GUIDELINE-DRIVEN MANAGEMENT

OF HYPERTENSION: AN EVIDENCE-
BASED UPDATE
Robert M. Carey, MD, MACP, FRCP, FRCPI, FAHA
Professor of Medicine
Dean, Emeritus, School of Medicine
University of Virginia
 Disclosures

• Chair, AHA Writing Committee for 2018 scientific statement on resistant hypertension.

• Member, AHA Writing Committee for 2019 scientific statement on BP measurement.

• Vice-Chair, ACC/AHA Writing Committee for the 2017 hypertension clinical practice guideline.

• Co-chair, Endocrine Society clinical practice guideline panel on primary aldosteronism (2022-).

“The recommendations and opinions presented by our guest speakers may not represent the official
position of the American Heart Association. The materials are for educational purposes only, and do
not constitute an endorsement or instruction by AHA/ASA. The AHA/ASA does not endorse any product
or device.”. 2
 OUTLINE

• Brief review of major guideline recommendations

• Optimal systolic BP and primordial disease prevention
• Current state of BP control
• Secondary hypertension: drug therapy
• Secondary hypertension: primary aldosteronism
• Treatment of hypertension in young adults at low short-term
CVD risk
• Lifestyle management of BP
• Pharmacologic management of hypertension
• BP management in older adults
• Concluding comments
BRIEF REVIEW OF MAJOR GUIDELINE
RECOMMENDATIONS
 BP CLASSIFICATION
(2003 JNC 7 and 2017 ACC/AHA Guidelines)
SBP DBP 2003 JNC7 2017 ACC/AHA

<120 and <80 Normal BP Normal BP

120–129 and <80 Elevated BP

Area of
difference
Prehypertension
130–139 or 80–89 Stage 1 hypertension

140–159 or 90-99 Stage 1 hypertension Stage 2 hypertension

≥160 or ≥100 Stage 2 hypertension Stage 2 hypertension

• Blood Pressure should be based on an average of ≥2 careful readings on ≥2 occasions

• Adults with SBP or DBP in two categories should be designated to the higher BP category
5
Whelton PK, Carey RM, et al. Hypertension. 2018;71:1269-1324./J Am Coll Cardiol. 2018;71:2199-2269.
2017 ACC/AHA BP Guideline: Thresholds for Drug Treatment
CVD Risk/other Recommended Treatment
SBP DBP
circumstances
<120 and <80 N/A Healthy Lifestyle
(Normal)
120–129 and <80 N/A Nonpharmacological therapy
(Elevated)
- No CVD
- 10-yr ASCVD risk <10%* Nonpharmacological therapy

130-139 or 80-89 - CVD, or

(Stage 1 Hypertension) - 10-year ASCVD risk ≥ 10%

Nonpharmacological therapy
Diabetes or CKD
and
130-139 Age ≥65 years
Antihypertensive drug therapy
(Stage 1 Hypertension)
≥140 or ≥90
(Stage 2 Hypertension)
+ N/A

* AHA/ACC 2013 Pooled Cohort CVD Risk Equations

Whelton PK, Carey RM, et al. Hypertension. 2018;71:1269-1324./J Am Coll Cardiol. 2018;71:2199-2269.
 2017 ACC/AHA BP Guideline: Treatment Targets
SBP DBP CVD Risk Recommended BP Target

<120 and <80 N/A N/A

120–129 and <80 N/A

N/A

130-139 or 80-89 No CVD and 10-year

ASCVD risk <10%

130–139 or 80–89 Clinical CVD or 10-

year ASCVD risk ≥ 10%
SBP <130 (DBP <80 mm Hg)
≥130 or ≥80
Diabetes or CKD
≥140 or ≥90
N/A
≥130
Age ≥65 years SBP <130 mm Hg

Whelton PK, Carey RM, et al. Hypertension. 2018;71:1269-1324./J Am Coll Cardiol. 2018;71:2199-2269.
 There was controversy surrounding the 2017
ACC/AHA guideline recommendations when they
initially appeared.

Have the major guideline recommendations

been validated?
COMPARISON OF CVD EVENTS AND DEATH PREVENTED
WITH ADHERENCE TO 2 GUIDELINE RECOMMENDATIONS
1) Estimation of proportion of US adults in BP categories using NHANES
2) Incidence of major CVD events & all-cause mortality by modeling 4 large
community-based cohort studies (ARCS, CV Health, Framingham, and MESA)
3) Network meta-analysis (42 RCTs) to estimate HRs for outcomes and determine
population-attributable risks and events reduced.

Characteristic 2014 Evidence-Based 2017 ACC/AHA Guideline

Guideline

BP threshold for initiation ≥140/90 (<age 60) ≥140/90 (gen.

of antihypertensive ≥150/90 (≥age 60) population)
drugs ≥130/80 (high CVD risk)
BP goal of treatment <140/90 (<age 60) <130/80
<150/90 (≥age 60)
Annual CVD event 270,000 610,000 (NNT=70)
reduction (≥age 40)
Annual reduction in 177,000 334,000 (NNT=129)
death
(≥age 40)
Bundy JD et al. JAMA Cardiol. 2018;doi:10.1001/jamacardio.2018.1240
SIMULATED POPULATION IMPACT OF ACHIEVING AND MAINTAINING
2017 ACC/AHA GL BP GOALS IN US ADULTS ≥45 Y WITH HYPERTENSION
Achieving and maintaining 2017 ACC/AHA guideline recommended BP goals
compared to:
• Maintaining current BP treatment and control levels
• Achieving BP goals recommended in the 2003 JNC7 guideline
• Achieving 2014 Eighth Joint National Committee panel report BP goals

Estimated using the following inputs:

• 10-year CVD event rates in hypertension treatment groups using the
REGARDS study, weighted to the US population.
• US adult population sizes for each group from NHANES
• Expected CVD risk reduction with BP lowering to goal based on response to
treatment to current and recommended BP levels in a meta-analysis of
antihypertensive drug treatment randomized trials from Bundy et al. JAMA
Cardiology. 2017.
• Expected risk of treatment-related SAEs with BP lowering based on
treatment-related harms observed in patients treated to standard and
intensive BP goals using pooled data from SPRINT and ACCORD.

Bress AP et al. Circulation.2019;139:24-36

PROJECTED CVD EVENTS PREVENTED x 10Y

Bress AP et al. Circulation.2019;139:24-36.

 POPULATION MODELING STUDIES SUMMARY
• Two well-performed simulation studies demonstrate a highly
positive population impact of following the 2017 ACC/AHA
hypertension guideline recommendations for lowering BP in
hypertensive persons compared to older guidelines.

• The increased risk of adverse events (largely reversible) with

the lower BP target should not be equated to the risk reduction
of major clinical events. Significant reduction in all-cause
mortality shows that benefit of treatment outweighs risks.

• These results strongly support a lower BP target (<130/80

mmHg) in the management of hypertension.
 Is there any association of BP
levels within the normotensive
range with cardiovascular events
or disease?

What does the data say about

the importance of primordial
prevention?
WHAT IS PRIMORDIAL PREVENTION?
Actions that inhibit the emergence of risk factors
in the form of environmental, economic, social and behavioral conditions
and cultural patterns of living.
 ASSOCIATION OF NORMAL RANGE BP
WITH SUBCLINICAL ASCVD
• The 2017 ACC/AHA guideline lowered the SBP goal of therapy
from <140 to <130 mm Hg. This recommendation focused on the
cut point at which there is likely to be benefit from
antihypertensive drug therapy.

• But many individuals classified as low risk based on their ASCVD

risk score have subclinical atherosclerosis (based on coronary
artery calcium scores) and may not truly be at low risk.

• Is there an association between SBP, within the normal range as

currently defined, and ASCVD in persons without traditional risk
factors?
Whelton S et al. JAMA Cardiol. 2020;5:1011-1018.
 ASSOCIATION OF NON-HYPERTENSIVE LEVELS OF SBP & CVD
In the Absence of Traditional CVD Risk Factors
MESA FU of 14.5 years in 1457 adults, mean age 58 y and free of ASCVD with SBP 90-129 mm Hg,
LDL-C <160 mg/dL, HDL-C 40+ mg/dL, no DM, no tobacco use, no treatment for hyperlipidemia or DM

Higher levels of SBP @ baseline associated Incident ASCVD Clinical Events by Baseline SBP
with development of CVD Risk Factors For a 10 mm Hg higher SBP 53% increase in ASCVD

Whelton S Percent CAC by Baseline SBP

et al. JAMA
Cardiol.
2020;5:1011-
1018.
 ASSOCIATION OF NORMAL RANGE BP
WITH SUBCLINICAL ASCVD
• In this cohort study including 1457 participants without
atherosclerotic cardiovascular disease, beginning with a SBP
level of 90 mm Hg, there was a stepwise increase in the
prevalence of traditional ASCVD risk factors, coronary artery
calcium scores, and the risk of ASCVD.

• For every 10 mm Hg increase in SBP, there was a 53% higher

risk for ASCVD.

• The results highlight the importance of primordial prevention

to maintain optimal SBP levels as well as other traditional risk
factors.
Whelton S et al. JAMA Cardiol. 2020;5:1011-1018.
Since the introduction of the current BP
guidelines, is there any evidence for
improvement in BP control?
 AGE-ADJUSTED ESTIMATED PROPORTION OF ADULTS
WITH HYPERTENSION AND CONTROLLED BP (<140 mm Hg)
Blood pressure control among all adults with hypertension
100

Muntner P et al. JAMA. 2020;324:1190-1200. 2014 Evidence- Based

Age-adjusted proportion of

80 Panel Report (ACP,

blood pressure controla
AAFP)
Muntner P, et
al, JAMA. 60
2020;324:1190
-1200.
40

20

0
1999- 2001- 2003- 2005- 2007- 2009- 2011- 2013- 2015- 2017-
2000 2002 2004 2006 2008 2010 2012 2014 2016 2018

NHANES cycle
 AGE-ADJUSTED ESTIMATED PROPORTION OF ADULTS
WITH HYPERTENSION AND CONTROLLED BP (<140 mm Hg)
Blood pressure control among adults taking antihypertensive medication
100

Muntner P et al. JAMA. 2020;324:1190-1200.

Age-adjusted proportion of

80
blood pressure controlb

Muntner P, et
al, JAMA. 60
2020;324:119
0-1200. 2014 Evidence-
Based Panel Report
40
(ACP, AAFP)

20

0
1999- 2001- 2003- 2005- 2007- 2009- 2011- 2013- 2015- 2017-
2000 2002 2004 2006 2008 2010 2012 2014 2016 2018

NHANES cycle
 What drugs should I worry about that might
induce secondary hypertension or aggravate
BP levels in hypertensive patients?
• Non-steroidal anti-inflammatory agents (NSAIDS) – the most
important category; at any dose level that controls pain, BP is
elevated. NSAIDS interfere with antihypertensive actions of ACEIs,
ARBs, diuretics & β-blockers.
• Oral contraceptives and hormone replacement therapy
• Immunosuppressive agents: cyclosporine
• Recombinant human erythropoietin
• Tyrosine kinase inhibitors
• Cocaine
• Amphetamines
• Antidepressants
Carey RM, et al. Hypertension. 2018;72:e53-e90.
Is there anything new in screening for
secondary hypertension due to
primary aldosteronism?
DISTRIBUTION OF RENIN-INDEPENDENT
ALDOSTERONE PRODUCTION

4 independent cohorts; 691 adults with suppressed renin

achieving urinary Na+ ≥ 190 mmol/d

Overt PA 11.3%
11.3% 15.7% 21.6% 22.0%

Brown JM, et al. Ann Int Med. 2020;173:10-20.

 STUDY CONCLUSIONS

• A continuum of autonomous and renin-independent aldosterone

production can be found across the spectrum from normotension
to resistant hypertension.

• The frequency of PA (primary aldosteronism) by confirmatory

testing ranged 6-12.7% in normotensives, 6.3-19.4% in stage 1
hypertensives, 14.9-25.2% in stage 2 hypertensives, and 17.8-52.4%
in resistant hypertensives, depending on the PA definition used.

• In the context of renin suppression, autonomous 24h urine

aldosterone is associated with blood pressure and urinary
potassium excretion, consistent with activation of MR.

• Unrecognized, and/or subclinical, primary aldosteronism likely

explains the pathogenesis of a substantial proportion of primary
hypertension.

Brown JM, et al. Ann Int Med. 2020;173:10-20

HOW MANY PATIENTS WITH PRIMARY HYPERTENSION
ARE EVER SCREENED FOR PRIMARY ALDOSTERONISM?
• One in 1,000 in the United Kingdom and Germany

• 2.1% of resistant hypertensives in the U.S.

• The cardiometabolic risk profile for patients with

primary aldosteronism without targeted therapy is at
least 3-fold higher than that for patients with primary
hypertension matched for age, sex and BP.

• Therefore, we need a new simplified diagnostic

approach, one that can be endorsed by the primary
care community.
Jaffe G et al. Hypertension. 2020;75:650-659.
 AUTONOMOUS ALDOSTERONE
PRODUCTION IN PRIMARY HYPERTENSION
Angiotensinogen
Renin
Renin
suppression
Hypertension
Ang I
ACE

Ang II

EXTRACELLULAR FLUID
VOLUME EXPANSION
K+ AT1
RECEPTOR

RENAL CORTICAL
COLLECTING DUCT
Autonomous
Carey RM et al. Aldosterone
Circulation Research. • H+ & K+ secretion
2021;128:827-846.
Production
(non-suppressible with • Na+ reabsorption
salt loading)
 Should all patients with primary
(essential) hypertension be screened
for primary aldosteronism?

If so, how?
 PROPOSED SCREENING FOR AUTONOMOUS
ALDOSTERONE PRODUCTION IN HYPERTENSIVE ADULTS
HYPERTENSION
Stage 1, Stage 2, Resistant

Quantify Circulating Renin

Renin Suppressed Renin Not Suppressed

PRA <1 ng/mL/h or
Neg PA Screen
direct renin concentration <8 mU/L
High Na+ diet
(200 mmol/d)

Urinary Urinary Urinary

Aldosterone Aldosterone Aldosterone
Excretion Excretion Excretion
≥12 mcg/d 6-11 mcg/d <6 mcg/d
Overtly Pos Pos PA Screen Neg PA Screen
PA Screen

Spironolactone Na+ restriction;

Refer for 25 mg/d X 4W continue current
workup at management
If BP falls >10 mm
expert center
Hg, strongly Funder JW, Carey RM. Hypertension. 2022
suspect PA
Treatment of hypertension in young and
low risk groups was not well covered in
the 2017 ACC/AHA guideline.

How should we manage young low-risk

adults in the absence of RCT evidence?
 DOES HIGH BP CONFER INCREASED CVD RISK
EVEN IN “LOW RISK” YOUNG ADULTS?
• For young adults with isolated hypertension, lifetime risk of ASCVD is high although
10-y ASCVD risk may be low.

• As the overall population BP level has shifted to a lower average value, more CVD
events are occurring at lower BP levels.

• This was demonstrated for young adults with hypertension who have earlier onset of
coronary heart disease, heart failure, stroke, transient ischemic attacks and
peripheral arterial disease requiring intervention.

• In the CARDIA (Coronary Artery Risk Development in Young Adults) study of 3,851
adults followed 18.8 years, only 4% were taking antihypertensive medication.

• Adjusted hazard ratios for CVD events were 1.67 , 1.75 and 3.49 for elevated BP,
stages 1 hypertension and stage 2 hypertension, respectively, compared to controls
with normal BP.
Yano Y et al. JAMA, 2018;320:1774-1782.
 CUMULATIVE INCIDENCE OF CVD EVENTS
IN THE CARDIA STUDY BY BP GROUP

Cumulative Incidence of CVD Events, % 20

Log-rank test P < .001

Yano Y et al. 15 Stage 2 hypertension

JAMA.
2018;320:
1774-1782
10

Stage 1 hypertension
Elevated blood pressure
5

Normal blood pressure

0
0 5 10 15 20
Follow-up, y
 CUMULATIVE INCIDENCE OF ALL CAUSE MORTALITY
IN THE CARDIA STUDY BY BP GROUP

Cumulative Incidence of CVD Events, % 20

Log-rank test P < .001

Stage 2 hypertension

Yano Y et al. 15
JAMA.
2018;320:
1774-1782
10

Stage 1 hypertension
Elevated blood pressure
5
Normal blood pressure

0
0 5 10 15 20
Follow-up, y
 AHA SCIENTIFIC STATEMENT: MANAGEMENT OF STAGE 1
HYPERTENSION IN YOUNG ADULTS WITH LOW 10-YEAR
ASCVD RISK
• Start with 6 months of vigorous lifestyle change.

• In all patients with stage 1 hypertension not achieving BP goal <130/80

mm Hg within 6 months, lifestyle therapy should be continued and
consideration of first-line antihypertensive drug therapy.

• Special consideration should be given to use of antihypertensive agents

in individuals with a family history of premature CVD, a history of
hypertension during pregnancy, or a personal history of premature birth.

• 10-y ASCVD risk should be assessed every 4-6 years in patients with 10-y
ASCVD risk <10%
Jones DW et al. Hypertension. 2021;77:e58-e67.
 2020 AHA Scientific Statement
Considerations for Clinical Practice for Low-Risk Younger Adults

BP thresholds for treatment initiation and follow-up

Normal BP Elevated BP Stage 1 Hypertension Stage 2

(BP 120-129/<80 mm Hg) (BP 130-139/80-89 mm Hg)
(BP < 120/80 mm Hg) Hypertension
(BP > 140/90 mm Hg)

Promote Clinical CVD or

optimal lifestyle Non-pharm therapy estimated 10y ASCVD
habits risk ≥ 10%

No Yes

Reassess in 1 yr Reassess in 3-6 mo Non-pharm therapy Non-pharm therapy Non-pharm therapy and
(for 6 mo) and BP lowering BP lowering medication
medication
Flow chart adapted from Whelton PK, Carey RM,
et al. Hypertension. 2018
If BP > target,
continue non-pharm
Red boxes are considerations from Jones DW et al. therapy and consider
Hypertension. 2021;77:e58-e67. These BP lowering Reassess in 1
medication mo
considerations are not included in the original
2017 Guidelines.
How important is lifestyle modification
in the treatment of hypertension?

Is there any new evidence supporting the

efficacy of dietary sodium restriction?
 LIFESTYLE MODIFICATION:
THE CORNERSTONE FOR PREVENTION
AND TREATMENT OF HYPERTENSION
Lifestyle Impact on SBP
Intervention Dose Hypertension Normotension
Weight loss Best goal is ideal body weight, but aim -5 mm Hg -2/3 mm Hg
for at least a 1-kg reduction in body
weight for most adults who are
overweight. Expect about 1 mm Hg for
every 1-kg reduction in body weight.
Healthy diet Consume a diet rich in fruits, vegetables, -11 mm Hg -3 mm Hg
whole grains, and low-fat dairy products,
with reduced content of saturated and
total fat.
Reduced intake of Optimal goal is <1500 mg/d, but aim for -5/6 mm Hg -2/3 mm Hg
dietary sodium at least a 1000-mg/d reduction in most
adults.
Enhanced intake of Aim for 3500–5000 mg/d, preferably by -4/5 mm Hg -2 mm Hg
dietary potassium consumption of a diet rich in potassium.

All 4 Recommendations COR:1; LOE:A

Whelton PK et. al. Hypertension. 2018;71:e13-e115
 LIFESTYLE MODIFICATION:
THE CORNERSTONE FOR PREVENTION AND
TREATMENT OF HYPERTENSION
Nonpharmacological Effect on SBP
Intervention Dose Hypertension Normotension
Physical Aerobic ● 90–150 min/wk -5/8 mm Hg -2/4 mm Hg
activity ● 65%–75% heart rate reserve
Dynamic ● 90–150 min/wk -4 mm Hg -2 mm Hg
resistance ● 50%–80% 1 rep maximum
● 6 exercises, 3 sets/exercise, 10
repetitions/set
Isometric ● 4 × 2 min (hand grip), 1 min -5 mm Hg -4 mm Hg
resistance rest between exercises, 30%–
40% maximum voluntary
contraction,
3 sessions/wk
● 8–10 wk
Moderation Alcohol In individuals who drink alcohol, -4 mm Hg -3 mm
in alcohol consumption reduce alcohol to:
intake ● Men: ≤2 drinks daily
● Women: ≤1 drink daily
Both Recommendations COR:1; LOE:A
Whelton PK et. al. Hypertension. 2018;71:e13-e115
BLOOD PRESSURE EFFECTS OF SODIUM REDUCTION
Dose-Response Meta-Analysis of Experimental Studies
• A comprehensive dose-response meta-analysis of trials
detailing the effects of change of dietary sodium on BP, using
the most up-to-date statistical dose-response modeling,
shows that the relationship is positive, and almost but not
entirely linear.

• Progressively large reduction in BP can be expected with

decreases in NaCl consumption down to 1 to 1.5 g/d, with no
evidence for a threshold benefit.

• The results suggest that this relationship is generally true for

both SBP and DBP, for adults with and without hypertension,
and during shorter and longer periods of sodium reduction.
Filippini T et al. Circulation. 2021;143:1542-1567.
 DOSE-RESPONSE META-ANALYSIS OF CHANGES IN SBP & DBP
ACCORDING TO DIFFERENCES IN SODIUM EXCRETION
No hypertension Hypertension
15.0 15.0

SBP difference (mmHg)

SBP difference (mmHg)

10.0 10.0

5.0 5.0

Filippini T et
0.0
al. . 0.0

Circulation. -2.0 -2.0

2021;143: 0.0 1.0 2.0 3.0 4.0 0.0 1.0 2.0 3.0 4.0 5.0
1542-1567. Sodium difference (g/day) Sodium difference (g/day)
10.0 10.0
DBP difference (mmHg)

DBP difference (mmHg)

5.0 5.0

0.0 0.0

-3.0 -3.0
0.0 1.0 2.0 3.0 4.0 0.0 1.0 2.0 3.0 4.0 5.0
Sodium difference (g/day) Sodium difference (g/day)
 EFFECT OF SALT SUBSTITUTION ON CVD EVENTS AND DEATH

• Salt substitutes with reduced Na+ and increased K+ levels have been shown to
lower BP, but their effects on CVD and safety outcomes have been uncertain.

• Neal et al. conducted an open-label, cluster randomized trial involving 600

villages in rural China. Participants had hypertension and a history of stroke
or were ≥ age 60.

• Villages were randomly assigned to an intervention group (a salt substitute

containing 75% NaCl and 25% KCl by mass) or a control group continuing to
use regular salt (100% NaCl).

• The primary outcome was stroke, the secondary outcomes were major
adverse cardiovascular events and death from any cause, and the safety
outcome was hyperkalemia.
Neal B et al. N Engl J Med. 2021;385:1067-1077.
 EFFECT OF SALT SUBSTITUTION ON CVD EVENTS AND DEATH

Neal B et al.
N Engl J Med.
2021;385:106
7-1077.
 EFFECT OF SALT SUBSTITUTION ON CVD EVENTS AND DEATH
A Stroke B Major Adverse Cardiovascular Events
100 25 P=0.006 100 25 P<0.001 Regular salt

Cumulative Incidence (%)

Cumulative Incidence (%)
90 90 20
20
80 Regular salt 80
15 15
70 70
10 60 10 Salt substitute
60
50 Salt substitute 50 5
5
40 40
0 0
30 0 12 24 36 48 60 30 0 12 24 36 48 60
20 20
10 10
Neal B et al. N 0 0
Engl J Med. 0 12 24 36 48 60 0 12 24 36 48 60
2021;385:1067- Month Month
1077.
C Death from Any Cause D Hyperkalemia
100 25 P<0.001 100 3 P=0.76
Regular salt

Cumulative Incidence (%)

Cumulative Incidence (%)

90 20 90
80 80 2 Salt substitute
15
70 70
60 10 Salt substitute 60 1
50 5 50
Regular salt
40 40
0 0
30 0 12 24 36 48 60 30 0 12 24 36 48 60
20 20
10 10
0 0
0 12 24 36 48 60 0 12 24 36 48 60
Month Month
What are the latest principles for
the pharmacological
management of hypertension?
 PHARMACOLOGICAL TREATMENT OF HYPERTENSION
Agree (patient and clinician) on BP goal

First-line therapeutic classes

• CCB* and/or
• ACEI or ARB and/or
• Thiazide-like** or thiazide diuretic
• Measure (minimum 2 readings in am & pm 3 d/week),
record and report home BP readings at each office visit.
Monthly visits
• Use fixed-dose drug combinations and 90-day prescription refills if
until BP goal possible
achieved • If BP not at goal, assess for social barriers and non-adherence to
treatment.
• Dose-titrate and/or add another first-line agent from a different class if
needed to achieve goal.

Second-line therapeutic classes

• β-blocker (first-line only in IHD and HF)
• MRA (preferred in low renin states and resistant HT)
• α1-antagonist
• Direct vasodilator (use with diuretic and β-blocker)
• K+-sparing diuretic (minimally effective in BP reduction)
• Loop diuretic (preferred in CKD with GFR < 30, in symptomatic HF
and when using potent direct vasodilator minoxidil)
Whelton PK et. al. Hypertension.
• Central α2-agonist (last-line due to CNS effects and potential for hypertensive crisis
2018;71:e13-e115 on withdrawal)
 KEYS TO EFFECTIVE BP LOWERING IN HYPERTENSION

• Agree (patient and provider) on BP target .

• Use fixed dose combinations.
• Substitute long-acting chlorthalidone for hydrochlorothiazide.
• Use long-acting amlodipine as first line calcium channel blocker.
• Monthly visits until blood pressure target achieved
• Replace prescriptions of 30 day with 90-day refills, if allowed.
• Use telehealth strategies to augment office-based management.
• Enhance connectivity between patient, provider and electronic health
record for better feedback and communication.
• Screen for social determinants of health and consideration of obstacles to
care.
• Use multidisciplinary team-based care to enhance lifestyle and medication
adherence and to solve social issues.

Carey RM et al. Circulation Research. 2021;128:827-846.

 CARDIOPROTECTIVE EFFECTS OF THIAZIDE-LIKE DIURETICS
Subgroup analysis Cardiac events
(random effects model) OR (95% Cl)

Thiazide-like diuretic
SHEP (1991) 0.63 (0.53, 0.75)
SHEP-PS (1989) 0.80 (0.37, 1.74)
Chen P et al. HYVET (2009) 0.68 (0.51, 0.90)
Am J VHAS (1997) 1.12 (0.65, 1.95)
Hypertens. ALLHAT (2002) 0.89 (0.85, 0.93)
ALLHAT (2000) 0.74 (0.68, 0.80)
2015;28:1453-
SHELL (2003) 0.94 (0.63, 1.40)
1463 Subtotal (I-squared = 79.3%, p =0.000) 0.78 (0.68, 0.90)

Thiazide-type diuretic
EWPHE (1985) 0.58 (0.31, 1.07)
MRC (1992) 0.69 (0.52, 0.91)
VA (1970) 0.69 (0.24, 1.96)
Australian (1980) 0.89 (0.67, 1.17)
PHSH (1977) 0.97 (0.65, 1.44)
Oslo (1980) 0.89 (0.48, 1.64)
HAPPY (1987) 0.84 (0.67, 1.06)
ANBP2 (2003) 1.12 (0.95, 1.32)
NICS-EH (1999) 1.48 (0.52, 4.23)
ACCOMPLISH (2008) 1.26 (1.11, 1.44)
MIDAS (1996) 0.49 (0.23, 1.02)
INSIGHT (2000) 0.97 (0.79, 1.19)
Subtotal (I squared = 64.5%, P = 0.001) 0.92 (0.79, 1.07)

Active treatment better Control better

.234 1 4.28
 Intensive BP lowering in hypertensive older adults
has been controversial, especially in light of risks,
such as orthostatic hypotension,
electrolyte abnormalities
and increased renal failure.

Is there any new evidence supporting the efficacy of

intensive BP lowering in older adults?
 MANAGEMENT OF HYPERTENSION IN OLDER ADULTS
THE STEP STUDY

• Chinese patients (9,624) ages 60-80 with hypertension

(including diabetics) randomized to SBP target 110-130 mm
Hg (intensive treatment) or 130-150 mm Hg (standard
treatment).
• Primary outcome: composite of stroke, acute coronary
syndrome, acute decompensated heart failure, coronary
revascularization, atrial fibrillation or death from a
cardiovascular cause.
• Median follow up 3.34 years

Zhang W, et al. N Engl J Med. 2021;385:1268-1279.

 MANAGEMENT OF HYPERTENSION IN OLDER ADULTS
Validation of SBP Goal <130 mm Hg

150

Systolic Blood Pressure (mm Hg)

145

140
Standard Treatment

135

130
Intensive Treatment

125

120

0 1 2 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45

Months Since Randomization

Zhang W, et al. N Engl J Med. 2021;385:1268-1279.

MANAGEMENT OF HYPERTENSION IN OLDER ADULTS
Validation of SBP Goal <130 mm Hg
1.0
0.10 Hazard Ratio with Intensive Treatment
0.74 (95% CI, 0.60-0.92); P=0.007
0.8 0.08
Cumulative Incidence

Standard Treatment
0.06
0.6
0.04

0.4 0.02 Intensive Treatment

0.00
0.2 0 6 12 18 24 30 36 42 48

0.0
0 6 12 18 24 30 36 42 48
Months Since Randomization

Zhang W, et al. N Engl J Med. 2021;385:1268-1279.

 MANAGEMENT OF HYPERTENSION IN OLDER ADULTS
• The 2017 ACC/AHA BP Guideline recommends a systolic BP treatment
goal of <130 mm Hg for non-institutionalized ambulatory free-living
older adults (≥65 y of age) and an individualized team-based
approach, based on clinical judgement and patient preference, for
those with higher burden of comorbidity and limited life expectancy.

• Concerns have been raised that the CVD event and all-cause
mortality benefit of intensive BP control may be offset by an
increased rate of adverse effects, especially in older adults.

• Several studies in the past 2 years have addressed this question and
also have provided evidence for protection from mild cognitive
impairment and dementia with SBP <130 mm Hg.

Carey RM et al. Circulation Research. 2021;128:827-846.

 MANAGEMENT OF HYPERTENSION IN OLDER ADULTS
• The concern about SAEs was put to rest by 2 reports by Juraschek et al.
Examining the SPRINT data and the aggregated individual patient data from
multiple clinical trials for association of intensive BP lowering with orthostatic
hypotension.

• In SPRINT, orthostatic hypotension was more common in the standard

treatment group and was not associated with a higher rate of CVD events or
with syncope, electrolyte abnormalities, injurious falls or acute renal failure.

• In the Juraschek et al. meta-analysis of 18,466 participants, intensive BP

lowering actually reduced the incidence of orthostatic hypotension, possibly
due to improved baroreceptor function.

• Thus, asymptomatic orthostatic hypotension during hypertension treatment

should not trigger automatic down-titration of therapy, even in the setting of a
lower BP goal.
Juraschek SP et al. Ann Int Med. 2021;174:58-68.
 EFFECTS OF BP TREATMENT ON RISK OF
ORTHOSTATIC HYPOTENSION
Effects of BP treatment on risk for orthostatic hypotension, by study

Trial Participants, n Visits, n P Value

AASK 1090 48771 0.43

ACCORD BP 4196 7162 0.88

Juraschek SP
SPRINT 9221 51227 0.02
et al. Ann
Int Med. SPS3 2887 18093 0.82
2021;174:58- UKPDS 1072 2629 0.74
68.
Primary analysis: trials
comparing BP goals (n=5) 18466 127882 0.030

HYVET 2404 4732 0.04

SHEP 4681 89356 0.54

Syst-Eur 4595 39329 0.37

TOMHS 897 13799 0.64

Secondary analysis: BP goal and 0.007

placebo-controlled trials (n=9) 31043 275098

0.5 0.75 1.0 1.5 2.0

OR (95% Cl)
 EFFECT OF INTENSIVE (SBP <120 mm Hg) VS STANDARD (SBP <140 mm Hg)
BP CONTROL ON DEMENTIA & MILD COGNITIVE IMPAIRMENT
Disorder Cases per 1000 person-years Hazard Ratio (95% CI) P value
(Number of events) (Number of events)

Intensive Standard
Dementia 7.2 (149) 8.6 (176) 0.83 (0.67-1.04) 0.10
Mild cognitive impairment (MCI) 14.6 (287) 18.3 (353) 0.81 (0.69-0.95) 0.007

Dementia and MCI 20.2 (402) 24.1 (469) 0.85 (0.74-0.97) 0.01

Probable Dementia by Treatment Group

(Trial and post-trial analysis by randomized groups)
MRI Sub-study (N=454)
Separation by
Significantly smaller increase in cerebral white
treatment arm
matter lesions in the Intensive BP-lowering
occurs later than
treatment group compared with the Standard
for CVD events
BP-lowering treatment group (p<0.004)

Carey RM, et al. Curr Opin Cardiol. 2021;36:429-435.

 MAJOR TAKE AWAY POINTS

• BP control rates increased steadily until 2013-14 after which they have declined.

• Be careful to avoid NSAIDS patients with high BP, substituting another class of agents to control
pain.

• Autonomous aldosterone production almost certainly plays a role in the pathogenesis of Stages 1
and 2 hypertension and resistant hypertension. All adults with hypertension should be screened for
primary aldosteronism. If renin is low, consider 24-hour urine aldosterone measurement during salt
loading (high sodium diet) conditions.

• Young adults with hypertension have earlier onset of CVD events compared with those with normal
BP. Thus, delay of treatment may be inappropriate, even though RCT evidence is lacking. The
evidence supports initial management with lifestyle modification for 6-12 months followed by
antihypertensive drug therapy if BP remains above goal.

• Lifestyle modification is the cornerstone of antihypertensive therapy. Each nonpharmacological

intervention is effective in lowering BP, and concurrent use of 2 or more interventions results in
additive effects. Lifestyle modification improves the effectiveness of pharmacologic therapy.
 MAJOR TAKE AWAY POINTS

• The relationship of dietary NaCl to BP is positive and almost linear. Decreases in BP can
be expected with decrease in dietary NaCl down to 1-1.5 g/d. Salt substitutes are
effective in lowering BP and improving outcomes.

• Intensive BP control is not associated with increased hospitalization and does not
increase the risk of orthostatic hypotension. Asymptomatic orthostatic hypotension in
hypertensive adults is not associated with higher rates of CVD events, syncope, injurious
falls or acute renal failure and should not be a reason to withdraw or down-titrate
treatment.

• For older adults with hypertension, intensive treatment with an SBP target 110-130
mmHg substantially lowers the incidence of CVD events over standard treatment with a
target 130-150 mm Hg. In addition, intensive BP lowering may prevent or at least
partially arrest cognitive decline with aging.

• Home BP self-monitoring and telemonitoring are effective in facilitating

antihypertensive drug titration leading to achievement and maintenance of BP goal.