Resistant and Secondary Hypertension

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Resistant and Secondary Hypertension

• Oliver Z. Graham, MD
• Hypertension Specialist
• Department of Internal Medicine

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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

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Benefits of Lowering BP

• Antihypertensive therapy has been associated
  with
• 35-40 reduction in stroke
• 20-25 reduction in MI
• 50 reduction in heart failure

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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!!

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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?

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New Hypertensive Patient The Physical
Examination

• Test accuracy of reading (check cuff size, check
  other arm, repeat office reading or home reading)
• fundoscopic evaluation
• Thorough exam heart/lung/JVP
• Auscultate for abdominal bruit (renal artery
  stenosis?)
• Femoral pulses (coarctation?)
• LE edema

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Diagnosis of HTNInitial 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)

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Diagnosis of HTNInitial Workup

• The Cardiovascular Risk labs
• EKG (get as baseline evaluate for LVH, prior
  MI)
• Lipid panel
• Fasting glucose

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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?

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Risk factors for secondary hypertension

• Poor response to therapy
• An acute rise of BP over a previously stable
  value
• Confirmed onset of hypertension before 20 or
  after 50 years (need accurate hx)
• Age lt 30 in non-obese, non-black patients with a
  negative family hx
• Stage 3 HTN (gt180/110)

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Prevalence of Secondary Causes of Hypertension
COMMON (prevalence) RARE (prevalence)
Sleep Apnea (? Really Common ?) Pheochromocytoma (lt0.5)
Renal Disease (1-8) Coarctation of Aorta (lt1)
Hyperaldosteronism (1.5-15) Cushings Syndrome (0.5)
Renal Artery Stenosis (3-4) Acromegaly
Thyroid disease (1-3) Carcinoid Syndrome
Hypercalcemia
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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)

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Primary Hyperaldosteronism and Hypertension
Primary hyperaldo excessive secretion
aldosterone from tumor or Hyperplasia ? salt
retention ? increase blood pressure
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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

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Hypertension and renal artery stenosis
?less blood flow

• Decreased blood to kidney ? kidney senses
  diminished BP
• Activation renin/angiotension system ?
  vasoconstriction
• ?Aldosterone secretion ? salt retention

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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

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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

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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
• HTN not responsive to treatment, esp if severely
  elevated over stable value
• Progressive renal failure
• Repeated episodes flash pulmonary edema
• Age lt 60
• Workup At our institution, order MRA

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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
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• Height 511
• Weight 129
• My BMI, circa 1991 17

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Back to our patient

• His blood pressure is 182/96.
• How many agents would you start him on?

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The Rule of 10s

• Each BP med will reduce SBP by about 10 mmHg
• Per JNC recommendations
• If BP gt 20/10 of goal, consider initial treatment
  with TWO agents (one should probably be diuretic)

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Case continued

• So you start the patient on lisinopril 10 mg
  daily HCTZ 25 daily
• When should you check his potassium and
  creatinine?

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Recommended intervals for Monitoring Creatinine/K
in ACE/ARB tx
GFR gt 60 GFR 30-59 GFR lt 30
After initiation or change of ACE/ARB dose 4-12 weeks 2-4 weeks lt2 weeks
After dose is stable 6-12 months 3-6 months 1-3 months
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Back to our patient

• A sleep study was ordered given the patients
  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 patients hypertension?

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White Coat Hypertension

• May be responsible for 30 those with resistant
  hypertension
• Appears 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

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Medication Adherence Possibly helpful tips

• Appropriately educate patient/family about
  benefits of good BP control
• Have patient check BP at home periodically and
  bring in logbook
• Use Rule of 10s to guide expectations
• Tell patient You will likely need 2 or more
  meds to get your BP under control

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Medication Adherence Possibly helpful tips

• Write 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

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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 (gt3-4 drinks/day)
• High Salt Diet
• Obesity

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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?

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Diuretics Cornerstone of HTN therapy

• Most 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

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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

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What about resistant HTN with GFR lt 50?

• HCTZ may not be not effective
• Options
• Substitiute another thiazide
• Metolazone 2.5 10 daily
• 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)

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Resistant HTN and Diuretics
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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 gt 2

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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

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My bullet points, continued

• Rule of 10s 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 lt 50
• Spirinolactone may be really great

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