What Is Resistant Hypertension?

  • Reema DevliaMaster of Science - MSc Pharmaceutical Technology, King’s College London
  • Shazia AsimPhD Scholar (Pharmacology), University of Health Sciences Lahore, Pakistan
  • Regina LopesSenior Nursing Assistant, Health and Social Care, The Open University

Introduction 

Do you suffer from high blood pressure (BP)? Have you made changes to your lifestyle and taken at least three BP medicines, but it’s not reducing? In that case, you may have resistant hypertension (RH), which can be difficult to treat and can have an underlying medical cause. 

Hypertension is a major health concern and silent killer that puts you at risk of cardiovascular disease (CVD), where 50% of strokes occurring in those with RH could be prevented by controlling BP.1

This article will explore the causes and symptoms of RH, how it’s diagnosed and the treatment options available to you.

Understanding hypertension

Hypertension, or high BP, is characterised by persistently high BP in the systemic arteries, whereby the heart must work harder to pump blood around the body. If your BP is too high, it puts extra strain on your blood vessels, heart, and other organs such as the brain, kidneys, and eyes.

BP is expressed as the ratio of the systolic BP (pressure in your arteries when the heart beats) and the diastolic BP (pressure when the heart relaxes).2 Ideal BP ranges from 90/60 mmHg and 120/80 mmHg. However, high BP is considered to be 140/90 mmHg and above. 

It’s not always clear what causes high BP, however, certain factors that increase your risk in developing hypertension are:

  • Being overweight 
  • Eating too much salt
  • Lack of exercise
  • Drinking too many caffeine-based drinks
  • Smoking
  • Being over 65
  • Having a relative with a high BP

High BP could also be caused by an underlying health condition or taking certain medications.

What is RH?

RH is defined as high BP above 140/90 mmHg despite taking at least three antihypertensive treatments (BP medications) from different classes, including one diuretic, at the correct combinations and maximum doses.3

However, if a patient achieves BP control with a fourth antihypertensive medication, they remain resistant. 

RH is a severe condition which is estimated to appear in 9-18% of hypertensive patients.3 The condition is crucial to address as it’s associated with a 50% higher risk of a cardiovascular (CV) event, such as a heart attack or stroke, compared to standard hypertension. 

Types of RH

1. True resistant hypertension

True RH is BP that remains uncontrolled despite optimal therapy.4 It’s caused by a combination of factors such as lifestyle, medication non-adherence, and underlying medical conditions.5

2. Pseudo-resistant hypertension

“Pseudo-resistance” is high BP that may seem resistant to treatment, but is attributed to other factors interfering with treatment or measurements.6 These can include

  • Stiffening of the arteries
  • Medicines and supplements
  • Wrong medications or wrong doses
  • The white-coat effect is when your BP measurements are higher in a medical setting compared to at home
  • Lifestyle
  • Improper measurement techniques

Both types of RH are important to diagnose and combat as both conditions raise your risk of heart attack or stroke.

Symptoms of RH

Untreated high BP is dangerous to your health, but symptoms are not easy to identify, and many people can go long periods without knowing they have RH. People with RH have noted getting headaches, pressure in the chest, shortness of breath, and nose bleeds. However, the best way of knowing is to get your BP measured by your doctor.

Causes of RH

Interfering medications 

Several prescription or over-the-counter (OTC) medications may induce RH or contribute to treatment resistance. Examples include:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) can alter renal function, and reduce renal blood flow and glomerular filtration rate, thus causing sodium retention and a rise in BP.7 Examples of drugs include ibuprofen and naproxen
  • Oral contraceptives result in an 80% increased risk of developing hypertension
  • Combined oral contraceptives such as progestin and estradiol are an example of such drugs that are associated with BP elevations8
  • Anti-vascular endothelial growth factor (anti-VEGF) agents stop abnormal blood vessels from leaking, growing, and bleeding under the retina. Studies show that VEGF inhibition can lead to increased blood flow resistance and therefore elevated BP8 

Secondary causes of RH 

Approximately 25% of RH patients have underlying medical conditions. Secondary hypertension is very hard to control unless these underlying causes are addressed. Common causes include:

  • Obstructive sleep apnea (OSA) is a tendency to stop breathing for seconds during sleep. Sudden drops in blood oxygen levels that increase BP and strain the CV system
  • Primary aldosteronism is when the adrenal glands make an excess of the hormone, aldosterone. This causes the body to retain salt and water, thus raising BP8
  • Chronic kidney disease (CKD) increases BP due to impaired sodium excretion and premature vascular aging.7 Over half of patients with CKD were reported to have RH8
  • Renal artery stenosis is the narrowing of arteries that prevents blood from reaching the kidneys. Reduced blood flow can increase BP9 
  • Pheochromocytoma is a rare and usually benign tumour in the adrenal gland. The tumour releases too much epinephrine and norepinephrine hormones which raise the BP

Lifestyle factors 

RH can be affected by several lifestyle factors, such as8

  • High salt intake
  • Obesity
  • Alcohol consumption
  • Physical inactivity

Diagnosis of RH

Diagnosis includes using various diagnostic criteria and monitoring techniques to rule out secondary causes and confirm medical adherence.

Clinical evaluation 

Your doctor will take a detailed medical history and gather further information about you to diagnose RH. They may want to confirm:10

  • Accuracy in BP readings. They will take a true measurement of your BP. Questions can include when your high BP started and how you measure it at home
  • Are you taking your prescribed medicines
  • That you don’t have white coat syndrome

Laboratory and imaging tests 

  • Urinalysis to check for protein or blood in urine
  • Blood tests to check glucose levels, kidney function, possible tumours in the adrenal glands, and electrolytes levels
  • Testing for thyroid disease as hypothyroidism can increase your risk of developing high BP10
  • X-rays to check for organ damage
  • Ultrasounds to look for structural abnormalities in the kidneys
  • Computed tomography (CT) scans to check for narrowing kidney arteries

Ambulatory BP monitoring

Ambulatory BP monitoring records your BP readings over 24 hours whilst awake and asleep,so that you can continue with daily life. This method is regarded as a more accurate measure due to the elimination of the white coat effect. 

Treatment of RH

Lowering and controlling your high BP prevents CVD such as heart attack and stroke. Treatment options include lifestyle changes, medications, treating underlying conditions, and sometimes surgical interventions. 

Lifestyle changes

Adopting a healthy lifestyle is an important aspect of managing RH. These include:3

Medicines

In most RH cases, medications are not working because people are not taking them correctly. For drugs to work you must ensure medication adherence. If, however, you have been taking your medications correctly but your BP is not reducing, your doctor may prescribe the following common BP medicines to relax blood vessels, reduce blood volume and improve blood flow:

Most people can manage their BP with these medications, but in some cases, your doctor may adjust the dosing and combinations of medicines. If after this, your BP remains above ideal measurements, a beta-blocker may be added as a fourth agent.6

Surgical interventions

In those where the use of maximal doses of antihypertensive medications was not effective at reaching BP target values, surgery, such as renal denervation (RDN) may be the next option. The brain, heart, and kidneys send signals throughout the body to regulate BP. However, overactivity in these signals increases BP, thus RDN targets renal nerves to help reduce BP.3 The device-based procedure is minimally invasive, has a low complication rate, and could potentially reduce mortality and morbidity risks associated with RH.11 

Complications of RH

If RH is poorly managed or left uncontrolled, serious complications can arise:12

  • CVD, including coronary artery disease, heart attack, heart failure, and peripheral disease. Persistent high BP damages artery walls, which lead to plaque buildup and causes partial or full artery blockage. If blockage occurs near the brain, this can cause a stroke and a heart attack if near the heart
  • Renal complications, such as CKD and accelerating the progression of kidney disease cause reduced kidney function and end-stage kidney disease
  • Vision damage, such as retinopathy, choroidopathy, and optic neuropathy. The lack of blood flow from high BP can result in blurred and distorted vision, scarring that impairs vision, and sometimes temporary or permanent vision loss

Impact on quality of life

The need for multiple medications and their frequent adjustments, side effects, and the burden of constantly monitoring and managing BP results in a decreased sense of control over your health and social interactions, and thus quality of life.5

Prognosis of RH

Patients with well-controlled BP and effective management of other conditions have a better prognosis compared to those with uncontrolled hypertension. It’s important to get an accurate diagnosis and to start treatment as soon as possible to minimise the risk of adopting life-threatening complications.

Prevention of RH

Regular monitoring is essential for early detection and follow-up visits with your doctor to address any BP management concerns. You should also comply with medication schedules and dietary modifications, as adopting a healthy lifestyle significantly reduces the risk of RH. It’s vital to promptly identify and treat underlying causes as they can lead to high BP.13 

Summary 

RH is a challenging condition caused by uncontrolled and elevated BP levels that could have serious consequences for your health. The key to combating RH is early detection and accurate diagnosis to ensure effective management. Medical adherence and lifestyle changes are crucial to avoid the associated risks of RH, including CVD and CKD. If you fear you may have RH, you should consult your doctor to gain more information and guidance on how to manage your condition effectively. 

References 

  1. Spence JD. Controlling resistant hypertension. Stroke Vasc Neurol [Internet]. 2018 [cited 2024 Feb 21]; 3(2):69–75. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047342/.
  2. Oparil S, Acelajado MC, Bakris GL, Berlowitz DR, Cífková R, Dominiczak AF, et al. Hypertension. Nat Rev Dis Primers [Internet]. 2018 [cited 2024 Feb 16]; 4:18014. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477925/.
  3. Doroszko A, Janus A, Szahidewicz-Krupska E, Mazur G, Derkacz A. Resistant Hypertension. Adv Clin Exp Med. 2016; 25(1):173–83. https://pubmed.ncbi.nlm.nih.gov/26935512/
  4. Judd E, Calhoun D. Apparent and true resistant hypertension: definition, prevalence and outcomes. J Hum Hypertens [Internet]. 2014 [cited 2024 Feb 19]; 28(8):463–8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090282/.
  5. Champaneria MK, Patel RS, Oroszi TL. When blood pressure refuses to budge: exploring the complexity of resistant hypertension. Frontiers in Cardiovascular Medicine [Internet]. 2023 [cited 2024 Feb 20]; 10. Available from: https://www.frontiersin.org/articles/10.3389/fcvm.2023.1211199.
  6. Sarafidis PA, Bakris GL. Resistant Hypertension. Journal of the American College of Cardiology [Internet]. 2008 [cited 2024 Feb 19]; 52(22):1749–57. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0735109708029896.
  7. Morgan T, Anderson A. The Effect of Nonsteroidal Anti‐Inflammatory Drugs on Blood Pressure in Patients Treated With Different Antihypertensive Drugs. J Clin Hypertens (Greenwich) [Internet]. 2007 [cited 2024 Feb 19]; 5(1):53–7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101828/.
  8. Faselis C, Doumas M, Papademetriou V. Common Secondary Causes of Resistant Hypertension and Rational for Treatment. International Journal of Hypertension [Internet]. 2011 [cited 2024 Feb 19]; 2011:e236239. Available from: https://www.hindawi.com/journals/ijhy/2011/236239/.
  9. Fay KS, Cohen DL. Resistant Hypertension in People With CKD: A Review. American Journal of Kidney Diseases [Internet]. 2021 [cited 2024 Feb 19]; 77(1):110–21. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0272638620308507.
  10. Tsioufis CP, Kasiakogias A, Tousoulis D. Clinical Diagnosis and Management of Resistant Hypertension. Eur Cardiol [Internet]. 2016 [cited 2024 Feb 19]; 11(1):12–7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159472/.
  11. Yap LB, Balachandran K. Renal Denervation in the treatment of Resistant Hypertension. Med J Malaysia. 2021; 76(6):893–7. Available from: https://pubmed.ncbi.nlm.nih.gov/34806679/
  12. Cai A, Calhoun DA. Resistant Hypertension: An Update of Experimental and Clinical Findings. Hypertension [Internet]. 2017 [cited 2024 Feb 20]; 70(1):5–9. Available from: https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.117.08929.
  13. Solini A, Ruilope LM. How can resistant hypertension be identified and prevented? Nat Rev Cardiol [Internet]. 2013 [cited 2024 Feb 21]; 10(5):293–6. Available from: https://www.nature.com/articles/nrcardio.2013.23.

This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Reema Devlia

Master of Science - MSc Pharmaceutical Technology, King’s College London

Reema is a MSc Pharmaceutical Technology and BSc Chemistry graduate with an in-depth knowledge of solid and liquid dosage form design and regulatory affairs, alongside a proven strong background in scientific writing, literature searches and reviews. She also has experience in pharmaceutical sales, where she provided technical information relating to pharmaceutical ingredients and fulfilled regulatory requests to support customer end use and strengthen client relations.

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