Il trattamento della ipertensione arteriosa resistente nella IRC: AGGIORNAMENTI IN NEFROLOGIA CLINICA  XIII Incontro Teramo, 11-12 ottobre 2013 Il trattamento della ipertensione arteriosa resistente nella IRC: Le misure igienico-dietetiche e la terapia farmacologica Alessandro Balducci

Definizione di Ipertensione Arteriosa Resistente a) PA >140/90(o >130/80 nei diabetici) malgrado l’uso di TRE farmaci, uno dei quali un diuretico b) PA controllata con QUATTRO o più farmaci

Controllo PA Dati Euroaspire (Kotseva, Lancet, 14/03/2009): 57%(1995-96) PA elevata nel 55%(1999-00) 64%(2006-07) Survey Italiana(Tocci, J Hypertension, June 2012): 150.000 pz. seguiti nei centri di ipertensione o negli ambulatori di Medicina Generale dal 2005 al 2011,si otteneva un controllo adeguato nel 37% dei soggetti.

Frequenza ipertensione resistente E’ associata ad un maggior rischio di eventi cardiovascolari e renali Prevalenza negli ipertesi in generale : 8-10%,negli USA cioè 6 milioni (Persell,Hypertension,2011), in Italia potrebbe essere di un milione In uno studio brasiliano (Massirier, Arquivos Brasileiros de Cardiologia, July 2012), la prevalenza è diminuita al 3% una volta escluse le ipertensioni secondarie,la scarsa compliance e la “white coat” Nei soggetti con CKD la prevalenza sale al 23-25%,dunque almeno TRE volte superiore rispetto agli ipertesi essenziali (Borrelli,Int J of Hypertension,2013)

Prevalence of Apparent Treatment-Resistant Hypertension among Individuals with CKD Results The prevalence of apparent treatment-resistant hypertension was 15.8%, 24.9%, and 33.4% for those participants with estimated GFR≥60, 45–59, and <45ml/min per 1.73m2, respectively, and 12.1%, 20.8%, 27.7%, and 48.3% for albumin-to-creatinine ratio <10, 10–29, 30–299, and ≥ 300 mg/g, respectively. The multivariable-adjusted prevalence ratios (95% confidence intervals) for apparent treatment-resistant hypertension were 1.25 (1.11 to 1.41) and 1.20 (1.04 to 1.37) for estimated GFR levels of 45–59 and <45 ml/min per 1.73 m2, respectively, versus ≥ 60 ml/min per 1.73 m2 and 1.54 (1.39 to 1.71), 1.76 (1.57 to 1.97), and 2.44 (2.12 to 2.81) for albumin-to-creatinine ratio levels of 10–29, 30–299, and ≥ 300mg/g, respectively, versus albumin-to-creatinine ratio <10 mg/g. After multivariable adjustment, men, black race, larger waist circumference, diabetes, history of myocardial infarction or stroke, statin use, and lower estimated GFR and higher albumin-to-creatinine ratio levels were associated with apparent treatment-resistant hypertension among individuals with CKD. Conclusions This study highlights the high prevalence of apparent treatment-resistant hypertension among individuals with CKD. Tanner,Clin J Am Soc Nephrol 8: 1583–1590, 2013. doi: 10.2215/CJN.00550113

Table 1: Determinants of resistant hypertension in general population. Clinical condition Diabetes mellitus Older age Obesity Drugs Nonsteroidal anti-inflammatory drugs Corticosteroids Oral contraceptive hormones Erythropoietin Cyclosporine and tacrolimus Sympathomimetics (decongestants) Exogenous substances Tobacco Alcohol Cocaine, amphetamines, and other illicit drugs Licorice Herbal supplements (ginseng, yohimbine) Secondary causes Common Chronic Kidney disease Primary aldosteronism (10-20%) Sleep apnea (71-85%) Hyper-hypothyroidism Renal artery disease Uncommon Cushing’s syndrome Pheochromocytoma Aortic coarctation Hyperparathyroidism Borrelli S,Int J of Hypertension,2013

Agabiti Rosei,Conoscere il Cuore,pag.346, 2013

Borrelli S,Int J of Hypertension,2013

Borrelli S,Int J of Hypertension,2013

Table 1: Determinants of resistant hypertension in general population. Clinical condition Diabetes mellitus Older age Obesity Drugs Nonsteroidal anti-inflammatory drugs Corticosteroids Oral contraceptive hormones Erythropoietin Cyclosporine and tacrolimus Sympathomimetics (decongestants) Exogenous substances Tobacco Alcohol Cocaine, amphetamines, and other illicit drugs Licorice Herbal supplements (ginseng, yohimbine) Secondary causes Common Chronic Kidney disease Primary aldosteronism (10-20%) Sleep apnea (71-85%) Hyper-hypothyroidism Renal artery disease Uncommon Cushing’s syndrome Pheochromocytoma Aortic coarctation Hyperparathyroidism Borrelli S,Int J of Hypertension,2013

(Pedrosa,Hypertension,2011,58,811-17) (26%GFR<60ml/min) (Pedrosa,Hypertension,2011,58,811-17)

(Pedrosa,Hypertension,2011,58,811-17)

Misure Igienico-Dietetiche Calo ponderale Riduzione introito di alcool Esercizio fisico (Dimeo, Hypertension 2012): 50 soggetti con RI, treadmill per 8-12 settimane: si aveva un calo della PA, non dati per CKD Dieta iposodica: la diminuzione dello introito sodico potenzia gli effetti antiipertensivi e anti proteinurici degli ACEI,con un probabile effetto antinfiammatorio che riflette la diminuzione del volume extracellulare

Tanner,Clin J Am Soc Nephrol 8: 1583–1590, 2013. doi: 10. 2215/CJN

Misure Igienico-Dietetiche Calo ponderale Riduzione introito di alcool Esercizio fisico (Dimeo, Hypertension 2012): 50 soggetti con RI, treadmill per 8-12 settimane: si aveva un calo della PA, non dati per CKD Dieta iposodica: la diminuzione dello introito sodico potenzia gli effetti antiipertensivi e anti proteinurici degli ACEI,con un probabile effetto antinfiammatorio che riflette la diminuzione del volume extracellulare

Ten recommendations to restrict sodium in your diet Borrelli S,Int J of Hypertension,2013

Projected Effect of Dietary Salt Reductions on Future Cardiovascular Disease Results Reducing dietary salt by 3 g per day is projected to reduce the annual number of new cases of CHD by 60,000 to 120,000, stroke by 32,000 to 66,000, and myocardial infarction by 54,000 to 99,000 and to reduce the annual number of deaths from any cause by 44,000 to 92,000. Such an intervention would be cost-saving even if only a modest reduction of 1 g per day were achieved gradually between 2010 and 2019 and would be more cost-effective than using medications to lower blood pressure in all persons with hypertension. Conclusions Modest reductions in dietary salt could substantially reduce cardiovascular events and medical costs and should be a public health target. (Bibbins-Domingo,NEJM,18 february 2010,pag.590)

(Bibbins-Domingo,NEJM,18 february 2010,pag.590)

(De Nicola,Kidney and BP Research,2011,34,58-67)

(De Nicola,Kidney and BP Research,2011,34,58-67)

I Farmaci Farmaci long-acting per consentire la monosomministrazione Una dose serale ? (non-dipper) clortalidone (azione più potente e maggiore emivita) Diuretici ( ↑ ANP e BNP in CKD) diuretici dell’ansa(se GFR< 30 ml/min) spironolattone( i livelli di aldosterone sono spesso elevati in CKD: relativo iperaldosteronismo col fenomeno dello dello escape)

(Bomback,NCP Nephrology,2007,3,9,pag.486)

Fig. 2. A graphical representation of relative hyperaldosteronism in various disease and experimental states. (Bomback,Blood Purification,2012,33,119-24)

Spironolattone 32 pz. stadio 3 trattati per un anno con spironolattone (Pisoni, J Hum Hypert, August 2012) : Potassio 4→4,4 p<0.0001 Creatinina 1,5 → 1,8 p<0.0004 GFR 48,6 → 41,2 p<0.0002