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Hipertensión Arterialen el paciente Diabético
Consideraciones en el Manejo Clínico
Carlos [email protected]
Servicio de Nefrología y Programa de Trasplantes RenalesHospital Privado - Centro Médico de Córdoba
21-11-2008
2
PREVALENCIA DE HIPERTENSIÓNEN INDIOS LATINOAMERICANOS
Tobas: población urbanaAymara: población ruralYanomamo: población de la foresta/selva
Mancilha J et al. J Hum Hypertens 1989Perez F et al. Rev Med Chil 1999Bianchi M et al. XIII Latin American Congress of Nephrology and Hypertension 2004
0
15.0
30.0
Aymara (Chile)
6.4
27.0
Tobas(Argentina)
Yanomamo(Brasil)
%
0.0
3
Edad e Hipertensión Arterial en Argentina > 140/90
Hypertension in Diabetic Study J Hyperten 11:309–317 1993
Prevalence of hypertension in newly presenting type 2 diabetic patients
0
40
20
60
%50
30
10
70
160/90< 160/90
< 160/90 160/90
2.5
5.0
0
Rate of CV events before
diagnosis of diabetes
(%)
p=0.001
39 %
61 %
5
Rol del riñón en el mantenimiento de la HTA crónica
Hall J. Hypertension 2003
6
Increased renal sodium reabsorption and hypertension in obesity
Hall J. Hypertension. 2003
< 6 g salt/day(2,3 g / Na
o100 mmol/ Na)
7
Objetivos de Presión Arterialen el paciente Diabético
8
INDICATIONS FOR INITIAL TREATMENT AND GOALS FOR ADULT HYPERTENSIVE DIABETIC PATIENTS
Goal (mmHg) < 130 < 80
Behavioral therapy 130-139 80-89alone (maximum 3 months) then add pharmacologic treatment
Behavioral therapy + 140 90pharmacologic treatment
Systolic Diastolic
American Diabetes Association, Diabetes Care 2008
9
The risk of macrovascular and microvascular complications in diabetes is strongly
associated with blood pressure
UKPDS (36): BMJ 2000;321:412-419
10
Rat
e/10
00 p
erso
n/y
ear
25 –
20 –
15 –
10 –
5 –
0 –
P <0.005 for trend
25 –
20 –
15 –
10 –
5 –
0 – Diabetic
n: 1501All patients
n: 18790
< 90
< 85
< 80
DBP Goal
P <0.5for trend
Rate of major cardiovascular events according to Diastolic Blood Pressure
HOT Study: Lancet 1998
11
CASO CLINICO I
•Mujer de 19 años, estudiante de medicina (cursillo)•Diabética tipo 1 (5 años de diagnóstico)•Sobrepeso (BMI: 27.5), sedentaria, come salado•F de Ojos: normal•Insulinoterapia (Hb glic: 8.2%)•PA: 135/85 (idem en 2 consultas previas)
refiere PA domiciliaria de 110/70 no usa hipotensores
•Creatinina: 0.45 mg/dl •Albuminuria: 14 mg/g•K: 4.8 mEq/l
12
La PA nocturna predice el desarrollo de microalbuminuria en DBT tipo 1 normotensos
13
- 530 type 1 diabetes
- Normotensive
- 86%: Normoalbum.
3 mmHg diferencia PA
Idem Hb glicosilada
The Lancet 1997
14
¿Qué pueden aportar las medidas higiénico-dietéticas para lograr los
objetivos de Presión Arterialen el paciente Diabético ?
15
Beneficios en la PA con dieta Hiposódica y alto contenido de Frutas y Vegetales (K+)
Sacks F, et al. N Engl J Med 2001
Sodio: Alta: 150 mmol/d Media: 100 mmol/d Baja: 50 mmol/d
16
Rol atribuible al sobrepeso y obesidad en los factores de riesgo y eventos cardiovasculares:
Framingham Study
Wilson P, et al. Arch Intern Med 2002
17Neter J, et al. Hypertension 2003
Influence of Weight Reduction on Blood Pressure: A Meta-Analysis of Randomized Controlled Trials
A net weight reduction of 5.1 kg
18
¿ 130 / 80 ?
19
The decrease in risk for each 10 mm Hg reduction of SBP for macro and microvascular complications
UKPDS (36): BMJ 2000;321:412-419
20
Isquemia Miocárdica e HTA
Prospective Studies Collaboration, Lancet 2002
21
Stroke e HTA
Prospective Studies Collaboration, Lancet 2002
22
0
-2
-4
-6
-8
-10
-12
-14
GF
R (
ml/m
in/y
ear)
95 98 113110107104101 119116
130/85 140/90 Untreated HTN
r = 0.69; p < 0.05
MAP (mmHg)
Parving et al., Br Med J, 1989Viberti et al., JAMA, 1993Hebert et al., Kidney Int, 1994Lebovitz et al., Kidney Int, 1994Bakris et al., Kidney Int, 1996Bakris et al., Hypertension, 1997
Klahr et al., N Engl J Med, 1993Maschio et al., N Engl J Med, 1996GISEN Group, Lancet, 1997
Bakris et al., Am J Kidney Dis, 2000
Diabetes Non-diabetes
23
CASO CLINICO II
Varón 58 años, comercianteDiabético tipo 2 (>15 años de diagnóstico)Obeso (BMI: 31), fumador, come saladoF de Ojos: RD (no prolif.)HVIEdemas en tobillos ++PA: 155/95
Creatinina: 1.35 mg/dl (MDRD: 58 ml/min)Albuminuria: 200 mg/gK: 5.0 mEq/lLDL: 160 mg/dlHb glicosilada: 9.1 %
Med: Amlodipina 10 mg/d, ADO, AAS, Atorvastatina 10
24
¿Qué beneficios aportaríareducir la PA a este
paciente?
25
EFFECTS OF CALCIUM-CHANNEL BLOCKADE IN OLDER PATIENTS WITH DIABETES AND SYSTOLIC HYPERTENSION
Syst-Eur trial(Post-hoc analysis)
492 patients60 years or older
Placebo vs Nitrendipine2 years follow up
Initial BP: 175 / 85BP fall: Placebo 14 / 3
BP fall: Nitrendipine 22 / 7
Tuomilheto J, et al. N Engl J Med 1999
26
¿ Todos los hipotensores le darían iguales beneficios?
27
ACE inhibitors versus dihydropyridine calcium channel blockers in diabetic patients
0
12
9
6
3
%
ABCD trial
470 Hipertensive patients5 years follow up
MI: secondary end point
Nisoldipine
Enalapril
0
16
12
8%
4
Amlodipine
Fosinopril
FACET trial
380 Hipertensive patients3.5 years follow up
Combined End Point: MI, stroke, angina
28Smith et al., Kidney Int, 1998
Nifedipine (n = 10)Diltiazem (n = 11)
SBP 10
-50
-40
-30
-20
-10
0
DIFFERENTIAL EFFECTS OF 21 MONTHS OF CCBs THERAPY IN TYPE 2 DIABETICS WITH NEPHROPATHY
DBP 24 h proteinuira 100
-500
-400
-300
-200
-100
0
29
CAPPP study: ACE inhibitor therapy associated withreduction in endpoints : Diabetic vs Total population
Hansson L , et al. Lancet 1999
30
EFFECTS ON RAMIPRIL ON CARDIOVASCULAR AND MICROVASCULAR OUTCOMES IN 3.577 PATIENTS WITH TYPE 2 DIABETES ENROLLED IN THE HOPE STUDY
THE MICRO-HOPE STUDY
- age > 55 years- no clinical proteinuria- previous cardiovascular event or at least one other cardiovascular risk factor
HOPE Study Investigators, Lancet, 2002
31
0 25%- 50%
THE MICROHOPE STUDY
Relative Risk (95% CI)
Combined
Myocardial infarction
Stroke
Cardiovascular death
Total mortality
Revascularization
Overt nephropathy
Clinical outcomes for Ramipril and placebo group
Primary outcomes
Secondary outcomes
- 25%
HOPE Study Investigators, Lancet, 2002
32
THE DREAM STUDY
DREAM Trial Group, NEJM 2006
- 5269 participants without cardiovascular disease - Impaired fasting glucose levels or impaired glucose tolerance- Treatment: ramipril (up to 15 mg per day) or placebo- Follow up: 3 years (median)- Baseline BP: 136/83 (both groups)
33
ATENOLOL AND CAPTOPRIL IN REDUCING RISK OF MACRO AND MICROVASCULAR COMPLICATIONS: UKPDS 39
UKPDS (39) BMJ, 1998
- 1148 hypertensive type 2 diabetic patients
Myocardial infarction, sudden death, stroke, peripheral vascular disease and renal failure
-Less tight BP control: 154/87
-Captopril: 144/83
-Atenolol: 143/81
34
Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE):
Inclusion criteria
Design
Treatment
Follow-up
Main end point
- Diabetes (both types)- Hypertension SBP: 160 - 200 mmHg and/or DBP: 95 - 115 mmHg- Left ventricular hypertrophy
- Randomized, double blind
- Losartan (50 - 100 mg/day) n = 586- Atenolol (50 - 100 mg/day) n = 609
- 4.7 ± 1.1 years
- Combined cardiovascular mortality, stroke, miocardial infarction
Lindholm et al., Lancet, 2002
35
Blood pressure and metabolic control were comparable
in the two treatment groups throughout
the whole study period
Lingholm et al., Lancet, 2002
36
THE ANTIHYPERTENSIVE AND LIPID-LOWERING
TREATMENT TO PREVENT HEART ATTACK TRIAL (ALLHAT) n = 33,357
Patients
Design
Treatment*
Follow-up
Primary end-point
Age > 55 yearsAt least 1 risk factor
Randomized, double blind
Chlortalidone 12,5 – 25 mg/day Amlodipine 2,5 – 10 mg/dayLisinopril 10 – 40 mg/day
4 – 8 years
Major (fatal and non fatal) cardiovascular events
* The doxazosin arm was prematurely interrupted because of the significantly worse outcome as compared to the diuretic arm
ALLHAT Group, JAMA 2002
37
ALLHAT Study: Clinical Outcomes in Type 2 Diabetic Patients
Whelton P et al., Arch Intern Med. 2005
Coronary Heart Disease
All-Cause Mortality
Combined CHD
Stroke
Heart Failure
Combined CVD
ESRD
20.5 1
Favors Lisinopril Favors Chlortalidone
Coronary Heart Disease
All-Cause Mortality
Combined CHD
Stroke
Heart Failure
Combined CVD
ESRD
20.5 1
Favors Lisinopril Favors Chlortalidone
Diabetes MellitusNormoglycemia
38
THE ALLHAT STUDY
Throughout the whole study period, systolic blood pressure was significantly lower (2 mmHg) with chlorthalidone than with lisinopril
Lisinopril
Chlorthalidone
mm
Hg
Years
145
1300 1 2 4 53 6
135
150
140
Mean Systolic Blood Pressure
* p < 0.0001
*
** * * *
*
ALLHAT Group, JAMA 2002
39
Número de drogas usadas por paciente para lograr los objetivos de PA en
diversos estudios
40
Asociar IECAs con ARAII
Beneficios sobre la PA?Beneficios en el riesgo CV ?Beneficios en la nefropatía ?
41
42
CANDESARTAN AND LISINOPRIL MICROALBUMINURIA (CALM) STUDY
Adjusted risk reduction (at 24 weeks) in SBP, DBP, and urinary A/C ratio in 197 type 2 diabetics with hypertension and microalbuminuria
Mogensen et al., Br Med J, 2000
Candesartan Lisinopril Combination
n = 66 n = 64 n = 67
1
SBP (mmHg)
10 20 30 40 50
DBP (mmHg)
urinary A/C ratio (%)
1 10 20 30 40 50 1 10 20 30 40 50 60
16
20
16 + 20
mg/day
43Jacobsen et. al. J Am Soc Nephrol 2003
ADDITIVE EFFECT OF ACE INHIBITION AND ANGIOTENSIN II RECEPTOR BLOCKADE
- Crossover study
-Type 1 DM
-Overt nephropathy
-Treatment:
Placebo
Benazepril 20 mg/day
Valsartan 80 mg/day
Combination (full doses)
50
150
100
mm
Hg
Placebo
Blood Pressure
0
Benazepril Valsartan Combination
1000
500
mg/
24 h
s
Placebo
Albuminuria
0
Benazepril Valsartan Combination
44
-50
Tight BP controlTight glucose control
%%
MicrovascularMicrovascularComplicationsComplications
Any diabetic Any diabetic endpointendpoint
0
-10
-20
-30
-40
StrokeStrokeDMDM
deathdeath
**
****
**
UKPDS 38. BMJ, 1998
** p<0.05p<0.05
Comparison between the cardiovascular risk reduction Comparison between the cardiovascular risk reduction between tight glucose control vs tight BP controlbetween tight glucose control vs tight BP control