case #1: difficult to control bp in an case studies in

Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.

Case studies in Hypertension(pearls for achieving control) 2019

KARO L E . W A T S O N , MD , P H D , F A C C

P R O F E S S O R O F M E D I C I N E / C A R D I O L O G Y

D A V I D G E F F E N S C HOO L O F M ED I C I N E A T U C L A

CO ‐ D I R E C T O R , U C L A P R O G R AM I N P R E V E N T I V E C A R D I O L O G Y

Brachial blood pressure is a strong predictor of clinical outcomes in people with hypertension and it is assumed that brachial blood pressure accurately reflects pressures in the central aorta and thus left ventricular load

This assumption may not be valid in all circumstances

The gold standard for measuring central aortic pressure is invasive, however, noninvasive methods exist as well

Case #1: Difficult to control BP in an elderly patient

52-year-OldNormal Pressure Wave

81-year-Old Early Pulse Wave Reflection

Elderly Patients have Stiffer Blood VesselsAverage Blood Pressure Waveform

Notch Notch

Shoulder

Time (sec)Time (sec)

Average Blood Pressure Waveform

www.lejacq.com/Symposia_Info/UMH_DC-0504/Pickering.ppt

140

70

Radial

Transferfunction

Central Aortic

140

70


Central blood pressure (CBP)

Diastolic and mean pressures are very similar at radial / brachial and central sites, but…

Systolic Central BP is not the same as brachial or radial systolic BP!

Case #1: Difficult to control BP in an elderly patient

Follow up: Central aortic BP 108/55

Follow up Medications: medications de‐escalated to Amlodipine 10 mg, Benazepril 20 mg, HCTZ 12.5 mg

Follow up Physical Exam: central aortic BP 128/55 mm Hg

Labs/studies: Unremarkable

Elderly patients are at risk for hypotension and falls after starting antihypertensive therapy

Butt DA et al. Arch Intern Med 2013

If your patient is dizzy when they stand up, it doesn’t matter what the guidelines say.


Case #2: Patient with creatinine increase on ACE inhibitor

Chief complaint: 66 year old female referred by PCP for “renal injury” after starting ACE inhibitor. Patient is asymptomatic

PMH: HTN, fibromyalgia

Medications: Lisinopril 10 mg, Amlodipine 10 mg, HCTZ 12.5 mg, Atorvastatin 10 mg

Physical Exam: BP 128/82 mm Hg

Labs/studies: Creatinine 1.17 (baseline 0.9)

Serum Creatinine increase with ACE inhibitors and ARBs

Starting an ACE inhibitor or ARB can result in a small, non‐progressive increase in serum creatinine that reflects decreased glomerular filtration rate from the favorable hemodynamic effect of reducing intra‐glomerular pressure

A 30% increase in serum creatinine is generally acceptable

Creatinine will usually peak within a week, then stabilize

If > 30% increase in creatinine occurs, stop the drug

ACE/ARB dilate here

CapillaryAfferent arteriole Efferent arteriole

Intraglomerular pressure decreases

Filtration gradient decreases

Less creatinine is filteredSerum creatinine rises

Intraglomerular pressure decreases

Nephrons are sparedRenal function is

preservedOutcomes are improved

Changes in GFR with ACE‐I or ARB therapy

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

Follow up Medications: No change

Follow up Physical Exam: BP 125/80 mm Hg

Labs/studies: Creatinine stable at 1.12

A 30% increase in serum Creatinine after addition of an ACE inhibitor or ARB is acceptable.

Case #3: 33 year old patient with new onset hypertension

Chief complaint: 33 year old male referred by PCP for new onset hypertension. 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 injury

PMH: back strain, current smoker

Medications: Amlodipine 10 mg, Ibuprofen prn



Renin‐Angiotensin‐Aldosterone Regulation of Blood Pressure

http://vasoactivetherapy.com/files/CORLOPAM.PPT

Blood Pressure

Vasoconstriction

Angiotensin IRenin Substrate

Angiotensin IIRenin

Sodium & Water Reabsorption

Aldosterone

The role of aldosterone is to retain sodium in the face of deficiency

Adrenal Cortex


Sympathetic Nervous System Regulation of Blood Pressure

http://vasoactivetherapy.com/files/CORLOPAM.PPT

Adrenergic Tone

Angiotensin

Cardiac Output

CatecholaminesAdrenal Gland

CNS

ArteriesResistance

Afterload

Blood Pressure

Reninsecretion

Aldosterone

Most cases of Resistant Hypertension are caused by:Sodium excess

Extracellular volume expansion

Sympathetic overactivation

Too Much Salt

Too Much Water

Too Much Sympathetic Activity

Interfering SubstancesSteroids

Pain Relievers (e.g., NSAIDs and COX‐2 inhibitors)

Sympathomimetics/Simulants (e.g., decongestants, Ritalin, diet pills)

Antidepressants (e.g., SSRIs, MAOi)

Herbal supplements ( e.g., Ephedra‐a.k.a. ma huang)

Random (erythropoietin, licorice root)

Effect of Ibuprofen (400 mg qid) for 3 weeks on BP in 30 treated hypertensive patients

-6

-4

-2

0

2

4

6

8

Placebo Ibuprofen

Diff

eren

ce (m

mH

g)

Diastolic BP Systolic BP

Radak et al, 1987


Case #3: 33 year old patient with new onset hypertension

Follow up: Ibuprofen discontinued; Amlodipine discontinued

Follow up Medications: None



Case #4: 58 year old with hypertension, worried about cancer scare

Chief complaint: 58 year old male referred by PCP for worry about cancer scare

PMH: hypertension, well controlled

Medications: Amlodipine 10 mg, Irbesartan 300 mg daily



•Several pharmaceutical companies have announced recalls of generic versions of valsartan, irbesartan and losartan.

•This is due to the contaminants NDMA and NDEA being found in certain lots

•The Food and Drug Administration has traced the contaminated products to a 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.

•Only generic versions are affected. Not all makers of genetic versions are affected.

•Check FDA website for most up‐to‐date information on recalls


Follow up: Patient called his pharmacy and checked the FDA website. There is no recall of his medication lot. He is reassured






Case #5: 68 year old with difficult to control hypertension

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 has become resistant to prescribed therapies.

PMH: hypertension, migraines

Medications: Amlodipine 10 mg, valsartan 320 mg daily, Chlorthalidone 50 mg daily

Physical Exam: BP 147/86 mm Hg, BMI 33


What Is Resistant Hypertension?

BP not on target

Three drugs used

At appropriate doses

One is a diuretic

You have a patient who is adherent to medications and lifestyle measures, BUT…

Resistant hypertension is primarily a systolic and age related problem

Diastolic BP goal achieved ≥ 90% in the major trials

Systolic BP goal achieved 60‐65% in the major trials

True resistance occurs in about 15%

Resistant Hypertension is more common in the elderly

Resistant HypertensionCause of resistance found in 94% of cases

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

Drug-relatedcauses

58%

Nonadherence16%

Unknown6%

Officeresistance

6%Psychologicalcauses

9%

SecondaryHTN5%

Interferingsubstances

1%


Secondary Cause of HTN

When to evaluate for secondary cause?

1.Unusual presentation of hypertension‐ Severe‐ Sudden‐ Very young or very old‐ Resistant

2.Clinical clues suggesting a particular form of secondary hypertension

Calhoun DA, et al. Circulation. 2008;117(25):e510‐e526.

Coarctation of aortaSleep ApneaIllicit drugsPheochromacytoma

Renal Artery StenosisRenal failureHypervolemiaPreeclampsia

HyperaldosteronismSalt overconsumptionNSAID useAcromegaly (anti-natriuretic action of GH)Hyperparathyroidism

Causes of Secondary HypertensionCauses of Secondary HypertensionTOO MUCH SYMPATHETIC ACTIVITY

TOO MUCH WATER

TOO MUCH SODIUM

Secondary Causes of Hypertension

COMMON RARESleep Apnea (Very Common) Pheochromocytoma (<0.5%)

Renal Disease (1‐8%) Coarctation of Aorta (<1%)

Hyperaldosteronism (1.5‐15%) Cushing’s Syndrome (0.5%)

Renal Artery Stenosis (3‐4%) Acromegaly

Obstructive Sleep Apnea

Obstructive Apnea◦ Apnea/Hypopnea ◦ Hypoxia◦ Hypercapnia

Resumption of breathing◦ Labile blood pressure

• Fragmented sleep• Increased sympathetic activity


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

Sympathetic Activity in Sleep Apnea Blood Pressure in OSA

Effect of CPAP on Blood Pressure

Becker et al, 2003

15

10

5

0

-5

-10

-15

-20

-25

MAP systolic diastolic

mm

Hg

* * *

Active CPAP Control CPAP

OSA is a common cause of resistant HTN. Effective treatment can decrease mean BP by 10mmHg.


Follow up: Patient underwent sleep study and found to have severe obstructive sleep apnea (apnea: hypopnea index of 32). CPAP begun




Case #5: 68 year old with difficult to control hypertension

Case #6: 58 year old who complains 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 she was able to gain control was when amlodipine was added. Patient complains of lower extremity edema

PMH: hypertension, metabolic syndrome

Medications: Amlodipine 10 mg, HCTZ 12.5 mg daily

Physical Exam: BP 118/78 mm Hg, 1‐2+ ankle edema


Calcium Channel Blockers and Edema

CCBs dilate here

ACE/ARB dilate here

CapillaryAfferent arteriole Efferent arteriole


Adding an ACE inhibitor or an ARB to a CCB can decrease edema

Follow up: Amlodipine dose lowered; An ARB was added to the regimen

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 #6: 58 year old who complains about amlodipine

Case #7: Young man referred by PCP for elevated BPChief complaint: 21 year old male track star referred by PCP for elevated BP. Secondary causes have been ruled out. Patient states “I won’t take medications”

PMH: Elevated BP

FH: Severe hypertension (early onset) in multiple family members. Father died at age 44 of MI, mother suffered TIA last year

Medications: None



Categories of BP in Adults

BP Category SBP DBP

Normal <120 mm Hg and <80mm 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

J Am Coll Cardiol. 2017 Nov

130 is the new 140


JAMA Cardiol. 2018;3(5):427-431. doi:10.1001/jamacardio.2018.0250

Trajectories of BP elevation preceding diagnosis of HTN: Framingham

Whelton PK et al. JAMA. 1997;277:1624-1632.

Nonpharmacologic Interventionsand BP Reduction

BP

Dec

reas

e(m

m H

g)

SBP DBP

ExerciseLow-Salt

DietAlcohol

ReductionPotassiumRepletion

5

4

3

2

1

0

6

7

Weight Loss(19.4 lb)

The Role of Potassium in Hypertension

Potassium deficit is critical in hypertension

Recent evidence as well as classic studies point to the interaction of sodium and potassium, as compared with an isolated abnormality of either alone, as a dominant factor in hypertension

Processed foods are high in sodium and low in potassium; Conversely, fruits and vegetables are sodium‐poor and potassium‐rich

The Institute of Medicine (IOM) recommendations: 4.7 grams K+ per day (4 ½ cups, 9‐10 servings)

‐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 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.

Salt Sensitivity related to potassium intake

J Am Coll Nutr June 2006 vol. 25 no. suppl 3 262S‐270S

• Black and White men were maintained on diets of varying Potassium levels.

• Then given 7‐days of salt loading and salt sensitivity measured

• On the low K+ diet, 80% of Black and 35% of White men were salt sensitive

• As potassium intake INCREASED, salt sensitivity DECREASED.

• On the high K+ diet, only 20% of the Black men, and none of the White men remained salt sensitive

African American White


DASH diet is rich in potassium

DASH = Dietary Approaches to Stop Hypertension

The diet is rich in fruits, vegetables (high K+), low fat dairy foods, and low in fat, total fat, cholesterol and salt

Appel, et al. Circulation, 102:852, 2000

Follow up: Dietary history reviewed. Patient admits to eating out most nights (high salt) and rarely, if ever, eating fruits and vegetables. Dietary counseling given and patient adopted recommendations

Follow up Medications: No medications



Case #7: Young man referred by PCP for elevated BP

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


Labs/studies: Cr – 1.2, K+ ‐ 3.9

Case #8: Middle aged woman with resistant hypertension

Aldosterone Levels are Increased in Obesity

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


Hyperaldosteronism is much more common today – in part due to the obesity epidemic

Spironolactone

• ASCOT Trial: 1,411 patients failing a 3‐drug regimen

• Spironolactone 25 mg once daily added

• Results: With addition of spironolactone, mean BP fell by 21.9/9.5 mm Hg (P<0.001).

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

Spironolactone can be effective in patients with resistant hypertension

• Adverse events: Gynecomastia (6%); biochemical abnormalities (2%) (mainly hyperkalemia)

Nishizaka MK, et al. Am J Hypertens 2003;16;925-930

Spironolactone (Aldosterone antagonist)

-21

-10

-23

-10

-25

-12

-30-25-20-15-10

-50

BP

resp

onse

(mm

Hg) 6wk 3mo 6mo

Systolic BP Diastolic BP

Patients with resistant hypertension who were documented to have normalaldosterone levels. Treated with a diuretic and ACE inhibitor or ARB In patients with resistant hypertension, it

is reasonable to give a trial of Spironolactone

But watch K+ carefully


Follow up: Spironolactone added to regimen

Follow up Medications: Amlodipine 10 mg, Chlorthalidone 50 mg, Olmesartan 40 mg, rosuvastatin 10 mg, Spironolactone 25 mg daily


Labs/studies: Cr – 1.2, K+ ‐ 4.6

Case #8: Middle aged woman with resistant hypertension

Chief complaint: 59 year old male with hypertension. Self‐referred with Chief complaint: “I take too many darn pills!”

PMH: Hypertension, BPH, GERD

Medications: Amlodipine 5 mg, HCTZ 12.5 mg, olmesartan 20 mg


Labs/studies: Cr – 0.9

Case #9: Patient with hypertension complains “I take too many darn pills!”

Shallow dose‐response for antihypertensives

mm Hg BP

drop

010

20

Fraction of pill

CCBACE‐i

¼ ½ 1 2 4 8 ¼ ½ 1 2 4

Thiazides

¼ ½ 1 2 4

BMJ volume 326 28 June 2003 bmj.com

BP lowering effect of “doubling dose” of 1 agent or “combination” of lower doses of 2 agents

-104 -100-116

-89

-19 -23 -20

-37

-140

-120

-100

-80

-60

-40

-20

0Thiazide β-blocker ACE-I CCB

% a

dditi

onal

SB

P re

duct

ion

Wald et al. Combination Versus Monotherapy for Blood Pressure Reduction, The American Journal of Medicine, Vol 122, No 3, March 2009

Combination

Doubling dose


Combining lower doses of antihypertensive agents improves BP control and limits side effects

Case #9: Patient with hypertension complains “I take too many darn pills!”

Follow up: Patient switched to the generic form of Tribenzor which contains olmesartan medoxomil 20 mg, amlodipine 5 mg, hydrochlorothiazide 12.5 mg

Follow up Medications: generic Tribenzor 1 tablet daily



Chief complaint: 89 year old woman with hypertension. Referred by PCP for very elevated HTN

PMH: Hypertension, hearing loss, HFpEF

Medications: Amlodipine 10 mg, Chlorthalidone 25 mg, valsartan 320 mg


Labs/studies: Cr – 1.5, GFR 35

Case #10: Very elderly woman with hypertension

Inclusion Criteria:Aged 80 or moreSystolic BP 160-199 mm Hg Informed consent

Target blood pressure150/80 mm Hg

3,845 elderly patients with STANDING SBP > 150 mm Hg randomized to Indapamide (thiazide‐like diuretic) + perindopril (ACE‐inhibitor)

Primary Endpoint:All strokes (fatal and non-fatal)

Exclusion Criteria:Standing SBP < 140 mm HgStroke in last 6 monthsDementiaNeed daily nursing care

N Engl J med 2008;358/ACC 2008


Blood pressure results

70

80

90

100

110

120

130

140

150

160

170

180

0 1 2 3 4 5Follow-up (years)

Blo

od P

ress

ure

(mm

Hg)

Placebo

Indapamide SR +/-perindoprilIMedian follow-up 1.8 years

15 mm Hg

6 mm Hg


P=0.055

Stroke results (30% reduction)


P=0.019


Total mortality (21% reduction)

P=0.046


Fatal stroke (39% reduction)


P<0.0001


Heart failure (64% reduction)

35%-40%

20%-25%

>50%

Average reduction

in events (%)

–60

–50

–40

–30

–20

–10

0Stroke Myocardial infarction Heart failure

Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet. 2000;355:1955-1964.

Long‐Term Antihypertensive Therapy Significantly Reduces CV Events

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



Case #10: Very elderly woman with hypertension

case #1: difficult to control bp in an case studies in

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