Download - Diabetes cardio
DIABETES COMO FACTOR DE DIABETES COMO FACTOR DE RIESGO CARDIOVASCULARRIESGO CARDIOVASCULAR
DR. LEOCADIO G. MUÑOZ DR. LEOCADIO G. MUÑOZ BELTRANBELTRAN
Lumen
Media:
Smooth muscle cell
Matrix proteins
Internal elastic membrane
Endothelium
Intima:
External elastic membrane
Normal Arterial WallNormal Arterial Wall
Risk Factors for Cardiovascular Risk Factors for Cardiovascular DiseaseDisease
ModifiableModifiable– SmokingSmoking– DyslipidaemiaDyslipidaemia
Raised LDL-CRaised LDL-C
Low HDL-CLow HDL-C
Raised triglyceridesRaised triglycerides
– Raised blood pressureRaised blood pressure– Diabetes mellitusDiabetes mellitus– ObesityObesity– Dietary factorsDietary factors– Thrombogenic factorsThrombogenic factors– Lack of exerciseLack of exercise– Excess alcohol consumptionExcess alcohol consumption
Non-modifiableNon-modifiable– Personal history Personal history
of CVDof CVD– Family history Family history
of CVDof CVD
– Age Age – GenderGender
Pyörälä K et al. Eur Heart J 1994;15:1300–1331.
The Progression from CV Risk Factors to The Progression from CV Risk Factors to Endothelial Injury and Clinical EventsEndothelial Injury and Clinical Events
Risk factors
Oxidative stress
Endothelial dysfunction
NO Local mediators Tissue ACE-Ang II
PAI-1 VCAM
ICAM cytokines
Endothelium Growth factors matrix
Proteolysis
LDL-C BP Heart failureSmokingDiabetes
Vasoconstriction Vascular lesion and remodelling
Plaque ruptureInflammationThrombosis
Clinical endpoints
NO Nitric oxideGibbons GH, Dzau VJ. N Engl J Med 1994;330;1431-1438.
Historical Model of AtherogenesisHistorical Model of Atherogenesis
healthy subclinical symptomatic
Threshold
Decades Years-Months Months-Days
Plaque
Intima
MediaLumen
• Stable angina• Stable plaques with narrowing• Simple diagnostic (ECG, angiography)• Rare MI• Easy to treat
Antischkow N. Beitr Path Anat Allg Path 1913;56:379-404.
New ParadigmNew Paradigm
healthy subclinical symptomatic
Threshold
Decades Years-Months Months-Days
Intima
Media
PlaquePlaque
Thrombus
Lumen
• Unstable angina• Unstable plaque no narrowing• Difficult to diagnose (IVUS, MRI)• Frequent MI with sudden death• Easy to prevent
Upregulation of endothelialadhesion molecules
Increased endothelial permeability
Migration of leucocytes into the artery wall
Leucocyte adhesion
Lipoprotein infiltration
Endothelial Dysfunction in AtherosclerosisEndothelial Dysfunction in Atherosclerosis
Formation of foam cells
Adherence and entry of leucocytes
Activation of T cells
Migration of smooth muscle cells
Adherence and aggregation of platelets
Fatty Streak Formation in Fatty Streak Formation in AtherosclerosisAtherosclerosis
Formation of the fibrous cap
Accumulation ofmacrophages
Formation ofnecrotic core
Formation of the Complicated Formation of the Complicated Atherosclerotic PlaqueAtherosclerotic Plaque
Haemorrhage from plaque microvessels
Rupture of the fibrous cap
Thinning of thefibrous cap
The Unstable Atherosclerotic PlaqueThe Unstable Atherosclerotic Plaque
Intraluminal thrombus
Intraplaque thrombus
Lipid pool
Atherosclerotic Plaque Rupture and Atherosclerotic Plaque Rupture and Thrombus FormationThrombus Formation
Libby P. Circulation 1995;91:2844-2850.
The Vulnerable Atherosclerotic PlaqueThe Vulnerable Atherosclerotic Plaque
Manifestaciones clinicas de Manifestaciones clinicas de la Aterosclerosisla Aterosclerosis
Enfermadad Arterial CoronariaEnfermadad Arterial Coronaria– Angina de pecho, infarto del miocardio, muerte Angina de pecho, infarto del miocardio, muerte
subita cardiacasubita cardiaca
Enfermedad Cerebrovascular Enfermedad Cerebrovascular – Isquemia Cerebral Transitoria, strokeIsquemia Cerebral Transitoria, stroke
Enfermedad vascular PerifericaEnfermedad vascular Periferica– Claudicacion intermitente, gangrenaClaudicacion intermitente, gangrena
Diabetes MellitusDiabetes MellitusOne of the most common non-communicable One of the most common non-communicable diseasesdiseases
Fourth leading cause of death in most developed Fourth leading cause of death in most developed countriescountries
More than 194 million people with diabetes More than 194 million people with diabetes worldwideworldwide
Incidence of diabetes is increasing – estimated to Incidence of diabetes is increasing – estimated to rise to 333 million by 2025rise to 333 million by 2025
– To more than double in Africa, the Eastern Mediterranean To more than double in Africa, the Eastern Mediterranean and Middle East, and South-East Asiaand Middle East, and South-East Asia
– To rise by 50% in North America, To rise by 50% in North America, 20% in Europe, 20% in Europe, 85% in 85% in South and Central Americas and 75% in the Western PacificSouth and Central Americas and 75% in the Western Pacific
: International Diabetes Federation website
The Chronic Complications of The Chronic Complications of Diabetes Mellitus (US)Diabetes Mellitus (US)
Macrovascular complications:Macrovascular complications:
Cardiovascular diseaseCardiovascular disease– Leading cause of diabetes related deaths (increases Leading cause of diabetes related deaths (increases
mortality and stroke by 2 to 4 times)mortality and stroke by 2 to 4 times)
Microvascular complications:Microvascular complications:
Retinopathy Retinopathy – Leading cause of adult blindnessLeading cause of adult blindness
NephropathyNephropathy– Accounts for 44% of new cases of ESRD Accounts for 44% of new cases of ESRD
NeuropathyNeuropathy– 60-70% of patients with diabetes have nervous system 60-70% of patients with diabetes have nervous system
damagedamage National Diabetes Statistics US 2000
PROCAM: Combination of Risk Factors PROCAM: Combination of Risk Factors Increases Risk of MIIncreases Risk of MI
0
20
40
60
80
100
120
In
cid
en
ce
of
MI/
10
00
pts
None
Hyper
tensi
on
only
Diabe
tes on
ly
Hyper
tens
+
diabe
tes
Dyslip
idae
mia
Dyslip
idae
mia
+
hyper
tens
+/-
diab
etes
Prevalence (%): 54.9 22.9 2.6 2.3 9.4 8.0
Assmann G, Schulte H. Am Heart J 1988;116:1713-1724.
East West Study: Patients with DiabetesEast West Study: Patients with Diabetesat Similar Risk to No Diabetes with MIat Similar Risk to No Diabetes with MI
0
10
20
30
40
50
7-y
ea
r in
cid
en
ce
ra
te o
f M
I (
%)
No prior MIMI
p<0.001
p<0.001
No diabetes (n=1373)
Diabetes (n=1059)
Haffner SM et al. N Engl J Med 1998;339:229-234.
ns
HPS: Percent of Patients with Major Vascular HPS: Percent of Patients with Major Vascular EventsEvents** by Prior Disease in Placebo Group by Prior Disease in Placebo Group
* CHD, stroke, revascularization
0
10
20
30
40
DM Alone CHD Alone CHD + DM
Prior Disease
Perc
en
t d
evelo
pin
g 1
st
majo
r vasc
ula
r even
t
Collins R et al. Diab Care 2003;361:2005-2016.
PARIS: CHD Mortality Increases with PARIS: CHD Mortality Increases with Increased Impaired Glucose ToleranceIncreased Impaired Glucose Tolerance
0
1
2
3
4
5
CH
D m
ort
ali
ty r
ate
/1
00
0
G<140 mg/dL
IGT G≥200 mg/dL
Newly diagnosed diabetes
Known diabetes
p<0.001
n=6055 n=690 n=158 n=135
Eschwege E et al. Horm Metab Res 1995;17(Suppl):41-46.
G - glucose
Pyörälä K et al. Diabetes Care 1997;20:614-620.
4S: CHD Event Reduction in 4S: CHD Event Reduction in Patients with DiabetesPatients with Diabetes
0
2
4
6
8
10
12
14
16
18
VALUE: incidencia de nuevos casos de diabetes
23% de reducción
del riesgo
con valsartan
p < 0.0001
13.1%
16.4%
Regímenes basados en amlodipino(n = 5,168)
Ap
ari
ció
n d
e n
ue
vo
s c
as
os
de
dia
be
tes
(%
de
pa
cie
nte
s e
n e
l g
rup
o d
e
tra
tam
ien
to)
Regímenes basados en valsartan(n = 5,254)
Julius S et al. Lancet. 2204; 363: 2022-31.
Sistema renina angiotensina
Nuevos casos de diabetes
ALLHAT Officers and Collaborators. JAMA. 2002; 288: 2998-3007. Yusuf S et al. JAMA. 2001; 286: 1882-85.Dahlof B et al. Lancet. 2002; 359: 995-1003. Lithell H et al. J Hipertensión. 2003; 21: 875-86.
Fármaco
LisinoprilRamiprilLosartan
CandesartanValsartan
Comparador
ClortalidonaConvencional
AtenololConvencional
Amlodipino
Reducción
43%33%25%19%23%
Protocolo
ALLHATHOPELIFE
SCOPEVALUE
Efecto Metabólico del Comparador
----+
Statins Reduce CVD Risk in Statins Reduce CVD Risk in Patients with DiabetesPatients with Diabetes
37% (p<0.001)
25 (p=0.05)
55 (p=0.002)
19 (ns)
22 (p<0.0001)
na
23 (p<0.001)
32 (p<0.001)
25 (p<0.001)
24 (p<0.0001)
40%
28%
36%
25%*0.9 mmol/L(35 mg/dL)
Primary prevention
CARDS1 (atorvastatin; n=1428)
Secondary prevention
CARE2 (pravastatin; n=586)
4S3 (simvastatin; n=202)
LIPID4 (pravastatin; n=1,077)
HPS5 (simvastatin; n=5963)
% CVD risk reduction (diabetes)
% CVD risk reduction (overall)
LDL-C lowering
Study
* value for overall group