Top

Published in:

Open Access 01-10-2015 | Original Paper

Leukocyte telomere length and left ventricular function after acute ST-elevation myocardial infarction: data from the glycometabolic intervention as adjunct to primary coronary intervention in ST elevation myocardial infarction (GIPS-III) trial

Authors: Vincent G. Haver, Minke H. T. Hartman, Irene Mateo Leach, Erik Lipsic, Chris P. Lexis, Dirk J. van Veldhuisen, Wiek H. van Gilst, Iwan C. van der Horst, Pim van der Harst

Published in: Clinical Research in Cardiology | Issue 10/2015

Abstract

Background

Telomere length has been associated with coronary artery disease and heart failure. We studied whether leukocyte telomere length is associated with left ventricular ejection fraction (LVEF) after ST-elevation myocardial infarction (STEMI).

Methods and results

Leukocyte telomere length (LTL) was determined using the monochrome multiplex quantitative PCR method in 353 patients participating in the glycometabolic intervention as adjunct to primary percutaneous coronary intervention in STEMI III trial. LVEF was assessed by magnetic resonance imaging. The mean age of patients was 58.9 ± 11.6 years, 75 % were male. In age- and gender-adjusted models, LTL at baseline was significantly associated with age (beta ± standard error; −0.33 ± 0.01; P < 0.01), gender (0.15 ± 0.03; P < 0.01), TIMI flow pre-PCI (0.05 ± 0.03; P < 0.01), TIMI flow post-PCI (0.03 ± 0.04; P < 0.01), myocardial blush grade (−0.05 ± 0.07; P < 0.01), serum glucose levels (−0.11 ± 0.01; P = 0.03), and total leukocyte count (−0.11 ± 0.01; P = 0.04). At 4 months after STEMI, LVEF was well preserved (54.1 ± 8.4 %) and was not associated with baseline LTL (P = 0.95). Baseline LTL was associated with n-terminal pro-brain natriuretic peptide (NT-proBNP) at 4 months (−0.14 ± 0.01; P = 0.02), albeit not independent for age and gender.

Conclusion

Our study does not support a role for LTL as a causal factor related to left ventricular ejection fraction after STEMI.

Available only for authorised users

Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van ‘t Hof A, Widimsky P, Zahger D, Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC) (2012) ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 33:2569–2619CrossRefPubMed

De Luca G, Dirksen MT, Spaulding C, Kelbæk H, Schalij M, Thuesen L, van der Hoeven B, Vink MA, Kaiser C, Musto C, Chechi T, Spaziani G, de la Llera LS, Pasceri V, Di Lorenzo E, Violini R (2014) Drug-eluting stents in patients with anterior STEMI undergoing primary angioplasty: a substudy of the DESERT cooperation. Clin Res Cardiol 103(9):685–699CrossRefPubMed

Joyce E, Hoogslag GE, Leong DP, Fox K, Schalij MJ, Marsan NA, Bax JJ, Delgado V (2013) Association between discharge heart rate and left ventricular adverse remodelling in ST segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention. Heart 99:556–561CrossRefPubMed

van der Vleuten PA, Rasoul S, Huurnink W, van der Horst IC, Slart RH, Reiffers S, Dierckx RA, Tio RA, Ottervanger JP, De Boer MJ, Zijlstra F (2008) The importance of left ventricular function for long-term outcome after primary percutaneous coronary intervention. BMC Cardiovasc Disord 8:4PubMedCentralCrossRefPubMed

Wong LS, de Boer RA, Samani NJ, van Veldhuisen DJ, van der Harst P (2008) Telomere biology in heart failure. Eur J Heart Fail 10:1049–1056CrossRefPubMed

Zhu H, Belcher M, van der Harst P (2011) Healthy aging and disease: role for telomere biology? Clin Sci (Lond) 120:427–440CrossRef

Mason PJ, Perdigones N (2013) Telomere biology and translational research. Transl Res 162:333–342PubMedCentralCrossRefPubMed

Abdallah P, Luciano P, Runge KW, Lisby M, Geli V, Gilson E, Teixeira MT (2009) A two-step model for senescence triggered by a single critically short telomere. Nat Cell Biol 11:988–993PubMedCentralCrossRefPubMed

Kurz DJ, Decary S, Hong Y, Trivier E, Akhmedov A, Erusalimsky JD (2004) Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells. J Cell Sci 117:2417–2426CrossRefPubMed

10.

Serra V, Grune T, Sitte N, Saretzki G, von Zglinicki T (2000) Telomere length as a marker of oxidative stress in primary human fibroblast cultures. Ann N Y Acad Sci 908:327–330CrossRefPubMed

11.

Samani NJ, van der Harst P (2008) Biological ageing and cardiovascular disease. Heart 94:537–539CrossRefPubMed

12.

Samani NJ, Boultby R, Butler R, Thompson JR, Goodall AH (2001) Telomere shortening in atherosclerosis. Lancet 358:472–473CrossRefPubMed

13.

Brouilette SW, Moore JS, McMahon AD, Thompson JR, Ford I, Shepherd J, Packard CJ, Samani NJ, West of Scotland Coronary Prevention Study Group (2007) Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Lancet 369:107–114CrossRefPubMed

14.

van der Harst P, Wong LS, de Boer RA, Brouilette SW, van der Steege G, Voors AA, Hall AS, Samani NJ, Wikstrand J, van Gilst WH, van Veldhuisen DJ, MERIT-HF Study Group (2008) Possible association between telomere length and renal dysfunction in patients with chronic heart failure. Am J Cardiol 102:207–210CrossRefPubMed

15.

Collerton J, Martin-Ruiz C, Kenny A, Barrass K, von Zglinicki T, Kirkwood T, Keavney B, Newcastle 85 + Core Study Team (2007) Telomere length is associated with left ventricular function in the oldest old: the Newcastle 85 + study. Eur Heart J 28:172–176CrossRefPubMed

16.

Jaguszewski M, Ghadri JR, Diekmann J, Bataiosu RD, Hellermann JP, Sarcon A, Siddique A, Baumann L, Stahli BE, Luscher TF, Maier W, Templin C (2014) Acute coronary syndromes in octogenarians referred for invasive evaluation: treatment profile and outcomes. Clin Res Cardiol 104:51–58CrossRefPubMed

17.

Vandecasteele EH, De Buyzere M, Gevaert S, de Meester A, Convens C, Dubois P, Boland J, Sinnaeve P, De Raedt H, Vranckx P, Coussement P, Evrard P, Beauloye C, Renard M, Claeys MJ (2013) Reperfusion therapy and mortality in octogenarian STEMI patients: results from the Belgian STEMI registry. Clin Res Cardiol 102:837–845CrossRefPubMed

18.

Huber M, Treszl A, Wehland M, Winther I, Zergibel I, Reibis R, Bolbrinker J, Stoll M, Schonfelder G, Wegscheider K, Voller H, Kreutz R (2012) Genetic variants implicated in telomere length associated with left ventricular function in patients with hypertension and cardiac organ damage. J Mol Med (Berl) 90:1059–1067CrossRef

19.

Lexis CP, van der Horst IC, Lipsic E, van der Harst P, van der Horst-Schrivers AN, Wolffenbuttel BH, de Boer RA, van Rossum AC, van Veldhuisen DJ, de Smet BJ, Investigators GIPS-III (2012) Metformin in non-diabetic patients presenting with ST elevation myocardial infarction: rationale and design of the glycometabolic intervention as adjunct to primary percutaneous intervention in ST elevation myocardial infarction (GIPS)-III trial. Cardiovasc Drugs Ther 26:417–426PubMedCentralCrossRefPubMed

20.

Lexis CP, van der Horst IC, Lipsic E, Wieringa WG, de Boer RA, van den Heuvel AF, van der Werf HW, Schurer RA, Pundziute G, Tan ES, Nieuwland W, Willemsen HM, Dorhout B, Molmans BH, van der Horst-Schrivers AN, Wolffenbuttel BH, ter Horst GJ, van Rossum AC, Tijssen JG, Hillege HL, de Smet BJ, van der Harst P, van Veldhuisen DJ, GIPS-III Investigators (2014) Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial. JAMA 311:1526–1535CrossRefPubMed

21.

Cawthon RM (2009) Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res 37:e21PubMedCentralCrossRefPubMed

22.

Huzen J, Wong LS, van Veldhuisen DJ, Samani NJ, Zwinderman AH, Codd V, Cawthon RM, Benus GF, van der Horst IC, Navis G, Bakker SJ, Gansevoort RT, de Jong PE, Hillege HL, van Gilst WH, de Boer RA, van der Harst P (2014) Telomere length loss due to smoking and metabolic traits. J Intern Med 275:155–163CrossRefPubMed

23.

van der Harst P, van der Steege G, de Boer RA, Voors AA, Hall AS, Mulder MJ, van Gilst WH, van Veldhuisen DJ, MERIT-HF Study Group (2007) Telomere length of circulating leukocytes is decreased in patients with chronic heart failure. J Am Coll Cardiol 49:1459–1464CrossRefPubMed

24.

Frenck RW Jr, Blackburn EH, Shannon KM (1998) The rate of telomere sequence loss in human leukocytes varies with age. Proc Natl Acad Sci U S A 95:5607–5610PubMedCentralCrossRefPubMed

25.

Gardner M, Bann D, Wiley L, Cooper R, Hardy R, Nitsch D, Martin-Ruiz C, Shiels P, Sayer AA, Barbieri M, Bekaert S, Bischoff C, Brooks-Wilson A, Chen W, Cooper C, Christensen K, De Meyer T, Deary I, Der G, Diez Roux A, Fitzpatrick A, Hajat A, Halaschek-Wiener J, Harris S, Hunt SC, Jagger C, Jeon HS, Kaplan R, Kimura M, Lansdorp P, Li C, Maeda T, Mangino M, Nawrot TS, Nilsson P, Nordfjall K, Paolisso G, Ren F, Riabowol K, Robertson T, Roos G, Staessen JA, Spector T, Tang N, Unryn B, van der Harst P, Woo J, Xing C, Yadegarfar ME, Park JY, Young N, Kuh D, von Zglinicki T, Ben-Shlomo Y, Halcyon study team (2014) Gender and telomere length: systematic review and meta-analysis. Exp Gerontol 51:15–27PubMedCentralCrossRefPubMed

26.

Fyhrquist F, Saijonmaa O, Strandberg T (2013) The roles of senescence and telomere shortening in cardiovascular disease. Nat Rev Cardiol 10:274–283CrossRefPubMed

27.

Raymond AR, Norton GR, Sareli P, Woodiwiss AJ, Brooksbank RL (2013) Relationship between average leucocyte telomere length and the presence or severity of idiopathic dilated cardiomyopathy in black Africans. Eur J Heart Fail 15:54–60CrossRefPubMed

28.

Nilsson PM, Tufvesson H, Leosdottir M, Melander O (2013) Telomeres and cardiovascular disease risk: an update 2013. Transl Res 162:371–380CrossRefPubMed

29.

Zhang WG, Zhu SY, Zhao DL, Jiang SM, Li J, Li ZX, Fu B, Zhang M, Li DG, Bai XJ, Cai GY, Sun XF, Chen XM (2014) The correlation between peripheral leukocyte telomere length and indicators of cardiovascular aging. Heart Lung Circ 23:883–890CrossRefPubMed

30.

Siegerink B, Maas R, Vossen CY, Schwedhelm E, Koenig W, Boger R, Rothenbacher D, Brenner H, Breitling LP (2013) Asymmetric and symmetric dimethylarginine and risk of secondary cardiovascular disease events and mortality in patients with stable coronary heart disease: the KAROLA follow-up study. Clin Res Cardiol 102:193–202CrossRefPubMed

31.

Thilo C, Bluthgen A, von Scheidt W (2013) Efficacy and limitations of a STEMI network: 3 years of experience within the myocardial infarction network of the region of Augsburg-HERA. Clin Res Cardiol 102:905–914CrossRefPubMed

32.

Honold J, Geiger L, Assmus B, Fischer-Rasokat U, Schaechinger V, Zeiher AM, Spyridopoulos I (2008) The initial slope of the VCO₂/VO₂-curve (s1) in cardiopulmonary exercise testing is a strong and independent predictor of outcome in patients with previous myocardial infarction. Clin Res Cardiol. 97(12):882–890CrossRefPubMed

33.

Werner C, Fürster T, Widmann T, Pöss J, Roggia C, Hanhoun M, Scharhag J, Büchner N, Meyer T, Kindermann W, Haendeler J, Böhm M, Laufs U (2009) Physical exercise prevents cellular senescence in circulating leukocytes and in the vessel wall. Circulation 120(24):2438–2447CrossRefPubMed

34.

Shacham Y, Leshem-Rubinow E, Steinvil A, Assa EB, Keren G, Roth A, Arbel Y (2014) Renal impairment according to acute kidney injury network criteria among ST elevation myocardial infarction patients undergoing primary percutaneous intervention: a retrospective observational study. Clin Res Cardiol 103(7):525–532CrossRefPubMed

35.

Volaklis KA, Tokmakidis SP, Halle M (2013) Acute and chronic effects of exercise on circulating endothelial progenitor cells in healthy and diseased patients. Clin Res Cardiol 102:249–257CrossRefPubMed

36.

Spyridopoulos I, Erben Y, Brummendorf TH, Haendeler J, Dietz K, Seeger F, Kissel CK, Martin H, Hoffmann J, Assmus B, Zeiher AM, Dimmeler S (2008) Telomere gap between granulocytes and lymphocytes is a determinant for hematopoetic progenitor cell impairment in patients with previous myocardial infarction. Arterioscler Thromb Vasc Biol 28(5):968–974CrossRefPubMed

37.

Palm W, de Lange T (2008) How shelterin protects mammalian telomeres. Annu Rev Genet 42:301–334CrossRefPubMed

Title: Leukocyte telomere length and left ventricular function after acute ST-elevation myocardial infarction: data from the glycometabolic intervention as adjunct to primary coronary intervention in ST elevation myocardial infarction (GIPS-III) trial
Authors: Vincent G. Haver
Minke H. T. Hartman
Irene Mateo Leach
Erik Lipsic
Chris P. Lexis
Dirk J. van Veldhuisen
Wiek H. van Gilst
Iwan C. van der Horst
Pim van der Harst
Publication date: 01-10-2015
Publisher: Springer Berlin Heidelberg
Published in: Clinical Research in Cardiology / Issue 10/2015
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI: https://doi.org/10.1007/s00392-015-0848-x

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Leukocyte telomere length and left ventricular function after acute ST-elevation myocardial infarction: data from the glycometabolic intervention as adjunct to primary coronary intervention in ST elevation myocardial infarction (GIPS-III) trial

Abstract

Background

Methods and results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods and results

Conclusion

Please log in to get access to this content

Other articles of this Issue 10/2015

Abnormal mitral–aortic intervalvular coupling in mitral valve diseases: a study using real-time three-dimensional transesophageal echocardiography

How does a clinical trial fit into the real world? The RELAX-AHF study population into the EAHFE registry

Limitations in S-ICD therapy: reasons for system explantation

Comparison of contact force-guided procedure with non-contact force-guided procedure during left atrial mapping and pulmonary vein isolation: impact of contact force on recurrence of atrial fibrillation

The impact of transcatheter aortic valve implantation on quality of life: results from the German transcatheter aortic valve interventions registry

Atrial fibrillation and hypertrophic cardiomyopathy: who to anticoagulate?

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page