Transcript Hypertension Management of the “Difficult Patient”

Hypertension
Management of the
“Difficult Patient”
Clay A. Block, M.D.
12-6-2004
What is the “difficult patient”?
The “Difficult Patient”
 Resistant
Hypertension
 Intolerant
of Multiple Medicines
Definition of Hypertension
 Normal<=
120/80
 Prehypertensive
120-139/80-89
 Stage
1 Htn 140-159/90-99
 Stage
2 Htn >= 160/100
Resistant Hypertension
 Failure
to reach goal BP in a patient
adhering to full doses of an
appropriate three drug regimen that
includes a diuretic
What are the goals of therapy?

<140/90 for patients without diabetes or
renal disease
– Most patients who achieve their systolic goal
will also achieve their diastolic goal

<130/80 for patients with diabetes or
renal disease
 (JNC
7)
What is the Benefit?
 Stroke
 Heart
Incidence Reduction 35-40%
Failure Reduction > 50%
 Myocardial
25%
Infarction Reduction 20-
What is the Benefit?
 Number
Needed to Treat to Prevent 1
Death Over 10 Years by Lowering
Systolic Pressure by 12 mmHg in
Stage 1 Hypertension: 11
 In
the Presence of CV Disease or
Target Organ Damage the NNT falls
to 9
Approach to the Patient With
Potentially Resistant Htn
 Review
Diagnosis
 Review Goals
 Get on Same Page:
– Most Patients Will Require Multiple
Agents to Achieve Control
– All Medicines Have Side Effects and
Costs
– Don’t Forget Lifestyle Modification and
Nonpharmacologic Approaches
Approach to Resistant
Hypertension
 Establish
“true resistance”
– Measure BP accurately
– Consider “White Coat Hypertension”
– Consider “pseudoresistance”
– Consider secondary causes
Accurate BP Measurement
“Persons should be seated quietly for 5
minutes with feet on the floor and the arm
supported at heart level”
 Cuff must be appropriately sized (cuff
bladder must encircle 80% of the arm)
 Check both arms and a leg (or palpate
pulses carefully)
 Caffeine and Tobacco can transiently raise
BP substantially

Approach to Resistant
Hypertension

Establish “true resistance”
– Measure BP accurately
– Consider “White Coat Hypertension” (WCH)
– Consider “pseudoresistance”
– Consider secondary causes
'White-coat hypertension' needs
attention

Q.My doctor wants to start both me
and my husband on blood-pressure
pills, and his blood pressure is only
145/95. And my blood pressure is
fine at home and only high in my
doctor's office — isn't this just
"white-coat hypertension"? We don't
have headaches, tiredness, dizziness
or anything
– 2002 Honolulu Newspaper Column
White Coat Hypertension



20-30% of Apparently Resistant
Hypertension May be due to “White-Coat
Hypertension”
Patients with WCH have an increased risk
of CV events and often have some degree
of end organ damage
Use home or ambulatory monitoring to
sort out
Home and Ambulatory BP
Monitoring (ABPM)
 Often
lower than office readings
 Useful to “calibrate” home monitors
 Nocturnal Dip (10-20% fall during
the night) is physiologically
important (Dippers vs. Non-Dippers)
 Can identify “windows of poor
control” or windows of low BP and
correlate with perceived symptoms
Dippers vs. Non-Dippers
 More
 More
 More
 More
 More
LVH
silent cerebrovascular disease
albuminuria
progression of CKD
CV mortality
Additional Information From
Ambulatory Monitoring
 Heart
rate: For each 10% less
reduction in heart rate,
cardiovascular mortality increases by
30% (J Htn 16, 1335-1343, 1998)
 Increase
in average 24 hour pulse
pressure of >= 53 mmHg confers
high risk
Why and When ABPM
 Suspected
 Excessive
 Apparent
Variability
Drug Resistance
 Symptoms
Episodes
WCH
Suggesting Hypotensive
Explanation of ABPM plots
An Example of “White Coat Hypertension”
Approach to Resistant
Hypertension
 Establish
“true resistance”
– Measure BP accurately
– Consider “White Coat Hypertension”
– Consider “pseudoresistance”
– Consider secondary causes
Pseudoresistance



Pseudohypertension
Non-adherence may account for up to 50% of
resistant cases
Inadequate Regimen
– Especially inadequate diuretic component

Interfering medicines and substances also need
to be considered
–
–
–
–
–
NSAIDs
Excessive Alcohol, Caffeine, or Tobacco
Excessive Salt Intake
Drugs of Abuse
Oral contraceptives
Critical Importance of Adequate
Diuretic Therapy
 23/32
patients referred for
management of “resistant
hypertension” had evidence of
expanded extracellular volume by
nuclear study
– None had clinical evidence of expanded
extracellular volume
– All were already on diuretic therapy
 Am
J Med Sci 1989; 298: 361-365
Critical Importance of Adequate
Diuretic Therapy
 Control
improved in patients treated
with potent thiazide diuretics
(indapamide, metolazone, or larger
doses of hctz, etc.) or given multiple
daily doses of loop diuretics
 Patients with co-existent renal
disease may require more intensive
diuretic therapy
Pseudohypertension
 Calcification
of the arteries resulting
in failure of the BP cuff to compress
and occlude flow
 Suspect if:
– severe hypertension by cuff but no end
organ injury
– Antihypertensive rx results in sx of
Hypoperfusion/hypotension without
measurable hypotension
– Pipe stem calcification on x-ray
Pseudohypertension

Osler’s Maneuver (the radial artery
remains palpable due to calcification and
thickening despite inflation of cuff above
systolic pressure)
– Poorly reproducible
“Dynamap”-like devices may be more
accurate in this setting
 Direct Intra-arterial measurement is the
only definitive way to establish the
diagnosis, but this is uncommonly done

The Importance of Adherence
 Only
1/2 to 2/3 of patients take at
least 75% of prescribed
antihypertensive medicines
– Of those taking < 75%, only 37%
achieved BP goal
– Of those taking >= 75%, 81% achieved
goal
 Arch
Int Med 1987; 147:1393-1396
The Importance of Adherence
 In
a more recent BMJ study, the
same rate of adherence was found in
both responsive and resistant
patients (82%)
 BMJ
2001; 323:142
Techniques to Improve Adherence
 Education
of the patient
– Increases awareness but less effect on
behavior
 Minimize
the number of pills
– Combination pills (acei/diuretic,
arb/diuretic, arb/ca-blocker, etc.)
 Increase
the frequency of visits
– Use of care managers
Approach to Resistant
Hypertension
 Establish
“true resistance”
– Measure BP accurately
– Consider “White Coat Hypertension”
– Consider “pseudoresistance”
– Consider secondary causes
Important Secondary Causes of
Hypertension
 Obstructive
Sleep Apnea
 Obesity (Metabolic Syndrome)
 Endocrinopathies
– Hyperaldosteronism, thyroid
problems, pheochromocytoma
 Kidney
Disease
– Renal Insufficiency and Renal Artery
Stenosis
Drug
Resistant
Htn
Logan
J Htn
2001
Stroke or
TIA
Basetti
Sleep,
1999
CHF
Javaheri
Circ 1999
All
Htn
Nieto
JAMA
2000
CAD
Shafer
Card 1999
Sleep Apnea and Hypertension
 Clear
dose response between
severity of OSA and the incidence of
hypertension
– May relate to the “Non-dipping”
 Clear
improvement in hypertension
of approximately 10mmHg with
effective CPAP therapy (and no effect
with ineffective CPAP)
Obesity and the Metabolic
Syndrome


According to the Framingham Heart Study,
65-78% of the risk for hypertension
can be related to obesity
Obesity is linked to:
– OSA
– Insulin resistance
– Resistance to antihypertensive effect of
medicines
– Activation of the RAAS and the SNS
Table 1. Forms of primary aldosteronism
Aldosterone-producing adenoma (APA)
Bilateral idiopathic hyperplasia (IHA)
Primary (unilateral) adrenal hyperplasia
Aldosterone-producing adrenocortical carcinoma
Familial hyperaldosteronism (FH)
Glucocorticoid-remediable aldosteronism (FH type I)
FH type II (APA or IHA)
Table 2. Prevalence of unrecognized primary aldosteronism in patients with
hypertension
Author (Ref.)
Country
No.
screened
Prevalenc
e
Gordon et al. (21 )
Australia
199
8.5%
Kumar et al. (22 )
India
103
8.7%
Kreze et al. (23 )
Slovakia
115
13.0%
Lim et al. (24 )
United
Kingdom
465
9.2%
Loh et al. (25 )
Singapore
350
4.6%
Fardella et al. (26 )
Chile
305
9.5%
Schwartz et al. (27
)
United States
117
12.0%
Rossi et al. (10 )
Italy
1,046
6.3%
Renal Artery Stenosis
Associations of Clinical Characteristics with Renal Artery Stenosis
Krijnen, P. et. al. Ann Intern Med 1998;129:705-711
Diagnosis of Renal Artery Stenosis
 Clinical
Features
– Severe hypertension, resistance, flash
pulmonary edema, cad/cvd/pvod,
abdominal bruits, hypokalemia, high
renin level, marked clinical response to
angiotensin blockade, ARF
 Imaging
Options
– Duplex ultrasound, MRA, CT
angiography
Diagnostic Tests for Renal Artery Stenosis in Patients Suspected of Having
Renovascular Hypertension: A Meta-Analysis
G. Boudewijn C. Vasbinder, MD; Patricia J. Nelemans, MD, PhD; Alfons G.H. Kessels,
MD, MSc; Abraham A. Kroon, MD, PhD; Peter W. de Leeuw, MD, PhD; and Jos M.A. van
Engelshoven, MD, PhD
18 September 2001 | Volume 135 Issue 6 | Pages 401-411

Our meta-analysis indicates that CTA and gadoliniumenhanced MRA are superior to the other studied
diagnostic tests for the detection of renal artery
stenosis. Careful selection based on clinical evaluation,
which can increase the pretest probability to 20% to
40%, is a prerequisite for cost-effective use of these
tests in the work-up strategy for patients with possible
renovascular hypertension Because only a limited
number of published studies on CTA and gadoliniumenhanced MRA could be included in our meta-analysis,
further research is recommended.
What is the definition of RAS?
Stenosis is considered >=50% luminal
narrowing
Clinically relevant (also called “critical”) stenosis
is not well defined (50-70% by some
pharmacologic studies vs. 80% by renal vein
renin
Response to intervention does not correlate well
with pre or post treatment degree of stenosis
What is the natural history of RAS?
RAS is part of a systemic disease that
effects the entire vascular tree and both
kidneys
 Patients are at greater risk for CV events
than of ESRD
 Angiographic progression occurs in 49%
and occlusion occurs 14%
 Renal atrophy over two years was 11.7%
vs. 20.8% for stenoses <60% and
>=60% respectively

Goals of Management of RAS
 Prevention
of clinical events such as
stroke, MI, chf, or renal failure
 Surrogate markers or goals are:
– Improvement or normalization of BP
– Restoration of renal artery patency
November 2003 • Volume 42 • Number 5
Controversies in nephrology
Stable patients with atherosclerotic renal artery stenosis should be treated first
with medical management
Medical Therapy vs.
Revascularization
Medical therapies such as
antihypertensives, antiplatelet agents and
lipid lowering agents will not restore
patency, may or may not improve BP, but
have proven efficacy in the reduction of
CV events and death
 Renal artery revascularization can restore
patency, has at best a modest effect on BP
, and has no clearly documented effect in
the prevention of renal failure or CV
events

The Role for Inhibition of the RAAS

108 patients at high risk for severe RAS
were treated with ACEI with diuretics
– 44 with bilateral stenosis
– 29 with a solitary functioning kidney
– 20 with unilateral stenosis

57 developed >=20% rise in creatinine
between 4 days and 4 weeks (about half
early)
– All recovered to baseline after stopping the
ACEI
– KI 1998; 53:986-993
Predictors of Poor Response to
Revascularization
 Elevated
Resistive Indices that are
indicative of glomerulosclerosis and
interstitial fibrosis
 Advancing Age
 Small kidney size
Complications of renal artery
revascularization
 Serious
complications excluding
hematomas occurred in 11% of renal
artery stent procedures
 9.5% incidence of clinical
atheroembolic events
 ~5% incidence of ARF
 5 fatalities in a meta-analysis of 644
patients
Role for Revascularization
 Resistant
hypertension
 Patients intolerant of ACEI or ARB
with severe hypertension (more than
20% increase in serum creatinine)
 Patients with rapidly declining renal
function (1/3 may benefit)
 Recurrent or intractable pulmonary
edema
Summary
 Establish
Dx, risks and benefits
 Eliminate interference and optimize
lifestyle, adherence and regimen
 Consider secondary causes
 See frequently and modify regimen
References




The Seventh Report of the
Joint National Committee
on Prevention, Detection,
Evaluation, and Treatment
of High Blood Pressure
European Society of
Hypertension Newsletter
2003; 4, No. 15
Minireview: Primary
Aldosteronism-Changing
Concepts in Diagnosis and
Treatment. Endo
144(6):2208-2213
Obesity, Sleep Apnea, and
Hypertension.
Hypertension Dec
2003:1067-1074


Clinical Usefulness of
Ambulatory Blood Pressure
Monitoring. J Am Soc Neph
15: S30-S33, 2004
Mayo Clinic Proceedings
March 2000. 278-284