Emerging Therapies for the Treatment of Resistant Hypertension

Introduction:

A common condition known as hypertension, or high blood pressure, is characterized by a constant increase in blood flow against the walls of the arteries. It is usually managed through lifestyle changes and medication. Conversely, resistant hypertension is the state in which high blood pressure persists even after using at least three distinct kinds of antihypertensive drugs, including diuretics. It is more challenging to control and may require additional investigations and treatments to address underlying causes or contributing factors.

What Is Resistant Hypertension?

Resistant hypertension refers to high blood pressure that remains uncontrolled despite treatment with three different antihypertensive medications of different classes, including a diuretic. It is essential to identify and manage underlying causes like secondary hypertension or medication non-adherence. Additional treatments may include lifestyle changes, medication adjustments, or interventions like renal denervation or baroreceptor stimulation.

How Does Resistant Hypertension Differ from Pseudo-Resistant Hypertension?

Pseudo-resistance and resistant hypertension both refer to challenges in controlling high blood pressure, but they arise from different causes:

• Pseudo Resistance: Pseudo resistance occurs when apparent treatment-resistant hypertension is actually due to factors such as inaccurate blood pressure measurements, white-coat hypertension (elevated readings in a clinical setting but normal elsewhere), or medication non-adherence. Once these factors are addressed, blood pressure control may improve without additional medications.

• Resistant Hypertension: When high blood pressure is not under control after using three or more antihypertensive drugs of different classes including diuretics along with lifestyle changes, it is referred to as resistant hypertension. It typically indicates true resistance to treatment and may require more aggressive management strategies to achieve blood pressure control.

What Could Be the Signs and Symptoms of Resistant Hypertension?

The signs and symptoms of resistant hypertension are often similar to those of regular hypertension and may include:

• Headaches.

• Shortness of breath.

• Nosebleeds.

• Chest pain.

However, since resistant hypertension is more difficult to control, individuals may experience more severe symptoms or complications, such as:

• Heart attack (blood flow to the heart is reduced or blocked).

• Stroke (blockage of blood to the brain).

• Kidney problems.

It is crucial for individuals with high blood pressure, especially those struggling to control it despite treatment, to keep a close watch on the symptoms and seek medical assistance if they exhibit any alarming symptoms.

Who Is Susceptible to Resistant Hypertension?

The following are some of the factors that can raise the chance of developing resistant hypertension:

• Poor Medication Adherence: Not taking prescribed medications as directed increases blood pressure.

• Obesity: Excess weight can make blood pressure harder to control.

• Advanced Age: Risk increases with age as blood vessels become less flexible.

• Chronic Kidney Disease: Impaired kidney function can lead to hypertension, which is harder to control.

• Sleep Apnea: Disturbance in breathing during sleep can contribute to resistant hypertension.

• Secondary Hypertension: Underlying medical conditions like kidney disease, hormonal disorders, or obstructive sleep apnea (airway blockade during sleep) can cause secondary hypertension.

• Lifestyle Factors: High sodium intake, excessive alcohol consumption, and lack of physical activity can contribute to resistant hypertension.

• Genetic Predisposition: A family history of hypertension may increase susceptibility.

• Certain Medications: Some drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), decongestants, and oral contraceptives, increase blood pressure or interfere with antihypertensive medications.

How Is Resistant Hypertension Confirmed?

Resistant hypertension is confirmed through previous medical history and examination. A blood pressure of more than 140/90 mmHg (millimeters of mercury) in a person over 18 years of age is considered Resistant hypertension.

• Confirmation of Hypertension: Several blood pressure readings are obtained to verify the existence of hypertension.

• Other Investigations: A serum creatinine test, globular filtration rate, urine dipstick, serum sodium, serum potassium, and serum glucose were taken. Though they are simple tests, they are helpful.

How Is Resistant Hypertension Treated?

Treatment for resistant hypertension typically involves a combination of lifestyle changes and medication adjustments. Here are some approaches:

• Lifestyle Modifications: Indulging in weight loss, adopting a low-sodium diet, increasing physical activity, limiting alcohol intake, and managing stress can help lower blood pressure.

• Medication Adjustments: The type or dose of medications is changed, and new medications or combination pills are used to improve blood pressure control. This may include diuretics, ACE inhibitors, angiotensin II receptor blockers, beta-blockers, calcium channel blockers, aldosterone antagonists, or other antihypertensive drugs.

• Identifying and Treating Underlying Causes: Addressing underlying medical conditions that contribute to hypertension, such as sleep apnea, kidney disease, or hormonal disorders, is essential for effective management.

• Monitoring and Compliance: Regular blood pressure monitoring and ensuring medication adherence are important. Sometimes, using devices like home blood pressure monitors can provide more accurate readings and help in curating the treatment.

• Specialized Interventions: Ambulatory Blood Pressure Monitoring (ABPM) involves wearing a device that measures blood pressure at regular intervals over 24 hours, providing a more comprehensive assessment of blood pressure control than single office measurements.

• Target Organ Damage Assessment: Evaluation for signs of target organ damage, such as heart, kidney, brain, or eye complications, may be performed to gauge the severity of hypertension.

Emerging Therapies:

Emerging therapies for managing resistant hypertension include:

• Renal Denervation: This minimally invasive procedure disrupts nerves in the kidneys that contribute to high blood pressure, potentially leading to better blood pressure control.

• Baroreceptor Stimulation: Devices implanted near the carotid arteries stimulate baroreceptors, which regulate blood pressure, helping to lower hypertension.

• Gene Therapy: Research is ongoing into using gene editing techniques to target genes associated with hypertension, potentially offering new avenues for treatment.

• Renal Artery Ablation: This procedure involves using radiofrequency energy to ablate nerves around the renal arteries, reducing their activity and lowering blood pressure.

• Novel Medications: Pharmaceutical companies are developing new classes of antihypertensive medications that target specific pathways involved in blood pressure regulation, offering promising alternatives for resistant hypertension management.

What Are the Complications of Resistant Hypertension?

Complications of resistant hypertension can be severe and include:

• Increased Risk of Cardiovascular Events: Resistant hypertension significantly raises the risk of heart attack, stroke, heart failure, and other cardiovascular diseases.

• Organ Damage: Persistently high blood pressure can damage organs such as the heart, kidneys, brain, and eyes, leading to conditions like hypertensive heart disease, chronic kidney disease, cognitive (conscious mental activities) impairment, and vision problems.

• Worsening of Other Health Conditions: Resistant hypertension can exacerbate other health conditions, such as diabetes (high blood sugar), making them harder to control and raising the possibility of consequences.

• Reduced Quality of Life: Uncontrolled hypertension and its associated complications can negatively impact quality of life, leading to symptoms like fatigue, difficulty concentrating, and reduced physical functioning.

• Increased Healthcare Costs: Managing complications of resistant hypertension can increase healthcare utilization and costs for individuals and healthcare systems.

• Mortality: Resistant hypertension is associated with higher mortality rates compared to controlled hypertension, particularly due to the increased risk of cardiovascular events.

If the blood pressure increases to 180/120 mmHg, then it is advisable to visit the emergency room. The signs include headaches, pounding in the chest, dizziness, and shortness of breath.

Conclusion:

Hypertension runs in the family. About 29 percent of adults have hypertension, among which 12 percent fall under the resistant category. A multidisciplinary approach is needed, along with lifestyle modification and pharmacotherapy. The use of ambulatory devices can also help in monitoring blood pressure. Once diagnosed, individuals with resistant hypertension undergo further evaluation and management to control blood pressure and minimize the risk of complications.