Letter to the Editor Effect of homocysteine-lowering vitamin treatment on electrocardiography stress tests in a randomized, placebo-controlled trial: comparison between ST-segment changes and Athen QRS-score E.G.J. Vermeulen a,d, * , M.I.A. van Engeland a,d , F.C. Visser b,d , C.D.A. Stehouwer c,d,e , J.W.R. Twisk e , C.M.C. van Campen b,d , J.A. Rauwerda a,d a Department of Surgery, Vascular Surgical Unit, VU University Medical Center, Amsterdam, The Netherlands b Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands c Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands d Institute for Cardiovascular Research ‘‘Vrije Universiteit’’ (ICaR-VU), Amsterdam, The Netherlands e Institute for Research in Extramural Medicine (EMGO), Amsterdam, The Netherlands Received 12 November 2002; accepted 30 January 2003 Keywords: Electrocardiography; Athen QRS-score; Homocysteine; Folic acid; Vitamin B 6 Assessment of whether homocysteine-lowering treatment with folic acid and vitamin B 6 reduces the risk of athero- thrombotic events is an important issue. We have reported a reduced rate of abnormal electrocardiography stress tests (xECGs), analyzed using ST-segment displacements, in a vitamin-treated group [odds ratio (OR) 0.40; 95% confidence interval (CI) 0.17 – 0.93], in a randomized placebo-controlled trial, in which progression of subclinical atherosclerosis was investigated in healthy siblings of patients with premature atherothrombotic disease and elevated concentrations of homocysteine [1]. Recently, a new diagnostic ECG evalua- tion has been introduced, the Athen QRS-score, reflecting ischemic depolarization abnormalities. Studies so far have demonstrated a higher sensitivity and specificity for detection of coronary artery disease than obtained through analysis of ST-segment displacement (72 –95 versus 68% and 77 versus 72 – 85%, respectively) [2–5]. In view of these considera- tions, we re-analyzed the xECGs from our placebo-controlled trial [1] according to the Athen QRS-score and compared the results to those obtained with traditional assessment of ST- segment displacement. After selection, as described in detail elsewhere [1], 158 healthy asymptomatic siblings (18 > age < 56 years; 104 hyper- and 54 normohomocysteinaemic after an oral methi- onine load) of patients with clinical atherosclerotic disease participated in the study. Seventy-eight participants were treated orally with daily folic acid (5 mg) plus vitamin B 6 (250 mg) and 80 with placebo medication for 2 years in double-blind fashion. At baseline and after 1 and 2 years, we collected demographic and clinical data, and performed an xECG. Traditional criteria for ST-segment displacement were used to analyze the xECGs [1]. The Athen QRS-score was calculated as described previously [2,3]. In short, of three beats the average amplitudes of Q-, R- and S-waves were measured in leads AVF and V5. The Q-, R- and S-wave values immediately after exercise were subtracted from the values prior to exercise. The Athen QRS-score (in mm) was calculated according to the formula: Athen QRS-score = (DR AVF ÀDQ AVF ÀDS AVF )+(DR V5 ÀDQ V5 ÀDS V5 ). A score of V 5 mm was considered positive for an abnormal xECG [2,3]. ST-segment analyses of the xECG were per- formed by two and the Athen QRS-score by one cardiolo- gist, all blinded for treatment allocation or clinical data, except gender and age. Generalized estimating equations (GEEs) were used to analyze the influence of therapy with vitamin B 6 and folic acid on the longitudinal development of the ST-segment 0167-5273/$ - see front matter D 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0167-5273(03)00168-2 * Corresponding author. Department of Surgery, Vascular Surgical Unit, Gelre Hospitals Apeldoorn, P.O. Box 9014, 7300 DS Apeldoorn, The Netherlands. Tel.: +31-55-581-8181; fax: +31-55-581-8131. E-mail address: egj.vermeulen@gelre.nl (E.G.J. Vermeulen). www.elsevier.com/locate/ijcard International Journal of Cardiology 93 (2004) 323 – 324