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Hypertension Update
Jonathan J. Taliercio, DO, FASN
Associate Program Director, Nephrology Fellowship
Assistant Professor, Cleveland Clinic Lerner College of Medicine
Outline
• Historical Perspective
• Epidemiology
• Physiology
• Define HTN Based on BP Techniques
– Discuss office, AOBP, Home, ABPM
• Target BP Goals
– Impact of SPRINT
• Treatment Guidelines
• Secondary/Resistant HTN
No Disclosures, portion of slides adapted and used with
permission, courtesy of George Thomas, MD2
Historical Perspective on the
Management of Hypertension
• 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, 1937
• 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.
– J.H. Hay, 1931
3
Admiral Ross McIntire (ENT) in the early 1940’s gave FDR a clean bill of health,
documenting BP’s 162/98, 180/88, 188/105, 200/100, 260/150
Howard Bruenn (cardiologist) diagnosed CHF and started treatment with digoxin. New
medical discoveries started to suggest the benefit of salt, smoking, and alcohol
restriction.
April 12, 1945 FDR LOC after complaining of a headache. SBP > 300/190. No
autopsy, but Dr. Bruenn certified cause of death as ICH
3 years after FDR’s death, President Truman signed the National Heart Act which led
to several cardiac studies; Framingham Heart Study
Moser. Journal of Clinical HTN 2006
4
Epidemiology
5
Bevan AT et al, Br. Heart J. 1969,
adopted from Comp. Clin Neph.
6
Prevalence:
NHANES 2007-2012
• 80 million (32.6%; 1 in 3 US adults)
• Awareness and Control:
– 83% aware of a diagnosis of hypertension
– 76% active treatment
– 54% controlled
• Prevalence by race:
– Whites: 30% men and 27% women
– Hispanics: 27% men and 28% women
– Blacks: 40% men and 43% women
AHA statistical update 2016, Circulation7
CV Mortality Increases Above
What BP level?
a) 110/75
b) 115/75
c) 120/80
d) 130/80
e) 140/90
8
CV Mortality Increases Above
What BP level?
a) 110/75
b) 115/75
c) 120/80
d) 130/80
e) 140/90
9
Relationship Between Hypertension
and Cardiovascular Mortality
Lewington S, et al. Lancet 2002
10
Changes in Systolic and Diastolic
Pressure With Age
Burt VL et al, Hypertension 1995
11
JNC 7 Classification
JNC 7, 2003
These definitions apply to adults on no antihypertensive
medications and who are not acutely ill
12
Primary Hypertension
13
Blood Pressure = Cardiac Output x SVR
Comp. Clinical Neph. 5th edition
β-blockers
clonidine
RAAS blockade
CCB
Hydralazine
α-blockers
Diuretics
14
Risk Factors
• Traditional Risk Factors
– Age, Obesity, Race, Family History
– Lifestyle (inactivity, sodium, alcohol)
• Other Risk Factors
– Reduced nephron number
– Salt sensitivity
15
Normal: Salt ingestion will result in elevated BP and prompt excretion of salt load.
Primary HTN/resistant: Defect in salt excretion: A higher BP is required to excrete salt load
Salt-sensitive: Requires a higher initial BP (right shift) and SLOPE to excrete salt load.
(Primary HTN)
At RISK:
AA
Older
CKD
DM
Comp. Clinical Neph. 5th edition
16
Choose the Correct Definition of
Hypertension According to the
Measurement Strategy?
a) 2 office visits; manual BP ≥ 140/90
b) 2 office visits; AOBP BP ≥ 135/85
c) Home BP measurement ≥ 135/85
d) 24 Hour Daytime Average ≥ 135/85
e) All the above
17
Choose the Correct Definition of
Hypertension According to the
Measurement Strategy?
a) 2 office visits; manual BP ≥ 140/90
b) 2 office visits; AOBP BP ≥ 135/85
c) Home BP measurement ≥ 135/85
d) 24 Hour Daytime Average ≥ 135/85
e) All the above
Hypertension Canada (CHEP) 2016
18
Measurement and Diagnosis
• 3 Methods:1. Office BP measurement
• Routine office pressure (manual/usual)
• Automated office BP devices (AOBP)
2. Home BP measurement
3. Ambulatory Blood Pressure Monitoring
(ABPM)
19
Diagnosis of HTN Using Office
Measurements
1. A mean of 2 or more seated office readings, 5
minutes apart, with at least 1 additional visit after
initial visit
2. OR >180/110 on initial visit
• Proper Technique, correct cuff size
– No smoking, exercise, eating, caffeine 30 minutes
beforehand
• Both arms on initial visit – discrepancy of SBP ≥
10 mm Hg may indicate subclavian stenosis
• All HTN guidelines are based on manual BP
measurements
20
Automated Office BP (AOBP)
• Pressure sensor that records oscillations of the
arteries and automatically inflate and deflate the
cuff
• Multiple readings averaged together
• Patient left alone in room (Reduces WCH)
• Readings correlate better with ABPM
• Compared to manual/ “usual” office BP
• AOBP and home measurements are routinely
lower (SBP 5-10; DBP 5 mmHg) than manual
office readings
Myers BMJ 2011
Wohlfahrt Journal of Hypertension 2016
21
Home BP Monitoring
• Take BP for 7 days at home
• Take BP in AM (before medication) and in the
evening (before eating)
• Take 2 measurements each time (separated by
1-2 minute pause)
• Average the results, after discarding 1st Day
• Monitors should be checked for accuracy
initially, and than annual
• Home measurements correlate more closely
with ABPM than office measurements
AHA, ESH/ESC
22
Ambulatory Blood Pressure
Monitoring (ABPM)
• Better Predictor of CV events and CKD
progression (Fan J HTN 2010; Agarwal. KI 2006)
• Indications:
– Suspected white-coat HTN
(only diagnosis reimbursed by Medicare)
– Prehypertension with target organ damage
– Assessment of resistant HTN
– Hypotensive symptoms
– Episodic hypertension
– Autonomic dysfunction23
Patterns of ABPM
White Coat
Hypertension
True
Normotension
Sustained
Hypertension
Masked
Hypertension
24-hour average ≤ 130/80 mmHg
Daytime average ≤ 135/85 mmHg
Clin
ic P
ressu
re
< 1
40/9
0
24
Nocturnal Dipping
Normal BP pattern should decrease by 10%−20% at night-time (during sleep)
25
• Absence of nocturnal fall of at least 10%
• Non-dippers: AA, DM, CKD, OSA, salt
sensitive
• Significance:
– Risk factor for LVH, heart failure, CKD
progression, and death in CKD
– Associated with albuminuria and faster
progression of diabetic nephropathy
• Nocturnal dosing of antihypertensive
medications may restore a dipping pattern
• Unknown if reversal is beneficial
Non-Dipping
Boggia. Lancet 2007
Fan. J Hypertension 2010
26
Population RecommendationGrade
A
Adults aged 18 years
or older
The USPSTF recommends screening for high blood
pressure in adults aged 18 years or older. The
USPSTF recommends obtaining
measurements outside of the clinical
setting for diagnostic confirmation
before starting treatment
The USPSTF
recommends the
service. There is
high certainty that
the net benefit is
substantial.
“ The USPSTF found convincing evidence that ABPM is the best method for
diagnosing hypertension… Elevated ambulatory systolic blood pressure was
consistently and significantly associated with increased risk for fatal and
nonfatal stroke and cardiovascular events, independent of office blood
pressure
For these reasons, the USPSTF recommends ABPM as the reference
standard for confirming the diagnosis of hypertension.”
Good-quality evidence suggests that confirmation of hypertension with
HBPM may be acceptable
2015
27
Treatment Considerations
28
Lifestyle Modification
Modification Comment Approx. SBP reduction
Sodium restrictionNo added salt.
Limit sodium to less than 2.4 g/day2 – 8 mmHg
DASH (DietaryApproaches to Stop Hypertension) diet
Diet rich in fruits, vegetables, low fat dairy, low in saturated fat 8 – 14 mmHg
Weight reduction If over ideal BMI 5 – 20 mmHg/ 10 kg
Physical activityAerobic activity for at least 30
minutes most days of the week4 – 9 mmHg
Limit alcohol
Limit to 2 drinks in men and 1 drink in women and lighter-
weight persons2 – 4 mmHg
JNC 7, AHA/ ACC Lifestyle Working Group, ASH/ISH
29
A 64 year old Caucasian female returns to your
office for her second visit for assessment of
HTN. Last manual office BP shows reading of
146/85.
PMH: None
Social Hx: Social ETOH, No tobacco
Family Hx: HTN
Current Vitals:
BP is 148/88 mmHg, HR 72, BMI 25 kg/m2.
Physical exam is unremarkable. Serum
creatinine is 0.7 mg/dl and UA is normal.
Question
30
Based on your understanding of JNC 8
guidelines, what is your recommendation
at this time?
a) Start therapy with HCTZ
b) Advise limiting alcohol intake to no more than 3
drinks daily
c) Limit sodium intake to 3 grams/day
d) No initiation of anti-HTN therapy required
Question
31
Based on your understanding of JNC 8
guidelines, what is your recommendation
at this time?
a) Start therapy with HCTZ
b) Advise limiting alcohol intake to no more than 3
drinks daily
c) Limit sodium intake to 3 grams/day
d) No initiation of anti-HTN therapy required
Question
32
Goals of Therapy
Recommendations from Recent
Guidelines
Population JNC 8 (2014)
General <140/90
Elderly <150/90 ( ≥ 60 y)
DM <140/90
CKD <140/90
JNC 7 (2003)
<140/90
<130/80
<130/80
ASH/ISH (2013)
<140/90
<150/90 ( ≥80 y)
<140/90
<140/90
Impact of SPRINT on Guidelines?
ESH/ESC (2013)
<140/90
<150/90 ( ≥80 y)
<140/90
<140/90<130/80 albuminuria
33
Examine effect of more intensive high blood pressure
treatment than is currently recommended
Randomized Controlled Trial
Target Systolic BP
Intensive Treatment
Goal SBP < 120 mm Hg
Standard Treatment
Goal SBP < 140 mm Hg
SPRINT Trial
34
Number of
Participants
Hazard Ratio = 0.75 (95% CI: 0.64 to 0.89)
Standard
Intensive(243 events)
Trial (median follow-up = 3.26 years)
Number Needed to Treat (NNT) = 61
Primary Outcome: Composite CV events
(319 events)
SPRINT TRIAL
Mean number of medications:
2.8 in intensive vs. 1.8 in standard
NEJM 21015
Average SBP
(During F/U)
Standard:
134.6 mm Hg
Intensive:
121.5 mm Hg
35
Serious Adverse Events* During Follow-up
Number (%) of Participants
Intensive Standard HR (p Value)
All SAE reports 1793 (38.3) 1736 (37.1) 1.04 (0.25)
Specific Conditions of InterestHypotension 110 (2.4) 66 (1.4) 1.67 (0.001)
Syncope 107 (2.3) 80 (1.7) 1.33 (0.05)
Injurious fall 105 (2.2) 110 (2.3) 0.95 (0.71)
Bradycardia 87 (1.9) 73 (1.6) 1.19 (0.28)
Electrolyte abnormality 144 (3.1) 107 (2.3) 1.35 (0.02)
AKI 193 (4.1) 117 (2.5) 1.66 (<0.001)
*Fatal or life threatening event, resulting in significant or persistent disability,requiring or prolonging hospitalization, or judged as important medical
event by adjudicators.36
What Does This All Mean?
• First large RCT that shows CV and mortality benefit with
intensive BP lowering
– In patients ≥ 50 years old; with any one CV risk
• Clinical or subclinical CVD
• CKD, eGFR 20 to 60
• Framingham Risk Score ≥ 15%
• Age ≥ 75 years
– Without DM or stroke
• SPRINT patients, in general, were not “uncontrolled” – mean
baseline SBP 139.7 mm Hg (Inclusion SBP ≥ 130-180)
– ~ 66% had SBP < 145 mm Hg
• Primary composite outcome results largely driven by HF and CV
mortality benefits
– No significant difference for MI, stroke
37
“Practice Changing Update”
“In patients 50 years or older with SBP 130 to 180
mmHg PLUS an additional risk factor for
cardiovascular disease (other than diabetes,
proteinuric CKD, or stroke…), we recommend:”
• Goal SBP of 125 to 130 mmHg if standard
manual/office measurements are used
• Goal SBP 120 to 125 mmHg if automated blood
pressure (AOBP) measurements are used, rather than
higher values
• Grade 1A recommendation: Strong
OR
38
Question
A 72 year old AA male comes to your office
for HTN. His BP is 155/95 mmHg, HR 83/min.
Physical exam is unremarkable. Labs shows
Cr 1.5 mg/dl and proteinuria 400 mg/24
hours.
What is the least appropriate first line anti-
HTN therapy in this patient?
a)Thiazide
b)B-Blocker
c)ACE-I
d)Dihydropyridine CCB 39
Question
A 72 year old AA male comes to your office
for HTN. His BP is 155/95 mmHg, HR 83/min.
Physical exam is unremarkable. Labs shows
Cr 1.5 mg/dl and proteinuria 400 mg/24
hours.
What is the least appropriate first line anti-
HTN therapy in this patient?
a)Thiazide
b)B-Blocker
c)ACE-I
d)Dihydropyridine CCB 40
General Population
Race Non black
Black
Initial A/C/D C/D
Drug choices for INITIAL treatment
A = ACEI/ARB; B=beta blocker; C = calcium channel blocker; D = thiazide type diuretic
JNC 8
DM
Non black
Black
A/C/D C/D
CKD
Non black
Black
A A
Beta blockers not first-line therapy for management of HTN
Thiazides are not preferred first-line therapy
41
CLASSES OF MEDICATIONS
42
Diuretics
• MOA: Increase salt excretion; vasodilatory properties
• Chlorthalidone is more potent than HCTZ (longer
half-life better nocturnal control)
• If GFR < 30, use loop diuretics
• Short acting loops: furosemide/ bumetanide must be
dosed at 2 times daily
• Urine diuretic screen if suspecting non-compliance
43
Beta Blockers
• MOA: Reduce CO and decrease renin release
• No longer first-line for hypertension management in
most guidelines
• Compelling indications: CAD (MI), CHF
• Newer beta blockers may have more ant-HTN
effects:
– Carvedilol/Labetolol – dual alpha/beta effect,
vasodilatory effect
– Nebivolol – high affinity for 1 receptors +
vasodilatory effects via NO pathway
44
Indications and Expectations with
ACE-I/ARB
• MOA: Blocks conversion of Angiotensin I to II
• Preferred in < 60 year old, non AA, CKD, CHF/MI
• ↓ in proteinuria by 30%. (Kunz R. Ann Intern Med. 2008)
• ↓ in ESRD risk by 30% (IDNT,RENAAL,REIN)
• Expect rise in serum creatinine via ↓in intra-glomerular pressure by 30%
• Cough: ACE-I (5-20%), ARB (3-10%)
• Angioedema: (ACE-I: 0.3%), (ARB: 0.1%)
45
ACEI/ ARB/ Direct Renin Inhibitor:
Combination Not Recommended
• ONTARGET (telmisartan + ramipril)
• NEPHRON-D (losartan + lisinopril)
• ALTITUDE (aliskiren + ACEI/ ARB)
– No benefit / adverse renal outcomes/
hypotension/ hyperkalemia
46
Calcium Channel Blockers
• MOA: Blocks inward flow of calcium in
arterial smooth muscles
• Dihydropyridines: amlodipine, nifedipine
• Non-Dihydropyridines: verapamil, diltiazem
• Dose dependent edema
– Diuretics may not help, but ACE-I/ARBS may attenuate
• ACCOMPLISH Trial (NEJM 2008)
– >11,000 HTN, ↑CV risk patients
– CCB + ACE-I had ↓ 20% RRR in CV outcomes than
diuretic + ACE-I
47
Spironolactone
Chapman et al, Hypertension 2007
• Spironolactone 25 to 50 mg effective in resistant hypertension
• Useful in CHF, OSA
• Side effects: gynecomastia, breast tenderness, hyperkalemia
SBP DBP
Pre
Post
85.375.8
DBP = 9.5(95% CI 9.0, 10.1)
SBP = 21.9(95% CI 20.8, 23.0)
156.9
135.1
0
40
80
120
160
Mean
blo
od
pre
ssu
re
(mm
Hg
)
48
Resistant Hypertension
49
Resistant Hypertension
• The failure to reach goal blood pressure in
spite of the concurrent use of 3
antihypertensive agents of different classes
in maximal tolerated doses, with one of the
agents being a diuretic (JNC 7)
• Patients whose blood pressure is controlled
but require 4 or more medications (AHA)
• Estimated prevalence ~ 12%
• Requires exclusion of “pseudoresistance”
Hypertension 200850
Indications for Further Evaluation
for Secondary Causes
• Resistant Hypertension
• Abrupt onset
• Age < 30, non-obese, non-AA with no FH of
HTN
• Hx: NSAIDS, OCPs, decongestion,
hypothyroid, OSA, drugs
• Labs- hypokalemia, creatinine, UA
• Exam: Abdominal Bruits, Striae, pulses 51
Conclusions
• Office (AOBP, manual), Home, ABPM are
all acceptable forms of diagnosing and
assessing HTN control
• The definition of HTN is based on BP
Measurement Technique
• Office manual BP ≥ 140/90
• AOBP BP, home, 24 average day ≥ 135/85
• 24 hour ≥ 130/80
52
Conclusions
• Β-Blockers are not first line unless
compelling indication (CHF/MI)
• Current Guidelines Target BP < 140/90 for
young patients and < 150/90 for elderly
• Shared decision making when
considering lower BP targets in SPRINT
like patients
53
Thank You
54
Blood Pressure Goals in Recent
Guidelines
55
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