|Year : 2016 | Volume
| Issue : 4 | Page : 252-256
Does Omega-3 supplementation decrease carotid intima-media thickening in hemodialysis patients?
Mohammad Hossein Kajbaf1, Fariborz Khorvash2, Mojgan Mortazavi3, Shahrzad Shahidi3, Firoozeh Moeinzadeh3, Ziba Farajzadegan4, Shahnaz Amani Tirani5
1 Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Neurology; Isfahan Neurosciences Research Center, Al-Zahra Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Internal Medicine; Isfahan Kidney Diseases Research Center, Al-Zahra Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
4 Department of Community and Family Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
5 Isfahan Kidney Diseases Research Center, Al-Zahra Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
|Date of Web Publication||18-Oct-2016|
Department of Internal Medicine; Isfahan Kidney Diseases Research Center, Al-Zahra Research Institute, Isfahan University of Medical Sciences, Isfahan
Source of Support: None, Conflict of Interest: None
Objective: A randomized, double-blind, placebo-controlled clinical trial was performed to assess the effect of omega-3 supplementation (3 g/day) on atherosclerosis progression by measuring carotid intima-media thickness (cIMT) in hemodialysis (HD) patients.
Methods: A total of 54 HD patients were randomized into two groups: Intervention group (n = 27), in which patients were given 3 g/day omega-3 for 6 months and placebo group (n = 27), in which patients received placebo using the same administration protocol. All patients underwent a carotid artery ultrasound scan to measure cIMT at baseline and at 6 months.
Findings: cIMT decreased significantly in omega-3 group (0.79 ± 0.21 mm at baseline vs. 0.65 ± 0.18 mm at 6 months, P< 0.001). On the other hand, a nonsignificant increase in cIMT was seen in placebo group (0.75 ± 0.17 mm at baseline vs. 0.79 ± 0.17 mm at 6 months, P = 0.12). Moreover, cIMT was statistically significantly different between omega-3 and placebo groups at 6 months (P < 0.001). After 6 months, a statistically significant increase was observed in high-density lipoprotein level in omega-3 group compared to placebo group (P = 0.03). Urea reduction ratio was also statistically significantly higher in omega-3 than placebo group at 6 months (P = 0.03). No significant difference was observed in terms of other variables between the two groups.
Conclusion: These data suggested that omega-3 supplementation plays a protective role in the progression of atherosclerosis in HD patients.
Keywords: Cardiovascular disease; carotid intima-media thickness; hemodialysis; Omega-3
|How to cite this article:|
Kajbaf MH, Khorvash F, Mortazavi M, Shahidi S, Moeinzadeh F, Farajzadegan Z, Tirani SA. Does Omega-3 supplementation decrease carotid intima-media thickening in hemodialysis patients?. J Res Pharm Pract 2016;5:252-6
|How to cite this URL:|
Kajbaf MH, Khorvash F, Mortazavi M, Shahidi S, Moeinzadeh F, Farajzadegan Z, Tirani SA. Does Omega-3 supplementation decrease carotid intima-media thickening in hemodialysis patients?. J Res Pharm Pract [serial online] 2016 [cited 2019 Oct 15];5:252-6. Available from: http://www.jrpp.net/text.asp?2016/5/4/252/192451
| Introduction|| |
Cardiovascular disease (CVD) is the main cause of mortality in end-stage renal disease (ESRD) patients. Mortality of CVD in these patients is 10–20 times higher than general population.,, Some traditional risk factors ,, and some factors which are related to ESRD patients contribute to the high incidence of CVD among these patients.,, Accelerated atherosclerosis is the most important reason of dialysis patients' mortality and morbidity, although volume overload and left ventricular hypertrophy are also among the important factors related to cardiovascular mortality.
Carotid artery intima-media thickness (cIMT) measurement by ultrasound is a well-established index of atherosclerosis which predicts CVD in general population. Some studies have also reported that cIMT is associated with cardiovascular mortality in hemodialysis (HD) patients.,
Cardioprotective effects of fish oil and omega-3 polyunsaturated fatty acids have been proved. It has been suggested that omega-3 fatty acids decrease CVD through affecting lipid profiles, arrhythmias, inflammation, endothelial function, and platelet activity., Some studies also investigated the relationship between omega-3 and CVD in HD patients, but their results are controversial. A study by Vernaglione et al. showed that blood pressure was the only factor which was influenced by omega-3 supplementation in patients on long-term HD. Conversely, some studies have indicated that serum omega-3 fatty acids reduce CVD risk and its mortality in HD patients independently.,
The aim of the present study was to assess omega-3 supplementation role on cIMT as an important index of CVD in ESRD patients who receive HD.
| Methods|| |
This was a double-blind, placebo-controlled, randomized clinical trial carried out on HD patients who were attending Al-Zahra and Noor-and-Ali-Asghar hospitals affiliated with Isfahan University of Medical Sciences (IUMS), Isfahan, Iran. Patients more than 18 years of age who had received HD for at least 3 months and had not consumed omega-3 fatty acids during the past 3 months were included in the study. Exclusion criteria were the presence of malignancy or ongoing chemotherapy, steatorrhea history, prolonged prothrombin time or partial thromboplastin time, anticoagulation therapy, shifting to peritoneal dialysis, and kidney transplantation during the study. A total of 60 patients were enrolled in the study, in which 8 of them were excluded from the study. Research Ethics Committee of IUMS approved (Research project number: 292281) the study, and all patients signed a written informed consent form.
Three omega-3 capsules (1 g) (Zahravi Company, Tabriz, Iran) were administered for intervention group per day. Each omega-3 capsule contains 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA). Placebo group received an equal amount of placebo capsules (3 capsules/day) which were produced by the same company. Both patients and doctors were blinded to treatments.
All patients received HD as we have described before. Blood samples were collected on the day of ultrasonography. Serum levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides (TGs), albumin (Alb), calcium (Ca), and phosphate (P) were measured using autoanalyzer (BT 3000). Systolic and diastolic blood pressures were also measured by an internal medicine resident. Serum parathyroid hormone (PTH) level was measured by a gamma counter.
An expert neurologist blinded to treatments assessed cIMT using an ultrasound machine (ATL Ultramark 9) with 5–7 MHz probes before and after the intervention in both groups. Atherosclerosis was considered cIMT >1.2 mm. Two echogenic bright lines in the vessel wall were considered as intima and media lines. The distance between the main edges of the first line to the main edge of the second line of distal common carotid arteries was considered cIMT. All the patients managed for 6 months, and their vital signs, laboratory data, and drug complications such as nausea, vomiting, and hypertension were assessed. cIMT were re-evaluated for omega-3 and placebo groups by the same nephrologist.
All statistical analyses were done using Statistical Package for Social Sciences software (version 15.0, SPSS, Inc., Chicago, IL, USA). Quantitative data were expressed as mean ± standard deviation whereas qualitative data were presented by percentages. Normality of quantitative data was evaluated using Kolmogorov–Smirnov test and Q-Q plot; non-normal data were subjected to logarithmic transformation. Paired-sample t-test was used to compare means before and after intervention of different variables in omega-3 and placebo groups. Means of the study variables after intervention between omega-3 and placebo groups were compared using analysis of covariance, considering the baseline values as covariate. A two-tailed P < 0.05 was considered statistically significant.
| Results|| |
Of the sixty patients enrolled in the study, 52 fulfilled the inclusion criteria. All participants were randomized to omega-3 (n = 26) or placebo (n = 26) group and completed the study. There was no previous or current history of transient ischemic attacks or strokes in our patients. As shown in [Table 1], there were no significant differences between omega-3 and placebo groups in terms of demographic and clinical characteristics except for mean blood pressure which was significantly lower in placebo group than omega-3 group (P = 0.03) [Table 1].
|Table 1: General characteristics of patients in omega-3 and placebo groups|
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cIMT decreased significantly in omega-3 group at 6 months (0.79 ± 0.21 vs. 0.65 ± 0.18, P < 0.001). However, a nonsignificant increase in cIMT was observed in placebo group (0.75 ± 0.17 mm at baseline vs. 0.79 ± 0.17 mm at 6 months, P = 0.12) [Table 2]. Moreover, there was a significant difference in cIMT between omega-3 and placebo groups at 6 months (P < 0.001). HDL level increased significantly among HD patients after omega-3 intervention (33.34 ± 7.29 vs. 42.5 ± 8.98, P < 0.001). At 6 months, there was a significant difference on HDL level in omega-3 in comparison to placebo group (P = 0.03). No significant change was seen in total cholesterol, LDL, and TG level in omega-3 or placebo group. Urea reduction ratio (URR) changes were not significant in omega-3 and placebo groups after 6 months; however, URR was significantly higher in omega-3 group when compared to placebo group (P = 0.03). Our findings also showed that PTH increased significantly both in placebo (P = 0.02) and omega-3 groups (P < 0.001). However, there were no significant differences between the two groups at 6 months on PTH (P = 0.73). Serum phosphorus increased significantly after omega-3 intervention in HD patients (P = 0.005) while there were no significant differences between placebo and omega-3 groups after 6 months (P = 0.27). Plasma Alb decreased significantly in placebo group (P = 0.04); however, no significant changes were observed in omega-3 group (P = 0.78). In addition, a nonsignificant difference was seen in plasma Alb level between omega-3 and placebo groups at 6 months (P = 0.06).
|Table 2: Comparison of clinical variables at baseline and at 6 months between omega-3 and placebo groups|
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| Discussion|| |
CVD morbidity and mortality among dialysis patients are greatly higher than normal population, and half of all deaths among these patients are related to CVD.,, Increased cIMT is an important predictor of cardiovascular mortality in ESRD patients., Previous studies have reported that low levels of plasma omega-3 are related with a high incidence of CVD in normal population., In the current study, we assessed the role of omega-3 supplementation on cIMT in HD patients.
Few studies have reported that CVD risk factors are reduced after fish oil supplementation in HD patients.,, However, we could not find any study evaluated atherosclerosis progress in HD patients after omega-3 supplementation by cIMT. The results of the current study showed that HD patients' treatment with 3 g of omega-3 for 6 months improved cIMT. There was also a significant difference between omega-3 and placebo groups at 6 months in terms of cIMT.
The results of the present study showed that PTH increased in both placebo and omega-3 groups significantly at 6 months, although changes between omega-3 and placebo groups were not significant. The changes in PTH level have been resulted from phosphorus retention and low levels of calcium as others suggested.,
A 6-month treatment with omega-3 increased HDL levels in HD patients significantly. We also found a significant difference between omega-3 and placebo groups at the end of the study. Khajehdehi showed a significant increase in HDL level after supplementation with 1.5 g of omega-3. Treatment of CRF patients with 2.4 g of omega-3 also increased HDL in a study which was done by Svensson et al.
TG did not decrease significantly after omega-3 supplementation among HD patients in the current study. This is in accordance to a study which was done by Christensen et al. Treatment of 24 HD patients with 3.2 g/day of omega-3 had no significant effect on serum TG. In contrast, TG has decreased significantly in studies which have administered lower doses of omega-3., We assume that the effect of omega-3 on TG among HD patients is dose dependent. It explains why the administration of 3 g/day had no impact on TG level in HD patients. In addition, it has been indicated that higher baseline levels of TG is associated with its greater serum decline after omega-3 supplementation. No effect of omega-3 was observed on LDL and total cholesterol which is in direction to other studies.,
After 6 months of intervention, there was a significant difference on URR between placebo and omega-3 groups. There is an association between URR and clinical outcome; thus, it seems that HD patients' treatment with omega-3 improves HD adequacy in ESRD patients.
A number of studies have investigated the association between hypoalbuminemia and cardiac disease in ESRD patients.,, The exact mechanism of hypoalbuminemia in HD patients has not been detected; however, it is possibly a result of inflammation rather than protein malnutrition., Alb level decreased significantly in placebo group while no significant difference was seen in omega-3 group. Furthermore, plasma Alb was not significantly different between the two groups at 6 months.
In the present study, we showed that omega-3 supplementation improves cIMT in HD patients. Thus, omega-3 administration in these patients as a part of primary prevention strategy reduces atherosclerosis.
| Authors' Contribution|| |
All authors contributed in conducting the study concept and design, acquisition of data, analysis and interpretation of data. Mortazavi M, Kajbaf MH and Amani Tirani S contributed in drafting of the manuscript, revising the draft, and approval of the final version of the manuscript.
The authors are grateful to Zahravi Company for their cooperation and the help of Al-Zahra and Noor and Ali Asghar hospitals' staffs and HD wards in this study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Collins AJ, Li S, Ma JZ, Herzog C. Cardiovascular disease in end-stage renal disease patients. Am J Kidney Dis 2001;38 4 Suppl 1:S26-9.
Lindner A, Charra B, Sherrard DJ, Scribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med 1974;290:697-701.
Foley RN, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol 1998;9 12 Suppl: S16-23.
Moustapha A, Naso A, Nahlawi M, Gupta A, Arheart KL, Jacobsen DW, et al.
Prospective study of hyperhomocysteinemia as an adverse cardiovascular risk factor in end-stage renal disease. Circulation 1998;97:138-41.
Querfeld U, Salusky IB, Nelson P, Foley J, Fine RN. Hyperlipidemia in pediatric patients undergoing peritoneal dialysis. Pediatr Nephrol 1988;2:447-52.
Avram MM, Goldwasser P, Burrell DE, Antignani A, Fein PA, Mittman N. The uremic dyslipidemia: A cross-sectional and longitudinal study. Am J Kidney Dis 1992;20:324-35.
Ribeiro S, Ramos A, Brandão A, Rebelo JR, Guerra A, Resina C, et al.
Cardiac valve calcification in haemodialysis patients: Role of calcium-phosphate metabolism. Nephrol Dial Transplant 1998;13:2037-40.
Block GA, Port FK. Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: Recommendations for a change in management. Am J Kidney Dis 2000;35:1226-37.
Terman DS, Alfrey AC, Hammond WS, Donndelinger T, Ogden DA, Holmes JH. Cardiac calcification in uremia. A clinical, biochemical and pathologic study. Am J Med 1971;50:744-55.
Soubassi LP, Chiras TC, Papadakis ED, Poulos GD, Chaniotis DI, Tsapakidis IP, et al
. Incidence and risk factors of coronary heart disease in elderly patients on chronic hemodialysis. Int J Nephrol Urol 2006;38:795-800.
Kato A, Takita T, Maruyama Y, Kumagai H, Hishida A. Impact of carotid atherosclerosis on long-term mortality in chronic hemodialysis patients. Kidney Int 2003;64:1472-9.
Nishizawa Y, Shoji T, Maekawa K, Nagasue K, Okuno S, Kim M, et al.
Intima-media thickness of carotid artery predicts cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 2003;41 3 Suppl 1:S76-9.
Kromhout D, Yasuda S, Geleijnse JM, Shimokawa H. Fish oil and omega-3 fatty acids in cardiovascular disease: Do they really work? Eur Heart J 2012;33:436-43.
Din JN, Newby DE, Flapan AD. Omega 3 fatty acids and cardiovascular disease – Fishing for a natural treatment. BMJ 2004;328:30-5.
Vernaglione L, Cristofano C, Chimienti S. Omega-3 polyunsaturated fatty acids and proxies of cardiovascular disease in hemodialysis: A prospective cohort study. J Nephrol 2008;21:99-105.
Shoji T, Kakiya R, Hayashi T, Tsujimoto Y, Sonoda M, Shima H, et al.
Serum n-3 and n-6 polyunsaturated fatty acid profile as an independent predictor of cardiovascular events in hemodialysis patients. Am J Kidney Dis 2013;62:568-76.
Umemoto N, Ishii H, Kamoi D, Aoyama T, Sakakibara T, Takahashi H, et al.
Reverse association of omega-3/omega-6 polyunsaturated fatty acids ratios with carotid atherosclerosis in patients on hemodialysis. Atherosclerosis 2016;249:65-9.
Mortazavi M, Moeinzadeh F, Saadatnia M, Shahidi S, McGee JC, Minagar A. Effect of magnesium supplementation on carotid intima-media thickness and flow-mediated dilatation among hemodialysis patients: A double-blind, randomized, placebo-controlled trial. Eur Neurol 2013;69:309-16.
Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, et al.
Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000;342:1478-83.
Bloembergen WE. Cardiac disease in chronic uremia: Epidemiology. Adv Ren Replace Ther 1997;4:185-93.
Desbien AM, Chonchol M, Gnahn H, Sander D. Kidney function and progression of carotid intima-media thickness in a community study. Am J Kidney Dis 2008;51:584-93.
Kromhout D, Bosschieter EB, de Lezenne Coulander C. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985;312:1205-9.
Dietary supplementation with n-3 polyunsaturated fatty acids and Vitamin E after myocardial infarction: Results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 1999;354:447-55.
Ando M, Sanaka T, Nihei H. Eicosapentaenoic acid reduces plasma levels of remnant lipoproteins and prevents in vivo
peroxidation of LDL in dialysis patients. J Am Soc Nephrol 1999;10:2177-84.
Dionisio P, Caramello E, Bergia R, Valenti M, Cornella C, Pagni R, et al.
Atherogenic risk in patients undergoing regular dialysis treatment: Improvement of lipid pattern and lipoproteins by polyunsaturated omega-3 fatty acids. Nephrol Dial Transplant 1994;9:458.
Saifullah A, Watkins BA, Saha C, Li Y, Moe SM, Friedman AN. Oral fish oil supplementation raises blood omega-3 levels and lowers C-reactive protein in haemodialysis patients – A pilot study. Nephrol Dial Transplant 2007;22:3561-7.
Slatopolsky E, Delmez JA. Pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis 1994;23:229-36.
Goodman WG. Medical management of secondary hyperparathyroidism in chronic renal failure. Nephrol Dial Transplant 2003;18 Suppl 3:iii2-8.
Khajehdehi P. Lipid-lowering effect of polyunsaturated fatty acids in hemodialysis patients. J Ren Nutr 2000;10:191-5.
Svensson M, Schmidt EB, Jørgensen KA, Christensen JH. The effect of n-3 fatty acids on lipids and lipoproteins in patients treated with chronic haemodialysis: A randomized placebo-controlled intervention study. Nephrol Dial Transplant 2008;23:2918-24.
Christensen JH, Sølling J, Schmidt EB. The effect of n-3 fatty acids on plasma lipids and lipoproteins and blood pressure in patients with CRF. Am J Kidney Dis 2004;44:77-83.
Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: A systematic review. Atherosclerosis 2006;189:19-30.
Fiedler R, Mall M, Wand C, Osten B. Short-term administration of omega-3 fatty acids in hemodialysis patients with balanced lipid metabolism. J Ren Nutr 2005;15:253-6.
Owen WF Jr., Lew NL, Liu Y, Lowrie EG, Lazarus JM. The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis. N Engl J Med 1993;329:1001-6.
Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE. Hypoalbuminemia, cardiac morbidity, and mortality in end-stage renal disease. J Am Soc Nephrol 1996;7:728-36.
Cooper BA, Penne EL, Bartlett LH, Pollock CA. Protein malnutrition and hypoalbuminemia as predictors of vascular events and mortality in ESRD. Am J Kidney Dis 2004;43:61-6.
Stenvinkel P, Heimbürger O, Paultre F, Diczfalusy U, Wang T, Berglund L, et al.
Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int 1999;55:1899-911.
Beddhu S, Kaysen GA, Yan G, Sarnak M, Agodoa L, Ornt D, et al.
Association of serum albumin and atherosclerosis in chronic hemodialysis patients. Am J Kidney Dis 2002;40:721-7.
[Table 1], [Table 2]
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