Serum Non-Esterified Fatty Acids, Carotid Artery Intima-Media Thickness and Flow-Mediated Dilation in Older Adults: The Cardiovascular Health Study (CHS)
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Population
2.2. Non-Esterified Fatty Acid (µmol/L) Determinations
2.3. Carotid Intima-Media Thickness and Flow-Mediated Dilation
2.4. Other Covariates
2.5. Statistical Analysis
3. Results
3.1. Characteristics of Study Participants
3.2. Association of Serum NEFAs, Carotid Intima-Media Thickness and Estimated Plaque Thickness
3.3. Association of Serum Non-Esterified FAs and Flow-Mediated Dilation
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Virani, S.S.; Alonso, A.; Aparicio, H.J.; Benjamin, E.J.; Bittencourt, M.S.; Callaway, C.W.; Carson, A.P.; Chamberlain, A.M.; Cheng, S.; Delling, F.N.; et al. Heart disease and stroke statistics-2021 update: A report from the American Heart Association. Circulation 2021, 143, e254–e743. [Google Scholar] [CrossRef]
- Kuller, L.; Borhani, N.; Furberg, C.; Gardin, J.; Manolio, T.; O’Leary, D.; Psaty, B.; Robbins, J. Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the Cardiovascular Health Study. Am. J. Epidemiol. 1994, 139, 1164–1179. [Google Scholar] [CrossRef]
- Jaffer, F.A.; O’Donnell, C.J.; Larson, M.G.; Chan, S.K.; Kissinger, K.V.; Kupka, M.J.; Salton, C.; Botnar, R.M.; Levy, D.; Manning, W.J. Age and sex distribution of subclinical aortic atherosclerosis: A magnetic resonance imaging examination of the Framingham Heart Study. Arterioscler. Thromb. Vasc. Biol. 2002, 22, 849–854. [Google Scholar] [CrossRef] [PubMed]
- Coskun, U.; Yildiz, A.; Esen, O.B.; Baskurt, M.; Cakar, M.A.; Kilickesmez, K.O.; Orhan, L.A.; Yildiz, S. Relationship between carotid intima-media thickness and coronary angiographic findings: A prospective study. Cardiovasc. Ultrasound. 2009, 7, 59. [Google Scholar] [CrossRef] [PubMed]
- De Caterina, R.; Zampolli, A.; Del Turco, S.; Madonna, R.; Massaro, M. Nutritional mechanisms that influence cardiovascular disease. Am. J. Clin. Nutr. 2006, 83, 421–426. [Google Scholar] [CrossRef]
- Yeboah, J.; Crouse, J.R.; Hsu, F.C.; Burke, G.L.; Herrington, D.M. Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: The Cardiovascular Health Study. Circulation 2007, 115, 2390–2397. [Google Scholar] [CrossRef] [PubMed]
- Manganaro, A.; Ciracì, L.; Andrè, L.; Trio, O.; Manganaro, R.; Saporito, F.; Oreto, G.; Andò, G. Endothelial dysfunction in patients with coronary artery disease: Insights from a flow-mediated dilation study. Clin. Appl. Thromb. Hemost. 2014, 20, 583–588. [Google Scholar] [CrossRef]
- Green, D.J.; Jones, H.; Thijssen, D.; Cable, N.T.; Atkinson, G. Flow-mediated dilation and cardiovascular event prediction: Does nitric oxide matter? Hypertension 2011, 57, 363–369. [Google Scholar] [CrossRef]
- O’Leary, D.H.; Polak, J.F.; Kronmal, R.A.; Manolio, T.A.; Burke, G.L.; Wolfson, S.K., Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N. Engl. J. Med. 1999, 340, 14–22. [Google Scholar] [CrossRef]
- Ly, L.D.; Xu, S.; Choi, S.K.; Ha, C.M.; Thoudam, T.; Cha, S.K.; Wiederkehr, A.; Wollheim, C.B.; Lee, I.K.; Park, K.S. Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes. Exp. Mol. Med. 2017, 49, e291. [Google Scholar] [CrossRef]
- Ghosh, A.; Gao, L.; Thakur, A.; Siu, P.M.; Lai, C.W.K. Role of free fatty acids in endothelial dysfunction. J. Biomed. Sci. 2017, 24, 50. [Google Scholar] [CrossRef]
- Delarue, J.; Magnan, C. Free fatty acids and insulin resistance. Curr. Opin. Clin. Nutr. Metab. Care. 2007, 10, 142–148. [Google Scholar] [CrossRef]
- Bentzon, J.F.; Otsuka, F.; Virmani, R.; Falk, E. Mechanisms of plaque formation and rupture. Circ. Res. 2014, 114, 1852–1866. [Google Scholar] [CrossRef]
- Fried, L.P.; Borhani, N.O.; Enright, P.; Furberg, C.D.; Gardin, J.M.; Kronmal, R.A.; Kuller, L.H.; Manolio, T.A.; Mittelmark, M.B.; Newman, A.; et al. The Cardiovascular Health Study: Design and rationale. Ann. Epidemiol. 1991, 1, 263–276. [Google Scholar] [CrossRef]
- Morrison, W.R.; Smith, L.M. Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride-methanol. J. Lipid Res. 1964, 5, 600–608. [Google Scholar] [CrossRef]
- Folch, J.; Lees, M.; Sloane Stanley, G.H. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 1957, 226, 497–509. [Google Scholar] [CrossRef]
- Agren, J.J.; Julkunen, A. Rapid separation of serum lipids for fatty acid analysis by a single aminopropyl column. J. Lipid Res. 1992, 33, 1871–1876. [Google Scholar] [CrossRef]
- Matthan, N.R.; Ip, B.; Resteghini, N.; Ausman, L.M.; Lichtenstein, A.H. Long-term fatty acid stability in human serum cholesteryl ester, triglyceride, and phospholipid fractions. J. Lipid Res. 2010, 51, 2826–2832. [Google Scholar] [CrossRef]
- O’Leary, D.H.; Polak, J.F.; Wolfson, S.K., Jr.; Bond, M.G.; Bommer, W.; Sheth, S.; Psaty, B.M.; Sharrett, A.R.; Manolio, T.A. Use of sonography to evaluate carotid atherosclerosis in the elderly. the Cardiovascular Health Study. CHS collaborative research group. Stroke 1991, 22, 1155–1163. [Google Scholar] [CrossRef]
- Polak, J.F.; Pencina, M.J.; Pencina, K.M.; O’Donnell, C.J.; Wolf, P.A.; D’Agostino, R.B., Sr. Carotid-wall intima–media thickness and cardiovascular events. N. Engl. J. Med. 2011, 365, 213–221. [Google Scholar] [CrossRef]
- Herrington, D.M.; Fan, L.; Drum, M.; Riley, W.A.; Pusser, B.E.; Crouse, J.R.; Burke, G.L.; McBurnie, M.A.; Morgan, T.M.; Espeland, M.A. Brachial flow-mediated vasodilator responses in population-based research: Methods, reproducibility and effects of age, gender and baseline diameter. J. Cardiovasc. Risk. 2001, 8, 319–328. [Google Scholar] [CrossRef]
- Plotnick, G.D.; Corretti, M.C.; Vogel, R.A. Effect of antioxidant vitamins on the transient impairment of endothelium-dependent brachial artery vasoactivity following a single high-fat meal. JAMA. 1997, 278, 1682–1686. [Google Scholar] [CrossRef]
- Macy, E.M.; Hayes, T.E.; Tracy, R.P. Variability in the measurement of C-reactive protein in healthy subjects: Implications for reference intervals and epidemiological applications. Clin. Chem. 1997, 43, 52–58. [Google Scholar] [CrossRef]
- Taylor, H.L.; Jacobs, D.R., Jr.; Schucker, B.; Knudsen, J.; Leon, A.S.; Debacker, G. A questionnaire for the assessment of leisure time physical activities. J. Chronic Dis. 1978, 31, 741–755. [Google Scholar] [CrossRef]
- Lichtenstein, A.H. Dietary trans fatty acids and cardiovascular disease risk: Past and present. Curr. Atheroscler. Rep. 2014, 16, 433. [Google Scholar] [CrossRef] [PubMed]
- Bendsen, N.T.; Christensen, R.; Bartels, E.M.; Astrup, A. Consumption of industrial and ruminant trans fatty acids and risk of coronary heart disease: A systematic review and meta-analysis of cohort studies. Eur. J. Clin. Nutr. 2011, 65, 773–783. [Google Scholar] [CrossRef] [PubMed]
- Laake, I.; Pedersen, J.I.; Selmer, R.; Kirkhus, B.; Lindman, A.S.; Tverdal, A.; Veierød, M.B. A prospective study of intake of trans-fatty acids from ruminant fat, partially hydrogenated vegetable oils, and marine oils and mortality from CVD. Br. J. Nutr. 2012, 108, 743–754. [Google Scholar] [CrossRef] [PubMed]
- Bruen, R.; Fitzsimons, S.; Belton, O. Atheroprotective effects of conjugated linoleic acid. Br. J. Clin. Pharmacol. 2017, 83, 46–53. [Google Scholar] [CrossRef] [PubMed]
- Wannamethee, S.G.; Jefferis, B.J.; Lennon, L.; Papacosta, O.; Whincup, P.H.; Hingorani, A.D. Serum conjugated linoleic acid and risk of incident heart failure in older men: The British Regional Heart Study. J. Am. Heart Assoc. 2018, 7, e006653. [Google Scholar] [CrossRef] [PubMed]
- Sluijs, I.; Plantinga, Y.; de Roos, B.; Mennen, L.I.; Bots, M.L. Dietary supplementation with cis-9,trans-11 conjugated linoleic acid and aortic stiffness in overweight and obese adults. Am. J. Clin. Nutr. 2010, 91, 175–183. [Google Scholar] [CrossRef] [PubMed]
- Bachmair, E.M.; Bots, M.L.; Mennen, L.I.; Kelder, T.; Evelo, C.T.; Horgan, G.W.; Ford, I.; de Roos, B. Effect of supplementation with an 80:20 cis9,trans11 conjugated linoleic acid blend on the human platelet proteome. Mol. Nutr. Food Res. 2012, 56, 1148–1159. [Google Scholar] [CrossRef]
- Bachmair, E.M.; Wood, S.G.; Keizer, H.G.; Horgan, G.W.; Ford, I.; de Roos, B. Supplementation with a 9c,11t-rich conjugated linoleic acid blend shows no clear inhibitory effects on platelet function in healthy subjects at low and moderate cardiovascular risk: A randomized controlled trial. Mol. Nutr. Food Res. 2015, 59, 741–750. [Google Scholar] [CrossRef]
- Sala-Vila, A.; Cofán, M.; Pérez-Heras, A.; Núñez, I.; Gilabert, R.; Junyent, M.; Mateo-Gallego, R.; Cenarro, A.; Civeira, F.; Ros, E. Fatty acids in serum phospholipids and carotid intima-media thickness in spanish subjects with primary dyslipidemia. Am. J. Clin. Nutr. 2010, 92, 186–193. [Google Scholar] [CrossRef] [PubMed]
- Wanders, A.J.; Zock, P.L.; Brouwer, I.A. Trans fat intake and its dietary sources in general populations worldwide: A systematic review. Nutrients 2017, 9, 840. [Google Scholar] [CrossRef] [PubMed]
- Cao, H.; Gerhold, K.; Mayers, J.R.; Wiest, M.M.; Watkins, S.M.; Hotamisligil, G.S. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 2008, 134, 933–944. [Google Scholar] [CrossRef]
- Mozaffarian, D.; Cao, H.; King, I.B.; Lemaitre, R.N.; Song, X.; Siscovick, D.S.; Hotamisligil, G.S. Circulating palmitoleic acid and risk of metabolic abnormalities and new-onset diabetes. Am. J. Clin. Nutr. 2010, 92, 1350–1358. [Google Scholar] [CrossRef] [PubMed]
- Luan, D.; Wang, D.; Campos, H.; Baylin, A. Adipose tissue palmitoleic acid is inversely associated with nonfatal acute myocardial infarction in Costa Rican adults. Nutr. Metab. Cardiovasc. Dis. 2018, 28, 973–979. [Google Scholar] [CrossRef]
- Gepner, A.D.; Young, R.; Delaney, J.A.; Budoff, M.J.; Polak, J.F.; Blaha, M.J.; Post, W.S.; Michos, E.D.; Kaufman, J.; Stein, J.H. Comparison of Carotid Plaque Score and Coronary Artery Calcium Score for Predicting Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis. J. Am. Heart Assoc. 2017, 6, e005179. [Google Scholar] [CrossRef]
- Longstreth, W.T., Jr.; Shemanski, L.; Lefkowitz, D.; O’Leary, D.H.; Polak, J.F.; Wolfson, S.K., Jr. Asymptomatic internal carotid artery stenosis defined by ultrasound and the risk of subsequent stroke in the elderly. The Cardiovascular Health Study. Stroke 1998, 29, 2371–2376. [Google Scholar] [CrossRef]
- Garg, P.K.; Koh, W.J.H.; Delaney, J.A.; Halm, E.A.; Hirsch, C.H.; Longstreth, W.T., Jr.; Mukamal, K.J.; Kucharska-Newton, A.; Polak, J.F. Risk Factors for Incident Carotid Artery Revascularization among Older Adults: The Cardiovascular Health Study. Cerebrovasc. Dis. Extra 2016, 6, 129–139. [Google Scholar] [CrossRef]
Characteristics | Carotid IMT | FMD | ||
---|---|---|---|---|
No ASCVD a (n = 1314) | with ASCVD (n = 255) | No ASCVD (n = 1462) | with ASCVD (n = 301) | |
Age, years | 77.3 ± 4.18 | 78.3 ± 4.35 | 77.4 ± 4.26 | 78.9 ± 4.66 |
Body mass index, kg/m2 | 26.8 ± 4.31 | 26.3 ± 3.98 | 26.9 ± 4.4 | 26.3 ± 4.05 |
Waist circumference, cm | 96.1 ± 12.6 | 96.3 ± 11.4 | 96.5 ± 12.8 | 96.5 ± 11.6 |
Female, % | 63.5 | 45.1 | 61.8 | 43.5 |
Black, % | 14.0 | 14.5 | 14.0 | 15.3 |
CHS clinic, % | ||||
California | 31.1 | 26.1 | 29.6 | 30.6 |
Maryland | 16.9 | 21.3 | 21.0 | 23.3 |
North Carolina | 23.4 | 26.6 | 22.1 | 17.9 |
Pennsylvania | 28.6 | 26.0 | 27.3 | 28.2 |
Educational attainment, % | ||||
≥High school | 54.6 | 49.2 | 52.1 | 46.3 |
Smoking status, % | ||||
Never smoked | 52.4 | 38.1 | 51.1 | 39.1 |
Former smoker | 40.2 | 55.2 | 41.0 | 53.5 |
Current smoker | 7.4 | 6.7 | 7.8 | 7.4 |
Alcoholic drinks/week, % | ||||
0 | 53.7 | 51.2 | 54.7 | 53.8 |
1–7 | 34.3 | 36.6 | 33.1 | 34.8 |
>7 | 12.0 | 12.2 | 12.1 | 11.4 |
Hypertension, % | 59.7 | 63.4 | 60.0 | 61.4 |
Diabetes, % | 2.1 | 3.5 | 2.2 | 4.7 |
Prevalent AF, % | 3.0 | 10.2 | 2.7 | 9.0 |
Prevalent CHF, % | 0 | 30.6 | 0 | 33.2 |
Prevalent Stroke, % | 0 | 27.8 | 0 | 27.6 |
Prevalent TIA, % | 2.1 | 8.2 | 2.4 | 7.6 |
Prevalent PAD, % | 0 | 13.3 | 0 | 12.0 |
Hypertension medication, % | 47.4 | 73.7 | 48.4 | 72.4 |
Estrogen (females only), % | 21.0 | 22.6 | 19.9 | 19.8 |
Fasting glucose, mg/dL | 97.3 ± 12.8 | 99.3 ± 14.3 | 97.4 ± 12.7 | 100.2 ± 18.3 |
Albumin, g/dL | 3.83 ± 0.29 | 3.82 ± 0.29 | 3.83 ± 0.29 | 3.82 ± 0.30 |
eGFRcysc b | 74.2 ± 18.0 | 65.9 ± 18.8 | 74.0 ± 17.9 | 65.6 ± 18.4 |
C-Reactive Protein, mg/dL, log2 | 1.15 ± 1.57 | 1.42 ± 1.53 | 1.17 ± 1.56 | 1.49 ± 1.61 |
Carotid IMT, mm | 2.13 ± 1.01 | 2.5 ± 1.17 | - | - |
FMD, % change | - | - | 3.25 ± 2.05 | 3.00 ± 1.80 |
NEFAs, µmol/L per SD | No ASCVD a | With ASCVD a | ||
---|---|---|---|---|
Regression Coefficient (95% CI) | Adjusted p-Value b | Regression Coefficient (95% CI) | Adjusted p-Value b | |
Carotid IMT | ||||
Sum of 18:1n-10–12t c | 3.61 (−5.09, 12.3) | 1.00 | 39.4 (14.0, 64.7) | 0.085 |
Elaidic acid, 18:1n-9t | −0.10 (−8.77, 8.58) | 1.00 | 38.6 (14.1, 63.1) | 0.077 |
Conjugated linoleic acid, 18:2tCLA | 2.16 (−6.74, 11.1) | 1.00 | 44.8 (19.2, 70.4) | 0.025 |
Flow-mediated dilation | ||||
Palmitoleic acid, 16:1n-7c | 19.7 (8.34, 31.0) | 0.024 | 4.91 (−17.4, 27.2) | 0.667 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Huang, N.K.; Bůžková, P.; Matthan, N.R.; Djoussé, L.; Kizer, J.R.; Mukamal, K.J.; Polak, J.F.; Lichtenstein, A.H. Serum Non-Esterified Fatty Acids, Carotid Artery Intima-Media Thickness and Flow-Mediated Dilation in Older Adults: The Cardiovascular Health Study (CHS). Nutrients 2021, 13, 3052. https://doi.org/10.3390/nu13093052
Huang NK, Bůžková P, Matthan NR, Djoussé L, Kizer JR, Mukamal KJ, Polak JF, Lichtenstein AH. Serum Non-Esterified Fatty Acids, Carotid Artery Intima-Media Thickness and Flow-Mediated Dilation in Older Adults: The Cardiovascular Health Study (CHS). Nutrients. 2021; 13(9):3052. https://doi.org/10.3390/nu13093052
Chicago/Turabian StyleHuang, Neil K., Petra Bůžková, Nirupa R. Matthan, Luc Djoussé, Jorge R. Kizer, Kenneth J. Mukamal, Joseph F. Polak, and Alice H. Lichtenstein. 2021. "Serum Non-Esterified Fatty Acids, Carotid Artery Intima-Media Thickness and Flow-Mediated Dilation in Older Adults: The Cardiovascular Health Study (CHS)" Nutrients 13, no. 9: 3052. https://doi.org/10.3390/nu13093052