heart failure prevention: hypertension update
TRANSCRIPT
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Heart Failure Prevention:
Hypertension Update
John MacKay, Pharm.D., BCPS
Providence St. Vincent Medical Center
Portland, Oregon
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I have no financial relationships with commercial interests to
disclose
My presentation does not include discussion of off-label or
investigational use.
Disclosure Slide
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Objectives
• Summarize the major recommendations of the American College of Cardiology-American Heart Association hypertension clinical practice guideline
• Review and interpret the evidence supporting the major changes to the guideline recommendations
• Apply these new recommendations to the management of patients with hypertension
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Pre-assessment questions
1. A 56 year old previously healthy female presents to your clinic with an average blood pressure of 138/82 mm Hg on separate measurements 1 month apart. According to the American Heart Association and American College of Cardiology 2017 guideline, how would you classify her blood pressure?
a. Normal blood pressure
b. Prehypertension
c. Stage 1 hypertension
d. Stage 2 hypertension
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2. Based on the current recommendations from the
American Heart Association and American College of
Cardiology, which of the following statements is/are true
regarding establishing a goal blood pressure goal of less
than 130/80 mmHg for patients with diabetes?
a. There is limited quality evidence to determine a
precise blood pressure target in adults with diabetes
b. The blood pressure goal is supported by several large
randomized, controlled clinical outcomes trials
targeting < 130/80 mmHg
c. There is consensus among the major guideline
documents over the last 15 years on the target blood
pressure for adult patients with diabetes
d. All of the above
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3. Based on the ACC/AHA 2017 hypertension guideline,
the threshold blood pressure for beginning
pharmacologic treatment is ≥ 140/90 mmHg for which of
the following patient groups?
a. Patients with chronic kidney disease
b. Patients with no clinical cardiovascular disease and a
10-year ASCVD risk of less than 10%
c. Patients with diabetes
d. All of the above
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4. Why is chlorthalidone considered a first line treatment
for hypertension?
a. Data from clinical trials such as ALLHAT demonstrate
chlorthalidone’s impact on cardiovascular outcomes
b. Chlorthalidone has a long half-life which in theory can
lead to less fluctuation and better BP control
throughout the dosing interval
c. Both A & B
d. None of the above, chlorthalidone should be reserved
for resistant hypertension only
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American Heart AssociationHeart Disease and Stroke Statistics
2021 Update
0
20
40
60
80
100
120
140
Hypertension Diabetes Coronary Heart
Disease (CHD)
Stroke Heart Failure (HF)
121.5
35.4
20.1
7.6 6
126.9 million patients in the United States have
Cardiovascular Disease
Circulation 2021;143:e254-e743
Mil
lio
ns
of
pa
tie
nts
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Lancet 2002;360:1903-1913
Establishing Blood Pressure Goals
• The risk of cardiovascular disease doubles for
every 20/10 mm Hg rise over 115/75 mm Hg
• Meta-analysis reviewing vascular mortality
and blood pressure
– 958,074 patients
• 11,960 deaths attributed to stroke
• 34,283 deaths attributed to ischemic heart disease
– Excluded studies enrolling patients with a history
of stroke or heart disease
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Lancet 2002;360:1903-1913
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Lancet 2002;360:1903-1913
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Hypertension and Heart Failure
• 75% of patients who develop chronic heart
failure have hypertension
• Lifetime risk of heart failure is greater with
higher blood pressure compared to SBP < 120
mm Hg
– 1.6 for SBP 120-139 mm Hg
– 2.2 for SBP 140-159 mm Hg
– 2.6 for SBP 160 or greater
JACC 2016;68:1476–88; Heart 2011;97:1204-1211
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Evolving Goal Blood Pressure
JNC 7
2003
JNC 8
2013
ESC
2013
Age < 60
< 140/90
< 140/90 < 140/90
Age ≥ 60 < 150/90
Age < 80< 150/90
< 140/90 (fit)
Age ≥ 80 < 150/90
Chronic kidney
disease< 130/80 < 140/90 < 140/90
Diabetes < 130/80 < 140/90 < 140/85
JAMA 2003;289:2560-2572;
JAMA 2014;311:507-520;
Eur Heart J 2013;34:2159–2219
JNC: Joint National Committee
ESC: European Society of Cardiology
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Evolving Goal Blood Pressure
• Kidney Disease: Improving Global Outcomes
(KDIGO) 2012
– ≤ 130/80 for patients with chronic kidney disease
and urine albumin excretion > 30 mg/24 hours
• American Diabetes Association 2017
– < 140/90 for most patients (A)
– < 130/80 mmHg may be appropriate if high
cardiovascular risk (C)
KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney disease:
http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO_BP_GL.pdf,
Diabetes Care 2018;41(Suppl. 1):S86–S104
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Published online November 13, 2017, available at: Hypertension
and Journal of the American College of Cardiology
JACC 2018;71:e127-248
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Question
1
Is there evidence that self-directed monitoring of BP and/or
ambulatory BP monitoring are superior to office-based
measurement of BP by a healthcare worker for 1) preventing
adverse outcomes for which high BP is a risk factor and 2)
achieving better BP control?
2What is the optimal target for BP lowering during
antihypertensive therapy in adults?
3In adults with hypertension, do various antihypertensive drug
classes differ in their comparative benefits and harms?
4
In adults with hypertension, does initiating treatment with
antihypertensive pharmacological monotherapy versus
initiating treatment with 2 drugs (including fixed-dose
combination therapy), either of which may be followed by the
addition of sequential drugs, differ in comparative benefits
and/or harms on specific health outcomes?
BP: Blood pressure
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Take Home Points
• < 130/80 mm Hg is the new < 140/90 mm Hg
• Use atherosclerotic risk estimation to guide decisions
• Measure blood pressure correctly
• Home/ambulatory blood pressure monitoring is in
• Beta-blockers are out (without a compelling indication), and most patients will need at least 2 drugs
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Redefining Hypertension
CategorySystolic
blood pressure
Diastolic
blood pressure
Normal < 120 mm Hg and < 80 mm Hg
Elevated 120-129 mm Hg and < 80 mm Hg
Hypertension
Stage 1 130-139 mm Hg or 80-89 mm Hg
Stage 2 ≥ 140 mm Hg or ≥ 90 mm Hg
JACC 2018;71:e127-248
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Implications
NEJM 2018;378:497-498
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Blood Pressure Thresholds and Goals
Clinical Condition(s)
BP
Threshold,
mm Hg
BP Goal,
mm Hg
General
Clinical CVD or 10-year ASCVD risk ≥10% ≥ 130/80 < 130/80
No clinical CVD and 10-year ASCVD risk <10% ≥ 140/90 < 130/80
Older persons (≥65 years of age; noninstitutionalized,
ambulatory, community-living adults)≥ 130 (SBP) < 130 (SBP)
Specific comorbidities
Diabetes mellitus ≥ 130/80 < 130/80
Chronic kidney disease ≥ 130/80 < 130/80
Chronic kidney disease after renal transplantation ≥ 130/80 < 130/80
Heart failure ≥ 130/80 < 130/80
Stable ischemic heart disease ≥ 130/80 < 130/80
Secondary stroke prevention ≥ 140/90 < 130/80
Secondary stroke prevention (lacunar) ≥ 130/80 < 130/80
Peripheral arterial disease ≥ 130/80 < 130/80
JACC 2018;71:e127-248
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ACC/AHA Pooled Cohort Equations
http://tools.acc.org/ASCVD-Risk-Estimator-Plus/
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Does targeting a systolic blood pressure
of less than 120 vs. less than 140 mm Hg
in patients with increased cardiovascular risk
but no diabetes improve cardiovascular
outcomes?
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SPRINT
• Inclusion: 50 years old, baseline SBP 130 - 180 mmHg, and at least one of the following:– Clinical or subclinical cardiovascular disease other than
stroke
– CKD, defined as eGFR 20 - 59 ml/min/1.73m2
– Framingham Risk Score for 10-year CVD risk ≥ 15%
– Age >75 years
• Primary outcome: composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure or CV death
• Open-label, goal SBP < 120 mmHg or < 140 mmHg
NEJM 2015;73:2103-2116
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SPRINT
• Medication choice
– ACE-inhibitors, ARBs, diuretics, calcium channel
blockers, beta-blockers, alpha-blockers
• Encouraged chlorthalidone as first line thiazide
• Encouraged amlodipine as the first line CCB
– Loop diuretics for chronic kidney disease
– Beta-blockers for patients with coronary artery disease
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Baseline Characteristics
NEJM 2015;73:2103-2116
Treatment Group
Goal < 120
(n=4678)
Goal < 140
(n=4683)
Criteria for increased CV risk (%)
Age ≥ 75 years old
CKD
CV disease
Framingham 10-year CV risk 15% or greater
1317 (28.2%)
1330 (28.4%)
940 (20.1%)
20.1% ± 10.9
1319 (28.2%)
1316 (28.1%)
937 (20%)
20.1% ± 10.8
Age (mean) 67.9 67.9
Systolic BP (mean) 139.7 139.7
Diastolic BP (mean) 78.2 78
Mean eGFR in ml/min/m2 71.8 71.7
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SPRINT Results
NEJM 2015;73:2103-2116
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SPRINT Results
NEJM 2015;73:2103-2116
NEJM 2021;384:1921-1930
Endpoint
Treatment GroupHR
(95% CI)Goal < 120
(n=4678)
Goal < 140
(n=4683)
Primary endpoint
(number of patients, %)
264
(5.7%)
354
(7.6%)
0.73
(0.63-0.86)
Myocardial infarction102
(2.2%)
140
(3%)
0.72
(0.56-0.93)
Heart failure68
(1.5%)
105
(2.2%)
0.63
(0.46-0.86)
Cardiovascular death41
(0.9%)
71
(1.5%)
0.58
(0.39-0.84)
All cause mortality163
(3.5%)
215
(4.6%)
0.75
(0.61-0.92)
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SPRINT Results
NEJM 2015;73:2103-2116
NEJM 2021;384:1921-1930
Endpoint
Treatment GroupHR
(95% CI)Goal < 120
(n=4678)
Goal < 140
(n=4683)
Patients with no CKD at baseline:
≥30% reduction in estimated GFR to <60
ml/min/1.73 m2
148
(3.8%)
41
(1.1%)
3.67
(2.62-5.26)
Hypotension99
(2.1%)
58
(1.3%)
1.71
(1.24-2.38)
Electrolyte abnormality138
(2.9%)
104
(2.2%)
1.33
(1.03-1.72)
Acute kidney injury193
(4.1%)
115
(2.5%)
1.69
(1.34-2.13)
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Do the results of SPRINT apply to
elderly patients?
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SPRINT: ≥ 75 Years Old
Endpoint
Treatment GroupHR
(95% CI)Goal < 120
(n=1317)
Goal < 140
(n=1319)
Primary endpoint
(number of patients, %)
102
(7.7%)
148
(11.2%)
0.6
(0.51-0.85)
Myocardial infarction37
(2.8%)
53
(4%)
0.69
(0.45-1.05)
Heart failure35
(2.7%)
56
(4.2%)
0.62
(0.4-0.95)
Cardiovascular death18
(1.4%)
29
(2.2%)
0.6
(0.33-1.09)
All cause mortality73
(5.5%)
107
(8.1%)
0.67
(0.49-0.91)
JAMA 2016;315:2673-2682
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SPRINT: ≥ 75 Years Old
Endpoint
Treatment GroupHR
(95% CI)Goal < 120
(n=1317)
Goal < 140
(n=1319)
Serious adverse event637
(48.4%)
637
(48.3%)
0.99
(0.89-1.11)
Hypotension 2.4% 1.4%1.71
(0.97-3.09)
Syncope 3% 2.4%1.23
(0.76-2)
Electrolyte abnormalities 4% 2.7%1.51
(0.99-2.33)
Acute kidney injury or renal failure 5.5% 4%1.41
(0.98-2.04)
Fall Injury 4.9% 5.5%0.91
(0.65-1.29)
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• 16 trials (52,235 patients) compared more versus less intensive BP lowering
• Mean follow-up of 3.7 years (minimum 6 months)
• Outcomes:
– Stroke; coronary death and nonfatal MI; hospitalization for heart failure; composite of the above events; CV death; and all-cause mortality
J Hypertens 2016; 34:613-22
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Outcome
Systolic blood
pressure achieved
(mm Hg)
Trials RR (95% CI)
Absolute RR
1000
patients per
5 years
P-value
for trend
Stroke
140-149 vs. ≥ 150
130-139 vs. ≥ 140
< 130 vs. ≥ 130
8
15
7
0.68 (0.6-0.79)
0.62 (0.51-0.76)
0.71 (0.61-0.84)
-20
-16
-8
< 0.001
Coronary death,
nonfatal MI
140-149 vs. ≥ 150
130-139 vs. ≥ 140
< 130 vs. ≥ 130
8
16
8
0.81 (0.68-0.95)
0.77 (0.7-0.86)
0.86 (0.76-0.97)
-6
-8
-8
0.35
Heart failure
140-149 vs. ≥ 150
130-139 vs. ≥ 140
< 130 vs. ≥ 130
7
10
5
0.52 (0.41-0.65)
0.75 (0.35-1.59)
0.81 (0.51-1.3)
-25
-22
-16
0.11
CV death
140-149 vs. ≥ 150
130-139 vs. ≥ 140
< 130 vs. ≥ 130
8
16
9
0.79 (0.71-0.89)
0.77 (0.63-0.93)
0.8 (0.67-0.97)
-16
- 8
-5
0.001
All-cause
mortality
140-149 vs. ≥ 150
130-139 vs. ≥ 140
< 130 vs. ≥ 130
8
16
9
0.89(0.82-0.96)
0.83(0.72-0.96)
0.84(0.73-0.95)
-16
-10
-10
0.008
J Hypertens 2016; 34:613-22
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Summary
• More intensive blood pressure lowering is
associated with better outcomes
– Meta-analyses support lower treated blood
pressure
– SPRINT supports targeting a systolic blood
pressure of < 120 mm Hg in patients with high
cardiovascular risk
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Diabetes Target Blood Pressure
• ACCORD 2010
– Targeted SBP < 120 mm Hg versus < 140 mm Hg
– Lower incidence of non-fatal stroke, no difference in
nonfatal MI or CV death
• ADVANCE 2007
– ACE-inhibitor/diuretic combination versus placebo
– Suggested improvements in micro- and macrovascular
outcomes, all cause and CV mortality
– Patients eligible regardless of baseline BP
NEJM 2010;362:1575-1585Lancet 2007;37-:829-840
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Antihypertensive Therapy Recommendations
• First line agents
– Thiazides, CCBs, ACE-I or ARB [Class I, LOE A-SR]
• Stage 1 (BP ≥ 130/80 mm Hg)
– ASCVD risk of < 10%:
• Non-pharmacologic therapy [Class I, LOE B-R)
– ASCVD risk of ≥ 10%:
• Antihypertensive monotherapy [Class IIa, LOE C-EO]
JACC 2018;71:e127-248
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Antihypertensive Therapy Recommendations
• Stage 2 (BP ≥ 140/90 mm Hg)
– Combination pharmacologic therapy [Class I, LOE B-R]
– If BP is ≥ 140/90 mm Hg and an average >20/10 mm
Hg above goal:
• Start with 2 antihypertensive medications, separate
medications or fixed dose combinations [Class I, LOE C-EO]
• Special Population based recommendations
– Black: CCB or thiazide-type diuretic
– Pregnancy: methyldopa, nifedipine, and/or labetalol
JACC 2018;71:e127-248
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Pharmacotherapy 2007;27:1322-1333
Selecting the Appropriate Agent
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Compelling IndicationsClinical Condition First Line Drug
Diabetes Mellitus Thiazide, CCB, ACE-I or ARB
Diabetes Mellitus with albuminuria ACE-I or ARB
Chronic kidney disease (Stage 3 or higher or
stage 1 or 2 with albuminuria)ACE-I or ARB
Heart failure with reduced ejection fraction Beta-blocker, ACE-I or ARB, ARA
Heart failure with preserved ejection fraction Beta-blocker, ACE-I or ARB
Stable ischemic heart disease Beta-blocker, ACE-I or ARB
Stable ischemic heart disease with angina Beta-blocker, CCB
Secondary stroke prevention Thiazide, ACE-I or ARB
JACC 2018;71:e127-248
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Thiazide-like Diuretics
Drug PK MOA Side Effects MonitoringCIs/
Precaution
Chlorthalidone
Half-Life:
40-60 hours
Metabolism:
hepatic
Inhibits
sodium and
chloride
reabsorption
in the distal
tubule
Hypokalemia
Photosensitivity
BP
Electrolytes
Renal
function
Severe
sulfa
allergy,
AnuriaHydrochlorothiazide
Half-Life:
6-15 hours
Not
metabolized
40
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Calcium Channel Blockers
Drug PK MOASide
EffectsMonitoring
Contraindications
/ Precautions
Amlodipine
Half-Life:
30-60 hours
Metabolism:
liver
Inhibits calcium
from entering
vascular smooth
muscle causing
relaxation and
peripheral
vasodilation
Peripheral
edema,
fatigue,
headache
Heart Rate,
BP, edema
Hypersensitivity
to amlodipine
Diltiazem ER
Half-Life: 5-10
hours
Metabolism:
liver
Non-DH CCB:
Inhibits calcium
from entering
vascular smooth
muscle causing
relaxation and
coronary
vasodilation
Peripheral
edema,
dizziness,
fatigue
LFTs, BP,
EKG, and HR
Sick sinus
syndrome, 2nd or
3rd degree AV
block, severe
hypotension,
acute MI,
pulmonary edema
41
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ACE-Inhibitors
Drug PK MOA Side Effects MonitoringCIs/
Precautions
Lisinopril
Half-Life:
11-12 hours
Not
metabolized
Prevents
conversion of
angiotensin I to
angiotensin II
leading to
increased renin
activity and
decreased
aldosterone
secretion
Syncope
Hyperkalemia
Cough
Angioedema
Acute ↑ SCr
Potassium
Renal
function
Angioedema
related to
previous ACEI
Concomitant
use with
aliskiren in
patients with
DM
Captopril
Half-Life:
< 3 hours
Renal
excretion
Enalapril
Half-Life:
2 hours
Prodrug
42
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ARB
Drug PK MOA Side Effects Monitoring
CIs/
Precautions
Losartan
Half-Life:
1.5-2 hours
Metabolism:
liver
Reversible,
non-
competitive
angiotensin II
receptor
antagonist
Chest pain
Hypotension
Hyperkalemia
Hypoglycemia
Diarrhea
Anemia
BP
Electrolytes
Renal
Function
Concomitant
use with
aliskiren in
patients with
DM
Candesartan
Half-Life:
5-9 hours
Metabolism:
bioactivated
during
absorption
Valsartan
Half-Life:
6 hours
Metabolism:
not identified
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When should home/ambulatory blood
pressure monitoring be incorporated
into a treatment plan for hypertension?
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Ambulatory BP monitoring
COR LOERecommendation for Out-of-Office and Self-Monitoring
of BP
I ASR
Out-of-office BP measurements are recommended to
confirm the diagnosis of hypertension and for titration of
BP-lowering medication, in conjunction with telehealth
counseling or clinical interventions.
JACC 2018;71:e127-248
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Corresponding Blood Pressure
Measurements
Clinic HBPMDaytime
ABPM
Nighttime
ABPM
24-Hour
ABPM
120/80 120/80 120/80 100/65 115/75
130/80 130/80 130/80 110/65 125/75
140/90 135/85 135/85 120/70 130/80
160/100 145/90 145/90 140/85 145/90
HBPM: home blood pressure monitoring
ABPM: ambulatory blood pressure monitoring
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White Coat Versus Masked Hypertension
JACC 2018;71:e127-248
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CVD Risk Factors Common in Patients With Hypertension
Modifiable Risk
Factors
Relatively Fixed Risk
Factors
• Active smoking,
secondhand smoke
• Diabetes mellitus
• Dyslipidemia/
hypercholesterolemia
• Overweight/obesity
• Physical inactivity/low
fitness
• Unhealthy diet
• CKD
• Family history
• Increased age
• Low socioeconomic/
educational status
• Male sex
• Obstructive sleep apnea
• Psychosocial stress
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Nonpharmacologic Interventions (Class I, LOE A)
Intervention DescriptionApproximate effect on SBP
in hypertensive patient
Weight lossRecommended for overweight or
obese patients-5 mm Hg
Healthy Diet
Diet rich in fruits, vegetables, whole
grains, low-fat dairy; reduced saturate
and total fat
-11 mm Hg
Reduced dietary
sodiumOptimal goal < 1500 mg/day -5 to -6 mm Hg
Enhanced dietary
potassiumGoal 3500-5000 mg/day -4 to -5 mm Hg
Physical activity
Structured exercise program
(dynamic/isometric resistance,
aerobic)
-5 to -8 mm Hg
Moderate alcohol
intake
Men: ≤ 2 per day
Women: ≤ 1 per day-4 mm Hg
JACC 2018;71:e127-248
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Summary
• < 130/80 mm Hg is the treatment goal and
threshold for the majority of patients
– Healthy lifestyle interventions are the cornerstone
of therapy
• First-line medications are ACE-inhibitors, ARB,
CCB or thiazides
• Combination therapy is required for most
patients
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Post-assessment questions
1. A 56 year old previously healthy female presents to your clinic with an average blood pressure of 138/82 mm Hg on separate measurements 1 month apart. According to the American Heart Association and American College of Cardiology 2017 guideline, how would you classify her blood pressure?
a. Normal blood pressure
b. Prehypertension
c. Stage 1 hypertension
d. Stage 2 hypertension
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2. Based on the current recommendations from the
American Heart Association and American College of
Cardiology, which of the following statements is/are true
regarding establishing a goal blood pressure goal of less
than 130/80 mmHg for patients with diabetes?
a. There is limited quality evidence to determine a
precise blood pressure target in adults with diabetes
b. The blood pressure goal is supported by several large
randomized, controlled clinical outcomes trials
targeting < 130/80 mmHg
c. There is consensus among the major guideline
documents over the last 15 years on the target blood
pressure for adult patients with diabetes
d. All of the above
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3. Based on the ACC/AHA 2017 hypertension guideline,
the threshold blood pressure for beginning
pharmacologic treatment is ≥ 140/90 mmHg for which of
the following patient groups?
a. Patients with chronic kidney disease
b. Patients with no clinical cardiovascular disease and a
10-year ASCVD risk of less than 10%
c. Patients with diabetes
d. All of the above
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4. Why is chlorthalidone considered a first line treatment
for hypertension?
a. Data from clinical trials such as ALLHAT demonstrate
chlorthalidone’s impact on cardiovascular outcomes
b. Chlorthalidone has a long half-life which in theory can
lead to less fluctuation and better BP control
throughout the dosing interval
c. Both A & B
d. None of the above, chlorthalidone should be reserved
for resistant hypertension only
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Heart Failure Prevention:
Hypertension Update
John MacKay, Pharm.D., BCPS
Providence St. Vincent Medical Center
Portland, Oregon