Factores a Tener en Cuenta para la Cuantificacin del Riesgo CV.

Risk Factors

Edad, Gnero (Masc.)

Hipertensin Arterial
Colesterol Total
Tabaco
Historia Evento CV Familiar
Glu Alt Ayunas, IR o DBT*
HDLCol Bajo,

Subclinic TOD

HVI
Microalbuminuria
Creatinina >1.3mg/dl
IMT Elevado
Rigidez Vascular Vascular
Retinopata Hipertensiva
(grado III/IV)

Clinical Events

CHD
MI
CHF
ACV, TIA
IRC
Enfermedad Arterial
Perifrica

TG elevados
LDLcol Elevado
Sobre Peso/Obesidad
(BMI>25Kg/m2)
Menopausia
Posicin Social/Economica**
Nivel de Educacin
J Hypertens 2009; 27: 905-822

INTERHEART:MultipleRiskFactors.
ImpactonCVRisk
512

2.9

2.4

1.9

3.3

13.0

42.3

68.5

182.9

333.7

256
128
Tasa de
Probab.
del
1*IMA

64

(99% IC)

32
16

20 veces
de riesgo

4
2
1
Tabaco
(1)

52 pases
12,461casos
12,467 controles

DM
(2)

HTA
(3)

ApoB- 1+2+3
ApoA1
(4)

Los 4

Los 4
Los 4
+ Obes + Estres

Todos
los F.R

Yusuf S et al. Lancet. 2004;364:937-52.

Risk Stratification related to BP Values.

NORMOTENSION
OtherRisk Factors
or Diseases

HYPERTENSION

Optimal

Normal

High
Normal

Grade 1

Grade 2

Grade 3

Mean Risk

Mean Risk

Mean Risk

Low Added
Risk

Moderate
Added Risk

High Added
Risk

1-2 RF or Social
Conditions of Risk

Low
Added
Risk

Low Added
Risk

Low Added
Risk0

Moderate
Added Risk

Moderate
Added Risk

Very High
Added Risk

3 RF or Social
Conditions of Risk
TOD or SM/DBT

Moderate
Added
Risk

Moderate
Added Risk

ModerateHigh Added
Risk

High Added
Risk

High Added
Risk

Very High
Added Risk

High
Added
Risk

High Added
Risk

Very High
Added
Risk

Very High
Added Risk

Very High
Added Risk

Very High
Added Risk

No RF

Clinical
Associated
Condition

Latin American guidelines on hypertension. Sanchez RA on behalf of the Latin America Expert Group. J Hypertens 2009; 27: 905-922.

TERAPEUTICA

NO FARMACOLOGICA

Impacto de Pequeas Reducciones de PA.

SBP

Each 10-14
mmHg

CHD

DBP

Each 5-6
mmHg

CV Events

Stroke

=
17%
33%
40%

World Health Organization-International Society of Hypertension. The Guidelines Subcommittee of the WHO-ISH. Mild
Hypertension Liaison Committee. 1999 Guidelines for the Management of Hypertension Memorandum.

Objetivos del Tratamiento

En sujetos hipertensos, el objetivo primario es lograr
la mxima reduccin del riego total a largo plazo de
enfermedad cardiovascular.

Ello requiere el tratamiento, no solo de los valores

aumentados de la PA sino tambin de TODOS los
factores de riesgo reversibles asociados.
En todos los sujetos con HTA la PA debe ser
reducida, por lo menos, a valores menores a los
140/90mmHg y, en caso de ser tolerado, a valores
menores.
2007 Guidelines for the Management of Arterial Hypertension .The Task Force for the Management of Arterial Hypertension of the ESH -ESC. J Hypertens 2007, 25:11051187.

Cambios del Estilo de Vida

Los cambios que son ampliamente reconocidos para bajar la PA o el
Riesgo CV y deben ser considerados son:
Dejar el Hbito de Fumar,
Reduccin del Peso y su Estabilizacin,
Reduction en la ingesta de alcohol (30g/da Alcohol Etlico),
Actividad Fsica AEROBICA
Reduccin en la ingesta de Sodio (4g ClNa+ o 60mEq/Na+/da),
Incrementar la ingesta de frutas y vegetales y reducir la de grasas
totales y saturadas,
Dado que la adherencia a largo plazo de estas medidas es bajo y la
respuesta de la PA es altamente variable, los pacientes en tratamiento
no farmacolgico deben ser controlados de cerca para poder instaurar
el tratamiento farmacolgico cuando sea necesario y en forma pautada.
2007 Guidelines for the Management of Arterial Hypertension .The Task Force for the Management of Arterial Hypertension of the ESH -ESC. J Hypertens 2007, 25:11051187.

Cigarette Smoking and Blood Presure

Data from Annual Health Survey for England (1994-1996)
Men (n = 15 861) Ages 16-97 Years
Observed Blood Pressure (mm Hg)

160

Systolic
Diastolic

140
120
BP
(mm Hg)

100
80
60
40
20
0
Never
(n = 4398)

Ex
(n = 7303)

1-9
(n = 1084)

10-19
(n = 1505)

20+
(n = 1571)

Smoking Categories
Mean of last 2 of 3 automated measurements after 5 min
seated. No food, alcohol, or smoking for >30 min before
measurement.

Primatesta P et al. Hypertension 2001;37:187-193

Cardiovascular Mortality by Smoking and Blood Pressure:

The Malm Preventive Project
22 444 men born 1921-1949, Mean Follow-Up 17 years
Smokers (n = 7848)

Non-smokers (n = 8228)
150

Mortality/10000 Person-Years in Quintiles of Systolic BP

100

50

Quintile

0
2
115-120

120-125

130-135

140-225

105-220

1.8

2.5

2.7

2.2

2.5

1.8

1.4-2.3

2.1-3.0

2.0-3.6

1.9-2.7

2.1-2.9

1.3-2.5

1
SBP (mm Hg) 75-115
RR
95% C.I.

Treated Hypertension

Khalili P et al. J Hypertens 2002;20:1759

Endpoint Rates by Smoking Status in Hypertensive Patients with Left

Ventricular Hypertrophy: The LIFE Study
Drug Groups Combined (n = 9188)
Endpoint Rates per 1000 Years of Follow-Up
Cardiovascular Death
Stroke
Myocardial Infarction
***

25

25

20

15
10

**

20
15

25

******
*

20
15

10

10

Never
(n = 4656)

Previous
(n = 3033)

1-5/d
(n = 454)

11-20/d

6-10/d
(n = 428)

(n = 435)

***

>20/d
(n = 182)

*P < 0.05, **P

< 0.01, ***P < 0.001 for Adjusted Hazard Ratios vs. Never-Smokers
Adjusted for alcohol consumption, exercise, gender, and age
Reims HM et al. Blood Press 2004;13:376

Falta de Actividad Fsica, Sobrepeso, etc, etc.............

Control del Peso: IMC 25 = MISION IMPOSIBLE ???

Prevalence of Hypertension by Body Mass Index

National Health and Nutrition Examination Survey III (1988-1994)
Body Mass Index (kg/m2)

100
75
%

<25

Men

25 - <27

27 - <30

30+

50
25
0
100
75

20-39

40-59

60+

40-59

60+

Women

50
25
0

20-39

Age (years)

Brown CD et al. Obes Res 2000;8:605

SBP change in randomized weight reduction controlled trials in function

of whether or not the patients follow an antihypertensive treatment.
Untreated patients
Wing (1998)a
Blumenthal (2000)a
Fagerberg (1984)
MacMahon (1985)
Wing (1998)b
Fortmann (1988)a
Anderssen (1995)a
Croft (1986)
Blumenthal (2000)b
Gordon (1997)
Anderssen (1991)
Anonymous (1990)
Stevens (1993)
Anderssen (1995)b
Fortmann (1988)b
Anonymous (1997)
Masuo (2002)a
Langford (1991)
He (2000)
Oberman (1990)
Haynes (1984)
Stamler (1989)
Blumenthal (2000)c
Anderssen (1995)c
Masuo (2002)b
Wing (1998)c

Treated patients
Singh (1990)
Reisin (1978)
Ard
(2000)
Jalkanen (1991)
Lalonde (2002)a
Singh (1995)
Whelton
(1998)
Lalonde
(2002)b
Combined
-30

-20

-10

10

Change in systolic blood pressure (mm Hg)

Combined
-20

-10

10

Change in systolic blood pressure (mm Hg)

Neter et al. Hypertens 2003; 42: 878-84.

Change in Blood Pressure by Weight Change

Trials of Hypertension Prevention (THOP) II
Normotensives, 110-165% of ideal body weight at
baseline
Combined Study Groups (n = 1191)
4
Diastolic

Change in BP (mm Hg)

Systolic
2
0
-2
-4
-6
-8
Weight change:

-8.8 kg

-2.6 kg

-0.1 kg

+2.6 kg

+7.3 kg

Quintiles of Weight Change

Data adjusted for age, ethnicity, and gender
Intervention: 3-year program of group meetings and individual counseling
(dietary change, physical activity, social support).

Stevens VJ et al. Ann Intern Med 2001;134:1-11

Change in Blood Pressure by Weight Change Pattern

Trials of Hypertension Prevention (THOP) II
Systolic BP Change
4

Weight loss <2.5 kg (n

= 198)

2
Control Group (n =
554)

0
-2

(mm Hg)

Weight loss 4.5 kg relapse to

<2.5 kg (n = 129)

-4
-6

Weight loss 4.5 kg,

maintained (n = 73)

-8
-10
0

12

18

24

30

36

Months

Intervention: Dietary change, physical activity, social support; goal: 4.5 kg

Data adjusted for age, ethnicity, and gender
Remaining (n = 195) not classified (other pattern or missing data)

Stevens VJ et al. Ann Intern Med 2001

17

Alcohol and Blood Pressure

Annual Health Survey for England (1994-1996)
Systolic Blood Pressure by Alcohol Consumption in 4398 Non-Smoking Men
Adjusted for Age and BMI
144

P <0.05

142
140

mm Hg

138
136
134
132
130

1-21

>21

Drinks per Week

Primatesta P et al. Hypertension 2001;37:187-193

Effect of Alcohol Reduction on SBP

Lang et al, 1995
Cushman et al, 1998
Wallace et al, 1988
Maheswaran et al, 1992
Ueshima et al, 1987
Ueshima et al, 1993
Rakic et al, 1981
Rakic et al, 1982
Puddey et al, 1985
Kawano et al, 1998
Parker et al, 1990
Puddey et al, 1992
Cox et al, 1993
Puddey et al, 1986
Howes and Reid, 1986

Systolic blood pressure

76%

Combined
Lang et al, 1995
Cushman et al, 1998
Maheswaran et al, 1992
Ueshima et al, 1987
Ueshima et al, 1993
Rakic et al, 1981
Rakic et al, 1982
Puddey et al, 1985
Kawano et al, 1998
Parker et al, 1990
Puddey et al, 1992
Cox et al, 1993
Puddey et al, 1986
Howes and Reid, 1986

Diastolic blood pressure

76%

Combined
-15

-10

0
-5
Reduction in blood pressure (mm Hg)

10

Reduction in self-reported daily consumption of alcohol

There is a dose-response relation between the reduction in blood pressure following a reduction in
alcohol intake.
Xin et al. Hypertension.2001;38:1112-7

ACTIVIDAD FISICA

DEBE RECORDARSE QUE DEBE SER GRADUADA

Risk of Hypertension by Physical Activity Level and Body Mass

Index (Adjusted Hazard Ratios)
Men Aged 25 - 64 years, Mean Follow-Up 11 Years (n = 8302)
1.0

1.0

0.8
0.6

0.78

0.4

0.62

0.58

0.49
0.44

0.2
0.0

Low

Moderate
Physical Activity

High

25
<25 BMI (kg/m2)

Adjusted for age, area, study year, education, alcohol intake, diabetes at baseline.
Low: Light levels of occupational, commuting (30 minutes), and leisure time physical activity
Moderate: 1 type of moderate-to-high physical activity
Hu G et al. Hypertension 2004;43;25-30
High: 2 - 3 types of moderate-to-high physical activity.

Effect of Aerobic Exercise on Blood Pressure MetaAnalysis of Randomized, Controlled Trials

Systolic
Hypertensives
(15 Trials)

Diastolic
Normotensives
(27 Trials)

0
-1
-2

Changes in
Blood Pressure
(mm Hg)

-3
-4
-5
-6
-7
-8
Whelton SP et al. Ann Intern Med 2002;196:493

Cardiovascular Mortality by Physical Activity in 9185 Hypertensive Patients

with Left Ventricular Hypertrophy: The LIFE Study
Proportion of Patients with an Event
0.10

Self-Reported Activity Level at Baseline:

Never (n = 2020)
30 min, 2 times/wk (n = 2407)
>30 min, 2 times/wk (n = 4758)

0.08

0.06

0.04
HR 0.49 (0.38-0.61)

0.02

0.00
Age 55-80 years

12

24

HR adjusted for alcohol use, smoking, gender, age, and race

36

48

60

Months
Fossum E et al. 2006

DOUBLE-BLIND STUDY OF THREE Na+ INTAKES AND

LONG-TERM EFFECTS OF SODIUM RESTRICTION.

25
Lancet 1989; ii:1244-7

Modest Salt Restriction in Older People

26

Lancet 1997; 350: 850-854

Difference in SBP after K+ supplementation as

Function of the BP Status and Urinary Na+.
Normotensive

Hypertensive

<140 mmol/d

140-164 mmol/d

>=165 mmol/d

-12
-10
-8
-6
-4
-2
Change in systolic blood pressure (mm Hg)

Whelton P et al. JAMA 1997; 277: 1624-1632

Effect of Fruit and Vegetable Intake on Blood Pressure

6 Months Randomized Controlled Trial in Healthy Men and Women

Changes in Intake, Body Weight, and Blood Pressure

Control (n = 346)
Intervention (n = 344)
1.5

P <0.0001

Intake
(Portions) 1.0

0.8

Body
Weight
(kg)

0.5
0.0

Systolic
BP
(mm Hg)

NS

0.6
0.4
0.2
0.0

1
Diastolic
BP
(mm Hg)

0
-1

0
-1

P <0.0001
-2
Intervention: Oral and written information and encouragement to
eat five-a-day.

-2

P <0.05

John JH et al. Lancet 2002;359:1969-1974

D.A.S.H. diet
132

Control

131
130
129

Fruit & Veg

128
127
126

Combination

125
124

8
7&

ne

123
Ba
se
li

High fruit & vegetables

Low fat dairy products
Whole grains & Nuts
Poultry & Fish
Little red meat, sweets,
sugar-containing drinks
Reduced total and saturated
fat
Reduced cholesterol

SBP (mmHg)

weeks
N Engl J Med 1997; 336: 1117-1124

Reduccin de la PAS por la Combinacin de la

dieta DASH y la Reduccin en la ingesta de Sal.
136

3.5
3
-4.6
(-5.9 to 3.2)

Systolic blood pressure (mmHg)

132

2.5

130
2
128
1.5
-1.3
(-2.6 to 0.0)

126

-1.7
(-3.0 to 0.4)

124

1
0.5

122
120

g of sodium consumed per day

-2.1
(-3.4 to 0.8)

134

0
High

Level of sodium consumption

Intermediate

Control Diet

Low

DASH Diet

Neter et al. Hypertens 2003; 42: 878-84.

BP Response to Dietary and Lifestyle Interventions

Meta-analysis of Controlled Trials in Finland, Italy, the Netherlands, UK and
USA
Blood Pressure Change weighted by trial sample size (95% C.I.)
Body
Weight

Physical
Activity

Alcohol

Coffee

Sodium

Potassium

Trials (n)

25

49

13

10

40

27

16

36

36

Changea

-6.5 kg

+2.5 h/wk

-41 ml

-4.9 cups

-2.1 g

+2.0 g

+483 mg

+1.2 g

+4.1 g

Magnesium Calcium

Fish oilb

0
-1
-2
-3
-4
Systolic

-5

Diastolic

-6
-7

mm Hg

Average change in dietary intake (per day) or lifestyle factor in trials.

Supplementation of fish fatty-acids (eicosapentaenoic acid and docosahexaenoic acid).

Geleijnse JM et al. J Hum Hypertens 2005;19:S1-S4

Implicancia de Pequeas Reducciones

de PAD en la Prevencion Primaria
DBP reduction
0

7.5 mm Hg

5-6 mm Hg

-6

-10

-21

-40
-50

-15

-16

-20

Risk
reduction
(%)
-30

2 mm Hg

-38

CHD
Stroke

-46

CHD, coronary heart disease. Cook NR et al. Arch Intern Med. 1995;155:701-709.

Dyslipidemia
Pharmacological
Treatment

Arterial
Hypertension
Pharmacological
Treatment

Ove
r
Obe weigh
t
s
Pha
i
t
y
rm
a

-Physical
Activity
-Weight Control
-Diet: Na+

colo
gi
Sur cal Tr
e
ger
y atmen
t,

Diabetes

Carbohydrates

-Tobacco,
-Alcohol
-Etc.

Pharmacological
Treatment

CV RISK REDUCTION

Conclusiones
Las modificaciones del estilo de vida son medidas efectivas para la
prevencin y el manejo de la HTA,
Las sugerencias son:
Mantener o llegar, en lo posible, a un peso normal (IMC: 20-25 kg/m2),
Reducir la ingesta de sal a <100 mmol/day (<6g NaCl or <2.4g Na+/day),
Limitar la ingesta de alcohol a <3 unidades/da para varones y a <2 unidades/da para las
mujeres,
Realizar ejercicio aerbico en forma regular (Caminar nadar, bicicleta) >30 min por da,
6 veces por semana, como mnimo,
Consumir, por lo menos, 5 porciones por da de frutas y vegetales frescos,
Reducir la ingesta de grasas totales y saturadas.

Hay un necesario compromiso por parte de los consumidores,

la industria y los gobiernos.
35

PERO FUNDAMENTALMENTE......

INDICACIONES FACTIBLES

TERAPEUTICA

FARMACOLOGICA

PAD: Cambios Promedios (48m seguimiento)

Tratamiento
Acebutolol
Amlodipine
Clortalidona
Doxazocina
Enalapril
Todas
Placebo

Varones
-13.2
-13.0
-12.2
-11.7
-11.7
-12.4
-9.1

Mujeres
-12.9
-12.8
-12.5
-11.3
-11.3
-12.2
-7.9

De Waeber B y Brunner, HR. J Hypertens 15(suppl 2): S17-S20; 1997 del Estudio THOMS. Arch Intern Med 156: 377-385; 1996

Respondedores a Monoterapia
Frmaco
Placebo
HCTZ
Atenolol
Cptopril
Diltiazem
Clonidina
Prazosin

n=
187 (138)
188 (108)
178 (80)
188 (110)
185 (88)
178 (84)
188 (80)

Titulacin
33
57
65
56
75
65
56

1 ao
31
55
60
50
72
62
54

Colaterales
6.4
1.1
2.2
4.8
6.5
10.1
13.8

De Waeber B y Brunner, HR. J Hypertens 15(suppl 2): S17-S20; 1997 del NEJM 328: 914-921; 1993 y Am J Hypertens 8: 189-192; 1995

Tratamiento de la HTA
OMS/ISH

Accin Central

Diurticos

IECA
Ca++ Antg

Diurticos

Ca++ Antg

Bloqueantes

IECA

Bloqueantes
IECA

Bloqueantes

Ca Antg
++

Diurticos
Ca++ Antg
Bloqueantes

Bloqueantes

IECA
ARA II

Bloqueantes

B
Diurticos

Bloq. + Efecto Vasodilatador

Bloqueantes de Renina

B
Diurticos
IECA

Ca++ Antg

DIABETES e HTA
TERAPEUTICA
De uso preferencial:
- IECA
- BRA II
- Calcio Antagonistas
SI
- Bloqueantes Beta
Cautela
- De accin central Considerar

- Bloqueantes Alfa
- Diurticos
- Bloqueantes y

Subclinical organ damage:

LVH:
Symptomatic atherosclerosis:
Microalbuminuria:
Renal dysfunction:

ACEI, CA, ARBA,

CA, ACEI
ACEI, ARB
ACEI, ARB

Clinical event:
Previous stroke:
Previous MI:
Angina pectoris:
Heart failure diuretics:

Any BP lowering agent

BB, ACEI, ARB
BB, CA
BB, ACEI, ARB, antialdosterone agents

Atrial fibrillation:
Recurrent:
Permanent:
ESRD/proteinuria:
Peripheral artery disease:

ARB, ACEI
BB, non-dihydropiridine CA
ACEI, ARB, loop diuretics
CA

Condition:
ISH (elderly):
Metabolic syndrome:
Diabetes mellitus:
Pregnancy:
Blacks:

Diuretics, CA
ACEI, ARB, CA
ACEI, ARB
CA, methyldopa, BB
Diuretics, CA

Conditions favouring use of some antihypertensive drugs.

Ms de 1 Frmaco Antihipertensivo
se requiere para el control de la HTA
Trial

Target BP (mm Hg)

No. of antihypertensive agents

1
UKPDS 1

DBP < 85

ABCD 2

DBP < 75

MDRD 3

MAP < 92

HOT 4

DBP < 80

AASK 5

MAP < 92

IDNT 6

SBP < 135/DBP < 85

DBP - Diastolic Blood Pressure; MAP - Mean Arterial Pressure; SBP -Systolic Blood Pressure

Solo el 30% de los pacientes con HTA

Responden con monoterapia.

1- UKPDS 38 BMJ. 1998; 317(7160):703-13.

2- Estacio RD et al. Am J Cardiol 1998; 82(9B):9R-14R
3- Lazarus JM et al. Hypertension, 1997; 29(2):641-50.
4- Hansson et al. Lancet 1998; 351(9118):1755-62.
5- Kusek JW et al. Control Clin. Trials 1996; 17(4 Suppl):47S-54S.
6- Lewis EJ et al. N Engl J Med. 2001, 345:851-60

Estudio HOT y las combinaciones...

63%
Inclusin
41%

161/98

144/85

Final
68%

68%

< 85
mmHg
142/83

74%

< 80
mmHg
140/81

142/83

Combinacin
Monoterapia
Hanson L et al. Lancet 1998; 351: 1755-1762

< 90 mmHg

Combinar antihipertensivos?

Moda o necesidad?

Asociaciones: Resea Histrica

Dcada del 60:
-Reserpina-hidralazina-HCTZ
-CH3-DOPA-Tiazida

Dcada del 70:

- Tiazidas-Conservadores de K+
- Tiazidas-Espironolactonas.
- Bloqueantes -Tiazidas
- Clonidina-Tiazidas

Dcada del 80:

- IECA-Tiazidas.
Dcada del 90:
- Bajas dsis de bloqueantes -Tiazidas
- IECA-Calcio Antagonistas

Siglo XXI:
-ARAII con Ca++ Antg
-ARA II con Ca++ Antg y Estatina

Modificado de Epstein M and Bakris G. Arch Int Med 156: 1969-1978; 1996

SINERGIA
Diurticos

Beta bloqueantes

Antagonista
Receptores de
Angiotensina II

Alfa bloqueantes

Antagonistas
Canales de Calcio

IECAs
Las familias de drogas que estn recuadrados han sido probados en estudios CONTROLADOS
Fuente: Guas para el Tratamiento de la Hipertensin Arterial. Sociedad Europea de HTA / Cardiologa 2003.

Asociaciones o Combinaciones
-Sabemos que solo 1/3 de la poblacin de hipertensos responde
a la Monoterapia,
-Segn el riesgo agregado, el objetivo terapetico es MAYOR,
-Las asociaciones y combinaciones son eficaces y acortan LOS
TIEMPOS en la reduccin de la PA,
-Que SIEMPRE hemos usado asociaciones o combinaciones.

POR LO TANTO:
CUANDO LAS USAMOS?

Tratamiento Farmacolgico.
2003 European Society of Hypertension European Society of Cardiology Guidelines for the Management of Arterial Hypertension, J Hypertens, 2003

Considerar :
Nivel de PA previo al tratamiento Ausencia o Presencia de DOB y FR.
Elegir entre:
Elevacin leve de PA
Elevacin marcada de PA
Riesgo CV: L a M
Objetivo PA convencional

Riesgo CV Alto o Muy A

Objetivo PA bajo.

Monodroga en
baja dsis

Combinacin de 2 Frmacos a
baja dsis

Si no se logra el objetivo teraputico :

Aumentar a
Cambiar a otro
dsis mxima frmaco en dsis baja

Subir a dsis
mxima

Agregar un 3er
frmaco a bajas dsis

Si no se logra el objetivo teraputico :

Asociacin de
2-3 frmacos

Terapia a
dsis mxima

Combinacin con 2-3

frmacos.

Evaluar probabilidad HTA sundaria

Aumento de Riesgo CV
Condiciones Asociadas
Microalbuminuria

Hypercoagulabilidad

Obesidad Visceral

DBT Tipo 2

Riesgo CV
Fumar

Hipertensin

Insulino Resistencia

Dislipemia
Sobrepeso
Obesidad

Ezatti M. et al, Lancet 2002; 360:1347-1360

INTERHEART:MultipleRiskFactors.
ImpactonCVRisk
512

2.9

2.4

1.9

3.3

13.0

42.3

68.5

182.9

333.7

256
128
Tasa de
Probab.
del
1*IMA

64

(99% IC)

32
16

20 veces
de riesgo

4
2
1
Tabaco
(1)

52 pases
12,461casos
12,467 controles

DM
(2)

HTA
(3)

ApoB- 1+2+3
ApoA1
(4)

Los 4

Los 4
Los 4
+ Obes + Estres

Todos
los F.R

Yusuf S et al. Lancet. 2004;364:937-52.

Predicted Reduction in Major

CVD (%)

Treating HT and Other Risk Factors

0
-5
-10

Treatment
Based on TC
(statin)

-6

-9

-15

Treatment
Based on BP
(-blocker,
diuretic)

-6
-12

-8

Treatment Based on
Overall Absolute Risk
(ASA, statin, ACEI,
-blocker, diuretic)

-10
-17

-20
-25
-30
-35
-40

Treatment thresholds
Top 10%
Top 20%
Top 30%
Adapted from Emberson et al. Eur Heart J. 2004;25:484-491.

-28
-37

PolyPill
The concept of a polypill was born in 2003, when British professors from the Wolfson
Institute of Preventive Medicine in London, UK, Nick J Wald and Malcolm R Law,
proposed a polypill containing six constituents in the BMJ [Wald NJ and Law MR. A strategy to reduce cardiovascular
disease by more than 80%. BMJ 2003; 326:1419.].
They settled on a hypothetical pill combining a statin; three blood-pressure-lowering
drugs, each at a half-standard dose (potentially a thiazide, beta blocker, and ACE
inhibitor); 0.8-mg folic acid; and 75-mg aspirin. Such a product could slash the risk of
cardiovascular events by 80% or more and benefit one in three people if everyone over the
age of 55 were to take the pill, they calculated. And by including only half-doses of the
antihypertensives, the risk of adverse effects would be minimized, they said.
Version of
polypill

Aspirin

Lisinopril

Simvastati HCTZ
n
(mg)
(mg)

(mg)

(mg)

Low-dose

75

10

12.5

Mediumdose

75

10

20

12.5

High-dose

75

10

40

12.5

PolyPill
January 19, 2007 (Hyderabad, India) . Just three and a half years on from the first
proposal for a polypill, an Indian company has begun clinical trials of such a product,
containing aspirin, lisinopril, simvastatin, and atenolol, in 250 Indian patients who have
already had a cardiovascular event.
Raghu Cidambi (Dr Reddy's Laboratories, Hyderabad, India) told heartwire the company
hopes to gain Indian approval of this version of the polypill for secondary prevention on the
basis of this trial, which has already completed enrollment.
"We believe that we don't need an elaborate outcomes trial for secondary prevention," he
said. "It is our understanding that as long as there is solid evidence of no drug-drug
interaction and that the pill achieves its goals of reducing blood pressure and cholesterol,
it will be approved.

Managing the Patient at Risk Multiple Risk

Factors Require Multiple Interventions
Modifiable risk factors

Smoking
Diet
Sedentary lifestyle
Alcohol/drug abuse
Obesity
CAD
Atrial fibrillation
Hypertension
Diabetes
Dyslipidemia

Goldstein LB, et al. Stroke. 2001;32:280-299.

Unmodifiable risk factors

Age
Male sex
Race
Family history of
stroke/TIA

Prior stroke/TIA

CAD=coronary artery disease; TIA=transient

ischemic attack; CHD=coronary heart disease

CONSTITUENTS OF SECONDARY-PREVENTION POLYPILL

Version of
Polypill

Aspirin dose
(mg)

Lisinopril dose
(mg)

Simvastatin
dose (mg)

Atenolol dose
(mg)

Low-Dose

75

10

25

Medium-Dose

75

10

20

50

High-Dose

75

10

40

50

CONSTITUENTS OF PRIMARY-PREVENTION
POLYPILL
Version of
Polypill

Aspirin dose
(mg)

Lisinopril dose
(mg)

Simvastatin
dose (mg)

Hydrochlorothiazide
(mg)

Low-Dose

75

10

12.5

Medium-Dose

75

10

20

12.5

High-Dose

75

10

40

12.5

Wald NJ and Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003; 326:1419.

NO TODO SE LOGRA CON MEDICACION