Incidence and Prognosis of Resistant Hypertension in Hypertensive Patients

Study Questions:

What is the incidence and importance of resistant hypertension in new-onset hypertension?


A retrospective cohort study was conducted in two integrated health plans that included patients with incident hypertension started on treatment from 2002-2006. Patients were followed for the development of resistant hypertension based on American Heart Association criteria of uncontrolled blood pressure (BP) (defined by Joint National Committee (JNC)-7 thresholds of systolic BP [SBP] ≥140 mm Hg or diastolic BP [DBP] ≥90 mm Hg with lower cut-offs of SBP ≥130 mm Hg or DBP ≥80 mm Hg for those with diabetes mellitus or chronic kidney disease) despite use of three or more antihypertensive medications using medication fill and BP measurement data. Primary outcome was incident cardiovascular events (CVEs = death or incident myocardial infarction, heart failure, stroke, or chronic kidney disease) in patients with and without resistant hypertension adjusting for patient and clinical characteristics.


Among 205,750 patients with incident hypertension, 21% were on three or more antihypertensive medications for at least 1 month. 1.9% developed resistant hypertension within a median 1.5 years from initial treatment, or 0.7 cases per 100 person-years of follow-up. Variables associated with resistant hypertension included men, older, higher baseline BP, diabetes, chronic kidney disease, and previous stroke and heart failure. Over 3.8 years of median follow-up, CVEs were significantly higher in those with resistant hypertension (unadjusted: 18.0% vs. 13.5%, p < 0.001). After adjusting for patient and clinical characteristics, resistant hypertension was associated with a higher risk of CVEs (hazard ratio, 1.47; 95% confidence interval, 1.33-1.62).


Among patients with incident hypertension started on treatment, 1 in 50 patients developed resistant hypertension. Resistant hypertension patients had an increased risk of CVEs, supporting the need for greater efforts toward improving hypertension outcomes in this population.


Resistant hypertension in this large cohort study is likely overestimated considering that the BPs were office-based rather than home-based or 24-hour ambulatory. Also, the definition based on the JNC-7 criteria may be considered too rigid by some. Nevertheless, the 50% increase in CVEs in patients with resistant hypertension despite four drugs, strongly supports a focus on diet and exercise, which have been shown to reduce BP and reduce CVEs and mortality.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Hypertension

Keywords: Stroke, Myocardial Infarction, Blood Pressure, Prognosis, Eye Abnormalities, Heart Failure, Confidence Intervals, United States, Diabetes Mellitus, Renal Insufficiency, Chronic, Hypertension

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