Advanced Topics in Hypertension

Resistant Hypertension

• Not “refractory”, as this implies that we can’t fix the BP.

• Definition:– Blood pressure that remains above goal despite

concurrent use of 3 antihypertensive agents (including a diuretic) of different classes in optimal dose amounts.

Resistant Hypertension

Lifestyle?

Common Secondary Causes?

Uncommon Secondary Causes?

Interfering Substances

Pseudo-resistance

Non-Adherence

Ambulatory BP Monitoring

Pseudoresistance

• Poor Blood Pressure Measurement– Patient must sit quietly for 5 mins b4– No caffeine, alcohol or smoking for 30 mins b4– Cuff must be appropriate size (2/3 of arm)– Patients’ claims of “rushing in” from parking or “backup on the

beltway” are not valid reasons to ignore elevated BP!• White Coat Hypertension

– True WCH refers to normal home values with elevated office values. – Rare, but real. Don’t take the patient’s word

• Home self-monitoring (if reliable patient) and ABPM equivalent for diagnosing this.

– Anxiety disorders common in patients with WCH– back

Lifestyle Factors

• Obesity• Excess Salt intake• Heavy Alcohol Intake• Lack of exercise• Low potassium diet

Lifestyle changes in order of effectiveness:

Lose 10 lbsReduce nacl to 6gms/dCut Alcohol to <2 drinks/dExercise 30 mins 5x dailyDASH diet

Ineffective Lifestyle Changes

• Eliminate coffee– Caffeine transiently raises bp for 30 mins

• Stress Management– No effect on BP control in vast majority– Some highly anxious patients benefit with lower BP

• “Macronutrients”• Chelation therapy• Perhaps soy protein, dark chocolate, accupuncture are

effective– More study needed– back

SS Bob

• Midshipman Bob is a 21 yo naval academy midshipman referred for evaluation of hypertension. He doesn’t meet the definition of resistant HTN, but you’re seeing him in the rHTN clinic anyway. He’s taking lisinopril 20 and has a BP of 148/98. Denies illicit drug use. Negative family history. Exam is o/w benign.

• What else should you ask about?

3 classes of Interfering Substances

• Prescription Medications

• Non-Prescription Medications (OTC), including herbal “GNC” preparations

• Drugs of Abuse

Prescription Medications

• NSAIDS, COX-2 inhibitors– Inhibit renal prostaglandin production with sodium and fluid

retention– Average increase in MAP of 5 mm Hg– Blunt effects of diuretics, ace-I, arb, bb– COX-2 inhibitors could be worst offenders!

• Stimulants– Methylphenidate, amphetamine, modafinil

• Glucocorticoids– Responsive to loop diuretics

• OCP’s, EPO, Cyclosporine

OTC medications

• Decongestants– Most of these are stimulants (pseudoephedrine,

phenylephrine, phenylpropanolamine)– Don’t use at all in adult hypertensive patients

• Ephedra, ma huang• Energy drinks (guarine/taurine)

Drugs of Abuse

• Cocaine• Crack cocaine• Crystal meth

– back

Miss Selma Bouvier

57 yo obese woman referred to you because of uncontrolled HTN. She is a smoker, with stable class 1 angina; CRI (cr 2.4); GERD; BPH; vasomotor rhinitis; and hyperlipidemia. She is taking HCTZ 25 daily, Lisinopril 40 daily, Felodipine 10 daily, Metoprolol 25 bid, simvastatin 40 qd, nexium 20 qhs, metamucil, surfak, and celebrex. She has no complaints, but wonders if estrogen therapy “will make her skin softer?”

BP 180/70, pulse 60. Lungs clear; CV rrr without mur; no abd bruits, masses; extremities with good pulses and no edema.

What are you going to do first?

Common Secondary Causes

• There are many items to discuss with Ms Bouvier, including smoking cessation, dangers of estrogen in someone with heart disease, weight loss, etc.

• Let’s focus on secondary causes!• Name the four most common secondary causes, in

order of prevalence– Obstructive Sleep Apnea– Primary Aldosteronism– Medical Renal Disease– Renal Artery Stenosis

Obstructive Sleep Apnea• Strongly associated with hypertension• Will not gain control of resistant HTN without addressing OSA

– I use a modified Epworth screen:• Do you snore?• Do you have early am headaches?• Do you stop breathing at night?• Do you feel fatigued during the day?

• 15% in adults; 30% in hypertensive adults; ??% in adults with resistant hypertension

• Mechanism unclear, but potential nitric oxide mechanism or increased sympathetic tone

• Not all OSA patients are obese• Rx: CPAP, other airway devices, UPPP

Primary Aldosteronism

• Prevalence of mild autonomous secretion of aldosterone is much greater than previously thought– 14% prevalence in our clinic (2001)– 6-16% in other studies– More common with severe hypertension

• Hypokalemia rarely present• Strong relationship with obesity and OSA• Rx: strong response to Spironolactone

– Unclear role of eplerenone.– Do not use with CClr <30; beware hyperkalemia

Diagnosis of PA

• Fasting renin and aldosterone levels are first test– Better if done off meds, but this is often impractical and ill-

advised in resistant HTN– Suppressed renin (<2.0) + elevated aldo (>15) are highly

suggestive– Should do CT to ensure no nodule; if goal is just HTN

treatment, can stop here.• Next test is 24 hr urine aldo with adequate sodium

intake• Then saline suppression test• Then localization with selective adrenal vein sampling.

Medical Renal Disease

• Common finding in resistant HTN patients• Chicken or egg?• Treatment resistance due to increased sodium

and fluid retention with intravascular volume expansion

• Answer is to use powerful diuresis with loop diuretics

Renal Artery Stenosis

• High prevalence in older patient groups (12%)• Degree of contribution to resistant HTN unclear

– BP in some patients will improve with stenting• Most are atherosclerotic; some in younger

patients are fibromuscular dysplasia• More likely in smokers, older patients, those with

CAD, PAD• Suspected with flash pulmonary edema• Noninvasive studies not very good.

How Common is Common?• OSA – 30% among resistant hypertensives• PA – 10% (conservatively)• RAS – 5%• Medical renal disease – 20%

• So, conservatively 65% of resistant hypertensive patients will have some secondary medical cause of their hypertension!

• Look for it!• Even if your patients have controlled BP on 3+ drugs, you’re probably missing one

of these diagnoses…• If you can’t find anything and can’t get their BP fixed, most experts recommend a

trial of spironolactone 25-100 daily– Do not use in CKD– Beware hyperkalemia!

• back

Uncommon Secondary Causes

• Pheochromocytoma• Cushing’s Syndrome• Hyperthyroidism• Hyperparathyroidism• Coarctation of Aorta• Brain Tumor

• Back

Mr. GK Willie

• Mr. Willie is a 48 yo groundskeeper whom you’re seeing in the resistant HTN clinic. He’s prescribed 4 antihypertensives (atenolol 50, lisinopril 40, hctz 25, and amlodipine 10). He is otherwise healthy, except for mild osteoarthritis. He tells you he’s taking his medications, but sometimes “forgets” to take them.

• You note via AHLTA that he last picked up a 3 months supply 4 months ago, and that his pill bottles are mostly full.

NonAdherence

• How do you figure this out?– Ask!– Pill Counts are the gold standard– Refill records from pharmacy

• One big advantage of our system

– Morisky Questionnaire• Do you ever forget to take your medications?• Are you careless at times bout taking your medication?• When you feel better, do you sometimes stop taking medications?• When you feel poorly do you sometimes stop taking medications?

How can you improve this behavior?

• Use combination medications• Once daily medications• Emphasize safety and effectiveness of

medications• Nursing/Corps staff have different

relationships with patients and can help• Pill boxes• back

Mrs. Clancy Wiggum

• 53 yo woman with PMH of HLP, hypothyroidism, osteoarthritis. Reports for routine checkup to your clinic. During the course of your visit, you note her BP was 148/88. She states (pick one):– “the traffic was bad”, or – “I rushed all the way from the parking lot”, or – “It’s always high when I come to the doctor and it’s normal at home.”

• You retake the BP and it’s 151/85. You review her record, and four of the past eight BPs were elevated over the past two years. She doesn’t want to take medications.

• What do you do?

Ambulatory Blood Pressure Monitoring

• Only indication that medicare will pay:– r/o white coat HTN– Intense conditions must be met

• Other indications:– Evaluate degree of control– Evaluate Circadian Response in BP– Convince a patient to take medications– Evaluate for hypotension– Adjunctive management of resistant HTN

ABPM Interpretation

• Daytime mean ABP should be below 135/85

• Blood pressure load (proportion of readings above 140/90)

– >=40% BP load is considered abnormally high

• Dipping refers to drop in BP with sleep– At least 10% is expected

• “Non-dipper” status is abnormal– Blunted decline seen in sleep disordered breathing, autonomic

failure, elderly patients– Associated with increased prevalence of

• LVH• Albuminuria• Peripheral Arterial Disease• Cerebral Lacunae• Increased Cardiovascular Mortality

Refer your patients for rHTN or for an ABPM!

• ABPM: Consult to General IM, say you want an ABPM– State the indication– We’ll call them, perform the test, interpret it and put

the results in AHLTA• rHTN: Consult to General IM, say how many and

which medications the patient is taking– State you want the patient to be seen in the resistant

HTN clinic– back