Resistant Hypertension

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study shows approximately 15% had resistant hypertension.

Approximately one in ten people with high blood pressure (nearly 100 million people worldwide) are resistant-hypertension.

What is Resistant Hypertension? Resistant hypertension refers to a blood pressure that stays stubbornly above the target in spite of the treatment with three drugs one among them is a diuretic. High blood pressure cannot be classified as “Resistant” until treatment failure with three-drug combination one among them should be a diuretic.

The true resistant hypertension is difficult to quantify because many patients suffer from ‘pseudo-resistant’ hypertension.

What is Pseudo-Resistant Hypertension? Pseudo-resistant hypertension refers to poorly controlled hypertension that appears to be resistant, but not. Most common reasons for pseudo-resistant hypertension are medication non-compliance, non-adhere to lifestyle advice, BP measurement error, white-coat hypertension, and other medication use that interfere with blood pressure.

Research suggests 28 % of treated hypertensive individuals are considered resistant to treatment.

Resistant hypertension diagnosis

How do I know whether I am resistant or pseudo-resistant hypertension?

Pseudo-resistance must be ruled out with a thorough hypertension adhesion review, followed by BP measurement with proper technique.

1. Assessing adherence to drug therapy - It is difficult to assert whether a patient truly adheres to an optimal dose of the 3-drug regimen. Hypertension adhesion review or patient noncompliance include whether taking the right medicines, correct dosage, and in time. Additionally, whether following healthy lifestyle choices that help lower blood pressure.
2. Rule out measurement error - Confirm BP measurement using an appropriately sized cuff, patient correctly positioned, and test after at least a 5-minute rest. Over 50% of apparent resistant hypertension are due to improper or inaccurate blood pressure measurement. The most common error is using the smaller cuff.
3. Rule out white-coat effect – Some individuals’ experience BP raise only in doctor’s office called white-coat effect. Confirm BP is not affected by white coat effect and wrongly consider as resistant hypertension. To burst this error, your doctor might order ambulatory blood pressure monitoring. For ambulatory BP monitoring, you need to wear a pager-sized automatic blood pressure recorder for 24 hours. Alternatively, you can use home blood pressure monitor to check your BP several times a day.
4. Other drugs that interfere BP control - heavy alcohol consumption, non-steroidal anti-inflammatory drugs (NSAIDs such as aspirin, ibuprofen, naproxen, and celecoxib), oral contraceptives or estrogen, antidepressants (such as bupropion, venlafaxine), and herbal supplements (such as Ginseng, licorice) will make BP difficult to control.

Patients with resistant hypertension are 50% more likely to experience an adverse cardiovascular event compared with patients with BP controlled by at least three antihypertensive agents.

If you ruled out all the above possible errors, then you are diagnosed with resistant hypertension. Otherwise pseudo-resistant hypertension and needs to correct the errors to achieve your target.

Resistant hypertension causes

High blood pressure causes arterial stiffness. Thus uncontrolled hypertension over time leads to resistant hypertension.

Patients with resistant hypertension have the common clinical characteristic that includes obesity, diabetes, chronic kidney disease, older age, arterial stiffness, and left ventricular hypertrophy.

1. Renal artery stenosis – Formation of artery plaque in blood vessels that nourish the kidneys. It is a hidden contributor to resistant hypertension.
2. Obstructive sleep apnea – Sleep conditions characterized by breath-pause while sleeping. Sympathetic nervous system activation plays a crucial role in the pathogenesis of hypertension in patients with OSA. Sympathetic overactivity may result in blood pressure elevation via vasoconstriction and increased systemic vascular resistance, increased cardiac output, and enhanced fluid retention. Increased aldosterone levels have been observed in OSA patients with resistant hypertension.
3. Arteriosclerosis – The hardening and stiffening of the arteries. High blood pressure stems from hardening of arteries.
4. Other BP interference - Obesity or heavy intake of alcohol or other substances that can interfere with blood pressure, which results in resistant hypertension.
5. Overactive adrenal glands (Cushing's syndrome) - Excess production of aldosterone by adrenal glands subsequently decrease renin levels. This excess leads to hypertension, metabolic alkalosis, hypernatremia, and potassium loss resulting in hypokalemia. This vicious cycle leads to resistant hypertension. Aldosterone stimulates sodium retention, increase arterial stiffness, endothelial dysfunction, and impaired baroreflex function.
6. Chronic Kidney Disease - renal disease represents one of the forms of target organ damage induced by hypertension. It seems that the relationship between hypertension and CKD is bidirectional; a vicious cycle leads to resistant hypertension. Treatment resistance in patients with CKD is due to sodium and fluid retention.

Laboratory evaluation includes renal function by assessing potassium, urea & creatinine levels and a urine dipstick to assess albumin and hemoglobin levels. An ultrasound test to assess renal size. It will help to identify small kidneys typical of the non-diabetic renal disease, or asymmetrical kidneys were seen in the renovascular disease.

Resistant hypertension treatment

Non-adherence to therapy may be a much more common cause of resistant (actually pseudo-resistant) hypertension than appreciated.

In the case of pseudo-resistant hypertension, the treatment should focus on to determine the cause of the noncompliance and to alleviate it.

7 Lifestyle change for resistant hypertension

You already know, resistant hypertension is difficult to manage. Thus you need to help the medication to work efficiently with some healthy changes in your lifestyle.

1. Strictly comply with the medicine - take right medicines, correct dosage, and in time.
2. Limit the sodium salt - stay away from foods high in sodium. You know processed foods are loads of sodium.
3. Healthy diet - Eat more vegetables and fruits, avoid sugar, and change to whole grain instead of refined carbs.
4. Watch your weight - Reducing calorie intake and increasing exercise help to lost weight.
5. Stop tobacco use - Tobacco will harden your arteries and thus raises the blood pressure. You BP are already resistant to treatment. Thus you must stop tobacco use.
6. Limit alcohol - Excess alcohol elevates your blood pressure; limit alcohol no more than one drink a day for women and two for men.
7. Reduce stress - Mental, emotional, physical stressors can raise your blood pressure. Meditation, yoga, tai chi, and breathing can lower it.

Treatment for secondary caused resistant hypertension

Studies show just 5 to 10% of resistant hypertension patients have an underlying secondary cause for their elevated blood pressure.

Resistant hypertension may be due to some underlying problem. Thus the treatment should focus on this underlying problem.

1. Abnormal body fluid balance is usually due to kidney disease, in such a case dialysis might help. Providing treatment to the kidney disease help to normalize body fluid and then blood pressure.
2. A hormone imbalance induced resistant hypertension can be corrected by normalizing the hormonal profile.
3. Renal artery stenosis induced resistant hypertension can be corrected by opening the blocked arteries with balloon angioplasty often improves blood pressure.
4. Obstructive sleep apnea induced resistant hypertension can be managed by using continuous positive airway pressure (CPAP), the best treatment choice for patients with OSA.
5. Obesity or heavy intake of alcohol or other substances induced resistant hypertension can be reversed by cutting down alcohol or other problematic substances and work to lose weight.

Resistant hypertension patients have a 3-fold increase in the risk of a cardiovascular event compared with controlled hypertension.

Medicinal treatment for resistant hypertension

No clinical trials have studied the effectiveness of specific drug regimens for the resistant hypertension treatment.

The available evidence emphasizes the use of low dose spironolactone as the preferred fourth drug if the potassium level in the blood is ≤4.5 mmol/L. With higher blood potassium levels, intensification of the thiazide-like diuretic drug should be considered.

Combinational medicine for resistant hypertension therapy

• An initial combination of thiazide diuretics, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and calcium channel blocker is often helping better control.
• For aged men who may have prostate disease, long-acting alpha-blockers such as doxazosin are very useful.
• For low potassium levels, aldosterone antagonist such as spironolactone or eplerenone may be very effective.
• Other most commonly used antihypertensive agents are hydralazine in multiple daily divided doses, along with beta-blocker for controlling the heart rate, methyldopa, and clonidine.