#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Diagnosis and treatment of hyperuricemia in cardiovascular prevention based on the pathophysiological mechanism of its occurrence: expert consensus of Czech and Slovak experts 2024


Authors: Michal Vrablík 1;  Claudio Borghi 2;  Hana Rosolová 3;  Blanka Stibůrková 4;  Ivana Šoo Šová 5;  Martin Čaprnda 6;  Ján Števlík 7;  Adriana Ilavská 8;  Peter Jackuliak 9;  Zuzana Zafarová
Authors place of work: Centrum preventivní kardiologie, III. interní klinika – endokrinologie a metabolismu 1. LF UK a VFN v Praze 1;  Settore scientifico disciplinare, Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Italia 2;  Centrum preventivní kardiologie, II. interní klinika LF UK a FN Plzeň Bory 3;  Revmatologický ústav, Praha 4;  Národný ústav srdcových a cievnych chorôb, a. s., Bratislava 5;  I. interná klinika LF UK a UNB, Nemocnica Staré Mesto, Bratislava 6;  Kardiologická a interná ambulancia II., V. interná klinika LF UK a UNB, Nemocnica Ružinov, Bratislava 7;  Diabetologické a metabolické centrum, Medispektrum s. r. o., Bratislava 8;  V. interná klinika LF UK a UNB, Nemocnica Ružinov, Bratislava 9
Published in the journal: AtheroRev 2024; 9(2): 61-71
Category: Guidelines

Summary

A panel of experts from the Czech and Slovak Republics, with the contribution of Professor C. Borghi from the University of Bologna, discussed the clinical approach for the investigation and treatment of hyperuricemia (HU) in patients with increased cardiovascular (CV) risk. Since elevated uric acid (UA) modifies CV risk, it should be considered as an important modifier of CV risk and patients in whom its therapeutic reduction may improve CV parameters should be identified. The lack of selection of suitable patients is probably the reason for the inconsistent results of studies evaluating the clinical outcomes of antihyperuricemic therapy to date. The expert panel suggests treating HU due to an increase in xanthine oxidase (XO) activity, which is associated with an increase in CV risk, rather than HU due to decreased renal excretion of UA, which is not as risky from a CV perspective. To differentiate, he proposes to use a new index of the ratio of serum UA to creatinine (sUA/sCr), which has been shown to correlate with the incidence of CV events. For the purpose of CV prevention, it is recommended to investigate UA levels in patients with increased CV risk (hypertension, diabetes, dyslipidemia, chronic kidney disease, accumulation of CV risk factors or CVD) and to initiate intervention to target serum UA levels < 360 µmol/l in men and < 300 µmol/l in women with sUA/sCr index > 3.6. Intervention consists of patient education and lifestyle modification, optimization of treatment of other CV risk factors and administration of an XO inhibitor, allopurinol in the first line. The dose of allopurinol should be gradually titrated, usually in the range of 100–300 mg/day, according to the achievement of the target level of UA, with regular checks every 4–6 weeks. After stabilization of the condition, continued treatment with regular monitoring every 6 months is recommended.

Keywords:

allopurinol – Uric acid – cardiovascular risk – hyperuricemia – xanthine oxidase inhibitors – sUA/sCr – xanthine oxidase


Zdroje

Rees F, Hui M, Doherty M. Optimizing current treatment of gout. Nat Rev Rheumatol 2014; 10(5): 271–283. Dostupné z DOI: Dostupné z DOI: <http://dx.doi.org/10.1038/nrrheum.2014.32>.

Du L, Zong Y, Li H et al. Hyperuricemia and its related diseases: mechanisms and advances in therapy. Signal Transduct Target Ther 2024; 9(1): 212. Dostupné z DOI: <http://doi: 10.1038/s41392-024-01916-y>.

Leung N, Yip K, Pillinger MH et al. Lowering and Raising Serum Urate Levels: Off-Label Effects of Commonly Used Medications. Mayo Clin Proc 2022; 97(7): 1345–1362. Dostupné z DOI: <http://dx.doi.org/10.1016/j.mayocp.2022.02.027>.

Borghi C, Tykarski A, Widecka K et al. Expert consensus for the diagnosis and treatment of patient with hyperuricemia and high cardiovascular risk. Cardiol J 2018; 25(5): 545–563. Dostupné z DOI: <http://dx.doi.org/10.5603/CJ.2018.0116>.

Borghi C, Domienik-Karłowicz J, Tykarski A et al. Expert consensus for the diagnosis and treatment of patients with hyperuricemia and high cardiovascular risk. 2023 update. Cardiol J 2024; 31(1): 1–14. Dostupné z DOI: <http://dx.doi.org/10.5603/cj.98254>.

Bieber JD, Terkeltaub RA. Gout: on the brink of novel therapeutic options for an ancient disease. Arthritis Rheum 2004 Aug; 50(8): 2400–2414. Dostupné z DOI: <http://dx.doi.org/10.1002/art.20438>.

Zhu Y, Pandya BJ, Choi HK. Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007–2008. Am J Med 2012; 125(7): 679–687.e1. Dostupné z DOI: <http://dx.doi.org/10.1016/j.amjmed.2011.09.033>.

Gaffo AL, Jacobs DR Jr, Sijtsma F et al. Serum urate association with hypertension in young adults: analysis from the Coronary Artery Risk Development in Young Adults cohort. Ann Rheum Dis 2013; 72(8): 1321–1327. Dostupné z DOI: <http://dx.doi.org/10.1136/annrheumdis-2012–201916>.

Zoccali C, Maio R, Mallamaci F et al. Uric acid and endothelial dysfunction in essential hypertension. J Am Soc Nephrol 2006; 17(5): 1466–1471. Dostupné z DOI: <http://dx.doi.org/10.1681/ASN.2005090949>.

Kuo CF, Yu KH, Luo SF et al. Role of uric acid in the link between arterial stiffness and cardiac hypertrophy: a cross-sectional study. Rheumatology (Oxford) 2010; 49(6): 1189–1196. Dostupné z DOI: <http://dx.doi.org/10.1093/rheumatology/keq095>.

Kang DH, Park SK, Lee IK et al. Uric acid-induced C-reactive protein expression: implication on cell proliferation and nitric oxide production of human vascular cells. J Am Soc Nephrol 2005; 16(12): 3553–3362. Dostupné z DOI: <http://dx.doi.org/10.1681/ASN.2005050572>.

Rao GN, Corson MA, Berk BC. Uric acid stimulates vascular smooth muscle cell proliferation by increasing platelet-derived growth factor A-chain expression. J Biol Chem 1991; 266(13): 8604–8608.

Moshkovits Y, Tiosano S, Kaplan A et al. Serum uric acid significantly improves the accuracy of cardiovascular risk score models. Eur J Prev Cardiol 2023; 30(7): 524–532. Dostupné z DOI: <http://dx.doi.org/10.1093/eurjpc/zwac275>.

Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA 2008; 300(8): 924–932. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.300.8.924>.

Agarwal V, Hans N, Messerli FH. Effect of allopurinol on blood pressure: a systematic review and meta-analysis. J Clin Hypertens (Greenwich) 2013; 15(6): 435–442. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1751–7176.2012.00701.x>.

Badve SV, Pascoe EM, Tiku A et al. [CKD-FIX Study Investigators[. Effects of Allopurinol on the Progression of Chronic Kidney Disease. N Engl J Med 2020; 382(26): 2504–2513. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1915833>.

Doria A, Galecki AT, Spino C et al. [PERL Study Group]. Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes. N Engl J Med 2020; 382(26): 2493–2503. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1916624>.

Mackenzie IS, Hawkey CJ, Ford I et al. [ALL-HEART Study Group]. Allopurinol versus usKMl care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial. Lancet 2022; 400(10359): 1195–1205. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(22)01657–9>.

Neogi T. Chapter 19 - Asymptomatic Hyperuricemia: Cardiovascular and Renal Implications. In: Terkeltaub R. Gout & Other Crystal Arthropathies. Elsevier Canada 2017: 226–238. ISBN 978–1437728644.

Williams B, Mancia G, Spiering W et al. [2018 ESC/ESH Guidelines for the management of arterial hypertension]. Kardiol Pol 2019; 77(2): 71–159. Dostupné z DOI: <http://dx.doi.org/10.5603/KP.2019.0018>.

Mancia G, Kreutz R, Brunström M et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens 2023; 41(12): 1874–2071. Dostupné z DOI: <http://dx.doi.org/10.1097/HJH.0000000000003480>. Erratum in J Hypertens 2024; 42(1):194. Dostupné z DOI: <http://dx.doi.org/10.1097/HJH.0000000000003621>.

Bletsa E, Paschou SA, Tsigkou V et al. The effect of allopurinol on cardiovascular outcomes in patients with type 2 diabetes: a systematic review. Hormones (Athens) 2022; 21(4): 599–610. Dostupné z DOI: <http://dx.doi.org/10.1007/s42000–022–00403–9>.

Rahimi-Sakak F, Maroofi M, Rahmani J et al. Serum uric acid and risk of cardiovascular mortality: a systematic review and dose-response meta-analysis of cohort studies of over a million participants. BMC Cardiovasc Disord 2019; 19(1): 218. Dostupné z DOI: <http://dx.doi.org/10.1186/s12872–019–1215-z>.

Virdis A, Masi S, Casiglia E et al. Identification of the uric acid thresholds predicting an increased total and cardiovascular mortality over 20 years. Hypertension 2020; 75(2): 302–308. Dostupné z DOI: <http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13643>.

Bos MJ, Koudstaal PJ, Hofman A et al. Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study. Stroke 2006; 37(6): 1503–1507. Dostupné z DOI: <http://dx.doi.org/10.1161/01.STR.0000221716.55088.d4>.

Tian X, Wang P, Chen S et al. Association of Normal Serum Uric Acid Level and Cardiovascular Disease in People Without Risk Factors for Cardiac Diseases in China. J Am Heart Assoc 2023; 12(10): e029633. Dostupné z DOI: <http://dx.doi.org/10.1161/JAHA.123.029633>.

Tian X, Wang A, Wu S et al. Cumulative Serum Uric Acid and Its Time Course Are Associated With Risk of Myocardial Infarction and All-Cause Mortality. J Am Heart Assoc 2021; 10(13): e020180. Dostupné z DOI: <http://dx.doi.org/10.1161/JAHA.120.020180>.

Tian X, Chen S, Xu Q et al. Cumulative Serum Uric Acid Exposure and Its Time Course With the Risk of Incident Stroke. Stroke 2023; 54(8): 2077–2086. Dostupné z DOI: <http://dx.doi.org/10.1161/STROKEAHA.123.042708>.

Lv Q, Meng XF, He FF et al. High serum uric acid and increased risk of type 2 diabetes: a systemic review and meta-analysis of prospective cohort studies. PLoS One 2013; 8(2): e56864. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0056864>.

Han T, Lan L, Qu R et al. Temporal Relationship Between Hyperuricemia and Insulin Resistance and Its Impact on Future Risk of Hypertension. Hypertension 2017; 70(4): 703–711. Dostupné z DOI: <http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.09508>.

Li B, Chen L, Hu X et al. Association of Serum Uric Acid With All-Cause and Cardiovascular Mortality in Diabetes. Diabetes Care 2023; 46(2): 425–433. Dostupné z DOI: <http://dx.doi.org/10.2337/dc22–1339>.

Adamstein NH, MacFadyen J, Weber BN et al. Abstract 12593: Associations of Serum Uric Acid and Cardiovascular Events in a Clinical Trial of IL-1β Blockade. Circulation 2023; 148(Suppl 1): A12593. Dostupné z DOI: <https://doi.org/10.1161/circ.148.suppl_1.12593>.

Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens 2023; 41(12): 1874–2071. Dostupné z DOI: <http://dx.doi.org/10.1097/HJH.0000000000003480>.

Williams B, Mancia G, Spiering W et al. 2018 Practice Guidelines for the management of arterial hypertension of the European Society of Hypertension and the European Society of Cardiology: ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens 2018; 36(12): 2284–2309. Dostupné z DOI: <http://dx.doi.org/10.1097/HJH.0000000000001961>.

Unger T, Borghi C, Charchar F et al. 2020 International society of hypertension global hypertension practice guidelines. Hypertension 2020; 75((6)): 1334–1357. Dostupné z DOI: <http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15026>.

Unger T, Borghi C, Charchar et al. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. Ann Rheum Dis 2022; 81(6): 768–779. Dostupné z DOI: <http://dx.doi.org/10.1136/annrheumdis-2021–221733>.

Sato Y, Feig DI, Stack AG et al. The case for uric acid-lowering treatment in patients with hyperuricaemia and CKD. Nat Rev Nephrol 2019; 15(12): 767–775. Dostupné z DOI: <http://dx.doi.org/10.1038/s41581–019–0174-z>.

Wu N, Xia J, Chen S et al. Serum uric acid and risk of incident chronic kidney disease: a national cohort study and updated meta-analysis. Nutr Metab (Lond) 2021; 18(1): 94. Dostupné z DOI: <http://dx.doi.org/10.1186/s12986–021–00618–4>.

Johnson RJ, Sanchez Lozada LG et al. Uric Acid and Chronic Kidney Disease: Still More to Do. Kidney Int Rep 2022; 8(2): 229–239. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ekir.2022.11.016>

Russo E, Viazzi F, Pontremoli R et al. Serum Uric Acid and Kidney Disease Measures Independently Predict Cardiovascular and Total Mortality: The Uric Acid Right for Heart Health (URRAH) Project. Front Cardiovasc Med 2021; 8: 713652. Dostupné z DOI: <http://dx.doi.org/10.3389/fcvm.2021.713652>.

Ferguson LD, Molenberghs G, Verbeke G et al. Gout and incidence of 12 cardiovascular diseases: a case-control study including 152 663 individuals with gout and 709 981 matched controls. Lancet Rheumatol 2024; 6(3): e156-e167. Dostupné z DOI: <http://dx.doi.org/10.1016/S2665–9913(23)00338–7>.

Desideri G, Borghi C. Xanthine oxidase inhibition and cardiovascular protection: Don’t shoot in the dark. Eur J Intern Med 2023; 113: Dostupné z DOI: <http://dx.doi.org/10–12.10.1016/j.ejim.2023.04.006>.

Miah R, Fariha KA, Sony SA et al. Association of serum xanthine oxidase levels with hypertension: a study on Bangladeshi adults. Sci Rep 2022; 12(1): 21727. Dostupné z DOI: <http://dx.doi.org/10.1038/s41598–022–26341–5>.

Hernandez-Hernandez ME, Torres-Rasgado E, Pulido-Perez P et al. Disordered Glucose Levels Are Associated with Xanthine Oxidase Activity in Overweight Type 2 Diabetic Women. Int J Mol Sci 2022; 23(19): 11177. Dostupné z DOI: <http://dx.doi.org/10.3390/ijms231911177>.

Gondouin B, Jourde-Chiche N, Sallee M et al. Plasma Xanthine Oxidase Activity Is Predictive of Cardiovascular Disease in Patients with Chronic Kidney Disease, Independently of Uric Acid Levels. Nephron 2015; 131(3): 167–174. Dostupné z DOI: <http://dx.doi.org/10.1159/000441091>.

Kotozaki Y, Satoh M, Tanno K et al. Plasma Xanthine Oxidoreductase Activity Is Associated with a High Risk of Cardiovascular Disease in a General Japanese Population. Int J Environ Res Public Health 2021; 18(4): 1894. Dostupné z DOI: <http://dx.doi.org/10.3390/ijerph18041894>.

Furuhashi M, Matsumoto M, Tanaka M et al. Plasma Xanthine Oxidoreductase Activity as a Novel Biomarker of Metabolic Disorders in a General Population. Circ J 2018; 82(7): 1892–1899. Dostupné z DOI: <http://dx.doi.org/10.1253/circj.CJ-18–0082>.

Borghi C, Fiorini G. Gout, urate-lowering drugs, and risk of cardiovascular disease: can we clinically trust in the adjusted real-life data? Eur Heart J 2021; 42(44): 4589–4591. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehab667>.

Casiglia E, Tikhonoff V, Virdis A et al; Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA). Serum uric acid / serum creatinine ratio as a predictor of cardiovascular events. Detection of prognostic cardiovascular cut-off values. J Hypertens. 2023; 41(1): 180–186. Dostupné z DOI: <http://dx.doi.org/10.1097/HJH.0000000000003319>.

Timsans J, Kauppi JE, Kerola AM et al. Hyperuricaemia-associated all-cause mortality risk effect is increased by non-impaired kidney function – Is renal hyperuricaemia less dangerous? Eur J Intern Med 2024; 121: 56–62. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ejim.2023.10.009>.

Larsen KS, Pottegård A, Lindegaard HM et al. Effect of Allopurinol on Cardiovascular Outcomes in Hyperuricemic Patients: A Cohort Study. Am J Med 2016; 129(3): 299–306.e2. Dostupné z DOI: <http://dx.doi.org/10.1016/j.amjmed.2015.11.003>.

Bredemeier M, Lopes LM, Eisenreich MA et al. Xanthine oxidase inhibitors for prevention of cardiovascular events: a systematic review and meta-analysis of randomized controlled trials. BMC Cardiovasc Disord 2018; 18(1): 24. Dostupné z DOI: <http://dx.doi.org/10.1186/s12872–018–0757–9>.

Gill D, Cameron AC, Burgess S et al [VA Million Veteran Program] Urate, Blood Pressure, and Cardiovascular Disease: Evidence From Mendelian Randomization and Meta-Analysis of Clinical Trials. Hypertension 2021; 77(2): 383–392. Dostupné z DOI: <http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16547>.

Su X, Xu B, Yan B et al. Effects of uric acid-lowering therapy in patients with chronic kidney disease: A meta-analysis. PLoS One 2017; 12(11): e0187550. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0187550>.

Borghi C, Rosei EA, Bardin T et al. Serum uric acid and the risk of cardiovascular and renal disease. J Hypertens 2015; 33(9): 1729–1741. Dostupné z DOI: <http://dx.doi.org/10.1097/HJH.0000000000000701>.

Puig JG, Martínez MA. Hyperuricemia, gout and the metabolic syndrome. Curr Opin Rheumatol. 2008; 20(2): 187–191. Dostupné z DOI: <http://dx.doi.org/10.1097/BOR.0b013e3282f4b1ed>.

Yu KH, Kuo CF, Luo SF et al. Risk of end-stage renal disease associated with gout: a nationwide population study. Arthritis Res Ther 2012; 14(2): R83. Dostupné z DOI: <http://dx.doi.org/10.1186/ar3806>.

Abbott RD, Brand FN, Kannel WB et al. Gout and coronary heart disease: the Framingham Study. J Clin Epidemiol 1988; 41(3): 237–242. Dostupné z DOI: <http://dx.doi.org/10.1016/0895–4356(88)90127–8>.

De Vera MA, Rahman MM, Bhole V et al. Independent impact of gout on the risk of acute myocardial infarction among elderly women: a population-based study. Ann Rheum Dis 2010; 69(6): 1162–1164. Dostupné z DOI: <http://dx.doi.org/10.1136/ard.2009.122770>.

Matsumura K, Arima H, Tominaga M, et al. Effect of losartan on serum uric acid in hypertension treated with a diuretic: the COMFORT study. Clin Exp Hypertens. 2015; 37(3): 192–196. Dostupné z DOI: <http://dx.doi.org/10.3109/10641963.2014.933968>.

Jacob RA, Spinozzi GM, Simon VA et al. Consumption of cherries lowers plasma urate in healthy women. J Nutr 2003; 133(6): 1826–1829. Dostupné z DOI: <http://dx.doi.org/10.1093/jn/133.6.1826>

Ralston SH, Capell HA, Sturrock RD. Alcohol and response to treatment of gout. Br Med J (Clin Res Ed) 1988; 296(6637): 1641–1642. Dostupné z DOI: <http://dx.doi.org/10.1136/bmj.296.6637.1641>.

Richette P, Poitou C, Manivet P et al. Weight loss, xanthine oxidase, and serum urate levels: a prospective longitudinal study of obese patients. Arthritis Care Res (Hoboken) 2016; 68(7): 1036–1042. Dostupné z DOI: <http://dx.doi.org/10.1002/acr.22798>.

Chen JH, Wen CP, Wu SB et al. AttenKMting the mortality risk of high serum uric acid: the role of physical activity underused. Ann Rheum Dis 2015; 74(11): 2034–2042. Dostupné z DOI: <http://dx.doi.org/10.1136/annrheumdis-2014–205312>.

Schlesinger N. Dietary factors and hyperuricaemia. Curr Pharm Des 2005; 11(32): 4133–4138. Dostupné z DOI: <http://dx.doi.org/10.2174/138161205774913273.>.

Bardin T, Richette P. Impact of comorbidities on gout and hyperuricaemia: an update on prevalence and treatment options. BMC Med 2017; 15(1): 123. Dostupné z DOI: <http://dx.doi.org/10.1186/s12916–017–0890–9>.

Mackenzie I, Ford I, Nuki G et al. Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial. Lancet 2020; 396(10264): 1745–1757. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(20)32234–0>.

Keenan RT, Pillinger MH. Febuxostat: A new agent for lowering serum urate. Drugs Today 2009; 45(4): 247. Dostupné z DOI: <http://dx.doi.org/10.1358/dot.2009.45.4.1354217>.

Becker MA, Schumacher HR, Wortmann RL et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med 2005; 353(23): 2450–2461. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa050373>.

Ghossan R, Aitisha O, Fayad F et al. POS0520 cardiovascular safety of febuxostat in patients with gout or hyperuricemia: a systematic review of randomized controlled trials. Scientific Abstracts 2023. Ann Rheum Diss 2024; 82(Suppl 1). Dostupné z DOI: <https://doi.org/10.1136/annrheumdis-2023-eular.1024>.

SPC Allopurinol. Dostupné z WWW: <www.sukl.cz>.

Štítky
Angiology Diabetology Internal medicine Cardiology General practitioner for adults

Článok vyšiel v časopise

Athero Review

Číslo 2

2024 Číslo 2
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#