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