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Resistant hypertension? Assessment of adherence by toxicological urine analysis

Jung, Olivera; Gechter, Janis L.a; Wunder, Corab; Paulke, Alexanderb; Bartel, Christinea; Geiger, Helmuta; Toennes, Stefan W.b

doi: 10.1097/HJH.0b013e32835e2286
ORIGINAL PAPERS: Resistant hypertension

Objective: Uncontrolled hypertension under antihypertensive multidrug regimen is not necessarily always true resistance. Incomplete adherence is one of several possible causes of uncontrolled hypertension. Nonadherence remains largely unrecognized and is falsely interpreted as treatment resistance, as it is difficult to confirm or exclude objectively. This is the first study assessing adherence in patients with apparent resistant hypertension systematically via toxicological urine screening.

Methods: All patients referred from primary care physicians because of uncontrolled hypertension between 2004 and 2011 were analysed. Adherence was assessed in all patients with uncontrolled hypertension despite the concurrent use of at least four antihypertensive agents by using liquid chromatography-mass spectrometry analysis for antihypertensive drugs or their corresponding metabolites in urine.

Results: A total of 375 patients with uncontrolled hypertension were referred. After optimization of drug therapy and exclusion of white coat hypertension, 108 patients met criteria for resistant hypertension. Of those, 15 patients had secondary causes of hypertension and 17 achieved goal blood pressure with quadruple antihypertensive therapy. Of the remaining 76 patients, 40 patients (53%) were found to be nonadherent. Among nonadherent patients, 30% had complete and 70% had incomplete adherence; 85% of the latter had taken less than 50% of drugs prescribed. Lack of adherence was almost evenly distributed between different classes of antihypertensive drugs.

Conclusion: Low adherence was the most common cause of poor blood pressure control in patients with apparent resistant hypertension, being twice as frequent as secondary causes of hypertension. Incomplete adherence was far more common than complete nonadherence; thus, assessment of adherence in patients on multiple drug regime is only reliable when all drugs are included in assessment. Assessing adherence by toxicological urine screening is a useful tool in detecting low adherence, especially in the setting of multidrug regimen as a cause of apparently resistant hypertension.

aInternal Medicine, Department of Nephrology

bInstitute of Legal Medicine, Forensic Toxicology Department, Goethe University, Frankfurt/Main, Germany

Correspondence to Oliver Jung, MD, Klinikum der Goethe-Universität, Zentrum der Inneren Medizin III-Funktionsbereich Nephrologie, Theodor Stern Kai 7, 60590 Frankfurt/Main, Germany. Tel: +49 69 6301 87849; fax: +49 69 6301 87850; e-mail:

Abbreviations: ABPM, 24-h ambulatory blood pressure monitoring; ACEi, angiotensin-converting enzyme-inhibitor; ARB, angiotensin-II receptor blocker; B-blocker, beta-blocker; BP, blood pressure; CCB, calcium channel blocker; eGFR, estimated glomerular filtration rate; EIC, extracted ion chromatogram; ESH, European Society of Hypertension; ESI+, positive electrospray ionization mode; GC-MS, gas chromatography-mass spectrometry; LC-MS, liquid chromatography-mass spectrometry; LDL, low-density lipoprotein; LVH, left ventricular hypertrophy; MEMS, Medication Events Monitoring Systems; RH, resistant hypertension; Sympathetic-B, sympathetic-blocker

Received 5 October, 2012

Accepted 19 December, 2012

© 2013 Lippincott Williams & Wilkins, Inc.