SEMINARI DEL GRG 2005 23 settembre 2005 - grg-bs.it · Diagnosis and Management of the Metabolic...

SEMINARI DEL GRG 2005200523 settembre 2005

LA SINDROME METABOLICA NELL’ANZIANO

ANGELO BIANCHETTI

Diagnosis and Management of the Metabolic Syndrome.

An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement.

Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr,

Spertus JA, Costa F.

Circulation, October, 18, 2005: 2-18

Definition• The metabolic syndrome is a constellation of

interrelated risk factors of metabolic origin—metabolic risk factors—that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD).

• Another set of conditions, the underlying risk factors, give rise to the metabolic risk factors.

• Diagnostic criteria to in general include a combination of both underlying and metabolic risk factors.

• Many investigations confirm that multiple cardiovascular risk factors of endogenous origin commonly aggregate in one individual.

• This aggregation was originally observed many years ago (Kylin 1923; Vague, 1947).

• More recently, several terms have been proposed to describe this clustering: metabolic syndrome (Bjorntorp, 1992); syndrome X (Reaven, 1993); the “deadly quartet” (Kaplan , 1989); insulin-resistance syndrome (DeFronzo, 1991; Stern, 1994), and hypertriglyceridemic waist(Lemieux, 2000).

• The term metabolic syndrome is most commonly used in the cardiovascular field (Alberti & Zimmet, 1998)

• Although the metabolic syndrome is often referred to as a discrete entity, it is important to recognize that it is a syndrome and not a defined uniform entity.

• No single pathogenesis has been elucidated, nor may one exist.

• Thus, the syndrome could range from a cluster of unrelated risk factors to a constellation of risk factors linked through a common underlying mechanism.

• From a clinical standpoint, presence of the metabolic syndrome identifies a person at increased risk for ASCVD and/or type 2 diabetes mellitus.

• Eventually, a better understanding of the specific cause(s) of the syndrome may provide an improved estimate of risk of developing ASCVD or type 2 diabetes mellitus for individuals.

• For now, however, the presence of the syndrome is a more general indicator of higher risk for these conditions.

Underlying risk factors

• abdominal obesity• insulin resistance• physical inactivity• aging

Metabolic risk factors

• atherogenic dyslipidemia (elevated serum triglyceride and apoB, increased small LDL, and a reduced level of HDL-C)

• hypertension• elevated plasma glucose or diabetes• prothrombotic state• proinflammatory state

The Prothrombotic StateThe Prothrombotic State

• High levels of plasmoginogen activator inhibitor

• Increased risk of CHD• Positive relationship between PAI-1 and

plasma triglycerides.• High levels of fibrinogen are associated

with MS which increases risk of clotting.

The Proinflammatory StateThe Proinflammatory State

• High levels of C-reactive protein (CRP)• Significant risk factor for CHD• CRP is present in atherosclerotic tissue• Inhibits the production of nitric oxide• Stimulates the production of adhesion

molecules in endothelial tissue• Considered as a target for therapy

AHA/NHLBI criteria formetabolicsyndrome(Circulation, 2005)

WaistWaist

Waist?Waist?

40–49

Prevalenza della SindromeMetabolica per età

Ford ES et al. JAMA 2002;287:356-359.

Prev

alen

za,

%

2020–70+70+Età

20–29 3030–3939 50–59 6060–6969 ≥70

Maschi

Femmine

24%24%23%23%

0%

10%

20%

30%

40%

50%

Slide SourceLipidsOnline

www.lipidsonline.org

EventiEventi cardiologicicardiologici maggiori (IMA; BPAC, maggiori (IMA; BPAC, mortemorte improvvisa) associati a quintiliimprovvisa) associati a quintili didiinsulinainsulina basale in soggetti non diabetici: basale in soggetti non diabetici: Helsinki Policemen StudyHelsinki Policemen Study

0,70

0,75

0,80

0,85

0,90

0,95

1,00

Years5 10 200 15 25

Pyörälä M et al. Circulation 1998;98:398-

Log rank:Overall P = .001Q5 vs. Q1 P < .001

Q1

Q2

Q3Q4Q5

Quota

in a

ssen

zadive

nti

card

iova

scola

rim

aggio

ri

0



PrevalenzaPrevalenza didi malattiamalattia coronarica in unacoronarica in unapopolazione con età > 50 anni (Studio prospettico, popolazione con età > 50 anni (Studio prospettico, 1209 soggetti)1209 soggetti)

CH

D P

reva

lenza

% della Populazione =

No SM/No DMNo SM/No DM

54.2%54.2%SM/No DMSM/No DM

28.7%28.7%DM/No SMDM/No SM

2.3%2.3%DM/SMDM/SM

14.8%14.8%

8.7%

13.9%

7.5%

19.2%

0%

5%

10%

15%

20%

25%

Alexander CM et al. Diabetes 2003;52:1210-1214..



SindromeSindrome metabolica e mortalità per malattiemetabolica e mortalità per malattiecardiovascolari: cardiovascolari: KuopioKuopio Ischaemic Heart Ischaemic Heart Disease Risk Factor StudyDisease Risk Factor Study

0

5

10

15

Lakka HM et al. JAMA 2002;288:2709-2716.

Ris

chio

Cum

ula

tivo

0 2 6 8 12Follow-up, anni

sisi

Sindrome Metabolica

nono

Mortalità per eventi cardiovascolari

RR (95% CI), 3.55 (1.98–6.43)

4 10



Rel

ati v

e Ris

kPCR aggiungePCR aggiunge informazioniinformazioni prognostice a qualsiasiprognostice a qualsiasilivellolivello didi didi rischiorischio cardiovascolarecardiovascolare definitodefinito dal dal Framingham Risk ScoreFramingham Risk Score

<1.0

PCR(mg/L)

Framingham 10-Year Risk (%)

1.0–3.0

>3.0

Ridker PM et al. N Engl J Med 2002;347:1557-1565.

10+ 5–9 2–4 0–10

5

10

15

20

25



ValoriValori medimedi di PCR per numerodi PCR per numero didi alterazionialterazionimetaboliche (Dislipidemia, Adipositàmetaboliche (Dislipidemia, Adiposità centrale, centrale, InsulinoInsulino Resistenza, Ipertensione): Resistenza, Ipertensione): Studio IRASStudio IRAS

0

Val

ori

med

idi Lo

g P

CR

Festa A et al. Circulation 2000;102:42–47.

Numero di Alterazioni metaboliche1 2 3 4

0,00,20,40,60,81,01,21,41,6



Incidenza a cinqueIncidenza a cinque annianni di DM Tipo 2 di DM Tipo 2 stratificata per quartilistratificata per quartili didi proteineproteineinfiammatorie: infiammatorie: Studio IRASStudio IRAS

Fibrinogeno PCR PAI-1

Inci

den

za,

%

1st

Festa A et al. Diabetes 2002;51:1131-1137.

2nd 3rd 4thQuartili:

P=0.06P=0.06 P=0.001P=0.001 P=0.001P=0.001

0

5

10

15

20

25



0

1

2

3

4

5

6

Live

llipla

smar

ici

di PC

R (

mg/ L

)RiduzioneRiduzione della PCR con Statinedella PCR con Statine(n=22)(n=22)

Jialal I et al. Circulation 2001;103:1933-1935.

** ** **

AtorvastatiAtorvastatinana

(10 mg/d)(10 mg/d)

SimvastatinSimvastatinaa

(20 mg/d)(20 mg/d)

PravastatinPravastatinaa

(40 mg/d)(40 mg/d)

BaselineBaseline

* p<0.025 vs. Baseline* * p<0.025 vs. Baselinep<0.025 vs. Baseline



L’insulinoL’insulino--resistenza è associata ad resistenza è associata ad aumentatiaumentati livellilivelli di PAIdi PAI--1, fibrinogeno e 1, fibrinogeno e PCRPCR

AumentatiAumentati livellilivelli di PAIdi PAI--1, PCR e 1, PCR e fibrinogenofibrinogeno predicono (debolmente) lo predicono (debolmente) lo svilupposviluppo didi diabetediabete mellitomellito tipo 2. In tipo 2. In alcunialcuni studistudi questequeste associazioniassociazioni risultanorisultanoindipendentiindipendenti dall’obesità e dall’insulinodall’obesità e dall’insulino--resistenzaresistenza

Therapeutic Goals and Recommendations for ClinicalManagement of Metabolic Syndrome



Sindrome metabolica, deficit cognitivi Sindrome metabolica, deficit cognitivi e stato infiammatorio (JAMA, 2004)e stato infiammatorio (JAMA, 2004)



JAMA, 2004JAMA, 2004

Conclusions• 1. The metabolic syndrome is a term for a constellation of endogenous

risk factors that increase the risk of developing both ASCVD and type 2 diabetes mellitus.

• 2. The syndrome is not a discrete entity known to be caused by a single factor. Moreover, it shows considerable variation in the componentsamong different individuals. This variation is even greater amongdifferent racial and ethnic groups.

• 3. In the United States, the syndrome is strongly associated with the presence of abdominal obesity.

• 4. The metabolic syndrome is a secondary target for reducingcardiovascular events. Smoking cessation, lowering the levels of LDL-C, and blood pressure management are primary targets for risk reduction.

• 5. Lifestyle interventions are the initial therapies recommended fortreatment of the metabolic syndrome. If lifestyle change is not sufficient, then drug therapies for abnormalities in the individual risk factors may beindicated.

• 6. To date, there is insufficient evidence for primary use of drugs thattarget the underlying causes of the metabolic syndrome.

• 7. Considerable additional research is needed to better refine the mostappropriate therapies for individuals with the metabolic syndrome.



ConclusioniConclusioni

La sindrome metabolica predice lo sviluppo di malattiecardiovascolari e diabete mellito

L’obesità caratterizza la maggior parte dei soggetti con sindrome metabolica

La terapia iniziale della sindrome metabolica consistenella restrizione dietetica e aumento dell’attività fisica

Trattamento farmacologico delle ipercolesterolemie LDL (150 mg/dl) e stretto controllo della pressionearteriosa sistemica nei soggetti diabetici

Attenta valutazione dei fattori di rischiocardiovascolare nei soggetti con decadimentocognitivo

SEMINARI DEL GRG 2005 23 settembre 2005 - grg-bs.it · Diagnosis and Management of the Metabolic...

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