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

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


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


Pati

en

ts (

%)

16

26

50

0

10

20

30

40

50


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

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.

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

“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.)


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)


Severe (DBP 115 mmHg) 187/121

29% 10:1 (1.5 Yr.)


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: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

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






Hypertension and Cardiovascular Disease (

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