Advertisement

Association Between Omega-3 Fatty Acid Levels and Aortic Valve Calcium (from the Multi-Ethnic Study of Atherosclerosis)

Published:September 17, 2022DOI:https://doi.org/10.1016/j.amjcard.2022.08.026
      Calcific aortic valve disease, a condition of chronic inflammation, is associated with increased cardiovascular events and all-cause mortality. Omega-3 fatty acids (O3FAs) reduce both acute and chronic inflammation, but their associations with aortic valve calcium (AVC) have not been studied. The Multi-Ethnic Study of Atherosclerosis is a prospective cohort study of 6,814 adults without clinical cardiovascular disease. Plasma fatty acid levels and cardiac computed tomography (CT) scans were performed at baseline, and CT scans were performed at subsequent clinical visits over a median 9-year period. We assessed whether plasma levels of O3FAs and their species correlate with the presence, severity, and progression of AVC measured by CT in Multi-Ethnic Study of Atherosclerosis. The mean age of the 6,510 included participants with baseline fatty acid levels, AVC, and covariate data was 62.1 ± 10.2 years, and 47.1% of the participants were male. Race distribution was 38.6% White, 27.2% Black, 22.1% Hispanic/Latino, and 12.1% Chinese. Among the 6,510 participants, 5,884 had a subsequent CT scan, and 3,304 had a third CT scan with AVC measurements. At baseline, 862 participants (13.2%) had prevalent AVC (Agatston score >0), and were more likely to be of older age, male, of the White race, have a lower education level, and have co-morbidities that are associated with a higher risk for AVC. Plasma tertiles of eicosapentaenoic acid, docosahexaenoic acid, and total O3FA were not associated with prevalent AVC at baseline, incident AVC, or change in AVC. In conclusion, plasma levels of O3FAs in subjects not routinely supplemented with O3FAs are not useful for predicting the presence or development of AVC. Whether high plasma O3FA levels, achievable by high-dose O3FA over-the-counter supplementation or pharmacotherapy, is associated with AVC requires further investigation.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      Reference

        • Carabello BA
        • Paulus WJ.
        Aortic stenosis.
        Lancet. 2009; 373: 956-966
        • Otto CM
        • Lind BK
        • Kitzman DW
        • Gersh BJ
        • Siscovick DS
        Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly.
        N Engl J Med. 1999; 341: 142-147
        • Horstkotte D
        • Loogen F
        The natural history of aortic valve stenosis.
        Eur Heart J. 1988; 9: 57-64
        • Sverdlov AL
        • Ngo DT
        • Chapman MJ
        • Ali OA
        • Chirkov YY
        • Horowitz JD
        Pathogenesis of aortic stenosis: not just a matter of wear and tear.
        Am J Cardiovasc Dis. 2011; 1: 185-199
        • Marquis-Gravel G
        • Redfors B
        • Leon MB
        • Généreux P
        Medical treatment of aortic stenosis.
        Circulation. 2016; 134: 1766-1784
        • Calder PC
        Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance.
        Biochim biophys acta. 2015; 1851: 469-484
        • Pisaniello AD
        • Psaltis PJ
        • King PM
        • Liu G
        • Gibson RA
        • Tan JTM
        • Duong M
        • Nguyen T
        • Bursill CA
        • Worthley MI
        • Nicholls SJ
        • Di Bartolo BA
        Omega-3 fatty acids ameliorate vascular inflammation: a rationale for their atheroprotective effects.
        Atherosclerosis. 2021; 324: 27-37
        • Kanai S
        • Uto K
        • Honda K
        • Hagiwara N
        • Oda H
        Eicosapentaenoic acid reduces warfarin-induced arterial calcification in rats.
        Atherosclerosis. 2011; 215: 43-51
        • Sekikawa A
        • Mahajan H
        • Kadowaki S
        • Hisamatsu T
        • Miyagawa N
        • Fujiyoshi A
        • Kadota A
        • Maegawa H
        • Murata K
        • Miura K
        • Edmundowicz D
        • Ueshima H
        • Research Group SESSA
        Association of blood levels of marine omega-3 fatty acids with coronary calcification and calcium density in Japanese men.
        Eur J Clin Nutr. 2019; 73: 783-792
        • Shang X
        • Sanders KM
        • Scott D
        • Khan B
        • Hodge A
        • Khan N
        • English DR
        • Giles GG
        • Ebeling PR
        Dietary alpha-linolenic acid and total omega-3 fatty acids are inversely associated with abdominal aortic calcification in older women, but not in older men.
        J Nutr. 2015; 145: 1778-1786
        • Steffen BT
        • Duprez D
        • Szklo M
        • Guan W
        • Tsai MY
        Circulating oleic acid levels are related to greater risks of cardiovascular events and all-cause mortality: the Multi-Ethnic Study of Atherosclerosis.
        J Clin Lipidol. 2018; 12: 1404-1412
        • Bild DE
        • Bluemke DA
        • Burke GL
        • Detrano R
        • Diez Roux AV
        • Folsom AR
        • Greenland P
        • Jacob Jr, DR
        • Kronmal R
        • Liu K
        • Nelson JC
        • O'Leary D
        • Saad MF
        • Shea S
        • Szklo M
        • Tracy RP
        Multi-Ethnic Study of Atherosclerosis: objectives and design.
        Am J Epidemiol. 2002; 156: 871-881
        • Cao J
        • Schwichtenberg KA
        • Hanson NQ
        • Tsai MY
        Incorporation and clearance of omega-3 fatty acids in erythrocyte membranes and plasma phospholipids.
        Clin Chem. 2006; 52: 2265-2272
        • Budoff MJ
        • Takasu J
        • Katz R
        • Mao S
        • Shavelle DM
        • O’Brien KD
        • Blumenthal RS
        • Carr JJ
        • Kronmal R
        Reproducibility of CT measurements of aortic valve calcification, mitral annulus calcification, and aortic wall calcification in the multi-ethnic study of atherosclerosis.
        Acad Radiol. 2006; 13: 166-172
        • Nasir K
        • Katz R
        • Al-Mallah M
        • Takasu J
        • Shavelle DM
        • Carr JJ
        • Kronmal R
        • Blumenthal RS
        • O’Brien K
        • Budoff MJ
        Relationship of aortic valve calcification with coronary artery calcium severity: the Multi-Ethnic Study of Atherosclerosis (MESA).
        J Cardiovasc Comput Tomogr. 2010; 4: 41-46
        • Agatston AS
        • Janowitz WR
        • Hildner FJ
        • Zusmer NR
        • Viamonte M
        • Jr Detrano R
        Quantification of coronary artery calcium using ultrafast computed tomography.
        J Am Coll Cardiol. 1990; 15: 827-832
        • Linefsky JP
        • O’Brien KD
        • Katz R
        • de Boer IH
        • Barasch E
        • Jenny NS
        • Siscovick DS
        • Kestenbaum B
        Association of serum phosphate levels with aortic valve sclerosis and annular calcification: the cardiovascular health study.
        J Am Coll Cardiol. 2011; 58: 291-297
        • Massera D
        • Buzkova P
        • Bortnick AE
        • Owens DS
        • Mao S
        • Li D
        • De Boer IH
        • Kestenbaum BR
        • Budoff MJ
        • Kizer JR
        Bone mineral density and long-term progression of aortic valve and mitral annular calcification: the Multi-Ethnic Study of Atherosclerosis.
        Atherosclerosis. 2021; 335: 126-134
        • Budoff MJ
        • Katz R
        • Wong ND
        • Nasir K
        • Mao SS
        • Takasu J
        • Kronmal R
        • Detrano RC
        • Shavelle DM
        • Blumenthal RS
        • O’Brien KD
        • Carr JJ
        Effect of scanner type on the reproducibility of extracoronary measures of calcification: the multi-ethnic study of atherosclerosis.
        Acad Radiol. 2007; 14: 1043-1049
        • Genuth S
        • Alberti KG
        • Bennett P
        • Buse J
        • Defronzo R
        • Kahn R
        • Kitzmiller J
        • Knowler WC
        • Lebovitz H
        • Lernmark A
        • Nathan D
        • Palmer J
        • Rizza R
        • Saudek C
        • Shaw J
        • Steffes M
        • Stern M
        • Tuomilehto J
        • Zimmet P
        Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Follow-up report on the diagnosis of diabetes mellitus.
        Diabetes Care. 2003; 26: 3160-3167
        • Stark KD
        • Van Elswyk ME
        • Higgins MR
        • Weatherford CA
        • Salem Jr, N
        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
        • Nicholls SJ
        • Lincoff AM
        • Garcia M
        • Bash D
        • Ballantyne CM
        • Barter PJ
        • Davidson MH
        • Kastelein JJP
        • Koenig W
        • McGuire DK
        • Mozaffarian D
        • Ridker PM
        • Ray KK
        • Katona BG
        • Himmelmann A
        • Loss LE
        • Rensfeldt M
        • Lundström T
        • Agrawal R
        • Menon V
        • Wolski K
        • Nissen SE
        Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: the STRENGTH randomized clinical trial.
        JAMA. 2020; 324: 2268-2280
        • Plunde O
        • Larsson SC
        • Artiach G
        • Thanassoulis G
        • Carracedo M
        • Franco-Cereceda A
        • Eriksson P
        • Bäck M
        FADS1 (fatty acid desaturase 1) genotype associates with aortic valve FADS mRNA expression, fatty acid content and calcification.
        Circ Genom Precis Med. 2020; 13e002710
        • Lindman BR
        • Clavel MA
        • Mathieu P
        • Iung B
        • Lancellotti P
        • Otto CM
        • Pibarot P
        Calcific aortic stenosis.
        Nat Rev Dis Primers. 2016; 2: 16006
        • Artiach G
        • Carracedo M
        • Plunde O
        • Wheelock CE
        • Thul S
        • Sjövall P
        • Franco-Cereceda A
        • Laguna-Fernandez A
        • Arnardottir H
        • Bäck M
        Omega-3 polyunsaturated fatty acids decrease aortic valve disease through the Resolvin E1 and ChemR23 Axis.
        Circulation. 2020; 142: 776-789
        • Lai HT
        • de Oliveira Otto MC
        • Lemaitre RN
        • McKnight B
        • Song X
        • King IB
        • Chaves PH
        • Odden MC
        • Newman AB
        • Siscovick DS
        • Mozaffarian D
        Serial circulating omega 3 polyunsaturated fatty acids and healthy ageing among older adults in the cardiovascular health study: prospective cohort study.
        BMJ (Clin Res Ed). 2018; 363: k4067