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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
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