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L’ipertensione arteriosa resistente

L’ipertensione arteriosa resistente. Carlo Basile Associazione Nefrologica Gabriella Sebastio Martina Franca. The disease burden of arterial hypertension. Cardiovascular disease (CVD) causes nearly 18 million deaths annually.

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L’ipertensione arteriosa resistente

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  1. L’ipertensione arteriosa resistente Carlo Basile Associazione Nefrologica Gabriella Sebastio Martina Franca

  2. The diseaseburden of arterialhypertension • Cardiovascular disease (CVD) causes nearly 18 million deaths annually. • Amongst the CVD risk factors, systemic hypertension remains as the leading root cause of excessive premature mortality and morbidity. • It is estimated that nearly 1.5 billion adults in the world will have hypertension in the decade ahead.

  3. Williams B et al. ESC Scientific Document Group. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J 2018; 39:3021 Whelton PK et al. 2017 guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the ACC/AHA task force on clinical practice guidelines. J Am Coll Cardiol 2018; 71:2199 • The latest European guidelinesretain the previous definition of hypertension (ie, BP > 140/90 mm Hg) whereas the American guidelineslowered the threshold to define hypertension to > 130/80 mm Hg. • The American guidelines (proposing new definition of hypertension) are driven largely by meta-analyses of important outcome trials including SPRINT (Systolic Blood Pressure Intervention Trial - Wright JT et al, NEJM 373: 2103, 2015). • The European guidelines are assembled largely on the basis of population attributable risk. • Yet, both the sets of guidelines recommend the same therapeutic BP goal of < 130/80 mm Hg.

  4. Williams B et al. ESC Scientific Document Group. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J 2018; 39:3021 Whelton PK et al. 2017 guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the ACC/AHA task force on clinical practice guidelines. J Am Coll Cardiol 2018; 71:2199

  5. Williams B et al. ESC Scientific Document Group. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J 2018; 39:3021

  6. Williams B et al. ESC Scientific Document Group. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J 2018; 39:3021

  7. Williams B et al. ESC Scientific Document Group. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J 2018; 39:3021

  8. Confirm Treatment Resistance

  9. Definition of treatment-resistanthypertension • Treatment-resistant hypertension (TRH)is defined by the 2018 AHA scientific statement, by the 2017 ACC/AHA hypertension guideline, and by the 2018 ESC statement as • blood pressure that remains above goal in spite of concurrent use of three antihypertensive agents of different classes. 

  10. Definition of treatment-resistanthypertension • If tolerated, one of the three agents should be a diuretic, and all agents should be prescribed at maximum recommended (or maximally tolerated) antihypertensive doses.

  11. Definition of uncontrolled and refractoryhypertension • Uncontrolled hypertension is characterized by in-office and out-of-office values that are above normal. • Refractory hypertension is said to be present when patients take > 5 antihypertensive drugs and remain uncontrolled after evaluation by a hypertension center or specialist.

  12. ExcludePseudoresistance

  13. The pseudoresistance-1 • Before diagnosing TRH, pseudoresistance must be excluded. It is inadequate BP control in a patient receiving appropriate treatment who does not actually have TRH. Most often, pseudo-resistant hypertension arises from: • Poor office BP measurement technique: sufficient rest, use of the right cuff, and repeated automated measurement in a quiet setting are critical. ABPM (or at least home BP measurement) is crucial to excluding “white coat” effect. • Poor patient concordance with prescribed therapy, which may be caused by side effects, complicated dosing schedules, pill burden, poor doctor-patient relationship, poor understanding or acceptance of the need for treatment, and medication cost.

  14. The pseudoresistance-2 • Suboptimal antihypertensive regimen: medical professionals must recognize and accept that “Clinical Inertia” has an important role to play in the suboptimal management of hypertension, particularly when patients require multiple drugs. The term Clinical Inertia can encompass • a poor knowledge of clinical guidelines • a misguided acceptance of elevated BP • or an underestimation of cardiovascular disease risk.

  15. Identify & Reverse LifestyleFactors

  16. MainLifestyleFactors • The 8th Joint National Commission (JNC-8) JNC-8 sodium recommendation for the general population is the equivalent of about 5.75 grams (1 teaspoon) of common table salt. • On average, a mean reduction in systolic blood pressure of 2-8 mm Hg is expected if dietary sodium intake is limited to no more than 2.4 grams per day.  • Further reduction of sodium to 1.5 grams is desirable for people with hypertension because it is associated with an even greater reduction in blood pressure. 

  17. MainLifestyleFactors Dietarysodiumexposure In a study a low-saltdiet (50 mmol ofsodium/day) comparedto a high-saltdiet (250 mmol ofsodium/day) had a 23/9-mm Hg(systolicoverdiastolic) difference, an amountremarkablysimilarto (if not betterthan) theeffectivenessofmostantihypertensivedrugswhenusedasmonotherapy in hypertension-treatment registrationtrials (Pimenta F et al, Hypertension 54: 475, 2009)

  18. MainLifestyleFactors • Obesity • Obesityis a commonfeatureofpatientswith TRH, partly due to an associationwith: • sodiumretention • enhancedsympatheticnervoussystemactivity • activationoftherenin-angiotensin-aldosteronesystem

  19. MainLifestyleFactors • Obesity • Thereis also an increasedlikelihoodof pseudo-resistanthypertension in obesepatientsiftoosmall a cuffisappliedto a large arm. • The benefitsofweightloss on BP arewelldocumented, typically in therangeofaround 6 to 10 mm Hgsystolic, with an averageof 8 kg ofweightloss.

  20. MainLifestyleFactors • Alcoholconsumption • The relationshipbetweentheprevalenceofhypertension, alcoholconsumption, and BP is linear. • Trials ofstructuredinterventionstoreducealcoholintakehaveresulted in significant falls in bothsystolicanddiastolic BP.

  21. Discontinue InterferingSubstances

  22. Discontinue InterferingSubstances

  23. Screen for SecondaryHypertension

  24. Screen for SecondaryHypertension • This step requires a combination of a high index of suspicion, tempered with a healthy dose of common sense and plausible pathophysiology.

  25. Screen for SecondaryHypertension • Adrenalglands • The adrenalcortexsynthesizes a numberofsteroidhormones, themostcommonlyimplicatedisaldosterone. • Severallinesofevidencehavedemonstratedthataldosteroneexcessmayplay a role in thepathogenesisof TRH. • Primary hyperaldosteronismisparticularlycommon in patientswith TRH, with a prevalenceof 14% to 21%.

  26. Screen for SecondaryHypertension • Obstructivesleepapnea (OSA) • Although not a classic „secondaryhypertension“, apneasandhypopneasarecommonlypresent in the TRH. • Activationofthesympatheticnervoussystemplays a crucialrole in thepathogenesisofhypertensionofthesepatients. • Increasedaldosteronelevelshavebeenobserved in OSA patientswith TRH.

  27. Screen for SecondaryHypertension

  28. Screen for SecondaryHypertension

  29. Pharmacological Treatment of TRH-1 • Patients defined as having TRH will already be receiving or have received at least three antihypertensive drugs. NICE (National Institute for Health and Clinical Excellence, UK) Clinical Guideline 127 has recommended that this combination should ideally include drugs with potentially synergistic actions, that is, an ACE inhibitor or angiotensin receptor blocker plus a calcium channel blocker plus a thiazide-type diuretic. • Optimising diuretic use appears very important, so use of a long-acting thiazide-type diuretic, such as chlortalidone or indapamide, may help. Loop diuretics should be considered in CKD patients.

  30. Pharmacological Treatment of TRH-2 • Low-dose spironolactone (25 mg, increased to 50 mg, once daily) or eplerenone (both mineralcorticoid receptor antagonists - MRAs -) are now guideline approved as suitable 4th line agents in patients with TRH. • Their success may be accounted for by the elevated aldosterone levels frequently found in TRH, either through undetected primary hyperaldosteronism or because aldosterone secretion escapes RAAS blockade (Williams B et al – PATHWAY - 2, Lancet 386: 2059, 2015). • Hyperkalemia is a risk when using any of these potassium sparing diuretics, especially in those patients with TRH who are already taking an ACE inhibitor or angiotensin receptor blocker and in individuals with CKD or diabetes mellitus.

  31. Pharmacological Treatment of TRH-3 • The only combination that cannot be recommended is the addition of a second agent to block the RAAS because of a lack of evidence in TRH and in light of an increased risk of adverse events seen in high-risk patients enrolled in the ONTARGET trial (Mann J et al, 372: 547, 2008).

  32. Non-pharmacological Treatment of TRH • Two promising non-pharmacological therapies have been under evaluation for the treatment of TRH – renal denervation (RDN) and baroreflex activation therapy (BAT). These are attractive targeted intervention options, with considerable evidence that sympathetic over-activity contributes to raised BP. • The first blinded and randomized study with RDN, SIMPLICITY HNT-3 (Bhatt D et al, NEJM 370: 1393, 2014) did no better than the sham procedure. • Currently, given their potential for adverse effects, and the lack of evidence of efficacy, RDN and BAT should only be used in the context of ongoing clinical research.

  33. In keeping with the AHA scientific statement, the 7thstepinvolvesreferral to a specialist with expertise in hypertension

  34. Summary-1 • TRH is a common medical disorder, defined as the failure to achieve goal BP despite 3 different antihypertensive medications at full dosages, one of which is a diuretic. • The pathogenesis of TRH is multifactorial, but the 2 pivotal factors include volume excess and the myriad effects of aldosterone and mineralcorticoid signalling at the level of the vasculature and the kidney. • MRAs, especially spironolactone, have been demonstrated to be the most effective add-on-drug for the treatment of TRH.

  35. Summary-2 • The risk of MRA-induced hyperkalemia is increased in patients with CKD, diabetes mellitus, or elderly patients. • Despite their early promise, RDN and BAT are not yet ready for clinical application in the management of TRH.

  36. I THANK YOU FOR YOUR ATTENTION Marcel Proust Botticelli – The Birth of Venus, Uffizi Gallery Museum, Florence

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