Intake of alpha-linolenic acid is not consistently associated with a lower risk of peripheral artery disease: results from a Danish cohort study

Intake of the plant-derived omega-3 fatty acid alpha-linolenic acid (ALA) has been associated with anti-atherosclerotic properties. However, information on the association between ALA intake and development of peripheral artery disease (PAD) is lacking. In this follow-up study, we investigated the association between dietary intake of ALA and the rate of PAD among middle-aged Danish men and women enrolled into the Danish Diet, Cancer and Health cohort between 1993 and 1997. Incident PAD cases were identified through the Danish National Patient Register. Intake of ALA was assessed using a validated food frequency questionnaire. Statistical analyses were performed using Cox proportional hazard regression allowing for separate baseline hazards among sexes and adjusted for established risk factors for PAD. During a median of 13.6 years of follow-up, we identified 950 valid cases of PAD with complete information on covariates. The median energy-adjusted ALA intake within the cohort was 1.76 g/d (95% central range: 0.94-3.28). In multivariable analyses, we found no statistically significant association between intake of ALA and the rate of PAD (P = 0.339). Also, no statistically significant associations were observed in analyses including additional adjustment for co-morbidities and in sex-specific analyses. In supplemental analyses with additional adjustment for potential dietary risk factors, we found a weak inverse association to PAD with ALA intake above the median, but the association was not statistically significant (P = 0.314). In conclusion, dietary intake of ALA was not consistently associated with decreased risk of PAD.

[1]  M. Hernán,et al.  Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra‐Virgin Olive Oil or Nuts , 2018, The New England journal of medicine.

[2]  A. Tjønneland,et al.  Dietary Intake of α-Linolenic Acid Is Not Appreciably Associated with Risk of Ischemic Stroke among Middle-Aged Danish Men and Women. , 2018, The Journal of nutrition.

[3]  A. Tjønneland,et al.  Validity of Peripheral Arterial Disease Diagnoses in the Danish National Patient Registry. , 2017, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[4]  Freya J. I. Fowkes,et al.  Peripheral artery disease: epidemiology and global perspectives , 2017, Nature Reviews Cardiology.

[5]  P. Calder,et al.  Metabolism and functional effects of plant-derived omega-3 fatty acids in humans. , 2016, Progress in lipid research.

[6]  James E. Helmreich.  Regression Modeling Strategies with Applications to Linear Models, Logistic and Ordinal Regression and Survival Analysis (2nd Edition) , 2016 .

[7]  P. Calder.  Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance. , 2015, Biochimica et biophysica acta.

[8]  M. Krucoff,et al.  Evaluation and treatment of patients with lower extremity peripheral artery disease: consensus definitions from Peripheral Academic Research Consortium (PARC). , 2015, Journal of the American College of Cardiology.

[9]  Mark A Pereira,et al.  The association between dietary omega-3 fatty acids and cardiovascular death: the Singapore Chinese Health Study , 2015, European journal of preventive cardiology.

[10]  E. Rimm,et al.  Association between the intake of α-linolenic acid and the risk of CHD. , 2014, The British journal of nutrition.

[11]  J. Koyama,et al.  Importance of Fatty Acid Compositions in Patients with Peripheral Arterial Disease , 2014, PloS one.

[12]  D. Mozaffarian,et al.  Plasma phospholipid and dietary α-linolenic acid, mortality, CHD and stroke: the Cardiovascular Health Study , 2014, British Journal of Nutrition.

[13]  D. Corella,et al.  Association of Mediterranean diet with peripheral artery disease: the PREDIMED randomized trial. , 2014, JAMA.

[14]  Igor Rudan,et al.  Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis , 2013, The Lancet.

[15]  R. Deckelbaum,et al.  Omega-3 fatty acids: mechanisms underlying ‘protective effects’ in atherosclerosis , 2013, Current opinion in lipidology.

[16]  S. Larsson,et al.  Dietary fats and dietary cholesterol and risk of stroke in women. , 2012, Atherosclerosis.

[17]  L. Lauritzen,et al.  Dietary α-linolenic acid, linoleic acid, and n-3 long-chain PUFA and risk of ischemic heart disease. , 2011, The American journal of clinical nutrition.

[18]  Elsebeth Lynge,et al.  The Danish National Patient Register , 2011, Scandinavian journal of public health.

[19]  K. Swedberg.  n-3 Fatty acids in cardiovascular disease. , 2011, The New England journal of medicine.

[20]  J. Boer,et al.  Alpha-Linolenic Acid Intake and 10-Year Incidence of Coronary Heart Disease and Stroke in 20,000 Middle-Aged Men and Women in The Netherlands , 2011, PloS one.

[21]  Sidney C. Smith,et al.  Atherosclerotic Peripheral Vascular Disease Symposium II: nomenclature for vascular diseases. , 2008, Circulation.

[22]  S. Greenfield,et al.  Nutrition impacts the prevalence of peripheral arterial disease in the United States. , 2008, Journal of vascular surgery.

[23]  B. Fielding,et al.  Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. , 2008, Progress in lipid research.

[24]  M. de Lorgeril,et al.  Mediterranean diet and n-3 fatty acids in the prevention and treatment of cardiovascular disease , 2007, Journal of cardiovascular medicine.

[25]  A. Tjønneland,et al.  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 , 2007, Scandinavian journal of public health.

[26]  Deepak L. Bhatt,et al.  One-year cardiovascular event rates in outpatients with atherothrombosis. , 2007, JAMA.

[27]  D. Mozaffarian,et al.  Interplay Between Different Polyunsaturated Fatty Acids and Risk of Coronary Heart Disease in Men , 2005, Circulation.

[28]  E. Feskens,et al.  alpha-Linolenic acid intake is not beneficially associated with 10-y risk of coronary artery disease incidence: the Zutphen Elderly Study. , 2001, The American journal of clinical nutrition.

[29]  D. Horrobin,et al.  Essential fatty acids and cardiovascular disease: the Edinburgh Artery Study , 1999, Vascular medicine.

[30]  T. F. Andersen,et al.  The Danish National Hospital Register. A valuable source of data for modern health sciences. , 1999, Danish medical bulletin.

[31]  W C Willett,et al.  Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. , 1997, American journal of epidemiology.

[32]  E. Rimm,et al.  Dietary fat and risk of coronary heart disease in men: cohort follow up study in the United States , 1996, BMJ.

[33]  P. Donnan,et al.  Plasma essential fatty acids, cigarette smoking, and dietary antioxidants in peripheral arterial disease. A population-based case-control study. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[34]  T. Dolecek,et al.  Epidemiological Evidence of Relationships between Dietary Polyunsaturated Fatty Acids and Mortality in the Multiple Risk Factor Intervention Trial , 1992, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[35]  A. Tjønneland,et al.  Validation of a semiquantitative food frequency questionnaire developed in Denmark. , 1991, International journal of epidemiology.

[36]  A. Tjønneland,et al.  Development of a semiquantitative food frequency questionnaire to assess food, energy and nutrient intake in Denmark. , 1991, International journal of epidemiology.

[37]  Meir J. Stampfer,et al.  Total energy intake: implications for epidemiologic analyses. , 1986, American journal of epidemiology.

[38]  Jeroen J. Bax,et al.  Editor's Choice - 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS). , 2018, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[39]  V. Aboyans,et al.  Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases , in collaboration with the European Society for Vascular Surgery ( ESVS ) – Web Addenda , 2017 .

[40]  J. Buring,et al.  Fish Consumption, Omega-3 Fatty Acids, and Risk of Cardiovascular Disease. , 2017, American journal of preventive medicine.

[41]  J. Manson,et al.  Dietary alpha-linolenic acid intake and risk of sudden cardiac death and coronary heart disease. , 2005, Circulation.

[42]  M. Criqui,et al.  Peripheral arterial disease detection, awareness, and treatment in primary care. , 2001, JAMA.

[43]  J. Manson,et al.  Dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease among women. , 1999, The American journal of clinical nutrition.