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  • Blood pressure above the recommended values (140/90 mm Hg) despite the use of greater than or equal to 3–4 antihypertensive agents, each belonging to a different class.

  • Insufficient treatment prescription and lack of adherence to prescribed drugs, dietary restrictions, and lifestyle recommendations are the most frequent causes.

  • Associated with obesity, sleep apnea, diabetes, chronic kidney disease, advanced age, high dietary salt intake, and black race.

Hypertension continues to be a common reason for office, urgent care center, and emergency room visits. Raised blood pressure is the leading global risk factor for cardiovascular diseases and chronic kidney disease. If not properly controlled, hypertension can lead to blindness, renal failure, heart disease, and stroke. A recent study from Rapsomaniki et al showed that the lifetime burden of hypertension remains substantial, despite modern therapy. The number of people with raised blood pressure in the world has increased by 90% during these four decades, with the majority of the increase occurring in low-income and middle-income countries, and largely driven by the growth and ageing of the population.

Common factors associated with the development of resistant hypertension include obesity, sleep apnea, diabetes, chronic kidney disease, advanced age, high dietary salt intake, and black race. Interfering substances such as nonsteroidal anti-inflammatory drugs and excessive alcohol consumption can worsen blood pressure control. However, an insufficient treatment prescription and the lack of adherence to the prescribed drug and lifestyle recommendations (eg, the moderation of alcohol consumption, the restriction of salt intake, the reduction of body weight) seem to be the most frequent causes of uncontrolled BP. Other causes of resistance to treatment include cases of spurious hypertension, such as isolated office (white-coat) hypertension, and failure to use large cuffs on large arms. Nevertheless, a significant number of patients adequately diagnosed and treated still have uncontrolled BP. The real prevalence of resistant hypertension is difficult to determine. Published observational studies describe a prevalence that oscillates between 10% and 15%.

This review focuses on those causes of resistance to treatment that can be evaluated in the outpatient setting. These include a search for nonadherence, assessing the adequacy of the treatment regimen, and ruling out drug interactions and associated conditions. In the absence of the above factors, assessment for secondary causes of hypertension is appropriate. This careful stepwise evaluation is not only cost effective, but also capable of identifying the contributing factors in the vast majority of patients with apparently resistant hypertension.


Resistant hypertension is defined as high blood pressure that remains uncontrolled (>140/90 mm Hg) despite the use of effective doses of three or more different classes of antihypertensive agents, including a diuretic. The first American Heart Association Scientific Statement on resistant hypertension included patients whose blood pressure was controlled (<140/90 mm Hg) with four or more medications within the category of resistant hypertension. Refractory hypertension has been used to ...

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