The effect of marine n-3 polyunsaturated fatty acids on cardiac autonomic and hemodynamic function in patients with psoriatic arthritis: a randomised, double-blind, placebo-controlled trial

Salome Kristensen, Erik Berg Schmidt, Annette Schlemmer, Claus Rasmussen, Esther Lindgreen, Martin Berg Johansen, Jeppe Hagstrup Christensen, Salome Kristensen, Erik Berg Schmidt, Annette Schlemmer, Claus Rasmussen, Esther Lindgreen, Martin Berg Johansen, Jeppe Hagstrup Christensen

Abstract

Background: The aim of this study was to investigate the effect of marine n-3 polyunsaturated fatty acids (PUFA) on cardiac autonomic function and vascular function in patients with psoriatic arthritis.

Methods: The study was conducted as a randomized, double-blind, placebo-controlled trial, where 145 patients with psoriatic arthritis were supplemented with 3 g of n-3 PUFA or olive oil (control) daily for 24 weeks. Blood pressure, heart rate, heart rate variability (HRV), central blood pressure, pulse wave velocity (PWV) and fatty acid composition of granulocytes, were determined at baseline and after supplementation.

Results: At baseline we found a significant difference in the mean of all normal RR intervals (inverse of heart rate, vary from beat to beat) when comparing subjects with the highest vs the lowest fish intake (p = 0.03). After supplementation for 24 weeks there was a trend towards an increase in RR (p = 0.13) and decrease in heart rate (p = 0.12) comparing the n-3 PUFA group with the control group. However, per-protocol analysis showed significantly increased RR (p = 0.01) and lowered heart rate (p = 0.01) in the n-3 PUFA supplemented patients compared with controls. Blood pressure, PWV and Central blood pressure did not change after supplementation with n-3 PUFA. Adjustment for disease activity and conventional cardiovascular risk factors did not change the results.

Conclusions: Marine n-3 PUFA increased RR intervals in patients with psoriatic arthritis which may suggest a protective effect of n-3 PUFA against cardiovascular disease in this population.

Trial registration: Clinicaltrials.gov Identifier: NCT01818804.

Keywords: Arterial stiffness; Cardiac autonomic function; Heart rate variability; Psoriatic arthritis; Pulse wave velocity; n-3 PUFA.

Figures

Fig. 1
Fig. 1
Flow diagram of the study participants
Fig. 2
Fig. 2
The relation between baseline RR (ms) and fish intake presented in tertiles. Footnote: RR: Mean of all normal RR-intervals in HRV recording; *: Significant difference in RR between the lower and the upper tertile
Fig. 3
Fig. 3
The relation between baseline RR (ms) and content of DHA in granulocytes presented in tertiles. Footnote: HRV: Heart Rate Variability; RR: Mean of all normal RR-intervals in HRV recording; DHA: docosahexaenoic acid; *: Significant difference in RR between the lower and the upper tertile

References

    1. Gelfand JM, Gladman DD, Mease PJ, Smith N, Margolis DJ, Nijsten T, Stern RS, Feldman SR, Rolstad T. Epidemiology of psoriatic arthritis in the population of the United States. J Am Acad Dermatol. 2005;53(4):573–7. doi: 10.1016/j.jaad.2005.03.046.
    1. Shbeeb M, Uramoto KM, Gibson LE, O’Fallon WM, Gabriel SE. The epidemiology of psoriatic arthritis in Olmsted County, Minnesota, USA, 1982–1991. J Rheumatol. 2000;27(5):1247–50.
    1. Wilson FC, Icen M, Crowson CS, McEvoy MT, Gabriel SE, Kremers HM. Incidence and clinical predictors of psoriatic arthritis in patients with psoriasis: a population-based study. Arthritis Rheum. 2009;61(2):233–9. doi: 10.1002/art.24172.
    1. Han C, Robinson DW, Jr, Hackett MV, Paramore LC, Fraeman KH, Bala MV. Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. J Rheumatol. 2006;33(11):2167–72.
    1. Ahlehoff O, Gislason GH, Charlot M, Jorgensen CH, Lindhardsen J, Olesen JB, Abildstrom SZ, Skov L, Torp-Pedersen C, Hansen PR. Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study. J Intern Med. 2011;270(2):147–57. doi: 10.1111/j.1365-2796.2010.02310.x.
    1. Gladman DD, Ang M, Su L, Tom BD, Schentag CT, Farewell VT. Cardiovascular morbidity in psoriatic arthritis. Ann Rheum Dis. 2009;68(7):1131–5. doi: 10.1136/ard.2008.094839.
    1. Kimhi O, Caspi D, Bornstein NM, Maharshak N, Gur A, Arbel Y, Comaneshter D, Paran D, Wigler I, Levartovsky D, Berliner S, Elkayam O. Prevalence and risk factors of atherosclerosis in patients with psoriatic arthritis. Semin Arthritis Rheum. 2007;36(4):203–9. doi: 10.1016/j.semarthrit.2006.09.001.
    1. Bruchfeld A, Goldstein RS, Chavan S, Patel NB, Rosas-Ballina M, Kohn N, Qureshi AR, Tracey KJ. Whole blood cytokine attenuation by cholinergic agonists ex vivo and relationship to vagus nerve activity in rheumatoid arthritis. J Intern Med. 2010;268(1):94–101.
    1. Huston JM, Tracey KJ. The pulse of inflammation: heart rate variability, the cholinergic anti-inflammatory pathway and implications for therapy. J Intern Med. 2011;269(1):45–53. doi: 10.1111/j.1365-2796.2010.02321.x.
    1. Stein PK, Kleiger RE. Insights from the study of heart rate variability. Annu Rev Med. 1999;50:249–61. doi: 10.1146/annurev.med.50.1.249.
    1. Tsuji H, Larson MG, Venditti FJ, Jr, Manders ES, Evans JC, Feldman CL, Levy D. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation. 1996;94(11):2850–5. doi: 10.1161/01.CIR.94.11.2850.
    1. La Rovere MT, Bigger JT, Marcus FI, Mortara A, Schwartz PJ. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI. Lancet. 1998;351(9101):478–84. doi: 10.1016/S0140-6736(97)11144-8.
    1. Schwartz PJ. The autonomic nervous system and sudden death. Eur Hear J. 1998;19(Suppl F):F72–80.
    1. Barron HV, Lesh MD. Autonomic nervous system and sudden cardiac death. J Am Coll Cardiol. 1996;27(5):1053–60. doi: 10.1016/0735-1097(95)00615-X.
    1. Airaksinen KEJ. Autonomic mechanisms and sudden death after abrupt coronary occlusion. Ann Med. 1999;31(4):240–5. doi: 10.3109/07853899908995886.
    1. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, Ducimetiere P, Benetos A. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001;37(5):1236–41. doi: 10.1161/01.HYP.37.5.1236.
    1. Willum-Hansen T, Staessen JA, Torp-Pedersen C, Rasmussen S, Thijs L, Ibsen H, Jeppesen J. Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population. Circulation. 2006;113(5):664–70. doi: 10.1161/CIRCULATIONAHA.105.579342.
    1. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296(14):1735–41. doi: 10.1001/jama.296.14.1735.
    1. Gisondi P, Fantin F, Del Giglio M, Valbusa F, Marino F, Zamboni M, Girolomoni G. Chronic plaque psoriasis is associated with increased arterial stiffness. Dermatology. 2009;218(2):110–3. doi: 10.1159/000182256.
    1. Costa L, Caso F, D’Elia L, Atteno M, Peluso R, Del Puente A, Strazzullo P, Scarpa R. Psoriatic arthritis is associated with increased arterial stiffness in the absence of known cardiovascular risk factors: A case control study. Clin Rheumatol. 2012;31(4):711–5. doi: 10.1007/s10067-011-1892-1.
    1. De Caterina R. N-3 Fatty Acids in Cardiovascular Disease. N Engl J Med. 2011;364(25):2439–50. doi: 10.1056/NEJMra1008153.
    1. Calder PC. Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance. Biochim Biophys Acta. 2014;1851(4):469–84. doi: 10.1016/j.bbalip.2014.08.010.
    1. Christensen JH, Gustenhoff P, Korup E, Aarøe J, Toft E, Møller J, Rasmussen K, Dyerberg J, Schmidt EB. Effect of fish oil on heart rate variability in survivors of myocardial infarction: a double blind randomised controlled trial. BMJ. 1996;312(7032):677–8. doi: 10.1136/bmj.312.7032.677.
    1. Saravanan P, Davidson NC, Schmidt EB, Calder PC. Cardiovascular effects of marine omega-3 fatty acids. Lancet. 2010;376(9740):540–50. doi: 10.1016/S0140-6736(10)60445-X.
    1. Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H. Classification criteria for psoriatic arthritis: Development of new criteria from a large international study. Arthritis Rheum. 2006;54(8):2665–73. doi: 10.1002/art.21972.
    1. Maksymowych WP, Mallon C, Morrow S, Shojania K, Olszynski WP, Wong RL, Sampalis J, Conner-Spady B. Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index. Ann Rheum Dis. 2009;68(6):948–53. doi: 10.1136/ard.2007.084244.
    1. Asmar R, Benetos A, Topouchian J, Laurent P, Pannier B, Brisac AM, Target R, Levy B. Assessment of arterial distensibility by automatic pulse wave velocity measurement. Validation and clinical application studies. Hypertension. 1995;26(3):485–90. doi: 10.1161/01.HYP.26.3.485.
    1. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H, A. European Network for Non-invasive Investigation of Large Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Hear J. 2006;27(21):2588–605. doi: 10.1093/eurheartj/ehl254.
    1. Van Bortel LM, Laurent S, Boutouyrie P, Chowienczyk P, Cruickshank JK, De Backer T, Filipovsky J, Huybrechts S, Mattace-Raso FUS, Protogerou AD, Schillaci G, Segers P, Vermeersch S, Weber T. Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens. 2012;30(3):445–8. doi: 10.1097/HJH.0b013e32834fa8b0.
    1. Dzeko M, Peters CD, Kjaergaard KD, Jensen JD, Jespersen B. Aortic pulse wave velocity results depend on which carotid artery is used for the measurements. J Hypertens. 2013;31(1):117–22. doi: 10.1097/HJH.0b013e32835b051b.
    1. Chen C-H, Nevo E, Fetics B, Pak PH, Yin FCP, Maughan WL, Kass DA. Estimation of Central Aortic Pressure Waveform by Mathematical Transformation of Radial Tonometry Pressure : Validation of Generalized Transfer Function. Circulation. 1997;95(7):1827–36. doi: 10.1161/01.CIR.95.7.1827.
    1. Pauca AL, O’Rourke MF, Kon ND. Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform. Hypertension. 2001;38(4):932–7. doi: 10.1161/hy1001.096106.
    1. Syngle A, Verma I, Krishan P, Garg N, Syngle V. Disease-modifying anti-rheumatic drugs improve autonomic neuropathy in arthritis: DIANA study. Clin Rheumatol. 2014;34(7):1233–41.
    1. Janse van Rensburg DC, Ker JA, Grant CC, Fletcher L. Effect of exercise on cardiac autonomic function in females with rheumatoid arthritis. Clin Rheumatol. 2012;31(8):1155–62. doi: 10.1007/s10067-012-1985-5.
    1. Task Force of the European Society of Cardiology; t. N. A. S. Electrophysiology Heart Rate Variability : Standards of Measurement, Physiological Interpretation, and Clinical Use. Circulation. 1996;93(5):1043–65. doi: 10.1161/01.CIR.93.5.1043.
    1. Kleiger RE, Miller JP, Bigger JT, Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol. 1987;59(4):256–62. doi: 10.1016/0002-9149(87)90795-8.
    1. La Rovere MT, Christensen JH. The autonomic nervous system and cardiovascular disease: role of n-3 PUFAs. Vascul Pharmacol. 2015;71:1–10. doi: 10.1016/j.vph.2015.02.005.
    1. Christensen JH. Omega-3 polyunsaturated Fatty acids and heart rate variability. Front Physiol. 2011;2:84. doi: 10.3389/fphys.2011.00084.
    1. Mozaffarian D, Geelen A, Brouwer IA, Geleijnse JM, Zock PL, Katan MB. Effect of fish oil on heart rate in humans: a meta-analysis of randomized controlled trials. Circulation. 2005;112(13):1945–52. doi: 10.1161/CIRCULATIONAHA.105.556886.
    1. Dallongeville J, Yarnell J, Ducimetière P, Arveiler D, Ferfières J, Montaye M, Luc G, Evans A, Bingham A, Hass B, Ruidavets JB, Amouyel P. Fish consumption is associated with lower heart rates. Circulation. 2003;108(7):820–5. doi: 10.1161/01.CIR.0000084542.64687.97.
    1. Palatini P, Julius S. Elevated Heart Rate: A Major Risk Factor for Cardiovascular Disease. Clin Exp Hypertens. 2004;26:637–44. doi: 10.1081/CEH-200031959.
    1. La Rovere MT, Staszewsky L, Barlera S, Maestri R, Mezzani A, Midi P, Marchioli R, Maggioni AP, Tognoni G, Tavazzi L, Latini R. n-3PUFA and Holter-derived autonomic variables in patients with heart failure: data from the Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza Cardiaca (GISSI-HF) Holter substudy. Heart Rhythm. 2013;10(2):226–32. doi: 10.1016/j.hrthm.2012.10.035.
    1. Billman GE. Heart Rate Variability ? A Historical Perspective. Front Physiol. 2011;2(November):1–13.
    1. Christensen JH, Schmidt EB. Autonomic nervous system, heart rate variability and n-3 fatty acids. J Cardiovasc Med. 2007;8 Suppl 1:S19–22. doi: 10.2459/01.JCM.0000289276.10675.a1.
    1. Grimsgaard S, Bønaa KH, Hansen JB, Myhre ES. Effects of highly purified eicosapentaenoic acid and docosahexaenoic acid on hemodynamics in humans. Am J Clin Nutr. 1998;68(1):52–9.
    1. Innis SM. Dietary (n-3) fatty acids and brain development. J Nutr. 2007;137(4):855–9.
    1. Helliwell PS. Assessment of disease activity in psoriatic arthritis. 2015;33(5 Suppl 93):S44–7.
    1. Stojanovich L. Autonomic dysfunction in autoimmune rheumatic disease. Autoimmun Rev. 2009;8(7):569–72. doi: 10.1016/j.autrev.2009.01.018.
    1. Gaydukova I, Rebrov A, Nikitina N, Poddubnyy D. Decreased heart rate variability in patients with psoriatic arthritis. Clin Rheumatol. 2012;31(9):1377–81.
    1. Proietti I, Raimondi G, Skroza N, Pampena R, Bernardini N, La Viola G, Nicolucci F, Tolino E, Zuber S, Scordamaglia B, Balduzzi V, Soccodato V, Potenza C. Cardiovascular Risk in Psoriatic Patients Detected by Heart Rate Variability (HRV) Analysis. Drug Dev Res. 2014;75:S81–4. doi: 10.1002/ddr.21204.
    1. Madsen T, Christensen JH, Toft E, Schmidt EB. C-reactive protein is associated with heart rate variability. Ann Noninvasive Electrocardiol. 2007;12(3):216–22. doi: 10.1111/j.1542-474X.2007.00164.x.
    1. Sloan RP, Mccreath H, Tracey KJ, Sidney S, Liu K, Seeman T. RR Interval Variability Is Inversely Related to Inflammatory Markers : The CARDIA Study. Mol Med. 2007;13(3–4):178–84.
    1. Spiegel TM, King W, Weiner SR, Paulus HE. Measuring disease activity: comparison of joint tenderness, swelling, and ultrasonography in rheumatoid arthritis. Arthritis Rheum. 1987;30:1283–8. doi: 10.1002/art.1780301111.
    1. Daunt AO, Cox NL, Robertson JC, Cawley MI. Indices of disease activity in psoriatic arthritis. J R Soc Med. 1987;80:556–8.
    1. Coates L. Outcome Measures in Psoriatic Arthritis. Rheum Dis Clin North Am. 2015;41(4):699–710. doi: 10.1016/j.rdc.2015.07.009.
    1. Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation. 1993;88(2):523–33. doi: 10.1161/01.CIR.88.2.523.
    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(7):974–80. doi: 10.1017/S0007114511002819.
    1. Monahan KD, Feehan RP, Blaha C, McLaughlin DJ. Effect of omega‐3 polyunsaturated fatty acid supplementation on central arterial stiffness and arterial wave reflections in young and older healthy adults. Physiol Rep. 2015;3(6):e12438. doi: 10.14814/phy2.12438.
    1. Booth AD, Wallace S, McEniery CM, Brown J, Jayne DR, Wilkinson IB. Inflammation and arterial stiffness in systemic vasculitis: a model of vascular inflammation. Arthritis Rheum. 2004;50(2):581–8. doi: 10.1002/art.20002.
    1. Provan SA, Semb AG, Hisdal J, Stranden E, Agewall S, Dagfinrud H, Angel K, Atar D, Kvien TK. Remission is the goal for cardiovascular risk management in patients with rheumatoid arthritis: a cross-sectional comparative study. Ann Rheum Dis. 2011;70(5):812–7. doi: 10.1136/ard.2010.141523.
    1. Kremer JM, Lawrence DA, Jubiz W, DiGiacomo R, Rynes R, Bartholomew LE, Sherman M. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects. Arthritis Rheum. 1990;33(6):810–20. doi: 10.1002/art.1780330607.
    1. Kirkegaard E, Svensson M, Strandhave C, Schmidt EB, Jorgensen KA, Christensen JH. Marine n-3 fatty acids, atrial fibrillation and QT interval in haemodialysis patients. Br J Nutr. 2012;107:903–9. doi: 10.1017/S0007114511003771.
    1. McLennan PL. Relative effects of dietary saturated, monounsaturated, and polyunsaturated fatty acids on cardiac arrhythmias in rats. Am J Clin Nutr. 1993;57(2):207–12.
    1. Knudsen VK, Matthiessen J, Biltoft-Jensen A, Sorensen MR, Groth MV, Trolle E, Christensen T, Fagt S. Identifying dietary patterns and associated health-related lifestyle factors in the adult Danish population. Eur J Clin Nutr. 2014;68(6):736–40. doi: 10.1038/ejcn.2014.38.

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