STH 19 - Day 2 - Track 1 - Session 2 - Watson - Hypertension - SN

Case #1: Difficult to control BP in an
elderly patient
Case studies in Brachial blood pressure is a strong predictor of clinical outcomes in
Hypertension people with hypertension and it is assumed that brachial blood
pressure accurately reflects pressures in the central aorta and thus
left ventricular load
(pearls for achieving control) 2019 This assumption may not be valid in all circumstances
KAROL E. WATSON, MD, PHD, FACC
PROFESSOR OF MEDICINE/CARDIOLOGY
DAVID GEFFEN SCHOOL OF MEDICINE AT UCLA
The gold standard for measuring central aortic pressure is invasive,
CO‐DIRECTOR, UCLA PROGRAM IN PREVENTIVE CARDIOLOGY however, noninvasive methods exist as well
Elderly Patients have Stiffer Blood Vessels
Average Blood Pressure Waveform Average Blood Pressure Waveform
Shoulder
Notch Notch
140 Transfer 140
function
Time (sec)
Time (sec)
52-year-Old 81-year-Old 70 70
Normal Pressure Wave Early Pulse Wave Reflection Radial Central Aortic
www.lejacq.com/Symposia_Info/UMH_DC-0504/Pickering.ppt
Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.
Case #1: Difficult to control BP in an
Central blood pressure (CBP) elderly patient
Diastolic and mean pressures are very similar at radial / brachial and Follow up: Central aortic BP 108/55
central sites, but…
Follow up Medications: medications de‐escalated to Amlodipine 10 mg,
Benazepril 20 mg, HCTZ 12.5 mg
Systolic Central BP is not the same as brachial or radial Follow up Physical Exam: central aortic BP 128/55 mm Hg
systolic BP! Labs/studies: Unremarkable
Elderly patients are at risk for hypotension and
falls after starting antihypertensive therapy
If your patient is dizzy when they
stand up, it doesn’t matter what
the guidelines say.
Butt DA et al. Arch Intern Med 2013
Case #2: Patient with creatinine Serum Creatinine increase with ACE
increase on ACE inhibitor inhibitors and ARBs
Chief complaint: 66 year old female referred by PCP for “renal injury” after Starting an ACE inhibitor or ARB can result in a small, non‐progressive
starting ACE inhibitor. Patient is asymptomatic increase in serum creatinine that reflects decreased glomerular filtration
PMH: HTN, fibromyalgia rate from the favorable hemodynamic effect of reducing intra‐glomerular
pressure
Medications: Lisinopril 10 mg, Amlodipine 10 mg, HCTZ 12.5 mg, Atorvastatin 10
mg A 30% increase in serum creatinine is generally acceptable
Physical Exam: BP 128/82 mm Hg Creatinine will usually peak within a week, then stabilize
Labs/studies: Creatinine 1.17 (baseline 0.9) If > 30% increase in creatinine occurs, stop the drug
Afferent arteriole Capillary Efferent arteriole

Changes in GFR with ACE‐I or ARB therapy
Intraglomerular pressure
decreases
Nephrons are spared
Renal function is ACE/ARB
preserved
Outcomes are improved dilate here
Intraglomerular pressure
decreases
Filtration gradient
decreases
Less creatinine is filtered
Serum creatinine rises
Aimun K. Ahmed et al. Nephrol. Dial. Transplant. 2010;25:3977-3982
Case #2: Patient with creatinine
increase on ACE inhibitor
Follow up: 0.9 to 1.17 is a 30% increase in creatinine A 30% increase in serum
Follow up Medications: No change Creatinine after addition of an ACE
Follow up Physical Exam: BP 125/80 mm Hg
inhibitor or ARB is acceptable.
Labs/studies: Creatinine stable at 1.12
Case #3: 33 year old patient with new Renin‐Angiotensin‐Aldosterone Regulation of
onset hypertension Blood Pressure
Renin Angiotensin I Angiotensin II
Substrate
Chief complaint: 33 year old male referred by PCP for new onset hypertension. Renin
Has been following this patient for over 10 years but for the last 3 visits his BP has
suddenly jumped up. Patient’s only complaint is back pain from an occupational Aldosterone Adrenal
Cortex
injury The role of
aldosterone is to
PMH: back strain, current smoker retain sodium in
the face of
Medications: Amlodipine 10 mg, Ibuprofen prn deficiency
Vasoconstriction
Physical Exam: BP 148/92 mm Hg
Sodium & Water
Labs/studies: Unremarkable
Reabsorption
Blood Pressure
http://vasoactivetherapy.com/files/CORLOPAM.PPT
Sympathetic Nervous System Regulation of Most cases of Resistant Hypertension are
Blood Pressure caused by:
CNS Adrenal Sodium excess
Catecholamines Gland
Extracellular volume expansion
Renin
Adrenergic Tone secretion
Sympathetic overactivation
Arteries
Resistance
Angiotensin
Too Much Salt
Afterload
Cardiac Output
Aldosterone
Too Much Water
Too Much Sympathetic Activity
Blood Pressure
http://vasoactivetherapy.com/files/CORLOPAM.PPT
Effect of Ibuprofen (400 mg qid) for 3 weeks
Interfering Substances on BP in 30 treated hypertensive patients
Steroids Placebo Ibuprofen
8
Difference (mmHg)
Pain Relievers (e.g., NSAIDs and COX‐2 inhibitors)
6
Sympathomimetics/Simulants (e.g., decongestants, Ritalin, diet pills) 4
2
Antidepressants (e.g., SSRIs, MAOi) 0
Herbal supplements ( e.g., Ephedra‐a.k.a. ma huang) -2
-4
Random (erythropoietin, licorice root) -6
Diastolic BP Systolic BP
Radak et al, 1987
Case #3: 33 year old patient with new Case #4: 58 year old with hypertension,
onset hypertension worried about cancer scare
Chief complaint: 58 year old male referred by PCP for worry about cancer scare
Follow up: Ibuprofen discontinued; Amlodipine discontinued
PMH: hypertension, well controlled
Follow up Medications: None
Medications: Amlodipine 10 mg, Irbesartan 300 mg daily
Case #4: 58 year old with hypertension, Case #4: 58 year old with hypertension,
worried about cancer scare worried about cancer scare
•Several pharmaceutical companies have announced recalls of generic versions
of valsartan, irbesartan and losartan.
Follow up: Patient called his pharmacy and checked the FDA website. There is no
•This is due to the contaminants NDMA and NDEA being found in certain lots recall of his medication lot. He is reassured
•The Food and Drug Administration has traced the contaminated products to a Follow up Medications: No change
large factory in China and later a second factory in India. Both used a similar
manufacturing process to make and supply generic drug companies worldwide. Follow up Physical Exam: BP 120/78 mm Hg
•Only generic versions are affected. Not all makers of genetic versions are Labs/studies: Unremarkable
affected.
•Check FDA website for most up‐to‐date information on recalls
Case #5: 68 year old with difficult to What Is Resistant Hypertension?
control hypertension
You have a patient who is adherent to medications
and lifestyle measures, BUT…
Chief complaint: 68 year old male referred by PCP for resistant hypertension.
Blood pressure has been slowly increasing over the past several years and now BP not on target
has become resistant to prescribed therapies.
PMH: hypertension, migraines Three drugs used
Medications: Amlodipine 10 mg, valsartan 320 mg daily, Chlorthalidone 50 mg
daily At appropriate doses
Physical Exam: BP 147/86 mm Hg, BMI 33
Labs/studies: Unremarkable One is a diuretic
Resistant hypertension is primarily a systolic Resistant Hypertension
and age related problem Cause of resistance found in 94% of cases
Office Unknown
resistance 6% Nonadherence
6%
Diastolic BP goal achieved ≥ 90% in the major trials Psychological 16%
causes
9%
Systolic BP goal achieved 60‐65% in the major trials Secondary
HTN
True resistance occurs in about 15% 5%
Interfering
Resistant Hypertension is more common in the elderly substances
1% Drug-related
causes
58%
Garg JP, et al. Am J Hypertens 2003;16:925-930
Secondary Cause of HTN Causes of Secondary Hypertension
TOO MUCH SYMPATHETIC ACTIVITY
When to evaluate for secondary cause? Coarctation of aorta
Sleep Apnea
1.Unusual presentation of hypertension TOO MUCH SODIUM
Illicit drugs
‐ Severe Hyperaldosteronism
Pheochromacytoma
‐ Sudden Salt overconsumption
‐ Very young or very old NSAID use
‐ Resistant TOO MUCH WATER Acromegaly (anti-natriuretic
Renal Artery Stenosis action of GH)
2.Clinical clues suggesting a particular form of
Renal failure Hyperparathyroidism
secondary hypertension
Hypervolemia
Preeclampsia
Calhoun DA, et al. Circulation. 2008;117(25):e510‐e526.
Secondary Causes of Hypertension Obstructive Sleep Apnea
COMMON RARE
• Fragmented sleep
Sleep Apnea (Very Common) Pheochromocytoma (<0.5%)
• Increased sympathetic activity
Renal Disease (1‐8%) Coarctation of Aorta (<1%)
Hyperaldosteronism (1.5‐15%) Cushing’s Syndrome (0.5%)
Obstructive Apnea
◦ Apnea/Hypopnea Resumption of breathing
Renal Artery Stenosis (3‐4%) Acromegaly
◦ Hypoxia ◦ Labile blood pressure
◦ Hypercapnia
Sympathetic Activity in Sleep Apnea Blood Pressure in OSA
Somers et al. J Clin Invest. 1995;96:1897.
Effect of CPAP on Blood Pressure
Active CPAP Control CPAP
15
10
MAP
*
systolic
*
diastolic
*
OSA is a common cause of resistant
5
0
HTN. Effective treatment can decrease
mean BP by 10mmHg.
mmHg
-5
-10
-15
-20
-25
Becker et al, 2003
Case #5: 68 year old with difficult to Case #6: 58 year old who complains
control hypertension about amlodipine
Chief complaint: 58 year old female referred by PCP for complaints about
amlodipine. PCP has tried multiple antihypertensive regimens and the only time
Follow up: Patient underwent sleep study and found to have severe obstructive
she was able to gain control was when amlodipine was added. Patient complains
sleep apnea (apnea: hypopnea index of 32). CPAP begun
of lower extremity edema
Follow up Medications: No change
PMH: hypertension, metabolic syndrome
Medications: Amlodipine 10 mg, HCTZ 12.5 mg daily
Physical Exam: BP 118/78 mm Hg, 1‐2+ ankle edema
Afferent arteriole Capillary Efferent arteriole
Calcium Channel Blockers and Edema
CCBs dilate
ACE/ARB
here
dilate here
Case #6: 58 year old who complains
about amlodipine
Adding an ACE
inhibitor or an ARB to a CCB Follow up: Amlodipine dose lowered; An ARB was added to the regimen
can decrease edema Follow up Medications: Amlodipine 5 mg, Benazepril 20 mg, HCTZ 12.5 mg daily
Follow up Physical Exam: BP 125/65 mm Hg, NO ankle edema
Case #7: Young man referred by PCP Categories of BP in Adults
for elevated BP
Chief complaint: 21 year old male track star referred by PCP for elevated BP.
BP Category SBP DBP
Secondary causes have been ruled out. Patient states “I won’t take medications” Normal <120 mm Hg and <80 mm Hg
PMH: Elevated BP
Elevated 120–129 mm Hg and <80 mm Hg
FH: Severe hypertension (early onset) in multiple family members. Father died at
age 44 of MI, mother suffered TIA last year Hypertension 130 is the new 140
Medications: None 130–139 mm Hg or 80–89 mm Hg

Stage 1
Stage 2 ≥140 mm Hg or ≥90 mm Hg
J Am Coll Cardiol. 2017 Nov
Trajectories of BP elevation preceding
Nonpharmacologic Interventions
diagnosis of HTN: Framingham and BP Reduction
Weight Loss Low-Salt Alcohol Potassium
(19.4 lb) Diet Exercise Reduction Repletion
0
1
2
BP Decrease
(mm Hg)
3
6 SBP DBP
7
JAMA Cardiol. 2018;3(5):427-431. doi:10.1001/jamacardio.2018.0250 Whelton PK et al. JAMA. 1997;277:1624-1632.
The Role of Potassium in Hypertension Salt Sensitivity related to potassium intake
African American White
• Black and White men were maintained on
Potassium deficit is critical in hypertension diets of varying Potassium levels.
Recent evidence as well as classic studies point to the interaction of sodium • Then given 7‐days of salt loading and salt
and potassium, as compared with an isolated abnormality of either alone, as a sensitivity measured
dominant factor in hypertension • On the low K+ diet, 80% of Black and 35% of
White men were salt sensitive
Processed foods are high in sodium and low in potassium; Conversely, fruits • As potassium intake INCREASED, salt
and vegetables are sodium‐poor and potassium‐rich sensitivity DECREASED.
The Institute of Medicine (IOM) recommendations: 4.7 grams K+ per day (4 ½ • On the high K+ diet, only 20% of the Black
men, and none of the White men remained
cups, 9‐10 servings) salt sensitive
‐Whelton PK. Potassium and blood pressure. In: Izzo JL Jr, Black HR, eds. Hypertension primer. 3rd ed. Dallas: American Heart Association/Council on HighBlood Pressure Research, 2003:280‐.;He

J Am Coll Nutr June 2006 vol. 25 no. suppl 3 262S‐270S
FJ, MacGregor GA. Beneficial effects of potassium. BMJ 2001;323:497‐501; Dietary reference intakes for water,potassium, sodium, chloride, and sulfate. National Academies Press, 2005.
Case #7: Young man referred by PCP
DASH diet is rich in potassium for elevated BP
DASH = Dietary Approaches to Stop Hypertension Follow up: Dietary history reviewed. Patient admits to eating out most nights
(high salt) and rarely, if ever, eating fruits and vegetables. Dietary counseling
The diet is rich in fruits, vegetables (high K+), low fat given and patient adopted recommendations
dairy foods, and low in fat, total fat, cholesterol and
salt Follow up Medications: No medications
Appel, et al. Circulation, 102:852, 2000
Case #8: Middle aged woman with Aldosterone Levels are Increased in Obesity
resistant hypertension
Chief complaint: 68 year old female referred by PCP for resistant HTN. Secondary
causes have been ruled out.
PMH: Severe hypertension, rheumatoid arthritis, CKD
Medications: Amlodipine 10 mg, Chlorthalidone 50 mg, Olmesartan 40 mg,
rosuvastatin 10 mg
Physical Exam: BP 158/92 mm Hg, BMI 34
Labs/studies: Cr – 1.2, K+ ‐ 3.9
Krug A W , and Ehrhart-Bornstein M Hypertension. 2008;51:1252-1258
Spironolactone
Spironolactone can be effective in patients with resistant hypertension
Hyperaldosteronism is much more
• ASCOT Trial: 1,411 patients failing a 3‐drug
common today – in part due to the regimen
obesity epidemic • Spironolactone 25 mg once daily added
• Results: With addition of spironolactone,
mean BP fell by 21.9/9.5 mm Hg (P<0.001).
• Adverse events: Gynecomastia (6%); biochemical
abnormalities (2%) (mainly hyperkalemia)
Chapman N, et al. Hypertension. 2007;49:839-845.
Spironolactone (Aldosterone antagonist)
Patients with resistant hypertension who were documented to have normal
aldosterone levels. Treated with a diuretic and ACE inhibitor or ARB In patients with resistant hypertension, it
6wk 3mo 6mo
is reasonable to give a trial of
BP response (mm Hg)
0
-5
-10 -10 -10
-12
Spironolactone
-15
-20
-25
-21
-23
-25
But watch K+ carefully
Systolic BP Diastolic BP
-30
Nishizaka MK, et al. Am J Hypertens 2003;16;925-930
Case #8: Middle aged woman with Case #9: Patient with hypertension
resistant hypertension complains “I take too many darn pills!”
Follow up: Spironolactone added to regimen Chief complaint: 59 year old male with hypertension. Self‐referred with Chief
complaint: “I take too many darn pills!”
Follow up Medications: Amlodipine 10 mg, Chlorthalidone 50 mg, Olmesartan 40
mg, rosuvastatin 10 mg, Spironolactone 25 mg daily PMH: Hypertension, BPH, GERD
Follow up Physical Exam: BP 128/70 mm Hg Medications: Amlodipine 5 mg, HCTZ 12.5 mg, olmesartan 20 mg
Labs/studies: Cr – 1.2, K+ ‐ 4.6 Physical Exam: BP 128/82 mm Hg, BMI 30
Labs/studies: Cr – 0.9
Shallow dose‐response for antihypertensives BP lowering effect of “doubling dose” of 1 agent
or “combination” of lower doses of 2 agents
20
0
Thiazides ACE‐i CCB
% additional SBP reduction
Thiazide β-blocker ACE-I CCB
-20
-19 -20
mm Hg BP drop
-23
-40
-37
-60
10
-80
-100 -89
-104 -100
-120 -116
0
¼ ½ 1 2 4 ¼ ½ 1 2 4 8 ¼ ½ 1 2 4 -140

Combination
Fraction of pill Doubling dose
Wald et al. Combination Versus Monotherapy for Blood Pressure Reduction,
BMJ volume 326 28 June 2003 bmj.com
The American Journal of Medicine, Vol 122, No 3, March 2009
Case #9: Patient with hypertension
complains “I take too many darn pills!”
Combining lower doses of Follow up: Patient switched to the generic form of Tribenzor which contains
antihypertensive agents improves olmesartan medoxomil 20 mg, amlodipine 5 mg, hydrochlorothiazide 12.5 mg

Follow up Medications: generic Tribenzor 1 tablet daily
BP control and limits side effects Follow up Physical Exam: BP 128/70 mm Hg
Case #10: Very elderly woman with
3,845 elderly patients with STANDING SBP > 150 mm Hg
hypertension randomized to Indapamide (thiazide‐like diuretic) + perindopril
(ACE‐inhibitor)
Chief complaint: 89 year old woman with hypertension. Referred by PCP for very
Target blood pressure
elevated HTN
PMH: Hypertension, hearing loss, HFpEF
150/80 mm Hg
Medications: Amlodipine 10 mg, Chlorthalidone 25 mg, valsartan 320 mg
Inclusion Criteria: Exclusion Criteria: Primary Endpoint:
Physical Exam: BP 188/82 mm Hg, BMI 22 Aged 80 or more Standing SBP < 140 mm Hg All strokes (fatal and non-fatal)
Systolic BP 160-199 mm Hg Stroke in last 6 months
Labs/studies: Cr – 1.5, GFR 35 Informed consent Dementia
Need daily nursing care
N Engl J med 2008;358/ACC 2008
Blood pressure results Stroke results (30% reduction)
180
170 15 mm Hg
160
150
P=0.055
Blood Pressure (mmHg)
140
Placebo
130
120 Indapamide SR +/-

Median follow-up 1.8 years I perindopril
110
100
6 mm Hg
90
80
70
0 1 2 3 4 5
Follow-up (years)
N Engl J med 2008;358/ACC 2008 N Engl J med 2008;358/ACC 2008
Total mortality (21% reduction) Fatal stroke (39% reduction)
P=0.019 P=0.046
N Engl J med 2008;358/ACC 2008 N Engl J med 2008;358/ACC 2008
Heart failure (64% reduction) Long‐Term Antihypertensive Therapy
Significantly Reduces CV Events
Stroke Myocardial infarction Heart failure
0
P<0.0001
–10
–20
Average
reduction –30 20%-25%
in events (%)
–40
35%-40%
–50
>50%
–60
N Engl J med 2008;358/ACC 2008 Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet. 2000;355:1955-1964.
Case #10: Very elderly woman with
hypertension
Follow up: Central aortic pressure was 145 mm Hg; Standing central aortic
pressure was 140 mm Hg; No change in her medications was made
Follow up Medications: Amlodipine 10 mg, Chlorthalidone 25 mg, valsartan 320
mg

STH 19 - Day 2 - Track 1 - Session 2 - Watson - Hypertension - SN

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Case #1: Difficult to control BP in an

140 Transfer 140

Butt DA et al. Arch Intern Med 2013

Afferent arteriole Capillary Efferent arteriole

Aimun K. Ahmed et al. Nephrol. Dial. Transplant. 2010;25:3977-3982

Garg JP, et al. Am J Hypertens 2003;16:925-930

Somers et al. J Clin Invest. 1995;96:1897.

Becker et al, 2003

Afferent arteriole Capillary Efferent arteriole

Medications: None 130–139 mm Hg or 80–89 mm Hg

JAMA Cardiol. 2018;3(5):427-431. doi:10.1001/jamacardio.2018.0250 Whelton PK et al. JAMA. 1997;277:1624-1632.

‐Whelton PK. Potassium and blood pressure. In: Izzo JL Jr, Black HR, eds. Hypertension primer. 3rd ed. Dallas: American Heart Association/Council on HighBlood Pressure Research, 2003:280‐.;He

Krug A W , and Ehrhart-Bornstein M Hypertension. 2008;51:1252-1258

Chapman N, et al. Hypertension. 2007;49:839-845.

¼ ½ 1 2 4 ¼ ½ 1 2 4 8 ¼ ½ 1 2 4 -140

antihypertensive agents improves olmesartan medoxomil 20 mg, amlodipine 5 mg, hydrochlorothiazide 12.5 mg

N Engl J med 2008;358/ACC 2008

120 Indapamide SR +/-

N Engl J med 2008;358/ACC 2008 N Engl J med 2008;358/ACC 2008

N Engl J med 2008;358/ACC 2008 N Engl J med 2008;358/ACC 2008

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