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Adipose tissue content of alpha-linolenic acid and development of peripheral artery disease: a Danish case-cohort study

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Abstract

Purpose

The aim of this study was to investigate the association between adipose tissue content of the plant-derived n-3 fatty acid, alpha-linolenic acid, and the rate of incident peripheral artery disease (PAD).

Methods

We conducted a case-cohort study nested within the Danish Diet, Cancer and Health cohort (n = 57,053), which was established between 1993 and 1997. Potential PAD cases were identified using linkage with The Danish National Patient Register and all potential cases were validated. Adipose tissue samples from the buttock were collected at baseline and fatty acid composition was determined in cases and in a random sample (n = 3500) from the cohort by gas chromatography. Statistical analyses were performed using weighted Cox regression allowing for different baseline hazards among sexes.

Results

During a median of 13.5 years of follow-up, we identified 863 PAD cases with complete information. The median adipose tissue content of ALA in the sub-cohort (n = 3197) was 0.84% (interquartile range 0.73–0.94%) of total fatty acids. In multivariate analyses including adjustment for established risk factors, we observed a U-shaped association between ALA in adipose tissue and rate of PAD, but the association was not statistically significant (P = 0.131). Similar pattern of associations were observed between ALA content in adipose tissue and the rate of PAD among men and women.

Conclusions

We found indications of a U-shaped association between adipose tissue content of ALA and the rate of PAD, but the association was not statistically significant.

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References

  1. Hiatt W, Goldstone J, Smith SJ et al (2008) Atherosclerotic peripheral vascular disease symposium II: nomenclature for vascular diseases. Circulation 118:2826–2829

    Article  PubMed  Google Scholar 

  2. Patel M, Conte M, Cutlip D et al (2015) Evaluation and treatment of patients with lower extremity peripheral artery disease: consensus definitions from peripheral academic research consortium (PARC). J Am Coll Cardiol 65:931–941

    Article  PubMed  PubMed Central  Google Scholar 

  3. Steg P, Bhatt D, Wilson P et al (2007) One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA 297:1197–1206

    Article  CAS  PubMed  Google Scholar 

  4. Fowkes F, Aboyans V, Fowkes F et al (2017) Peripheral artery disease: epidemiology and global perspectives. Nat Rev Cardiol 14:156–170

    Article  PubMed  Google Scholar 

  5. Fowkes F, Rudan D, Rudan I et al (2013) Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 382:1329–1340

    Article  PubMed  Google Scholar 

  6. De Caterina R (2011) n-3 Fatty acids in cardiovascular disease. N Engl J Med 364:2439–2450

    Article  PubMed  Google Scholar 

  7. Chang C, Deckelbaum R (2013) Omega-3 fatty acids: mechanisms underlying “protective effects” in atherosclerosis. Curr Opin Lipidol 24:345–350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Calder P (2015) Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta 1851:469–484

    Article  CAS  PubMed  Google Scholar 

  9. Lasota A, Grønholdt M, Bork C et al (2018) Marine n-3 fatty acids and the risk of peripheral arterial disease. J Am Coll Cardiol 72:1576–1584

    Article  CAS  PubMed  Google Scholar 

  10. Ruiz-Canela M, Estruch R, Corella D et al (2014) Association of mediterranean diet with peripheral artery disease: the PREDIMED randomized trial. JAMA 311:415–417

    Article  CAS  PubMed  Google Scholar 

  11. Estruch R, Ros E, Salas-Salvadó J et al (2018) Primary prevention of cardiovascular disease with a mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med 378:e34

    Article  CAS  PubMed  Google Scholar 

  12. Rajaram S (2014) Health benefits of plant-derived alpha-linolenic acid. Am J Clin Nutr 100:443–448

    Article  CAS  Google Scholar 

  13. Bork C, Jakobsen M, Lundbye-Christensen S et al (2016) Dietary intake and adipose tissue content of alpha-linolenic acid and risk of myocardial infarction: a Danish cohort study. Am J Clin Nutr 104:41–48

    Article  CAS  PubMed  Google Scholar 

  14. Hu F, Stampfer M, Manson J et al (1999) Dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease among women. Am J Clin Nutr 69:890–897

    Article  CAS  PubMed  Google Scholar 

  15. Gebauer S, Psota T, Harris W, Kris-Etherton P (2006) n-3 Fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Am J Clin Nutr 83:1526–1535

    Article  Google Scholar 

  16. Baker E, Miles E, Burdge G et al (2016) Metabolism and functional effects of plant-derived omega-3 fatty acids in humans. Prog Lipid Res 64:30–56

    Article  CAS  PubMed  Google Scholar 

  17. Hodson L, Skeaff C, Fielding B (2008) Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog Lipid Res 47:348–380

    Article  CAS  PubMed  Google Scholar 

  18. Arab L, Akbar J (2002) Biomarkers and the measurement of fatty acids. Public Health Nutr 5:865–871

    Article  PubMed  Google Scholar 

  19. Tjønneland A, Olsen A, Boll K et al (2007) Study design, exposure variables, and socioeconomic determinants of participation in diet, cancer and health: a population-based prospective cohort study of 57,053 men and women in Denmark. Scand J Public Health 35:432–441

    Article  PubMed  Google Scholar 

  20. Beynen A, Katan M (1985) Rapid sampling and long-term storage of subcutaneous adipose-tissue biopsies for determination of fatty acid composition. Am J Clin Nutr 42:317–322

    Article  CAS  PubMed  Google Scholar 

  21. Joensen A, Overvad K, Dethlefsen C et al (2011) Marine n-3 polyunsaturated fatty acids in adipose tissue and the risk of acute coronary syndrome. Circulation 124:1232–1238

    Article  CAS  PubMed  Google Scholar 

  22. Bork C, Venø S, Lundbye-Christensen S et al (2018) Adipose tissue content of alpha-linolenic acid and the risk of ischemic stroke and ischemic stroke subtypes: a Danish case-cohort study. PLoS One 13:e0198927

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. IUPAC (1987) Standard methods for analysis of oils, fats and derivatives. Standard method 2.301, 7th edn. Blackwell Scientific Publications, Oxford

    Google Scholar 

  24. Gammelmark A, Nielsen M, Bork C et al (2016) Adipose tissue content of marine n-3 polyunsaturated fatty acids is inversely associated with myocardial infarction. J Am Coll Cardiol 67:1008–1009

    Article  CAS  PubMed  Google Scholar 

  25. Wareham N, Jakes W, Rennie K et al (2003) Validity and repeatability of a simple index derived from the short physical activity questionnaire used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Public Health Nutr 6:407–413

    Article  PubMed  Google Scholar 

  26. Overvad K, Tjønneland A, Haraldsdóttir J et al (1991) Development of a semiquantitative food frequency questionnaire to assess food, energy and nutrient intake in Denmark. Int J Epidemiol 20:900–905

    Article  CAS  PubMed  Google Scholar 

  27. Tjønneland A, Overvad K, Haraldsdóttir J et al (1991) Validations of a semiquantative food frequency questionnaire developed in Denmark. Int J Epidemiol 20:906–912

    Article  PubMed  Google Scholar 

  28. Andersen T, Madsen M, Jørgensen J et al (1999) The Danish national hospital register. A valuable source of data for modern health sciences. Dan Med Bull 46:263–268

    CAS  PubMed  Google Scholar 

  29. Lynge E, Sandegaard J, Rebolj M (2011) The Danish national patient register. Scand J Public Health 39:30–33

    Article  PubMed  Google Scholar 

  30. Lasota A, Overvad K, Eriksen H et al (2017) Validity of peripheral arterial disease diagnoses in the Danish national patient registry. Eur J Vasc Endovasc Surg 53:679–685

    Article  CAS  PubMed  Google Scholar 

  31. Bork C, Lasota A, Lundbye-Christensen S et al (2019) Intake of α-linolenic acid is not consistently associated with a lower risk of peripheral artery disease: results from a Danish cohort study. Br J Nutr 122:86–92

    Article  CAS  PubMed  Google Scholar 

  32. Kalbfleisch J, Lawless J (1988) Likelihood analysis of multi-state models for disease incidence and mortality. Stat Med 7:149–160

    Article  CAS  PubMed  Google Scholar 

  33. Harrell F (2015) Regression modeling strategies: with applications to linear models, logistic and ordinal regression, and survival analysis, 2nd edn. Springer, New York

    Book  Google Scholar 

  34. Katan M, Harryvan J, van de Bovenkamp P (2003) n-3 Fatty acids in human fat tissue aspirates are stable for up to 6 years. Eur J Clin Nutr 57:816–818

    Article  CAS  PubMed  Google Scholar 

  35. Burdge G (2018) Is essential fatty acid interconversion an important source of polyunsaturated fatty acids in humans? Br J Nutr 27:1–28. https://doi.org/10.1017/S0007114518003707

    Article  CAS  Google Scholar 

  36. Venø S, Bork C, Jakobsen M et al (2019) Marine n-3 polyunsaturated fatty acids and the risk of ischemic stroke. Stroke 50:274–282

    Article  PubMed  CAS  Google Scholar 

  37. Guallar E, Aro A, Jiménez F et al (1999) Omega-3 fatty acids in adipose tissue and risk of myocardial infarction: the EURAMIC study. Arterioscler Thromb Vasc Biol 19:1111–1118

    Article  CAS  PubMed  Google Scholar 

  38. Pedersen J, Ringstad J, Almendingen K et al (2000) Adipose tissue fatty acids and risk of myocardial infarction—a case-control study. Eur J Clin Nutr 54:618–625

    Article  CAS  PubMed  Google Scholar 

  39. Lopes C, Aro A, Azevedo A et al (2007) Intake and adipose tissue composition of fatty acids and risk of myocardial infarction in a male Portuguese community sample. J Am Diet Assoc 107:276–286

    Article  CAS  PubMed  Google Scholar 

  40. Campos H, Baylin A, Willett W (2008) α-Linolenic acid and risk of nonfatal acute myocardial infarction. Circulation 118:339–345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Leng G, Taylor G, Lee A et al (1999) Essential fatty acids and cardiovascular disease: the Edinburgh Artery Study. Vasc Med 4:219–226

    Article  CAS  PubMed  Google Scholar 

  42. Leng G, Horrobin D, Fowkes F et al (1994) Plasma essential fatty acids, cigarette smoking, and dietary antioxidants in peripheral arterial disease. A population-based case-control study. Arterioscler Thromb 14:471–478

    Article  CAS  PubMed  Google Scholar 

  43. Gautam M, Izawa A, Shiba Y et al (2014) Importance of fatty acid compositions in patients with peripheral arterial disease. PLoS One 9:e107003

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Funding

The Danish Cancer Society funded the Diet, Cancer and Health study. The current study has been financially supported by The Danish Heart Foundation (17-R115-A7415-22060), Helene and Georg Jensens and Ethel Merethe and Christian Pontoppidan’s Fund. The funding agencies had no influence on study design, data collection and analysis, decision to publish or writing of this paper.

Author information

Authors and Affiliations

  1. Department of Cardiology, Aalborg University Hospital, Søndre Skovvej 15, 9000, Aalborg, Denmark

    Christian S. Bork, Kim Overvad & Erik B. Schmidt

  2. Department of Vascular Surgery, Aalborg University Hospital, Aalborg, Denmark

    Anne N. Lasota

  3. Unit of Clinical Biostatistics, Aalborg University Hospital, Aalborg, Denmark

    Søren Lundbye-Christensen

  4. Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark

    Marianne U. Jakobsen

  5. Danish Cancer Society Research Center, Copenhagen, Denmark

    Anne Tjønneland

  6. Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Anne Tjønneland

  7. Department of Public Health, Aarhus University, Aarhus, Denmark

    Kim Overvad

  8. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

    Erik B. Schmidt

Authors
  1. Christian S. Bork
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  2. Anne N. Lasota
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  3. Søren Lundbye-Christensen
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  4. Marianne U. Jakobsen
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  5. Anne Tjønneland
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  6. Kim Overvad
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  7. Erik B. Schmidt
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Contributions

All authors contributed to the conceptualization of the present study. CSB conducted the statistical analyses, prepared the tables and figures, and wrote the first draft of the manuscript. CSB, ANL, SLC, MUJ, EBS and KO contributed to the planning of the statistical analyses, interpretation of the data and writing of the manuscript. SLC supervised the conduct of the statistical analyses. AT contributed to the interpretation of the data and writing of the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Christian S. Bork.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Bork, C.S., Lasota, A.N., Lundbye-Christensen, S. et al. Adipose tissue content of alpha-linolenic acid and development of peripheral artery disease: a Danish case-cohort study. Eur J Nutr 59, 3191–3200 (2020). https://doi.org/10.1007/s00394-019-02159-2

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  • DOI: https://doi.org/10.1007/s00394-019-02159-2

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