The role of serum monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) in cardiovascular disease risk

Main Article Content

Jasmin Kharazmi-Khorassani
Roshanak Ghafarian Zirak
Hamideh Ghazizadeh
Reza Zare-Feyzabadi
Sara Kharazmi-Khorassani
Sharzad Naji-Reihani-Garmroudi
Elham Kazemi
Habibollah Esmaily
Ali Javan-Doust
Hamed Banpour
Maryam Mohammadi-Bajgiran
Mohhamad reza Besharatlou
Gordon A. Ferns
Mohammad Hashemi
Majid Ghayour-Mobarhan

Keywords

Keywords: Free fatty acids, cardiovascular diseases, Risk factors

Abstract

Abstract


Background:


Fatty acids have been observed as independent risk factors of cardiovascular diseases (CVD). In this study we investigated FFA levels in patients with CVD, and, its risk factors.


Material and Methods:


In this case-control study, 346 unrelated Iranian patients who underwent coronary angiography were enrolled. Participants were categorized into two groups: who had >50% stenosis were assigned to the angiogram positive group (N=90) and those with <30% stenosis were assigned to the angiogram negative group (N=124) and also 222 subjects were healthy. Several risk factors were assessed in all participants, including anthropometric indices, blood pressure, lipid profiles, and biochemical factors. The levels of FFAs were determined using gas chromatography. Serum FFA concentrations were compared between healthy and patients with positive and negative angiograms. The association of serum FFA levels with four major risk factors (hypertension, high fasting blood glucose (FBG) level, high BMI and WHR) were also assessed.


Results:


According to our data, it has been shown that median of FFAs was higher in patients than healthy subjects (p<0.0001), such as SFA and n6-FFAs (in patients 1.59 (1.27) and 1.22 (1.06), respectively and healthy subjects 0.33 (0.38) and 0.36 (0.35)). According to anthropometric and biochemical data, we did not show statistical differences between the groups, except FBG, SBP and hs-CRP that showed significantly higher levels in the patients than controls (p<0.0001, p=0.001). Also, lower median levels of total cholesterol, LDL-C, HDL-C and DBP were observed in patients which can due to lipid-lowering medication use like Statins.


Conclusion:


High serum levels of FFAs are considered as an independent risk factor for CVDs, while various types of FFAs can have different influences on CVD risk factors. Therefore, longitudinal studies are needed to clarify the association between FFAs and CVD risk factors. High serum levels of FFAs are considered as an independent risk factor for CVDs, while various types of FFAs can have different influences on CVD risk factors. Therefore, longitudinal studies are needed to clarify the association between FFAs and CVD risk factors.

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References

1. Pilz, S. and W. März, Free fatty acids as a cardiovascular risk factor. Clinical chemistry and laboratory medicine, 2008. 46(4): p. 429-434.
2. Sanchis-Gomar, F., et al., Epidemiology of coronary heart disease and acute coronary syndrome. Annals of translational medicine, 2016. 4(13).
3. Gordon, T. and W.B. Kannel, Multiple risk functions for predicting coronary heart disease: the concept, accuracy, and application. American heart journal, 1982. 103(6): p. 1031-1039.
4. Kannel, W. and D. McGee, Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham study. Diabetes care, 1979. 2(2): p. 120-126.
5. KANNEL, W.B. and T.R. DAWBER, Diabetes, Blood Lipids, and the Role of Obesity in Coronary Heart Disease Risk for Women. Annals of Internal Medicine, 1977. 87: p. 393-397.
6. Roy, V.K., et al., Plasma free Fatty Acid concentrations as a marker for acute myocardial infarction. Journal of Clinical and Diagnostic Research: JCDR, 2013. 7(11): p. 2432.
7. Tripathy, D., et al., Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects. Diabetes, 2003. 52(12): p. 2882-2887.
8. Pirro, M., et al., Plasma free fatty acid levels and the risk of ischemic heart disease in men: prospective results from the Quebec Cardiovascular Study. Atherosclerosis, 2002. 160(2): p. 377-384.
9. Steinberg, H.O., et al., Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. The Journal of clinical investigation, 1997. 100(5): p. 1230-1239.
10. Bays, H., L. Mandarino, and R.A. DeFronzo, Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. The Journal of Clinical Endocrinology & Metabolism, 2004. 89(2): p. 463-478.
11. Hendrickson, S.C., et al., Free fatty acid metabolism during myocardial ischemia and reperfusion. Molecular and cellular biochemistry, 1997. 166(1-2): p. 85-94.
12. Oliver, E.F. and L. Opie, Effects of glucose and fatty acids on myocardial ischaemia and arrhythmias. The Lancet, 1994. 343(8890): p. 155-158.
13. Mathew, M., E. Tay, and K. Cusi, Elevated plasma free fatty acids increase cardiovascular risk by inducing plasma biomarkers of endothelial activation, myeloperoxidase and PAI-1 in healthy subjects. Cardiovascular diabetology, 2010. 9(1): p. 9.
14. Shishehbor, M.H., et al., Statins promote potent systemic antioxidant effects through specific inflammatory pathways. Circulation, 2003. 108(4): p. 426-431.
15. Shishehbor, M.H., et al., Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy. Jama, 2003. 289(13): p. 1675-1680.
16. Boden, G., et al., Mechanisms of fatty acid-induced inhibition of glucose uptake. The Journal of clinical investigation, 1994. 93(6): p. 2438-2446.
17. Zhou, H.G., et al., Glutathione Prevents Free Fatty Acids‐Induced Oxidative Stress and Apoptosis in Human Brain Vascular Endothelial Cells Through A kt Pathway. CNS neuroscience & therapeutics, 2013. 19(4): p. 252-261.
18. Malfitano, C., et al., Glucose and fatty acid metabolism in infarcted heart from streptozotocin-induced diabetic rats after 2 weeks of tissue remodeling. Cardiovascular diabetology, 2015. 14(1): p. 149.
19. Hazen, S.L. and R. Zhang, Combined F2-isoprostane and myeloperoxidase detection, a risk indicator for cardiovascular disease. 2015, Google Patents.
20. Steinberg, D. and J.L. Witztum, Is the oxidative modification hypothesis relevant to human atherosclerosis? Do the antioxidant trials conducted to date refute the hypothesis? Circulation, 2002. 105(17): p. 2107-2111.
21. Chisolm, G.M. and D. Steinberg, The oxidative modification hypothesis of atherogenesis: an overview. Free radical biology and medicine, 2000. 28(12): p. 1815-1826.
22. Guo, S.-X., et al., Association of serum free fatty acids with hypertension and insulin resistance among rural uyghur adults in far Western China. International journal of environmental research and public health, 2015. 12(6): p. 6582-6590.
23. Zhang, H.-W., et al., Free fatty acids and cardiovascular outcome: a Chinese cohort study on stable coronary artery disease. Nutrition & metabolism, 2017. 14(1): p. 41.
24. Ma, P., et al., In-hospital free fatty acids levels predict the severity of myocardial ischemia of acute coronary syndrome. BMC cardiovascular disorders, 2016. 16(1): p. 29.
25. Yang, R.-F., et al., A study on the relationship between waist phenotype, hypertriglyceridemia, coronary artery lesions and serum free fatty acids in adult and elderly patients with coronary diseases. Immunity & Ageing, 2018. 15(1): p. 14.
26. Pilz, S., et al., Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease. The Journal of Clinical Endocrinology & Metabolism, 2006. 91(7): p. 2542-2547.
27. Tajfard, M., et al., Relationship between serum high sensitivity C‐reactive protein with angiographic severity of coronary artery disease and traditional cardiovascular risk factors. Journal of cellular physiology, 2019. 234(7): p. 10289-10299.
28. Aline Charles, M., et al., High plasma nonesterified fatty acids are predictive of cancer mortality but not of coronary heart disease mortality: results from the Paris Prospective Study. American journal of epidemiology, 2001. 153(3): p. 292-298.
29. Pilz, S., et al., Elevated plasma free fatty acids predict sudden cardiac death: a 6.85-year follow-up of 3315 patients after coronary angiography. European heart journal, 2007. 28(22): p. 2763-2769.
30. Khawaja, O., et al., Plasma free fatty acids and risk of atrial fibrillation (from the Cardiovascular Health Study). The American journal of cardiology, 2012. 110(2): p. 212-216.
31. Havmoeller, R., et al., Elevated plasma free fatty acids are associated with sudden death: a prospective community-based evaluation at the time of cardiac arrest. Heart rhythm, 2014. 11(4): p. 691-696.
32. Rupp, H., A. Zarain-Herzberg, and B. Maisch, The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure. Herz, 2002. 27(7): p. 621-636.
33. Alexopoulos, N., D. Katritsis, and P. Raggi, Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis. Atherosclerosis, 2014. 233(1): p. 104-112.
34. Mattacks, C.A. and C.M. Pond, Interactions of noradrenalin and tumour necrosis factor α, interleukin 4 and interleukin 6 in the control of lipolysis from adipocytes around lymph nodes. Cytokine, 1999. 11(5): p. 334-346.
35. van Hall, G., et al., Interleukin-6 stimulates lipolysis and fat oxidation in humans. The Journal of Clinical Endocrinology & Metabolism, 2003. 88(7): p. 3005-3010.
36. Li, H., et al., Free fatty acids induce endothelial dysfunction and activate protein kinase C and nuclear factor-κB pathway in rat aorta. International journal of cardiology, 2011. 152(2): p. 218-224.
37. Tang, Y. and G. Li, Chronic exposure to high fatty acids impedes receptor agonist-induced nitric oxide production and increments of cytosolic Ca2+ levels in endothelial cells. Journal of molecular endocrinology, 2011. 47(3): p. 315.
38. Koenig, W., High-sensitivity C-reactive protein and atherosclerotic disease: from improved risk prediction to risk-guided therapy. International journal of cardiology, 2013. 168(6): p. 5126-5134.
39. Ridker, P.M., Inflammation, C-reactive protein, and cardiovascular disease: moving past the marker versus mediator debate. 2014, Am Heart Assoc.
40. Harris, W.S., n-3 fatty acids and serum lipoproteins: human studies. The American journal of clinical nutrition, 1997. 65(5): p. 1645S-1654S.
41. Geelen, A., et al., Antiarrhythmic effects of n-3 fatty acids: evidence from human studies. Current opinion in lipidology, 2004. 15(1): p. 25-30.
42. Calder, P.C., Polyunsaturated fatty acids, inflammation, and immunity. Lipids, 2001. 36(9): p. 1007-1024.
43. Oster, P., et al., Blood pressure and adipose tissue linoleic acid. Research in Experimental Medicine, 1979. 175(3): p. 287-291.
44. Miettinen, T., et al., Fatty-acid composition of serum lipids predicts myocardial infarction. Br Med J (Clin Res Ed), 1982. 285(6347): p. 993-996.
45. Berry, E.M. and J. Hirsch, Does dietary linolenic acid influence blood pressure? The American journal of clinical nutrition, 1986. 44(3): p. 336-340.
46. Ciocca, S., et al., Lack of association between arterial blood pressure and erythrocyte fatty acid composition in an Italian population sample. Scandinavian journal of clinical and laboratory investigation, 1987. 47(2): p. 105-110.
47. Leng, G., et al., Relationship between plasma essential fatty acids and smoking, serum lipids, blood pressure and haemostatic and rheological factors. Prostaglandins, leukotrienes and essential fatty acids, 1994. 51(2): p. 101-108.
48. Simon, J.A., J. Fong, and J.T. Bernert Jr, Serum fatty acids and blood pressure. Hypertension, 1996. 27(2): p. 303-307.
49. Kritchevsky, D., Stearic acid metabolism and atherogenesis: history. The American journal of clinical nutrition, 1994. 60(6): p. 997S-1001S.
50. Grundy, S.M., Influence of stearic acid on cholesterol metabolism relative to other long-chain fatty acids. The American journal of clinical nutrition, 1994. 60(6): p. 986S-990S.
51. Goodnight Jr, S.H., et al., Polyunsaturated fatty acids, hyperlipidemia, and thrombosis. Arteriosclerosis: An Official Journal of the American Heart Association, Inc., 1982. 2(2): p. 87-113.
52. CAMBIEN, F., et al., An epidemiologic appraisal of the associations between the fatty acids esterifying serum cholesterol and some cardiovascular risk factors in middle-aged men. American journal of epidemiology, 1988. 127(1): p. 75-86.
53. Jin, J.-L., Y.-L. Guo, and J.-J. Li, Plasma free fatty acids in relation with the severity of coronary artery disease in non-diabetics: a Gensini score assessment. IJC Metabolic & Endocrine, 2017. 14: p. 48-52.
54. Semenkovich, C.F., Fatty acid metabolism and vascular disease. Trends in cardiovascular medicine, 2004. 14(2): p. 72-76.
55. Arsenault, B.J., et al., The hypertriglyceridemic-waist phenotype and the risk of coronary artery disease: results from the EPIC-Norfolk prospective population study. Cmaj, 2010. 182(13): p. 1427-1432.
56. Wallhaus, T.R., et al., Myocardial free fatty acid and glucose use after carvedilol treatment in patients with congestive heart failure. Circulation, 2001. 103(20): p. 2441-2446.
57. Murray, A.J., et al., Uncoupling proteins in human heart. The Lancet, 2004. 364(9447): p. 1786-1788.
58. Ginsberg, H.N., Insulin resistance and cardiovascular disease. The Journal of clinical investigation, 2000. 106(4): p. 453-458.
59. Keys, A., J.T. Anderson, and F. Grande, Serum cholesterol response to changes in the diet: IV. Particular saturated fatty acids in the diet. Metabolism, 1965. 14(7): p. 776-787.
60. Hegsted, D., et al., Quantitative effects of dietary fat on serum cholesterol in man. The American journal of clinical nutrition, 1965. 17(5): p. 281-295.
61. Mensink, R.P. and M.B. Katan, Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arteriosclerosis and thrombosis: a journal of vascular biology, 1992. 12(8): p. 911-919.
62. Yu, S., et al., Plasma cholesterol-predictive equations demonstrate that stearic acid is neutral and monounsaturated fatty acids are hypocholesterolemic. The American journal of clinical nutrition, 1995. 61(5): p. 1129-1139.
63. Kurisu, S., et al., Effects of lipid-lowering therapy with strong statin on serum polyunsaturated fatty acid levels in patients with coronary artery disease. Heart and vessels, 2013. 28(1): p. 34-38.
64. Nozue, T. and I. Michishita, Statin treatment alters serum n-3 to n-6 polyunsaturated fatty acids ratio in patients with dyslipidemia. Lipids in health and disease, 2015. 14(1): p. 67.
65. Nakamura, N., et al., Effect of HMG-CoA reductase inhibitors on plasma polyunsaturated fatty acid concentrations in patients with hyperlipidemia. International Journal of Clinical and Laboratory Research, 1998. 28(3): p. 192.
66. Jula, A., et al., Effects of diet and simvastatin on fatty acid composition in hypercholesterolemic men: a randomized controlled trial. Arteriosclerosis, thrombosis, and vascular biology, 2005. 25(9): p. 1952-1959.
67. Sahebkar, A., et al., Statin therapy and plasma free fatty acids: a systematic review and meta‐analysis of controlled clinical trials. British journal of clinical pharmacology, 2016. 81(5): p. 807-818.
68. Tanko, L.B., et al., Enlarged waist combined with elevated triglycerides is a strong predictor of accelerated atherogenesis and related cardiovascular mortality in postmenopausal women. Circulation, 2005. 111(15): p. 1883-1890.
69. Scapagnini, G., et al., Dose response biology of resveratrol in obesity. Journal of cell communication and signaling, 2014. 8(4): p. 385-391.
70. Arner, P. and M. Rydén, Fatty acids, obesity and insulin resistance. Obesity facts, 2015. 8(2): p. 147-155.
71. Raatz, S., et al., Relationship of the reported intakes of fat and fatty acids to body weight in US adults. Nutrients, 2017. 9(5): p. 438.

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