Enzo Manzato

1. Iperuricemia con deposito di urato: nuovi approcci terapeutici Enzo Manzato

2. Uricemia ≤ 5,1 mg/dl Uricemia > 5,1 mg/dl HR = 1,30 (IC 95% 1,13-1,51) anni • n = 2.910; follow-up 4,4 anni Diabetes Care 32, 153, 2009

3. Uricemia ≤ 5,1 mg/dl sopravvivenza cumulata Uricemia > 5,1 mg/dl HR = 1,30 (IC 95% 1,13-1,51) anni • n = 2.910; follow-up 4,4 anni Diabetes Care 32, 153, 2009

4. Uricemia ≤ 5,1 mg/dl Sindrome Metabolica NO sopravvivenza cumulata Uricemia > 5,1 mg/dl Sindrome Metabolica SÌ HR = 1,30 (IC 95% 1,13-1,51) HR=1,25 (p<0,01) anni • n = 2.910; follow-up 4,4 anni Diabetes Care 32, 153, 2009

5. Cardiovascular Conditions and Risk Factors Associated with Elevated Uric Acid • - Hypertensionand prehypertension • - Renal disease (including reduced glomerular filtration rate and microalbuminuria) • -Metabolic syndrome (including abdominal obesity, hypertriglyceridemia, low level of HDL • cholesterol, insulin resistance, impaired glucose tolerance, elevated leptin level) • - Obstructivesleep apnea • - Vasculardisease (carotid, peripheral, coronaryartery) • - Strokeand vasculardementia • - Preeclampsia • - Inflammationmarkers (CRP, PAI 1 inhibitor, s-ICAM 1) • - Endothelialdysfunction • - Oxidativestress • - Sex and race (postmenopausal women, blacks) • - Demographic (movement from rural to urban communities, Westernization, immigration to • Western cultures) N Engl J Med359, 1811, 2008

6. Q1 > 4,22 Q2 4,22 - 4,74 Q3 4,74 - 5,50 Q4 5,50 - 6,41 Q5 > 6,41 mg/dl n = 4.385; follow-up 8,4 anni Stroke 37, 1503, 2006

7. HealthProfessionals Follow-up Study * * RISCHIO RELATIVO MULTIVARIATO SENZA GOTTA CON GOTTA SENZA GOTTA CON GOTTA CON PRECEDENTE CHD SENZA PRECEDENTE CHD n = 51.297; follow-up 12 anni Circulation 116, 894, 2007

8. HealthProfessionals Follow-up Study * * RISCHIO RELATIVO MULTIVARIATO SENZA GOTTA CON GOTTA SENZA GOTTA CON GOTTA CON PRECEDENTE CHD SENZA PRECEDENTE CHD n = 51.297; follow-up 12 anni Circulation 116, 894, 2007

9. HealthProfessionals Follow-up Study Rischio di diabete aggiustato per età, sesso, IMC, circonferenza vita, pressione arteriosa e colesterolo HDL per quartili di acido urico Rischio relativo di diabete 5,22-6,22 4,50-5,21 ≤ 4,49 ≥ 6,23 mg/dl ACIDO URICO p for trend < 0.001 n = 4.536; follow-up 10,1 anni Diabetes Care 31, 361, 2008

10. Framingham Heart Study original (n 4883) and offspring (n 4292) cohorts aged 29-62 years at time of recruitment in 1948, followedbiennially, 26° examination [2000-2002] for the original cohort relative risk of incident diabetes mg/dL URIC ACID relative risk of incident diabetes adjusting for age, sex, physical activity, alcohol consumption, smoking, hypertension, body mass index, and blood levels of glucose, cholesterol, creatinine, and triglycerides. Am J Med 123, 957, 2010

11. Evidence Linking Uric Acid and Hypertension • - An elevated uric acid level consistently predicts the development of hypertension. • - An elevated uric acid level is observed in 25–60% of patients with untreated essential • hypertension and in nearly 90% of adolescents with essential hypertensionof recentonset. • - Raising the uric acid level in rodents results in hypertension with the clinical, hemodynamic, and histologic characteristics of hypertension. • - Reducing the uric acid level with xanthine oxidase inhibitors lowers blood pressure in adolescents with hypertension of recent onset. N Engl J Med359, 1811, 2008

12. Veterans Administration - Boston Multivariable-adjustedassociationof baseline serum uric acid level with incidenthypertension p trend = 0,02 Relative risk mg/dl uric acid n = 2.062; follow-up 21,5 anni Hypertension 48, 1031, 2006

13. n = 30 adolescents (aged 11-17 years) with newlydiagnosedessentialhypertension and uric acid >6 mg/dl, treated for 4 weeks with allopurinol 200 mg twicedaily JAMA 300, 924, 2008

14. n = 30 adolescents (aged 11-17 years) with newlydiagnosedessentialhypertension and uric acid >6 mg/dl, treated for 4 weeks with allopurinol 200 mg twicedaily JAMA 300, 924, 2008

15. Change in total exercise time from baseline n = 65 patients with angiographicallydocumentedcoronaryarterydisease Lancet 375, 2161, 2010

16. J Clin Invest 120, 1791, 2010

17. CASO CLINICO Arch Gerontology Geriat 55, 497, 2012

18. CASO CLINICO Arch Gerontology Geriat 55, 497, 2012

19. PharmReviews 58, 87, 2006

20. % patients with uric acid <6 mg/dl at last visit p < 0.001 % patients N Engl J Med353, 2450, 2005

21. Subjects Requiring Treatment for Gout Flares N Engl J Med353, 2450, 2005

22. Proportion of subjects with serum uratelevels <6.0 mg/dl at final visit Proportion of subjects (%) Arthritis & Rheumatism 59, 1540, 2008

23. J Rheumatol36, 1273, 2009

24. Effect of baseline characteristics on treatment response subjects achieving sUA <6.0 mg/dL at final visit (%) Febuxostat 40 mg/day n = 757 Allopurinol 200/300 mg/day n = 755 Febuxostat 80 mg/day n = 756 Arthritis Research & Therapy 12, R63, 2010

25. Proportion of patients who achieved sUA < 6.0 mg/dL Clinical Therapeutics 35, 180, 2013

26. Nota 91 • Determinazione 2 novembre 2010 (GU 12 novembre 2010, n. 265): • Modifiche, relative all’inserimento della Nota 91, alla determinazione 4 gennaio 2007 : “Note AIFA 2006-2007 per l’uso appropriato dei farmaci”. • La prescrizione a carico del SSN è limitata alle seguenti condizioni: • Trattamento dell'iperuricemia cronica con anamnesi o presenza di tofi e/o di artrite gottosa in soggetti che non siano adeguatamente controllati con allopurinolo o siano ad esso intolleranti.

27. Xanthineoxidaseinhibitors allopurinol febuxostat Lancet 377, 165, 2011