Documentos de Académico
Documentos de Profesional
Documentos de Cultura
de la Enfermedad Cardiovascular
Ateroesclertica
Dr. Jaime Roberto Ventura Umanzor
Mdico Cardilogo
Post. Paleoltico
Neoltico
Subsistencia
Casa colectiva
Siglo 19
Siglo 21
Alimentos
procesados
Grasa animales
Fibras dietticas
Alto nivel de
actividad fsica
Genotipo estable
Vida sedentaria
Genotipo susceptible
Riesgo a 5 aos
Riesgo absoluto
22.6 Prevencin
secundaria
15.9
13.2
7.9 Prevencin
primaria
2.8
4S
(simvastatin)
LIPID
(pravastatin)
CARE
(pravastatin)
34%
24%
24%
31%
WOSCOPS
(pravastatin)
AFCAPS/TexCAPS
(lovastatin)
37%
TNT
Prove-It
Reversal
Alliance:
101 vs 77
22
95 vs 62
16
110 vs 79 (%AV)-0.4/2.7
111 vs 79
17
DM = CI
www.drsarma.in
FACTORES DE RIESGO Y
ENFERMEDAD CARDIOVASCULAR
Factores
Proinflamatorios
OBESIDAD
STRESS
MODIFICABLES
COLESTEROL ELEVADO
DIABETES
Factores infecciosos
Factores
Procoagulantes
HIPERTENSIN
EDAD
TABAQUISMO
HISTORIA FAMILIAR
SEXO
INALTERABLES
Mltiples
Mltiples Factores
Factores de
de Riesgo
Riesgo para Desarrollar Aterotrombosis
Estilo de vida
Tabaco
Dieta
Sedentarismo
Desrdenes
generalizados
Edad
Obesidad
Rasgos genticos
Gnero
PlA2
Manifestaciones
Aterotrombticas
(IAM, ACV,
Muerte vascular)
Inflamacin
PCR elevada
CD40 Ligand, IL-6
Factores protrombticos (F I - II)
Fibringeno
Yusuf S. Circulation. 2001;104:2746-2753.
Drouet L. Cerebrovasc Dis. 2002;13(suppl 1):1-6.
Condiciones
sistmicas
Hipertensin
Hiperlipidemia
Diabetes
Hipercoagulabilidad
Homocisteinemia
Factores locales
Patrn de flujo
Shear stress
Dimetro del vaso
Estructura pared arterial
% estenosis arterial
IAM, Angina
ECV
Insuficiencia cardiaca
Insuficiencia Renal
Arteriopata Perifrica
Arteriosclerosis
Remodelado
HT
DM
Dislipemia
Obesidad
Gentica
Estilo de vida
Episodios
reincidentes
IR terminal
Dialisis
Demencia
Ateroesclerosis
Ateroesclerosis
Muerte
20
-7.4
aos
Aos
16
-9.2
aos
12
-12
aos
8
4
0
Sano
Historia de
Enf. Cardiovascular
Historia
de IAM
Historia de
Stroke
La Aterotrombosis es la primer
causa de muerte en todo el mundo
EPOC
6.3
Accidentes
SIDA
9.7
Cncer
12.6
19.3
Infecciones
22.3
Aterotrombosis
0
10
15
20
25
30
2.2
1.7
1.3
1.0
40 70 100
130
160
190
LDL-Colesterol (mg/dL)
Grundy, S. et al., Circulation 2004;110:227-39.
Metabolismo de Lipoprotenas
Hgado
B48
QM
AI CII
intestino
col
TG
R suprarrenal
B100
B100
R mbs cel
LDL
VLDL
CII E
bilis
colesterol
sales biliares
R gnadas
LPL
IDL
LH
oxidasa
LDLox
JAMA 2001; 285: 2486-2497
Metabolismo de HDL
Hgado
HDL
VLDL
LDL
bilis
colesterol
sales biliares
CETP
HDL
intestino
tejidos
perifricos
LCAT
HDL
CETP:
PROTENA DE TRANSFERENCIA DE
COLESTEROL STER.
Estudio de Framingham
Suma de factores de riesgo
Tabaco
X 1.4
X6
X 4.5
X 16
Colesterol
X4
X9
HTA
X3
INTERHEART
15152 p. y 14820 controles de 52
paises(analisis multivariado)
OR
Dislipidemia
RA
3.25
49%
Tabaquismo
2.87
35%
Factores psicosociales
Diabetes
Hipertensin
2.70
2.37
Alcohol
10%
1.91
Indice cintura/cadera
32%
18%
1.62
0.90
20%
7%
Actividad fsica
0.86
12%
Frutas y vegetales
0.70
13%
Riesgo
Riesgo Sumatorio
Sumatorio
27
13
19
8
TA 165/95
TA 165/95
Edad 56 aos
TA 165/95
TA 165/95
Edad 56 aos Edad 56 aos
LDL 155mg/dL LDL 155mg/dL
Fumador
Grundy SM et al.J Am Coll Cardiol 1999;34:1348-58
512
182,9
256
68,5
ndice de probabilidad
128
42,3
64
32
13,0
16
8
4
2,9
2,4
3,3
1,9
2
1
TAB
(1)
DM
(2)
HTN
(3)
ApoBApoA1
(4)
1+2+3
Todos FR
LA ATEROSCLEROSIS
COMIENZA EN LA NIEZ
Endotelio anormal
A2, endotelina, prostaciclina, tromboxano, estrs oxidativo
Estras
grasas
Placa
fibrosa
Placa
arterioesc.
obstructiva
Ruptura de
placa / fisura
/ trombosis
Angina
inestable
IAM
Muerte
sbita
Stroke
Etapa silente
Angor de
esfuerzo
Claudicacin
Isquemia
de
miembros
/ otros
Modificado de
Professional Postgraduate Services
(Courtesy of P Ganz.)
Incremento de edad
Por lo tanto
con la ateroesclerosis
estamos frente a un proceso patolgico,
constante, dinmico, progresivo, agresivo
y fatal.
PA
cigarrillo
Sedent.,FRS,
Estres oxidativo
Disfuncion endotelial
NO
PAI-1
Mediadores locales
Tissue ACE-Ang II
Endothelium
VCAM
ICAM cytokines
Thrombosis
Inflammation
Vasoconstriction
Growth factors
matrix
Vascular lesion
and remodelling
Proteolysis
Plaque rupture
EVENTOS CLINICOS
NO Nitric oxide
VULNERABILIDAD DE LA
PLACA
Caractersticas
PLACA
Histolgicas
VULNERABLE
Matriz colgena
(+)
CORE lipdico
(++++)
N de Macrfagos
(+++)
Factor Tisular
(++++)
Apoptosis
(++++)
Inflamacin
(++++)
Patgenos Intracelulares
(++++)
PLACA
ESTABLE
(++++)
(+)
(+)
(+)
(+)
(+)
(+)
0.06
Placebo
Drug therapy
PLAC I. Prav.
0.05
REGRESS. Prav.
CCAIT. Lov.
0.04
LCAS. Fluv.
MARS. Lov.
PLAC I
0.03
MAAS. Simv.
CCAIT
0.02
MARS
REGRESS
LCAS
0.01
MAAS
0
70
(1.8)
90
(2.3)
110
(2.8)
130
(3.4)
150
(3.9)
170
(4.4)
190
(5.0)
Estudio Jupiter
Prevencin Primaria
Reduccin de Eventos Coronarios segn LDL-C
Y = 0.0599 X - 3.3952
R2 = 0.9305
P < 0.0019
Eventos EC (%)
10
8
WOSCOPS-PL
WOSCOPS-Tr
6
AFCAPS-PL
AFCAPS-Tr
4
ASCOT-Tr
ASCOT-PL
2
0
50
70
90
110
130
150
170
190
210
Conclusiones
Conclusiones del
del uso
uso de
de estatinas
estatinas en
en
prevencin
prevencin primaria.
primaria.
El
El beneficio
beneficio es
es >> en
en los
los subgrupos
subgrupos con
con riego
riego basal
basal alto.
alto.
Cualquiera
Cualquiera sea
sea el
el valor
valor basal
basal de
de LDL
LDL que
que se
se parta,
parta, la
la
de
de LDL
LDL
muestra
muestra beneficios.
beneficios.
La
La mortalidad
mortalidad total
total no
no es
es afectada,
afectada, por
por el
el bajo
bajo riesgo
riesgo absoluto
absoluto ..
En
En el
el estudio
estudio Jupiter
Jupiter se
se demostr
demostr que
que pacientes
pacientes con
con colesterol
colesterol
normal
normal yy PCR
PCR alta
alta se
se benefician
benefician con
con tratamiento
tratamiento
Prevencin Secundaria
1993
4S-PL
Eventos EC (%)
25
20
2004
HPS-PL
4S-Tr
15
10
5
LIPID-PL
CARE-PL
HPS-Tr
LIPID-Tr
PROVE
AT
Y = 0.1629 X - 4.6776
R2 = 0.9029
P < 0.0001
CARE-Tr
TNT-AT80
TNT-AT10
A to Z-PL
PROVE
PR
A to Z
0
50
70
90
110
130
150
170
190
210
Meta-anlisis de 90.056p.de
14estudios randomizados con
<mortalidad estatinas
por todas las causas
12%
<mortalidad por EAC 23%
<Revascularizacin coronaria 24%
<Stroke 17%
No hubo incremento de cncer
CTT.Lancet 2005;366:1267-1278
Interacciones rosuvastatina-frmacos
Antes
Despu
s
p
ANOVA
Colesterol
Total mg/dL
195.31
3.5
74.96.
5
<.0005
HDL mg/dL
37.47.
1
37.66.
5
NS
LDL mg/dL
142.21
5.0
32.65.
0
<.0005
LDLoxidado
ng/mL
111.62
2.8
30.05.
4
<.005
Previo
Posterior
50
(ml/min/100ml)
Parmetros
60
40
30
p < 0.01
20
10
0
C
16
24
Acetilcolina (g/min)
En corto tiempo remover el LDL oxidado mejora la vasodilatacin dependiente del endotelio
Tamai O. Circulation 1997;95:76-82
30
4S - Pl
25
Secondary Prevention
Rx - Statin therapy
Pl Placebo
Pra pravastatin
Atv - atorvastatin
20
4S - Rx
LIPID - Pl
15
10
LIPID - Rx
CARE - Rx
HPS - Rx
TNT Atv10
PROVE-IT - Pra
TNT Atv80
PROVE-IT Atv
CARE - Pl
Primary Prevention
HPS - Pl
WOSCOPS Pl
AFCAPS - Pl
6
AFCAPS - Rx
WOSCOPS - Rx
ASCOT - Pl
ASCOT - Rx
0
40
(1.0)
60
(1.6)
80
(2.1)
100
(2.6)
120
(3.1)
140
(3.6)
160
(4.1)
180
(4.7)
200
(5.2)
Referente
0.80 (0.59, 1.07)
0.67 (0.50, 0.92)
0.61 (0.40, 0.91)
Ms bajo mejor
Ms alto mejor
PROVE-IT
A TO Z
TNT
IDEAL
n
pacientes
4.162
4.497
10.001
8.888
Total
27.548
Cannon C. J Am Coll Cardiol 2006;48:438-45
LDL-C (mg%)
120
Mediana LDL-C
100
80
21%
95 (79 - 113)
Pravastatina 40mg
62 (50 - 79)
60
49%
Atorvastatina 80mg
En 2 aos de RR
16 % en el grupo
Atorvastatina.
40
P<0.001
20
<24h Rand. 30 Das 4 Mes. 8 Mes. 16 Mes.
Final
Cannon C. N Engl J Med. 2004;350:15
Estudio TNT
Muerte Cardiovascular, IM no Fatal, Resucitacin,
o Accidente Cerebrovascular Fatal o no Fatal
0.15
Atorvastatina 10 mg
Atorvastatina 80 mg
Eventos
0.10
22%
reduccin
0.05
0
0
Tiempo (aos)
LaRosa JC. N Engl J Med 2005;352(14):142535
IVUS
parmetros
medidos
77.9%
78.1%
10
rosuvastatina 40 mg
20
30
40
50
60
63.6%
70
80
90
100
BENEFICIOS
DE ROSUVASTATINA +
+
--STELLAR, MERCURY I, MERCURY II, ORBITAL, DISCOVERY,
COMETS, LUNAR, PLUTO, POLARIS, PULSAR, ECLIPSE,
EXPLORER
PR
EV
EN
CI
JUPITER
ASTEROID
METEOR, ORION
REGRESIN
CORONA
AURORA
Dao vascular
Arteriosclerosis
Enferm. clnica establecida
Insuf Cardiaca
IRC, ACV
Factores Riesgo
Cardiovascular
ESTILO DE VIDA
GENES
MUERTE
NCEP
ATP I
Guas
1988
NCEP
ATP II
Guas
1993
NCEP
ATP III
Guas
2001
Actualizacin
2004
2013 ACC/AHA
Guidelines
Guas Canadienses
2009
Framingham Angiographic Trials
MRFIT
(FATS, POSCH,
4S, WOSCOPS,
LRC-CPPT
SCOR, STARS,
CARE,LIPID,
Coronary Drug Ornish, MARS)
AFCAPS/TEXCAPS.
Project
VAHIT, otros
Helsinki Heart
Metaanlisis
CLAS (angio) (Holme, Rossouw)
TNT, IDEAL,
REVERSAL,
PROVE-IT,
ESTABLISH
JUPITER
30
Estatina
Placebo
25
4S
20
Prevencin
secundaria
4S
LIPID
CARE LIPID
CARE
PROVE-IT
IDEAL
(Atv)
(Sim)
HPS
IDEAL
TNT
(Atv)
WOSCOPS
(Atv 10 mg)
PROVE-IT (Pra)
AFCAPS
HPS
TNT
AFCAPS
(Atv 80 mg)
WOSCOPS
15
10
5
ASCOT
0
0
40
(1,0)
60
(1,6)
80
(2,1)
100
(2,6)
Prevencin
primaria
ASCOT
120
(3,1)
140
(3,6)
160
(4,1)
180
(4,7)
200
(5,2)
CV: Cardiovascular
Atv = atorvastatina; Pra = pravastatina; Sim = simvastatina; PROVE-IT = Pravastatin or AtorVastatin Evaluation and Infection Therapy;
IDEAL = Incremental Decrease in Endpoints through Aggressive Lipid Lowering; ASCOT = Anglo-Scandinavian Cardiac Outcomes Trial;
AFCAPS = Air Force Coronary Atherosclerosis Prevention Study; WOSCOPS = West of Scotland Coronary Prevention Study
Rosenson RS. Expert Opin Emerg Drugs. 2004;9:269279; LaRosa JC, et al. N Engl J Med. 2005;352:14251435; Pedersen TR, et al. JAMA. 2005;294:2437
2445.
Objetivo
Mortalidad Total
RR
95% CI
0.91
0.83 1.01
Objetivo
RR
95% CI
Mortalidad Total
0.88
0.81 0.96
0.70
0.61 0.81
0.81
0.71 0.93
Taylor, Fiona; Ward, Kirsten; Moore, HM Theresa; Burke, Margaret; Davey Smith, George; Casas, JuanPablo; Ebrahim, Shah
Cochrane Heart Group
Objetivo
RR
95% CI
Mortalidad Total
0.83
0.73 0.95
0.70
0.61 0.79
Revascularizacin
0.66
0.53 0.83
Background
Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of coronary heart disease
(CHD) is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in
people with coronary artery disease. The case for primary prevention, however, is less clear.
Objectives
To assess the effects, both harms and benefits, of statins in people with no history of CVD.
Selection criteria
Randomised controlled trials of statins with minimum duration of one year and follow-up of six months, in adults with no restrictions on their total low density
lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD, were included.
Data collection and analysis
Two authors independently selected studies for inclusion and extracted data. Outcomes included all cause mortality, fatal and non-fatal CHD, CVD and stroke
events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), change in blood total cholesterol concentration, revascularisation, adverse
events, quality of life and costs. Relative risk (RR) was calculated for dichotomous data, and for continuous data pooled weighted mean differences (with 95%
confidence intervals) were calculated.
Main results
Fourteen randomised control trials (16 trial arms; 34,272 participants) were included. Eleven trials recruited patients with specific conditions (raised lipids,
diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (RR 0.83, 95% CI 0.73 to 0.95) as was combined fatal and non-fatal CVD
endpoints (RR 0.70, 95% CI 0.61 to 0.79). Benefits were also seen in the reduction of revascularisation rates (RR 0.66, 95% CI 0.53 to 0.83). Total cholesterol
and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no clear evidence of any significant harm caused
by statin prescription or of effects on patient quality of life.
Authors' conclusions
Although reductions in all-cause mortality, composite endpoints and revascularisations were found with no excess of adverse events, there was evidence of
selective reporting of outcomes, failure to report adverse events and inclusion of people with cardiovascular disease. Only limited evidence showed that
primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary
prevention among people at low cardiovascular risk.
Systematic Review.
Dislipidemias: tratamiento
http://clincal.com/Cardiology/ASCVD/PooledChohort.aspx
Dislipidemias: tratamiento
Grupo
teraputico
Antecede
ntes de
ECV
c-LDL >
190
mg/dl
(1)
Diabetes (1
y 2)
40-75 aos
40-75 a. y
riesgo (10
a) > 7,5%
Tratamiento
< 75
a
> 75
a
Riesg
o
>
7,5%
Ries
go
<
7,5%
Atorva 80
(40)
Rosu 20
Estatina de
gran
potencia
(c-LDL
c-LDL
>
< 40
mg/dl
x2
50%)
Estatina de
potencia
moderada
( c-LDL
de 30
Atorva
10 a
(20)
50%)
Rosu 10
(5)
Simva 2040
35
45
55
65
20
40
80
10
20
40
80
10
20
40
80
10
20
40
R
os
uv
a
Si
m
va
a
av
P
it
ra
va
P
to
rv
a
Fl
uv
a
Lo
va
0
5
15
25
% reduccin c-LDL
Estatina (mg/da)
10
1
2
4
5
10
20
40
20
40
80