Oral L-Arginine Supplementation Effects on Cardiometabolic Factors in Hypertensive Patients with Rheumatoid Arthritis and its Relationship with Body Mass Index
DOI:
https://doi.org/10.6000/1929-5634.2015.04.02.2Keywords:
L-arginine, endothelial dysfunction, insulin resistance, adiponectin, obesity.Abstract
Hypertension and rheumatoid arthritis are regarded as a conditions associated with higher risk for cardiovascular disease. As known endothelial dysfunction is an early pathophysiological feature and an independent predictor cardiovascular disease. L-arginine is the amino acid with potential to improve endothelial function and is expected to play a role in the prevention or treatment of cardiovascular disease. In addition, data exists that L-arginine aspartate can reduce insulin resistance. We aimed to evaluate the effects of oral L-arginine supplementation on cardiometabolic factors by determining endothelial function, insulin resistance, adiponectin level in hypertensive patients combined with rheumatoid arthritis and its relationship with body mass index. 69 females with mean age – 54 [50,3; 61,5] years were enrolled. The 1st group made up 29 patients with hypertension combined with rheumatoid arthritis, 2nd group – 20 patients with rheumatoid arthritis, 3rd group – 20 patients with hypertension. In the endpoint patients were randomized to study subgroups patients, which received L-Arginine aspartate 30 ml/day during 4 weeks in addition to standard treatment, and control subgroups – received only the standard treatment. The levels of total cholesterol, triglycerides, C-reactive protein, serum creatinine, body mass index, body area index were determined. Insulin resistance, adiponectin level, endothelial-dependent flow mediated vasodilatation of brachial artery were measured at baseline and after 4 weeks. In patients with hypertension combined with rheumatoid arthritis identified a significant increase in insulin levels, insulin resistance, adiponectin, which were associated with cardiovascular risk, abdominal obesity, inflammatory activity levels. Oral supplementation of L-arginine causes multiple beneficial effects on the complex of cardiometabolic factors including: endothelial dysfunction, peripheral insulin resistance, adiponectin level in hypertensive patients with rheumatoid arthritis, mainly in obesity case. With the correction of endothelial function were established more significantly changes in the investigated parameters.
References
Naranjo A, Sokka T, Descalzo MA, et al. Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study. Arthritis Research Therapy 2008; 10(2): R30. http://dx.doi.org/10.1186/ar2383 DOI: https://doi.org/10.1186/ar2383
Peters MJ, Symmons DP, McCarey D. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Annals of the Rheumatic Diseases 2010; 69: 325-331. http://dx.doi.org/10.1136/ard.2009.113696 DOI: https://doi.org/10.1136/ard.2009.113696
Panoulas VF, Douglas KM, Milionis HJ, Stavropoulos-Kalinglou A, Nightingale P, Kita MD, Tselios AL, Metsios GS, Elisaf MS, Kitas GD. Prevalence and associations of hypertension and its control in patients with rheumatoid arthritis. Rheumatology 2007; 46(9): 1477-1482. http://dx.doi.org/10.1093/rheumatology/kem169 DOI: https://doi.org/10.1093/rheumatology/kem169
Panoulas VF, Metsios GS, Pace AV, John H, Treharne GJ, Banks MJ, Kitas GD. Hypertension in rheumatoid arthritis. Rheumatology 2008; 47: 1286-1298. http://dx.doi.org/10.1093/rheumatology/ken159 DOI: https://doi.org/10.1093/rheumatology/ken159
Singh G, Miller JD, Huse DM, Pettitt D, D'Agostino RB, Russell MW. Consequences of increased systolic blood pressure in patients with osteoarthritis. J Rheumatol April 2003; 30(4): 714-719.
Protogerou AD, Panagiotakos DB, Zampeli E, Argyris AA, Arida K, Konstantonis GD, Pitsavos C. Arterial hypertension assessed “out-of-office” in a contemporary cohort of rheumatoid arthritis patients free of cardiovascular disease is characterized by high prevalence, low awareness, poor control and increased vascular damage-associated “white coat” phenomenon. Arthritis Research & Therapy 2013; 15: 142-146. http://dx.doi.org/10.1186/ar4324 DOI: https://doi.org/10.1186/ar4324
Kuryata O, Sirenko O. Subclinical manifestations of atherosclerosis, the functional state of the endothelium and vascular stiffness in hypertensive patients with rheumatoid arthritis. Actual problems of modern medicine: Bulletin of Ukrainian Medical Stomatological Academy 2014; 14 № 3(47): 89-96.
Lago F, G´omez R, Conde J, Scotece M, G´omez-Reino JJ. Cardiometabolic comorbidities and rheumatic diseases: focus on the role of fat mass and adipokines. Arthritis Care and Research 2011; 63(8): 1083-1090. http://dx.doi.org/10.1002/acr.20488 DOI: https://doi.org/10.1002/acr.20488
Amaro F, et al. Insulin resistance and rheumatoid arthritis. Reumatol Clin 2011; 7(2): 124-129. http://dx.doi.org/10.1016/j.reuma.2010.03.010 DOI: https://doi.org/10.1016/S2173-5743(11)70023-5
Castro JP, El-Atat FA, McFarlane SI, Aneja A, Sowers JR. Cardiometabolic syndrome: pathophysiology and treatment. Curr Hypertens Rep 2003; 5(5): 393-401. http://dx.doi.org/10.1007/s11906-003-0085-y DOI: https://doi.org/10.1007/s11906-003-0085-y
Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 2006; 6(10): 772-83. http://dx.doi.org/10.1038/nri1937 DOI: https://doi.org/10.1038/nri1937
Rho YH. Adipocytokines, Insulin Resistance and Coronary Atherosclerosis in Rheumatoid Arthritis. Arthritis Rheum 2010; 62(5): 1259-1264. http://dx.doi.org/10.1002/art.27376 DOI: https://doi.org/10.1002/art.27376
Dessein PH, Norton GR, Badenhorst M, Woodiwiss AJ, Solomon A. Rheumatoid arthritis impacts on the independent relationships between circulating adiponectin concentrations and cardiovascular metabolic risk. Mediators of Inflammation 2013; 20: 461849. http://dx.doi.org/10.1155/2013/461849 DOI: https://doi.org/10.1155/2013/461849
Davignon J, Ganz P. Role of Endothelial Dysfunction in Atherosclerosis. Circulation 2004; 109: (23 Suppl 1): III27-32. DOI:10.1161/01. DOI: https://doi.org/10.1161/01.CIR.0000131515.03336.f8
Sitia S, Tomasoni L, Atzeni F, Ambrosio G, Cordiano C, Catapano A, Tramontana S, Perticone F, Naccarato P, Camici P, Picano E, Cortigiani L, Bevilacqua M, Milazzo L, Cusi D, Barlassina C, Sarzi-Puttini P, Turiel M. From endothelial dysfunction to atherosclerosis. Autoimmunity Reviews 2010; 9: 830-834. http://dx.doi.org/10.1016/j.autrev.2010.07.016 DOI: https://doi.org/10.1016/j.autrev.2010.07.016
Dong JY, et al. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J 2011; 162: 959-965. http://dx.doi.org/10.1016/j.ahj.2011.09.012 DOI: https://doi.org/10.1016/j.ahj.2011.09.012
Maradit-Kremers H, Crowson CS, Nicola PJ, Ballman KV, Roger VL, Jacobsen SJ. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum 2005; 52(2): 402-11. http://dx.doi.org/10.1002/art.20853 DOI: https://doi.org/10.1002/art.20853
Amaya-Amaya J, Sarmiento-Monroy JC, Mantilla RD, Pineda-Tamayo R, Rojas-Villarraga A, Anaya JM. Novel risk factors for cardiovascular disease in rheumatoid arthritis. Immunol Res 2013; 56(2-3): 267-86. http://dx.doi.org/10.1007/s12026-013-8398-7 DOI: https://doi.org/10.1007/s12026-013-8398-7
Kerekes G, Nurmohamed MT, González-Gay MA, Seres I, Paragh G, Kardos Z, et al. Rheumatoid arthritis and meta-bolic syndrome. Nat Rev Rheumatol 2014; 10(11): 691-96. http://dx.doi.org/10.1038/nrrheum.2014.121 DOI: https://doi.org/10.1038/nrrheum.2014.121
Bremer AA, Devaraj S, Afify A, Jialal I. Adipose Tissue Dysregulation in Patients with Metabolic Syndrome. J Clin Endocrinol Metab 2011; 96(11): E1782-8. http://dx.doi.org/10.1210/jc.2011-1577 DOI: https://doi.org/10.1210/jc.2011-1577
Böger RH, Ron ES. L-Arginine improves vascular function by overcoming deleterious effects of ADMA, a novel cardiovascular risk factor. Altern Med Rev 2005; 10(1): 14-23. DOI: https://doi.org/10.1191/1358863x05vm594ed
Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S. Endothelial dysfunction as a target for prevention of cardiovascular disease. Diabetes Care 2009; 32: 314-321. http://dx.doi.org/10.2337/dc09-S330 DOI: https://doi.org/10.2337/dc09-S330
He M, Liang X, He L, Wen W, Zhao S, Wen L, Liu Y, Shyy JY, Yuan Z. Endothelial dysfunction in rheumatoid arthritis. The role of monocyte chemotactic protein-1-induced protein. Arterioscler Thromb Vasc Biol 2013; 33: 1384-1391. http://dx.doi.org/10.1161/ATVBAHA.113.301490 DOI: https://doi.org/10.1161/ATVBAHA.113.301490
der Stoep DF VB-V, Klop B, Van Zeben D, Hazes JM, Castro Cabezas M. Cardiovascular risk in rheumatoid arthritis: how to lower the risk. Atherosclerosis 2013; 231: 163-172. http://dx.doi.org/10.1016/j.atherosclerosis.2013.09.006 DOI: https://doi.org/10.1016/j.atherosclerosis.2013.09.006
Lucotti P, Setola E, Monti LD, et al. Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients. Am J Physiol Endocrinol Metab 2006; 291(5): 906-12. http://dx.doi.org/10.1152/ajpendo.00002.2006 DOI: https://doi.org/10.1152/ajpendo.00002.2006
Piatti PM, et al. Long term oral L–arginine administration improves peripheral and hepatic insulin sensitivity in Type 2 diabetic patients. Diabetes Care 2001; 24(5): 875-80. http://dx.doi.org/10.2337/diacare.24.5.875 DOI: https://doi.org/10.2337/diacare.24.5.875
Cersosimo E, DeFronzo RA. Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases. Diabetes Metab Res Rev 2006; 22(6): 423-36. http://dx.doi.org/10.1002/dmrr.634 DOI: https://doi.org/10.1002/dmrr.634
Vita JA, Keaney JF Jr. Endothelial function: a barometer for cardiovascular risk? Circulation 2002; 106: 640-642. http://dx.doi.org/10.1161/01.CIR.0000028581.07992.56 DOI: https://doi.org/10.1161/01.CIR.0000028581.07992.56
Nadar S, Blann AD, Lip GY. Endothelial dysfunction: methods of assessment and application to hypertension. Curr Pharm Des 2004; 10: 3591-605. http://dx.doi.org/10.2174/1381612043382765 DOI: https://doi.org/10.2174/1381612043382765
Nakamura M, Yoshida H, Arakawa N, Saitoh S, Satoh M, Hiramori K. Effects of tumor necrosis factor-alpha on basal and stimulated endothelium-dependent vasomotion in human resistance vessel. J Cardiovasc Pharmacol 2000; 36: 487-92. http://dx.doi.org/10.1097/00005344-200010000-00011 DOI: https://doi.org/10.1097/00005344-200010000-00011
Gonzalez-Gay MA, Gonzalez-Juanatey C. Inflammation and endothelial dysfunction in rheumatoid arthritis. Clin Exp Rheumatol 2006; 24(2): 115-7.
Sattar N, Mccarey DW, Capell H, Mcinnes IB. Explaining how "high-grade" systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation 2003; 108: 2957-63. http://dx.doi.org/10.1161/01.CIR.0000099844.31524.05 DOI: https://doi.org/10.1161/01.CIR.0000099844.31524.05
Moncada S. Nitric oxide in the vasculature: physiology and pathophysiology. Ann N Y Acad Sci 1997; 811: 60-7. 16. DOI: https://doi.org/10.1111/j.1749-6632.1997.tb51989.x
Ignarro LJ. Nitric oxide: a unique endogenous signaling molecule in vascular biology. Biosci Rep 1999; 19: 51-71. http://dx.doi.org/10.1023/A:1020150124721 DOI: https://doi.org/10.1023/A:1020150124721
Downloads
Published
How to Cite
Issue
Section
License
Policy for Journals/Articles with Open Access
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are permitted and encouraged to post links to their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work
Policy for Journals / Manuscript with Paid Access
Authors who publish with this journal agree to the following terms:
- Publisher retain copyright .
- Authors are permitted and encouraged to post links to their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work .
