Review Article | Published:

Diagnosis and management of resistant hypertension: state of the art

Nature Reviews Nephrologyvolume 14pages428441 (2018) | Download Citation


Resistant hypertension is defined as a lack of ambulatory blood pressure response to optimized medical treatment after exclusion of secondary hypertension in patients who are fully adherent to antihypertensive therapy. Patients with resistant hypertension are at high risk of complications, particularly cardiovascular events, and optimization of medical treatment remains the cornerstone of their management. Such optimization should be based on simple algorithms and include the use of aldosterone antagonists. The available data from clinical trials do not support the use of device-based approaches such as renal denervation, baroreflex activation therapy or arteriovenous anastomosis for the treatment of resistant hypertension in the majority of patients. Therefore, device treatment remains a last-resort for patients with truly resistant hypertension in the context of clinical research in highly skilled tertiary referral centres. Future research should focus on improving understanding of the intrinsic (physiological and psychological factors) and extrinsic (environmental stressors) mechanisms that contribute to a lack of response to blood-pressure-lowering drugs in adherent patients. The use of biomarkers to identify patients with early target organ damage and new technologies, such as renal nerve stimulation, to predict blood pressure responses to renal denervation could aid the selection of patients who might benefit from device therapies.

Key points

  • Resistant hypertension is an elevated ambulatory blood pressure after exclusion of secondary hypertension in patients who are fully adherent to treatment with antihypertensive drugs.

  • Resistant hypertension is associated with increased risks of adverse health outcomes, including cardiovascular and renal events and all-cause mortality.

  • Ambulatory blood pressure monitoring is the gold standard for diagnosis of resistant hypertension; this method enables the identification of patients with isolated nocturnal hypertension, sustained hypertension or white-coat hypertension.

  • Optimization of medical treatment using simple, easy-to-understand algorithms is the cornerstone of management of resistant hypertension.

  • The available data from clinical trials do not support the use of renal denervation, baroreflex activation therapy or arteriovenous anastomosis for the treatment of resistant hypertension in routine clinical practice.

  • The use of biomarkers of early target organ damage and new technologies such as renal nerve stimulation could aid the selection of patients with resistant hypertension who might benefit from device therapies.

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The European Union (HEALTH-F7-305507-HOMAGE), the European Research Council (Advanced Researcher Grant 2011-294713-EPLORE and Proof-of-Concept Grant 713601-uPROPHET), the European Research Area Net for Cardiovascular Diseases (JTC2017-046-PROACT) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13), currently support the Studies Coordinating Centre in Leuven, Belgium. The funders had no role in the preparation of this manuscript.

Author information


  1. Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium

    • Fang-Fei Wei
    • , Zhen-Yu Zhang
    • , Qi-Fang Huang
    •  & Jan A. Staessen
  2. Institut universitaire de médicine sociale et préventive, University of Lausanne, Lausanne, Switzerland

    • Zhen-Yu Zhang
  3. Department of Cardiovascular Diseases, Shanghai General Hospital, Shanghai, China

    • Zhen-Yu Zhang
  4. Center for Epidemiological Studies and Clinical Trials and Center for Vascular Evaluations, Shanghai Institute of Hypertension, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    • Qi-Fang Huang
  5. Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, Netherlands

    • Jan A. Staessen


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F.-F.W. and J.A.S. researched the data for the article. All authors made substantial contributions to discussions of the content and writing, reviewing and editing the manuscript before submission.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Jan A. Staessen.


Secondary hypertension

Elevated blood pressure that results from an underlying, identifiable and often correctable cause.

White-coat effect

An increase in blood pressure due to arousal of the patient in response to a medical environment or the observer measuring the blood pressure.

White-coat hypertension

A raised in-office blood pressure in the presence of a normal 24 h or daytime ambulatory blood pressure.

Terminal digit preference

A tendency to round measurements to a particular end digit, resulting in the occurrence of this digit at a higher frequency than would be expected by chance alone. When blood pressure is measured by the auscultatory approach, the last digits of the systolic and diastolic readings should always be even and should not be rounded to 0 or 5. The terminal digits 0, 2, 4, 6 and 8 should each have a frequency of approximately 20%.

Nocebo effect

Adverse events occurring as a result of negative expectations (the opposite of the placebo effect). A nocebo response occurs when a patient’s symptoms are worsened by the administration of an inert, sham or placebo treatment.

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