Hypertension: Does it matter how to lower blood pressure?
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Transcript of Hypertension: Does it matter how to lower blood pressure?
P H Y S I C I A N S ’ A C A D E M Y F O R C A R D I O V A S C U L A R E D U C A T I O N
Hypertension:Does it matter how to lower blood pressure?
Luis Ruilope, MDHospital 12 de Octubre,Madrid, Spain
Cardio Diabetes Master ClassOctober 15-17, 2010, Dublin
Slide lecture prepared and held by:
CARDIORENAL CONTINUUM
1- CVRF2- ASYMPTOMATIC TOD3- SYMPTOMATIC TOD
DiabetesNo diabetes
CVD
dea
th ra
te(p
er 1
0,00
0 pe
rson
-yea
r)250
0
200
150
100
50
Systolic blood pressure (mmHg)
< 120 120–139 140–159 160–179 180–199 200
‘Double jeopardy’: type 2 diabetes and hypertension and cardiovascular risk
1
2
3
75 %
25 %
COST
%EVENTS
Treatment is effective
Mean-DBP at randomisation 99 mm Hg, mean difference 5-6 mm Hg, n=37 000, mean time to event 2-3 years
Collins et al. Lancet 1990;335:827
•Results of antihypertensive therapy in randomised controlled trials
BENEFIT OF BP CONTROL
•A fixed amount of benefit corresponds to a fixed amount of drop in BP
BPLTTC Lancet 2003; 362: 1527– 35; Arch I ntern 1995;155:701-9
23% RR stroke
15% RR major CV events
Beneficios de pequeños descensos de PA
Risk Stratification
Other CVRF. OD or Disease
NormalSBP 120-129 orDBP 80-84
High Normal
SBP 130-139 or
DBP 85-89
Grade 1 HTSBP 140-159
or DBP 90-99
Grade 2 HT
SBP 160-179or
DBP 100-109
Grade 3 HT
SBP≥ 180or
DBP≥ 110
No other CVRF Average risk Average risk Low added
riskModerate added risk
High added risk
1-2 CVRF Low added risk
Low added risk
Moderate added risk
Moderate added risk
Very high added risk
3 or more CVRF, MS, OD or DM
Moderate added risk
High added risk
High added risk
High added risk
Very high added risk
Established CV or renal disease
High added risk
Very high added risk
Very high added risk
Very high added risk
Very high added risk
Initiation of antihypertensive treatment
Other CVRF. OD or Disease
NormalSBP 120-129 orDBP 80-84
High NormalSBP 130-139
orDBP 85-89
Grade 1 HTSBP 140-159
or DBP 90-99
Grade 2 HTSBP 160-179
or DBP 100-109
Grade 3 HTSBP≥ 180
orDBP≥ 110
No other CVRF No BP intervention
No BP intervention
Lifestyle changes for several months
then drug treatment if BP
uncontrolled
Lifestyle changes for several weeks
then drug treatment if BP uncontrolled
Lifestyle changes
+Immediate
drug treatment
1-2 CVRF Lifestyle changes
Lifestyle changes
Lifestyle changes for several weeks
then drug treatment if BP
uncontrolled
Lifestyle changes for several weeks
then drug treatment if BP uncontrolled
Lifestyle changes
+Immediate
drug treatment
3 or more CVRF, MS or OD
Lifestyle changes
Lifestyle changes and consider drug
treatment Lifestyle changes+
Drug treatment
Lifestyle changes+
Drug treatment
Lifestyle changes
+Immediate
drug treatmentDiabetes Lifestyle
changesLifestyle
changes +Drug treatment
Established CV or renal disease
Lifestyle changes
+Immediate
drug treatment
Lifestyle changes
+Immediate drug
treatment
Lifestyle changes+
Immediate drug treatment
Lifestyle changes+
Immediate drug treatment
Lifestyle changes
+Immediate
drug treatment
0 25 50 100 mg Losartan0 80 160 320 mg Valsartan0 75 150 300 mg Irbesartan
Reduction in diastolic BP (mmHg)
LosartanValsartanIrbesartan
-10
-8
-6
-4
-2
-0
Elmfeldt et al 2002
Meta-Analysis based on US New Drug Application Evaluation Reports
Candesartan
0 4 8 16 mg Candesartan
Non-fatal MI (excluding silent) + fatal CHD
Total coronary endpoint
Total CV events and procedures
All-cause mortality
CV mortality
Fatal/non-fatal stroke
Fatal/non-fatal HF
Development of renal impairment
0.5 1 2
ASCOT BPLA1
Amlodipine-based better
Atenolol-based better
Valsartan and Amlodipine: Cardiovascular Endpoints in High-risk Hypertension1,2
0.5 2
Primary cardiac compositeendpoint
Cardiac mortality
Cardiac morbidity
All MI
All congestive heart failure
All stroke
All-cause death
New-onset diabetes
1
VALUE trial2
Favorsvalsartan
Favorsamlodipine
Development of diabetes
1. Dahlöf et al. Lancet 2005;366:895–906; 2. Julius et al. Lancet 2004;363:2022–31
Amlodipine/Valsartan Provides Powerful BP Reductions Across Hypertension Severities1,2
Ad hoc analysis¶DBP 9099 mmHg, SBP 140159 mmHg‡DBP ≥100 mmHg, SBP ≥160 mmHgBP = blood pressure; DBP = diastolic BP; SBP = systolic BP; MSSBP = mean sitting SBP
1. Smith et al. J Clin Hypertens 2007;9:355–64 (Dose 10/160 mg)2. Poldermans et al. Clin Ther 2007;29:279–89 (Dose 5–10/160 mg)
Mild HTN1¶
Mea
n ch
ange
in M
SSB
Pfr
om b
asel
ine
(mm
Hg)
0
–10
–20
–30
–40
–50
n=69 n=140 n=15
–20
–43
–30
Moderate HTN1‡Baseline SBP≥180 mmHg2
0
–10
–20
–30
–40
–50
Prevent CKD
Prevent ESRD
Prevent Microalbuminuria
PreventStroke/CVD
PreventCVD/Stroke
Hypertension
Diabetes
Micro-albuminuria
Chronic Kidney Disease
OBJECTIVES:• BP <130/80 mmHg (<125/75 mmHg if U/prot >1
g/24h) with ACEi, ARBs, CCB’s, diuretics• Start with 2 drug-fixed dose combination if SBP
>20 mmHg and/or DBP >10 mmHg above target• Reduce proteinuria using ACEi, ARBs, Aldo-
antagonists ndCCBs (dCCBs may increase proteinuria)
• Slow GFR decline with ACEi, ARBs (dCCBs may not alter GFR decline, in the absence of an ACEi/ARB)
• Reduce CV Risk with ACEi• ACEi, ARBs and diuretics reduce CHF, ACEi and
ARBs do not worsen IR
OBJECTIVES:• BP goal <140/90
mmHg with ACEi, ARBs, CCB’s
• Other CVRF control, lipid profile
• Spot urine albumin/creatinine ratio
OBJECTIVES: • Intensive diabetes control
(HbA1c <6.5% or lower, PG fasting, postprandial)
• Intensive BP control <130/80mmHg
• RAS blockade• Lipid profile: TChol, LDL, HDL,
TGL goals…• Microalbuminuria - Proteinuria• Serum creatinine, GFR• Eye examination, ECG
OBJECTIVES:• BP goal <130/80 mmHg • ACEi, ARBs, combination• Treat other CRFs• Monitor urine Alb/Cr ratio
annually
Pre-Hypertension
IGTMetabolic Syndrome
Prevent
Prevent
Ruilope et al, Blood Press 2007rR Ruilope et al, Blood Press 2007
Baseline BP predicts progression to hypertension 4 year hypertension incidence rates,
adjusted for sex, age, BMI, and baseline BP
Age 35-64
5,3
17,6
37,3
0
10
20
30
40
50
60
Optimal Normal HighNormal
4 Ye
ar H
yper
tens
ion
Inci
denc
e %
Age 65-94
16
25,5
49,5
0
10
20
30
40
50
60
Optimal Normal High Normal
Optimal = <120/80 mm Hg Normal = 120-130/80-85 mm Hg High Normal = 130-139/85-89 mm Hg
Vasan RS Lancet 2001
Impact of high-normal BP on CV risk
Cumulativeincidence ofCV events(%)
PreHTN
PreHTN
Vasan RS et al. N Engl J Med 2001;345:1291-7
1210
86420
14
1210
86420
0 2 4 6 8 10 12Years
Optimal BP
High-normal BP
Normal BP
High-normal BP
Optimal BP
Normal BP
Women
Men
Optimal BP: <120/80 mmHgNormal BP: 120-129/80-84 mmHgHigh-normal BP: 130-139/85-89 mmHg
16
Cumulativeincidence ofCV events(%)
Kaplan-Meier curves of clinical hypertension in the two groups
Numbers under the graph refer to hypertension-free individuals
0 1 2 3 4
Years in study
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
% C
umul
ativ
e in
cide
nce Candesartan
Placebo
Candesartan 391 356 309 191 128Placebo 381 269 184 118 85
CONFIDENTIAL
ROADMAP BP goal (ie. < 130/80 mmHg):
0
10
20
30
40
50
60
70
80
90
100
Screening Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 Visit 7 Visit 8 Visit 9 Visit 10
% pts reaching goal BP <130/80mmHg% pts reaching BP <140/90mmHg
1 y 2 y 3 y6 mo3 mo1 moRand.
ALPINE
New-onset diabetes (n=362)
0123456789 p<0.05
No ofpatients
Lindholm LH, J Hypertens 2003
HCTZCandesartan
NormalLV structure and function
Hypertension HF
Overt heart failure
SmokingDyslipidaemiaDiabetes
ObesityDiabetes
LV remodelling
LVH
MISystolic
dysfunction
Diastolicdysfunction
Subclinical LV
dysfunction
Time: decades Time: months
Death
Progression from hypertension to heart failure
DN = diabetic nephropathy.Adler et al. Kidney Int. 2003;63:225-232.
Annual Transition Rates Through Stages of DN
No nephropathy
Microalbuminuria
Macroalbuminuria
Elevated plasma creatinine or Renal replacement therapy
2.0%(1.9% to 2.2%)
2.8%(2.5% to 3.2%)
2.3%(1.5% to 3.0%)
1.4%(1.3% to 1.5%)
3.0%(2.6% to 3.4%)
4.6%(3.6% to 5.7%)
19.2%(14.0% to 24.4%)
Hallan, S. I. et al. J Am Soc Nephrol 2009;20:1069-1077
HR (95% CI) for ESRD associated with urine albumin excretion
Primary composite endpoint of the LIFE stratified by time-varying albuminuria.
Ibsen H et.al J Hypertension 2004;22:1805
23
GUARD trial BP Results SBP
DBP
-20.49*
-13.05*
*P<0.0001 vs baseline; †P=0.0176 vs benazepril/amlodipine
-18.75*
-9.97*†
Cha
nge
in B
P fr
om b
asel
ine
Bakris G et.al. Kidney International 19 March 2008;doi:10.1038/ki.2008.102
PREVALENCE AND TREATMENT OF HYPERTENSION IN EUROPE
44% ( > 140/90 mmHg), age and sex adjusted
> 200 million europeans are actually treated
ACEi/ARB are the most widely used classes (30-50%)
ESH-ESC Guidelines recomend ACEi/ARB as initial therapy whenever there is a high added risk
Wolf-Maier et al, JAMA 2003; Wang et al, Arch Intern Med 2007; Falaschetti et al, Hypertension 2009; Corrao et al, J Hypertens 2008; Mancia et al, J Hypertens 2007.
ONTARGETONTARGET: Changes in urinary albumin excretion
0
0,5
1
1,5
2
2,5
UAE initial(mg/mmol)
Second yearRatio to initial
FinalRatio to initial
Ramipril Telmisartan Ram+Telm
<0.0001 0.0009
Occurrenceproteinuria
0.019
Mann J et al. Lancet 2008
Evolución de la proteinuria a lo largo del estudio
J Am Soc Nephrol 2005;16:3038-3045
CARDIORENAL CONTINUUM
1- CVRF2- ASYMPTOMATIC TOD3- SYMPTOMATIC TOD
Systolic Pressures (mean + 95% CI)
Average : 133.5 Standard vs. 119.3 Intensive, Delta = 14.2
Mean # Meds Intensive: 3.2 3.4 3.5 3.4 Standard: 1.9 2.1 2.2 2.3
Systolic Blood Pressure Over Timem
m H
g
N=5723
N=5700
Month
130.0 mmHg
129.3 mmHg
ACEI/HCTZ N=5762
ACEI/CCB N=5744
Jamerson K et.al. N Engl J Med 2008;359:2417-28
Blood pressure control according to clinic-based measurement and ambulatory monitoring
Clinic-based Control = 23.6%
Ambulatory monitoring control = 51.6%
Clinic-based control
Controlled(<140/90 mmHg)
No controlled (140/90 mmHg)
Ambulatory monitoring
control
Controlled (<135/85 mmHg)
18.2% 33.4%
No controlled(135/85 mmHg)
5.4% 43%
Banegas JR, Segura J, Sobrino J, Ruilope LM, et al. Hypertension 2007;49:62-68.
Am J Med 2009, december
Discrepancies between office and ambulatory blood pressure: clinical implications
José R. Banegas,a MD; Franz H. Messerli,b MD; Bernard Waeber,c MD; Fernando Rodríguez-Artalejo,a Alex de la Sierra,d MD; Julián Segura,e MD; Alex Roca-Cusachs,f MD; Pedro Aranda,g MD; Luis M. Ruilope,e MD
aDepartment of Preventive Medicine and Public Health. Universidad Autónoma de Madrid, and CIBER en Epidemiología y Salud Pública (CIBERESP), Spain. bDivision of Cardiology, St Luke's-Roosevelt Hospital, Columbia University College of Physicians and Surgeons, New York, USA. cDivision of Clinical Pathophysiology, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland.dHypertension Unit, Clinic Hospital, Barcelona, Spain. eHypertension Unit, Doce de Octubre Hospital, Madrid, Spain. fHypertension Unit, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. gNephrology Department, Hospital Regional Universitario Carlos Haya, Málaga, Spain.
Am J Med 2009; in press.
Office BP (mmHg) CHD Stroke Diabetes
<120/80 129 (88.4) 68 (82.9) 144 (81.8)
120-129/80-84 130 (75.6) 90 (73.2) 228 (74.3)
130-139/85-89 224 (65.1) 123 (59.7) 408 (57.1)
140-159/90-99 401 (45.2) 260 (43.0) 1142 (43.2)
≥160/100 205 (25.3) 126 (23.7) 624 (22.3)
Total 1089 (46.1) 667 (43.1) 2546 (38.3)
P for trend <0.001 <0.001 <0.001
N=4,729
Number and percentage of treated high-risk hypertensive patients whose 24-h ambulatory blood pressure is controlled (<130/80 mm Hg),
according to office blood pressure and type of associated disease