Hypertension and Cardiovascular Disease (
description
Transcript of Hypertension and Cardiovascular Disease (
Blood Pressure & CV Disease
Stanley S. Franklin, MD University of California, Irvine
Korotkoff, 1905
Agenda: BP & CV Disease
BP as an independent risk factor for CV disease
Interaction of BP with other CV risk factors
JNC VI guidelines for determining risk & therapy
Hypertension intervention trials: what do they tell us?
Therapeutic strategies for successful goal BP
Agenda: BP & CV Disease
BP as an independent risk factor for CV disease
Interaction of BP with other CV risk factors
JNC VI guidelines for determining risk & therapy
Hypertension intervention trials: what do they tell us?
Therapeutic strategies for successful goal BP
Prevalence of Cardiovascular DiseasePrevalence of Cardiovascular Disease
10 20 30 40 50 60
High BP
CAD
CHF
Stroke
Other
50,000,000
12,200,000
4,600,000
4,400,000
2,800,000
Prevalence (millions)
BP=blood pressure, CAD=coronary artery disease, CHF=congestive heart failure
Estimated Number of Persons With Cardiovascular Disease in the US
American Heart Association® . 2000 Heart and Stroke Statistical Update. 1999.
(24%)
JNC VI BP Classification
Category
Optimal
Normal
High-normal
Hypertensionstage 1stage 2stage 3
Systolic
120
130
130–139
140–159160–179180
and
and
or
ororor
Diastolic
80
85
85–89
90–99100–109110
BP (mm Hg)
Adapted from JNC VI. Arch Intern Med. 1997;157:2413-2446.
4-Year Progression To Hypertension: The Framingham Heart Study
5
18
37
0
10
20
30
40
50
Optimal Normal High-Normal
Pati
en
ts (
%)
5
18
37
0
10
20
30
40
50
Optimal Normal High-Normal
Pati
en
ts (
%)
(<120/80 mm Hg) (130/85 mm Hg) (130-139/85-89 mm Hg)
Vasan, et al. Lancet 2001;358:1682-86
Participants age 36 and older
4-Year Progression To Hypertension: The Framingham Heart Study
16
26
50
0
10
20
30
40
50
Optimal Normal High-Normal
Pati
en
ts (
%)
16
26
50
0
10
20
30
40
50
Optimal Normal High-Normal
Pati
en
ts (
%)
Vasan, et al. Lancet 2001;358:1682-86
Participants age 65 and older
(<120/80 mm Hg) (130/85 mm Hg)
(130-139/85-89 mm Hg)
Residual Lifetime Risk of Hypertension in Women Aged 65 Years
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20
Years
Ris
k o
f H
yp
ert
en
sio
n (
%)
1952-1975
1976-1998
Vasan, et al, JAMA 2002;287:1003-1010.
How Does ABPM Work?
• Monitor programmed to take BP measurements repeatedly over 24 hours
• Patients go about normal activities
• Report shows variation in BP over time
• Monitor programmed to take BP measurements repeatedly over 24 hours
• Patients go about normal activities
• Report shows variation in BP over time
Burt VL et al. Prevalence of hypertension in the US adult population: Results from the Third National Health and Nutrition Examination Survey, 1988-1991. Hypertension. 1995;25:305-
313.
What Is the ‘Normal’ 24-Hour, Awake,and Sleep Blood Pressure?
• Recommendations of ASH (1996) and O’Brien & Staessen (1999)– Daytime <135/85 probably normal, >140/90
probably abnormal
– Nighttime <120/70 probably normal, >125/75probably abnormal
– 24 hour <130/80 probably normal, >135/85probably abnormal
• Recommendations of ASH (1996) and O’Brien & Staessen (1999)– Daytime <135/85 probably normal, >140/90
probably abnormal
– Nighttime <120/70 probably normal, >125/75probably abnormal
– 24 hour <130/80 probably normal, >135/85probably abnormal
135/85135/85
140/90140/90
ClinicClinicPressurePressure
SustainedSustainedHypertensionHypertension
White CoatWhite CoatHypertensionHypertension
TrueTrueNormotensionNormotension
MaskedMaskedHypertensionHypertension
Ambulatory PressureAmbulatory Pressure
Clinic BP versus ABP ?
18-29 30-39 40-49 50-59 60-69 70-79 80+0
70
80
110
130
150
18-29 30-39 40-49 50-59 60-69 70-79 80+0
70
80
110
130
150
0
70
80
110
130
150
0
70
80
110
130
150
DB
P(m
m
Hg
)
SB
P(m
m
Hg
)
DB
P(m
m
Hg
)
SB
P(m
m
Hg
)
DB
P(m
m
Hg
)
SB
P(m
m
Hg
)
DB
P(m
m
Hg
)
SB
P(m
m
Hg
)Men, Age (y) Women, Age (y)
Non-Hispanic BlackNon-Hispanic BlackNon-Hispanic WhiteNon-Hispanic WhiteMexican AmericanMexican American
Pulse pressurePulse pressure Pulse pressurePulse pressure
SBP & DBP by Age & Race/Ethnicity &Gender (US Population Age 18 Years, NHANES III)
Burt VI, et al. Hypertension.1995;25:305-313.
Age Distribution of Hypertensives in US Population (NHANES III and the 1991 Census)
3.7
9.5
13
21.3
23.7
19.2
9.6
0
5
10
15
20
25
30
18-29 30-39 40-49 50-59 60-69 70-79 80+
Hyp
ert
en
siv
es W
ith
in A
ge
Gro
up
(%
)
Franklin SS. J Hypertension. 1999;17(suppl 5):S29-S36.
Age Groups (y)
47.4 million 47.4 million hypertensiveshypertensives
26.0% of US 26.0% of US populationpopulation
26% 74%
<40 40-49 50-59 60-69 70-79 80+Age (y)
17% 16% 16% 20% 20% 11%
Distribution of Hypertension Subtype in the untreated Distribution of Hypertension Subtype in the untreated Hypertensive Population in NHANES III by AgeHypertensive Population in NHANES III by Age
ISH (SBP 140 mm Hg and DBP <90 mm Hg) SDH (SBP 140 mm Hg and DBP 90 mm Hg)IDH (SBP <140 mm Hg and DBP 90 mm Hg)
0
20
40
60
80
100
Numbers at top of bars represent the overall percentage distribution of untreated hypertension by age. Franklin et al. Hypertension 2001;37: 869-874.
Frequency of hypertension
subtypes in all untreated
hypertensives (%)
Mortality According to Blood Pressure in Men Age 50–69
DBP (mm Hg)SBP (mm Hg)
68–8283–87
88–9293–97
98–102
98–127128–137
138–147 148–157158–167
0
50
100
150
200
250
Mo
rta
lity
Ra
tio
(%
)
Actuarial Society of America: Blood Pressure Study 1939
Risk Pyramid: SBP and CHD Mortality for Men Screened in MRFIT
Adapted from Stamler J et al. Arch Intern Med. 1993;153:598-615.Hypertension Control. WHO Technical Reports Series, 1996. No. 862.
SBP (mm Hg) Excess CHD deaths (%) Men (%)
180 7.2 0.9170-179 6.8 1.2160-169 10.1 2.7150-159 19.5 6.2140-149 23.4 12.8
130-139 20.7 22.8 120-129 9.9 28.4 110-119 1.3 19.0 <110 0.0 6.1
High BP
Blood Pressure and Risk for Coronary Heart Disease in Men
Based on 30 year follow-up of Framingham Heart Study Subjects free of CHD at base line but not adjusted for other risk factors.
<7575-84
85-9495-104
105+
Diastolic Blood Pressure (mm Hg)
0
10
20
30
40
50
60
Ag
e-a
dju
ste
d A
nn
ua
l In
cid
en
ce
pe
r 1
00
0
Age 35-64 Age 65-94
<120120-139
140-159160-179
180+
Systolic Blood Pressure (mm Hg)
0
10
20
30
40
50
60
Ag
e-a
dju
ste
d A
nn
ua
l In
cid
en
ce
pe
r 1
00
0
Age 35-64 Age 65-94
*Men aged 35-57 years followed for a mean of 12 years Neaton and Wentworth, Arch Intern Med. 1992;152:56.
DBPDBP(mm Hg)(mm Hg)
SBPSBP(mm Hg)(mm Hg)
10090-99
80-8975-79
70-74<70
<120
120-139
140-159
160
Multiple Risk Factor Intervention Trial* (MRFIT) (Effect of BP on CHD Mortality Rate)
Pulse Pressure
• Increase in pulse pressure (PP) indicates greater stiffness in large conduit arteries, primarily the thoracic aorta.
• PP, therefore, is a surrogate measure of dynamic, cyclic stress during systole.
• PP may be a better marker of increased CV risk than either systolic BP or diastolic BP alone in older persons.
• Increase in pulse pressure (PP) indicates greater stiffness in large conduit arteries, primarily the thoracic aorta.
• PP, therefore, is a surrogate measure of dynamic, cyclic stress during systole.
• PP may be a better marker of increased CV risk than either systolic BP or diastolic BP alone in older persons.
PP = SBP – DBPPP = SBP – DBP
Agenda: BP & CV Disease
BP as an independent risk factor for CV disease
Interaction of BP with other CV risk factors
JNC VI guidelines for determining risk & therapy
Hypertension intervention trials: what do they tell us?
Therapeutic strategies for successful goal BP
Seven Countries Study: Absolute Risks of Death from CHD
Van Den Hoogen et al. NEJM. 2000; 342 (1): 3.
0
20
40
60
80
100
120
140
110 120 130 140 150 160 170
Systolic Blood Pressure (mm Hg)
Mo
rtal
ity
fro
m C
HD
(no
./10
,000
per
son
-yr)
U.S.
N. Europe
Mediterranean S. Europe
Inland S. Europe
Serbia
Japan
Estimated CHD Rate Over 10 Years According to Risk Factors
0
10
20
30
40
50
60
70
SBP (mm Hg) 120 160 160 160 160 160 160Cholesterol (mg/dL) 220 220 259 259 259 259 259HDL (mg/dL) 50 50 50 35 35 35 35Diabetes - - - - + + +Smoking - - - - - + +LVH by ECG - - - - - - +
Framingham Heart Study
Est
imat
ed 1
0-ye
ar
CH
D r
ate
(%)
Adapted from Kannel. JAMA 1996;275:1571.
MenWomen
Levels of risk associated with smoking,hypertension, and hypercholesterolemia
Smoking
Serum total cholesterol level(>240 mg/dL)
Hypertension(DBP >90 mm Hg)
x2.5
x7
x11x6x3
x3 x3
Adapted from Kannel WB, et al. Am Heart J. 1986;12:825-836.
None One Two Three
5%
0%
10%
15%
20%
25%
30%
MenWomen
17%19%
26% 27% 25% 24%22%
20%
8%12%
Four or more
Risk Factor Clustering with Hypertension
Risk Factor Clustering with Hypertension
Risk factor clustering with hypertension, ages 18-74 years. Framingham offspring.
Kannel WB. Am J Hypertens. 2000.
% o
f ris
k fa
ctor
s
Number of risk factors
Metabolic Syndrome: A Cluster of Abnormalities
(1) Hypertension (or Hi-Norm)
(2) Decreased HDL-C
(3) Increased triglycerides
(Small dense LDL-C
and ↑ Apo B)
(1) Hypertension (or Hi-Norm)
(2) Decreased HDL-C
(3) Increased triglycerides
(Small dense LDL-C
and ↑ Apo B)
(Insulin resistance &
Hyperinsulinemia)
(4) Impaired glucose tolerance
(Diabetes)
(5) Abdominal obesity
(Insulin resistance &
Hyperinsulinemia)
(4) Impaired glucose tolerance
(Diabetes)
(5) Abdominal obesity
Adapted from Reaven GM. Clinical Diabetes 1994;12:32-36.
Agenda: BP & CV Disease
BP as an independent risk factor for CV disease
Interaction of BP with other CV risk factors
JNC VI guidelines for determining risk & therapy
Hypertension intervention trials: what do they tell us?
Therapeutic strategies for successful goal BP
Components of CVD Risk Stratification in Hypertensive Patients
Adapted from JNC VI. Arch Intern Med. 1997;157:2413-2446.
Major Risk Factors
– Smoking
– Dyslipidemia
– Diabetes
– Age 60 years
– Gender (men and postmenopausal women)
– Family Hx of early CVD
(W <65 yrs, M<55 yrs)
Target Organ Damage/Clinical CVD
– Heart diseases- LVH- Angina or prior MI- Prior coronary revascularization- CHF
– Stroke or TIA
– Proteinuria, Nephropathy: SCR
– Peripheral arterial disease
– Retinopathy
JNC VI. Arch Intern Med 1997;157:2413.
JNC VI: BP Risk Stratification
• Risk Group A– No CV risk factors
– No diabetes, target-organ damage, or clinical CVD
• Risk Group B– At least one other risk factor: age >60, male gender or
postmenopausal status, dyslipidemia, smoking, +FH
– (No diabetes, target-organ damage, or clinical CVD)
• Risk Group C– Diabetes or target-organ damage or clinical CVD
with or without other risk factors
• Risk Group A– No CV risk factors
– No diabetes, target-organ damage, or clinical CVD
• Risk Group B– At least one other risk factor: age >60, male gender or
postmenopausal status, dyslipidemia, smoking, +FH
– (No diabetes, target-organ damage, or clinical CVD)
• Risk Group C– Diabetes or target-organ damage or clinical CVD
with or without other risk factors
JNC VI: Treatment Strategies by Risk Stratification Risk Groups
BP stage (mm Hg) A B C
High-normal Lifestyle Lifestyle Drug therapy*†
(130-139/85-89) modification modification
Stage 1 Lifestyle Lifestyle Drug therapy*
(140-159/90-99) modification modification (up to 12 mo) (up to 6 mo)‡
Stages 2+ Drug therapy* Drug therapy* Drug therapy* (≥160/≥100)
Risk GroupsBP stage (mm Hg) A B C
High-normal Lifestyle Lifestyle Drug therapy*†
(130-139/85-89) modification modification
Stage 1 Lifestyle Lifestyle Drug therapy*
(140-159/90-99) modification modification (up to 12 mo) (up to 6 mo)‡
Stages 2+ Drug therapy* Drug therapy* Drug therapy* (≥160/≥100)* Lifestyle modification should be adjunctive for all patients starting pharmacologic therapy.
† For patients with heart failure, renal insufficiency, or diabetes.‡ For patients with multiple risk factors, drug therapy should be considered in addition
to lifestyle modification.
Adapted from JNC VI. Arch Intern Med 1997;157:2413.
Intervention
Exercise
Weight reduction
Alcohol intake reduction
Sodium intake reduction
DASH diet
Intervention
Exercise
Weight reduction
Alcohol intake reduction
Sodium intake reduction
DASH diet
Lifestyle Interventions for Prevention or Treatment of Hypertension
Blood Pressure Effect
5-10 mm Hg (>30 min >3x/wk)
1-2 mm Hg/Kg
1 mm Hg/drink/d
1-3 mm Hg/40 mmol/d
3-10 mm Hg
Blood Pressure Effect
5-10 mm Hg (>30 min >3x/wk)
1-2 mm Hg/Kg
1 mm Hg/drink/d
1-3 mm Hg/40 mmol/d
3-10 mm Hg
Adapted from Cushman et al. Endocrine Practice 1997;3:106 & Sacks, et al. NEJM 2001;334:3
JNC VI Lifestyle Treatment Measures
Nonpharmacologic treatments are used for:
Lowering blood pressure
Reducing need for antihypertensive agents
Minimizing associated risk factors
Primary prevention of hypertension
Agenda: BP & CV Disease
BP as an independent risk factor for CV disease
Interaction of BP with other CV risk factors
JNC VI guidelines for determining risk & therapy
Hypertension intervention trials: what do they tell us?
Therapeutic strategies for successful goal BP
“Hypertension may be an importantcompensatory mechanism whichshould not be tampered with, even ifit were certain that we could control it.”
Paul Dudley White, Textbook of Cardiology, 1931
Randomized controlleddouble-blind trials
Animal, in vitro & cell models
Editorials, reviews, "expert" opinions
Case reports
Case series & Cross-sectional studies
Case-control studies
Cohort studies
RCT
DBRCT
Randomizedcontrolled trials
META-ANALYSES
Clin
ical stu
die
s
Non-randomized trials
The evidence pyramid
© G Reboldi, 2001
Hypertension Intervention Trials: 1959-1970
Trial Severity of Hypertension
CV events/yr. In CTRL Group
CV events/yr: CTRL vs Ther. Group
Harrington, et al (1959)
Malignant Hypertension
90% Mortality 90% vs 50% (Mortality / Yr)
VA Coop. Study (1967)
Severe (DBP 115 mmHg) 187/121
29% 10:1 (1.5 Yr.)
VA Coop. Study (1970)
Moderate (DBP 105-114 mmHg) 165/105
5.5% 3.5:1 (4.5 Yr.)
Trial Severity of Hypertension
CV events/yr. In CTRL Group
CV events/yr: CTRL vs Ther. Group
Harrington, et al (1959)
Malignant Hypertension
90% Mortality 90% vs 50% (Mortality / Yr)
VA Coop. Study (1967)
Severe (DBP 115 mmHg) 187/121
29% 10:1 (1.5 Yr.)
VA Coop. Study (1970)
Moderate (DBP 105-114 mmHg) 165/105
5.5% 3.5:1 (4.5 Yr.)
Stroke: - 38% (95% CI 31-45%)
Ischemic heart disease: - 16% (95% CI 8-23%)
Cardiovascular death: - 21% (95% CI 13-28%)
Source: meta-analysis of 17 RCTs (diuretics & B therapy) Average DBP reduction: 5-6 mmHg.
Antihypertensive treatment: Relative benefit for mild HTN
(DBP 90-104 mmHg)
Collins R, Peto R. In: Swales JD. Textbook of Hypertension, Oxford, UK, 1994
“Antihypertensive agents produce no obvious benefit in patients over 65” Fry J, Lancet 1974
“Hypertensive drugs should probably notbe given (in the elderly) unless the bloodpressure is more than 200/110 mm Hg.” Editorial, Br Med J, 1978
SHEP Trial:Design
• N: 4736; 43% male
• Age: >60 (mean age = 71 y)
• BP: SBP 160-219 and DBP <90
• Design: Placebo control, double blind• Active Rx: Chlorthalidone (atenolol as step 2)
• SBP difference: 12 mm Hg
• Duration: 4.5 years
• N: 4736; 43% male
• Age: >60 (mean age = 71 y)
• BP: SBP 160-219 and DBP <90
• Design: Placebo control, double blind• Active Rx: Chlorthalidone (atenolol as step 2)
• SBP difference: 12 mm Hg
• Duration: 4.5 years
JAMA 1991;265:3255
SHEP Trial:Design
• N: 4736; 43% male
• Age: >60 (mean age = 71 y)
• BP: SBP 160-219 and DBP <90
• Design: Placebo control, double blind• Active Rx: Chlorthalidone (atenolol as step 2)
• SBP difference: 12 mm Hg
• Duration: 4.5 years
• N: 4736; 43% male
• Age: >60 (mean age = 71 y)
• BP: SBP 160-219 and DBP <90
• Design: Placebo control, double blind• Active Rx: Chlorthalidone (atenolol as step 2)
• SBP difference: 12 mm Hg
• Duration: 4.5 years
JAMA 1991;265:3255
SHEP Trial:Cardiovascular Disease Endpoints
JAMA 1991;265:3255
All-cause death: - 10% (95% CI -121%)
Cardiovascular death: - 16% (95% CI 225%)
Coronary events: - 23% (95% CI 536%)
Stroke: - 30% (95% CI 1248%)
Source: meta-analysis of 7 RCTs (most placebo-controlled) n=13299, age 60+ years (average SBP reduction 10 mm Hg)
Treating isolated systolic hypertension in the elderly: Relative benefit
Staessen JA, et al. Lancet 2000; 355: 865-872
Meta-analysis of 5 Randomized Controlled Trials in Very Old People (Age >80 Years)
6%
-39%
-22%
-34%
-50
-40
-30
-20
-10
0
10
Stroke CHD CHF Death
6%
-39%
-22%
-34%
-50
-40
-30
-20
-10
0
10
Stroke CHD CHF Death
n=1,670n=1,670
p=.014p=.014
p=nsp=ns
p=.01p=.01
p=nsp=ns
Gueyffier F, et al. Lancet 1999;353:793-6Gueyffier F, et al. Lancet 1999;353:793-6
0 0.5 1 1.5
death
CVD death
Relative risk (95% CI)
treatment better
Endpoint
no treatment better
Long-term benefits of antihypertensive treatmentSecular trends in the Framingham Heart Study
Sytkowski PA, et al. Circulation 1996;93:697-703
Trial duration is <10 years; treatment benefits should be considered in the very long term (decades).
Drop-in effect (subjects under placebo are given active drug) and drop-out effect (drop-outs in the active treatment group.
Subjects included in the trials are generally healthier than those treated in the clinical practice (selection of low-risk subjects).
Secondary end-points & subgroup analyses difficult to interperet.
Trials & meta-analyses:What we do not know (...and maybe will never know)
Are “new” antihypertensive drugs more
effective than “old” ones in preventing
the complications of hypertension
?
Study Year N Follow-up Age Primary (years) (years) End-points (N/O)
UKPDS 1998 758 8.4 56.4 259/170
CAPPP* 1999 10985 6.1 52.4 363/335
STOP 2 1999 6614 5.0 76.0 438/221
INSIGHT 2000 6321 2.9 65.0 200/182
NORDIL 2000 10881 13.3 60.5 403/400
* proper randomization?
Randomized Controlled Trials: “New”: ACEI, CCB, B vs.“Old” Diuretic, B
UKPDS 39 captopril atenolol diabetes-related event
CAPPP captopril diur/-blockers MI + stroke + CV death
STOP 2 CCB/ACEI diur/-blockers MI + stroke + CV death
INSIGHT nifedipine diur + amiloride MI + stroke + CHD death + CHF
NORDIL diltiazem diur/-blockers MI + stroke + CV death
Randomized trials comparing (as primary endpoint) the effect of different drug classes on CV morbidity and mortality
Benefits of antihypertensive therapy: "new" vs "old" drugs
Primary endpoint
Relative risk (95% CI)
"new" better "old" better
0.51
1.5
200 400 600 800 1000
Power,%
50
60
70
80
90
100
Number of events per treatment group
=0.05 Power to detect a 15% between-group difference in event occurrence
Size (of the study) does matter!
Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet 2000; 356: 1955-1964
A Prospectively Planned Meta-analysis of Antihypertensive Treatment Trials
To minimize selection bias, studies selected:
before hypothesis were formulated
before outcomes were established
before results were known
CCB superior to placebo: strokes & CV deaths
ACE-I superior to placebo: strokes, CHD, CV deaths
0.5 1 1.5
* CCB 1251/11685 1234/11769 diur/-blockers
† ACE-I 1018/8097 1004/8064 diur/-blockers
‡ ACE-I 559/2440 619/2431 CCB
Benefits of antihypertensive therapyMajor cardiovascular events
* 99% of the events were from the INSIGHT, STOP-2 and NORDIL studies† identical results after excluding CAPPP‡ 94% of the events were from the STOP-2 study
Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet 2000; 356: 1955-1964
“Old” & “new” antihypertensive drugs:Where do we stand?
The efficacy of different antihypertensive therapies in preventing CV complications was compared directly in 6 randomized studies
No significant difference among the different drug classes in: combined primary end-points all-cause & cardiovascular mortality cardiovascular morbidity
CCB versus ACE-I: better for stroke prevention & worse for CHD prevention (vs ACE-1)
Are antihypertensive drugs that block the
renin-angiotensin system more specific in
preventing cardiovascular complications,
i.e. is it the BP, the agent, or both
?
HOPE StudyHypertension Outcomes Prevention Evaluation
(Cause-Specific Class C Disease) n=9297 patients with CVD, or diabetes and 1 additional risk factor
ramipril vs placebo; baseline BP 139/79 mmHg, 47% hypertensive
stroke (-31%), CHD (-19%), mortality (-15%), diabetes (-32%)
n=9297 patients with CVD, or diabetes and 1 additional risk factor
ramipril vs placebo; baseline BP 139/79 mmHg, 47% hypertensive
stroke (-31%), CHD (-19%), mortality (-15%), diabetes (-32%)
HOPE Study investigators. N Engl J Med 2000; 342: 145-153
Add-on placebo after treating hypertension with non-renin-AII drugs
Agenda: BP & CV Disease
BP as an independent risk factor for CV disease
Interaction of BP with other CV risk factors
JNC VI guidelines for determining risk & therapy
Hypertension intervention trials: what do they tell us?
Therapeutic strategies for successful goal BP
CV events
BP
Special Recommendations for Therapeutic Goal Blood Pressure
• For class A & B patients, treatment goal = SBP < 140
mm Hg &
DBP < 90 mm Hg (Should it be <150-160/<90 mmHg?)
• For high-risk class C patients, treatment goal =
DM: <130/85 mm Hg (<140/85 from trials)
CRI: <125/75 mm Hg (if >1 gm Uprotein/ 24h)
• For class A & B patients, treatment goal = SBP < 140
mm Hg &
DBP < 90 mm Hg (Should it be <150-160/<90 mmHg?)
• For high-risk class C patients, treatment goal =
DM: <130/85 mm Hg (<140/85 from trials)
CRI: <125/75 mm Hg (if >1 gm Uprotein/ 24h)
Approximately 50 Million Americans Have Hypertension
American Heart Association, February 1999.
Uncontrolled72.6%
Controlled27.4%
13.7 million
36 million
28% 22%
USA Canada UK
6%
24% 27% 25%
BelgiumItalyFrance
<140/90 mmHg
140/90 mmHg
Treated hypertensive subjects with BP <140/90 mmHg
9%
2%
India
Zaire
3%
10%
China
Egypt
85
69
91
48
92
34
0
20
40
60
80
100
DBP Goal SBP Goal
% C
ontr
olle
d
Age <=60 (n=295)Age 61-75 (n=533)Age >75 (n=361)
85
69
91
48
92
34
0
20
40
60
80
100
DBP Goal SBP Goal
% C
ontr
olle
d
Age <=60 (n=295)Age 61-75 (n=533)Age >75 (n=361)
Hypertension Control by Age Group
Cross-sectional analysis among 1189 treated hypertensive subjects from FraminghamLloyd-Jones Hypertension 2000;36:594
Why is ISH so Difficult to Treat to Goal?
1. Focus on DBP rather than SBP goal
2. Fear of reaching excessively low DBP
3. Failure to lower goal in high-risk subjects
4.Truly resistant systolic hypertension
5. Failure to use a diuretic
6. Failure to use poly-pharmacy
Rationale for Combination Drug Therapy in HypertensionNecessary for Good Control: All resistant, severe, or secondary hypertension Approx. 2/3 of mild/ moderate hypertension Almost all class C patients, esp. DM, CRI
Maximizes Efficacy: Supplementary mechanisms of action Blockade of contra regulatory mechanisms
Minimizes Side Effects: Lower doses of each drug May antagonize adverse pharm. actions of other drug
Number of Medications to Achieve Goal BP in 5 Trials of DM &/or Renal Disease
3.8
3.3
3.6
2.8
2.7
0 1 2 3 4
AASK (<92 mm Hg MAP)
HOT (<80 mm Hg DBP)
MDRD (<92 mm Hg MAP)
ABCD (< 75 mm Hg DBP)
UKPDS (<150/85 mm Hg)
Number of BP Meds
3.8
3.3
3.6
2.8
2.7
0 1 2 3 4
AASK (<92 mm Hg MAP)
HOT (<80 mm Hg DBP)
MDRD (<92 mm Hg MAP)
ABCD (< 75 mm Hg DBP)
UKPDS (<150/85 mm Hg)
Number of BP Meds
Bakris. Bakris. J Clin HypertensJ Clin Hypertens 1999;1:141-7 1999;1:141-7
Recommendations for Improving Outcomes
Physician
Establish treatment goals
Maintain adherence
Minimize side effects
Physician
Establish treatment goals
Maintain adherence
Minimize side effects
Patient
Self-Monitor BP
Keep diary of BP therapy
Make life-style changes
Patient
Self-Monitor BP
Keep diary of BP therapy
Make life-style changes
Summary: BP & CV Disease
BP as an independent risk factor for CV disease
Interaction of BP with other CV risk factors
JNC VI guidelines for determining risk & therapy
Hypertension intervention trials: what do they tell us?
Therapeutic strategies for successful goal BP