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Ideal cardiovascular health and liver enzyme levels in European adolescents; the HELENA study

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Abstract

There is an increasing interest for the role of liver enzymes as predictors of non-liver-related morbidity and mortality. The American Heart Association (AHA) described the ideal cardiovascular health concept as a score of seven cardiovascular health behaviors and factors that can be used to monitor and predict ideal cardiovascular health over time. This study aimed to examine the association of the ideal cardiovascular health (ICH), as defined by the AHA, with liver enzyme levels in European adolescents. A total of 637 adolescents (54.6% females), aged 14.6 ± 1.2 years from nine European countries participated in this cross-sectional study. Blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase were measured and the AST/ALT ratio calculated. Ideal cardiovascular health was defined as meeting ideal levels of the following components: four behaviors (smoking, body mass index, physical activity, and diet) and three factors (total cholesterol, blood pressure, and glucose). A higher number of ideal cardiovascular health behaviors, factors, and ideal cardiovascular health index were associated with lower ALT (P < 0.05, P < 0.001, and P < 0.001, respectively) and gamma-glutamyltransferase (P < 0.001, P < 0.01, and P < 0.001, respectively) levels. Similarly, a higher number of ideal cardiovascular health behaviors (P < 0.01), factors (P < 0.01), and ideal cardiovascular health index (P < 0.001) were associated with a higher aspartate aminotransferase to alanine aminotransferase ratio. These findings reinforce the usefulness of the ICH index as an instrument to identify target individuals and promote cardiovascular health in adolescents, and it also extends these observations to the liver manifestation of the metabolic syndrome.

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Abbreviations

AHA:

American Heart Association

ALT:

Alanine aminotransferase

AST/ALT:

Aspartate aminotransferase to alanine aminotransferase ratio

AST:

Aspartate aminotransferase

Gamma-GT:

Gamma glutamyltransferase

HELENA:

Healthy Lifestyle in Europe by Nutrition in Adolescence

HELENA-DIAT:

HELENA-Dietary Assessment Tool

ICH:

Ideal cardiovascular health

MSM:

Multiple Source Method

NAFLD:

Non-alcoholic fatty liver disease

References

  1. Aatola H, Hutri-Kahonen N, Juonala M, Laitinen TT, Pahkala K, Mikkila V, Telama R, Koivistoinen T, Lehtimaki T, Viikari JS et al (2014) Prospective relationship of change in ideal cardiovascular health status and arterial stiffness: the Cardiovascular Risk in Young Finns Study. J Am Heart Assoc 3:e000532

    Article  PubMed  PubMed Central  Google Scholar 

  2. Alkerwi A, Vernier C, Crichton GE, Sauvageot N, Shivappa N, Hebert JR (2014) Cross-comparison of diet quality indices for predicting chronic disease risk: findings from the Observation of Cardiovascular Risk Factors in Luxembourg (ORISCAV-LUX) study. Br J Nutr 5:1–11

    Google Scholar 

  3. Alman AC, Talton JW, Wadwa RP, Urbina EM, Dolan LM, Daniels SR, Hamman RF, D’Agostino RB, Marcovina SM, Mayer-Davis EJ, Dabelea DM (2014) Cardiovascular health in adolescents with type 1 diabetes: the SEARCH CVD study. Pediatr Diabetes 15:502–510

    Article  PubMed  PubMed Central  Google Scholar 

  4. Armstrong MJ, Adams LA, Canbay A, Syn WK (2014) Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology 59:1174–1197

    Article  CAS  PubMed  Google Scholar 

  5. Ayer J, Charakida M, Deanfield JE, Celermajer DS (2015) Lifetime risk: childhood obesity and cardiovascular risk. Eur Heart J 36:1371–1376

    Article  PubMed  Google Scholar 

  6. Breitling LP, Arndt V, Drath C, Rothenbacher D, Brenner H (2010) Smoking and gamma-glutamyltransferase: opposite interactions with alcohol consumption and body mass index. PLoS One 5(9)

  7. Burgert TS, Taksali SE, Dziura J, Goodman TR, Yeckel CW, Papademetris X, Constable RT, Weiss R, Tamborlane WV, Savoye M et al (2006) Alanine aminotransferase levels and fatty liver in childhood obesity: associations with insulin resistance, adiponectin, and visceral fat. J Clin Endocrinol 91:4287–4294

    Article  CAS  Google Scholar 

  8. Cole TJ, Lobstein T (2012) Extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity. Pediatr Obes 7:284–294

    Article  CAS  PubMed  Google Scholar 

  9. Danielsson J, Kangastupa P, Laatikainen T, Aalto M, Niemela O (2014) Impacts of common factors of life style on serum liver enzymes. World J Gastroenterol 20:11743–11452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Georgoulis M, Kontogianni MD, Margariti A, Tiniakos D, Fragopoulou E, Zafiropoulou R, Papatheodoridis G (2015) Associations between dietary intake and the presence of the metabolic syndrome in patients with non-alcoholic fatty liver disease. J Hum Nutr Diet 28:409–415

    Article  CAS  PubMed  Google Scholar 

  11. Gonzalez-Gross M, Breidenassel C, Gomez-Martinez S, Ferrari M, Beghin L, Spinneker A, Diaz LE, Maiani G, Demailly A, Al-Tahan J et al (2008) Sampling and processing of fresh blood samples within a European multicenter nutritional study: evaluation of biomarker stability during transport and storage. Int J Obes 32(Suppl 5):S66–S75

    Article  CAS  Google Scholar 

  12. Hallsworth K, Thoma C, Moore S, Ploetz T, Anstee QM, Taylor R, Day CP, Trenell MI (2015) Non-alcoholic fatty liver disease is associated with higher levels of measured sedentary behaviour and lower levels of physical activity than matched healthy controls. Frontline Gastroenterol 6:44–51

    Article  PubMed  Google Scholar 

  13. Higashikawa A, Suwazono Y, Okubo Y, Uetani M, Kobayashi E, Kido T, Nogawa K (2005) Association of working conditions and lifestyle with increased serum gamma-glutamyltransferase: a follow-up study. Arch Med Res 36:567–573

    Article  CAS  PubMed  Google Scholar 

  14. Kelishadi R, Cook SR, Amra B, Adibi A (2009) Factors associated with insulin resistance and non-alcoholic fatty liver disease among youths. Atherosclerosis 204:538–543

    Article  CAS  PubMed  Google Scholar 

  15. Kong AP, Choi KC, Ho CS, Chan MH, Ozaki R, Chan CW, Chan JC (2013) Associations of uric acid and gamma-glutamyltransferase (GGT) with obesity and components of metabolic syndrome in children and adolescents. Pediatr Obes 8:351–357

    Article  CAS  PubMed  Google Scholar 

  16. Kontogianni MD, Tileli N, Margariti A, Georgoulis M, Deutsch M, Tiniakos D, Fragopoulou E, Zafiropoulou R, Manios Y, Papatheodoridis G (2014) Adherence to the Mediterranean diet is associated with the severity of non-alcoholic fatty liver disease. Clin Nutr 33:678–683

    Article  CAS  PubMed  Google Scholar 

  17. Kotronen A, Juurinen L, Tiikkainen M, Vehkavaara S, Yki-Jarvinen H (2008a) Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. Gastroenterology 135:122–130

    Article  CAS  PubMed  Google Scholar 

  18. Kotronen A, Seppala-Lindroos A, Bergholm R, Yki-Jarvinen H (2008b) Tissue specificity of insulin resistance in humans: fat in the liver rather than muscle is associated with features of the metabolic syndrome. Diabetologia 51:130–138

    Article  CAS  PubMed  Google Scholar 

  19. Kozakova M, Palombo C, Eng MP, Dekker J, Flyvbjerg A, Mitrakou A, Gastaldelli A, Ferrannini E (2012) Fatty liver index, gamma-glutamyltransferase, and early carotid plaques. Hepatology 55:1406–1415

    Article  CAS  PubMed  Google Scholar 

  20. Labayen I, Ruiz JR, Ortega FB, Huybrechts I, Rodriguez G, Jimenez-Pavon D, Roccaldo R, Nova E, Widhalm K, Kafatos A et al (2014) High fat diets are associated with higher abdominal adiposity regardless of physical activity in adolescents; the HELENA study. Clin Nutr 33:859–866

    Article  CAS  PubMed  Google Scholar 

  21. Labayen I, Ruiz JR, Ortega FB, Davis CL, Rodriguez G, Gonzalez-Gross M, Breidenassel C, Dallongeville J, Marcos A, Widhalm K, Kafatos A, Molnar D, DeHenauw S, Gottrand F, Moreno LA (2015) Liver enzymes and clustering cardiometabolic risk factors in European adolescents: the HELENA study. Pediatric Obesity 10:361–370

    Article  CAS  PubMed  Google Scholar 

  22. Laitinen TT, Pahkala K, Magnussen CG, Viikari JS, Oikonen M, Taittonen L, Mikkila V, Jokinen E, Hutri-Kahonen N, Laitinen T, Kahonen M, Lehtimaki T, Raitakari OT, Juonala M (2012) Ideal cardiovascular health in childhood and cardiometabolic outcomes in adulthood: the Cardiovascular Risk in Young Finns Study. Circulation 125:1971–1978

    Article  PubMed  Google Scholar 

  23. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, Arnett DK, Fonarow GC, Ho PM, Lauer MS, Masoudi FA, Robertson RM, Roger V, Schwamm LH, Sorlie P, Yancy CW, Rosamond WD (2010) Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic impact goal through 2020 and beyond. Circulation 121:586–613

    Article  PubMed  Google Scholar 

  24. Minihane AM, Vinoy S, Russell WR, Baka A, Roche HM, Tuohy KM, Teeling JL, Blaak EE, Fenech M, Vauzour D, McArdle HJ, Kremer BH, Sterkman L, Vafeiadou K, Benedetti MM, Williams CM, Calder PC (2015) Low-grade inflammation, diet composition and health: current research evidence and its translation. Br J Nutr 114:999–1012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Mohammadi F, Qorbani M, Kelishadi R, Baygi F, Ardalan G, Taslimi M, Mahmoudarabi M, Motlagh ME, Asayesh H, Larijani B, Heshmat R (2014) Association of cardiometabolic risk factors and hepatic enzymes in a national sample of Iranian children and adolescents: the CASPIAN-III study. J Pediatr Gastroenterol Nutr 58:463–468

    Article  PubMed  Google Scholar 

  26. Moreno LA, De Henauw S, Gonzalez-Gross M, Kersting M, Molnar D, Gottrand F, Barrios L, Sjostrom M, Manios Y, Gilbert CC, Leclercq C, Widhalm K, Kafatos A, Marcos A (2008) Design and implementation of the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. Int J Obes 32(Suppl 5):S4–11

    Article  Google Scholar 

  27. Oikonen M, Laitinen TT, Magnussen CG, Steinberger J, Sinaiko AR, Dwyer T, Venn A, Smith KJ, Hutri-Kahonen N, Pahkala K, Mikkila V, Prineas R, Viikari JS, Morrison JA, Woo JG, Chen W, Nicklas T, Srinivasan SR, Berenson G, Juonala M, Raitakari OT (2013) Ideal cardiovascular health in young adult populations from the United States, Finland, and Australia and its association with cIMT: the International Childhood Cardiovascular Cohort Consortium. J Am Heart Assoc 2:e000244

    Article  PubMed  PubMed Central  Google Scholar 

  28. Pahkala K, Hietalampi H, Laitinen TT, Viikari JS, Ronnemaa T, Niinikoski H, Lagstrom H, Talvia S, Jula A, Heinonen OJ, Juonala M, Simell O, Raitakari OT (2013) Ideal cardiovascular health in adolescence: effect of lifestyle intervention and association with vascular intima-media thickness and elasticity (the Special Turku Coronary Risk Factor Intervention Project for Children [STRIP] study). Circulation 127:2088–2096

    Article  PubMed  Google Scholar 

  29. Patel DA, Srinivasan SR, Xu JH, Chen W, Berenson GS (2007) Persistent elevation of liver function enzymes within the reference range is associated with increased cardiovascular risk in young adults: the Bogalusa Heart Study. Metabolism 56:792–798

    Article  CAS  PubMed  Google Scholar 

  30. Ruiz JR, Ortega FB, Warnberg J, Sjostrom M (2007) Associations of low-grade inflammation with physical activity, fitness and fatness in prepubertal children; the European Youth Heart Study. Int J Obes 31:1545–1551

    Article  CAS  Google Scholar 

  31. Ruiz JR, Ortega FB, Martinez-Gomez D, Labayen I, Moreno LA, De Bourdeaudhuij I, Manios Y, Gonzalez-Gross M, Mauro B, Molnar D, Widhalm K, Marcos A, Beghin L, Castillo MJ, Sjostrom M (2011) Objectively measured physical activity and sedentary time in European adolescents the HELENA study. Am J Epidemiol 174:173–184

    Article  PubMed  Google Scholar 

  32. Ruiz JR, Labayen I, Ortega FB, Moreno LA, Rodriguez G, Breidenassel C, Manios Y, Kafatos A, Molnar D, De Henauw S, Gottrand F, Widhalm K, Castillo MJ, Sjostrom M (2014) Physical activity, sedentary time, and liver enzymes in adolescents: the HELENA study. Pediatr Res 75:798–802

    Article  CAS  PubMed  Google Scholar 

  33. Ruiz JR, Huybrechts I, Cuenca-Garcia M, Artero EG, Labayen I, Meirhaeghe A, Vicente-Rodriguez G, Polito A, Manios Y, Gonzalez-Gross M, Marcos A, Widhalm K, Molnar D, Kafatos A, Sjostrom M, Moreno LA, Castillo MJ, Ortega FB (2015) Cardiorespiratory fitness and ideal cardiovascular health in European adolescents. Heart 101:766–773

    Article  PubMed  Google Scholar 

  34. Schneider AL, Lazo M, Ndumele CE, Pankow JS, Coresh J, Clark JM, Selvin E (2013) Liver enzymes, race, gender and diabetes risk: the Atherosclerosis Risk in Communities (ARIC) Study. Diabet Med 30:926–933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Schwimmer JB, McGreal N, Deutsch R, Finegold MJ, Lavine JE (2005) Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents. Pediatrics 115:e561–e565

    Article  PubMed  Google Scholar 

  36. Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S (2008) Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation 118:277–283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Shay CM, Ning H, Daniels SR, Rooks CR, Gidding SS, Lloyd-Jones DM (2013) Status of cardiovascular health in US adolescents: prevalence estimates from the National Health and Nutrition Examination Surveys (NHANES) 2005-2010. Circulation 127:1369–1376

    Article  PubMed  Google Scholar 

  38. Sorbi D, Boynton J, Lindor KD (1999) The ratio of aspartate aminotransferase to alanine aminotransferase: potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease. Am J Gastroenterol 94:1018–1022

    Article  CAS  PubMed  Google Scholar 

  39. Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC (2000) Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med 343:16–22

    Article  CAS  PubMed  Google Scholar 

  40. Strauss RS, Barlow SE, Dietz WH (2000) Prevalence of abnormal serum aminotransferase values in overweight and obese adolescents. J Pediatr 136:727–733

    CAS  PubMed  Google Scholar 

  41. Swinburn B, Kraak V, Rutter H, Vandevijvere S, Lobstein T, Sacks G, Gomes F, Marsh T, Magnusson R (2015) Strengthening of accountability systems to create healthy food environments and reduce global obesity. Lancet 385:2534–2545

    Article  PubMed  Google Scholar 

  42. Vereecken CA, Covents M, Sichert-Hellert W, Alvira JM, Le Donne C, De Henauw S, De Vriendt T, Phillipp MK, Beghin L, Manios Y, Hallstrom L, Poortvliet E, Matthys C, Plada M, Nagy E, Moreno LA (2008) Development and evaluation of a self-administered computerized 24-h dietary recall method for adolescents in Europe. Int J Obes 32(Suppl 5):S26–S34

    Article  Google Scholar 

  43. Waxman A (2003) Prevention of chronic diseases: WHO global strategy on diet, physical activity and health. Food Nutr Bull 24:281–284

    Article  PubMed  Google Scholar 

  44. Wicklow BA, Wittmeier KD, Macintosh AC, Sellers EA, Ryner L, Serrai H, Dean HJ, McGavock JM (2012) Metabolic consequences of hepatic steatosis in overweight and obese adolescents. Diabetes Care 35:905–910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank the children and adolescents who participated in the study and their parents and teachers for their collaboration. Many thanks to Anke Carstensen for her contribution to the laboratory work. We also acknowledge the members involved in the fieldwork for their efforts.

Author’s contribution

IL conceived the hypothesis, wrote the manuscript, and performed the statistical analysis; JRR, JRR, IH, FBO MCG, MC, MS, MGG, YM, KW, AK, CB, GR, JD, FG, and LAM contributed to the interpretation and discussion of the results. All authors contributed to the interpretation and discussion of the results and critically revised the drafted manuscript.

Author information

Authors and Affiliations

  1. Department of Nutrition and Food Sciences, University of the Basque Country, UPV/EHU, Vitoria-Gasteiz, Spain

    Idoia Labayen

  2. Nutrition, Exercise and Health Research Group, Elikadura, Ariketa Fisikoa eta Osasuna, ELIKOS Group, University of the Basque Country, UPV/EHU, Vitoria-Gasteiz, Spain

    Idoia Labayen

  3. PROmoting FITness and Health Through Physical Activity Research Group (PROFITH), Department of Physical Education and Sports, Faculty of Sport Sciences, University of Granada, Granada, Spain

    Jonatan R. Ruiz & Francisco B. Ortega

  4. Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, Huddinge, Sweden

    Jonatan R. Ruiz, Francisco B. Ortega & Michael Sjöstrom

  5. Department of Public Health, Ghent University, Ghent, Belgium

    Inge Huybrechts

  6. International Agency for Research on Cancer, Dietary Exposure Assessment Group, Lyon, France

    Inge Huybrechts

  7. Departament of Physiology, Medicine School, University of Granada, Granada, Spain

    Manuel Castillo

  8. Faculty of Physical Activity and Sport Sciences (INEF), Universidad Politécnica de Madrid, Madrid, Spain

    Marcela González-Gross

  9. Department of Nutrition and Dietetics, Harokopio University, Athens, Greece

    Yannis Manios

  10. Division of Nutrition and Metabolism, Department of Pediatrics, Medical University of Vienna, Vienna, Austria

    Kurt Widhalm

  11. School of Medicine, University of Crete, Crete, Greece

    Anthony Kafatos

  12. Department of Nutrition and Food Science, University of Bonn, Bonn, Germany

    Christina Breidenassel

  13. Department of Pediatrics, University of Zaragoza, Instituto Aragonés de Ciencias de la Salud, Zaragoza, Spain

    Gerardo Rodríguez

  14. INSERM, U744, Univ Lille Nord de France, Institut Pasteur de Lille, F-59000, Lille, France

    Jean Dallongeville

  15. Department of Pediatrics, Jeanne de Flandre Children’s University Hospital, Lille, France

    Frédéric Gottrand

  16. GENUD (Growth, Exercise, Nutrition and Development) Research Group, University of Zaragoza, Zaragoza, Spain

    Luis A. Moreno

  17. Department of Preventive Medicine, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil

    Luis A. Moreno

Authors
  1. Idoia Labayen
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  2. Jonatan R. Ruiz
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  3. Inge Huybrechts
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  4. Francisco B. Ortega
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  5. Manuel Castillo
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  6. Michael Sjöstrom
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  7. Marcela González-Gross
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  8. Yannis Manios
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  9. Kurt Widhalm
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  10. Anthony Kafatos
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  11. Christina Breidenassel
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  12. Gerardo Rodríguez
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  13. Jean Dallongeville
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  14. Frédéric Gottrand
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  15. Luis A. Moreno
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Corresponding author

Correspondence to Idoia Labayen.

Ethics declarations

All procedures involving human participants were approved by the ethics committee of each involved city. Written informed consent and assent were obtained from both adolescents and their parents before being enrolled in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

The authors declare no relationship with an industry that might pose a conflict of interest. The HELENA project was supported by the European Community Sixth RTD Framework Programme (contract FOOD-CT-2005-007034), by the Spanish Ministry of Science and Innovation (RYC-2010-05957, RYC-2011-09011), and by the University of the Basque Country (GIU14/21). This study was also supported by the Spanish Ministry of Health (CIBERobn CB12/03/30038). The content of this paper reflects the authors’ views alone and the European Community is not liable for any use that may be made of the information contained herein.

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Labayen, I., Ruiz, J.R., Huybrechts, I. et al. Ideal cardiovascular health and liver enzyme levels in European adolescents; the HELENA study. J Physiol Biochem 73, 225–234 (2017). https://doi.org/10.1007/s13105-016-0546-9

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