Highlights
- •Evidence concerning LCn-3PUFAs and atherosclerosis is limited in the general population.
- •Cross-sectionally examined the relationship of LCn-3 PUFAs to aortic calcification in asymptomatic middle aged men.
- •Overall, LCn-3PUFAs especially DHA was inversely and significantly associated with aortic calcification.
- •No significant interaction between race/ethnicity and total LCn-3 PUFAs, EPA or DHA on aortic calcification.
- •In the general middle-aged male population, DHA may be more anti-atherogenic than EPA.
Abstract
Background and aim
Few studies have examined the association of long-chain n-3 polyunsaturated fatty
acids (LCn-3PUFAs) with the measures of atherosclerosis in the general population.
This study aimed to examine the relationship of total LCn-3PUFAs, eicosapentaenoic
acid (EPA), and docosahexaenoic acid (DHA) with aortic calcification.
Methods and results
In a multiethnic population-based cross-sectional study of 998 asymptomatic men aged
40–49 years (300 US-White, 101 US-Black, 287 Japanese American, and 310 Japanese in
Japan), we examined the relationship of serum LCn-3PUFAs to aortic calcification (measured
by electron-beam computed tomography and quantified using the Agatston method) using
Tobit regression and ordinal logistic regression after adjusting for potential confounders.
Overall 56.5% participants had an aortic calcification score (AoCaS) > 0. The means
(SD) of total LCn-3PUFAs, EPA, and DHA were 5.8% (3.3%), 1.4% (1.3%), and 3.7% (2.1%),
respectively. In multivariable-adjusted Tobit regression, a 1-SD increase in total
LCn-3PUFAs, EPA, and DHA was associated with 29% (95% CI = 0.51, 1.00), 9% (95% CI = 0.68,
1.23), and 35% (95% CI = 0.46, 0.91) lower AoCaS, respectively. Results were similar
in ordinal logistic regression analysis. There was no significant interaction between
race/ethnicity and total LCn–3PUFAs, EPA or DHA on aortic calcification.
Conclusions
This study showed the significant inverse association of LCn-3PUFAs with aortic calcification
independent of conventional cardiovascular risk factors among men in the general population.
This association appeared to be driven by DHA but not EPA.
Keywords
List of abbreviations:
ALA (α-linolenic acid), AoCaS (Agatston aortic calcification score), ARA (arachidonic acid), BMI (body mass index), CAC (coronary artery calcification), CI (confidence interval), CIMT (carotid intima-media thickness), CHD (coronary heart disease), CRP (C-reactive protein), CVD (cardiovascular disease), DHA (docosahexaenoic acid), DPA (docosapentaenoic acid), EBCT (Electron beam computed tomography), EPA (eicosapentaenoic acid), HDL-C (high-density lipoprotein cholesterol), LA (linoleic acid), LCn-3PUFAs (long-chain n-3 polyunsaturated fatty acids), LDL-C (low-density lipoprotein cholesterol), RCT (randomized controlled trial), SD (standard deviation), SEM (standard error of mean), TR (tobit ratio)To read this article in full you will need to make a payment
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References
- A meta-analysis of randomized controlled trials and prospective cohort studies of eicosapentaenoic and docosahexaenoic long-chain omega-3 fatty acids and coronary heart disease risk.Mayo Clin Proc: Elsevier. 2017; : 15-29
- Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events.J Am Coll Cardiol. 2011; 58: 2047-2067
- Dietary n-3 PUFA and CVD: a review of the evidence.Proc Nutr Soc. 2014; 73: 57-64
- Fish intake, contaminants, and human health: evaluating the risks and the benefits part 2-health risks and optimal intakes.Cardiol Rounds. 2006; 10: 1-6
- Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia.N Engl J Med. 2018;
- Omega-3 polyunsaturated fatty acid (fish oil) supplementation and the prevention of clinical cardiovascular disease: a science advisory from the American heart association.Circulation. 2017; (CIR. 0000000000000482)
- A randomized controlled trial of eicosapentaenoic acid in patients with coronary heart disease on statins.J Cardiol. 2017; 70: 537-544
- Eicosapentaenoic acid reduces the progression of carotid intima-media thickness in patients with type 2 diabetes.Atherosclerosis. 2007; 191: 162-167
- Effects of the addition of eicosapentaenoic acid to strong statin therapy on inflammatory cytokines and coronary plaque components assessed by integrated backscatter intravascular ultrasound.Circ J. 2016; 80: 450-460
- Effect of eicosapentaenoic and docosahexaenoic acids added to statin therapy on coronary artery plaque in patients with coronary artery disease: a randomized clinical trial.J Am Heart Assoc. 2017; 6
- The role of marine omega-3 (n-3) fatty acids in inflammatory processes, atherosclerosis and plaque stability.Mol Nutr Food Res. 2012; 56: 1073-1080
- Eicosapentaenoic acid (EPA) from highly concentrated n− 3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability.Atherosclerosis. 2010; 212: 252-259
- Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial.Lancet. 2003; 361: 477-485
- Evaluation of four animal models of intrarenal calcium deposition and assessment of the influence of dietary supplementation with essential fatty acids on calcification.Urol Res. 1995; 23: 239-242
- Ectopic calcification of rat aortas and kidneys is reduced with n-3 fatty acid supplementation.Prostagl Leukot Essent Fat Acids. 1998; 59: 221-227
- N-3 fatty acids inhibit vascular calcification via the p38-mitogen-activated protein kinase and peroxisome proliferator-activated receptor-γ pathways.Circ Res. 2006; 98: 727-729
- Omega-3 fatty acids, inflammation and angiogenesis: basic mechanisms behind the cardioprotective effects of fish and fish oils.Cell Mol Biol (Noisy-le-Grand, France). 2009; 56: 59-82
- Intakes of long-chain n–3 polyunsaturated fatty acids and fish in relation to measurements of subclinical atherosclerosis.Am J Clin Nutr. 2008; 88: 1111-1118
- Intake of fish and marine n− 3 fatty acids in relation to coronary calcification: the Rotterdam Study.Am J Clin Nutr. 2010; 91: 1317-1323
- Dietary α-linolenic acid and total ω-3 fatty acids are inversely associated with abdominal aortic calcification in older women, but not in older men.J Nutr. 2015; (jn211789)
- Differential association of docosahexaenoic and eicosapentaenoic acids with carotid intima-media thickness.Stroke. 2011; 42: 2538-2543
- Abdominal aortic calcification identified on lateral spine images from bone densitometers are a marker of generalized atherosclerosis in elderly women.Arterioscler Thromb Vasc Biol. 2016; 36: 166-173
- Calcification of the abdominal aorta as an independent predictor of cardiovascular events: a meta-analysis.Heart. 2012; 98: 988-994
- Calcification of the aortic arch: risk factors and association with coronary heart disease, stroke, and peripheral vascular disease.JAMA. 2000; 283: 2810-2815
- Abdominal aortic calcium, coronary artery calcium, and cardiovascular morbidity and mortality in the Multi-Ethnic Study of Atherosclerosis.Arterioscler Thromb Vasc Biol. 2014; 34: 1574-1579
- Risk factor differences for aortic versus coronary calcified atherosclerosis the multiethnic study of atherosclerosis.Arterioscler Thromb Vasc Biol. 2010; 30: 2289-2296
- Coronary and aortic calcification among women 8 Years after menopause and their premenopausal risk factors the healthy women study.Arterioscler Thromb Vasc Biol. 1999; 19: 2189-2198
- Cardiovascular event prediction and risk reclassification by coronary, aortic, and valvular calcification in the framingham heart study.J Am Heart Assoc. 2016; 5e003144
- Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese-American, and white men: a cross-sectional study.J Am Coll Cardiol. 2008; 52: 417-424
- A cross-sectional association of obesity with coronary calcium among Japanese, Koreans, Japanese Americans, and US whites.Eur Heart J–Cardiovasc Imaging. 2013; (jet080)
- Serum n− 6 fatty acids and lipoprotein subclasses in middle-aged men: the population-based cross-sectional ERA-JUMP Study.Am J Clin Nutr. 2010; 91: 1195-1203
- Less subclinical atherosclerosis in Japanese men in Japan than in white men in the United States in the post–World War II birth cohort.Am J Epidemiol. 2007; 165: 617-624
- Much lower prevalence of coronary calcium detected by electron-beam computed tomography among men aged 40–49 in Japan than in the US, despite a less favorable profile of major risk factors.Int J Epidemiol. 2005; 34: 173-179
- Quantification of coronary artery calcium using ultrafast computed tomography.J Am Coll Cardiol. 1990; 15: 827-832
- Coronary artery calcification and cardiovascular risk factors: impact of the analytic approach.Atherosclerosis. 2004; 173: 69-78
- Estimation of relationships for limited dependent variables.Econometrica: J Econom Soc. 1958; : 24-36
- Higher plasma docosahexaenoic acid is associated with reduced progression of coronary atherosclerosis in women with CAD.J Lipid Res. 2006; 47: 2814-2819
- The independent effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors in humans.Curr Opin Clin Nutr Metab Care. 2006; 9: 95-104
- Does fish oil lower blood pressure? A meta-analysis of controlled trials.Circulation. 1993; 88: 523-533
- Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans.Hypertension. 1999; 34: 253
- Fatty acid modulation of endothelial activation.Am J Clin Nutr. 2000; 71: 213S-223S
- Marine n−3 fatty acids and prevention of cardiovascular disease and cancer.N Engl J Med. 2018;
- Meat intake and cause-specific mortality: a pooled analysis of Asian prospective cohort studies.Am J Clin Nutr. 2013; 98: 1032-1041
- Association of dietary, circulating, and supplement fatty acids with coronary riska systematic review and meta-analysis.Ann Intern Med. 2014; 160: 398-406
- Novel lipid mediators and resolution mechanisms in acute inflammation: to resolve or not?.Am J Pathol. 2010; 177: 1576-1591
Article info
Publication history
Published online: May 07, 2019
Accepted:
April 27,
2019
Received:
March 10,
2019
Handling Editor: M. AvernaIdentification
Copyright
© 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
