A1260830706zBGtn

1
Treating Hypertension in Special
Populations
Ronald G. Victor, M.D.
Chief, Hypertension Division
SO HWESTERN Medical Center
2
Two Contemporary Paradigmsin Antihypertensive Rx
CV Renal Protection
Drug Class (beyond BP)
BP Level
3
Special Populations

• Older patients
• African Americans
• Diabetics

4
Question
If a woman has a normal BP by age 65, what is her
risk of developing hypertension over the next 20
years?
5
Residual Lifetime Risk of HTN 90
100
Risk of HTN ()
50
1952-1975
1976-1998
0
0
5
10
15
20
Years
Vasan, et al, JAMA 2002
6
Question
Which hypertensive patient has the greater risk
of fatal MI 160/70 ?
or 150/110 ?
7
Aging and Blood Pressure
Pulse Pressure (SBP-DBP) widens with age. In
older persons, isolated systolic hypertension
is a major CV risk factor.
V Burt et al., Hypertension, 1995
8
Isolated Systolic Hypertension (ISH)
ISH SBP gt140 DBP lt90 mm Hg SDH SBPgt140 DBP
gt90 mm Hg IDH SBP lt140 DBP lt90 mm Hg
Frequency of hypertension subtypes in all
untreated hypertensives ()
lt40
40-49
50-59
60-69
70-79
80
Age (y)
Franklin et al. Hypertension 2001
9
Atherosclerosis vs. Arteriosclerosis
Atherosclerosis Arteriosclerosis
Distribution Focal Diffuse
Location Intima Media
Geometry Occlusive Dilatory
Pathology Plaque Elastin, collagen, Ca
Physiology Hemodynamics Inflammation Ischemia Large artery stiffness LV workload
10
Isolated Systolic Hypertension
11
Pulse Wave Reflection
Young compliant arteries normal PW velocity 8
m/sec
Systole
Diastole
(1) Peripheral amplification (2) ? coronary
blood flow
12
Pulse Wave Reflection
Elderly stiff arteries with ISH increased PW
velocity 12 m/sec
Systole
(1) Ventricular-vascular mismatch (2) The
reflected wave augments aortic BP in late systole

• ? Increased vascular afterload with a propensity
  to develop LVH
• ? Decreased coronary perfusion pressure
• ? Increased MVO2 and subendocardial ischemia
• ? Increased endothelial dysfunction and
  atherogenesis
• All recognized by a wide brachial artery pulse
  pressure

13
Risk of Fatal Stroke
9
Systolic
MRFIT
Diastolic
Rel. Risk
7
5
3
1
1
2
3
4
5
6
7
8
9
10
Decile
(lowest 10)
(highest 10)
Systolic
lt112 lt71
112- 71-
118- 76-
121- 79-
125- 81-
129- 84-
132- 86-
137- 89-
142- 92-
gt151 gt98
Diastolic
Stamler J, Stamler R, Neaton JD. Arch Intern Med
1993
14
Risk of Fatal CHD
300,000 men aged 35-57 years followed for a
mean of 12 years
Systolic BP mm Hg
Diastolic BP mm Hg
Neaton and Wentworth, Arch Intern Med.
199215256.
15
Treated Hypertensives
Systolic vs. Diastolic BP Goals
Systolic BP
Diastolic BP
DBP 90
100
90
SBP 140
80
57
60
at Goal
40
20
0
All
NHANES 1999-2000 (CD-ROM) NHANES III
(1988-1994).
16
Antihypertensive Drugs for Isolated
Systolic Hypertension
Proven to reduce CV events vs. placebo

• Thiazide diuretics (SHEP)
• DHP-CCBs (Syst-Eur, Syst-China)

17
Special Populations

• Older patients
• Diabetics
• Blacks

18
(No Transcript)
19
Metabolic Syndrome

• ? BP
• Abdominal obesity
• Insulin resistance
• Atherogenic dyslipidemia
• Proinflammatory state
• Prothrombotic state

SM Grundy et al., Arterioscler Thromb Vasc Biol.,
2004
20
U.S. Obesity Epidemic
1991
2002
lt10 1014 1519
2024 25
21
Type 2 Diabetes Epidemic
1991
1991
2001
1998
lt4 46 68
810 10
22
Treating Hypertension in Type 2 Diabetics

• 1. Achieving Goal BP?
• 2. Ancillary benefits of ACEIs/ARBs?

23
Tight Control of BP vs. Glucose
1991
Risk Reduction





p lt .05
Tight Glucose Control
Tight BP Control
144/82 vs. 154/87 mmHg
HBA1c 7.0 vs. 7.9
UKPDS 33, 38, BMJ, 1998.
24
Systolic vs. Diastolic BP Goals
JNC 7 BP Goals for Diabetics
Systolic lt130 Diastolic lt80
25
HOT Study Diabetic Subgroup n1,501
Diastolic BP Goal
25
Felodipine ACEI HCTZ
Major CV events/ 1,000 patient-years
20
p 0.005
15
10
5
0
Achieved DBP mmHg
85
83
81
Target DBP mm Hg
?90
?85
?80
Hansson et al., Lancet. 1998.
26
Systolic BP and Renal Protection
Systolic BP, mm Hg
180
130
138
146
154
0
-4

• GFR
• ml/min
• per
• year

Untreated HTN
-8
In a 50 y/o with GFR of 50 ml/min, dialysis will
be delayed 8Y if SBP is lowered to 134 vs. 144 mm
Hg.
-12
Modified from Bakris et al., AJKD, 2000.
27
Ancillary Benefits of ACEI/ARBs?
Angiotensinogen
Renin
Angiotension I
ACE
Angiotension II
AT1R
28
CV protection beyond BP?
Other drugs
Risk of CV events
BP
29
MICRO-HOPE studyCardiovascular Death
0.12
3,577 diabetics
Placebo

• Office BP
• -2/1 mmHg

0.09
Cumulative rate
0.06
Ramipril
37 risk reduction Plt0.0001
0.03
0.00
1500
0
500
1000
2000
Days of Follow-Up
Lancet 355253, 2000
30
HOPE ABPM Substudy
180
Ramipril n20
baseline
140
Blood Pressure mm Hg
year one
100
Placebo n18
60
1
3
5
7
9
11
13
15
17
19
21
23
Time hours
Svensson et al. Hypertension. 200138e28-e32.
31
LIFE Study 1195 Diabetics
24
25 Risk Reduction p0031

• of patients
• with 1st event
• MI
• stroke
• death

12
0
0
12
24
36
48
60
Study Month
L Lindholm et al. Lancet, March 23, 2002.
32
LIFE Study 1195 diabetics
mm Hg
180
Atenolol
Losartan
148 mmHg
140
146 mmHg
BP
100
79 mmHg
79 mmHg
60
0
12
24
36
48
Study Month
L Lindholm et al. Lancet, 2002.
33
Current Drug Trials and Systolic BPDiabetic
Patients
mm Hg
200
180
STOP-2
160
140
130
Entry
Rx
Mancia and Grassi. J.Hypertens. 2002201461-1464.
34
VALUE Trial Composite 10 Outcome
12
8
of subjects
Valsartan
Amlodipine
4
0
Months
0 6 12 18 24 30 36 42 48 54 60 66
Julius S et al. Lancet. June 2004363.
35
Question
How to test for a BP-independent effect of the
ARB?
36
CV Protection Beyond BP?
1.50
Recent trials
Older
Recent
ALLHAT/Dox
AASK L vs H
Older trials placebo
ATMH
ABCD/NT L vs H
1.25
EWPHE
ALLHAT/Aml
Older trials active
HEP
ALLHAT/Lis
HOPE
ALLHAT/Lis ?65
Plt.0001
HOT
ALLHAT/Lis Blcks
HOT M vs H
ANBP2
1.00
INSIGHT
CONVINCE
MIDAS/NICS/VHAS
DIABHYCAR
L vs H
ELSA
Odds Ratio (Experimental/Reference)
MRC
IDNT2
MRC2
LIFE/ALL
0.75
PART2/SCAT
LIFE/DM
PATS
NICOLE
PROGRESS/Per
PREVENT
PROGRESSION/Com
SCOPE
RCT70-80
0.50
RENAAL
SHEP
STONE
STOP 1
STOP2/CCBs
0.25
STOP2/ACEIs
Syst-China
Syst-Eur
UKPDS C vs A
Difference (reference minus experimental) in
Systolic BP (mm Hg)
UKPDS L vs H
Staessen et al. J Hypertens. 2003211055-1076.
37
BP-Lowering Treatment Trialists
Stroke
CHD
1.50
1.25
1.00
RR of Outcome Event
RR of Outcome Event
0.75
0.50
0.25
Systolic BP Difference Between Randomized Groups
(mm Hg)
Systolic BP Difference Between Randomized Groups
(mm Hg)
A CA vs placebo B ACE inhibitor vs placebo
C more intensive vs less intensive blood-
pressure-lowering D ARB vs control E ACE
inihibitor vs CA F CA vs diuretic or
ß-blocker G ACE inhibitor vs diuretic and
ß-blocker. Blood Pressure Lowering Treatment
Trialists Collaboration. Lancet.
20033621527-1535.
38
Renal protection beyond BP?
DHP-CCB
Other drugs
Risk of ESRD
ACEI or ARB
BP
39
DHP- CCB
BP
Afferent arteriole dilates
Ang II
Intraglomerular pressure can remain elevated
40
IDNT Renal Endpoint
1715 patients w/ HTN and diabetic nephropathy
Amlodipine
of subjects with Doubling of SCr, ESRD, Death
37 risk reduction irbesartan vs. amlodipine
Placebo
Irbesartan
0
6
12
18
24
30
36
42
48
54
60
Follow-up (months)
Lewis et al. NEJM, 2001.
41
IDNT 20 CV Endpoints
Secondary composite endpoint
CV death
Nonfatal MI
Hospitalization for HF
Stroke
Above-ankle-amputation
Relative Risk
FavorsIrbesartan
FavorsAmlodipine
www.fda.gov/ohrms/dockets/ac/02/slides/
3829sl_03_Bristol-Myers-IDNT_Clinical_EandS.pdf
T Berl et al., Ann Int Med, 2003
42
RENAAL Trial
Placebo
28 risk reduction
30
p.002
Losartan
of subjects with ESRD
20
10
0
0
12
24
36
48
Months
Brenner B et al., NEJM, 2001
43
RENAAL in Clinical Practice?
-12
Rate of loss of GFR mL/min/year
-6
0
Untreated HTN
Bakris et al., Am J Kidney Dis. 2000.
44
Multiple Agents Required to Approach Stringent BP
Goals
UKPDS (lt85 mm Hg, diastolic)
MDRD (92 mm Hg, MAP)
HOT (lt80 mm Hg, diastolic)
AASK (lt92 mm Hg, MAP)
RENAAL (lt140/90 mm Hg)
IDNT (?135/85 mm Hg)
4
3
2
1
Number of BP Medications
Modified from Bakris et al, Am J Kidney Dis.
200036646-661.
45
Drug Class vs. BP Level

On 3 Drugs
On ACEI or ARB

Hypertension Control in Dallas County Clinics
Non-diabetics 38 lt140/90 Diabetics
14 lt130/80
100
50
1.7 Drugs
n249
1.5 Drugs
K Spranger et al. Am J Med. 2004.
0
46
Special Populations

• Older patients
• Diabetics
• Blacks

47
Barry White(1944-2003)
Singer Barry White dead at 58 'I am thrilled
throughout my soul to be creating
music' Saturday, July 5, 2003
   
"It was just a series of things brought on by
his high blood pressure, which triggered kidney
failure and a stroke they just couldn't get on
top of," Shankman said.
48
Hypertension in Blacks
1. Why such advanced target organ damage at
a young age? 2. Preferred drug classes
Diuretics? DHP-CCBs? ACEIs/ARBs?
BP? Events?
49
Men
Hypertension Prevalence,
I Hajjar, T Kotchen, NHANES 1999-2000, JAMA, 2003
50
HTN Control Rates 40-59Y
100
Whites
80
60
with BP lt140/90
40
20
0
Women
Men
I Hajjar, T Kotchen, JAMA, 2003
51
Stroke Mortality Risk in U.S. Blacks vs. Whites
4
3
Relative Risk
2
Whites
1
0
gt85
45-54
55-64
65-74
35-44
75-84
Age, y
CDC, MMWR, 2000
52
Hypertension in Blacks
1. Why such advanced target organ damage at
a young age? 2. Preferred drug classes
Diuretics? DHP-CCBs? ACEIs/ARBs?
BP? CV risk?
53
QUESTION?
Are ACEIs and ARBs less effective
in Blacks?

• BP?
• CV protection?
• Renal protection?

54
Lisinopril
Chlorthalidone vs.
Amlodipine
Systolic BP
10 Endpoint
150
.2
Fatal MI/Non-Fatal CHD
.16
145
n 33,357 (35 Blacks)
.12
mm Hg
140
Cumulative CHD Event Rate
.08
135
.04
0
130
0
1
2
3
4
5
6
Years to CHD Event
Years
ALLHAT Officers, JAMA, 2002
55
Stroke Risk
Total
1.15 (1.02, 1.30)
Age lt 65
1.21 (0.97, 1.52)
Age gt 65
1.13 (0.98, 1.30)
Men
1.10 (0.94, 1.29)
Women
1.22 (1.01, 1.46)
Black
1.40 (1.17, 1.68)
Non-Black
1.00 (0.85, 1.17)
Diabetic
1.07 (0.90, 1.28)
Non-Diabetic
1.23 (1.05, 1.44)
0.50
1
2
Lisinopril Better
Chlorthalidone Better
JAMA, 2002
56
Importance of COMBINATION Rx
150
Whites (n170)
Blacks (n151)

140
Systolic
BP
mmHg
130
120
Baseline
Captopril
Captopril HCTZ
VA Cooperative Study Group, Br J Clin Pharm, 1982
57
JNC 7 on Combination Rx

• Most patients will require two or more
  antihypertensive drugs to achieve goal BP.
• If BP is gt20/10 mmHg above goal, initiate therapy
  with two agents, one usually should be a diuretic.

JAMA May 21, 2003
58
Final HTN Control Rates in ALLHAT
70
Whites
Blacks
with BP lt140/90

• Still on mono-Rx
• after Year 5
• 40 of women
• 35 of men

60
50
Women
Men
WC Cushman et al., J Clin Hypertens 2003
59
African American Study of Kidney Disease
(Baseline Proteinuria gt300 mg/d, n313)
Blood Pressure
Pre
Post
135/82
156/100
Ramipril
133/81
Amlodipine
157/100

• Additional drugs
• 1. loop diuretics
• 2. sympatholytics

Agodoa et al. JAMA, 2001
60
Longterm prognosis
BP lt 130/80
0
Ramipril
? GFR ml/min/1.73m2
-10
Amlodipine
-20
36
24
12
0
Months
61
?
Two Contemporary Paradigmsin Antihypertensive Rx
CV Renal Protection
Drug Class (beyond BP)
BP Level
62
Dallas Heart Study (DHS)
Dallas
63
Household Survey
n 6,101, Ages 18-65Y 54 Blacks
Computer-assisted structured interview
Blood Pressure X 5
64
(No Transcript)
65
Worst Hypertension Burden in Black Men
Black Men
HTN Prevalence
31
Control Rate lt 140/90 mm Hg
15
Dallas Heart Study 2000-2002 ages 18-65Y
66
DHS Blacks with HTN
Men
Unaware
46
15
Aware Untreated
13
Controlled
26
Treated Uncontrolled
67
Attitudes to Health Care Similar in Black and
White Men
Feels discriminated in health care
Believes erectile dysfunction common with Rx
Distrusts doctors
100
100
100
of men with hypertension
50
50
50
0
0
0
B
W
B
W
B
W
Dallas Heart Study 2000-2002 Ages 18-65Y
68
Hypertension Knowledge Gaps Equally
Prevalent in Black and White Men
Understands high BP requires lifelong Rx
Understands high BP usually asymptomatic
100
100
of men with hypertension
50
50
0
0
B
W
W
B
Dallas Heart Study 2000-2002 Ages 18-65Y
69
Odds Ratios (95 CI) for Hypertension Rx
Has a primary source of health care
Has correct medical knowledge about BP
Believes Rx causes erectile dysfunction
Believes in home/alternative remedies
0.5
1.0
2.0
4.0
Rx more likely
Rx less likely
(Also controlled for age, gender, ethnicity, BMI,
and diabetes)
70
Need for New Intervention Site in Black Men
Has Primary Care Physician
Whites
Blacks

Men
Women
Men
Women
Dallas Heart Study Hypertensive individuals ages
18-65Y
71
Barbershops for Hypertension Screening and
Referral

• Social environment
• User friendly hours
• Barber-client relation

Previous Barbershop Programs Ferdinand, J
Health Care Poor Underserved, 1997 Kong, J
Health Care Poor Underserved, 1997 Saunders,
Personal communication
72
Pilot Study Barbers can do BP too!
1200
1200
Haircuts
800
800
Adult Haircuts per Month
400
400
0
0
Dec
Jan
Feb
Mar
Apr
May
Jun
Jul
Aug
73
Barbershop HTN Rx Rates
80
70
Treated
60
50
40
Dec
Jan
Feb
Mar
Apr
May
Jun
Jul
Number of Hypertensives
156
237
224
298
275
255
299
151

74
Some treated patients still have not achieved
goal BP values...
147/84
75
?
Two Contemporary Paradigmsin Antihypertensive Rx
CV Renal Protection
Drug Class (beyond BP)
BP Level
76
Hypertension Prevalence
Germany
80
Finland
Italy
60
Canada
England

40
Sweden
Spain
20
United States
0
35-44
45-54
55-64
65-74
Age years
Wolf-Maier et al. JAMA. 2003.
77
Hypertension Prevalence vs. BMI African Diaspora
35
Maywood, IL.
30
St. Lucia
Barbados
Jamaica
25
Hypertension Prevalence
Cameroon urban
20
Cameroon rural
15
Nigeria
10
22 24 26 28 30
32
Average Body Mass Index
Cooper et al., Am J Public Health 1997
78
Current Drug Trials and Systolic BPNon-diabetic
patients
mm Hg
200
180
160
140
Entry
Rx
Mancia and Grassi. J.Hypertens. 2002201461-1464.