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Author: Alan Weder, M.D., 2008
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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.
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
“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
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