Anti-TNFα therapy transiently improves high density lipoprotein cholesterol levels and microvascular endothelial function in patients with rheumatoid arthritis: a Pilot Study

BMC Musculoskeletal Disorders

George D Kitas³  Douglas Carroll¹  Tracey E Toms²  Jet J C S Veldhuijzen van Zanten¹  Aamer Sandoo¹ 

[1] School of Sport and Exercise Sciences, University of Birmingham, Birmingham, UK;Department of Rheumatology, Dudley Group of Hospitals NHS Foundation Trust, Russells Hall Hospital, Pensnett Road, Dudley, West Midlands, DY1 2HQ, United Kingdom;Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester, UK

关键词: Cardiovascular disease;    Rheumatoid arthritis;    Endothelial function;    Anti-TNFα;    Dyslipidaemia;   

Others  :  1149075
DOI  :  10.1186/1471-2474-13-127

 received in 2012-03-03, accepted in 2012-07-10,  发布年份 2012

【 摘 要 】

Background

Rheumatoid arthritis (RA) is associated with increased morbidity and mortality from cardiovascular disease (CVD). This can be only partially attributed to traditional CVD risk factors such as dyslipidaemia and their downstream effects on endothelial function. The most common lipid abnormality in RA is reduced levels of high-density lipoprotein (HDL) cholesterol, probably due to active inflammation. In this longitudinal study we hypothesised that anti-tumor necrosis factor-α (anti-TNFα) therapy in patients with active RA improves HDL cholesterol, microvascular and macrovascular endothelial function.

Methods

Twenty-three RA patients starting on anti-TNFα treatment were assessed for HDL cholesterol level, and endothelial-dependent and -independent function of microvessels and macrovessels at baseline, 2-weeks and 3 months of treatment.

Results

Disease activity (CRP, fibrinogen, DAS28) significantly decreased during the follow-up period. There was an increase in HDL cholesterol levels at 2 weeks (p < 0.05) which was paralleled by a significant increase in microvascular endothelial-dependent function (p < 0.05). However, both parameters returned towards baseline at 12 weeks.

Conclusion

Anti-TNFα therapy in RA patients appears to be accompanied by transient but significant improvements in HDL cholesterol levels, which coexists with an improvement in microvascular endothelial-dependent function.

【 授权许可】

   
2012 Sandoo et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Kitas GD, Erb N: Tackling ischaemic heart disease in rheumatoid arthritis. Rheumatology (Oxford) 2003, 42:607-613.
• [2]Lindhardsen J, Ahlehoff O, Gislason GH, Madsen OR, Olesen JB, Torp-Pedersen C, et al.: The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: a Danish nationwide cohort study. Ann Rheum Dis 2011, 70:929-934.
• [3]Kitas GD, Gabriel SE: Cardiovascular disease in rheumatoid arthritis: state of the art and future perspectives. Ann Rheum Dis 2011, 70:8-14.
• [4]Toms TE, Panoulas VF, Douglas KM, Griffiths H, Sattar N, Smith JP, et al.: Statin use in rheumatoid arthritis in relation to actual cardiovascular risk: evidence for substantial undertreatment of lipid-associated cardiovascular risk? Ann Rheum Dis 2010, 69:683-688.
• [5]Park YB, Lee SK, Lee WK, Suh CH, Lee CW, Lee CH, et al.: Lipid profiles in untreated patients with rheumatoid arthritis. J Rheumatol 1999, 26:1701-1704.
• [6]Peters MJ, Vis M, van Halm V, Wolbink GJ, Voskuyl AE, Lems WF, et al.: Changes in lipid profile during infliximab and corticosteroid treatment in rheumatoid arthritis. Ann Rheum Dis 2007, 66:958-961.
• [7]Toms TE, Panoulas VF, Smith JP, Douglas KM, Metsios GS, Stavropoulos-Kalinoglou A, et al.: Rheumatoid arthritis susceptibility genes associate with lipid levels in patients with rheumatoid arthritis. Ann Rheum Dis 2011, 70:1025-1032.
• [8]Halm V, Nielen MM, Nurmohamed MT, van Schaardenburg D, Reesink HW, Voskuyl AE, et al.: Lipids and inflammation: serial measurements of the lipid profile of blood donors who later developed rheumatoid arthritis. Ann Rheum Dis 2007, 66:184-188.
• [9]Dursunoglu D, Evrengul H, Polat B, Tanriverdi H, Cobankara V, Kaftan A, et al.: Lp(a) lipoprotein and lipids in patients with rheumatoid arthritis: serum levels and relationship to inflammation. Rheumatol Int 2005, 25:241-245.
• [10]Chapman MJ: Metabolic syndrome and type 2 diabetes: lipid and physiological consequences. Diab Vasc Dis Res 2007, 4(Suppl 3):S5-S8.
• [11]Feingold KR, Pollock AS, Moser AH, Shigenaga JK, Grunfeld C: Discordant regulation of proteins of cholesterol metabolism during the acute phase response. J Lipid Res 1995, 36:1474-1482.
• [12]Van Lenten BJ, Hama SY, de Beer FC, Stafforini DM, McIntyre TM, Prescott SM, et al.: Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures. J Clin Invest 1995, 96:2758-2767.
• [13]Deakin S, Moren X, James RW: HDL oxidation compromises its influence on paraoxonase-1 secretion and its capacity to modulate enzyme activity. Arterioscler Thromb Vasc Biol 2007, 27:1146-1152.
• [14]Toms TE, Symmons DP, Kitas GD: Dyslipidaemia in rheumatoid arthritis: the role of inflammation, drugs, lifestyle and genetic factors. Curr Vasc Pharmacol 2010, 8(3):301-326. 1-1-2010. Ref Type: Journal (Full)
• [15]Feldmann M: Development of anti-TNF therapy for rheumatoid arthritis. Nat Rev Immunol 2002, 2:364-371.
• [16]Jacobsson LT, Turesson C, Gulfe A, Kapetanovic MC, Petersson IF, Saxne T, et al.: Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J Rheumatol 2005, 32:1213-1218.
• [17]Peters MJ, van Sijl AM, Voskuyl AE, Sattar N, Smulders YM, Nurmohamed MT: The effects of tumor necrosis factor inhibitors on cardiovascular risk in rheumatoid arthritis. Curr Pharm Des 2012, 18:1502-1511.
• [18]Sorrentino SA, Besler C, Rohrer L, Meyer M, Heinrich K, Bahlmann FH, et al.: Endothelial-vasoprotective effects of high-density lipoprotein are impaired in patients with type 2 diabetes mellitus but are improved after extended-release niacin therapy. Circulation 2010, 121:110-122.
• [19]Nofer JR, van der Giet M, Tolle M, Wolinska I, von Wnuck LK, Baba HA, et al.: HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3. J Clin Invest 2004, 113:569-581.
• [20]Spieker LE, Sudano I, Hurlimann D, Lerch PG, Lang MG, Binggeli C, et al.: High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation 2002, 105:1399-1402.
• [21]Nicholls SJ, Dusting GJ, Cutri B, Bao S, Drummond GR, Rye KA, et al.: Reconstituted high-density lipoproteins inhibit the acute pro-oxidant and proinflammatory vascular changes induced by a periarterial collar in normocholesterolemic rabbits. Circulation 2005, 111:1543-1550.
• [22]Ford MA, McConnell JP, Lavi S, Rihal CS, Prasad A, Sandhu GS, et al.: Coronary artery endothelial dysfunction is positively correlated with low density lipoprotein and inversely correlated with high density lipoprotein subclass particles measured by nuclear magnetic resonance spectroscopy. Atherosclerosis 2009, 207:111-115.
• [23]Johansson J, Carlson LA, Landou C, Hamsten A: High density lipoproteins and coronary atherosclerosis. A strong inverse relation with the largest particles is confined to normotriglyceridemic patients. Arterioscler Thromb 1991, 11:174-182.
• [24]Pahor A, Hojs R, Gorenjak M, Rozman B: Accelerated atherosclerosis in pre-menopausal female patients with rheumatoid arthritis. Rheumatol Int 2006, 27:119-123.
• [25]Wallberg-Jonsson SW, Backman C, Johnson O, Karp K, Lundstrom E, Sundqvist KG, et al.: Increased prevalence of atherosclerosis in patients with medium term rheumatoid arthritis. J Rheumatol 2001, 28:2597-2602.
• [26]Wallberg-Jonsson S, Ohman M, Rantapaa-Dahlqvist S: Which factors are related to the presence of atherosclerosis in rheumatoid arthritis? Scand J Rheumatol 2004, 33:373-379.
• [27]Amarenco P, Labreuche J, Touboul PJ: High-density lipoprotein-cholesterol and risk of stroke and carotid atherosclerosis: a systematic review. Atherosclerosis 2008, 196:489-496.
• [28]National Institute for Health and Clinical Excellence: Adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis. 2009. http://www.nice.org.uk/nicemedia/pdf/TA130QRGFINAL.pdf webcite
• [29]Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al.: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988, 31:315-324.
• [30]Prevoo ML, Van 't Hof MA, Kuper HH, Van Leeuwen MA, van de Putte LB, van Riel PL: Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995, 38:44-48.
• [31]Kirwan JR, Reeback JS: Stanford Health Assessment Questionnaire modified to assess disability in British patients with rheumatoid arthritis. Br J Rheumatol 1986, 25:206-209.
• [32]Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, et al.: International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 2003, 35:1381-1395.
• [33]Turner J, Belch JJ, Khan F: Current concepts in assessment of microvascular endothelial function using laser Doppler imaging and iontophoresis. Trends Cardiovasc Med 2008, 18:109-116.
• [34]Sandoo A, Veldhuijzen van Zanten JJ, Metsios GS, Carroll D, Kitas GD: The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J 2010, 4:302-312.
• [35]Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al.: Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002, 39:257-265.
• [36]Irace C, Mancuso G, Fiaschi E, Madia A, Sesti G, Gnasso A: Effect of anti TNFalpha therapy on arterial diameter and wall shear stress and HDL cholesterol. Atherosclerosis 2004, 177:113-118.
• [37]Kerekes G, Soltesz P, Der H, Veres K, Szabo Z, Vegvari A, et al.: Effects of rituximab treatment on endothelial dysfunction, carotid atherosclerosis, and lipid profile in rheumatoid arthritis. Clin Rheumatol 2009, 28:705-710.
• [38]Hafstrom I, Rohani M, Deneberg S, Wornert M, Jogestrand T, Frostegard J: Effects of low-dose prednisolone on endothelial function, atherosclerosis, and traditional risk factors for atherosclerosis in patients with rheumatoid arthritis–a randomized study. J Rheumatol 2007, 34:1810-1816.
• [39]Vis M, Nurmohamed MT, Wolbink G, Voskuyl AE, de Koning M, van de Stadt R, et al.: Short term effects of infliximab on the lipid profile in patients with rheumatoid arthritis. J Rheumatol 2005, 32:252-255.
• [40]Gonzalez-Juanatey C, Llorca J, Vazquez-Rodriguez TR, az-Varela N, Garcia-Quiroga H, Gonzalez-Gay MA: Short-term improvement of endothelial function in rituximab-treated rheumatoid arthritis patients refractory to tumor necrosis factor alpha blocker therapy. Arthritis Rheum 2008, 59:1821-1824.
• [41]Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, et al.: Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 2006, 54:2793-2806.
• [42]Khovidhunkit W, Memon R, Feingold K, Grunfeld C: Infection and inflammation GÇÉ induced proatherogenic changes of lipoproteins. J Infect Dis 2000, 181:S462-S472.
• [43]Popa C, van Tits LJH, Barrera P, Lemmers HLM, van den Hoogen FHJ, Van Riel PLCM, et al.: Anti-inflammatory therapy with tumour necrosis factor alpha inhibitors improves high-density lipoprotein cholesterol antioxidative capacity in rheumatoid arthritis patients. Ann Rheum Dis 2009, 68:868-872.
• [44]Ghitescu L, Robert M: Diversity in unity: the biochemical composition of the endothelial cell surface varies between the vascular beds. Microsc Res Tech 2002, 57:381-389.
• [45]Sandoo A, Carroll D, Metsios GS, Kitas GD, Veldhuijzen van Zanten JJ: The association between microvascular and macrovascular endothelial function in patients with rheumatoid arthritis: a cross-sectional study. Arthritis Res Ther 2011, 13:R99. BioMed Central Full Text
• [46]Stokes KY, Granger DN: The microcirculation: a motor for the systemic inflammatory response and large vessel disease induced by hypercholesterolaemia? J Physiol 2005, 562:647-653.
• [47]Scognamiglio R, Negut C, de Kreutzenberg SV, Tiengo A, Avogaro A: Postprandial myocardial perfusion in healthy subjects and in type 2 diabetic patients. Circulation 2005, 112:179-184.
• [48]Kiortsis DN, Mavridis AK, Filippatos TD, Vasakos S, Nikas SN, Drosos AA: Effects of infliximab treatment on lipoprotein profile in patients with rheumatoid arthritis and ankylosing spondylitis. J Rheumatol 2006, 33:921-923.
• [49]Lamarche B, Moorjani S, Cantin B, Dagenais GR, Lupien PJ, Despres JP: Associations of HDL2 and HDL3 subfractions with ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study. Arterioscler Thromb Vasc Biol 1997, 17:1098-1105.
• [50]Watanabe J, Charles-Schoeman C, Miao Y, Elashoff D, Lee YY, Katselis G, et al.: Proteomic profiling following immunoaffinity capture of HDL: Association of acute phase proteins and complement factors with pro-inflammatory HDL in rheumatoid arthritis. Arthritis Rheum 2012, 64(6):1828-1837.
• [51]Charles-Schoeman C, Lee YY, Grijalva V, Amjadi S, Fitzgerald J, Ranganath VK, et al.: Cholesterol efflux by high density lipoproteins is impaired in patients with active rheumatoid arthritis. Ann Rheum Dis 2012, 71(7):1157-1162.
• [52]Faul F, Erdfelder E, Lang AG, Buchner A: G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007, 39:175-191.