ST-T Wave Abnormality in Lead aVR and Reclassification of Cardiovascular Risk (from the National Health and Nutrition Examination Survey-III)

      Electrocardiographic lead aVR is often ignored in clinical practice. The aim of this study was to investigate whether ST-T wave amplitude in lead aVR predicts cardiovascular (CV) mortality and if this variable adds value to a traditional risk prediction model. A total of 7,928 participants enrolled in the National Health and Nutrition Examination Survey (NHANES) III with electrocardiographic data available were included. Each participant had 13.5 ± 3.8 years of follow-up. The study sample was stratified according to ST-segment amplitude and T-wave amplitude in lead aVR. ST-segment elevation (>8 μV) in lead aVR was predictive of CV mortality in the multivariate analysis when not accounting for T-wave amplitude. The finding lost significance after including T-wave amplitude in the model. A positive T wave in lead aVR (>0 mV) was the strongest multivariate predictor of CV mortality (hazard ratio 3.37, p <0.01). The addition of T-wave amplitude in lead aVR to the Framingham risk score led to a net reclassification improvement of 2.7% of subjects with CV events and 2.3% of subjects with no events (p <0.01). Furthermore, in the intermediate-risk category, 20.0% of the subjects in the CV event group and 9.1% of subjects in the no-event group were appropriately reclassified. The absolute integrated discrimination improvement was 0.012 (p <0.01), and the relative integrated discrimination improvement was 11%. In conclusion, T-wave amplitude in lead aVR independently predicts CV mortality in a cross-sectional United States population. Adding T-wave abnormalities in lead aVR to the Framingham risk score improves model discrimination and calibration with better reclassification of intermediate-risk subjects.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • George A.
        • Arumugham P.S.
        • Figueredo V.M.
        aVR—the forgotten lead.
        Exp Clin Cardiol. 2010; 15: e36-e44
        • Kireyev D.
        • Arkhipov M.V.
        • Zador S.T.
        • Paris J.A.
        • Boden W.E.
        Clinical utility of aVR—the neglected electrocardiographic lead.
        Ann Noninvasive Electrocardiol. 2010; 15: 175-180
        • Riera A.R.P.
        • Ferreira C.
        • Ferreira Filho C.
        • Dubner S.
        • Barbosa Barros R.
        • Femenía F.
        • Baranchuk A.
        Clinical value of lead aVR.
        Ann Noninvasive Electrocardiol. 2011; 16: 295-302
        • Williamson K.
        • Mattu A.
        • Plautz C.U.
        • Binder A.
        • Brady W.J.
        Electrocardiographic applications of lead aVR.
        Am J Emerg Med. 2006; 24: 864-874
        • Anttila I.
        • Nikus K.
        • Nieminen T.
        • Jula A.
        • Salomaa V.
        • Reunanen A.
        • Nieminen M.S.
        • Lehtimäki T.
        • Virtanen V.
        • Kähönen M.
        Relation of positive T wave in lead aVR to risk of cardiovascular mortality.
        Am J Cardiol. 2011; 108: 1735-1740
        • Tan S.Y.
        • Engel G.
        • Myers J.
        • Sandri M.
        • Froelicher V.F.
        The prognostic value of T wave amplitude in lead aVR in males.
        Ann Noninvasive Electrocardiol. 2008; 13: 113-119
        • Wong C.K.
        • Gao W.
        • Stewart R.A.H.
        • French J.K.
        • Aylward P.E.G.
        • White H.D.
        The prognostic meaning of the full spectrum of aVR ST-segment changes in acute myocardial infarction.
        Eur Heart J. 2011; 33: 384-392
        • Badheka A.O.
        • Rathod A.
        • Marzouka G.R.
        • Patel N.
        • Bokhari S.S.I.
        • Moscucci M.
        • Cohen M.G.
        Isolated nonspecific ST-segment and T-wave abnormalities in a cross-sectional United States population and mortality (from NHANES III).
        Am J Cardiol. 2012; 110: 521-525
        • Badheka A.O.
        • Patel N.
        • Tushar T.
        • Rathod A.
        • Marzouka G.R.
        • Moscucci M.
        • Cohen M.G.
        Electrocardiographic changes and reclassification of cardiovascular risk: insights from national health and nutrition examination survey-III.
        J Am Coll Cardiol. 2012; 59: e1761
        • United States Preventive Services Task Force
        Screening for coronary heart disease: recommendation statement.
        Ann Intern Med. 2004; 140: 569-572
        • Chou R.
        • Arora B.
        • Dana T.
        • Fu R.
        • Walker M.
        • Humphrey L.
        Screening asymptomatic adults with resting or exercise electrocardiography: a review of the evidence for the U.S. Preventive Services Task Force.
        Ann Intern Med. 2011; 155: 375-385
      1. Plan and operation of the Third National Health and Nutrition Examination Survey 1988–94. Series 1: programs and collection procedures.
        Vital Health Stat 1. 1994; 32: 1-407
      2. National Center for Health Statistics. Electrocardiography Data File Documentation of the NHANES-III 1988–1994. Series 11, No. 2A 1998. Available at: Accessed October 2012.

      3. National Center for Health Statistics. Electrocardiogram Manual of the NHANES-III 1991 1988–1994. Revised September 1991. Available at: Accessed October 2012.

        • Rautaharju P.M.
        • MacInnis P.J.
        • Warren J.W.
        • Wolf H.K.
        • Rykers P.M.
        • Calhoun H.P.
        Methodology of ECG interpretation in the Dalhousie program; NOVACODE ECG classification procedures for clinical trials and population health surveys.
        Methods Inf Med. 1990; 29: 362-374
        • Blackburn H.
        • Keys A.
        • Simonson E.
        • Rautaharju P.
        • Punsar S.
        The electrocardiogram in population studies. A classification system.
        Circulation. 1960; 21: 1160-1175
        • Rautaharju P.M.
        • Calhoun H.P.
        • Chaitman B.R.
        Novacode serial ECG classification system for clinical trials and epidemiologic studies.
        J Electrocardiol. 1992; 24: 179-187
      4. Schafer JL. Analyzing the NHANES III Multiply Imputed Data Set: Methods and Examples. Available at: Accessed October 2012.

        • Harrell F.E.
        Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis.
        Springer, New York2001 (465–506)
        • Pencina M.J.
        • D'Agostino Sr., R.B.
        • D'Agostino Sr., R.B.
        • Vasan R.S.
        Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond.
        Stat Med. 2008; 27: 157-172
        • Hanley J.A.
        • McNeil B.J.
        The meaning and use of the area under a receiver operating characteristic (ROC) curve.
        Radiology. 1982; 143: 29-36
        • D’Agostino R.B.
        • Nam B.H.
        Evaluation of the performance of survival analysis models: discrimination and calibration measures.
        in: Handbook of Statistics. Elsevier, London, United Kingdom2004
        • Ridker P.M.
        • Paynter N.P.
        • Rifai N.
        • Gaziano J.M.
        • Cook N.R.
        C-reactive protein and parental history improve global cardiovascular risk prediction: the Reynolds risk score for men.
        Circulation. 2008; 118: 2243-2251
        • Kannel W.B.
        • Anderson K.
        • McGee D.L.
        • Degatano L.S.
        • Stampfer M.J.
        Nonspecific electrocardiographic abnormality as a predictor of coronary heart disease: the Framingham study.
        Am Heart J. 1987; 113: 370-376
        • Prineas R.J.
        • Grandits G.
        • Rautaharju P.M.
        • Cohen J.D.
        • Zhang Z.M.
        • Crow R.S.
        • MRFIT Research Group
        Long-term prognostic significance of isolated minor electrocardiographic T-wave abnormalities in middle-aged men free of clinical cardiovascular disease (the Multiple Risk Factor Intervention Trial [MRFIT]).
        Am J Cardiol. 2002; 90: 1391-1395
        • Jacobsen M.D.
        • Wagner G.S.
        • Holmvang L.
        • Macfarlane P.W.
        • Naslund U.
        • Grande P.
        • Clemmensen P.
        Clinical significance of abnormal T waves in patients with non-ST-segment elevation acute coronary syndromes.
        Am J Cardiol. 2001; 88: 1225-1229
        • Yeboah J.
        • McClelland R.L.
        • Polonsky T.S.
        • Burke G.L.
        • Sibley C.T.
        • O'Leary D.
        • Carr J.J.
        • Goff D.C.
        • Greenland P.
        • Herrington D.M.
        Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals.
        JAMA. 2012; 308: 788-795
        • Uthamalingam S.
        • Zheng H.
        • Leavitt M.
        • Pomerantsev E.
        • Ahmado I.
        • Gurm G.S.
        • Gewirtz H.
        Exercise-induced ST-segment elevation in ECG lead aVR is a useful indicator of significant left main or ostial LAD coronary artery stenosis.
        JACC Cardiovasc Imaging. 2011; 4: 176
        • Taglieri N.
        • Marzocchi A.
        • Saia F.
        • Marrozzini C.
        • Palmerini T.
        • Ortolani P.
        • Cinti L.
        • Rosmini S.
        • Vagnarelli F.
        • Alessi L.
        Short- and long-term prognostic significance of ST-segment elevation in lead aVR in patients with non-ST-segment elevation acute coronary syndrome.
        Am J Cardiol. 2011; 108: 21-28
        • Kosuge M.
        • Kimura K.
        • Ishikawa T.
        • Ebina T.
        • Hibi K.
        • Toda N.
        • Umemura S.
        ST-segment depression in lead aVR.
        Chest. 2005; 128: 780-786