HYPERTENSON TREATMENT A SUCCESS STORY

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HYPERTENSON TREATMENT A SUCCESS STORY
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• On Feb. 14, 2007 a 2-hour program on P.B.S. -
• Documentary Heart Disease in America
• Excellent review of risk factor concepts
• Emphasis on sudden death - Gloom Doom
• Little attention was paid to dramatic decreases
  in
• morbidity/mortality as a result of
  modification of
• risk factors

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Many papers or lectures on Hypertension have
been introduced as follows Hypertension
treatment and control rates at goal BPS are
unacceptably low. New methods for specific
diagnoses and new novel treatments for
hypertension must be found to improve outcome.
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The literature tells us that1-Prevalence of
hypertension is increasing.2-Goal BP is being
reached in fewer and fewer diabetics3-ESRD is
increasing ----a discouraging picture??? Are
these just attempts to change approaches to
management?
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JUST THE FACTS PLEASE
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Coronary Heart Disease Deaths 1980-2000
341,745 fewer deaths from CHD in 2000
(from 543/100,000 to
267/100,000) About 47 of benefit attributable to
Rx post MI, revascularization for
angina, etc 44 are probably result of changes in
risk factors 24 cholesterol 20 BP 12 smok
ing 5 exercise These are partially offset by
BMI diabetes
N Eng J Med 200735623
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Approximately 149,600 decrease in CHD deaths
from 1980 to 2000 were attributable to changes
in risk factors Decrease in SBP by only 5.1 mm
Hg - 69,800 Decrease in Chol 13 mg/dL -
82,800 Decrease in smoking prevalence by 11 -
39,900
N Eng J Med 200735623
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AN HISTORIC JOURNEY WE SOMETIMES FORGET WHERE
WE HAVE BEEN
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Comments about Hypertension-1931
The greatest danger to a man with high blood
pressure lies in its discovery, because then some
fool is certain to try and reduce it.
Hay, Brit Med J, 1931
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Hypertension may be an important compensatory
mechanism which should not be tampered with,
even were it certain that we could control it.
Paul Dudley White, 1931
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It is well to emphasize that many cases of
essential hypertension not only do not need
any treatment but are much better off without
it.
Tice, Practice of Medicine, 1946
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1946 Textbook - Diseases of the Heart,
Friedberg People with mild
benign hypertension with levels up to 210/110
need not be treated There is a
psychopathologic personality associated with
hypertension
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Benign Hypertension
No. 300 Av. age at time of diagnosis 40
yrs Av. follow up 14 yrs Complications
Percent CHF
27 Cardiac enlargement 68 CVA 10 Pr
oteinuria 14 One is forced to conclude
that..hypertension lasts longer than generally
supposed - causing death most frequently in the
fifties.
Perera.In Bell ET. Hypertension, Minnesota Press,
1957
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Treatment of Hypertension
Remedies suggested - watermelon and cucumber
seeds, mistletoe and garlic - red meat and sex
were forbidden.
Page, late 1940s
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1940s - 1950s
Treatment of Hypertension

• Injection of typhoid bacilli
• Kempner Rice Diet
• Sympathectomy -Adrenalectomy
• Ganglion and peripheral blocking agents

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Goodman and Gilman The
Pharmacologic Basis of Therapeutics,
1941
10 mentions of hypertension in 1386 pages
Therapy of Hypertension Barbiturates Thi
ocyanates Bismuth Bromides
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1949
Dr. page, after trying pyrogen injections with
some success in patients with malignant
hypertension, stated that I need hardly say
this is an unpleasant treatment but considering
the danger of the disease to the life of the
patient it is a small price to pay for the
benefits.
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HYPERTENSION TREATMENTS
Year Treatment Non Drug Treatment 1922 Strict
low-sodium diet 1929 Lumbar
sympathectomy 1930s - 1950 Sedatives
1944 Kempner rice diet
Year Treatment Early Antihypertensive
Drugs 1930s Veratrum alkaloids 1940s Thiocyanate
s 1948 Antimalarials 1949 Reserpine Phenoxybenza
mine 1950 Ganglion blockers 1951 Vasodilato
rs Monamine oxidase inhibitors 1953 Centra
l Alpha agonists
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The role of height, weight and use of alcohol or
tobacco in hypertension In the opinion of the
committee there is sufficient evidence to
justify the con- clusion that none of these are
concerned in the genesis of primary diastolic
hypertension.
Report of the AHA Committee on Hypertension, 1957
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HYPERTENSION TREATMENTS
Year Treatment The Modern Era of Drug
Therapy 1957 Chlorothiazide 1959
Peripheral sympathetic nerve
blockers 1959 Aldosterone
antagonists 1962 B-blockers
Year Treatment 1964 Loop
diuretics 1970 Alpha-beta blockers
Calcium channel
blockers 1974 Nitroprusside
1980 Angiotensin converting
enzyme inhibitors 1990s Angiotensin
II receptor blockers
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Early 1950s
Preferred Therapy for Hypertension
1) A combination of rauwolfia and ansolysen 2) A
combination of hydralazine and
hexamethonium or 3) A
combination of hydralazine, rauwolfia and
ansolysen
Moser M, Mattingly TW, Postgrad Med 1955
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FDRA Classic Case of Untreated Hypertension
Blood pressure(mm Hg)
Complications
Treatment
Year
PhenobarbitolLow-salt and low-fat
dietMassagesDigitalis
LVH CHF Renal failure
CVAs
April 12, 1945, cerebral hemorrhage. Death at
63.

BruenHG. Ann Intern Med. 197072579-591.
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Reversal of Malignant Hypertension With
Antihypertensive Combinations
280
Parenteral ganglion-blocking agents
29-year-old woman with malignant hypertension
260
240
220
200
BP(mm Hg)
180
160
140
120
100
80
60
LVHPapilledemaBUN, 26 mg/dL
Fundi, grade 1BUN, 18 mg/dL
Fundi, grade 1BUN, 15 mg/dLECG Normal
BUN, 18 mg/dL
Moved lost to follow-up


Therapy
Hydrochlorothiazide 50 mg/day

Rauwolfia 50 mg/day
Year
1954
55
56
57
58
59
60
61
62
63
64
65
66
78
Hydralazine 200 mg/day Guanethidine 20-30
mg/day Mecamylamine 40-60 mg/day
Moser M. The Treatment of Hypertension. Le Jacq,
2002.
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Response to Rauwolfia, Hydralazine, and
Ganglion- Blocking AgentsWith Addition of
Thiazide
42-year-old male with Stage 4 hypertension and LVH
270
BUN, 13.6 mg/dL
BUN, 12.8 mg/dL
BUN, 14.4 mg/dL
250
V5
ECG normal
200
Thiazide
150
mm Hg
100
V6

LVH
1
50
2
3
4
5
6
Year
53
55
1956
1957
1958
1959
1960
1961
1962
1963
1964
1965
1 - Chlorothiazide 1 gm/d 2 - 2 - Mecamylamine
75 mg/d 3 - Hydrochlorothiazide 50 mg/d 4 -
Hydralazine 600 mg/d 5 - Guanethidine 10 mg/d 6
- Rauwolfia 50 mg/d
died suddenly at the age of 67 while chopping
wood. Moser M. The Treatment of
Hypertension. Le Jacq, 2002.
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Relationship Between GFR and Mortality in Renally
Impaired HypertensivesTreated vs Untreated, 2-5
Year Follow-Up
Treated
Untreated
Initial GFR(mL/min)
No.
Dead ()
No.
Dead ()

• gt100 19 10 14 3660-99 31 16 21 4340-59 5 20 10 1
  00lt40 7 43 9 100
• Total 62 18 54 61

Medications included hydralazine, rauwolfia
drugs, and ganglion-blocking agents. Moyer JH et
al. Am J Med. 195824177-192.
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Treatment of Hypertension1960
Subsequenttreatment
Initialtreatment
Next step
Next step
Classification
Moser M. The Treatment of Hypertension. Le Jacq,
2002.
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History of Hypertension
Milestones

• VA trial begins
• VA trial demonstrates the
• benefit of treating hypertension
• National High Blood Pressure
• Education program begins
• 1977 JNC I

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When to Start Antihypertensive Drug Therapy1977
Diastolic BP (mm Hg)
Antihypertensivetreatment
Age gt60 (y)
Age 40-59 (y)
Age lt40 (y)
At age gt70, treatment not advisable except in
severe cases.Simpson FO, 1977.
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Hypertension Guidelines the JNCs and Drug Therapy
JNC V
JNC I
Guidelines
JNC IV
Low-dose
.
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Results of PLACEBO CONTROLLED TRIALS

• Effect of Antihypertensive Drug
• Treatment on Cardiovascular Events

Reduction in Events
CHF Strokes LVH CVD CHD events Fatal/Non-fatal D
eaths Fatal/Non-fatal
Combined results from 17 randomized placebo
controlled treatment trials (48.000 subjects)
Diuretic or Beta-blocker based All differences
are statistically significant Moser,J Am
Coll Cardiol. 1996271214-1218 Arch Intern Med
1993S76-S71
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It is generally forgotten that hyper- tensive
vascular disease kills more people than cancer
and AIDS com- bined. But hypertension is a dull
disease to most of us, and its cure does not
excite as that of cancer does.
Page, Modern Medicine 1988
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Example of Some Attitudes Regarding Treatment
of Hypertension 1996
The strategic targets for our attention in
primary care should be patients with
severe hypertension (diastolic pressures over 110
mm Hg), elderly patients, those with diabetes,
patients who are at high risk for stroke, and
those with known heart disease.
Am Fam Phys 1996532427
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SOME NEW DATA CONFIRM THAT WE MUST BE DOING
SOMETHING RIGHT
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Hypertension in the Very Elderly HYVET Study
3845 people gt80 years of age
Baseline BPs 160-189 or ISH
gt140 (mm Hg) 90-109
lt 90
Low-dose diuretic (indapamide 1.5 mg SR)
ACE-I (perindopril 2-4 mg/d) added, if necessary
placebo-controlled Trial stopped early
Strokes
Mortality
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Status of Treatment Control in Hypertensive
Adults 1976 2007
Harris Poll
BRFSS
NHANES
1976-80 1988-91 1991-94 1999-2000
2003-2004 2007 2007
Percent
Self Reported
Specific Treatment 31 55 54 59
65 73 gt90 Control 10 29
27 34 37 ---- gt60
SBP lt140 mm Hg and DBP lt90 mm Hg
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A SUCCESS STORY INDEED
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Advice About the Early Treatment of Hypertension
A little fire is quickly trodden out which,
being suffered, rivers cannot quench.
Henry VIShakespeare
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(No Transcript)
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A few diseases may eventually predispose to
early hypertension- syphilis, chronic lead
poisoning, gout, and rheumatic fever. No evidence
that foci of infections in teeth or
tonsils responsible for hypertension.
Levine, Clinical Heart Disease, 1945
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Hypertension Treatment, 1946
In a patient with mild benign hypertension, i.e.,
blood pressure lt200/lt100 mm Hg, there is no
indication for use of hypotensive drugs.
Continued observation is desirable and
conservative treatment consisting of reassurance,
mild sedatives, and weight reduction is
indicated.
Friedberg. Diseases of Heart, 1946
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Antihypertensive Therapy 1970s - 1990s
1970s Alpha adrenergic inhibitors Alpha-Beta
blockers Converting enzyme inhibitors 1980s Calc
ium channel blockers 1990s Angiotensin-II (AT1)
receptor blockers
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A significant proportion of men who exhibited
a transient pressor response during examination
for military service later developed sustained
arterial hypertension. (3.6 x greater than
group without it)
Levy, et al. JAMA 194713577
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Physician Non Adherence or Inertia? Specific
treatment and control rates in hypertensive
patients have increased. BUT Approximately 30 of
treated patients do not have their therapy
changed, even when BPs remain elevated.
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Long-Term Blood Pressure Response to
Chlorothiazide Therapy
Average BP before addition of chlorothiazide
Average BP after addition of chlorothiazide
No. of cases
Average BP change

• Chlorothiazide 15 174/108 159/100 15/8
• Rauwolfia(chlorothiazide) 39 184/112 166/98 18/
  14
• Hydralazine Reserpine(chlorothiazide) 17 170/10
  2 156/94 14/8
• Mecamylamine Hydralazine Reserpine
  (chlorothiazide) 35 174/101 154/85 20/16
• Total 106

Moser M et al. AMA Arch Intern Med.
196289708-723.
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Hypertension Management
Benefits and various modalities of treatment
continue to be questioned. Are treatment trial
data being overanalyzed? Are the debates truly
based on science or on attempts to promote new
devices or medical treatments?