From the Guidelines
Testing for resistant hypertension involves a systematic approach to confirm true resistance and identify underlying causes, as outlined in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1. First, ensure accurate blood pressure measurement using proper technique and equipment, confirming readings with ambulatory or home monitoring to exclude white coat hypertension. Verify medication adherence through direct questioning, pill counts, or pharmacy records, as non-adherence is the most common cause of apparent resistance. Evaluate lifestyle factors including sodium intake, alcohol consumption, physical inactivity, and obesity. Review all medications including over-the-counter drugs, supplements, and substances like NSAIDs, decongestants, stimulants, and oral contraceptives that can elevate blood pressure. Laboratory testing should include basic metabolic panel, urinalysis, lipid profile, glucose, and thyroid function tests. Screen for secondary causes such as primary aldosteronism (aldosterone-to-renin ratio), pheochromocytoma (plasma metanephrines), renal artery stenosis (duplex ultrasound or CT angiography), and sleep apnea (sleep study) as recommended by the American College of Cardiology/American Heart Association 1. Consider rare causes like Cushing's syndrome, hyperparathyroidism, or coarctation of the aorta in appropriate clinical contexts. This comprehensive evaluation helps distinguish between true resistant hypertension and pseudoresistance, guiding appropriate management strategies including medication adjustments, addressing secondary causes, or referral to hypertension specialists when necessary. Key management strategies for resistant hypertension include maximization of diuretic therapy, addition of a mineralocorticoid receptor antagonist, and use of loop diuretics in patients with chronic kidney disease, as outlined in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1. Referral to a hypertension specialist is recommended if blood pressure remains uncontrolled after 6 months of treatment 1. By following this systematic approach, clinicians can effectively diagnose and manage resistant hypertension, reducing the risk of cardiovascular complications and improving patient outcomes. The most recent and highest quality study, the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline, provides the foundation for this approach, emphasizing the importance of accurate diagnosis, lifestyle modification, and evidence-based treatment strategies in the management of resistant hypertension 1.
From the Research
Definition and Diagnosis of Resistant Hypertension
- Resistant hypertension is defined as failure to achieve target blood pressure despite the use of optimal or maximum doses of at least 3 agents, one of which is a diuretic, or requiring 4 or more medications to achieve blood pressure goal 2.
- It can also be defined as high blood pressure requiring 3 or more medications for adequate control or controlled blood pressure requiring 4 or more medications 3.
- Diagnosis of resistant hypertension requires confirmation of blood pressure levels above target by out-of-office blood pressure measurements and exclusion of secondary causes of hypertension 4.
Causes of Resistant Hypertension
- Apparent resistant hypertension may be caused by medication nonadherence, substances that either interfere with antihypertensive medications or cause blood pressure elevation, and under- or inappropriate medication treatment 2.
- Secondary causes of resistant hypertension include obstructive sleep apnea, chronic kidney disease, primary aldosteronism, renal artery stenosis, pheochromocytoma, and Cushing's disease 2, 4, 3, 5.
- Patient characteristics associated with resistant hypertension include chronic kidney disease, diabetes, obesity, and presence of end-organ damage 2.
Management of Resistant Hypertension
- Initial medication management usually includes adding or increasing the dose of a diuretic, which is effective in lowering the blood pressure of a large number of patients with resistant hypertension 2.
- Additional management options include maximizing lifestyle modification, combination therapy of antihypertensive agents depending on individual patient characteristics, and referral to a hypertension specialist 2, 4.
- The fourth line of treatment for patients with resistant hypertension should include mineralocorticoid receptor antagonists such as spironolactone 4, 6.
- Alternatives to spironolactone include amiloride, doxazosin, eplerenone, clonidine, and beta-blockers, as well as any other antihypertensive drugs not already in use 4.