Adverse Health Outcomes Associated With Refractory and Treatment-Resistant Hypertension in the Chronic Renal Insufficiency Cohort

Hypertension. 2021 Jan;77(1):72-81. doi: 10.1161/HYPERTENSIONAHA.120.15064. Epub 2020 Nov 9.


Refractory hypertension (RfH) is a severe phenotype of antihypertension treatment failure. Treatment-resistant hypertension (TRH), a less severe form of difficult-to-treat hypertension, has been associated with significantly worse health outcomes. However, no studies currently show how health outcomes may worsen upon progression to RfH. RfH and TRH were studied in 3147 hypertensive participants in the CRIC (Chronic Renal Insufficiency Cohort study). The hypertensive phenotype (ie, no TRH or RfH, TRH, or RfH) was identified at the baseline visit, and health outcomes were monitored at subsequent visits. Outcome risk was compared using Cox proportional hazards models with time-varying covariates. A total of 136 (4.3%) individuals were identified with RfH at baseline. After adjusting for participant characteristics, individuals with RfH had increased risk for the composite renal outcome across all study years (50% decline in estimated glomerular filtration rate or end-stage renal disease; hazard ratio for study years 0-10=1.73 [95% CI, 1.42-2.11]) and the composite cardiovascular disease outcome during later study years (stroke, myocardial infarction, or congestive heart failure; hazard ratio for study years 0-3=1.25 [0.91-1.73], for study years 3-6=1.50 [0.97-2.32]), and for study years 6-10=2.72 [1.47-5.01]) when compared with individuals with TRH. There was no significant difference in all-cause mortality between those with refractory versus TRH. We provide the first evidence that RfH is associated with worse long-term health outcomes compared with TRH.

Keywords: chronic kidney failure; heart failure; hypertension; mortality; myocardial infarction; prognosis; stroke.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / therapeutic use*
  • Cohort Studies
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / epidemiology
  • Male
  • Middle Aged
  • Patient Outcome Assessment
  • Proportional Hazards Models
  • Renal Insufficiency, Chronic / complications*


  • Antihypertensive Agents