Update on the Management ofHypertention

Timothy A. Denton, M.D.Divisions of Cardiology and Cardiothoracic Surgery

Cedars-Sinai Medical CenterLos Angeles

Outline

• Role of BP• Etiology of HTN• Evaluation• JNC VI

Why do we need blood pressure?

Why do we need blood pressure?

• Get blood to the scalp• Distribute flow quickly

Classification of HTN

• Primary

• Secondary

Physiology of HTN

Primary Hypertension• ? Central / peripheral adrenergic• ? renal• ? hormonal• ? vascular

Physiology of HTN

Secondary• Wide Pulse Pressure

Aortic complianceStroke volume

•Normal Pulse PressureRenalEndocrineNeurogenicMisc

Etiology of HTN

•RenalChronic pyelonephritisGlomerulonephritisPolycystic kidneyRenovascularOther renal

•EndocrineOral contraceptivesAdrenocortical (Cushing, hyperaldo,

17 hydroxylase, 11-hydroxylase)PheochromocytomaMyxedemaAcromegaly

Normal Pulse Pressure•Neurogenic

PsychogenicFamilial dysautonomiaPolyneuritisIncreased intracranial pressureSpinal cord section

•MiscCoarctationIntravascular volumePolyarteritis nodosaHypercalcemiaAcute intermittent porphyriaPre-eclampsia

Etiology of HTN

•Decreased aortic compliance•Increased stroke volume

AIThyrotoxicosisHyperkinetic heart syndromeFeverAV fistula / PDA

Wide Pulse Pressure

Epidemiology of HTNDiagnosis % Population

PrimaryRenal Parenchymal RenovascularEndocrine Primary aldo Cushing’s Pheo Oral contraceptiveMisc

92-94

2-31-2

0.3<0.1<0.12-40.2

Harrison’s Principles of Internal Medicine, 12th Edition

JNC VI

Joint National Committee onPrevention, Detection, Evaluation,

and Treatment ofHigh Blood Pressure

JNC VI -- Arch Int Med 1997;157:2413

Category Systolic DiastolicOptimal <120 <80Normal <130 <85High-normal 130-139 85-89Hypertension Stage I 140-159 90-99 Stage II 160-179 100-109 Stage III >180 >110

Classification of HTN

JNC VI -- Arch Int Med 157:2413, 1997

Category Risk factors Target OrganDamage

CV Disease

Group A 0 0 0

Group B >1 (not DM) 0 0

Group C >1 or DM + +

Risk Classification

JNC VI -- Arch Int Med 157:2413, 1997

Category Group A Group B Group C

High-normal Lifestyle Lifestyle Drugs

Stage I Lifestyle Lifestyle (6 mo) Drugs

Stages II, III Drugs Drugs Drugs

Undertreatment

National Data on HTN

51

73

31

55

10

29

0

10

20

30

40

50

60

70

80

90

100

NHANES II NHANES III

National Health and Nutrition Examination SurveyII - 1976-1989, III - 1988-1991

Per

cen

t Aware HTN

Rx HTN

HTN Goal

Undertreatment of Hypertension

Percentage of Patients withBP > 160/90

46.339.4

0102030405060708090

100

Index 2 years

Office Visit

Pe

rce

nt

Berlowitz, NEJM 1998;339:1957

Undertreatment of Hypertension

Percentage of Patients with BP "controlled"

60.6

25

0102030405060708090

100

<160/90 <140/90

Threshold for "control"

Pe

rce

nt

Berlowitz, NEJM 1998;339:1957

Undertreatment of Hypertension

Increases in HTN Therapy

35

3.2

0102030405060708090

100

DBP>90 <90, <165

BP Findings

Pe

rce

nt

Berlowitz, NEJM 1998;339:1957

Classes of Anti-Hypertensives(1999 PDR)

Adrenergic blockersAlpha/Beta adrenergic blockersACE inhibitorsACE + Ca blockersACE + diureticsARB’sARB’s with diureticsBeta blockersBeta blockers with diureticsCalcium blockersDiureticsRauwolfia derivativesVasodilators

Preparations of Anti-Hypertensives by Class(1999 PDR)

Adrenergic blockersAlpha/Beta adrenergic blockersACE inhibitorsACE + Ca blockersACE + diureticsARB’sARB’s with diureticsBeta blockersBeta blockers with diureticsCalcium blockersDiureticsRauwolfia derivativesVasodilators

65

114542

156

25242

18

Total = 127

Special Considerations

In African-Americans: -- low probability of success with Beta blockers or ACE

or ARB’s

-- higher probability of success with diuretics or Ca blockers

If you have not achieved goal,

you must change your therapy

You push a medication’s doseto EFFECT

or SIDE EFFECTor maximal recommended dose

“The committee recognizes thatthe responsible clinician’sjudgment of the individual

patient’s needs remains paramount.”

JNC VI -- Arch Int Med 1997;157:2413

Compelling Indications

Condition RecommendedTherapy

DM (type 1) + proteinuria ACE

CHF (low EF) ACE, diuretics

Sys HTN diuretics, Ca blockers

MI beta blockers, ACE

JNC VI -- Arch Int Med 157:2413, 1997

Pressure/Volume Relation

Pressure = 150 mmHg

FluidFlux

Pressure = 120 mmHg

FluidFlux

Vasculature

Combination Drugs:A Different Animal

• Beta blocker + diuretic• ACE + diuretic• ACE + calcium blocker• ARB + diuretic• Diuretic + diuretic• “other” + diuretic

HOPE Trial

Heart Outcomes Prevention Evaluation Study

NEJM 2000;342:145-153

Backgroud

• Activation of renin-angiotensin-aldosterone system may be amortality risk factor

• ACE therapy can reduce MI’s Circ 1994;90:2056, Lancet 1992;340:1173,JNC VI NEJM 1992;327:669

HOPE Trial, NEJM 2000;342:145-153

Design

• Prospective, randomized• Two-by-two factorial

ramipril + vitamin E• 9,541 patients

HOPE Trial, NEJM 2000;342:145-153

Inclusion Criteria

• > 55 years old• CAD or CVA or PVD or

DM + (HTN or high LDL orlow HDL orcigarettes ormicroalbuminuria)

HOPE Trial, NEJM 2000;342:145-153

Run-In

• 10,576 patients• ramipril 2.5 mg qd 7-10 days

then placebo 10-14 days• 1,035 excluded

(noncompliance, side effects, creat, K, withdrawal)

HOPE Trial, NEJM 2000;342:145-153

Follow-up

• First follow-up 1 month• Subsequent follow-ups q 6 months• Scheduled for 5 years

HOPE Trial, NEJM 2000;342:145-153

Outcome Measures• Primary endpoint:

CV death or MI or CVA• Secondary endpoints:

All cause mortalityRevascularizationHospitalization for UA or CHFDM complicationsWorsening anginaCardiac Arrestany CHFUA with ECG changesDM development HOPE Trial, NEJM 2000;342:145-153

Results

Ramipril or other ACE Compliance100.0

87.4 85.082.2

75.178.8

0

10

20

30

40

50

60

70

80

90

100

0 1 year 2 years 3 years 4 years last visit

Visit

Per

cent

HOPE Trial, NEJM 2000;342:145-153

Angiotensinogen

Angiotensin I

Angiotensin II

ReninInhibitor

ACEInhibitor

AT1 receptorInhibitor

Renin

ACE

Endothelin-1

Vasopressin

Vaso-constriction

Vaso-dilatation

Adapted, Bonn, D. Lancet 1998;352:378

non-ACEalternativepathways(chymase,

cathepsin G,chymostatin

ATII generation)

Bradykinin

Inactiveproducts

ACE

? angioedema

cough

increase nitric oxide,prostacyclin

(improved endothelial function ?anti-atherosclerotic?)

hypotension

Results

Discontinued for Cough

1.87.3

0

10

20

30

40

50

60

70

80

90

100

Placebo Ramipril

Visit

Per

cent

HOPE Trial, NEJM 2000;342:145-153

Results

Systolic BP (placebo/ramipril)

139 137 138 139139 133 135 136

0

20

40

60

80

100

120

140

160

180

200

Baseline 1 month 2 years end

Visit

mm

Hg

HOPE Trial, NEJM 2000;342:145-153

Results

Diastolic BP (placebo/ramipril)

79 78 78 7779 76 76 76

0

20

40

60

80

100

120

140

160

180

200

Baseline 1 month 2 years end

Visit

mm

Hg

HOPE Trial, NEJM 2000;342:145-153

Results

HOPE Trial, NEJM 2000;342:145-153

Results

HOPE Trial, NEJM 2000;342:145-153

Outcome Ramipril(n=4,645)

Placebo(n=4,652)

P Value

MI, CVA or Death CV Death MI CVA

651 (14%)282 (6.1%)459 (9.9%)156 (3.4%)

826 (17.8%)377 (8.1%)570 (12.3%)226 (4.9%)

<0.001<0.001<0.001<0.001

Non-CV Death 200 (4.3%) 192 (4.1%) 0.74All Cause Death 482 (10.4%) 569 (12.2%) 0.005

Results

HOPE Trial, NEJM 2000;342:145-153

Outcome Ramipril(n=4,645)

Placebo(n=4,652)

P Value

Secondary Outcomes Revascularization Hosp for Unstable Angina DM complications Hosp for CHF

742 (16.0%)554 (11.9%)299 (6.4%)141 (3.0%)

852 (18.3%)565 (12.1%)354 (7.6%)160 (3.4%)

<0.0020.680.030.25

Other Outcomes CHF Arrest Worsening Angina New DM Unstable Angina w ECG

417 (9.0%)37 (0.8%)

1107 (23.8%)102 (3.6%)175 (3.8%)

535 (11.5%)59 (1.3%)

1220 (26.2%)155 (5.4%)180 (3.9%)

<0.0010.02

0.004<0.001

0.76

Results

HOPE Trial, NEJM 2000;342:145-153

Summary• Ramipril decreased

CV mortalityMI and CVAall-cause mortalityRevascularization ratesDM complicationsCHFWorsening anginaNew onset DM

• Effects were see in all groups except those withoutcardiovascular disease

HOPE Trial, NEJM 2000;342:145-153

Implications

• We have a new standard of care

• All patients with vascular disease should beconsidered for ACE inhibition (e.g., ramipril)

How to Initiate Therapy

• Initial Evaluation• Good history and physical exam (note comorbidities)• Take BP in both arms• Take BP at least 2 min apart and average them• Take BP at least on two separate office visits• Look for end-organ damage• Stratify patient• Initiate drug therapy based on comorbidity and risk

EyesspasmAV nickingexudatesedema

Evidence of End-organ Damage

NeckbruitsJVD

thyroid

HeartS4S3Murmur

Abdbruitsmasses

Extpulsesedema

Lungsrales

LabsChem ICBCLipidsECG

The patient must become expert on their own blood

pressure

Long-term Therapy

Take BP at home

Write each BP down in a logDate Time BP Pulse

• 1x / day• 2x / day• 3x / day• 3x / week• etc…..

Summary

• Please, find more hypertensive patients

• Please, treat more hypertensive patients

• Consider risk / comorbidities

• Please, achieve goal in more hypertensive patients