Download Hypertension: The Latest

9/25/2014
Hypertension:
The Latest
Frankel Cardiovascular Center
University of Michigan
Kim A. Eagle, MD
Director
Lecture Outline
• Epidemiology
• Etiology
• Pathophysiology
• Clinical Studies
• Management
• Refractory HTN
73 Million Americans Have Hypertension
Untreated HTN:  Life expectancy by 5 years
BAD NEWS
81.5%
90
80
•  Absolute # uncontrolled pts
– 1 billion HTN patients worldwide
74.9%
• #1 chronic disease mortality
– 7.6 million (13.5%) of all deaths
70
52.5%
60
50
40
29.1%
69.1%
30
**Improvement
35.1% (1988-94)
20
10
0
Prevalence Awareness
Treated
Controlled
NHANES 2007-2010
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Prevalence of Hypertension
by Age, Gender, and Race*
80
70
Population %
60
50
White Men
Black Men
White Women
Black Women
40
30
20
10
0
25-34
35-44
45-54
55-64
65-74
≥75
Age (Years)
*United States: 1988-1994.
AHA. Heart Disease and Stroke Statistics – 2003 Update
Woltz M. et al. Amer J Hypertens 2000;13:103-104.
Hypertension
A Risk Factor for Cardiovascular Disease
Coronary
Disease
Peripheral Artery
Disease
Stroke
Heart Failure
45.4
Biennial
AgeAdjusted
Rate per
1000
Patients
Normotensive
Hypertensive
22.7
21.3
Men
Women
2.2
9.9
6.2
3.3
Risk Ratio: 2.0
13.9
12.4
9.5
5.0
2.4
Men
3.8
7.3
Women
2.6
Men
2.0
6.3
3.5
2.0
Women
3.7
2.1
Men
4.0
Women
3.0
Kannel WB. JAMA 1996;275:1571-1576.
Effect of Systolic BP and Diastolic BP on
CHD Mortality: MRFIT Screenees
CHD Death Rate per
10,000 Person-Years
(N=316,099)*
48.3
37.4
31.0
20.6
16.9
10.3
100+
13.9
11.8
25.3
12.8
8.8
90-99
80-89
Diastolic BP
(mm Hg)
80.6
43.8
25.5
23.8
8.5
12.6
38.1
25.2
11.8
9.2
75-79
70-74
*Men aged 35-57 years followed for a
mean of 12 years.
<70
<120
24.9
160+
140-159
120-139
Systolic BP
(mm Hg)
Neaton et al. Arch Intern Med. 1992;152:56-64.
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Blood Pressure Patterns in the
General Population (NHANES III)
Men
Women
150
150
130
130
SBP
110
PP
SBP
110
80
PP
80
DBP
70
DBP
70
30-39 40-49 50-59 60-69 70-79  80
30-39 40-49 50-59 60-69 70-79
Age
 80
Age
Adapted from: Burt V. et al. Hypertension 1995;25:305-313.
Relative Importance of DBP and SBP as
Predictors of CHD as a Function of Age
1.0
Favors SBP
0.5
β(SBP)β(DBP)*
0.0
-0.5
Favors DBP
-1.0
p=0.008
-1.5
25
35
*The difference between SBP and DBP proportional
hazard regression coefficients, ie, β(SBP) – β(DBP), was
estimated for each age group.
45
55
Age (Years)
65
75
Franklin SS et al. Circulation 2001;103:1245-1249.
Risk of Adverse Outcomes by Age
and Blood Pressure
Aronow WS, et al. JAMA 2011;57;2037-2114.
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Hypertension Etiology
RISK FACTORS
Obesity visceral fat (~70% of HTN)
Aging (ISH)  compliance
Gender/Race AA, genetics (~30%),
mass (REE) Lean body mass/ muscle
Family History 30% BP
genetics/inherited
Metabolic DM, insulin resistance,
dyslipidemia, uric acid
Diet (Na, K, Mg, Ca), EtOH,
tobacco, caffeine, herbs, drugs
Lifestyle Stress level, anger,
sedentary/lack of exercise
SNS heart rate
PRIMARY HTN = 90% of cases
Angiotensin II Plays a Central Role in
Target Organ Damage
Atherosclerosis*
Vasoconstriction
Vascular hypertrophy
Endothelial dysfunction
A II
AT1
receptor
LV hypertrophy
Fibrosis
Remodeling
Apoptosis
GFR
Proteinuria
Aldosterone release
Glomerular sclerosis
Stroke
Hypertension
Heart failure
MI
DEATH
Renal failure
*preclinical data
LV = left ventricular; MI = myocardial infarction; GFR = glomerular filtration rate
Average Number of Antihypertensive
Agents Needed to Achieve BP Goals = 3.2
ALLHAT (<140/90 mm Hg BP)
2.2 medications with only 67% controlled
UKPDS (<85 mm Hg DBP)
ABCD (<75 mm Hg DBP)
MDRD (<92 mm Hg MAP)
HOT (<80 mm Hg DBP)
AASK (<92 mm Hg MAP)
1.0
1.5
2.0
2.5
3.0
3.5
Number of antihypertensive agents
4.0
MAP, mean arterial pressure.
Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.
Cushman WC et al. J Clin Hypertens 2002; 4:393-404.
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Use of Blood Pressure Lowering Drugs in the Prevention of
Cardiovascular Disease: Meta-Analysis of 147 Randomised Trials in the
Context of Expectations from Prospective Epidemiological Studies
Greater BP reductions yield larger CVD event benefits regardless of starting BP
BMJ 2009;338:b1665.
Management
of
Hypertension
Current Published Hypertension Guidelines
1. Eighth Joint National Committee (JNC 8) & related statements 2. American Society of Hypertension (ASH) & the International Society of Hypertension (ISH)
3. American Heart Association/American College of Cardiology/Centers for Disease Control
4. Canadian Hypertension Education Program
5. National Institute for Clinical Excellence (NICE)
… and a bunch of others
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JNC-8 Blood Pressure Classification
BP Classification
Normal
SBP mmHg
DBP mmHg
<120
and
<80
Prehypertension
120–139
or
80–89
Stage 1 HTN
140–159
or
90–99
Stage 2 HTN
≥160
or
≥100
Measurement and Definition
• Manual office avg. BP >140/90 (5 visits) unless
– Urgency/emergency
– Macrovascular target organ damage, DM,
CKD
– >180/110
– Avg. BP >160/100 3 visits
• Automated office BP>135/85
• Home BP>135/85
• Daytime ABPM>135/85
CHEP Guidelines.
Recommendations for Follow-Up Based on Initial
BP for Adults Without Acute End Organ Damage
Initial Blood
Pressure, mmHg
Normal
Follow-Up Recommended
Recheck in 2 years
Prehypertension
Recheck in 1 year
Stage 1 HTN
Confirm within 3 months
Stage 2 HTN
Evaluate or refer to source of care
within 2-4 weeks
For those with higher pressures
(eg.>180/110 mm/Hg), evaluate
and treat immediately or within 1
week depending on clinical
situation and complications
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Advantages of Home BP Monitoring
•
•
•
•
•
•
•
•
Better measure of “true” BP and “basal” BP
No white coat effect
Better assess BP control during entire day
Assess “masked HTN”
Better reproducibility and CV prognosis than office BP
Evaluate resistant and pre-HTN states
BP variability (day-to-day; day vs. night)
Assess BP during symptoms (lightheaded, spell, H/A)
Home BP Monitoring
• Targets
Sustained HTN
MASKED HTN
(10-15%)
Uncontrolled HTN
135/85
HOME BP
• HBP Schedule
<135/85 mmHg
(<130/80 high risk)
- Class IIa, Level B
7 days total minimum
Average 2-3 x in AM and in PM
Use trough values before meds
Discard day 1 readings
Average 12 measures
Use weeks 2-4 averages after treatment
change
Long-term: 1 week session per quarter
Sustained normal BP
Controlled HTN
White Coat HTN
(15-20%)
140/90
OFFICE BP
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Disparate Estimates of
Hypertension Control
Comparison of clinic systolic BP (SBP) and nighttime ambulatory SBP. Horizontal line represents the limit for normal
nighttime ambulatory SBP (120 mm Hg); the vertical line represents the limit for normal clinic SBP (140 mm Hg).
Pogue V, et al. Hypertension 2009;53:20-27.
White Coat HTN
NL BP
119.7 / 72.6
WC HTN
125.6 / 74.9
J Hypertension 2007;25:2193.
Masked HTN
Normal BP
119.7 / 72.6
Masked HTN
141.1 / 83.2
J Hypertension 2007;25:2193.
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Evaluation: Diagnostic Work Up
Risk Factors?
Comorbidities?
Target Organ
Damage?
Causes of HTN?
Careful History
and Exam
Evaluation: Risk Factors
Hypertension
Microalbumin
Inactivity
Dyslipidemia
Microalbuminuria
Diabetes Mellitus
Age
Cigarette Smoking
Family History
↓ GFR
Target Organ Damage
Assessment in HTN
• Cardiovascular ( ECG minimum, consider echo, stress testing)
– Left ventricular hypertrophy
– Angina or prior myocardial infarction (CHD risk equivalent)
– Prior coronary revascularization
– Heart failure
• Cerebrovascular ( brief neuro exam minimal)
– Previous stroke, hemorrhage or transient ischemic attack
• Chronic kidney disease ( basic chemistry, UA minimum)
– Increased creatinine, UMA/creatinine (>30mg/g)
• Peripheral arterial disease ( physical exam)
– Carotid disease
– ABI < 1.0
– Aortic disease
• Retinopathy ( fundiscopic exam)
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Echocardiography
• Routine use not recommended
• Use for Dx of LVH useful in selected
cases
• Indicated for suspected LV dysfunction
or CAD
• HPT and HF (EF)
CHEP Guidelines.
Prognosis and LV Hypertrophy
LVH ≥ 143 g/m3 (men), 102 g/m3 (women)
CVD
(per 100/4 years)
12
9
6
LVH
+
3
0
+
CVD
+
CVD
All-Cause
Mortality Mortality
IHD Risk Is Related to Microalbuminuria
and BP in Non-diabetics
Relative risk
N=2085, 10-y follow-up
6
5
4
3
2
1
0
Microalbuminuria
Systolic
Systolic
BP <140 BP 140–160
Normoalbuminuria
Systolic
BP >160
Borch-Johnsen et al. Arterioscler Thromb Vasc Biol 1999;19:1992.
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Controlling Hypertension
in Adults: JNC 8
Systolic 140-159 or diastolic 90-99
(Stage 1 hypertension)
• Lifestyle modification as a trial
• Consider adding thiazide
Recheck and review
readings in 3 months*
Systolic >160 or diastolic >100
(Stage 2 hypertension)
• Lifestyle modification and
• Thiazide and ACEI, ARB, or CCB
• Or consider ACEI and CCB
BP at goal?
No
Yes
• Thiazide for most patients or ACEI, ARB, CCB, or combo
• If currently on BP med(s), titrate and/or add drug from
different class
• Encourage self-monitoring
and adherence to meds
• Advise patient to alert
office if he/she notes BP
elevation or side effects
• Continue office visits as
clinically appropriate
Recheck and review
readings in 2-4 weeks*2
No
Yes
BP at goal?
• Optimize dosage(s) or add medications
• Address adherence, advise on self-monitoring, and
request readings from home and other settings
• Consider secondary causes
Recheck and review
readings in 2-4 weeks*2
*Recheck interval should be based on patient’s risk of
adverse outcomes.
This algorithm should not be used to counter the
treating healthcare provider’s best clinical judgment.
Hypertension 2013.
Consider referral to HTN specialist
Lifestyle Modifications (LM)
Modification
Approximate
SBP Reduction
(Range)**
Recommendation
Reduce weight
Maintain normal body weight (body mass index 18.5-24.9
kg/m2
5-20 mmHg/10kg
Adopt DASH*
Eating plan
Consume a diet rich in fruits, vegetables, and low-fat dairy
products with a reduced content of saturated and total fat
8-14 mmHg
a.
b.
Lower sodium intake
c.
Consume no more than 2,400mg of sodium/day
Further reduction of sodium intake to 1,500mg/day is
desirable since it is associated with even greater
reduction in BP; and
Reduce intake by at least 1,000mg/day since that will
lower BP, even if the desired daily sodium intake is not
achieved
2-8 mmHg
Physical activity
Engage in regular aerobic physical activity such as brisk
walking (at least 30 min/day, most days of the week)
4-9 mmHg
Moderation of alcohol
consumption
Limit consumption to no more than 2 drinks (e.g., 24oz.
beer, 10oz. wine, or 3oz. 80 proof whiskey) per day in most
men, and to no more than 1 drink per day in women and
lighter weight persons
2-4 mmHg
*DASH, dietary approached to stop hypertension
**The effects of implementing these modifications are dose and time dependent, and could be greater for
some individuals
National Institute of Health, 2004.
Suggested Medications for Treatment
Based on Certain Medical Conditions
Condition
Recommended Medications
Diuretic
BB ACEI ARB
CCB
Thiazide
CAD/PMI
●
●
Systolic HF
●
●
● or ●
Diastolic HF
●
●
● or ●
Diabetes
●
●
● or ●
Kidney Disease
Stroke/TIA
Aortic Disease
Aldo
ANT
●
●
● or ●
●
●
●
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JNC 8 RECOMMENDATIONS FOR THE MANAGEMENT OF HYPERTENSION:
1. New SBP treatment goal for >60 years old: <150/90 mmHg
2. Same DBP treatment goal for <60 years old: <90 mmHg
3. Same SBP treatment goal for <60 years old: <140 mmHg
4. New SBP treatment goal for CKD: <140 mmHg
5. New SBP treatment goal for diabetes mellitus: <140 mmHg
6. Initial drug therapy in nonblacks: thiazides CCB, ACEI, ARB
7. Initial therapy in blacks: thiazides or CCB
8. In CKD therapy should include an ACEI or ARB 9. Treatment strategy: start w/ 1 drug, increase dose or add second drug if not controlled
JNC 8: Recommendations
How to Adjust Therapy?
• If goal BP not reached in 1 month:
– Increase dose of initial agent or
– Add a second drug from preferred list
• If goal BP not reached with two drugs:
– Add a third agent from preferred list
– Add a fourth if necessary
• Avoid using ARB and ACEI in same
patient
James PA, et al. JAMA 2014;311:507-520.
JNC 8: New Recommendations Recommendation 1: Corollary Recommendation “In the general population aged 60 years or older, if pharmacologic treatment for high BP results
in lower achieved SBP (for example, <140 mm Hg) and treatment is not associated with adverse effects
on health or quality of life, treatment does not need to be adjusted.”
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Treatment of
Isolated Systolic Hypertension
SYST-EUR
SYST-CHIINA
Calcium Blocker
Calcium Blocker
SHEP
Diuretic
#
4736
4696
Age (y)
>60
>60
2394
BP ‐ baseline
(mmHg) ‐ treated 170/77
144/68
174/86
151/79
Stroke
-33%
-42%
-38%
CV Death
-20%
-27%
-39%
CHD Death
-33%
-27%
-32%
>60
171/86
151/81
SHEP: JAMA 265:3255‐64, 1991; Syst‐Eur: Lancet 350:757‐64, 1997; Syst‐China: J Hypertens 16:1823‐39, 1998
JNC 8: New Recommendations Recommendations 2 (DBP) & 3 (SBP): UNCHANGED
For general population <60 years old, initiate pharmacological treatment at BP ≥140 or ≥90 mmHg to lower BP to <140 and < 90 mmHg
ASH/ISH: same
Comparison of BP < 135/85 vs 140‐160/90‐100 mmHg
Achieved difference = ‐6.8/‐5.5 mmHg
Total Mortality
0.99 [0.86, 1.15]
Cardiovascular Mortality
1.03 [0.83, 1.28]
Non‐CV Mortality
0.96 [0.78, 1.18]
Myocardial Infarction
0.90 [0.74, 1.09]
Stroke
0.99 [0.79, 1.25]
Congestive Heart Failure
0.88 [0.59, 1.32]
8 Major CV Events
0.94 [0.83, 1.07]
0.2
Lower target
0.5
0
Risk Ratio
[95% CI]
2
5
Higher target
Arguedas, Perez, Wright. Treatment blood pressure targets for hypertension. Cochrane Database of Systemic Reviews, 2009 Issue 3
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JNC 8: New Recommendations Recommendation 4: NEW TARGET FOR CKD For the population ≥18 years old with CKD (< 60 mL/min/1.73 m2 or albuminuria), treat to <140 and <90 mmHg
ASH/ISH: same but “…some experts still recommend <130/80 mmHg if albuminuria
is present in patients with CKD.”
JNC 8: New Recommendations Recommendation 5: NEW TARGET FOR DM
In the population ≥18 years old with diabetes mellitus, treat to <140 and <90 mmHg
ASH/ISH: same UKDPS: Risk Reduction of Diabetes-Related
End Points with Tight BP Control
144/82 mm Hg (tight BP control) vs
154/87 mm Hg (less tight BP control)
Diabetes-related
Mortality*
†
Stroke
Microvascular Myocardial
End Points‡
Infarction
Risk Reduction (%)
0
10
20
21%
30
32%
37%
40
50
44%
* MI, sudden death, stroke, peripheral vascular disease, renal disease, hyperglycemia, or hypoglycemia.
† Fatal or nonfatal.
‡ Retinopathy requiring photocoagulation, vitreous hemorrhage and fatal or nonfatal renal failure.
Adapted from UK Prospective Diabetes Study Group. BMJ. 1998;317:703-713.
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ACCORD: Mean Systolic Blood‐Pressure at Each Study Visit
The ACCORD Study Group. N Engl J Med 2010;362:1575‐1585
CV Death, MI, Stroke
Nonfatal Stroke
Nonfatal Myocardial Infarction
Death from CV Disease
The ACCORD Study Group. N Engl J Med 2010;362:1575-1585
American Diabetes Association
Standards of diabetes care 2014 Diabetes Care 37 (Suppl 1):514‐580, 2014
People with diabetes and hypertension should be treated to a SBP goal of <140 mmHg.
Lower systolic targets, such as <130 mmHg, may be appropriate for certain individuals, such as younger patients, if it can be achieved without undue treatment burden.
Patients with diabetes should be treated to a diastolic blood pressure (DBP) <80 mmHg.
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JNC 8: New Recommendations Recommendation 6: RACE IS CONSIDERED IN SELECTION OF INITIAL DRUG THERAPY
In the nonblack population (including those with diabetes) initial therapy should include
• thiazide‐type diuretic
• calcium channel blocker
• ACE inhibitor
• angiotensin receptor blocker
ASH/ISH: Race is also considered
JNC 8: New Recommendations Recommendation 7: RACE IS CONSIDERED IN SELECTION OF INITIAL DRUG THERAPY
In the black population (including those with diabetes) initial therapy should include
• thiazide‐type diuretic
• calcium channel blocker
ASH/ISH: same JNC 8: New Recommendations Recommendation 6 (cont): SOME CLASSES ARE LESS APPROPRIATE FOR 1ST LINE THERAPY Not recommended: ‐blockers, ‐blockers
No evidence: /‐blockers, vasodilating ‐
blockers, central 2‐agonists, direct vasodilators, loop diuretic, aldosterone
receptor antagonists
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JNC 8: Drug treatment strategies
1. Maximize dose of selected first agent
2. Add a second drug before maximizing dose of first drug
3. Start with 2 drug classes
JNC 8
ASH/ISH Initial Treatment Recommendations General Population (no DM or CKD)
Stage 1
Stage 2 (140‐159/90‐99)
(>160/100)
Nonblack Black
≥60 y <60 y
Thiazide ACEI or Thiazide
or CCB
ARB
or CCB
All
Start 2 drugs
Thiazide or CCB
+
ACEI or ARB
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JNC 8: New Recommendations Recommendation 8: ACEI/ARB FOR CKD
In the population aged ≥18 years old with CKD (GFR <60 ml/min/1.73m2 or proteinuria), initial (or add‐on) therapy should include an ACE inhibitor or ARB. This applies to all CKD patients with hypertension regardless of race or diabetes status
JNC 8: New Recommendations Recommendation 9: TREATMENT APPROACHES • If not at goal BP after 1 month, increase dose(s) or add a second drug (ASH/ISH: adjust at 2 to 3‐week intervals)
• If still not at goal, add a 3rd drug
• If still not at goal, use other classes and/or refer to a hypertension specialist
Additional Considerations in
Antihypertensive Drug Choices
Drug Class
HCTZ
β Blockers
CCB’s
α Blockers
Favorable Special Effects
Slows demineralization in osteoporosis
Atrial arrhythmias
Migraine
Thyrotoxicosis
Essential tremor
↓ Perioperative Risk
Raynauds’
AVN Arrhythmias
Prostatism
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Additional Considerations in
Antihypertensive Drug Choices
Drug Class
HCTZ
Potential Unfavorable Effects
Gout
Hx of ↓ Na+ or K+
β Blockers
Asthma
Reactive airways
2nd or 3rd degree Heart Block
ACE/ARB
Pregnant women or those
likely to become pregnant
Aldo
Antagonists
↑ Potassium
Persistent HTN: ESC
• Appropriate life style + 2 drugs from
different classes/adequate doses
• Recommend add one or more:
– Mineralocorticoid receptor antagonist
– Amiloride
– Β-blocker - doxazosin
2103 ESH/ESC Guidelines for HTN.
Etiology of Refractory Hypertension
Primary Causes
Examples
Poor adherence to
medical regimen
Dietary interference
Medication or drug
interference
White coat (office) effect
Skipped or missed drugs; D/C drugs; Poor office
follow-up; Avoiding behavioral modifications
Excess salt, caffeine, alcohol
Pseudo-hypertension
Sub-optimal medication
regimen
Obesity
Secondary hypertension
Isolated office hypertension; Office refractory
hypertension
Poor measurement techniques; Decreased
arterial compliance; Cuff-inflation artifact;
Reactive anxiety/pain; Paroxysmal hypertension
Physician under-treatment; Poor medication
combinations; Wrong diuretic class; Pseudotolerance to medications
Metabolic syndrome; Sleep apnea, habitual snoring
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True Refractory Hypertension
• Strong direct-vasodilator
• Lower aortic or SBP
• Non-traditional combos
Minoxidil (+ loop diuretic + β-blocker)
• Non-traditional dosing
QOD long-acting meds (amlodipine, reserpine,
aliskerin) Chronotherapy (Nocturnal dose of meds or
ASA 81 mg)
• Rx activated-SNS
• Add non-BP medications
α-Blocker ± β-blocker
Alternative therapy
“Tailored” therapy
Novel invasive approaches
Isometric hand grip, slow breathing, nutracuticals
Nitrates; Vasodilating β-blocker (Nebivolol)
2 CCBs (verapamil + amlodipine); ACEI + (DRI)
aliskiren
Silendifil 50 TID, statins, ET-blocker
Renin-sodium profile; hemodynamics; cardiac ICG
Carotid baro-pacing; renal nerve ablation
RVLM neurovascular decompression
Low Dose Spironolactone in
Resistant Hypertension
Mean reduction: 25/12 mmHg
Aldactone  BP 23/12 mmHg vs  7/6 mmHg for other medications
≥3 meds (mean=4) with BP uncontrolled (most on ARB/ACEI and HCTZ) Aldactone dose = 12.5-50 mg QD
Am J Hypertens 2003;16:925 and AJH 2006;19:750.
Renal Denervation?
SYMPLICITY HTN-3 Efficacy Endpoint
Δ = -2.39 (95% CI -6.89 to 2.12) p = 0.26
Δ = -14.1±23.9 (p < 0.001)
Δ = -11.7±25.9 (p < 0.001)
Office SBP (mmHg)
200
150
180 mmHg
166 mmHg
180 mmHg
168 mmHg
100
50
0
Baseline
6 Months
(N =364) (N =353)
Denervation
(N =171) (N =171)
Sham
Bhatt DL et al. N Eng J Med. 2014 (Epub before print).
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When to Suspect
Secondary Hypertension?
• Early onset (age < 30 years)
• Resistant (3 drugs, including diuretic, at
optimal doses)
• Severe (BP ≥ 180/110)
• Sudden increase in previously stable
patient
• Non-Dipping or Reverse-Dipping during
24hr ambulatory BP monitoring
• Presence of target organ damage
Rimoldi SF, et al. Eur Heart J 2014.
Secondary Causes of Hypertension
Cause
Common
Etiologies/Signs/Symptoms
Intrinsic renal disease Any cause of renal
Renovascular disease
Hyperaldrosteronism
Sleep breathing
disorders
insufficiency/edema
Atherosclerosis, FMD/renal bruit,
sudden BP change, underlying
atherosclerosis, increase in
creatinine with ACEI, intermittent
pulmonary edema, FMD-young
women
Adrenal hyperplasia or adenoma/ ↓
potassium, metabolic alkalosis, 
sodium, ↓ ↓ potassium on diuretic,
any refractory HTN
Sleep apnea, habitual
snoring/snoring, witnessed apneas,
day-time somnolence, headache,
obesity
Screening Test(s)/Follow-Up Tests
Creatinine (>1.4-1.8)GFR, UA renal
DUS
Renal MRA ± DUS for resistance
indicies/renal angiography ± pressure
gradients
Plasma PRA-ALDO/24-hour urine
ALDO, saline suppression test, adrenal
imaging
Sleep study/CPAP trial
Effects of Continuous Positive Airway Pressure vs.
Supplemental Oxygen on 24 - Hour Ambulatory
Blood Pressure
Meta-analysis: J Hypertens 2010;28:875
(SBP 2 -3 mm Hg; 1 mm Hg per 10 AHI)
Hypertension 2006;47:1.
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Primary Aldosteronism
Significance & Barriers
• Most Common Cause of Secondary HTN
• Prevalence Relatively High
• Greater End-Organ Damage
• Curable or Manageable With Therapy
• Confusion About Approach
• Fear of Embarking On Workup
• Low Rates of Screening
Funder, et al. JCEM 2009;93:3266.
Hyperaldosteronism
• Consider screening for
– Spontaneous hypokalemia (<3.5)
– Marked diuretic-induced hypokalemia (<3.0)
– HPT refractory to 3 or more drugs
– Adrenal adenoma
• Screen with aldosterone/PRA (ratio 19.6)
• Confirm screening test (ratio 50 and aldo>15.7
suffices)
• Localize if Dx confirmed (AVS only with - imaging)
CHEP Guidelines.
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Primary Aldosteronism (5-15% HTN)
Refractory HTN, hypokalemia adrenal mass
Sit 5-15 mins in am (on meds)
ARR: PRA (ng/ml/hr) / serum aldosterone ratio (ng/dL)
Low PRA < 0.65- 1.0
ARR < 25
Aldo < 10-14
ARR > 25
+ aldo < 10-14
ARR > 50-100
+ aldo >14
ARR > 20-49
+ aldo > 10-14
Low renin HTN
High suspicion
Confirm
Other mineralocorticoids
(DOC, CAH, PCOS,
SAME, Liddle’s)
• D/C med interference
• Correct K+
• Repeat test or 24 h urine
24h urine aldosterone
IV saline suppression
Captopril suppression
OR
 BP  to spironolactone
+
IMAGE
ADRENAL
Vein
Sampling
Endocrine Society Guidelines: Funder JW. J Clin Endocrinol Metab 2008;93:3266.
ARR Sensitivity & Specificity
Nishizaka, Am J Hypertens 2005;18:805.
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)
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Sensitivity and Specificity of Tests for
Renovascular Hypertension
Sensitivity Specificity
(%)
(%)
Test
Intravenous pyelography
Routine renography
Plasma renin activity
Captopril plasma renin activity
Captopril scintigraphy
Doppler flow ultrasonography
Magnetic resonance angiography
75
75-85
50-80
74
93
90
90-95
86
75-85
84
89
95
90-95
95
Source: Adapted from Mann SJ, et al. Ann Intern Med 1992;117:845-853.
Pheochromocytoma
Clinical Features
•
•
•
•
•
•
Pressure: Sustained HTN + Spikes
Pain: Throbbing HA, Chest Pain
Perspiration: Heavy, Generalized
Palpitations
Pallor
Other: Hyperglycemia, Weight Loss,
Tremor, Orthostasis, Hypercalcemia
• 5-10% Asymptomatic (!!)
Pheochromocytoma
The Pheo Paroxysm (“Spell”)
•
•
•
•
•
•
Throbbing HA & Chest Pain
Drenching Sweat
Pounding Tachycardia
Extreme BP Elevation
Pallor, All Lasting 10-60 Min
NO Flush, Wheezing, Itching, Diarrhea,
Syncope, Dermatographia
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Pheochromocytoma
Differential Diagnosis of Spells
+ HTN &/Or Tachycardia
•
•
•
•
•
•
•
•
•
Labile Essential HTN
Sleep Apnea
Clonidine Withdrawal
Neuroblastoma
Arrhythmia
Thyrotoxicosis
Panic Attacks
Hypoglycemia
Drugs
Flushing, No HTN
•
•
•
•
•
•
•
•
Menopause
Mastocytosis
Carcinoid
Medullary Thy CA
Diencephalic Sz
Diabetes/Autonomic
Drugs
(Panic Attacks)
Pheochromocytoma
Screening Tests
• 24 h Urine Catecholamines & Metabolites
− Fractionated Catechols/Metanephrines (LC-MS/MS)
− > 2x Normal = 1.3 mg tot MN, 35 mg E, 170 mg NE
• Plasma Metanephrines: More False Positives
− Seated 5 Min; Indwelling Catheter Best
− NMN > 0.9 or MN > 0.5 nmol/L (2 & 1 for Sure)
− Quest Assay: Different Units
− Avoid Caffeine, Acetaminophen, TCA, a-Blockers
• Grossly Positive Screen Sufficient (Clonidine)
• Most Slightly Abnormal Screens Not Pheo
Pheochromocytoma
• Consider screening for:
– Paroxysmal and/or severe (>180/110) sustained
HPT refractory to usual Tx
– HPT and multiple symptoms suggestive (H/A
(pain), palpitations, sweating (perspiration), panic
attacks, pallor)
– HPT triggered by BB, MAO inhibitors,
micturition, or changes in abdominal pressure
– Adrenal mass, MEN 2A/B, neurofibromatosis, or
von Hippel-Lindau
• Localize MRI (pref), CT, MIBG
CHEP Guidelines.
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26