title: Prevalence and Prognostic Significance of Apparent Treatment Resistant Hypertension in Chronic Kidney Disease: Report From the Chronic Renal Insufficiency Cohort Study.
abstract: The association between apparent treatment resistant hypertension (ATRH) and clinical outcomes is not well studied in chronic kidney disease. We analyzed data on 3367 hypertensive participants in the Chronic Renal Insufficiency Cohort (CRIC) to determine prevalence, associations, and clinical outcomes of ATRH in nondialysis chronic kidney disease patients. ATRH was defined as blood pressure ≥140/90 mm Hg on ≥3 antihypertensives, or use of ≥4 antihypertensives with blood pressure at goal at baseline visit. Prevalence of ATRH was 40.4%. Older age, male sex, black race, diabetes mellitus, and higher body mass index were independently associated with higher odds of having ATRH. Participants with ATRH had a higher risk of clinical events than participants without ATRH-composite of myocardial infarction, stroke, peripheral arterial disease, congestive heart failure (CHF), and all-cause mortality (hazard ratio [95% confidence interval], 1.38 [1.22-1.56]); renal events (1.28 [1.11-1.46]); CHF (1.66 [1.38-2.00]); and all-cause mortality (1.24 [1.06-1.45]). The subset of participants with ATRH and blood pressure at goal on ≥4 medications also had higher risk for composite of myocardial infarction, stroke, peripheral arterial disease, CHF, and all-cause mortality (hazard ratio [95% confidence interval], (1.30 [1.12-1.51]) and CHF (1.59 [1.28-1.99]) than those without ATRH. ATRH was associated with significantly higher risk for CHF and renal events only among those with estimated glomerular filtration rate ≥30 mL/min per 1.73 m(2). Our findings show that ATRH is common and associated with high risk of adverse outcomes in a cohort of patients with chronic kidney disease. This underscores the need for early identification and management of patients with ATRH and chronic kidney disease.
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: George
authors.initials: G
authors.lastname: Thomas
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: Dawei
authors.initials: D
authors.lastname: Xie
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: Hsiang-Yu
authors.initials: HY
authors.lastname: Chen
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: Amanda H
authors.initials: AH
authors.lastname: Anderson
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Appel
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: Shirisha
authors.initials: S
authors.lastname: Bodana
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: Brecklin
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: Paul
authors.initials: P
authors.lastname: Drawz
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: John M
authors.initials: JM
authors.lastname: Flack
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: Edgar R
authors.initials: ER
authors.lastname: Miller
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: Susan P
authors.initials: SP
authors.lastname: Steigerwalt
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Townsend
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Weir
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: Jackson T
authors.initials: JT
authors.lastname: Wright
authors.affiliation: From the Department of Nephrology and Hypertension, Cleveland Clinic, OH (G.T.); Departments of Medicine (R.R.T.) and Biostatistics and Epidemiology (A.H.A., D.X., H.-Y.C.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Departments of Medicine (L.J.A., E.R.M.) and Epidemiology (L.J.A.), Johns Hopkins University, Baltimore, MD; Department of Nephrology, Ochsner Medical Center, New Orleans, LA (S.B.); Department of Medicine, University of Illinois at Chicago (C.B.); Department of Medicine, University of Minnesota, Minneapolis (P.D.); Hypertension Section, Division of General Medicine, Department of Medicine, Southern Illinois University, Springfield (J.M.F.); Division of Nephrology and Hypertension, St John Hospital and Medical Center, Detroit, MI (S.P.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (M.R.W.); Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Louis Stokes Cleveland VA Medical Center Cleveland, OH (J.T.W., M.R.).
authors.forename: Mahboob
authors.initials: M
authors.lastname: Rahman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000503:physiopathology; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D000959:Antihypertensive Agents
keywords: antihypertensive agents; hypertension; hypertension resistant to conventional therapy; myocardial infarction; renal insufficiency, chronic