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Cardiovascular disease in diabetic patients: the facts
Cardiovascular disease accounts for 75% of death causes in Type 2 diabetic patients
Cardiovascular disease accounts for 75% of death causes in Type 2 diabetic patients
According to WHO the prevalence of CVD in diabetic patients ranges within 26 - 36%
The relative risk of CHD is 1.5-1.7 in male and 1.7-4.0 in female diabetic patients
In the diabetic patient life expectancy is 5 -10 years lower than in the non-diabetic general population
Decrease in CHD mortality rates between 1981 and
2000
Decrease in CHD mortality rates between 1981 and
2000
-70
-60
-50
-40
-30
-20
-10
0
Men WomenR
edu
ctio
n i
n C
HD
mo
rtal
ity
rate
s (%
)
– 62%
– 45%
Data from England and Wales between 1981 and 2000 in men and women aged 35–84 years. There were 68,230 fewer CHD deaths than expected from baseline mortality rates in 1981.
Unal B, et al. Circulation 2004; 109:1101–1107
Effect of risk factors/ treatments on CHD mortality
Effect of risk factors/ treatments on CHD mortality
2000
Dea
ths
prev
ente
d or
pos
tpon
ed in
200
0
• 68,230 fewer deaths in 2000Treatments 42%
Risk factors: better 71%
Risk factors: worse 13%
Year1981
10,000
0
–10,000
–20,000
–30,000
–40,000
–50,000
–60,000
–70,000
• e.g. diabetes, obesity
• e.g. smoking, cholesterol, BP
• e.g. secondary prevention, heart failure treatments
CHD deaths prevented or postponed by risk factor changes and treatments in England and Wales, 1981 to 2000
Unal B, et al. Circulation 2004; 109:1101–1107
• 2,888 more deaths due to diabetes• 2,662 more deaths due to physical inactivity• 2,097 more deaths due to obesity
12%
Stroke
Relative risk reductions for a 1% fall in HbA1c
P < 0.0001 for all reductions except stroke, P = 0.035
Diabetes-related death
14%
All-cause mortality
14%
Myocardial infarction
Microvascular disease
Stratton IM, et al. UKPDS 35. BMJ 2000; 321:405–412.
UKPDS: reducing blood glucose levels reduces the risk of complications
UKPDS: reducing blood glucose levels reduces the risk of complications
21%
37%
Over 10 years, each 1% reduction in HbA1c was associated with:
Any diabetes-related endpoint
21%
UKPDS: elevated blood glucose levels increase the risk of
diabetic complications
UKPDS: elevated blood glucose levels increase the risk of
diabetic complications
20
40
60
80
Incidence per1,000 patient-years
Study population: White, Asian Indian and Afro-Caribbean UKPDS patients (n = 4,585) Adjusted for age, sex and ethnic groupError bars = 95% CI
5 6 7 8 9 10 11
Myocardialinfarction
Microvasculardisease
Updated mean HbA1c (%)
00
Adapted from Stratton IM, et al. BMJ 2000; 321:405–412.
†Lower extremity amputation or fatal peripheral vascular disease*P = 0.035; **P < 0.0001 Adapted from Stratton IM, et al. UKPDS 35. BMJ 2000; 321:405–412.
UKPDS: increased risk of diabetes-related complications corresponding with a 1% increase
in HbA1c
UKPDS: increased risk of diabetes-related complications corresponding with a 1% increase
in HbA1c
Per
cen
tag
e in
crea
se i
n r
elat
ive
risk
co
rres
po
nd
ing
to
a 1
% r
ise
in H
bA
1c
0
5
10
15
20
25
30
35
40
45
50
**
Any diabetes-related endpoint
21%
**
Diabetes-related death
21% **
All cause
mortality
14%
*
Stroke
12%
**
Peripheral vascular disease†
43%
**
Myocardial infarction
14%
**
Micro-vascular disease
37%
**
Cataract extraction
19%
Observational analysis from UKPDS study data
1 Koro CE, et al. Diabetes Care 2004; 27:17–20. 2 Liebl A. Diabetologia 2002; 45:S23–S28.
La maggior parte dei pazienti diabetici di tipo 2 in USA e in Europa non è in
adeguato controllo glicemico
La maggior parte dei pazienti diabetici di tipo 2 in USA e in Europa non è in
adeguato controllo glicemico
Per
cen
tual
e d
i so
gg
etti
0
20
40
60
80
100
< 7% 7%
HbA1c (%)
US1
36%
64%
Per
cen
tual
e d
i so
gg
etti
0
20
40
60
80
100
6.5% > 6.5%
HbA1c (%)
EU2
31%
69%
Obiettivi glicemici definiti nel DMT2
1. American Diabetes Association. Diabetes Care 2004;27(suppl 1):S15―35.2. American Association of Clinical Endocrinologists. Endocr Pract 2002;8(suppl 1):43―84.3. Japan Diabetes Society. Available at: http://www.jds.or.jp.4. International Diabetes Federation. Diabet Med 1999;16:716―30.
*1―2 ore postprandiali; **2 ore postprandiali.
Controllo glicemico
Sani ADA1 AACE2 JDS3 IDF4
HbA1c (%) <6 <7 6.5 5.8―6.4 6.5
Glicemia a digiunommol/l (mg/dl)
<5.6 (<100)
5―7.2(90―13
0)
<6 (<110)
5.6―6.6 (100―11
9)
<6 (<110)
Glicemia postprandialemmol/l (mg/dl)
<7.8 (<140)
<10* (<180)
<7.8** (<140)
― <7.8** (<140)
Treat to target…….
Control blood glucose FPG <130 mg/dl
PPG <140 mg/dlHbA1c <6.5%
In quali pazienti?????
I livelli medi di HBA1c in Italia è di 8,6%......
Control blood glucose FPG <130 mg/dl
PPG <140 mg/dlHbA1c <6.5%
In quali pazienti?????
I livelli medi di HBA1c in Italia è di 8,6%......
0
10
20
30
40
50
60
70
80
Glycosylatedhemoglobin
<6.5%
Pat
ien
ts r
each
ing
inte
nsi
ve-t
reat
men
t g
oal
s at
mea
n 7
.8 y
(%
)
Intensive Therapyn = 67
Cholesterol<175 mg/dl
Triglycerides<150 mg/dl
Systolic BP<130 mm Hg
Diastolic BP<80 mm Hg
Conventional Therapyn = 63
P = 0.06
P < 0.001
P = 0.19
P = 0.001
P = 0.21
Adapted from Gaede P, et al. N Engl J Med 2003; 348:383–393.
Steno-2: effect of intensive vs conventional therapy on proportion of patients meeting goals
Steno-2: effect of intensive vs conventional therapy on proportion of patients meeting goals
Glycemic control and macrovascular diseaseMetaanalysis of RCT:s in type 1 & 2 diabetes
Incidence Rate Ratio
Incidence Rate Ratio (95% CI) % weight
Studies
Type 1 DM
(Stettler et al. Am Heart J 2006; 152:27-38)
Glycemic control and macrovascular diseaseMetaanalysis of RCT:s in type 1 & 2 diabetes
Incidence Rate Ratio (95% CI) % weight
Incidence Rate Ratio
Studies
Type 2 DM
(Stettler et al. Am Heart J 2006; 152:27-38)
Perché trattare precocemente e in maniera intensiva
Perché trattare precocemente e in maniera intensiva
Ka
pla
n-M
eie
r E
ve
nt
Ra
teTime to Death, MI or Stroke
Placebo
Pioglitazone
Placebo 358/ 2633 14.4%PIO 301 / 2605 12.3%
N events3-year estimate:
HR P value
PIO vs placebo
0.15
0.10
0.05
0
0 6 12 18 24 30 36TIME (months)
0.841 0.027
Ictus fatale e non fatale in pazienti con precedente ictus
Ictus fatale e non fatale in pazienti con precedente ictus
N a rischio:
Tempo dalla randomizzazione (mesi)
984 952 926 903 877 849 132
Kaplan-Meier % eventi
0.04
0.06
0.08
0.10
0.00
0.12
0 6 12 18 24 30 36
pioglitazone (27 / 486)
placebo (51 / 498)
0.02
0.0080.34, 0.850.53pioglitazone vs placebo
p value95% CIHR
- 47%
Studio AccordCirculation.National Heart lung and blood istitute 7.2.08
Studio AccordCirculation.National Heart lung and blood istitute 7.2.08
NHLBI ha deciso di stoppare il braccio dello studio della terapia intensiva diabetologica per eccesso di mortalità.
Nel gruppo di pazienti con obiettivo metabolico hba1c<6 si è avuto significativo incremento mortalità rispetto a Hba1c >7…. anche se minore
rispetto agli studi di controllo.
NHLBI ha deciso di stoppare il braccio dello studio della terapia intensiva diabetologica per eccesso di mortalità.
Nel gruppo di pazienti con obiettivo metabolico hba1c<6 si è avuto significativo incremento mortalità rispetto a Hba1c >7…. anche se minore
rispetto agli studi di controllo.
“The Metabolic Memory”Evidence for a long-term persistence of
hyperglycaemia-induced damage
N Engl J Med, 2005
DCC/EDIC Research Group
7
6
9
8
Hb
A1
c (%
)
10
OAD monotherapy
DietOAD
combinationOAD
+ basal insulin
Conservative management of glycemia:
traditional stepwise approach
OAD monotherapy
uptitration
Duration of diabetes
OAD + multiple dailyinsulin injections
OAD + basal insulin
OAD + multiple daily insulin injections
Diet
OAD monotherapy
OAD combinations
Proactive management of glycemia
OADs uptitration
Duration of diabetes
7
6
9
8
Hb
A1
c (%
)
10
APRROCCIO PRECOCE EAGGRESSIVO
(insulin resistance and -cell dysfunction)
Campbell IW. Br J Cardiol 2000; 7:625–631.
Intervention!
Intervention!
Intervention!
Intervention!
Intervention!
Proactive management of glycemia
Intervention!
Duration of diabetes
7
6
9
8
Hb
A1
c (%
)
10
Early aggressive approach in type 2 management. Intensive therapeutic strategy
Immediately upon diagnosis
Argomenti di discussione.Argomenti di discussione.
Quanto è importante il trattamento glicemico nella prevenzione secondaria delle pcv.??
A quali livelli glicemici??E’ impoetante la durata del diabete
nei target di trattamento??Trattamento precoce e aggressivo sia
nella prevenzione primaria e secondaria ?? (linee guida EASD-ADA)
Quanto è importante il trattamento glicemico nella prevenzione secondaria delle pcv.??
A quali livelli glicemici??E’ impoetante la durata del diabete
nei target di trattamento??Trattamento precoce e aggressivo sia
nella prevenzione primaria e secondaria ?? (linee guida EASD-ADA)
Intervallo di Tempo fino a: Decesso, IM (Silente Escluso) o Ictus
Intervallo di Tempo fino a: Decesso, IM (Silente Escluso) o Ictus
Tasso di eventi Kaplan-Meier
N at Risk:
5238 5102 4991 4877 4752 4651 786 (256)
Tempo dalla randomizzazione (mesi)0 6 12 18 24 30 36
0.0
0.05
0.10
0.15
pioglitazone
placebo
N eventi:
301 / 2605
358 / 2633
stima a 3 anni
12.3%
14.4%
HR 95% CI p value
pioglitazone vs placebo
0.841 0.722, 0.981 0.0273
-16%
Intervallo di Tempo fino a: Decesso, IM (Silente Escluso) o Ictus
Intervallo di Tempo fino a: Decesso, IM (Silente Escluso) o Ictus
Tasso di eventi Kaplan-Meier
N at Risk:
5238 5102 4991 4877 4752 4651 786 (256)
Tempo dalla randomizzazione (mesi)0 6 12 18 24 30 36
0.0
0.05
0.10
0.15
pioglitazone
placebo
N eventi:
301 / 2605
358 / 2633
stima a 3 anni
12.3%
14.4%
HR 95% CI p value
pioglitazone vs placebo
0.841 0.722, 0.981 0.0273
-16%
IM fatale/non fatale (escluso IM silente)IM fatale/non fatale (escluso IM silente)
0.02
0.04
0.06
0.08
0.10
0 6 12 18 24 30 36
Kaplan-Meier event rate
Tempo dalla randomizzazione (mesi)
N a Rischio: 2445 2387 2337 2293 2245 2199 399(139)
pioglitazone (65 / 1230)
placebo (88 / 1215)
0.0
HR 95% CI p value
pioglitazone vs placebo
0.72 0.52, 0.99
0.045
-28%
Endpoint Cardiaco composto (Morte cardiaca, IM non fatale, Rivascolarizzazione coronarica o SCA)
Endpoint Cardiaco composto (Morte cardiaca, IM non fatale, Rivascolarizzazione coronarica o SCA)
N a Rischio:
Tempo dalla randomizzazione (mesi)
HR 95% CI p value
pioglitazone vs placebo
0.81 0.66, 0.98
0.034
2445 2350 2260 2186 2116 2036 357(127)
Kaplan-Meier event rate
0.05
0.10
0.15
0.20
0.0
0.25
0 6 12 18 24 30 36
pioglitazone (180 / 1230)
placebo (217 / 1215)-19%
Sindrome Coronarica Acuta (SCA)
Sindrome Coronarica Acuta (SCA)
Kaplan-Meier event rate
0.01
0.02
0.03
0.05
0.00
0.06
N a Rischio:
0 6 12 18 24 30 36
Tempo dalla randomizzazione (mesi)
pioglitazone (35 / 1230)
placebo (54 / 1215)
HR 95% CI p value
pioglitazone vs placebo
0.63 0.41, 0.97
0.035
0.04
2445 2397 2351 2308 2265 2222 406(139)
-37%