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10th

South

China

International

Congress

of

CardiologyACE

trialsymposiumPrognostic

and

potential

therapeuticimplications

of

the

European

and

ChinaHeart

surveysLars

RydénKarolinska

InstitutetStockholm,

SwedenImplications

of

the

European

and

China

Heart

SurveysEuropean

Guidelines

on

Diabetes,

prediabetes

and

Cardiovascular

Diseasemay

be

downloadedfrom

Implications

of

the

European

and

China

Heart

SurveysDiabetes

and

prediabetes

is

more

common

amongpatients

with

coronary

artery

disease

than

imaginedGAMI1n=16434%NormoglycaemiaPrediabetesType

2

diabetes35%31%(1.

Norhammar

et

al.

Lancet.

2002;359:2140–4)(2.

Bartnik

et

al.

Eur

Heart

J.

2004;25:1880–90)(3.

Hu

et

al.

Eur

Heart

J.2006;27:2573–9)Dysglycemia

and

coronary

artery

diseaseGlucometabolic

category

by

OGTT

in

patients

without

known

perturbationsEHS2n=1,920CHS3n=2,26336%37%27%45%37%18%DMIGTIFGNormalOGTTOGTTFPGWHOFPGADA020406080100%WHO

1999

criterion(FPG

<

6.1mmol/l)ADA

2003

criterion(FPG

<

5.6mmol/l)5%21%27%5%8%8%%

of

all

with

OGTT(Bartnik,

Rydén

et

al

Heart

2007;

93:72)Dysglycemia

and

coronary

artery

diseaseClassification

according

to

FPG

or

OGTTMortality

in

CVDRelation

to

fasting

and

postprandial

glycemia

in

patients

without

diabetesAdjusted

for

age,

gender

andarea00.5<6.1 6.1-

6.9 7.0-

7.7

>7.8Fasting

glucose

(mmol/L)(The

DECODE

study

group

Lancet

1999;

354:617)<7.8>11.17.8-11.0

OGTTRelative

risk2.521.51(mmol/L)Guideline

recommendationsRecommendationClassLevelEarly

stages

of

hyperglycemia

and

asymptomatictype

2

DM

best

diagnosed

by

an

OGTT

that

givesfasting

and

2-hour

post-load

glucosevaluesIBOGTT

at

discharge(n=

168)DM33%NGT33%IGT34%Abnormal

67%Follow-uptime

(months)NormalAbnormalProbability

of

event

free

survivaltwo-sided

p

=

0.0020

10

20

30

4050Time

to

Major

Cardiovascular

Event0.80.70.01.00.9GAMI

-

major

cardiovascular

events(Bartnik

et

al

Europ

Heart

J

2004;

25:1990)GlucometabolicstateEuro

Heart

Survey

diabetes

and

the

heartSurvival

in

relation

to

glucometabolic

stateKnownDMNew

DM1.000.960.980100

200400300Follow

up

time

(days)(Lentzen

et

al

Europ

Heart

J

2006;

27:2969)0.92NormalIGT0.94Log

rank

test

p

<0.001Survival

probabilityGlucometabolic

stateGuideline

recommendationsRecommendationClassLevelThe

definition

and

diagnostic

classification

of

DMandprestates

should

be

based

on

the

level

of

subsequentrisk

for

cardiovascular

complicationsInformation

on

post-load

glucose

provides

betterinformation

about

future

risk

for

CV

disease

thanfasting

glucose,

and

elevated

post-load

glucosealso

predicts

increased

CV

risk

in

subjectswithnormal

fasting

glucoseIIBAProject

team

every

3

monthsStrict

therapeutic

targetsBehavioural

modificationfat

<30%

(satur

<10%)exercise

30

min

x3-5/weeksmoking

cess

coursesVitamin

supplementationStepwise

introduced

drugsHypoglycemic

regimenaccording

to

strict

rulesBy

their

GPGuidelines

byDanish

Med

Ass

1998&

2000Referral

if

neededn

=

53

(average

3

times/pat)Intensive

treatmentConventional

treatmentMultifactorial

intervention

in

type

2

diabetes(Gaede

et

al

New

Engl

Med

2003;348:383)The

Steno

2

study

8

year

follow

upManagement

principlesMultifactorial

intervention

in

type

2

diabetesThe

Steno

2

study

8

years

of

follow

upComposite

endpointCV-death,

MI

or

stroke,

CABG

or

PCI,

limb

amputation

or

vascularsurgeryImpact

of

intensive

therapyonCardiovascular

diseaseOR0.470.3995%

CI0.24-0.730.17-0.87NephropathyRetinopathy0.420.21-0.86Autonomic

neuropathy0.370.18-0.79(Gaede

et

al

New

Engl

Med

2003;348:383)MicrovascularMortality4

years13yearsn=80n=80n=160MicrovascularMortality4

years13yearsMacrovascular8

yearsMacrovascular8

yearsPrimaryendpoint1993199720012006Multifactorial

intervention

in

type

2

diabetes(Gaede

et

al

New

Engl

J

Med

2008;

358:

580

)The

Steno

2

study

13

years

follow

upExtendend

study

protocolConventionalIntensiveImpact

of

intensive

therapyonOR95%

CIARRp-valueAll-cause

mortality0.540.32-0.8920%0.015Cardiovascular

mortality0.430.19-0.9413%0.036Major

cardiovascular

events0.410.25-0.6329%<0.001Multifactorial

intervention

in

type

2

diabetesThe

Steno

2

study

13

year

follow

upNumber

of

patients

needed

to

treat

for13

years

to

aviodone...Death5Cardiovascular

death8Major

cardiovascular

event3Progression

tonephropathy5(Gaede

et

al

New

Engl

J

Med

2008;

358:

580

)p<0.00104000,910,920,940,930,960,950,970,981,000,99No

DM

EBM

+No

DM

EBM

-DM

EBM

+DM

EBM

-100

200

300Time

of

follow

up

(days)Euro

Heart

Survey

diabetes

and

the

heartImpact

of

Evidence

Based

Medicine

(EBM)

on1-yearmortality(Anselmino

et

al

Europ

J

Cardiovasc

Prev

Rehab

2008;

In

press)Cumulative

survivalEuro

Heart

Survey

diabetes

and

the

heartImpact

of

Evidence

Based

Medicine

(EBM)

on1-year

CVE0,820,860,900,941,000,98p<0.0010300400No

DM

EBM

+No

DM

EBM

-DM

EBM

+DM

EBM

-(Anselmino

et

al

Europ

J

Cardiovasc

Prev

Rehab

2008;

In

press)100

200Time

of

follow

up

(days)Cumulative

survivalp<0.00101004000,910,920,940,930,950,960,970,981,000,99DM

RV

+DM

RV

-No

DM

RV

+No

DM

RV

-Euro

Heart

Survey

diabetes

and

the

heartImpact

of

Revascularisation

on

1-year

mortality(Anselmino

et

al

Europ

J

Cardiovasc

Prev

Rehab

2008;

In

press)Cumulative

event

free

rate200

300Time

of

follow

up

(days)p<0.0010,800,820,840,860,880,900,920,940100200

300Time

of

follow

up

(days)400No

DM

RV

+No

DM

RV

-DM

RV

+DM

RV

-1,000,96Euro

Heart

Survey

diabetes

and

the

heartImpact

of

Revascularisation

on

1-year

cardiovascular

events(Anselmino

et

al

Europ

J

Cardiovasc

Prev

Rehab

2008;

In

press)Cumulative

event

free

rateEuro

Heart

Survey

diabetes

and

the

heartNumber

needed

to

treat

(NNT)

with

EBM

and

RevascularisationTreatment

typeDiabetesNNT

to

avoid

one

eventFatalCardiovascularEvidenceBasedNo1826141MedicineYes2432RevascularisationNo10541Yes3414Evidence

Based

MedicineRevascularization(Anselmino

et

al

Europ

J

Cardiovasc

Prev

Rehab

2008;

In

press)Guideline

recommendationsLifestyle

modificationSmokingcessationBPHbA1c (DCCT

standard)Venous

plasma

glucoseCholesterolLDLHDLTriglyceridesStructured

educationObligatory<130

/

80

mm

HgRenal

dysf

<125/75≤6.5%mmol/l<6.0mg/dl108<4.5175<1.870male

>1.0;

female>1.240;

76<1.7150VariableTargetImplications

of

the

European

and

China

Heart

SurveysDiabetes

and

prediabetes

is

more

common

amongpatients

with

coronary

artery

disease

than

imaginedNewly

detecteddysglycemia

relatesto

impairedprognosisA

multifactorial

riskfactor

management

importantGlucose

controlIn

patients

with

established

diabetesIn

patients

with

newly

detected

glycemic

perturbationswiwitthh

CCAADD(Stettler

C

et

al.

Am

Heart

J

2006;

152:

27)PeripheralCardiacCerebrovascularAny

macrovascularIncidence

Rate

Ratio●●●●●●●●Glycemic

controlEvidence

for

impact

on

cardiovasculareventsGlycemic

controlEvidence

for

impact

on

cardiovasculareventsThe

STOP

NIDDM

trial,

testing

the

possibility

to

preventprogression

from

impaired

glucose

tolerance

to

diabeteswith

acarbose….demonstrated

a

49%

relative

risk

reduction

of

the

three-year

risk

for

CVE

compared

to

placebo(Chiasson,

J.L.

et

al.

JAMA

2003;

290:486)Glycemic

controlIncidence

of

composite

cardiovascular

events

in

the

STOP-NIDDM

trial2

3

4

5Follow

up

time

(years)Cumulative

incidence

(%)01AcarbosePlacebo5(Chiasson,

J.L.

et

al.

JAMA

2003;

290:486)43210Log

rank

testp=0.04Cox

proportional

model

p=0.03496146763940EnrolledLostto

follow-upStudy

populationGlucometabolicstate

availableGlucometabolic

state

unknown285*736*1819OGTT 696FPG947Normal

glucoseregulation1116Impairedglucoseregulation1425Knowndiabetes452Newly

detecteddiabetes452Newly

detecteddiabetesGlycemic

controlExperiences

from

the

Euro

Heart

SurveyStudy

population(Lentzen

et

al

Europ

Heart

J

2006;

27:2969)Prescribedglucoselowering

drugs77(17%)1%16%<1%83%InsulinOraldrugsCombinationsNoprescriptionNewly

detecteddiabetesn

=

452Not

prescribedglucoselowering

drugs375

(83%)Glycemic

control(Anselmino

et

al;

Europ

Heart

J

2008;

29:177)Experiences

from

the

Euro

Heart

SurveyGlucose

lowering

drugs

at

follow

up

in

patients

with

newly

detected

diabetes0,900,940,920,960,981,00Log

rank

testp=0.047YesNo0100

200300400Cumulative

event

free

rateTime

of

follow

up

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