Resistant and Secondary Hypertension Oliver Z. Graham, MD Hypertension Specialist Department of Internal Medicine.

Resistant and Secondary Hypertension

Oliver Z. Graham, MD

“Hypertension Specialist”

Department of Internal Medicine

What I am going to talk about Why BP control is important Initial workup of newly diagnosed HTN Secondary hypertension

Sleep apnea Primary Hyperaldosteronism Renal Artery Stenosis

White coat HTN Tips for improving adherence Resistant hypertension and diuretic use

Benefits of Lowering BPAntihypertensive therapy has been

associated with: 35-40% reduction in stroke 20-25% reduction in MI 50% reduction in heart failure

Treating HTN – A Clear Reduction in MORTALITY If patient with BP 140-159/90-99, (and

other cardiac RF) achieving a 12 mm Hg decrease in SBP over 10 years will prevent one death for every 11 patients treated!!

In the presence of CVD or target-organ damage, same tx will prevent one death for every 9 patients treated!!

Slide SourceHypertensionOnline

www.hypertensiononline.org

Diabetes: Tight Glucose Diabetes: Tight Glucose vsvs Tight BP Tight BP Control and CV Outcomes in UKPDSControl and CV Outcomes in UKPDS

StrokeAny Diabetic

EndpointDM

DeathsMicrovascularComplications

-50

-40

-30

-20

-10

0

% R

ed

ucti

on

In

Rela

tive R

isk

Tight Glucose Control(Average HA1c 7.9 vs 7.0)

Tight BP Control(Average 154/ 87 vs 144/ 82)

32%

37%

10%

32%

12%

24%

5%

44%

Bakris GL, et al. Am J Kidney Dis. 2000;36(3):646-661.Reprinted by permission, Harcourt I nc.

*

*

*

**P <0.05 compared to tight glucose control

www.hypertensiononline.org

A Case Study… A 55 year old Hispanic man comes to your

clinic for a first visit. He recently immigrated from Mexico several years ago, he was on some medications for blood pressure previously but has not taken anything for several years.

PE 5’ 8” 190 pounds BP 172/105 HR 82 What are you looking for on PE? What kind of screening labs do you order?

New Hypertensive Patient –The Physical ExaminationTest accuracy of reading (check cuff

size, check other arm, repeat office reading or home reading)

“fundoscopic evaluation”Thorough exam heart/lung/JVPAuscultate for abdominal bruit (renal

artery stenosis?)Femoral pulses (coarctation?)LE edema

Diagnosis of HTN:Initial Workup The “cheap screening for secondary hypertension”

labs: Creatinine Sodium, Potassium (hyperaldosteronism) U/A (nephrotic syndrome, nephritic syndrome) Calcium (secondary hyperparathyroidism) CBC (polycythemia) UTox (CCRMC special) Consider TSH (both hyper and hypothyroidism

associated with hypertension)

Diagnosis of HTN:Initial WorkupThe “Cardiovascular Risk” labs:

EKG (get as baseline + evaluate for LVH, prior MI)

Lipid panel Fasting glucose

Back to case study…. Repeat SBP 182/96, Obese (BMI 35).

CV/lungs WNL. No abd bruit. No edema. Na 141 K 4.2 Creat 1.2 U/A neg, except 30

protein. Spot urine protein 0.14 g/24 hours. EKG – LVH. CBC, Calcium, TSH, WNL. Utox neg. Fasting Glucose 145, HA1c 8.1

Would you do a secondary HTN workup? If so, what would you focus on?

Risk factors for secondary hypertensionPoor response to therapyAn acute rise of BP over a previously

stable valueConfirmed onset of hypertension before

20 or after 50 years (need accurate hx)Age < 30 in non-obese, non-black

patients with a negative family hxStage 3 HTN (>180/110)

Prevalence of Secondary Causes of Hypertension

COMMON (prevalence) RARE (prevalence)

Sleep Apnea

(? Really 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

Thyroid disease (1-3%) Carcinoid Syndrome

Hypercalcemia

Obstructive Sleep Apnea In one study, 83% of those with resistant HTN

had sleep apnea Intervention Studies (using CPAP in pts with

sleep apnea + resistant HTN): Two studies show decrease SBP 10-15 Other studies showed little or no reduction after CPAP

administration BOTTOM LINE: Reasonable to screen those

with resistant hypertension, especially if with risk factors (obesity, daytime somulence, apnea history)

Primary Hyperaldosteronism and Hypertension

Primary hyperaldo – excessive secretion aldosterone from tumor or Hyperplasia salt retention increase blood pressure

Primary Hyperaldosteronism May be present in 1.5 - 15% those with resistant

hypertension Etiologies

Adrenal adenoma Bilateral adrenal hyperplasia

Clinical features Hypokalemia (although normal K in 30%) Hypernatremia Metabolic alkalosis

Workup – AM plasma renin and aldosterone levels, go to Uptodate

Hypertension and renal artery stenosis

Decreased blood to kidney kidney “senses” diminished BPActivation renin/angiotension system vasoconstrictionAldosterone secretion salt retention

less blood flow

Renal Artery Stenosis –Etiologies Fibromuscular dysplasia (young women)

Atherosclerotic (HTN/DM/lipids/FH etc)

Suspect in resistant hypertension and: Elevation Cr with admin ACE/ARB Unilateral small kidney on imaging Abdominal bruit Repeated episodes flash pulmonary edema Acute rise in BP over previously stable value

Renal Artery Stenosis and Resistant HTN – Does Dx/Intervention matter? RAS from fibromuscular dysplasia responds well

to angioplasty (HTN improved in 20-80%) RAS from atherosclerosis: sustained response

to intervention “unusual” (lesions usually too diffuse) NEJM study: 106 pts randomized to angioplasty vs

med tx. No difference in BP control or renal insufficiency noted at 1 year

No good studies using angioplasty + stents Complications from intervention include

atheroembolism dialysis

Renal Artery Stenosis and Resistant HTN – Does Dx/Intervention matter?

BOTTOM LINE: If you suspect RAS, people who may benefit from intervention:

Young women (may have dysplasia) Suspicion for atherosclerotic RAS + any of the

following:

1) HTN not responsive to treatment, esp if severely elevated over stable value

2) Progressive renal failure

3) Repeated episodes flash pulmonary edema

4) Age < 60

Workup: At our institution, order MRA

Screening for the rare stuff – Reasonable to go by Hx/PE

Pheochromocytoma Paroxysmal elevations in BP, HA, Palpitations, sweating

Cushings disease Moon facies, central obesity, striae, inc glucose

Coarctation of aorta Hypertension in arms but not legs, decreased femoral pulse, abnl murmur/bruits

Acromegaly Looks like they have acromegaly

Height: 5’11”Weight: 129

My BMI, circa 1991: 17

Back to our patient…His blood pressure is 182/96.How many agents would you start him

on?

“The Rule of 10’s”Each BP med will reduce SBP by about

10 mmHgPer JNC recommendations:

If BP > 20/10 of goal, consider initial treatment with TWO agents (one should probably be diuretic)

Case continuedSo you start the patient on lisinopril 10

mg daily + HCTZ 25 dailyWhen should you check his potassium

and creatinine?

Recommended intervals for Monitoring Creatinine/K in ACE/ARB tx

GFR > 60 GFR 30-59 GFR < 30

After initiation or change of ACE/ARB dose

4-12 weeks 2-4 weeks <2 weeks

After dose is stable

6-12 months 3-6 months

1-3 months

Back to our patient…A sleep study was ordered given the

patient’s obesity.He comes back for followup, and is on

HCTZ 25 daily, Lisinopril 20 daily. His BP in office is 174/96

What are some other features that may be contributing to the patient’s hypertension?

White Coat HypertensionMay be responsible for 30% those with

resistant hypertensionAppears that BP values obtained at

home correlate better with target organ involvement

If a consideration – have patient check BP at home, have therapy target those values

Medication Adherence –Possibly helpful tipsAppropriately educate patient/family

about benefits of good BP controlHave patient check BP at home

periodically and bring in logbookUse “Rule of 10’s” to guide expectations

Tell patient: “You will likely need 2 or more meds to get your BP under control”

Medication Adherence –Possibly helpful tipsWrite on prescription: “take 1 tablet daily

to get blood pressure less than 140/90”

Use fixed-dose combinations Benazepril/HCTZ combo on both CCHP

and MediCal formularies

Other things that can increase Blood Pressure Medications

NSAIDS (inc SBP by approx 4 mmHg) Cocaine, Amphetamines Phenylephrine Anabolic Steroids Erythropoietin Oral Contraceptives

Excessive EtOH (>3-4 drinks/day) High Salt Diet Obesity

Another patient comes in…. A 65 YO woman is seen in your clinic for f/u

of longstanding HTN. She is on HCTZ 12.5 mg, Toprol XL 200 mg daily, amlodipine 10 daily, lisinopril 40 daily. Her BP is 162/94. Creat 1.4 (GFR 45), no protienuria. Utox neg.

She emphatically states that she takes her medications as directed. What is your next step in managing her HTN?

Diuretics – Cornerstone of HTN therapyMost patients with resistant

hypertension have inappropriate sodium/fluid retention EFFECTIVE DIURETIC THERAPY ESSENTIAL for HTN control

60% of those with resistant HTN improve BP by add/increasing diuretic therapy

What is the proper HCTZ dose? In uncomplicated patients without

resistant HTN or renal disease, no real benefit in HTN control with increase from 12.5 vs 25/50 daily

Those with resistant HTN and normal renal function – may need increase in HCTZ 12.5 25 50

What about resistant HTN with GFR < 50? HCTZ may not be not effective

Options:1. Substitiute another thiazide:

Metolazone 2.5 – 10 daily2. Substitute for loop diuretic:

Lasix 20-80 BID or Bumex 0.5-2 BID (Dosed BID because of short half life)

Toresemide 2.5 – 5 daily (longer half life, more expensive)

Resistant HTN and Diuretics

Spirinolactone for Resistant Hypertension Study patients with uncontrolled HTN and

on 4 agents were given spirinolactone 12.5-50 mg daily

Avg BP reduction at 6 months: 25/12 (!!)

Degree of antihypertensive benefit similar in subjects with and without primary hyperaldosteronism

**Follow K very closely, esp in renal failure Probably avoid in Creatinine > 2

My bullet points… Blood pressure control is a worthwhile

endeavor and improves mortality more than most other stuff you do in clinic

Strongly consider sleep apnea screening in hypertensive patients

Think of primary hyperaldosteronism in those with hypertension and low K

Renal artery stenosis relatively common, but unclear if invasive procedures work

My bullet points, continued “Rule of 10’s” guideline helpful for guidance tx OK to follow home BPs if patient with white

coat HTN Try combination medication and writing BP

goals on prescription to improve adherence If patient has resistant hypertension, ensure

s/he is on proper diuretic dose HCTZ may not work at GFR < 50 Spirinolactone may be really great