Ασθενής με σακχαρώδη διαβήτη και αρτηριακή υπέρταση Τι το νεότερο το 2017; Πετίδης Κωνσταντίνος Παθολόγος Β ΠΠ Κλινική ΑΠΘ

Ασθενής με σακχαρώδη διαβήτη και αρτηριακή υπέρταση Τι το νεότερο το 2017; Πετίδης Κωνσταντίνος Παθολόγος Β ΠΠ Κλινική ΑΠΘ

Diabetes alone Hypertension Is Prevalent Among Diabetic Adults 29% 71% Diabetes + HTN* NHANES III = Third US National Health and Nutrition Examination Survey (1988 1994). * Hypertension defined according to JNC-6: BP 130/85 mm Hg Geiss LS et al. Am J Prev Med. 2002;22:42-8. 18

Impacts of hypertension and Diabetes Mellitus on all-cause and cardiovascular mortality The Rancho Bernardo Study Journal of Hypertension35(1):55-62, 2017.

Διάγνωση υπέρτασης Παρακολούθηση αρτηριακής πίεσης

ADA guidelines 2017 Διάγνωση αρτηριακής υπέρτασης Recommendations Blood pressure should be measured at every routine clinical care visit. Patients found to have an elevated blood pressure (140/90 mmhg) should have blood pressure confirmed using multiple readings, including measurements on a separate day, to diagnose hypertension. B All hypertensive patients with diabetes should have home blood pressure monitored to identify white-coat hypertension. B Orthostatic measurement of blood pressure should be performed during initial evaluation of hypertension and periodically at follow-up, or when symptoms of orthostatic hypotension are present, and regularly if orthostatic hypotension has been diagnosed. E

Έναρξη θεραπείας

ADA guidelines 2017 Έναρξη θεραπείας Patients with confirmed office based BP 140/90mmHg should, in addition to lifestyle therapy, have timely titration of pharmacologic therapy to achieve blood pressure goals. A Patients with confirmed office based BP 160/100mmHg should, in addition to lifestyle therapy, have prompt initiation and timely titration of two drugs or a single-pill combination of drugs demonstrated to reduce cardiovascular events in patients with diabetes. A

2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)

ADA position statement Αλγόριθμος De Boer, Diabetes Care 2017

ADA, Diabetes Care 2017 ADA guidelines 2017 Έναρξη θεραπείας Απώλεια βάρους Περιορισμός άλατος Άσκηση

Vogt, JASN 2008 ARBs+αλάτι 38pts Πρωτεϊνουρία: 3.8gr Περιορισμός άλατος: 196 σε 92 meq/24ωρο Ελάττωση πρωτεϊνουρίας: 22% Λοσαρτάνη: ελάττωση 30% Λοσαρτάνη+αλάτι: ελάττωση 70%

Άσκηση και θνητότητα: Σ.Δ. Kokkinos Diab Care 2009

Στόχος θεραπείας

Κατευθυντήριες οδηγίες Στόχος θεραπείας ESH JNC-8 ASH ADA - 2013 ADA - 2016 <140/85 mmhg <140/90 mmhg <140/90 mmhg <140/80 mmhg <140/90 mmhg < 130/80 mmhg (νέοι, λευκωματουρία, >1 CV RF)

Diabetes and Hypertension: A Position Statement by the ADA Blood Pressure Targets Recommendations Most patients with diabetes and hypertension should be treated to a systolic blood pressure goal of 140 mmhg and a diastolic blood pressure goal of 90 mmhg. A Lower systolic and diastolic blood pressure targets, such as 130/80 mmhg, may be appropriate for individuals at high risk of cardiovascular disease if they can be achieved without undue treatment burden. B

Reduction in Risk (%) UKPDS: Tight BP Control Confers CV Benefits in Diabetic Patients Tight control (n=758): mean achieved BP of 144/82 mmhg Less tight control (n=390): mean achieved BP of 154/87 mmhg 0 Stroke Any DM endpoint DM death Microvascular complications -10-20 -30-40 -50 DM=diabetes mellitus FPG=fasting plasma glucose *P<0.05. * * Tight glucose control (FPG < 107 mg/dl) UKPDS 35. BMJ. 2000;321:405-412; UKPDS 38. BMJ. 1998;317:703-713. * Tight BP control (<150/85 mm Hg ) * vs <180/105 mm Hg

Significant Benefits From Intensive BP Reduction in Diabetic Patients 30 24,4 25 20 18,6 HOT STUDY Major CV Events/1000 Patient-yr P = 0.005 for trend 15 10 11,9 5 0 < 90 mm Hg <85 mm Hg (target DBP) < 80 mm Hg Hansson, Lancet, 1998

ACCORD Study N Engl J Med 2010;362:1575-1585

ACCORD 37% 13% Cushman, NEJM 2010

SPRINT prediabetes Bress, Doumas, Diabetes Care 2017

Με ποια φάρμακα;

ADA guidelines 2017 Είδος θεραπείας ADA, Diabetes Care 2017

ADA position statement Αλγόριθμος De Boer, Diabetes Care 2017

Effects of BP-lowering treatment on outcome incidence in patients with Hypertension with and without Diabetes Mellitus. Journal of Hypertension35(5):922-944, May 2017. 24

Effects of BP-lowering treatment on outcome incidence in patients with Hypertension with and without Diabetes Mellitus. 25 Journal of Hypertension35(5):922-944, May 2017.

Microalbuminuria or Low-grade proteinuria

% change in urinary albumin excretion Microalbuminuria DM pts UA IRMA II 20 10 0 Placebo -10-20 150 mg of irbesartan -30-40 -50 0 3 6 12 18 22 24 Months of Follow-up 300 mg of irbesartan *P<0.001 for difference between both irbesartan groups and placebo Parving, NEJM 2001

Incidence of Diabetic Nephropathy (%) Microalbuminuria DM pts Renal progression IRMA II 20 15 10 P<0.001 for difference between 300 mg irbesartan group and placebo Placebo 150 mg of irbesartan Placebo (n) Irbesartan 150 mg (n) Irbesartan 300 mg 5 0 0 3 6 12 18 22 24 Months of Follow-up 201 201 164 154 139 195 195 167 161 148 194 194 180 172 159 300 mg of irbesartan 129 142 150 36 45 49 Parving, NEJM 2001

ARBs vs placebo or Ca-antagonists Albuminuria Kunz, Ann Intern Med 2008

Angiotensin-Receptor Blockade versus Converting Enzyme Inhibition in Type 2 Diabetes and Nephropathy-RESULTS Baseline GFR 91 ml/min Barnett AH et.al N Engl J Med 2004;351:1952-1961.

ARBs vs ACE-inh Albuminuria Kunz, Ann Intern Med 2008

Advanced Diabetic Nephropathy

ACE-I is More Renoprotective than Conventional Therapy in Type 1 Diabetes (Total N = 409) % with Doubling of Baseline Creatinine 0 25 50 75 Captopril Conventional therapy 100 Baseline creatinine > 1.5 mg/dl Decrease in Mean Blood Pressure (mm Hg) - 2 0-2 - 4-6 0 1 2 3 4 % Reduction in Proteinuria - 40-20 0-20 - 40 P <.001-8 NS - 60 Lewis et al. N Engl J Med. 1993;329:1456-1462.

RENAAL ARB Reduction of Renal Failure 16% 25% 28% 20% Brenner BM et al, N Eng J Med 345:861, 2001

IDNT ARB Reduction of Renal Failure 20% 23% 33% Lewis EJ et al, N Eng J Med 345:851, 2001

Ποιοι συνδυασμοί;

ACCOMPLISH Diabetics 21% n=6,946 Weber, JACC 2010

ACCOMPLISH Renal outcome 48% Lancet, Feb 2010

Percentage of Adults with Diabetes Who Achieved Recommended Goals of Cardiovascular Risk Factors in NHANES NHANES III NHANES IV 50 % 40 30 20 10 Saydah S et.al JAMA 2004;291:335 0 HbA1c<7% BP <130/80 mmhg TC <200 mg/dl Good Control

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