Cardiomiopatia diabetica - Ospedale di Circolo e Fondazione Macchi

Transcript

Cardiomiopatia diabetica :
alterazioni micro e macrovascolari
del circolo coronarico
B.Castiglioni
Responsabile Struttura Semplice Cardiologia Interventistica
Unita’ Operativa Cardiologia II
AO Ospedale di Circolo e Fondazione Macchi
Varese
Maccagno 2012
Cardiomiopatia diabetica : alterazioni micro e macrovascolari del circolo coronarico
Causes of Death in Diabetes
20%
46%
8%
11%
15%
CV
CVA
Sepsis
Cancer
Other
Hux JE, et al. Diabetes in Ontario, an ICES Practice Atlas 2003.
www.cardiologiavarese.it
BC 2012
Life Expectancy
100
90
80
70
60
50
40
30
20
10
0
Years
DM
No DM
Men
Women
BC 2012
Heart attacks in people with and without diabetes over a period of
seven years
50
Incidence (%)
40
35
30
25
20
15
10
5
0
People without diabetes
No prior heart attack
Prior heart attack
People with diabetes
Haffner e coll. N. Engl. J. Med. 1998
BC 2012
Diabetes and cardiovascular disease
70%–80% of people with diabetes die of cardiovascular
disease.
For each risk factor present, the risk of cardiovascular death
is about three times greater in people with diabetes as
compared to people without the condition.
Cardiovascular disease is the number one cause of death in
industrialized countries. It is also set to overtake infectious
diseases as the most common cause of death in many parts
of the less developed world.
BC 2012
The clinical consequences of diabetes and cardiovascular disease
People with diabetes have the same risk of heart attack as
people without diabetes who have already had a heart
attack.
Women with diabetes are subject to sudden death 300%
more often and men with diabetes 50% more often than
their counterparts without diabetes of the same age.
Strokes occur twice as often in people with diabetes and
hypertension as in those with hypertension alone.
A person with diabetes has a two to three-fold greater risk
of heart failure compared to a person without diabetes.
BC 2012
Changes in coronary heart disease mortality rates in the USA
Coronary heart disease mortality (%)
Men
Women
30
20
10
0
-10
-20
-30
-40
People without diabetes
People with diabetes
BC 2012
The major diabetic complications
Stroke
(cerebrovascular disease)
Heart disease
(cardiovascular disease)
Bacterial and fungal
infections of the skin
Severe hardening of
the arteries (atherosclerosis)
Sexual dysfunction
Visual impairment:
diabetic retinopathy,
cataract and glaucoma
Kidney disease
(diabetic nephropathy)
Autonomic neuropathy
(including slow emptying
of the stomach and diarrhea)
Poor blood supply to lower limbs
(peripheral vascular disease)
Necrobiosis lipidoica
Sensory impairment
(peripheral neuropathy)
Gangrene
Ulceration
BC 2012
The long term effects of diabetes
The long term effects of diabetes can be divided into
– macrovascular complications
– microvascular complications.
• Macrovascular complications affect the larger blood vessels,
such as those supplying blood to the heart, brain and legs.
The most common macrovascular fatal complication is
coronary artery disease. Strokes are also a common cause of
disability and death in people with diabetes.
• Microvascular complications affect the small blood vessels,
such as those supplying blood to the eyes and kidneys. The
microvascular complications of diabetes are retinopathy,
nephropathy and neuropathy.
BC 2012
Il rischio di sviluppare una coronaropatia
aterosclerotica nei soggetti diabetici e’da 3 a
5 volte superiore a quello dei soggetti non
diabetici;
L’evoluzione della malattia coronarica
aterosclerotica nei diabetici e’ largamente
piu’ aggressiva
Maccagno 2012
TL, aa 41, fumtore
Diabete mellito con scarso controllo profilo glicemico
IMA anteriore
Malattia diffusa della coronaria destra
con stenosi critica tratto medio
Occlusione ramo discendente anteriore
lesione colpevole
BC 2012
Occlusione de ramo discendente anteriore prossimale e malattia diffusa ramo
circonflesso
BC 2012
BC 2012
Dysfunctional Endothelium
BC 2012
Endothelial cell functions
• Maintaining the vascular tone: Vasodilation and Vasoconstriction
BC 2012
BC 2012
Endothelium, as a complex endocrine and paracrine organ, plays a crucial role in the
maintenance of vascular homeostasis.
Xu J , Zou M Circulation 2009;120:1266-1286
Copyright © American Heart Association
. Origin of endothelial dysfunction in diabetes mellitus.
BC 2012
Insulin resistance induces endothelial dysfunction in diabetes.
BC 2012
Illustration based on: Beckman JA et al. JAMA. 2002;287:2572.
BC 2012
BC 2012
BC 2012
Moreno PR et al. Circulation. 2000;102:2180.
Diabetes
No Diabetes
Coronary atherectomy specimes of diabetic
(N= 47) and nondiabetic patients (N=48)
«Diabetic plaque»
• Lipid rich atheroma↑
• Thrombus↑
• Inflammatory component↑
BC 2012
BC 2012
BC 2012
BC 2012
BC 2012
Diabetes – Aspirin Resistance
N=172
62%
62%
17%
17%
Responders
21%
21%
PFAPFA-100 Analyzer Closure Time
(CT)
• Responders CT >300 sec
• SemiSemi-responsers CT 166166-300 sec
• NonNon-responders CT <165 sec
Semi-responders Non-responders
Fateh-Moghadam S. et al. Acta Diabetol 2005;42:99-103
Upregulation of P2Y12 receptor signaling in type 2 diabetes mellitus
Clopidogrel
Clopidogrel
ATP
ATP
ADP
ADP
P2 Y
G12
N
Shape change
IP3
PIP2
Gi
PKC
Cl
Gastro-intestinal absorption
12
α
βγ
AC
PI3K
i
MLCK-P
GP IIb/IIIa
receptor activation
S
P2
Y
+ DAG
Ca2+
mobilization
Cl
“Rho”
Shape change
PLCβ
CH3
15% active metabolite
1
Gq
O
N
* HS
Ca2+ flux
O
C
HOOC
P2X1
OCH3
O
Hepatic CYP Biotransformation
85% inactive metabolites
(Esterases in blood)
Granule secretion
PKB/Akt Rap1b
Cilostazol
GP IIb/IIIa receptor activation
Initiation
Initiation of
of Platelet
Platelet Aggregation
Aggregation
cAMP
VASP
VASP
VASP-P
VASP-P
PDE-III
PDE-III
Gs
cAMP
AC
GP IIb/IIIa receptor activation
Stabilization
Stabilization of
of Platelet
Platelet Aggregation
Aggregation
PGE
PGE11
Angiolillo DJ et al JACC 2007
PCI con impianto DES ramo DA
PCI con impianto DES cor DX
BC 2012
Decorso favorevole. FEVS 45% . Non aritmie
Clopidogrel 150 mg per 7 giorni
Verify now (valutazione inibizione piastrinica ) in 8° giornata
Inibizione piastrinica 0%
BC 2012
Influence of Diabetes Mellitus on
Clopidogrel-induced Antiplatelet Effects
Acute Phase of Treatment
80
Long-term Phase of Treatment
No-DM
DM
P=0.04
8%
38%
14%
56%
6%
78%
24 hrs post 300 mg LD
Platelet aggregation (%)
P=0.002
P<0.0001
60
40
20
Non-responders
(Platelet inhibition <10%)
Low responders
(Platelet inhibition 10-29%)
Responders
(Platelet inhibition >30%)
Angiolillo DJ et al. Diabetes. 2005;54:2430-5.
0
DM
No DM
ADP 20µM
DM
No DM
ADP 6µM
Angiolillo DJ et al. J Am Coll Cardiol. 2006;48:298-304.
OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)
Impact of high clopidogrel maintenance dosing on platelet function
in DM patients with suboptimal clopidogrel response
VerifyNow P2Y12 substudy
PRU
%IPA
60
300
p=0.009
P2Y12 Reactivity Units
Platelet inhibition (%)
80
p=0.007
250
Only ~40% of patients reach therapeutic target!
40
20
200
150
100
50
0
0
75 mg
150 mg
75 mg
150 mg
Angiolillo DJ et al. Circulation. 2007;115:708-16.
Angiolillo DJ et al. Am J Cardiol. 2008;101:440-5.
Diabetes as Predictor of Stent Thrombosis
at 1 Year in the Era of DES
Odds/hazard ratio
5
OR=2.0
(0.8-4.9)
OR=2.8
(1.7-4.3)
HR=3.7
(1.7-7.9)
IDDM
IDDM
Diabetes
Diabetes
Kuchulakanti et al.
Circulation 2006
Urban et al.
Circulation 2006
Iakovou et al.
JAMA 2005
Daemen et al.
Lancet 2007
HR=2.03
(1.07-3.83)
4
3
2
1
0
Biotransformation and Mode of Action of Clopidogrel, Prasugrel, and Ticagrelor
Schomig A. N Engl J Med 2009;10.1056/NEJMe0906549
BC 2012
Efficacy of New Drugs/Approaches in Reducing
Adverse Outcomes in Diabetes Mellitus From
Large-Scale Clinical Trials
Study
% of Events
Standard
Hazard Ratio (95% confidence interval)
New Drug/Approach
TRITON-TIMI 38
17.0
12.2
0.70 (0.58 – 0.85)
PLATO
16.2
14.1
0.88 (0.76 – 1.03)
5.6
4.9
0.87 (0.66 – 1.15)
CURRENT OASIS 7
(PCI Cohort)
0
0.5
New Drug/Approach
Better
1
1.5
Standard Clopidogrel
Better
CURRENT-OASIS= Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events Optimal Antiplatelet Strategy
for Interventions; PCI=percutaneous intervention; PLATO= A Study of Platelet Inhibition and Patient Outcomes; TRITONTIMI= Trial To Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With
Prasugrel Thrombolysis in Myocardial Infarction.
Reprinted with permission from Ferreiro JL, Angiolillo DJ. Circulation 2011.
Perdita di
miociti
Cardiomiopatia diabetica
Fibrosi miocardica
Ridotta
contrattilita’
del miocita
Aterosclerosi
Microangiopatia diabetica
Neuropatia diabetica
Scompenso
cardiaco
IMA
Angina microvascolare
Ipertono simpatico
BC 2012
Impact of Diabetes on Risk for New CHF
Following Acute Coronary Syndromes: OASIS
Diabetes(+) and CVD(+)
No Diabetes and CVD(+)
Event Rate
Event Rate and RR for
Long-term Outcomes
Diabetes(+) and CVD(CVD(-)
No Diabetes and CVD(CVD(-)
.30
Crude Event
Rate
RR= 3.43 (2.85(2.85-4.13)
.25
Parameter
DM
No
DM
Adjusted RR
(95% CI)
P
.20
RR= 2.19 (1.86(1.86-2.58)
.15
RR= 1.98 (1.52(1.52-2.57)
.10
.05
RR= 1.00
0
0
3
6
Total mortality 18
10
1.57
<0.001
CVD death
14
8
1.49
<0.001
New MI
12
9
1.34
<0.001
Stroke
5
3
1.45
0.009
New CHF
21
12
1.41
<0.001
9 12 15 18 21 24
Months
Malmberg K et al. Circulation. 2000;102:10142000;102:1014-1019
FRISC II: Diabetes Not CAD Extent is the Most
Important Independent Predictor of Death and MI
RR
95% CI
Age
0.98
(0.74-1.32)
NS
Gender
0.80
(0.64-0.99)
0.039
Hypertension
1.31
(0.86-2.00)
0.21
Diabetes
2.40
(1.47-3.91)
0.001
Smoking
0.96
(0.75-1.22)
0.73
Previous Angina
1.22
(0.87-1.72)
0.25
Previous MI
1.85
(1.17-2.93)
0.008
ST-depression
1.22
(0.80-1.86)
0.348
Troponin T >0.03 µg/l
1.66
(1.03-2.68)
0.038
3-VD/LMD
1.06
(0.84-1.33)
0.62
0.5
1
Norhammer A et al. JACC 2004; 43: 585-91
4
p
Diabetes Confers a Doubling of Risk for Early MI Mortality Despite Advances in Cardiac Care
Early Mortality from Acute MI
Diabetes
Total Group
Digoxin
Diuretics
Defibrillation
Hemodynamic
Monitoring
Pre-CCU Era
(pre-1962)
CCU Era
(1962-1984)
Thrombolysis
Beta-blockade
Aspirin
PCI
IIbIIIa Inhibitors
Clopidrogel
Statins
Lytic Era
(1984-2000)
PCI Era
(2000-- )
From Richard Nesto
BC 2012
BC 2012

Cardiomiopatia diabetica - Ospedale di Circolo e Fondazione Macchi

Transcript

Documenti analoghi

ETIOPATOGENESI DELLA CARDIOMIOPATIA DIABETICA PROF

Prevenzione del diabete di tipo 1: a che punto siamo?

So you have an ulcer (Italian) - the NSW Multicultural Health

Burden of disease e costi della patologia diabetica

Scarica la circolare

DA VICO

Scarica scheda tecnica PDF

Slides

Un caso di “diabete doppio” Casistica

Informativo Ci Vediamo NOVEMBRO de 2015 PDF