Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. The voltage of R wave in lead aVL improves risk stratification in hypertensive patients without ECG left ventricular hypertrophy Paolo Verdecchia a , Fabio Angeli a , Claudio Cavallini a , Giovanni Mazzotta a , Salvatore Repaci a , Silvia Pede a , Claudia Borgioni a , Giorgio Gentile b and Gianpaolo Reboldi b Objectives We tested the hypothesis that the voltages of QRS on ECG improve risk stratification in hypertensive patients without left ventricular hypertrophy on ECG. Methods and results We studied 2042 initially untreated patients with hypertension (mean age 49 years, 46% women) without left ventricular hypertrophy on ECG and no history of cardiovascular disease. At entry, all patients underwent diagnostic tests, including 24-h ambulatory blood pressure monitoring and echocardiography. Among the different ECG voltages, the R wave in lead aVL showed the closest association with left ventricle (LV) mass (r U 0.31; P < 0.001), followed by the R wave in D1 (r U 0.25) and the S wave in V 3 (r U 0.22). Patients were followed up for a mean of 7.7 years (range 1–22 years), and treatment was tailored individually. During follow-up, there were 188 major cardiovascular events. The relationship between LV voltage and outcome was assessed using a Cox model with adjustment for age, sex, diabetes, smoking, total cholesterol, serum creatinine, LV mass on echocardiography and average 24-h ambulatory blood pressure. A 0.1 mV higher R wave voltage in lead aVL was associated with a 9% higher risk of cardiovascular disease (95% confidence interval U 0.04–0.15%; P < 0.001). Other ECG voltages and minor repolarization changes were not related to clinical outcome. Conclusion Our results show for the first time that the voltage of the R wave in lead aVL improves cardiovascular risk stratification in hypertensive patients without left ventricular hypertrophy on ECG. Its prognostic value is independent of LV mass on echocardiography and 24-h ambulatory blood pressure. J Hypertens 27:1697–1704 Q 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins. Journal of Hypertension 2009, 27:1697–1704 Keywords: echocardiography, electrocardiography, epidemiology, hypertension, left ventricular hypertrophy, left ventricular mass, risk factors Abbreviations: ABP, ambulatory blood pressure; ACE, angiotensin- converting-enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; CCBs, calcium channel blockers; ECG, electrocardiogram; LV, left ventricle; LVH, left ventricular hypertrophy; LVM, left ventricular mass; PIUMA, Progetto Ipertensione Umbria Monitoraggio Ambulatoriale; ROC, receiver-operated characteristic a Department of Cardiology, Clinical Research Unit ‘Preventive Cardiology’, Hospital S. Maria della Misericordia, Cardiologia and b Department of Internal Medicine, University of Perugia, Perugia, Italy Correspondence to Dr Paolo Verdecchia, MD, FACC, FAHA, Unita ` di Ricerca Clinica ‘Cardiologia Preventiva’, Ospedale ‘S. Maria della Misericordia’, Piazzale G. Menghini, Perugia 06132, Italy Tel: +39 075 5782213; fax: +39 075 5782214; e-mail: verdec@tin.it Received 3 January 2009 Revised 18 March 2009 Accepted 23 March 2009 See editorial commentary on page 1538 Introduction The traditional resting ECG remains a simple, non- invasive and relatively inexpensive diagnostic tool in patients with high blood pressure (BP). Hypertension guidelines recommend ECG as first-line diagnostic test in patients with a clinical diagnosis of hypertension [1,2]. Indeed, there is evidence from longitudinal studies that left ventricular hypertrophy (LVH) diagnosed by stan- dard 12-lead ECG is a powerful predictor of cardiovas- cular disease not only in the general population [3,4], but also in specific groups of patients with arterial hyperten- sion [5–7], coronary artery disease [8] and congestive heart failure [9]. Although the prognostic value of ECG LVH is well established, surprisingly few data are available on the prognostic value of ECG findings in hypertensive patients without evidence of ECG LVH and no overt cardiovascular disease. In such patients, echocardiogra- phy would be the obvious diagnostic choice because ECG is less sensitive than echocardiography for diagnosis of LVH [10,11]. However, a further exploitation of the ECG features in this large proportion of patients with generally mild or moderate hypertension and without ECG LVH would be relevant for cost and convenience reasons, if supported by evidence. For example, it was suggested that a prolonged ventricular repolarization [12] and minor repolarization abnormalities [13] may improve prediction of cardiovascular risk even after adjustment for the confounding effect of LVH. The present study was conducted to test a hypothesis generated by some previous studies. In one study, ECG voltages showed a direct and consistent association with Original article 1697 0263-6352 ß 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/HJH.0b013e32832c0031