RESISTANT
HYPERTENSION

RESISTANT HYPERTENSION Defintion

Blood pressure greater than 160/100 mmHg on two visits not less than two months apart in spite of triple antihypertensive therapy:

1. Diuretics.

2. Beta – adrenegic blocker or sympatholytic.

3. Vasodilator, ACE inhibitor or calcium antagonist.

Prevalence

2.9 to 13% of patients seen in specialized clinics.

Causes

1. Lack of patient’s Compliance and Non – Adherence to Therapy:

Patient is not taking drugs as prescribed. Estimates of non-compliance vary from 20-80%.

2. Error in Measuring Blood Pressure (see chapter 3):

a. Improper equipment (Sphygmomanometer):

· Small bladder in relation to arm size in obese individuals. 

· Inaccurate manometer.

b. Inaccurate readings:

· Bladder is not centered over brachial artery.

· Using wrong values.

· Missing auscultatory gap.

· Variations due to arrhythmia.

· Position of the arm is not level with the heart.

· Too rapid deflation and/or too slow inflation.

Resistant Hypertension

c. Pseudohypertension:

· Due to arterial stiffness in elderly patients.

· There is a significant difference between intraarterial pressure and the cuff pressure.

· Osler-positive patients: A palpable radial artery is felt after inflation of the cuff above the systolic pressure.

3. lnadequate Drugs

a. Small dose: Giving less than the recommended dose and failure to increase to the upper dosage.

b. lnappropriate combination: Using two agents from the same pharmacologic group, e.g, using two sympatholytics.

c. lncomplete absorption (food intake), e.g., captopril should be administered one hour before meals on an empty stomach.

d. Antagonism from other drugs:

1. Sympathomimetics.

2. Antidepressants.

3. Adrenal steroids.

4. Non-steroidal anti-inflammatory drugs, e.g., indomethacin.

e. Reduced bioavailability:

1. Cimetidine.

2. Cholestyramine.

4. Volume Overload

Possibly the most common cause of true resistance.

Causes:

a. lnadequate diuretics.

b. Excessive sodium intake.

c. Progressive renal damage.

d. Fluid retention secondary to blood pressure reduction and the use of antihypertensive drugs such as sympatholytics and arterial

Resistant Hypertension

vasodilators.

5. Associated Conditions

a. Renal insufficiency.

b. Excessive alcohol intake.

c. Renovascular hypertension.

d. Pheochromocytoma.

e. Other forms of secondary hypertension. 

6. Hyperkinetic Circulation

Increased cardiac output secondary to reflex sympathetic stimulation can limit hypotensive action of direct arterial vasodilators. Beta-blockers or central sympatholytics are administered in combination with vasodilators to prevent the excessive adrenergic activity.

7. Office or White Coat Hypertension

· A common cause of false resistance.

· This is an exaggerated elevation of blood pressure during office or clinic measurement secondary to stress and anxiety and is mediated by sympathetic activity.

· Anxiety raises blood pressure as much as 30 mmHg.

· There is a defense or alarm reaction that develops when doctor is checking individual’s blood pressure causing a rise in pressure.

· Blood pressure measurements taken at the clinic (office) setting are higher than home readings.

· 25% of office (clinic) hypertensives are normotensives at home.

· Organ damage and serious cardiovascular complications are uncommon in patients with white coat hypertension. However, the prognosis is less favorable than in normotensive subjects.

· The possibility that the clinical setting, the procedure and the particular physician might be associated with bad news incorporated into the

Resistant Hypertension

patient's psychological outlook.

8. Severe Volume Depletion

Overdiuresis with subsequent reduction in intravascular fluid volume will reflexly activate two potent pressor systems: The sympathetic nervous system and the renin-angiotensin-aldosterone system.

9. Other Conditions

a. Idiopathic orthostatic hypotension: Some patients with this rare disorder have very high supine blood pressure readings with severe fall of blood pressure when standing.

b. Aortic atherosclerosis: The aorta loses its elasticity and becomes stiff. Decreased aortic distensibility in old age accounts for rise in systolic pressure and pulse pressure.

Management of Resistant Hypertension

1. Make sure that the patient is taking his antihypertensive drugs as prescribed, i.e., patient is compliant.

· Adherence to pharmacological treatment is difficult to measure.

· Patient self-reporting or irregular intake of prescribed medications can be a measure of compliance.

· Patient education is necessary to improve compliance.

2. If patient is compliant check that treatment is adequate, i.e., proper dosages and proper combinations.

3. Rule out drug interactions and excessive salt or alcohol intake. Drugs that commonly attenuate the actions of hypotensive agents are NSAIDs.

4. In elderly patients pseudohypertension should be excluded. In obese patients the proper cuff size should be used.

Resistant Hypertension

5. Office (white coat) hypertension is suspected when there is marked discrepancy between home and clinic blood pressure readings and especially when patient is complaining of low blood pressure symptoms, e.g., faintness, dizziness and syncope in spite of persistently elevated clinic readings and in absence of target organ damage. Ambulatory 24 hour blood pressure recording is indicated.

6. Exclude secondary hypertension, e.g., renal artery stenosis, renal parenchymal disease, pheochromocytoma.

7. Hypervolemia is probably the most common cause of true resistance. It should be suspected in every resistant case especially when the patient is gaining weight. Correct by salt restriction and administering potent (loop) diuretics.

8. If blood pressure remains uncontrolled after using aggressive antihypertensive regimen, it is recommended to hospitalize the patient, observe his blood pressure, evaluate possible pressor mechanisms and treat accordingly.

The following are some laboratory guidelines and relevant therapeutic approaches:

a. 24 hour urinary sodium: If increased use aggressive diuresis with salt restriction.

b. Plasma catecholamines: If increased add clonidine, methyldopa or prazosin.

c. Plasma renin activity: If elevated add beta blockers or ACE inhibitors.

d. Plasma and urinary aldosterone: If increased use spironolactone.

e. Plasma volume: If increased use loop diuretics and reinforce salt restriction.