title: Treatment-resistant hypertension and the incidence of cardiovascular disease and end-stage renal disease: results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
abstract: Apparent treatment-resistant hypertension (aTRH) is defined as uncontrolled hypertension despite the use of ≥3 antihypertensive medication classes or controlled hypertension while treated with ≥4 antihypertensive medication classes. Although a high prevalence of aTRH has been reported, few data are available on its association with cardiovascular and renal outcomes. We analyzed data on 14 684 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants to determine the association between aTRH (n=1870) with coronary heart disease, stroke, all-cause mortality, heart failure, peripheral artery disease, and end-stage renal disease. We defined aTRH as blood pressure not at goal (systolic/diastolic blood pressure ≥140/90 mm Hg) while taking ≥3 classes of antihypertensive medication or taking ≥4 classes of antihypertensive medication with blood pressure at goal during the year 2 ALLHAT study visit (1996-2000). Use of a diuretic was not required to meet the definition of aTRH. Follow-up occurred through 2002. The multivariable adjusted hazard ratios (95% confidence intervals) comparing participants with versus without aTRH were as follows: coronary heart disease (1.44 [1.18-1.76]), stroke (1.57 [1.18-2.08]), all-cause mortality (1.30 [1.11-1.52]), heart failure (1.88 [1.52-2.34]), peripheral artery disease (1.23 [0.85-1.79]), and end-stage renal disease (1.95 [1.11-3.41]). aTRH was also associated with the pooled outcomes of combined coronary heart disease (hazard ratio, 1.47; 95% confidence interval, 1.26-1.71) and combined cardiovascular disease (hazard ratio, 1.46; 95% confidence interval, 1.29-1.64). These results demonstrate that aTRH increases the risk for cardiovascular disease and end-stage renal disease. Studies are needed to identify approaches to prevent aTRH and reduce risk for adverse outcomes among individuals with aTRH.
authors.affiliation: From the Department of Epidemiology (P.M.) and Cardiovascular Disease (D.A.C.), University of Alabama at Birmingham; Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston (B.R.D., S.L.P.); Preventive Medicine Section, Memphis Veterans Affairs Medical Center, TN (W.C.C.); Cardiovascular Outcomes Group, New York University School of Medicine (S.B.); New York University Langone Medical Center (H.R.B.); Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ (J.B.K.); Clinical Trials Services Unit, University of Washington School of Medicine, Seattle (J.L.P.); Global Public Health, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH (M.R.); and Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH (M.R.).
authors.forename: Paul
authors.initials: P
authors.lastname: Muntner
authors.affiliation: From the Department of Epidemiology (P.M.) and Cardiovascular Disease (D.A.C.), University of Alabama at Birmingham; Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston (B.R.D., S.L.P.); Preventive Medicine Section, Memphis Veterans Affairs Medical Center, TN (W.C.C.); Cardiovascular Outcomes Group, New York University School of Medicine (S.B.); New York University Langone Medical Center (H.R.B.); Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ (J.B.K.); Clinical Trials Services Unit, University of Washington School of Medicine, Seattle (J.L.P.); Global Public Health, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH (M.R.); and Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH (M.R.). Barry.R.Davis@uth.tmc.edu.
authors.forename: Barry R
authors.initials: BR
authors.lastname: Davis
authors.affiliation: From the Department of Epidemiology (P.M.) and Cardiovascular Disease (D.A.C.), University of Alabama at Birmingham; Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston (B.R.D., S.L.P.); Preventive Medicine Section, Memphis Veterans Affairs Medical Center, TN (W.C.C.); Cardiovascular Outcomes Group, New York University School of Medicine (S.B.); New York University Langone Medical Center (H.R.B.); Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ (J.B.K.); Clinical Trials Services Unit, University of Washington School of Medicine, Seattle (J.L.P.); Global Public Health, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH (M.R.); and Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH (M.R.).
authors.forename: William C
authors.initials: WC
authors.lastname: Cushman
authors.affiliation: From the Department of Epidemiology (P.M.) and Cardiovascular Disease (D.A.C.), University of Alabama at Birmingham; Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston (B.R.D., S.L.P.); Preventive Medicine Section, Memphis Veterans Affairs Medical Center, TN (W.C.C.); Cardiovascular Outcomes Group, New York University School of Medicine (S.B.); New York University Langone Medical Center (H.R.B.); Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ (J.B.K.); Clinical Trials Services Unit, University of Washington School of Medicine, Seattle (J.L.P.); Global Public Health, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH (M.R.); and Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH (M.R.).
authors.forename: Sripal
authors.initials: S
authors.lastname: Bangalore
authors.affiliation: From the Department of Epidemiology (P.M.) and Cardiovascular Disease (D.A.C.), University of Alabama at Birmingham; Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston (B.R.D., S.L.P.); Preventive Medicine Section, Memphis Veterans Affairs Medical Center, TN (W.C.C.); Cardiovascular Outcomes Group, New York University School of Medicine (S.B.); New York University Langone Medical Center (H.R.B.); Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ (J.B.K.); Clinical Trials Services Unit, University of Washington School of Medicine, Seattle (J.L.P.); Global Public Health, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH (M.R.); and Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH (M.R.).
authors.forename: David A
authors.initials: DA
authors.lastname: Calhoun
authors.affiliation: From the Department of Epidemiology (P.M.) and Cardiovascular Disease (D.A.C.), University of Alabama at Birmingham; Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston (B.R.D., S.L.P.); Preventive Medicine Section, Memphis Veterans Affairs Medical Center, TN (W.C.C.); Cardiovascular Outcomes Group, New York University School of Medicine (S.B.); New York University Langone Medical Center (H.R.B.); Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ (J.B.K.); Clinical Trials Services Unit, University of Washington School of Medicine, Seattle (J.L.P.); Global Public Health, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH (M.R.); and Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH (M.R.).
authors.forename: Sara L
authors.initials: SL
authors.lastname: Pressel
authors.affiliation: From the Department of Epidemiology (P.M.) and Cardiovascular Disease (D.A.C.), University of Alabama at Birmingham; Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston (B.R.D., S.L.P.); Preventive Medicine Section, Memphis Veterans Affairs Medical Center, TN (W.C.C.); Cardiovascular Outcomes Group, New York University School of Medicine (S.B.); New York University Langone Medical Center (H.R.B.); Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ (J.B.K.); Clinical Trials Services Unit, University of Washington School of Medicine, Seattle (J.L.P.); Global Public Health, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH (M.R.); and Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH (M.R.).
authors.forename: Henry R
authors.initials: HR
authors.lastname: Black
authors.affiliation: From the Department of Epidemiology (P.M.) and Cardiovascular Disease (D.A.C.), University of Alabama at Birmingham; Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston (B.R.D., S.L.P.); Preventive Medicine Section, Memphis Veterans Affairs Medical Center, TN (W.C.C.); Cardiovascular Outcomes Group, New York University School of Medicine (S.B.); New York University Langone Medical Center (H.R.B.); Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ (J.B.K.); Clinical Trials Services Unit, University of Washington School of Medicine, Seattle (J.L.P.); Global Public Health, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH (M.R.); and Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH (M.R.).
authors.forename: John B
authors.initials: JB
authors.lastname: Kostis
authors.affiliation: From the Department of Epidemiology (P.M.) and Cardiovascular Disease (D.A.C.), University of Alabama at Birmingham; Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston (B.R.D., S.L.P.); Preventive Medicine Section, Memphis Veterans Affairs Medical Center, TN (W.C.C.); Cardiovascular Outcomes Group, New York University School of Medicine (S.B.); New York University Langone Medical Center (H.R.B.); Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ (J.B.K.); Clinical Trials Services Unit, University of Washington School of Medicine, Seattle (J.L.P.); Global Public Health, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH (M.R.); and Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH (M.R.).
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Probstfield
authors.affiliation: From the Department of Epidemiology (P.M.) and Cardiovascular Disease (D.A.C.), University of Alabama at Birmingham; Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston (B.R.D., S.L.P.); Preventive Medicine Section, Memphis Veterans Affairs Medical Center, TN (W.C.C.); Cardiovascular Outcomes Group, New York University School of Medicine (S.B.); New York University Langone Medical Center (H.R.B.); Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ (J.B.K.); Clinical Trials Services Unit, University of Washington School of Medicine, Seattle (J.L.P.); Global Public Health, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH (M.R.); and Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH (M.R.).
authors.forename: Paul K
authors.initials: PK
authors.lastname: Whelton
authors.affiliation: From the Department of Epidemiology (P.M.) and Cardiovascular Disease (D.A.C.), University of Alabama at Birmingham; Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston (B.R.D., S.L.P.); Preventive Medicine Section, Memphis Veterans Affairs Medical Center, TN (W.C.C.); Cardiovascular Outcomes Group, New York University School of Medicine (S.B.); New York University Langone Medical Center (H.R.B.); Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ (J.B.K.); Clinical Trials Services Unit, University of Washington School of Medicine, Seattle (J.L.P.); Global Public Health, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (P.K.W.); Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH (M.R.); and Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH (M.R.).
authors.forename: Mahboob
authors.initials: M
authors.lastname: Rahman
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control*; D012307:Risk Factors; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D000960:Hypolipidemic Agents
keywords: agents; antihypertensive; cardiovascular diseases; diuretics; kidney failure, chronic