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HYPERTENSION TREATMENT A SUCCESS STORY. 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

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slide2

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
slide3

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.”

slide4

The literature tells us that—1-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?

slide6

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% smoking

5% exercise

These are partially offset by BMI & diabetes

*N Eng J Med 2007;356:23

slide7

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 2007;356:23

slide9

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

slide10

“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

slide11

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”

slide12

“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%

Proteinuria 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

slide13

William Evans, Chief of Cardiology, London Hospital – 1940s

Letter to a Friend

“I cannot but pour contempt on any who worry about a

complaint which is but a figment of the imagination…..

You have hypertension (if indeed your blood pressure has

been raised from time to time to values like 230/130), which

is a normal physiological state, and one which does not in

time change into the pathological state of hypertension.

So for goodness sake cease to worry about something

which cannot but make you unhappy.”

Clin Card. 2001

Clin Card. 2001

slide14

William Evans, Chief of Cardiology, London Hospital – 1940s

Letter to a Friend

“Above all, take no tablets, and keep away from doctors!

In no other fields do these two agents create greater

unwarranted invalidism than in this, where the blood

pressure in health is mistaken for that in disease.

I cannot bear to see healthy subjects made to suffer

from the mendations of medical meddlers.”

Clin Card. 2001

slide15

Treatment of Hypertension

…Remedies suggested - “watermelon

and cucumber seeds, mistletoe and

garlic” - “red meat and sex were

forbidden.”

Page, late 1940s

slide16

Goodman and Gilman

The Pharmacologic Basis of Therapeutics,

1941

10 mentions of hypertension in 1386 pages

Therapy of Hypertension

Barbiturates

Thiocyanates

Bismuth

Bromides

slide17

1940s - 1950s

Treatment of Hypertension:

  • Injection of typhoid bacilli
  • Kempner Rice Diet
  • Sympathectomy -Adrenalectomy
  • Ganglion and peripheral blocking agents
slide18

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.”

slide19

HYPERTENSION TREATMENTS

YearTreatment

Non Drug Treatment

1922 Strict low-sodium diet

1929 Lumbar

sympathectomy

1930s -

1950 Sedatives

1944 Kempner rice diet

YearTreatment

Early Antihypertensive Drugs

1930s Veratrum alkaloids

1940s Thiocyanates

1948 Antimalarials

1949 Reserpine

Phenoxybenzamine

1950 Ganglion blockers

1951 Vasodilators

Monamine oxidase inhibitors

1953 Central Alpha agonists

slide20

The role of height, weight and use of

alcohol or tobacco in hypertension

In the opinion of the committee there is

no evidence to justify the con-

clusion that any these are concerned

in the genesis of primary diastolic

hypertension.

Report of the AHA Committee on Hypertension, 1957

slide21

HYPERTENSION TREATMENTS

YearTreatment

The Modern Era of Drug Therapy

1957 Chlorothiazide

1959 Peripheral

sympathetic nerve

blockers

1959 Aldosterone

antagonists

1962 B-blockers

YearTreatment

1964 Loop diuretics

1970 Alpha-beta blockers

Calcium channel blockers

1974 Nitroprusside

1980 Angiotensin converting enzyme inhibitors

1990s Angiotensin II

receptor blockers

slide22

Nothing new under the sun -----combination therapy

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

fdr a classic case of untreated hypertension
FDR—A 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. Bruen–HG. Ann Intern Med. 1970;72:579-591.

reversal of malignant hypertension with antihypertensive combinations
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.

slide25

Response to Rauwolfia, Hydralazine, and Ganglion-

Blocking Agents—With 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.

slide26
Relationship Between GFR and Mortality in Renally Impaired HypertensivesTreated vs Untreated, 2-5 Year Follow-Up

>100 19 10 14 3660-99 31 16 21 4340-59 5 20 10 100<40 7 43 9 100

Total 62 18 54 61

Treated

Untreated

Initial GFR(mL/min)

No.

Dead (%)

No.

Dead (%)

Medications included hydralazine, rauwolfia drugs, and ganglion-blocking agents.

Moyer JH et al. Am J Med. 1958:24:177-192.

treatment of hypertension 1960
Treatment of Hypertension1960

Initialtreatment

Subsequenttreatment

Next step

Next step

Classification

Moser M. The Treatment of Hypertension. Le Jacq, 2002.

when to start antihypertensive drug therapy 1977
When to Start Antihypertensive Drug Therapy1977

Diastolic BP (mm Hg)

Antihypertensivetreatment

Age 40-59 (y)

Age >60 (y)*

Age <40 (y)

*At age >70, treatment not advisable except in severe cases.Simpson FO, 1977.

hypertension guidelines the jncs and drug therapy

JNC III

JNC 7

JNC II

JNC VI

1973 1976 1980 1984 1988 1993 1997 2003

>30 drugs

Diuretics

>50 drugs

ACEI, CAs

added

>80 drugs

7 options

NHBPEP

STARTS

>40 drugs

diuretics,

b-blockersAdded

>25 drugs

DBP 105Diuretics

>60 drugs

Diuretics/

b-blockers

  • 100 drugs
  • Diuretics
Hypertension Guidelines: the JNCs and Drug Therapy

JNC V

JNC I

Guidelines

JNC IV

Low-dose

.

results of placebo controlled trials
Results of PLACEBO CONTROLLED TRIALS

Effect of Antihypertensive Drug

Treatment on CardiovascularEvents

% Reduction in Events **

CHF Strokes LVH CVD CHD events

Fatal/Non-fatal Deaths 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. 1996;27:1214-1218; Arch Intern Med 1993;S76-S71

slide31

“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

slide32

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 1996;53:2427

slide34

Hypertension in the Very Elderly – HYVET Study

3845 people >80 years of age

Baseline BPs 160-189 or ISH >140

(mm Hg) 90-109 < 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

slide35

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

Treatment31 55 54 59 6573>90

Control* 10 29 27 34 37 ---- >60

*SBP <140 mm Hg and DBP <90 mm Hg

advice about the early treatment of hypertension
Advice About the Early Treatment of Hypertension

A little fire is quickly trodden out; which, being suffered, rivers cannot quench.

Henry VIShakespeare

slide39

“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

slide40

Hypertension Treatment, 1946

“In a patient with mild benign hypertension,

i.e., blood pressure <200/<100 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

slide41

Antihypertensive Therapy 1970s - 1990s

1970s Alpha adrenergic inhibitors

Alpha-Beta blockers

Converting enzyme inhibitors

1980s Calcium channel blockers

1990s Angiotensin-II (AT1) receptor

blockers

slide42

“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 1947;135:77

slide43

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.

long term blood pressure response to chlorothiazide therapy
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) 17 170/102 156/94 –14/–8

Mecamylamine Hydralazine Reserpine (+chlorothiazide) 35 174/101 154/85 –20/–16

Total 106

Moser M et al. AMA Arch Intern Med. 1962;89:708-723.

slide45

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?

slide46

“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

slide47

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