nephrology - resistant htn

7/27/2019 Nephrology - Resistant HTN

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Resistant hypertensionM3 renal ambulatory teaching session



Clinical case

A 70 yo woman with a long-standing h/o HTN comes forfollowup. Her medications include atenolol 100 mgdaily, HCTZ 12.5 mg daily, lisinopril 40 mg daily and

ibuprofen 400 mg bid for osteoarthritis. She doe notsmoke or drink alcohol. Range of systolic and diastolicBPs (measured 3 x while she is seated) range from 164-170 mmHg/92-96 mm Hg and her pulse is 72 bpm. Her

BMI is 32.Fundoscopic exam reveals arteriolarnarrowing. Cardovascular exam is normal. She has noabdominal bruites. Lab data: K 3.8 mq/L, cr 1.2 mg/dL.No microalbuminuria.

Adapted from Moser et al, Resistant or Difficult-to-Control HTN, NEngJMed 354 (4), 2006, pp385-392.



How common is resistance?

More common than we think

Prevalence ?

Best estimates from HTN outcomes studies Medications provided free of charge

Adherence is monitored

Titration of BP dictated by protocols

ALLHAT (Antihypertensive and Lipid LoweringTreatment to Prevent Heart Attack Trial) 5 yr f/u 34% uncontrolled on average 2 medications

23% on 3 or more medications

8% prescribed 4 or more medications

More conservatively perhaps15%



Queries……

1. Common clinical characteristics of patients withresistant hypertension include all of the following except:

a. Obesity

b. DM

c. CKD

d. Black race

e. Male sex



Common characteristics of

patients with resistant HTN

Older age

Obesity Presence of sleep apnea

Excessive dietary Na ingestion

DM

CKD Female

African American

Left ventricular hypertrophy



What compels us to recognizepatients with resistant hypertension

and treat more aggressively?

Identify patients with reversible causes of HTN

Disproportionately high risk cardiovascular events

The higher the degree of BP elevation the more likelythe patient will have

CHF

Stroke

MI

Renal failure

Higher healthcare cost and use of resources



White coat HTN

Adherence

Exogenous substances



Drugs that can raise BP

• Cyclosporine, tacrolimus, corticosteroids

• Ibuprofen, piroxicam

• Celecoxib, rofecoxib

• 30-35 mcg estrogen oral contraceptives

• Sibutramine (meridia), phentermine(adipex), ma huang (ephedra)

• Nicotene, amphetamines

• Fludrocortisone

• Bromocriptine

• Phenelzine

• Testosterone

• Pseudoephedrine

Immunosuppressive

NSAIDs

COX-2 inhibitors

Estrogens

Weight loss agents

Stimulants

Mineralocorticoids

Anti-parkinsonian

MAO inhbitiors

Anabolic steroids

Sympathomimetics



White coat HTN

Adherence

Exogenous substances

Obesity

Secondary causes



Obesity

Associated with

Increasing severity of HTN

Use of increasing number of antihypertensive medications

Increased likelihood of never achieving goal BP

“On a population basis, the probability of lack of BP controlin obese patients is about 50% higher than hypertensivepatients who are at normal weight.”

Mechanisms:

Increased Na and fluid retention

Greater sympathetic activation

Increased stimulation of the renin-angiotensin-aldosterone

system



OSATreatment

Treatment with CPAP likely benefits BP control

Reduction in daytime and nighttime SBP and DBPs by10 mm Hg in recent study

Other studies variable results

http://www.smart-kit.com/wp-content/uploads/2006/12/cpap%20mayo.jpg

http://www.medgadget.com/archives/img/398792dij.jpg



Queries……..

3. You would suspect a secondary cause of HTN in allof the following patients with HTN except a patient

a. with previously well controlled and nowuncontrolled HTN

b. who develops hypokalemia on a diuretic

c. with snoring and daytime somnolenced. who develops HTN at the age of 75



When to suspect secondary HTN

• Severe HTN at a young age (age of onset <20-30 yrsin absence of family hx) or older (onset > 50 yrs)

• HTN refractory to medical management or onceresponsive now difficult to control

• Episode of hypertensive crisis or paroxysmal BPelevations

• Symptoms related to the underlying diagnosis (muscle weakness, episodes of tachycardia, sweating,tremor, thinning of skin, flank pain)



When to suspect secondary HTN

• Loud snoring, awaken with H/A, sleep inappropriatelythroughout day

• Ingestion of medications that affect BP (decongestants, estrogens, appetite suppressants,NSAIDS, exogenous thyroid hormone, recent EtOH,illicit stimulants, adrenal steroids)

• A patient with significant HTN and unprovokedhypokalemia and metabolic alkalosis



Lab and Diagnostic evaluationfor suspected secondary HTN

BUN, cr, electrolytes

Serum calcium

Urine protein/creatinine

U/A and microscopic

EKG

Plasma renin andaldosterone

Plasma free

metanephrines TFTs

Renal U/S with dopplers

If appropriate consider

other tests: cortisol,polysomnography



Back to our case……

A 70 yo woman with a long-standing h/o HTN comes forfollowup. Her medications include atenolol 100 mgdaily, HCTZ 12.5 mg daily, lisinopril 40 mg daily and

ibuprofen 400 mg bid for osteoarthritis. She doe notsmoke or drink alcohol. Range of systolic and diastolicBPs (measured 3 x while she is seated) range from 164-170 mmHg/92-96 mm Hg and her pulse is 72 bpm. Her

BMI is 32.Fundoscopic exam reveals arteriolarnarrowing. Cardovascular exam is normal. She has noabdominal bruites. Lab data: K 3.8 mq/L, cr 1.2 mg/dL.No microalbuminuria.

Adapted from Moser et al, Resistant or Difficult-to-Control HTN, NEngJMed 354 (4), 2006, pp385-392.



What would you suggest for this patient?

Adherence to medication

Discontinue NSAID

Exercise, weight loss Dietary Na restriction

Increase dose of HCTZ or change to furosemide

Add another agent like a CCB



Clinical case #2

A 49 yo AA man returns for f/u to your clinic. He is currently onmetoprolol XL 100 mg qd, lisinopril 40 mg qd, losartan 100 mgqd, and clonidine 0.2 mg tid. He has a strong FH of HTN. Hefollows a strict low Na diet. Previous evaluation for secondarycauses of HTN, including evaluation for OSA, was unrevealing.

BP today is 150/100, pulse 65. His urinalysis has trace proteinand is blood chemistries are normal. What would be the nextdrug of choice for this patient?

a. Amlodipine 10 mg qd

b. Minoxidil 5 mg qdc. Furosemide 40 mg qdd. Chlorthalidone 25 mg qde. Spironolactone 25 mg qd

Modified from The Journal of Clinical Hypertension, suppl 1, vol 9, no 1, Jan 2007, p 31.



Algorithm for treatment of HTN

http://www.nhlbi.nih.gov/guidelines/hypertension/express.pdf



Which is the ideal drugcombination

I don’t know

Combination of CCB, ACE-inhibitor/ARB, diuretic oftenrecommended

A different approach based on PE physiology

High systemic vascular resistance Increased catecholamine secretion

Volume excess

Hirsch, Cleveland Clinic Journal of Medicine: Vol 74, N 6, June 2007, pp449-456.



http://www.nhlbi.nih.gov/guidelines/hypertension/express.pdf



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http://www.servier.com/imgs/Pro/cardio/cch/issues/17/7.gif

CKD✔

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Diuretic options and prescription

Thiazide diuretic

Consider using long-acting

chlorthalidone

Dosing

not widely available infixed dosing combinations

Loop diuretic

Consider in those

with CKD (GFR < 60)

on potent vasodilators

Dosing

bid to maximizeeffectiveness of diuresis

For both Monitor electrolytes after initiation Aim for weight loss of not more than 0.5

kg/day



Na excess and BP control

“Increasing the dose of antihypertensive agents

in the presence of an expanded extracellular

fluid volume has no effect on the arterialpressure.” Finnerty 1971

http://www.healthcarevox.com/uploads/US.jpg



Education

x



Hyperaldosteronism:the link to resistant HTN

Hypothesis is that aldosterone contributes more broadlyto hypertension beyond cases of classical primaryaldosteronism, first described by Conn in 1955

How common is it?

Epstein and Calhoun, Current Hypertension Reports 2007, 9: 98-105



Hyperaldosteronism:Biochemical Diagnosis

PAC = plasma aldosterone concentration (ng/dL)

PRA = plasma renin activity (ng/ml/min)

ARR = PAC/PRA

ARR < 20, reliably excludes hyperaldosteronism

ARR > 20, suggestive but not diagnostic

Based on elevated aldosterone levels in plasma and urine in the faceof suppressed renin activity

Biochemical confirmation of aldosterone excess

On 24 hour urine collection: Urinary aldosterone (> 12 mcg) in the face

of high sodium excretion ( 200 mEq)



Spironolactone-inducedreductions in SBP and DBP

Nishizaka et al, Am J Hypertension 2003; 16: 925-930.Modified in Epstein and Calhoun, Current Hypertension Reports 2007, 9: 98-105



Spironolactone-inducedreductions in SBP and DBP

Pimenta and Calhoun, Current Hypertension Reports 2007, 9: 353-359.



Hyperaldosteronism:additional information

Primary aldosteronism

Based on aggregate averages from studies: 40-66%of patients with primary aldosteronism are found to

have aldosterone adenomas

Is there a broader anti-hypertensive benefit of aldosterone antagonists?

The impact of hyperaldosteronism on resistanthypertension may be greater than the typicalparameters of primary hyperaldosteronism wouldindicate.

Low renin HTN as a variant of aldosterone-induced HTN?



Spironolactone-induced BP responses inpts with and without primary

aldosteronism

Nishizaka et al, Am J Hypertension 2003; 16: 925-930

SBP DBP

+ -



Responses toaldosterone blockade

Contribution of hyperaldosteronism to HTN may begreater than indicated by hormone levels alone.

Levels of aldosterone, renin, ARR, urine aldosterone arenot necessarily predictive of BP response to aldosteroneblockade.

It is important to check biochemical parameters toascertain aldosterone excess to ultimately identify thosewith adenomas.



Clinical use of aldosterone blocking agents

Spironolactone

Begin at 12.5-25 mg daily

Maximum dose generally 25-50 mg daily

Monitor K after 1 week in high risk patients, 4 weeksif lower risk

10% breast tenderness



Take Home Points

1. Modifying contributing risk factors can have a favorableimpact on BP control, eg. obesity, exogenous medications.

2. Both the severity of HTN and the number of patients with

hypertension increase with sleep apnea severity, asindicated by the respiratory disturbance index.

3. In general, diuretics are under-prescribed in the treatmentof resistant hypertension and use of diuretics in

appropriate doses may improve the efficacy of other anti-hypertensive agents.



Take Home Points

4. In patients with resistant hypertension, the prevalenceof hyperaldosteronism is particularly high.

5. Aldosterone antagonists have been shown to providesignificant additional BP benefit in patients with resistanthypertension when added to existing multi-drugregimens, which already include a diuretic and an ACEinhibitor.

nephrology - resistant htn

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