Long chain n-3 polyunsaturated fatty acids and vascular function in patients with chronic kidney disease and healthy subjects: a cross-sectional and comparative study

Morten Borg, My Svensson, Johan V Povlsen, Erik B Schmidt, Christian Aalkjær, Jeppe H Christensen, Per Ivarsen, Morten Borg, My Svensson, Johan V Povlsen, Erik B Schmidt, Christian Aalkjær, Jeppe H Christensen, Per Ivarsen

Abstract

Background: Patients with chronic kidney disease have a markedly increased cardiovascular mortality compared with the general population. Long chain n-3 polyunsaturated fatty acids have been suggested to possess cardioprotective properties. This cross-sectional and comparative study evaluated correlations between hemodynamic measurements, resistance artery function and fish consumption to the content of long chain n-3 polyunsaturated fatty acids in adipose tissue, a long-term marker of seafood intake.

Methods: Seventeen patients with chronic kidney disease stage 5 + 5d and 27 healthy kidney donors were evaluated with hemodynamic measurements before surgery; from these subjects, 11 patients and 11 healthy subjects had vasodilator properties of subcutaneous resistance arteries examined. The measurements were correlated to adipose tissue n-3 polyunsaturated fatty acids. Information on fish intake was obtained from a dietary questionnaire and compared with adipose tissue n-3 polyunsaturated fatty acids.

Results: Fish intake and the content of n-3 polyunsaturated fatty acids in adipose tissue did not differ between patients and controls. n-3 polyunsaturated fatty acid levels in adipose tissue were positively correlated to systemic vascular resistance index; (r = 0.44; p = 0.07 and r = 0.62; p < 0.05, chronic kidney disease and healthy subjects respectively) and negatively correlated to cardiac output index (r = -0.69; p < 0.01 and r = -0.50; p < 0.05, chronic kidney disease and healthy subjects respectively). No correlation was observed between n-3 polyunsaturated fatty acid levels in adipose tissue and vasodilator properties in resistance arteries. n-3 PUFA content in adipose tissue increased with increasing self-reported fish intake.

Conclusions: The correlations found, suggest a role for n-3 polyunsaturated fatty acids in hemodynamic properties. However, this is apparently not due to changes in intrinsic properties of the resistance arteries as no correlation was found to n-3 polyunsaturated fatty acids.

Keywords: Chronic kidney disease; Hemodynamic; Polyunsaturated fatty acids; Resistance artery.

Figures

Fig. 1
Fig. 1
The participants’ fish score divided into three groups as low (2–5), moderate (6–8) and high (9–12). Each group’s content of n-3 PUFA in adipose tissue. The 3 groups significantly differ from each other (Box plot; (p < 0.01); Kruskal-Wallis test)
Fig. 2
Fig. 2
The association between n-3 PUFA in adipose tissue and systemic vascular resistance index. Chronic kidney disease patients (r = 0.44; p = 0.07) (red symbols/red dash line, fitted line and 95% confidence interval); healthy subjects (r = 0.62; p < 0.05) (green symbols and solid line). Regression formulas were y = 8.0*x + 43.0 and y = 6.3*x + 40.0 for CKD patients and healthy subjects, respectively
Fig. 3
Fig. 3
The association between n-3 PUFA in adipose tissue and cardiac output index. Chronic kidney disease patients (r = −0.69; p < 0.01) (red symbols/red dash line, fitted line and 95% confidence interval); healthy subjects (r = −0.50; p < 0.05) (green symbols and green solid line). Regression formulas were y = −0.79*x + 2.06 and y = −0.68*x + 1.87 for ESRD patients and control subjects, respectively
Fig. 4
Fig. 4
The association between n-3 PUFA in adipose tissue and acetylcholine-induced vasodilator response in resistance arteries. Chronic kidney disease patients red symbols/red dash line, fitted line and 95% coefficient interval); healthy subjects (green symbols and green solid line). Regression formulas were y = −0.07*x + 6.86 and y = −0.11*x + 6.81 for ESRD patients and control subjects, respectively

References

    1. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–305. doi: 10.1056/NEJMoa041031.
    1. Roberts MA, Polkinghorne KR, McDonald SP, Ierino FL. Secular trends in cardiovascular mortality rates of patients receiving dialysis compared with the general population. Am J Kidney Dis. 2011;58:64–72. doi: 10.1053/j.ajkd.2011.01.024.
    1. Swaminathan S, Shah SV. Novel inflammatory mechanisms of accelerated atherosclerosis in kidney disease. Kidney Int. 2011;80:453–63. doi: 10.1038/ki.2011.178.
    1. Shanahan CM. Mechanisms of vascular calcification in CKD-evidence for premature ageing? Nat Rev Nephrol. 2013;9:661–70. doi: 10.1038/nrneph.2013.176.
    1. Meier-Kriesche HU, Schold JD, Srinivas TR, Reed A, Kaplan B. Kidney transplantation halts cardiovascular disease progression in patients with end-stage renal disease. Am J Transplant. 2004;4:1662–8. doi: 10.1111/j.1600-6143.2004.00573.x.
    1. Guerin AP, Pannier B, Metivier F, Marchais SJ, London GM. Assessment and significance of arterial stiffness in patients with chronic kidney disease. Curr Opin Nephrol Hypertens. 2008;17:635–41. doi: 10.1097/MNH.0b013e32830dcd5c.
    1. De CR. n-3 fatty acids in cardiovascular disease. N Engl J Med. 2011;364:2439–50. doi: 10.1056/NEJMra1008153.
    1. Saravanan P, Davidson NC, Schmidt EB, Calder PC. Cardiovascular effects of marine omega-3 fatty acids. Lancet. 2010;376:540–50. doi: 10.1016/S0140-6736(10)60445-X.
    1. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet. 1999;354:447–55. doi: 10.1016/S0140-6736(99)07072-5.
    1. Mozaffarian D, Micha R, Wallace S. Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Med. 2010;7:e1000252. doi: 10.1371/journal.pmed.1000252.
    1. Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA. 2012;308:1024–33. doi: 10.1001/2012.jama.11374.
    1. Hjerkinn EM, Abdelnoor M, Breivik L, Bergengen L, Ellingsen I, Seljeflot I, et al. Effect of diet or very long chain omega-3 fatty acids on progression of atherosclerosis, evaluated by carotid plaques, intima-media thickness and by pulse wave propagation in elderly men with hypercholesterolaemia. Eur J Cardiovasc Prev Rehabil. 2006;13:325–33.
    1. Root M, Collier SR, Zwetsloot KA, West KL, McGinn MC. A randomized trial of fish oil omega-3 fatty acids on arterial health, inflammation, and metabolic syndrome in a young healthy population. Nutr J. 2013;12:40. doi: 10.1186/1475-2891-12-40.
    1. Takaki A, Umemoto S, Ono K, Seki K, Ryoke T, Fujii A, et al. Add-on therapy of EPA reduces oxidative stress and inhibits the progression of aortic stiffness in patients with coronary artery disease and statin therapy: a randomized controlled study. J Atheroscler Thromb. 2011;18:857–66. doi: 10.5551/jat.7260.
    1. Pase MP, Grima NA, Sarris J. Do long-chain n-3 fatty acids reduce arterial stiffness? A meta-analysis of randomised controlled trials. Br J Nutr. 2011;106:974–80. doi: 10.1017/S0007114511002819.
    1. Chong MF, Lockyer S, Saunders CJ, Lovegrove JA. Long chain n-3 PUFA-rich meal reduced postprandial measures of arterial stiffness. Clin Nutr. 2010;29:678–81. doi: 10.1016/j.clnu.2010.02.001.
    1. Tousoulis D, Plastiras A, Siasos G, Oikonomou E, Verveniotis A, Kokkou E, et al. Omega-3 PUFAs improved endothelial function and arterial stiffness with a parallel antiinflammatory effect in adults with metabolic syndrome. Atherosclerosis. 2014;232:10–6. doi: 10.1016/j.atherosclerosis.2013.10.014.
    1. Sanders TA, Hall WL, Maniou Z, Lewis F, Seed PT, Chowienczyk PJ. Effect of low doses of long-chain n-3 PUFAs on endothelial function and arterial stiffness: a randomized controlled trial. Am J Clin Nutr. 2011;94:973–80. doi: 10.3945/ajcn.111.018036.
    1. Luksha L, Agewall S, Kublickiene K. Endothelium-derived hyperpolarizing factor in vascular physiology and cardiovascular disease. Atherosclerosis. 2009;202:330–44. doi: 10.1016/j.atherosclerosis.2008.06.008.
    1. Aalkjaer C, Pedersen EB, Danielsen H, Fjeldborg O, Jespersen B, Kjaer T, et al. Morphological and functional characteristics of isolated resistance vessels in advanced uremia. Clin Sci (Lond) 1986;71:657–663. doi: 10.1042/cs0710657.
    1. Morris ST, McMurray JJ, Spiers A, Jardine AG. Impaired endothelial function in isolated human uremic resistance arteries. Kidney Int. 2001;60:1077–1082. doi: 10.1046/j.1523-1755.2001.0600031077.x.
    1. Luksha N, Luksha L, Carrero JJ, Hammarqvist F, Stenvinkel P, et al. Impaired resistance artery function in patients with end-stage renal disease. Clin Sci (Lond) 2011;120:525–536. doi: 10.1042/CS20100277.
    1. Luksha L, Stenvinkel P, Hammarqvist F, Carrero JJ, Davidge ST, et al. Mechanisms of endothelial dysfunction in resistance arteries from patients with end-stage renal disease. PLoS One. 2012;7:e36056. doi: 10.1371/journal.pone.0036056.
    1. Borg MK, Ivarsen P, Brondum E, Povlsen JV, Aalkjaer C. Hemodynamics and function of resistance arteries in healthy persons and end stage renal disease patients. PLoS One. 2014;9:e94638. doi: 10.1371/journal.pone.0094638.
    1. Halpern W, Mulvany MJ. Tension responses to small length changes of vascular smooth muscle cells [proceedings] J Physiol. 1977;265:21P–3P.
    1. Christensen JH, Skou HA, Fog L, Hansen V, Vesterlund T, Dyerberg J, et al. Marine n-3 fatty acids, wine intake, and heart rate variability in patients referred for coronary angiography. Circulation. 2001;103:651–7. doi: 10.1161/01.CIR.103.5.651.
    1. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37:911–7. doi: 10.1139/o59-099.
    1. Christoffersen SW, Glass RL. Preparation of milk fat methyl esters by alcoholysis in an essentially non-alcoholic solution. J Dairy Sci. 1969;52:1289–90. doi: 10.3168/jds.S0022-0302(69)86739-1.
    1. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461–70. doi: 10.7326/0003-4819-130-6-199903160-00002.
    1. Institute for digital research and education, UCLA: STATA FAQ: . Accessed 1 May 2014.
    1. Marckmann P, Lassen A, Haraldsdottir J, Sandstrom B. Biomarkers of habitual fish intake in adipose tissue. Am J Clin Nutr. 1995;62:956–9.
    1. Friedman AN, Moe SM, Perkins SM, Li Y, Watkins BA. Fish consumption and omega-3 fatty acid status and determinants in long-term hemodialysis. Am J Kidney Dis. 2006;47:1064–71. doi: 10.1053/j.ajkd.2006.03.033.
    1. Madsen T, Christensen JH, Svensson M, Witt PM, Toft E, Schmidt EB. Marine n-3 polyunsaturated fatty acids in patients with end-stage renal failure and in subjects without kidney disease: a comparative study. J Ren Nutr. 2011;21:169–75. doi: 10.1053/j.jrn.2010.06.020.
    1. An WS, Kim SE, Kim KH, Lee S, Park Y, Kim HJ, et al. Comparison of fatty acid contents of erythrocyte membrane in hemodialysis and peritoneal dialysis patients. J Ren Nutr. 2009;19:267–74. doi: 10.1053/j.jrn.2009.01.027.
    1. Nikolakakis N, Kounali D, Tornaritis M, Anastassou A, Papadakis E, Kassotakis G, et al. Adipose tissue fatty acid composition, serum lipids, and serum alpha-tocopherol in continuous ambulatory peritoneal dialysis patients living on the island of Crete. Perit Dial Int. 1999;19:154–9.
    1. Mekki K, Remaoun M, Belleville J, Bouchenak M. Hemodialysis duration impairs food intake and nutritional parameters in chronic kidney disease patients. Int Urol Nephrol. 2012;44:237–44. doi: 10.1007/s11255-010-9875-8.
    1. Svensson M, Schmidt EB, Jorgensen 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. doi: 10.1093/ndt/gfn180.
    1. Rontoyanni VG, Hall WL, Pombo-Rodrigues S, Appleton A, Chung R, Sanders TA. A comparison of the changes in cardiac output and systemic vascular resistance during exercise following high-fat meals containing DHA or EPA. Br J Nutr. 2012;108:492–9. doi: 10.1017/S0007114511005721.
    1. Kattus AA, Rivin AU, Cohen A, Sofio GS. Cardiac output and central volume as determined by dye dilution curves; resting values in normal subjects and patients with cardiovascular disease. Circulation. 1955;11:447–55. doi: 10.1161/01.CIR.11.3.447.
    1. Zebrowska A, Mizia-Stec K, Mizia M, Gasior Z, Poprzecki S. Omega-3 fatty acids supplementation improves endothelial function and maximal oxygen uptake in endurance-trained athletes. Eur J Sport Sci 2014;1–10.
    1. Jefimow M, Wojciechowski MS. Effect of dietary fatty acids on metabolic rate and nonshivering thermogenesis in golden hamsters. J Exp Zool A Ecol Genet Physiol. 2014;321:98–107. doi: 10.1002/jez.1840.
    1. Hamazaki K, Terashima Y, Itomura M, Sawazaki S, Inagaki H, Kuroda M, et al. The relationship between n-3 long-chain polyunsaturated fatty acids and pulse wave velocity in diabetic and non-diabetic patients under long-term hemodialysis. A horizontal study. Clin Nephrol. 2009;71:508–13. doi: 10.5414/CNP71508.
    1. Saijo Y, Utsugi M, Yoshioka E, Fukui T, Sata F, Nakagawa N, et al. Inflammation as a cardiovascular risk factor and pulse wave velocity as a marker of early-stage atherosclerosis in the Japanese population. Environ Health Prev Med. 2009;14:159–64. doi: 10.1007/s12199-009-0080-2.
    1. Terashima Y, Hamazaki K, Itomura M, Tomita S, Kuroda M, Hirata H, et al. Inverse association between docosahexaenoic acid and mortality in patients on hemodialysis during over 10 years. Hemodial Int. 2014;18:625–31. doi: 10.1111/hdi.12128.
    1. Svensson M, Schmidt EB, Jorgensen KA, Christensen JH. N-3 fatty acids as secondary prevention against cardiovascular events in patients who undergo chronic hemodialysis: a randomized, placebo-controlled intervention trial. Clin J Am Soc Nephrol. 2006;1:780–6. doi: 10.2215/CJN.00630206.
    1. MacLeod DC, Heagerty AM, Bund SJ, Lawal TS, Riemersma RA. Effect of dietary polyunsaturated fatty acids on contraction and relaxation of rat femoral resistance arteries. J Cardiovasc Pharmacol. 1994;23:92–8. doi: 10.1097/00005344-199401000-00012.

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