Effect of Telomere Length on Prognosis in Men With Acute Coronary Syndrome Jose-Angel Perez-Rivera, MD a,b, *, Pedro Pabon-Osuna, MD, PhD a,b , Clara Cieza-Borrella, PhD b,c,d , Olga Duran-Bobin, MD a,b , Francisco Martin-Herrero, MD, PhD a,b , Jose-Ramon Gonzalez-Porras, MD, PhD b,e , and Rogelio Gonzalez-Sarmiento, MD, PhD b,c,d Telomere length is related to cellular aging and cardiovascular disease. Nevertheless, the specific role of cellular aging in this process is still unclear. The aim of this report was to analyze the prognostic value of telomere length in men admitted for acute coronary syn- drome. Telomere length was measured by quantitative polymerase chain reaction in peripheral blood leukocytes of 203 men classified into 2 groups: those aged 50 to 75 years and those >75 years. Clinical follow-up had been done for >600 days, and a prognostic combined event was defined. In men aged 50 to 75 years, we found a statistically significant worse prognosis in patients with short telomeres (log-rank: 5.22, p <0.05) but not in men >75 years (log-rank: 0.01, p [ 0.91). Cox analysis confirmed short telomeres in men aged 50 to 75 years as an independent prognostic risk factor. In conclusion, telomere length is a good predictor of cardiovascular prognosis in men admitted for acute coronary syndrome, but this relation depends on the chronological age of the population studied. Ó 2014 Elsevier Inc. All rights reserved. (Am J Cardiol 2014;113:418e421) Cardiovascular diseases, especially coronary artery dis- ease (CAD), are one of the most frequent health problems in all over the world. 1 Telomeres are noncoding regions of DNA that preserve genomic stability. 2 During life, telo- meres get shorter because of the typical DNA replication 3 and other factors such as oxidative stress. 4 Recently, telo- meres have been related to cardiovascular diseases 5 ; for example, different researches have established that patients with CAD have shorter telomeres than healthy subjects. 6 However, there is low evidence about the prognostic value of telomere length in cardiovascular disease, although it seems that in stable CAD, people with shorter telomeres present a poor prognosis during the follow-up. 7 Neverthe- less, in the framework of acute coronary syndrome (ACS), telomere effect has been poorly studied. 8 Moreover, elderly patients are not represented enough in most reports and results are less conclusive. 9e11 The aim of this study was to analyze the prognostic value of telomere length in men admitted for an ACS and the possible differences in this value according to the chronological age of the population studied. Methods We collected, after obtaining informed consent from each patient, peripheral blood samples from 203 men consecutively admitted for ACS in our coronary care unit from January 2004 to October 2005. Whole population was divided into 2 groups: 150 men aged 50 to 75 years (mean, 62  7) and 53 men aged >75 years (mean, 82  5). This classification was made ac- cording to data available in other significant reports. 12 We excluded women to avoid confounding factors because some investigations have revealed that telomere length is longer in women than men. 13,14 All the information was collected in a clinical and epidemiological questionnaire. The study was approved by the Ethical Committee of our hospital and con- forms to the Declaration of Helsinki. Genomic DNA was extracted from leukocytes, and telomere length was measured by relative and comparative quantitative polymerase chain reaction that compares mean telomere repeat sequence copy number to a reference single copy gene. For each DNA sample, we performed 6 quan- titative polymerase chain reaction runs: 3 “T” runs (for telomere repeat sequence copy number) and 3 “S” runs (for single copy gene copy number). The reference single copy gene used in this study was 36b4. The method performed was essentially described by Gil and Coetzer 15 in 2004 using the same primers developed by Cawthon 16 in 2002 and the 36b4 gene as the endogenous control. The telomere-specific primers were forward, 5 0 -GGTT TTTGAGGGTGAGGGTGAGGGTGAGGGTGAGGGT-3 0 and reverse, 5 0 -TCCCGACTATCCCTATCCCTATCCC TATCCCTATCCCTA-3 0 . The 36b4-specific primers were forward, 5 0 -CAGCAAGTGGGAAGGTGTAATCC-3 0 and reverse, 5 0 -CCCATTCTATCATCAACGGGTACAA-3 0 . The DNA amount for each reaction was 10 ng, and the quantities added of each primer were 1 ml of “forward” primer (5 mM) and 2.33 ml of “reverse” primer (5 mM) for the a Department of Cardiology, University Hospital of Salamanca, Sala- manca, Spain; b Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain; c Molecular Medicine Unit, Department of Medicine, University of Salamanca, Salamanca, Spain; d Cancer Research Centre of Salamanca (CIC-IBMCC), Spanish National Research Council (CSIC), Salamanca, Spain; and e Department of Hematology, University Hospital of Salamanca, Salamanca, Spain. Manuscript received August 13, 2013; revised manuscript received and accepted October 5, 2013. This work was supported by the FIS Grant PI 100219 to Dr. Gonzalez- Sarmiento. See page 421 for disclosure information. *Corresponding author: Tel: (þ34) 923291100; fax: (þ34) 923270008. E-mail address: jangel.perezrivera@gmail.com (J.-A. Perez-Rivera). 0002-9149/13/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. www.ajconline.org http://dx.doi.org/10.1016/j.amjcard.2013.10.009