Author: Alan Weder, M.D., 2008

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Hypertension

M2 Cardiovascular Sequence

Dr. Alan Weder

Fall 2008

Key Points• Hypertension is a disease of blood pressure regulation

• Hypertension is a risk factor for atherosclerosis.

• Blood pressure measurement is important and requires attention to technique.

• Treatment decisions made in the context of overall risk factor burden.

• Secondary forms of hypertension are infrequently encountered and are usually recognized by resistance to treatment and distinctive biochemical features.

Hypertension

= high blood pressure

≠ being “hyper”, anxious

Blood pressure

n

A. Weder

Systolic(upper #)

Diastolic(lower #)

“Normal” is less than 140/90 mmHg

A. Weder

JNC-7* Blood Pressure Classification

<80and<120Normal

80–89 or120–139Prehypertension

90–99 or140–159Stage 1 Hypertension

>100 or>160Stage 2 Hypertension

DBP mmHgSBP mmHgBP Classification

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and treatment of High Blood Pressure JAMA 289:2560, 2003.

Burt et al. Hypertension. 1995;25:305

40% greater relative prevalence in African-Americans

Hypertension: Ethnic Variation (United States)

32.4

23.3 22.6

0

5

10

15

20

25

30

35

African African AmericanAmerican

WhiteWhite HispanicHispanic

Ag

e-ad

just

ed p

reva

len

ce o

f h

yper

ten

sio

n (

%)

Blood pressure regulation

• Hemodynamic (descriptive)

• Sympathetic nervous system (short-term)

• Renal pressure natriuresis (long-term)

Blood pressure regulationHemodynamic

Mean arterial blood pressure = Cardiac output X Peripheral vascular resistance

MAP = C.O. X TPR

See discussion in Lilly hypertension chapter

Blood pressure regulationSympathetic nervous system

BrainstemCarotid Sinus

Source: Undetermined

Source Undetermined

Mean Arterial Pressure (mmHg)

0 50 100 150

1

2

3

4

5

6

SodiumIntake

orOutput

(fold increase)

Chronic BP Regulation

Blood pressure regulationRenal pressure natriuresis

“Normal” Na Intake

A. Weder

Hypertension

Heart Failure

MyocardialIschemia and

Infarction

Stroke

Nephrosclerosisand Renal Failure

Retinopathy

Sequelae of Essential Hypertension

Cardiovascular Disease Risk by BP Status in Persons Aged 35–64 Years

Framingham Heart Study 36-Year Follow–Up

00

1010

2020

3030

4040

5050

Bie

nn

ial A

ge-

Ad

just

ed R

ate

per

100

0B

ien

nia

l Ag

e-A

dju

sted

Rat

e p

er 1

000

MenMen MenMen MenMen MenMenWomenWomen WomenWomen WomenWomen WomenWomen

Coronary Heart Disease

Stroke Peripheral Arterial Disease

Congestive Heart Failure

Risk ratio 2Risk ratio 2 22 44 33 2 2 44 4 3 4 3

Excess risk 23 12Excess risk 23 12 9 9 4 4 5 5 5 5 10 4 10 4

Normal Normal

HTNHTN

Risk ratio: Rate in HTN/Rate in Normals Excess risk: Rate in HTN - Rate in NormalsA. Weder

RISK

Trait Value

Trait level affects

risk of disease(risk factor)

A B C

1 1 12 2 3Total

Total burden of risk factorsaffects disease severity Total

Total

A. Weder

A. Weder

Cornary Heart Disease Mortality vs Usual BP by Age

Prospective Studies Collaboration. Lancet. 2002;360:1903-1913.

Systolic Blood PressureSystolic Blood Pressure Diastolic Blood PressureDiastolic Blood Pressure

Usual Diastolic BP (mm Hg)Usual Diastolic BP (mm Hg)

50-5950-59

60-6960-69

70-7970-79

80-8980-89

Age at risk:Age at risk:

40-4940-49

256256

128128

6464

3232

1616

88

44

22

11

00

8080 9090 100100 1101107070

IHD

Mo

rtal

ity

IHD

Mo

rtal

ity

(flo

atin

g a

bso

lute

ris

k an

d 9

5% C

I)(f

loat

ing

ab

solu

te r

isk

and

95%

CI)

Usual Systolic BP (mm Hg)Usual Systolic BP (mm Hg)

50-5950-59

60-6960-69

70-7970-79

80-8980-89

Age at risk:Age at risk:

40-4940-49

256256

128128

6464

3232

1616

88

44

22

11

00

120120 140140 160160 180180

Components of CVD Risk Stratification in Patients With Hypertension

Major Risk FactorsMajor Risk Factors• SmokingSmoking• DyslipidemiaDyslipidemia• Diabetes MellitusDiabetes Mellitus• Age >60 yearsAge >60 years• Gender (men and postmenopausal women)Gender (men and postmenopausal women)• Family history of early onset Coronary Heart Disease: Family history of early onset Coronary Heart Disease:

– women <65 yearswomen <65 years– men <55 yearsmen <55 years

Source: JNC VI. Arch Intern Med. 1997;157:2413

X HypertensionDiabetesMellitus

Obesity

Hyperlipidemia

The “Metabolic Syndrome” is a Cluster of “Diseases of Civilization”

A. Weder

Rate of CHD in HypertensionRate of CHD in HypertensionAccording to Risk FactorsAccording to Risk Factors

Adapted with permission from Kannel WB. JAMA. 1996;275:1571

1201202202205050––––––

SBP (mm Hg)SBP (mm Hg)Cholesterol (mg/dL)Cholesterol (mg/dL)HDL (mg/dL)HDL (mg/dL)DMDMCigarette smoking Cigarette smoking LVH by ECGLVH by ECG

1601602202205050––––––

1601602592595050––––––

1601602592593535– – ––––

1601602592593535++ – –––

160160259 259 3535++++++

1601602592593535++++++

0

10

20

30

40

50

60

WomenMen

Rat

e (%

)R

ate

(%)

Blood Pressure Measurement

• Patients should be seated with back supported and arm bared and supported at heart level.

• Patients should refrain from smoking or ingesting caffeine for 30 minutes before measurement.

• Measurement should begin after at least 5 minutes of rest.

• Appropriate cuff size and calibrated equipment should be used.

• Both SBP and DBP should be recorded.

• Two or more readings should be averaged.

24-h BP ProfileTypical Medical Student

Time of day

23:00 02:00 06:00 10:00 14:00

Blo

od

pre

ssu

re (

mm

Hg

)

160

140

120

100

80

60

AwakeningSleepAwake Awake

SBP

DBP

A. Weder

Office

Home

120/80 mmHg 110/70 mmHg120/80 mmHg

160/90 mmHg

“White Coat” or “Office” Hypertension

Source Undetermined

Cu

mu

lati

ve I

nci

den

ce (

%)

16

12

10

8

6

4

2

0

14

0 2 4 6 8 10 12

Time (years)

<120/80 mm Hg

120-129/ 80-84 mm Hg

130-139/85-89 mm Hg

Impact of “Normal” BP on CV Disease Risk In Men

Vasan, et al. N Engl J Med. 2001;345:1291-97.

Objectives of the InitialEvaluation of Hypertensives

• To identify other risk factors or disorders that might guide treatment

• To assess presence or absence of target organ damage and cardiovascular disease

• To identify known causes

Evaluation Components

• Medical history

• Physical examination

• Routine laboratory tests

• Optional tests

Medical History• Duration and classification (stage)

• Patient history of cardiovascular disease

• Family history

• Symptoms suggesting causes of hypertension

• Lifestyle factors

• Current and previous medications

0 1 2 3 4 5

1 affected

1 before age 55y

≥2 affected

≥ 2 before age 55y

20-39 y40-49 y

Relative Risk for Hypertension

# of 1o

Relatives Age of hypertensiononset in offspring

Hypertension Runs in Families

Source Undetermined

Physical Examination• Blood pressure readings (two or more).

• Verification in contralateral arm.

• Height, weight, and waist circumference.

• Fundiscopic examination.

• Examination of the neck, heart, lungs, abdomen, and

extremities.

• Neurological assessment.

Objectives of the InitialEvaluation of Hypertensives

• To identify other risk factors or disorders that might guide treatment

• To assess presence or absence of target organ damage and cardiovascular disease

• To identify known causes (secondary HTN)

Causes of Hypertension

• “Essential” 90-95%

• Renal 3-5 %– Chronic renal failure– Renovascular disease

• 1o aldosteronism < 1%• Pheochromocytoma < 1%• Hypertension of pregnancy

Identifiable Causes of Hypertension Renovascular disease Primary aldosteronism Pheochromocytoma Pseudopheochromocytoma

Sleep apnea Drug-induced or related causes Chronic kidney disease Chronic steroid therapy and Cushing’s

syndrome Coarctation of the aorta Thyroid or parathyroid disease

Atherosclerotic Renovascular Disease

Courtesy of Dr. James Stanley, University of Michigan Division of Vascular Surgery

Vasoconstriction

Renin-Angiotensin-Aldosterone System

Angiotensinogen

Angiotensin I

Angiotensin II

ACEACE

ReninRenin

Aldosterone secretion

Sodium & fluid retention

Fromkidney

Fromliver

A. Weder

Atherosclerosis is a systemic disease

Courtesy of Dr. James Stanley, University of Michigan Division of Vascular Surgery

Courtesy of Dr. James Stanley, University of Michigan Division of Vascular Surgery

Courtesy of Dr. James Stanley, University of Michigan Division of Vascular Surgery

“String of Beads”

Fibromuscular Renovascular Disease (FMD)• Frequently bilateral• May be associted with cerebral arterial FMD

Courtesy of Dr. James Stanley, University of Michigan Division of Vascular Surgery

Courtesy of Dr. James Stanley, University of Michigan Division of Vascular Surgery

Courtesy of Dr. James Stanley, University of Michigan Division of Vascular Surgery

Clinical Clues Suggesting Renovascular Hypertension

• Onset of hypertension under age 25 or over age 55

• An abdominal bruit, particularly in diastole

• Refractory, accelerated, or malignant hypertension or worsening of previously controlled hypertension

• Undiagnosed renal failure, with or without hypertension (particularly with normal urine sediment)

• Acute renal failure precipitated by hypertension treatment, particularly with ACE inhibitors

• A unilateral small kidney (by any prior investigational procedure)

PathophysiologicEffects on

CardiovascularSystem

Ang IIAng IIAng IIAng IIAng IAng IAng IAng IAngiotensinogenAngiotensinogenAngiotensinogenAngiotensinogen

Renin

Na+/H2ORetention

K+, Mg++ Loss

AldosteroneAldosteroneAldosteroneAldosterone

ACE

Non-RAASStimulators

Aldosterone: Important Component of Renin-Angiotensin-Aldosterone System

A. Weder

RAASRAASAngiotensin IIAngiotensin IIRAASRAASAngiotensin IIAngiotensin II

Non-RAASNon-RAASPotassiumPotassium

Adrenocorticotropic HormoneAdrenocorticotropic Hormone

NorepinephrineNorepinephrine

EndothelinEndothelin

SerotoninSerotonin

Non-RAASNon-RAASPotassiumPotassium

Adrenocorticotropic HormoneAdrenocorticotropic Hormone

NorepinephrineNorepinephrine

EndothelinEndothelin

SerotoninSerotonin

AldosteroneAldosterone

Stimulators of Aldosterone

RAAS = renin-angiotensin-aldosterone system

1o Aldosteronism

Aldosteronesecretion

independent of normal regulators

A. Weder

Pheochromocytoma

• Tumors of chromaffin cells (adrenal or extra-adrenal)

• “Rule of 10s”– 10% are extra-adrenal– 10% of extra-adrenal are extra-abdominal

• “5 Ps”– Pressure, palpitations, perspiration, pallor,

pain

Secondary Hypertensions

Pheochromocytoma• Pl. free

metanephrine

99% sensitive and 89% specific

JAMA 287: 1427-1434, 2002

1o Aldosteronism• Plasma aldosterone-

renin ratio (ARR)PRA (ng/mL/hr)

Plasma aldosterone (ng/dl)

• ARR > 30 suggests 1o Aldosteronism

AJ Kid Dis 37:699-705, 2001

NorepinephrineEpinephrine

Pheochromocytoma = TumorPheochromocytoma = Tumor

Pseudopheochromcytoma = Pseudopheochromcytoma = Physiological hyperactivityPhysiological hyperactivity

Mayo Foundation for Medical Education and Research

Wikimedia Commons

Primary Prevention• Primary prevention offers an opportunity to

interrupt the costly cycle of managing hypertension.

• Lifestyle modifications have been shown to lower blood pressure

• A population-wide approach may reduce morbidity and mortality; trials are lacking.

• Most patients with hypertension do not sufficiently change their lifestyle or adhere to drug therapy enough to achieve control.

Goal of HypertensionPrevention and Management

• To reduce morbidity and mortality by the least intrusive means possible. This may be accomplished by

– Achieving and maintaining SBP < 140 mm Hg and DBP < 90 mm Hg.

– Controlling other cardiovascular risk factors.

Additional Source Informationfor more information see: http://open.umich.edu/wiki/CitationPolicy

Slide 5: A. WederSlide 6: A. WederSlide 7: Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and treatment of High Blood Pressure JAMA 289:2560,

2003.Slide 8: Burt et al. Hypertension. 1995;25:305Slide 11: Source UndeterminedSlide 12: A. WederSlide 14: A. WederSlide 15: A. WederSlide 16: Prospective Studies Collaboration. Lancet. 2002;360:1903-1913.Slide 17: JNC VI. Arch Intern Med. 1997;157:2413Slide 18: A. WederSlide 19: Adapted with permission from Kannel WB. JAMA. 1996;275:1571Slide 20: Slide Modified from Dzau VJ. J Cardiovasc Pharmacol. 1990:15(Suppl 5):S59-S64. Cohn JN. J Hypertens.1998: 16:2117-2124. Glasser SP

et al. Am Heart J. 1996: 131:379-384. Zhuo JL et al. Circulation. 1997: 96:174-182Slide 22: A. WederSlide 23: Source UndeterminedSlide 24: Vasan, et al. N Engl J Med. 2001;345:1291-97.Slide 28: Source UndeterminedSlide 33: Courtesy of Dr. James Stanley, University of Michigan Division of Vascular SurgerySlide 34: A. WederSlide 35: Courtesy of Dr. James Stanley, University of Michigan Division of Vascular SurgerySlide 36: Courtesy of Dr. James Stanley, University of Michigan Division of Vascular SurgerySlide 37: Courtesy of Dr. James Stanley, University of Michigan Division of Vascular SurgerySlide 38: Courtesy of Dr. James Stanley, University of Michigan Division of Vascular SurgerySlide 39: Courtesy of Dr. James Stanley, University of Michigan Division of Vascular SurgerySlide 40: Courtesy of Dr. James Stanley, University of Michigan Division of Vascular SurgerySlide 42: A. WederSlide 43: A. WederSlide 46: Wikimedia Commons, http://commons.wikimedia.org/wiki/File:Illu_adrenal_gland.jpg; Mayo Foundation for Medical Education and Research