Arachidonic Acid, but Not Omega-3 Index, Relates to the Prevalence and Progression of Abdominal Aortic Aneurysm in a Population-Based Study of Danish Men

Jes S Lindholt, Katrine L Kristensen, Elena Burillo, Diego Martinez-Lopez, Carlos Calvo, Emilio Ros, Jose L Martín-Ventura, Aleix Sala-Vila, Jes S Lindholt, Katrine L Kristensen, Elena Burillo, Diego Martinez-Lopez, Carlos Calvo, Emilio Ros, Jose L Martín-Ventura, Aleix Sala-Vila

Abstract

Background: Animal models support dietary omega-3 fatty acids protection against abdominal aortic aneurysm (AAA), but clinical data are scarce. The sum of red blood cell proportions of the omega-3 eicosapentaenoic and docosahexaenoic acids, known as omega-3 index, is a valid surrogate for long-term omega-3 intake. We investigated the association between the omega-3 index and the prevalence and progression of AAA. We also investigated associations between AAA and arachidonic acid, an omega-6 fatty acid that is a substrate for proinflammatory lipid mediators.

Methods and results: We obtained blood samples from 498 AAA patients (maximal aortic diameter ≥30 mm) within a population-based ultrasound-screening trial in men and from 199 age-matched controls who screened negative. We determined the fatty acids of red blood cells by gas chromatography. During a median follow-up of 4.85 years, 141 AAA patients reached criteria for vascular surgical repair. Participants were high consumers of omega-3 (average omega-3 index: 7.6%). No significant associations were found for omega-3 index. In contrast, arachidonic acid in AAA patients was higher than in controls (P<0.001), and individuals in the upper tertile of arachidonic acid at baseline had higher probability of having AAA (odds ratio: 1.309; 95% confidence interval, 1.021-1.678; P=0.033). AAA patients at the upper tertile of arachidonic acid at baseline had a 54% higher risk of needing surgical repair during follow-up (hazard ratio: 1.544; 95% confidence interval, 1.127-2.114; P=0.007).

Conclusions: Omega-3 index is unrelated to men with AAA from a country in which fish consumption is customarily high. Arachidonic acid is associated with AAA presence and progression.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00662480.

Keywords: abdominal aortic aneurysm; diet; inflammation.

© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1
Figure 1
Red blood cell proportions (percentage of total fatty acids) of (A) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)(EPA+DHA=omega‐3 index) and (B) arachidonic acid in 498 patients with abdominal aortic aneurysm (AAA) and 199 age‐matched controls who screened negative. Dots are individual participant data, and bars represent mean±SD. P obtained by Student t test. In panel (A), discontinuous lines at 8% and 4% indicate proposed low‐ and high‐risk cutoffs for cardiovascular risk, respectively.10
Figure 2
Figure 2
In 498 patients with abdominal aortic aneurysm (AAA), (A) a scatter plot shows the red blood cell proportion of arachidonic acid and the maximal aneurysm diameter, and (B) the Kaplan–Meier curve shows cumulative freedom from needing vascular repair, stratified by being in the upper tertile of red blood cell proportion of arachidonic acid at baseline vs not. Data were obtained using a multivariate Cox proportional hazards model adjusted for active smoking, hypertension, use of low‐dose aspirin, use of statins, peripheral arterial disease at screening, body mass index, diabetes mellitus, use of beta blockers, C‐reactive protein, and baseline maximal aortic diameter.

References

    1. Meital LT, Sandow SL, Calder PC, Russell FD. Abdominal aortic anurysm and omega‐3 polyunsaturated fatty acids: mechanisms, animal models, and potential treatment. Prostaglandins Leukot Essent Fatty Acids. 2017;118:1–9.
    1. Wang JH, Eguchi K, Matsumoto S, Fujiu K, Komuro I, Nagai R, Manabe I. The ω‐3 polyunsaturated fatty acid, eicosapentaenoic acid, attenuates abdominal aortic aneurysm development via suppression of tissue remodeling. PLoS One. 2014;9:e96286.
    1. Yoshihara T, Shimada K, Fukao K, Sai E, Sato‐Okabayashi Y, Matsumori R, Shiozawa T, Alshahi H, Miyazaki T, Tada N, Daida H. Omega 3 polyunsaturated fatty acids suppress the development of aortic aneurysms through the inhibition of macrophage‐mediated inflammation. Circ J. 2015;79:1470–1478.
    1. Kavazos K, Nataatmadja M, Wales KM, Hartland E, Williams C, Russell FD. Dietary supplementation with omega‐3 polyunsaturated fatty acids modulate matrix metalloproteinase immunoreactivity in a mouse model of pre‐abdominal aortic aneurysm. Heart Lung Circ. 2015;24:377–385.
    1. Aikawa T, Miyazaki T, Shimada K, Sugita Y, Shimizu M, Ouchi S, Kadoguchi T, Yokoyama Y, Shiozawa T, Hiki M, Takahashi S, Al Shahi H, Dohi S, Amano A, Daida H. Low serum levels of EPA are associated with the size and growth rate of abdominal aortic aneurysm. J Atheroscler Thromb. 2017;24:912–920.
    1. Grøndal N, Søgaard R, Henneberg EW, Lindholt JS. The Viborg Vascular (VIVA) screening trial of 65‐74 year old men in the central region of Denmark: study protocol. Trials. 2010;11:67.
    1. Hodson L, Skeaff CM, Fielding BA. Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog Lipid Res. 2008;47:348–380.
    1. Harris WS, Thomas RM. Biological variability of blood omega‐3 biomarkers. Clin Biochem. 2010;43:338–340.
    1. Sala‐Vila A, Harris WS, Cofán M, Pérez‐Heras AM, Pintó X, Lamuela‐Raventós RM, Covas MI, Estruch R, Ros E. Determinants of the omega‐3 index in a Mediterranean population at increased risk for CHD. Br J Nutr. 2011;106:425–431.
    1. Harris WS. The omega‐3 index: from biomarker to risk marker to risk factor. Curr Atheroscler Rep. 2009;11:411–417.
    1. Grøndal N, Bramsen MB, Thomsen MD, Rasmussen CB, Lindholt JS. The cardiac cycle is a major contributor to variability in size measurements of abdominal aortic aneurysms by ultrasound. Eur J Vasc Endovasc Surg. 2012;43:30–33.
    1. Harris WS, Pottala JV, Vasan RS, Larson MG, Robins SJ. Changes in erythrocyte membrane trans and marine fatty acids between 1999 and 2006 in older Americans. J Nutr. 2012;142:1297–1303.
    1. Lauritzen L, Harsløf LB, Hellgren LI, Pedersen MH, Mølgaard C, Michaelsen KF. Fish intake, erythrocyte n‐3 fatty acid status and metabolic health in Danish adolescent girls and boys. Br J Nutr. 2012;107:697–704.
    1. Stark KD, Van Elswyk ME, Higgins MR, Weatherford CA, Salem N Jr. Global survey of the omega‐3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults. Prog Lipid Res. 2016;63:132–152.
    1. Micha R, Khatibzadeh S, Shi P, Fahimi S, Lim S, Andrews KG, Engell RE, Powles J, Ezzati M, Mozaffarian D; Global Burden of Diseases Nutrition and Chronic Diseases Expert Group NutriCoDE . Global, regional, and national consumption levels of dietary fats and oils in 1990 and 2010: a systematic analysis including 266 country‐specific nutrition surveys. BMJ. 2014;348:g2272.
    1. Welch AA, Lund E, Amiano P, Dorronsoro M, Brustad M, Kumle M, Rodriguez M, Lasheras C, Janzon L, Jansson J, Luben R, Spencer EA, Overvad K, Tjønneland A, Clavel‐Chapelon F, Linseisen J, Klipstein‐Grobusch K, Benetou V, Zavitsanos X, Tumino R, Galasso R, Bueno‐De‐Mesquita HB, Ocké MC, Charrondière UR, Slimani N. Variability of fish consumption within the 10 European countries participating in the European Investigation into Cancer and Nutrition (EPIC) study. Public Health Nutr. 2002;5:1273–1285.
    1. Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA. 2006;296:1885–1899.
    1. Li X, Zhao G, Zhang J, Duan Z, Xin S. Prevalence and trends of the abdominal aortic aneurysms epidemic in general population‐a meta‐analysis. PLoS One. 2013;8:e81260.
    1. Houard X, Ollivier V, Louedec L, Michel JB, Bäck M. Differential inflammatory activity across human abdominal aortic aneurysms reveals neutrophil‐derived leukotriene B4 as a major chemotactic factor released from the intraluminal thrombus. FASEB J. 2009;23:1376–1383.
    1. Bhamidipati CM, Whatling CA, Mehta GS, Meher AK, Hajzus VA, Su G, Salmon M, Upchurch GR Jr, Owens GK, Ailawadi G. 5‐Lipoxygenase pathway in experimental abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 2014;34:2669–2678.
    1. Grøndal N, Søgaard R, Lindholt JS. Baseline prevalence of abdominal aortic aneurysm, peripheral arterial disease and hypertension in men aged 65‐74 years from a population screening study (VIVA trial). Br J Surg. 2015;102:902–906.
    1. Laustsen J, Jensen LP, Hansen AK; Danish National Vascular Registry . Accuracy of clinical data in a population based vascular registry. Eur J Vasc Endovasc Surg. 2004;27:216–219.

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