Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on Conduction System Disease | Acute Coronary Syndromes | JAMA Internal Medicine | JAMA Network
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Zhang  Z-M, Rautaharju  PM, Soliman  EZ,  et al.  Mortality risk associated with bundle branch blocks and related repolarization abnormalities (from the Women’s Health Initiative [WHI]).  Am J Cardiol. 2012;110(10):1489-1495. PubMedGoogle ScholarCrossref
Badheka  AO, Singh  V, Patel  NJ,  et al.  QRS duration on electrocardiography and cardiovascular mortality (from the National Health and Nutrition Examination Survey-III).  Am J Cardiol. 2013;112(5):671-677. PubMedGoogle ScholarCrossref
Stephenson  K, Skali  H, McMurray  JJV,  et al.  Long-term outcomes of left bundle branch block in high-risk survivors of acute myocardial infarction: the VALIANT experience.  Heart Rhythm. 2007;4(3):308-313. PubMedGoogle ScholarCrossref
Mandyam  MC, Soliman  EZ, Heckbert  SR, Vittinghoff  E, Marcus  GM.  Long-term outcomes of left anterior fascicular block in the absence of overt cardiovascular disease.  JAMA. 2013;309(15):1587-1588. PubMedGoogle ScholarCrossref
Cheng  S, Keyes  MJ, Larson  MG,  et al.  Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block.  JAMA. 2009;301(24):2571-2577. PubMedGoogle ScholarCrossref
Magnani  JW, Wang  N, Nelson  KP,  et al; Health, Aging, and Body Composition Study.  Electrocardiographic PR interval and adverse outcomes in older adults: the Health, Aging, and Body Composition Study.  Circ Arrhythm Electrophysiol. 2013;6(1):84-90. PubMedGoogle ScholarCrossref
Schneider  JF, Thomas  HE  Jr, Kreger  BE, McNamara  PM, Kannel  WB.  Newly acquired left bundle-branch block: the Framingham Study.  Ann Intern Med. 1979;90(3):303-310.PubMedGoogle ScholarCrossref
Schneider  JF, Thomas  HE, Kreger  BE, McNamara  PM, Sorlie  P, Kannel  WB.  Newly acquired right bundle-branch block: the Framingham Study.  Ann Intern Med. 1980;92(1):37-44.PubMedGoogle ScholarCrossref
Thrainsdottir  IS, Hardarson  T, Thorgeirsson  G, Sigvaldason  H, Sigfusson  N.  The epidemiology of right bundle branch block and its association with cardiovascular morbidity: the Reykjavik Study.  Eur Heart J. 1993;14(12):1590-1596.PubMedGoogle ScholarCrossref
Eriksson  P, Hansson  PO, Eriksson  H, Dellborg  M.  Bundle-branch block in a general male population: the study of men born 1913.  Circulation. 1998;98(22):2494-2500.PubMedGoogle ScholarCrossref
Bussink  BE, Holst  AG, Jespersen  L, Deckers  JW, Jensen  GB, Prescott  E.  Right bundle branch block: prevalence, risk factors, and outcome in the general population: results from the Copenhagen City Heart Study.  Eur Heart J. 2013;34(2):138-146. PubMedGoogle ScholarCrossref
ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group; Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.  Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).  JAMA. 2002;288(23):2981-2997.PubMedGoogle ScholarCrossref
Davis  BR, Cutler  JA, Gordon  DJ,  et al; ALLHAT Research Group.  Rationale and design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).  Am J Hypertens. 1996;9(4 Pt 1):342-360.PubMedGoogle ScholarCrossref
ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group; Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.  Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT).  JAMA. 2002;288(23):2998-3007.PubMedGoogle ScholarCrossref
ALLHAT Collaborative Research Group.  Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).  JAMA. 2000;283(15):1967-1975.PubMedGoogle ScholarCrossref
Casale  PN, Devereux  RB, Alonso  DR, Campo  E, Kligfield  P.  Improved sex-specific criteria of left ventricular hypertrophy for clinical and computer interpretation of electrocardiograms: validation with autopsy findings.  Circulation. 1987;75(3):565-572.PubMedGoogle ScholarCrossref
Prineas  RJ, Crow  RS, Blackburn  HW.  The Minnesota Code Manual of Electrocardiographic Findings: Standards and Procedures for Measurements and Classifications. Littleton, MA: John Wright–PSG Inc; 1982.
Li  D, Shinagawa  K, Pang  L,  et al.  Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure.  Circulation. 2001;104(21):2608-2614.PubMedGoogle ScholarCrossref
Shiroshita-Takeshita  A, Schram  G, Lavoie  J, Nattel  S.  Effect of simvastatin and antioxidant vitamins on atrial fibrillation promotion by atrial-tachycardia remodeling in dogs.  Circulation. 2004;110(16):2313-2319. PubMedGoogle ScholarCrossref
Haywood  LJ, Ford  CE, Crow  RS,  et al; ALLHAT Collaborative Research Group.  Atrial fibrillation at baseline and during follow-up in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).  J Am Coll Cardiol. 2009;54(22):2023-2031. PubMedGoogle ScholarCrossref
Gottdiener  JS, Reda  DJ, Massie  BM, Materson  BJ, Williams  DW, Anderson  RJ; Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.  Effect of single-drug therapy on reduction of left ventricular mass in mild to moderate hypertension: comparison of six antihypertensive agents.  Circulation. 1997;95(8):2007-2014.PubMedGoogle ScholarCrossref
Liebson  PR, Grandits  GA, Dianzumba  S,  et al.  Comparison of five antihypertensive monotherapies and placebo for change in left ventricular mass in patients receiving nutritional-hygienic therapy in the Treatment of Mild Hypertension Study (TOMHS).  Circulation. 1995;91(3):698-706.PubMedGoogle ScholarCrossref
Schmieder  RE, Martus  P, Klingbeil  A.  Reversal of left ventricular hypertrophy in essential hypertension: a meta-analysis of randomized double-blind studies.  JAMA. 1996;275(19):1507-1513.PubMedGoogle ScholarCrossref
Mathew  J, Sleight  P, Lonn  E,  et al; Heart Outcomes Prevention Evaluation (HOPE) Investigators.  Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor ramipril.  Circulation. 2001;104(14):1615-1621.PubMedGoogle ScholarCrossref
Moss  AJ, Hall  WJ, Cannom  DS,  et al; MADIT-CRT Trial Investigators.  Cardiac-resynchronization therapy for the prevention of heart-failure events.  N Engl J Med. 2009;361(14):1329-1338. PubMedGoogle ScholarCrossref
Cleland  JGF, Daubert  J-C, Erdmann  E,  et al; Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators.  The effect of cardiac resynchronization on morbidity and mortality in heart failure.  N Engl J Med. 2005;352(15):1539-1549. PubMedGoogle ScholarCrossref
Davis  BR, Piller  LB, Cutler  JA,  et al; Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Collaborative Research Group.  Role of diuretics in the prevention of heart failure: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.  Circulation. 2006;113(18):2201-2210. PubMedGoogle ScholarCrossref
Fahy  GJ, Pinski  SL, Miller  DP,  et al.  Natural history of isolated bundle branch block.  Am J Cardiol. 1996;77(14):1185-1190.PubMedGoogle ScholarCrossref
Freedman  RA, Alderman  EL, Sheffield  LT, Saporito  M, Fisher  LD.  Bundle branch block in patients with chronic coronary artery disease: angiographic correlates and prognostic significance.  J Am Coll Cardiol. 1987;10(1):73-80.PubMedGoogle ScholarCrossref
Sumner  G, Salehian  O, Yi  Q,  et al; HOPE Investigators.  The prognostic significance of bundle branch block in high-risk chronic stable vascular disease patients: a report from the HOPE trial.  J Cardiovasc Electrophysiol. 2009;20(7):781-787. PubMedGoogle ScholarCrossref
Hesse  B, Diaz  LA, Snader  CE, Blackstone  EH, Lauer  MS.  Complete bundle branch block as an independent predictor of all-cause mortality: report of 7,073 patients referred for nuclear exercise testing.  Am J Med. 2001;110(4):253-259.PubMedGoogle ScholarCrossref
Aro  AL, Anttonen  O, Tikkanen  JT,  et al.  Intraventricular conduction delay in a standard 12-lead electrocardiogram as a predictor of mortality in the general population.  Circ Arrhythm Electrophysiol. 2011;4(5):704-710. PubMedGoogle ScholarCrossref
Barsheshet  A, Goldenberg  I, Garty  M,  et al.  Relation of bundle branch block to long-term (four-year) mortality in hospitalized patients with systolic heart failure.  Am J Cardiol. 2011;107(4):540-544. PubMedGoogle ScholarCrossref
Davies  M, Harris  A.  Pathological basis of primary heart block.  Br Heart J. 1969;31(2):219-226.PubMedGoogle ScholarCrossref
Demoulin  JC, Simar  LJ, Kulbertus  HE.  Quantitative study of left bundle branch fibrosis in left anterior hemiblock: a stereologic approach.  Am J Cardiol. 1975;36(6):751-756.PubMedGoogle ScholarCrossref
Halaweish  I, Alam  HB.  Changing demographics of the American population.  Surg Clin North Am. 2015;95(1):1-10. PubMedGoogle ScholarCrossref
Boyle  JP, Thompson  TJ, Gregg  EW, Barker  LE, Williamson  DF.  Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence.  Popul Health Metr. 2010;8(1):29. PubMedGoogle ScholarCrossref
Jensen  PN, Gronroos  NN, Chen  LY,  et al.  Incidence of and risk factors for sick sinus syndrome in the general population.  J Am Coll Cardiol. 2014;64(6):531-538. PubMedGoogle ScholarCrossref
Alonso  A, Agarwal  SK, Soliman  EZ,  et al.  Incidence of atrial fibrillation in whites and African-Americans: the Atherosclerosis Risk in Communities (ARIC) study.  Am Heart J. 2009;158(1):111-117. PubMedGoogle ScholarCrossref
Marcus  GM, Alonso  A, Peralta  CA,  et al; Candidate-Gene Association Resource (CARe) Study.  European ancestry as a risk factor for atrial fibrillation in African Americans.  Circulation. 2010;122(20):2009-2015. PubMedGoogle ScholarCrossref
Dewland  TA, Olgin  JE, Vittinghoff  E, Marcus  GM.  Incident atrial fibrillation among Asians, Hispanics, blacks, and whites.  Circulation. 2013;128(23):2470-2477. PubMedGoogle ScholarCrossref
Menon  DV, Arbique  D, Wang  Z, Adams-Huet  B, Auchus  RJ, Vongpatanasin  W.  Differential effects of chlorthalidone versus spironolactone on muscle sympathetic nerve activity in hypertensive patients.  J Clin Endocrinol Metab. 2009;94(4):1361-1366. PubMedGoogle ScholarCrossref
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    1 Comment for this article
    RE: Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on Conduction System Disease
    Dr.Rajiv Kumar, Dr.Jagjit Singh. | Faculty, Deptt. of Pharmacology.
    This is good to read an investigational research article, which is a secondary analysis of a RCT to determine the effects of pharmacologic therapy on CAD events and cardiovascular and renal outcomes.
    The investigators assessed the incidence of conduction system disease by the 12-lead electrocardiogram and this is pertinent to mention here that ECG findings in presence of conduction system diseases are not reliable although patients with prevalent conduction system disease were not included.
    The effect of angiotensin II receptor type 1 (AT1) antagonist has not been taken in this secondary analysis but this should also be in trial study.
    The ALLHAT investigators rightly said the views expressed are those of the authors and do not necessarily reflect the official positions of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the US Department of Health and Human Services.
    Regards ,
    Dr Rajiv Kumar, Dr Jagjit Singh. Faculty, Deptt. of Pharmacology. Government Medical College & HospitalChandigarh, 160030, India. DRrajiv.08@gmail.com

    Original Investigation
    August 2016

    Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on Conduction System Disease

    Author Affiliations
    • 1Knight Cardiovascular Institute, Oregon Health and Science University, Portland
    • 2Department of Epidemiology and Prevention, Section of Cardiology, Wake Forest School of Medicine, Winston-Salem, North Carolina
    • 3Department of Internal Medicine, Section of Cardiology, Wake Forest School of Medicine, Winston-Salem, North Carolina
    • 4Section of Cardiovascular Medicine, Boston University School of Medicine, Boston, Massachusetts
    • 5Department of Biostatistics, University of Texas School of Public Health, Houston
    • 6Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles
    • 7Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis
    • 8Center for Arrhythmia Prevention, Division of Preventive Medicine and Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
    • 9Section of Electrophysiology, Division of Cardiology, Department of Medicine, University of California, San Francisco
    JAMA Intern Med. 2016;176(8):1085-1092. doi:10.1001/jamainternmed.2016.2502

    Importance  Cardiac conduction abnormalities are associated with an increased risk for morbidity and mortality, and understanding factors that accelerate or delay conduction system disease could help to identify preventive and therapeutic strategies. Antifibrotic and anti-inflammatory properties of angiotensin-converting enzyme inhibitors and treatment for hyperlipidemia may reduce the risk for incident conduction system disease.

    Objective  To identify the effect of pharmacologic therapy randomization and clinical risk factors on the incidence of conduction system disease.

    Design, Setting, and Participants  This secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) investigation acquired data from 623 North American centers. A total of 21 004 ambulatory individuals 55 years or older with hypertension and at least 1 other cardiac risk factor were included in the analysis.

    Interventions  Participants were randomly assigned to receive amlodipine besylate, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin sodium vs usual care.

    Main Outcomes and Measures  An electrocardiogram (ECG) was obtained at study enrollment and every 2 years of follow-up. The development of incident first-degree atrioventricular block, left anterior fascicular block, incomplete left bundle branch block (LBBB), LBBB, incomplete right bundle branch block (RBBB), RBBB, or intraventricular conduction delay was assessed by serial ECGs.

    Results  The 21 004 participants (11 758 men [56.0%]; 9246 women [44.0%]; mean [SD] age, 66.5 [7.3] years) underwent a mean (SD) follow-up of 5.0 (1.2) years. Among the 1114 participants who developed any conduction defect, 389 developed LBBB, 570 developed RBBB, and 155 developed intraventricular conduction delay. Compared with chlorthalidone, randomization to lisinopril was associated with a significant 19% reduction in conduction abnormalities (hazard ratio [HR], 0.81; 95% CI, 0.69-0.95; P = .01). Treatment with amlodipine, however, was not associated with a significant difference in conduction outcome events (HR, 0.94; 95% CI, 0.81-1.09; P = .42). Similarly, pravastatin treatment was not associated with a reduced adjusted risk for incident disease compared with usual hyperlipidemia treatment (HR, 1.13; 95% CI, 0.95-1.35; P = .18). Increased age (HR, 1.47; 95% CI, 1.34-1.63; P < .001), male sex (HR, 0.59; 95% CI, 0.50-0.73; P < .001), white race (HR, 0.59; 95% CI, 0.50-0.70; P < .001), diabetes (HR, 1.23; 95% CI, 1.07-1.42; P = .003), and left ventricular hypertrophy (HR, 3.20; 95% CI, 2.61-3.94; P < .001) were also independently associated with increased risk for conduction system disease.

    Conclusions and Relevance  Incident conduction system disease is significantly reduced by lisinopril therapy and is independently associated with multiple clinical factors. Further studies are warranted to determine whether pharmacologic treatment affects conduction abnormality outcomes, including pacemaker implantation.

    Trial Registration  clinicaltrials.gov Identifier: NCT00000542