo%in", cholesterol 8both

/D/ and HD/9, and diabetes. Hoe!er, these ris% assessment tools do not capture the ris% of abdominal

obesity and the related abnormalities of the metabolic syndrome. This is especially important ith the

recent seepin" epidemic of abdominal obesity, here many indi!iduals are at increased ris% of

cardio!ascular disease because of the presence of a constellation of metabolic abnormalities. It has been


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su""ested that the cardio!ascular disease ris% of abdominal obesity andFor metabolic syndrome may be

independent from or "o beyond the ris% predicted by traditional ris% factors . Moreo!er, the 6ramin"ham

ris% score does not assess properly lifetime ris% particularly amon" youn" adults ith abdominal obesity

and metabolic syndrome ho may not be considered at ele!ated ris% of cardio!ascular disease because of

their youn" a"e.

Therefore, the e$istin" cardio!ascular disease ris% assessment tools pro!ed cumbersome in clinical

practice and ere not sufficient to adeAuately capture the additional ris% related to the metabolic

syndrome, such as the abdominal obesity, insulin resistance and related complications .

:n the other hand, the metabolic syndrome as a clinical entity could not impro!e prediction of ris% of

cardio!ascular disease, because it did not incorporate important traditional ris% factors, such as smo%in",

a"e and "ender. The current recommendations stress the need to focus on the assessment of the total

burden of ris%, the so-called "lobal ris% profile, rather than on indi!idual or particular ris% factor. This is

because, the absolute ris% of an acute coronary e!ent depends on the totality of interactin" ris%

determinants# some associated ith adult lifestyle, others operatin" from early childhood.

:n the hole, the presence of metabolic syndrome alone cannot predict "lobal cardio!ascular disease

ris%, nor do the a!ailable ris% scores. Meanhile, better ris% assessment al"orithms are needed to Auantify

diabetes and cardio!ascular disease ris% on a "lobal scale. This unremittin" debate, as to hether the

metabolic syndrome increases cardio!ascular disease ris% beyond the ris% posed by traditional

cardio!ascular disease ris% factors, has spurred the creation of a ne concept named the "lobal

2cardiometabolic ris% 8CM+9. In order to mo!e the field forard, a multidisciplinary International Chair

on CM+ as created, at the end of 4;;, to pro!ide a platform to discuss the concepts of abdominal

obesity, metabolic syndrome, and "lobal cardio!ascular disease ris%. 0lobal CM+ is defined as the ris%

of cardio!ascular disease resultin" from the presence of traditional ris% factors alon" ith features of the

metabolic syndrome . Jnder this model, CM+ encompasses the o!erall cardio!ascular disease ris%,

resultin" from traditional ris% factors 8a"e, se$, smo%in", hypertension, /D/ cholesterol, HD/

cholesterol, diabetes9 and from the additional ris%s of intra-abdominal obesity or related features of the

metabolic syndrome. Jnder this or%in" model, the metabolic syndrome is one of the potentially

modifiable cardio!ascular disease ris% factors, besides smo%in" 86i"ure 19. It has been su""ested that the

cardio!ascular ris% of abdominal obesityFmetabolic syndrome may be independent of or "o beyond the

ris% predicted by traditional ris% factors.


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6i". 1. The 2buildin" bloc%s of "lobal cardiometabolic ris%, ith adaptation from Desprs et al

.3 E4idemiolo0y o1 metabolic ,ydrome

The metabolic syndrome is a cluster of cardio!ascular ris% factors associated ith an increased ris% of

type 4 diabetes mellitus and cardio!ascular morbidity and mortality. This section aims to shed li"ht on the

current state-of-art ith re"ards to the pre!alence of the metabolic syndrome orldide and its %ey

determinants. Jnderstandin" the epidemiolo"y of the metabolic syndrome, as re"ards the !ariation of its

freAuencies and its potential determinants, are essential pre-reAuisites to addressin" public health needs.

.3* Pre2alece o1 metabolic ,ydrome

The multiplicity of pre!alence data su""est that the metabolic syndrome is common orldide,

especially amon" older people and in certain ethnic populations. The syndrome ill undoubtedly become


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e!en more common o!er time, in parallel ith the e$plodin" epidemic of obesity and type 4 diabetes. In

addition, the orldide increase in the pre!alence of metabolic syndrome amon" children and

adolescents, constitutes a "reater public health concern, as emer"in" e!idence has su""ested that children

ith the metabolic syndrome increase their ris% of de!elopin" ad!erse cardio!ascular e!ents later in life.

In this settin", the present section describes and compares the metabolic syndrome pre!alence rates

reported in different studies, carried out durin" the current decade, in !arious countries all o!er the orld.

' thorou"h literature search for publications, documentin" the pre!alence of the metabolic syndrome

accordin" to the e$istin" definitions, as conducted ith an emphasis on international pre!alence

comparison.

0lobally, the pre!alence of the metabolic syndrome as different across the countries in terms of "ender,

a"e "roups and ethnicity, re"ardless of the definition used. In JS population, the ID6 definition led to a

hi"her pre!alence estimate 83=Q9 than that based on the +-'T(III criteria 83?.Q9. ' spectacular

increase in the pre!alence as recorded amon" the same population, from 4?Q in 1=


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populations. y applyin" the uropean definition of aist circumference, the pre!alence of metabolic

syndrome as "enerally loer amon" 'sian populations than amon" uropean populations, hoe!er,

hen modified 'sian aist circumference criteria ere used, the pre!alence of metabolic syndrome

increased and became similar 87orean population9 to or e!en hi"her 8urban Indians9 than uropean

populations. In JS', 5C( 'T( III defined metabolic syndrome is more pre!alent in Me$ican

'mericans 831.=Q9 than in Caucasian 843.


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Moreo!er, only a fe international studies reported a"e-adjusted pre!alence rates, to enable meanin"ful

comparison.

.3( Potetial determiat, o1 t/e metabolic ,ydrome

't e!ery sta"e of life, health is determined by comple$ interactions beteen a multitude of factors that

influence a persons disease or health status. Eith re"ards to the metabolic syndrome, the determinants

hich are centrally in!ol!ed in its multi-factorial causation can be cate"ori&ed as) biolo"ical or "enetic

susceptibility# socio-economic# en!ironmental and beha!ioural factors.

.3(3* %iolo0ical or 0eetic ,",ce4tibility

'lthou"h tin and family studies shoed a hi"h heritability for each of the indi!idual components , the

"enetic basis of the metabolic syndrome, as a composite phenotype, has not yet been thorou"hly

in!esti"ated. ' number of researches indicated a "enetic susceptibility of the metabolic syndrome.

Hoe!er, the associations ere ea% and the replication of findin"s as poor. Ehile the pre!alence of

the metabolic syndrome has increased mar%edly in the last decades, the human "enome has not chan"ed.

't present, no sin"le "ene or cluster of "enes has been consistently replicated for the e$pression of this

phenotype 8metabolic syndrome9 amon" different populations, probably due to the comple$ interactions

beteen "ene and en!ironment.

The thrifty "enotype hypothesis as proposed to e$plain the emer"ence of insulin resistance and

diabetes in populations, shifted from !i"orous acti!ity to pro!ide subsistence nutrition to sedentary life

style ith food abundance. In urban societies, the modern abundant food en!ironment may be responsible

for the ele!ated insulin le!els and e$cessi!e ener"y stores in some type 4 diabetic indi!iduals, leadin" in

conseAuence to insulin resistance and obesity.

0enetic bac%"round can interact ith habitual dietary fat composition, thereby affectin" predisposition to

the metabolic syndrome, and may also determine the indi!idualUs responsi!eness to altered dietary fat

inta%e. +ecent research indicates that currently ineffecti!e therapeutic dietary recommendations may

reAuire a Upersonalised nutrition approach, herein the "enetic profile may determine the responsi!eness

of patients to specific dietary fatty acid inter!entions.

.3(3( Socio


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amon" socio-economically disad!anta"ed indi!iduals, in indi!iduals ith lo education le!el, and in

those doin" menial jobs. There is increasin" e!idence that the distribution of the metabolic syndrome

!aries amon" different "eo"raphic and socioeconomic cate"ories of the population, demonstratin" notable

health ineAualities.

.3(3+ %e/a2io"ral or li1e,tyle determiat,

/ifestyle choices imposed by modern ci!ili&ation ha!e been demonstrated to be centrally in!ol!ed in the

multi-factorial causation of se!ere atherosclerotic disease . There has been an increasin" body of e!idence

demonstratin" that unhealthy beha!iours ere substantially responsible for epidemic pre!alence and

mortality of cardio!ascular disease, diabetes and metabolic disorders. In contrast, a healthy lifestyle

includin" nonsmo%in", appropriate diet, satisfactory physical acti!ity le!el and healthy ei"ht pro!ided

substantial cardio!ascular and metabolic benefits. 'mon" the major potentially modifiable ris% factors for

metabolic syndrome and its components are the folloin")

*3 Smo:i0

0roin" e!idence pointed to smo%in" as an independent ris% factor for metabolic syndrome and type 4

diabetes. Smo%in" is a stron" ris% factor for atherosclerotic cardio!ascular disease, ith a dose dependent

relationshipR. Se!eral population-based studies confirmed that ci"arette smo%in" as independently

associated ith the metabolic

syndrome, in particular in men. The "eneral belief is that insulin resistance or hyperinsulinemia is the

main underlyin" mechanism. Increased insulin resistance may underlie the clusterin" of the metabolic and

hemodynamic abnormalities that ha!e potential atheroslerotic properties, desi"nated the metabolic

syndrome . Hoe!er, this hypothesis still needs to be tested in prospecti!e studies.

(3 Dietary /abit,

'lthou"h dietary inta%e has been lin%ed to indi!idual components of the metabolic syndrome, the role of

diet in its ori"in is not ell understood. Cross-sectional epidemiolo"ical studies demonstrated that dietary

inta%e rich in hole"rain foods as lin%ed to a loer pre!alence of the metabolic syndrome , althou"h

other study found no relation. Dairy inta%e as in!ersely associated ith the metabolic syndrome both

prospecti!ely and in cross-sectional studies . 0reater inta%es of fruits and !e"etables ere associated ith

a loer pre!alence of the metabolic

syndrome. Inta%es of soft drin%s ere also positi!ely associated ith the pre!alence of the metabolic

syndrome, but the diet soda-metabolic syndrome incidence association as not yet hypothesi&ed and

needs further prospecti!e studies.


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'lthou"h !arious indi!idual foods and nutrients ere associated ith the de!elopment or the pro"ression

of the metabolic syndrome, only a fe studies e$amined the association ith dietary patternsV14


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other pat, to increased ener"y inta%e. Therefore, understandin" ho sedentary beha!iour relates to the

metabolic syndrome may pro!ide ne opportunities for clinical and public health approaches in its

pre!ention and control.

.3 P,yc/o,ocial 1actor,

'ccumulatin" e!idence implied that psycholo"ical mechanisms ere possibly underlyin" the

de!elopment of the metabolic syndrome. The syndrome appeared to be tri""ered by ad!erse psycho-

social circumstances, certain chronic psycholo"ical patholo"ies and chronic stress. Indi!iduals ho had

hostile personality and certain beha!iour traits, ere particularly predisposed to de!elop the metabolic

syndrome. Such factors mi"ht interact ith others to encoura"e the de!elopment of metabolic syndrome.

The stress is e$acerbated by lac% of social support andFor poor copin" s%ills. 's a !icious cycle, the

ne"ati!e psycholo"ical beha!iours may induce unhealthy lifestyle andFor ad!erse social circumstances. '

lar"e population study demonstrated a hi"her incidence of the metabolic syndrome amon" youn" omen,

but not in men, ith a history of depression after controllin" for other associated factors . 6eatures of the

metabolic syndrome also appeared more common amon" omen e$periencin" social an$iety . These

findin"s su""est the possibility of different "ender specific causal pathays to the metabolic syndrome

de!elopment.

.3(35 E2irometal 1actor,

+ecently, the scientific e!idence lin%in" air pollution to heart attac%s, stro%es and cardio!ascular death,

has been substantially supported, especially for the fine particulate matter 8(M9. The major source of (M

is fossil fuel combustion from industry, traffic, and poer "eneration. iomass burnin", heatin", coo%in",

indoor acti!ities and forest fires may also be rele!ant sources, particularly in certain re"ions.

Se!eral interrelated pathophysiolo"ic mechanisms underlyin" the obser!ed short-term and lon"-term

ad!erse cardiac effects of ambient air pollution ha!e been elucidated, for instance, the pi!otal role of

!ascular inflammation in patho"enesis and pro"ression of atherosclerosis and coronary heart disease.

Systemic inflammatory response to inhaled ambient particles has emer"ed as an important mediator of the

(M-associated acute cardiac effects. Hoe!er, human data are still scant and conflictin" ith respect to

the pathophysiolo"ic mediators of cardio!ascular disease associated ith lon"-term e$posure to fine (M.

+esearchers hypothesi&ed that lon"-term e$posure is associated ith increased systemic inflammation,

and that people ith metabolic syndrome ha!e a hi"her de"ree of inflammatory responses to (M.

.3(3. Emer0et 1actor,

In a recent research study, a "roin" number of other factors, called 2emer"in" or no!el ris% factors,

ha!e been described and lin%ed ith features of the metabolic syndrome. Se!eral ne bio-mar%ers or

candidate cardio!ascular ris% factors ha!e been proposed as si"nificant predictors of the atherosclerotic

disease and its complications. These include inflammatory-, hemostasis or thrombosis-, lipid-related


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mar%ers, o$idati!e stress, hormonal factors and infectious a"ents. :!er the past fe years, the concept of

atherosclerosis as an inflammatory disorder has been substantially established. Hoe!er, the role of

systematic inflammation needs further e$ploration.

73 Cocl",io

The metabolic syndrome is a multi-factorial disorder and its de!elopment is the result of interactions

beteen biolo"ical, beha!ioural and en!ironmental factors. Despite disa"reement o!er the rele!ance and

clinical utility of the metabolic syndrome, most in!esti"ators a"ree that the clusterin" of metabolic ris%

factors is a real and relati!ely common phenomenon. 'round the orld, the metabolic syndrome is no

considered as one of the major public health challen"es of the 41st century, associated ith a -fold and

4- to 3-fold increase in type 4 diabetes and cardio!ascular disease, respecti!ely . In conseAuence, the

related premature morbidity and mortality could o!erchar"e the health care system bud"ets of both

de!eloped and de!elopin" countries. The introduction of the metabolic syndrome concept as a stimulus

for a lar"e number of epidemiolo"ical, metabolic, and "enetic studies that mo!ed up the scientific

research field.

In addition, the metabolic syndrome constitutes a comprehensi!e public health messa"e and an easily

educational tool for patients and health professionals, focusin" on the multifactorial nature of the

atherosclerotic diseases. This approach recommends the same pre!ention and mana"ement strate"ies for

both metabolic syndrome and its indi!idual components 8e."., a healthy diet, re"ular physical acti!ities,

smo%in" cessation, ei"ht loss and control, plus pharmacolo"ical inter!ention here necessary9.

Mod"l ta,:,

1. Define the term cardiometabolic or metabolic syndrome.

2. Describe the pathophysiology of cardiometabolic syndrome.

3. What is the criteria of metabolic syndrome ?


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4. How to make a therapeutic strategy to patient with cardiometabolic syndrome?

. What are the lifestyle determinants of cardiometabolic syndrome?

Re1erece

'l%eri 'laa, 'lbert 'delin and 0uillaume Michle 84;149. Cardiometabolic Syndrome, Cardio!ascular

+is% 6actors, (rof. 'rmen 0asparyan 8d.9, IS5) =@

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Metabolic Syndrome Student