Resistant Hypertension

Resistant Hypertension Definition

Uncontrolled Resistant Hypertension

What is Resistant hypertension? Resistant hypertension is a common clinical condition faced by physicians. It is defined as blood pressure that remains elevated despite concurrent use of three optimal antihypertensive medications, which includes a diuretic.

Those whose blood pressure is controlled with four or more medications are considered to have resistant hypertension, and is an evidence of a more severe stage of hypertension, which has fourfold greater risk of cardiovascular disease as compared with patients whose blood pressure are controlled by less than four drugs.

The Joint National Committee’s recommendations on high blood pressure define resistant hypertension as “the failure to reach goal blood pressure despite full doses of an appropriate 3 drug regimen including diuretics”.

The European Society of Hypertension definition is “hypertension resistant or refractory to lifestyle measures and at least three medications, including a diuretic to lower blood pressure to target”.

Pseudoresistance, including white coat hypertension (a phenomenon wherein blood pressure is elevated only at the doctor’s clinic), poor blood pressure technique or secondary to poor medication adherence, must be excluded. End organ damage including hypertensive retinopathy and albuminuria are more mostly found to have true resistant hypertension compared with white coat hypertension.

Resistant Hypertension Causes

The causes of resistant hypertension is almost always multi-factorial. The main categories to consider for patients with resistant hypertension include secondary hypertension, longstanding uncontrolled hypertension, interfering medications, non adherence to therapy and lifestyle factors.

Resistant hypertension is most likely due to secondary causes as compared to patients with easily controlled blood pressure. This can be secondary to chronic kidney disease, obstructive sleep apnea, pheochromocytoma, Cushing’s Syndrome, Renal Artery Stenosis, renovascular disease or primary hyperaldosteronism.

Drug regimen lacking a diuretic often results to uncontrolled hypertension leading to resistant hypertension. Interfering medications like nonsteroidal anti-inflammatory agents interfere with antihypertensive medications by blocking prostaglandin and inducing salt retention, aggravating the condition. Other medicines like sympathomimetic agents (e.g. decongestants), stimulants (e.g. amphetamine, methylphenidate), corticosteroid, oral contraceptives, herbal components (e.g. ma huang), erythropoietin, licorice and cyclosporine also interfere with antihypertensive drug efficacy.

Improper behavior and attitude like sedentary lifestyle, excessive alcohol intake and indiscriminate sodium intake all have a negative impact on drug efficacy. Clues to poor adherence to medications are elicited by thorough patient history which includes careful review of prescription refills. Clinical characteristics of patients with resistant hypertension include old age, chronic kidney disease, diabetes mellitus, female sex, black race, obesity, left ventricular hypertrophy and arterial stiffness. High blood pressure per se causes stiffness of the arterial walls and if left untreated or uncontrolled, it is likely to be resistant to therapy.

Resistant Hypertension Guidelines

Before diagnosing a person with resistant hypertension, great care should be taken to ensure that blood pressure measurements are precise and reflective of genuine blood pressure. Improper blood pressure techniques can lead to a misdiagnosis of resistant hypertension. Accurate assessment of treatment adherence, use of good blood pressure technique, identification of causes contributing to treatment resistance including lifestyle factors and documentation of end organ damage are essential to correct diagnosis.

Medical history should include the duration, progression and severity of the hypertension; treatment response; adherence to therapy; concurrent medications; and other co-morbidities. In a nonjudgemental fashion, patient should be asked on how adherent they are taking all the prescribed medications. A history of peripheral or atherosclerotic disease suggests the possibility of renal artery stenosis while labile hypertension with palpitations and diaphoresis increases the likelihood of pheochromocytoma.

Before taking the blood pressure, ask the patient to sit quietly in a chair with his back supported for 5 to 10 minutes. Use the correct cuff size with the air bladder covering at least 80% of the arm and supporting the arm at the heart level. The blood pressure should be taken in both arms and the arm with the higher reading generally should be used to make future measurement.

A careful and thorough physical examination will also help you to the diagnosis or will reveal complications or end organ damage. A fundoscopic examination will reveal arteriolar constrictions, AV nipping, cotton wool appearance and/or swelling of the optic disk.

Resistant Hypertension Diagnosis Evaluation

The presence of carotid, abdominal or femoral bruits increases the likelihood that renal artery stenosis exists. Aortic coarctation is suggested by diminished femoral pulses or a discrepancy between arm and thigh blood pressure. Moon facie, abdominal striae, prominent interscapular fat deposition suggests Cushing’s disease.

Laboratory evaluation includes sodium, potassium, creatinine and urea to assess renal function, a urine dipstick for albumin and hemoglobin; paired, morning plasma aldosterone and plasma renin or plasma renin activity (PRA) to screen for primary aldosteronism. A 24-hour urine collected during a patient’s normal diet can aid in estimating dietary salt and potassium intake; calculating of creatinine clearance and aldosterone excretion and for measurement of urinary metanephrines or plasma metanephrines in patients suspicious to have pheochromocytoma.

When faced with individuals whose blood pressure is truly not controlled in spite of three full doses of anti-hypertensive medications, it is prompt to refer him to a cardiologist.

Management of Resistant Hypertension

Most resistant hypertension can be controlled with the addition of more medications and higher dosage in combination of lifestyle changes. A diuretic should always be a part of the treatment regimen as the absence of a diuretic may be the cause of unresponsiveness.

Resistant Hypertension Treatment

How to treat resistant hypertension? The treatment of resistant hypertension is directed towards reversal of lifestyle factors which contribute to treatment resistance; accurate diagnosis and treatment of secondary causes of hypertension; and use of effective multi-drug regimens.

Lifestyle changes include weight loss, regular physical exercise, reduction of sodium intake to below 100mmol/day, moderation of alcohol intake of fewer than 14 drinks per week for men and 7 for women, and ingestion of high fiber, low fat, low cholesterol diet. Potentially interfering substances should be withdrawn or substituted. Obstructive sleep apnea, if present, should be treated.

Renal Denervation for Resistant Hypertension

Renal sympathetic denervation (RSDN), or simply renal denervation is an approved therapy for resistant hypertension. It is a minimally invasive catheter based procedure using ultrasound or radio-frequency ablation targeted at treating uncontrolled hypertension.

Drug Resistant Hypertension

An initial combination of a thiazide diuretic, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with a calcium channel blocker often leads to control and generally well tolerated. The addition of other drugs is often tailored according to individual patient’s determinants. Spironolactone or eplerenone, may be effective for patients with low potassium levels. Other medications like hydralazine, methyldopa and clonidine should be used in caution, particularly clonidine for patients whose adherence is in question, may lead to sympathetic rebound if discontinued suddenly.

Resistant Hypertension PDF


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