Υπέρταση και Σακχαρώδης Διαβήτης Σύγχρονη Αντιμετώπιση της Αρτηριακής Υπέρτασης Π. Ζεμπεκάκης Καθηγητής Παθολογίας Διευθυντής Α! Παθολογικής Κλινικής ΑΠΘ Νοσοκομείο ΑΧΕΠΑ, Θεσσαλονίκη
Η Υπέρταση αποτελεί κύριο παράγοντα κινδύνου στην καρδιαγγειακή νόσο Biennial age-adjusted rate per 1000 patients at risk 50 40 30 20 10 0 Risk ratio 22.7 Coronary Disease 45.4 9.5 21.3 Stroke 12.4 3.3 2.4 6.2 5.0 Peripheral Artery Disease 9.9 2.0 7.3 3.5 Cardiac Failure Men Women Men Women Men Women Men Women 2.0 2.2 3.8 2.6 2.0 3.7 4.0 3.0 Normotensive 13.9 2.1 6.3 Hypertension Kannel WB. JAMA 1996;275:1571-1576.
Η θνητότητα από ΣΝ αυξάνεται ανάλογα με την Αρτηριακή πίεση (ΣΑΠ και ΔΑΠ) και την ηλικία IHD Mortality (Floating Absolute Risk and 95% CI) 256 32 4 0 120 140 Age at Risk (y) 80-89 70-79 60-69 50-59 40-49 160 180 256 32 4 0 70 80 Age at Risk (y) 80-89 70-79 60-69 50-59 40-49 90 100 110 Usual SBP (mm Hg) Usual DBP (mm Hg) Adapted from Prospective Studies Collaboration. Lancet. 2002;360:1903-1913.
CV Mortality Risk Doubles With Each 20/10 mm Hg BP Increment* CV mortality risk 8 7 6 5 4 3 2 1 0 8x 4x 2x 115/75 135/85 155/95 175/105 SBP/DBP (mm Hg) *Individuals aged 40-69 years, starting at BP 115/75 mm Hg. CV, cardiovascular; SBP, systolic blood pressure; DBP, diastolic blood pressure Lewington S, et al. Lancet. 2002; 60:1903-1913.
2013 ESH/ESC Guidelines for the management of arterial hypertension European Society of Hypertension European Society of Cardiology Journal of Hypertension 2013;31:1281-1357 Powered by
2013 ESH/ESC Guidelines for the management of arterial hypertension Definitions and classification of office BP levels (mmhg)* Hypertension: SBP >140 mmhg ± DBP >90 mmhg Category Systolic Diastolic Optimal <120 and <80 Normal 120 129 and/or 80 84 High normal 130 139 and/or 85 89 Grade 1 hypertension 140 159 and/or 90 99 Grade 2 hypertension 160 179 and/or 100 109 Grade 3 hypertension 180 and/or 110 Isolated systolic hypertension 140 and <90 * The blood pressure (BP) category is defined by the highest level of BP, whether systolic or diastolic. Isolated systolic hypertension should be graded 1, 2, or 3 according to systolic BP values in the ranges indicated. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
JNC-8 Blood Pressure Classification Blood Pressure Classification Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Normal < 120 < 80 Pre-hypertension 120-139 80-89 Stage 1 hypertension 140-159 90-99 Stage 2 hypertension > 160 > 100 Chobanian AV et al. JAMA 2003;289:2560-72.
2013 ESH/ESC Guidelines for the management of arterial hypertension Definitions of hypertension by office and out-of-office BP levels Category Systolic BP (mmhg) Diastolic BP (mmhg) Office BP 140 and 90 Ambulatory BP Daytime (or awake) 135 and/or 85 Nighttime (or asleep) 120 and/or 70 24-h 130 and/or 80 Home BP 135 and/or 85 BP, blood pressure. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
Η συχνότητα της Υπέρτασης αυξάνει με την πάροδο των ετών Year Overall, % (95% CI) 2000 26.4 (26.0-26.8) 2025 29.2 (28.8-29.7) Men, % (95% CI) 26.6 (26.0-27.2) 29.0 (28.6-29.4) Women, % (95% CI) 26.1 (25.5-26.6) 29.5 (29.1-29.9) Kearney PM et al. Lancet 2005; 365:217-223.
Ο επιπολασμός του ΣΔτ2 συνεχώς αυξάνει 387 εκατομμύρια ασθενών παγκοσμίως, ζουν με ΣΔ 1 Αναμένεται να αυξηθεί σε 592 εκατομμύρια το 2035 1 Hazard ratio (95% CI) (με διαβήτη vs χωρίς διαβήτη) 68% των ασθενών >65 ετών με ΣΔ, πεθαίνουν από καρδιαγγειακή νόσο 2 3 2 1 0 Κίνδυνος θνησιμότητας που σχετίζεται με τον διαβήτη (n=820,900) 3 Καρδιαγγιεκός (ΚΔ) θάνατος Θνησιμότητα κάθε αιτιολο 1. IDF Diabetes Atlas 6th Edition 2014 http://www.idf.org/diabetesatlas; 2. Centers for Disease Control and Prevention 2011; 3. Seshasai et al. N Engl J Med 2011;364:829-41 12
www.easoobesity.org Παχυσαρκία στην Ευρώπη
Αρτηριακή Υπέρταση και ΣΔ Η αρτηριακή υπέρταση στον ΣΔ τύπου 1 εμφανίζεται μετά την εμφάνιση της διαβητικής νεφροπάθειας Στον ΣΔ τύπου 2 η υπέρταση πολλές φορές συνυπάρχει κατά τη διάγνωση του ΣΔ και η εμφάνισή της εξαρτάται από την ηλικία, το φύλο και το βάρος του ατόμου (παχυσαρκία) Οι διαβητικοί έχουν διπλάσια συχνότητα Υπέρτασης από τους μη διαβητικούς Αλλά και η συχνότητα εμφάνισης ΣΔ στους υπερτασικούς είναι περίπου διπλάσια και πλέον απ ότι στους νορμοτασικούς
2013 Guidelines for the Management of Arterial Hypertension European Society of Hypertension European Society of Cardiology Journal of Hypertension 2013;31:1281-1357
Παράγοντες που επηρεάζουν την πρόγνωση του υπερτασικού ατόμου Σακχαρώδης Διαβήτης Σάκχαρο νηστείας πλάσματος 7.0 mmol/l (126 mg/dl) σε επανειλημμένες μετρήσις, ή Μετά φόρτιση σάκχαρο πλάσματος >11.0 mmol/l (198 mg/dl) HbA1C>6.5% ESC/ESH 2013 Εγκατεστημένη Καρδιαγγειακή ή Νεφρική Νόσος Αγγειοεγκεφαλική Νόσος: Ισχαιμικό ή Αιμορραγικό ΑΕΕ; Παροδικό ισχαιμικό ΑΕΕ Καρδιακή Νόσος: ΟΕΜ, Στηθάγχη, Αορτοστεφανιαία παράκαμψη, Καρδιακή ανεπάρκεια Νεφρική Νόσος: Διαβητική Νεφροπάθεια, Νεφρική Ανεπάρκεια (Κρεατινίνη Α>1.5, Γ > 1.4 mg/dl), Πρωτεινουρία (>300 mg/24 h) Περιφερική Αγγειοπάθεια Προχωρημένη Αμφιβληστροειδοπάθεια: Αιμορραγίες ή Εξιδρώματα, Οίδημα θηλής
2013 ESH/ESC Guidelines for the management of arterial hypertension Stratification of total CV risk in categories Other risk factors, asymptomatic organ damage or disease High normal SBP 130 139 or DBP 85 89 Blood pressure (mmhg) Grade 1 HT SBP 140 159 or DBP 90 99 Grade 2 HT SBP 160 179 or DBP 100 109 Grade 3 HT SBP 180 or DBP 110 No other RF Low risk Moderate risk High risk 1 2 RF Low risk Moderate risk Moderate to high risk High risk 3 RF Low to moderate risk Moderate to high risk High risk High risk OD, CKD stage 3 or diabetes Moderate to high risk High risk High risk High to very high risk Symptomatic CVD, CKD stage 4 or diabetes with OD/RFs Very high risk Very high risk Very high risk Very high risk Stratification of total CV risk in categories of low, moderate, high and very high risk according to SBP and DBP and prevalence of RFs, asymptomatic OD, diabetes, CKD stage or symptomatic CVD. Subjects with a high normal office but a raised out-of-office BP (masked hypertension) have a CV risk in the hypertension range. Subjects with a high office BP but normal out-of-office BP (white-coat hypertension), particularly if there is no diabetes, OD, CVD or CKD, have lower risk than sustained hypertension for the same office BP. BP, blood pressure; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; DBP, diastolic blood pressure; HT, hypertension; OD, organ damage; RF, risk factor; SBP, systolic blood pressure. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
Υπέρταση και διαβήτης τύπου 2: πληθυσμός υψηλού κινδύνου Eπιπολασμός (%) 12 10 8 6 4 2 * * * * * Nορμοτασικοί διαβητικοί άντρες Yπερτασικοί διαβητικοί άντρες Nορμοτασικές διαβητικές γυναίκες Yπερτασικές διαβητικές γυναίκες 0 Έμφραγμα μυοκαρδίου AEE/παροδικό ισχαιμικό επεισόδιο Yπερτροφία της αριστερή κοιλίας * Statistically significant, hypertensive vs normotensive. LVH on ECG. The Hypertension in Diabetes Study Group. J Hypertens 1993a;11:309-317.
Ποσοστό καρδιαγγειακής θνησιμότητας/ 10.000 έτη-ασθενών Συσχέτιση συστολικής AΠ και καρδιαγγειακού θανάτου σε ασθενείς με ΣΔ τύπου 2 250 225 200 175 150 125 100 75 50 25 0 Mη διαβητικοί Διαβητικοί < 120 120 139 140 159 160 179 180 199 200 Συστολική αρτηριακή πίεση (mm Hg) Stamler J et al. Diabetes Care 1993;16:434-444.
Βασική αιτία ΧΝΝ τελικού σταδίου ασθενών που εντάσσονται σε πρόγραμμα υποκατάστασης της νεφρικής λειτουργίας Άλλα Σπειραματονεφρίτις Αριθμός αιμοκαθαιρόμενων (χιλιάδες) 700 600 500 400 300 200 100 ΣΔ 10% 13% 243,524 ΑΥ 27% 281,355 520,240 No. ασθενών Προέκταση 95% CI 0 1984 1988 1992 1996 2000 2004 2008 United States Renal Data System. Annual data report. 2000.
Prevalence of Hypertension in Diabetic and Nondiabetic Kidney Disease Type of Kidney Disease Prevalence (%) Diabetic 1 Type 1, microalbuminuria 30-50 Type 1, macroalbuminuria 65-88 Type 2, microalbuminuria 40-83 Type 2, macroalbuminuria 78-96 Nondiabetic 2 Glomerular 85 Vascular 100 Tubulointerstitial 62 PKD 87 1, http://www.kdoqi.org; 2, MDRD Trial. Am J Kidney Dis 28:811-821, 1996
Πότε και Πως θεραπεύουμε την Υπέρταση στο ΣΔ;
2013 ESH/ESC Guidelines for the management of arterial hypertension Initiation of lifestyle changes and antihypertensive drug treatment Other risk factors, asymptomatic organ damage or disease High normal SBP 130 139 or DBP 85 89 Blood pressure (mmhg) Grade 1 HT SBP 140 159 or DBP 90 99 Grade 2 HT SBP 160 179 or DBP 100 109 Grade 3 HT SBP 180 or DBP 110 No other RF 1 2 RF 3 RF OD, CKD stage 3 or diabetes No BP intervention Lifestyle changes No BP intervention Lifestyle changes No BP intervention Lifestyle changes No BP intervention Lifestyle changes for several months Then add BP drugs targeting <140/90 Lifestyle changes for several weeks Then add BP drugs targeting <140/90 Lifestyle changes for several weeks Then add BP drugs targeting <140/90 Lifestyle changes BP drugs targeting <140/90 Lifestyle changes for several weeks Then add BP drugs targeting <140/90 Lifestyle changes for several weeks Then add BP drugs targeting <140/90 Lifestyle changes BP drugs targeting <140/90 Lifestyle changes BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting <140/90 BP, blood pressure; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; DBP, diastolic blood pressure; HT, hypertension; OD, organ damage; RF, risk factor; SBP, systolic blood pressure. Symptomatic CVD, CKD stage 4 or diabetes with OD/RFs Lifestyle changes No BP intervention Lifestyle changes BP drugs targeting <140/90 Lifestyle changes BP drugs targeting <140/90 Lifestyle changes Immediate BP drugs targeting The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World <140/90 Powered by
2013 ESH/ESC Guidelines for the management of arterial hypertension Blood pressure goals in hypertensive patients Recommendations SBP goal for most Patients at low moderate CV risk Patients with diabetes Consider with previous stroke or TIA Consider with CHD Consider with diabetic or non-diabetic CKD SBP goal for elderly Ages <80 years Initial SBP 160 mmhg SBP goal for fit elderly Aged <80 years SBP goal for elderly >80 years with SBP 160 mmhg DBP goal for most <140 mmhg 140-150 mmhg <140 mmhg 140-150 mmhg <90 mmhg DB goal for patients with diabetes <85 mmhg SBP, systolic blood pressure; CV, cardiovascular; TIA, transient ischaemic attack; CHD, coronary heart disease; CKD, chronic kidney disease; DBP, diastolic blood pressure. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
Επίδραση μεταβολών του τρόπου ζωής στην ΑΥ Μεταβολή Μείωση ΣΒ Αποδοχή δίαιτας DASH Μεσογειακή διατροφή Μείωση της ΣΑΠ 5 20 mmhg/10 kg μείωσης ΣΒ 8 14 mmhg Μείωση άλατος Άσκηση Περιορισμός αλκοόλ 2 8 mmhg 4 9 mmhg 2 4 mmhg JNC VII ESC/ESH 2007
2013 ESH/ESC Guidelines for the management of arterial hypertension Lifestyle changes for hypertensive patients Recommendations to reduce BP and/or CV risk factors Salt intake Restrict 5-6 g/day Moderate alcohol intake Limit to 20-30 g/day men, 10-20 g/day women Increase vegetable, fruit, low-fat dairy intake BMI goal 25 kg/m 2 Waist circumference goal Exercise goals Men: <102 cm (40 in.)* Women: <88 cm (34 in.)* 30 min/day, 5-7 days/week (moderate, dynamic exercise) Quit smoking * Unless contraindicated. BMI, body mass index. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
2013 ESH/ESC Guidelines for the management of arterial hypertension Monotherapy vs. drug combination strategies to achieve target BP Mild BP elevation Low/moderate CV risk Choose between Marked BP elevation High/very high CV risk Single agent Two drug combination Switch to different agent Previous agent at full dose Previous combination at full dose Add a third drug Full dose monotherapy Two drug combination at full doses Switch to different two drug combination Three drug combination at full doses Moving from a less intensive to a more intensive therapeutic strategy should be done whenever BP target is not achieved. BP, blood pressure; CV, cardiovascular. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
2013 ESH/ESC Guidelines for the management of arterial hypertension Possible combinations of classes of antihypertensive drugs Thiazide diuretics β-blockers Angiotensin-receptor blockers Other antihypertensives Calcium antagonists ACE inhibitors Green continuous lines: preferred combinations; green dashed line: useful combination (with some limitations); black dashed lines: possible but less well tested combinations; red continuous line: not recommended combination. Although verapamil and diltiazem are sometimes used with a beta-blocker to improve ventricular rate control in permanent atrial fibrillation, only dihydropyridine calcium antagonists should normally be combined with beta-blockers. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
CBPM 140/90 mmhg & ABPM/HBPM 135/85 mmhg Stage 1 hypertension CBPM 160/100 mmhg & ABPM/HBPM 150/95 mmhg Stage 2 hypertension Care pathway If target organ damage present or 10-year cardiovascular risk > 20% Offer antihypertensive drug treatment If younger than 40 years Consider specialist referral Offer lifestyle interventions Offer patient education and interventions to support adherence to treatment Offer annual review of care to monitor blood pressure, provide support and discuss lifestyle, symptoms and medication
Aged under 55 years A Aged over 55 years or black person of African or Caribbean family origin of any age C 2 Step 1 Summary of antihypertensive drug treatment A + C 2 A + C + D Resistant hypertension A + C + D + consider further diuretic 3, 4 or alpha- or beta-blocker 5 Consider seeking expert advice Step 2 Step 3 Step 4 Key A ACE inhibitor or low-cost angiotensin II receptor blocker (ARB) 1 C Calcium-channel blocker (CCB) D Thiazide-like diuretic See slide notes for details of footnotes 1-5
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2013 ESH/ESC Guidelines for the management of arterial hypertension Hypertension treatment for people with diabetes Recommendations Mandatory: initiate drug treatment in patients with SBP 160 mmhg Additonal considerations Strongly recommended: start drug treatment when SBP 140 mmhg SBP goals for patients with diabetes: <140 mmhg DBP goals for patients with diabetes: <85 mmhg All hypertension treatment agents are recommended and may be used in patients with diabetes RAS blockers may be preferred Especially in presence of preoteinuria or microalbuminuria Choice of hypertension treatment must take comorbidities into account Coadministration of RAS blockers not recommended Avoid in patients with diabetes SBP, systolic blood pressure; DBP, diastolic blood pressure; RAS, renin angiotensin system. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
2013 ESH/ESC Guidelines for the management of arterial hypertension Hypertension treatment for people with nephropathy Recommendations Additonal considerations Consider lowering SBP to <140 mmhg Consider SBP <130 mmhg with overt proteinuria RAS blockers more effective to reduce albuminuria than other agents Combination therapy usually required to reach BP goals Combination of two RAS blockers Aldosterone antagonist not recommended in CKD Monitor changes in egfr Indicated in presence of microalbuminuria or overt proteinuria Combine RAS blockers with other agents Not recommended Especially in combination with a RAS blocker Risk of excessive reduction in renal function, hyperkalemia SBP, systolic blood pressure; CKD, chronic kidney disease; egfr, estimated glomerular filtration rate; RAS, renin angiotensin system. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) - J Hypertension 2013;31:1281-1357 Medical Education & Information for all Media, all Disciplines, from all over the World Powered by
American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guidelines for Developing a Diabetes Mellitus Comprehensive Care Plan Writing Committee Cochairpersons Yehuda Handelsman MD, FACP, FACE, FNLA Zachary T. Bloomgarden, MD, MACE George Grunberger, MD, FACP, FACE Guillermo Umpierrez, MD, FACP, FACE Robert S. Zimmerman, MD, FACE ENDOCRINE PRACTICE Vol 21 No. 4 April 2015 Copyright 2015 AACE. May not be reprinted in any form without express written permission from AACE. 35
Q7. How should hypertension be managed? Blood Pressure Targets Parameter Blood pressure Treatment Goal Individualize on the basis of age, comorbidities, and duration of disease, with general target of: Systolic, mm Hg ~130 Diastolic, mm Hg ~80 A more intensive goal (such as <120/80 mm Hg) should be considered for some patients, provided the target can be safely reached without adverse effects from medication. More relaxed goals may be considered for patients with complicated comorbidities or those experience adverse medication effects. Copyright 2015 AACE. May not be reprinted in any form without express written permission from AACE. 36
Q7. How should hypertension be managed? Blood Pressure Treatment Employ therapeutic lifestyle modification DASH or other low-salt diet Physical activity Select antihypertensive medications based on BP-lowering effects and ability to slow progression of nephropathy and retinopathy ACE inhibitors or ARBs Add additional agents when needed to achieve blood pressure targets Calcium channel antagonists Diuretics Combined α/β-adrenergic blockers β-adrenergic blockers Do not combine ACE inhibitors with ARBs ACE = angiotensin converting enzyme; ARB = angiotensin II receptor blocker; BP = blood pressure; DASH = Dietary Approaches to Stop Hypertension. Copyright 2015 AACE. May not be reprinted in any form without express written permission from AACE. 37
JNC 8 CKD and/or DM SBP <140 mmhg DBP <90 mmhg ACEI/ARB alone or in combination with other drug class James PA et al. JAMA 2014
ESH/ESC CKD and/or DM SBP <140 mmhg DBP <85 mmhg 2013 ESH/ESC Guidelines. J Hypertens 2013
ESH/ESC Sarafidis PA & Ruilope LM. ESH Newsletter 2013, No. 55
KDIGO Non-diabetic adults with CKD: 140 mmhg systolic and 90 mmhg diastolic if normoalbuminuric 130 mmhg systolic and 80 mmhg diastolic if micro or macroalbuminuric Diabetic adults with non dialysis-dependent CKD: 140 mmhg systolic and 90 mmhg diastolic if normoalbuminuric 130 mmhg systolic and 80 mmhg diastolic if micro or macroalbuminuric Kidney transplant recipients: 130 mmhg systolic and 80 mmhg diastolic Elderly people with CKD: probably 140 mmhg systolic and 90 mmhg diastolic, but set targets after consideration of co-morbidities KDIGO Blood Pressure Work Group. Kidney Int Suppl 2012
Comparisons to Other Guidelines Non-black (no DM or CKD) Black (no DM or CKD) Diabetes JNC-7 JNC-8 ASH/ISH ESC/ESH CHEP Thiazide Thiazide ACEI, ARB, CCB, BB, thiazide Thiazide, ACEI, ARB, CCB Thiazide, CCB CCB, thiazide <60:ACEI, ARB >60:CCB, thiazide Thiazide, CCB ACEI, ARB, CCB, thiazide Thiazide, ACEI, ARB, CCB, BB Thiazide, ACEI, ARB, CCB, BB ACEI, ARB Thiazide, ACEI, ARB (BB if <60) Thiazide, ARB (BB if <60) ACEI, ARB, CCB, thiazide CKD ACEI, ARB ACEI, ARB ACEI, ARB ACEI, ARB ACEI, ARB Adapted from Salvo M et al. Ann Pharmacother 2014;48:1242-8.
43 The Renin Angotensin System Angiotensin Receptor Blocker X AT 1 Receptor Angiotensinogen Angiotensin I X Angiotensin II Renin AT 2 Receptor ACE-inhibitor X Angiotensin Converting Enzyme Bradykinin Degradation Products Glomerulosclerosis Na/fluid retention Vasoconstriction SMC proliferation Vasodilation Antiproliferation
Angiotensin II plays a major role in hypertension of diabetics VSMC Angiotensinogen Fat cells Renin Aldosterone (Adrenal/cardiovascular tissues) Angiotensin I Increased blood pressure Vasoconstriction Increased SNS activity Increased ROS Decreased NO Decreased compliance Angiotensin II ACE Reduced baroreceptor sensitivity Kidney failure Stroke Increased inflammation and atherosclerosis Increased SNS activity Increased CNS RAS Heart failure Myocardial fibrosis Hypertrophy Ischaemia Increased QT interval Decreased R-R variability Increased renin production Renal fibrosis Nephropathy Albuminuria McFarlane SI, et al. Am J Cardiol 2003; 91(Suppl.): 30H-37H.
Ο ρόλος της Αγγειοτενσίνης II στη χρόνια νεφρική βλάβη Mechanical stress Mesangial changes Oxidative stress Proteinuria NF-κB activation Glomerular capillary pressure Single nephron GFR Angiotensin II Adhesion molecules Chemotactic factors Cell growth Apoptosis TGF-β, CTGF PAI-1 Macrophage infiltration Renal disease Adapted from B. Berk, 2001 Nephron loss Glomerulosclerosis & Tubulo-interstitial fibrosis
Παθολογικές διεργασίες που οδηγούν στη σπειραματική βλάβη και πρωτεινουρία Glucose Urinary protein Glycoxidation (glycation) AGEs =angiotensin AT 1 receptor Increased glomerular pressure Efferent arteriolar constriction Ang II Ang II
ΜΕΤΑΒΟΛΙΚΟ ΣΥΝΔΡΟΜΟ ΚΑΙ ΣΔ-2: ΠΑΘΟΦΥΣΙΟΛΟΓΙΑ ΑΙ και Υπέρταση Sarafidis P & Lasaridis A, Am J Hypertens 2006
48 Η πρόοδος της διαβητικής νεφρικής νόσου Pre- Microalbuminuria Macroproteinuria End-stage renal disease GFR (ml/min) 150 100 50 0 5 10 15 20 25 Years 5000 1000 200 20 Albuminuria (mg/24 h) Strippoli et al. J Nephrol 2003;16:487 499
49 Definition of chronic kidney disease GFR < 60 ml/min/1.73m 2 for 3 months and/or Kidney damage for 3 months Identifying kidney damage Proteinuria-microalbuminuria Urine sediment abnormalities Imaging tests Abnormalities in blood or urine composition Biopsy National Kidney Foundation. Am J Kidney Dis 2004; 43(5 Suppl 1):S65 S230
50 GFR definition Glomerular filtration rate (GFR) is a test used to check how well the kidneys are working Specifically, it estimates how much blood passes through the glomeruli each minute Glomeruli are the tiny filters in the kidneys that filter waste from the blood
51 GFR markers Plasma creatinine Plasma cystatin C Creatinine clearance Creatinine-based GFR prediction equations Cystatin C-based GFR prediction equations
52 Gold standard methods to estimate GFR Plasma clearance of inulin, iohexol, 51 Cr-EDTA, 125 I- iothalamate, 99m Tc-diethylenetriaminepenta-acetic acid (DTPA)
Implications of Doubling of Serum Creatinine Creatinine Clearance U cr V Relationship Between Serum Creatinine and GFR P cr 125 100 75 50 25 0 0 1 2 3 4 5 6 P cr Serum Creatinine (mg/dl) GFR = glomerular filtration rate; P cr = plasma creatinine U cr = urinary creatinine; V = volume.
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Equations-formulae that are used in determination of glomerular filtration fraction (GFR) where : Ccr: creatinine clearance MDRD: Modification of Diet in Renal Disease, Scr: serum creatinine in mg/dl, Age: age in years Weight: Body weight in Kg.
Chronic Kidney Disease EPIdemiology Collaboration (CKD-EPI) formula 2009 CKD-EPI Creatinine equation: 141 x min(scr/k,1)a x max(scr/k, 1)-1.209 x 0.993 Age {x1.159 if black} Newer equations in GFR estimation : Cystatin C serum levels or better : 2012 CKD-EPI cystatin C equation:133 x min(scysc/0.8, 1)- 0.499x max (SCysC/0.8, 1)-1.328 x 0.996Age {x0.932 if female}
Stages of Chronic Kidney Disease Stage Description GFR, ml/min/1.73 m 2 US Prevalence, 1000s US Prevalence*, % 1 G1 2G2 Kidney damage with normal or increased GFR Kidney damage with mildly decreased GFR 90 5900 3.3 60 89 5300 3.0* 3 G3a G3b Mildly to Moderately Moderately to severely decreased GFR 45 59 30-44 7600 4.3 4 G4 Severely decreased GFR 15 29 400 0.2 4,6% 5 G5 Kidney failure <15 or dialysis 300 0.1 GFR = glomerular filtration rate. Total prevalence 11%, 19.2 million *Prevalence data for stages 1 and 2 are based on NHANES III patients with persistent albuminuria and are likely underestimated. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Part 4. Definition and classification of stages of chronic kidney disease. Available at: http://www.kidney.org/professionals/kdoqi/guidelines_ckd/p4_class_g1.htm. Accessed November 9, 2005. Adapted with permission from the National Kidney Foundation.
58 Definitions of microalbuminuria and Proteinuria Normal ( A1) Spot collection (mg/g creatinine) Timed collection (µg/min) 24-h collection (mg/24 h) < 30 < 20 < 30 Microalbuminuria (A2) (incipient nephropathy) TOD=target organ damage Macroproteinuria (A3) (clinical nephropathy) 30 299 20 199 30 299 300 200 300 American Diabetes Association. Diabetes Care 2004; 27:S79 S83 J Hypertens 2003;21:1011-1053
Is CKD risk factor for Cardiovascular morbidity and mortality?
Relative Risk of Death per GFR Level Age-Standardized Rate of Death From Any Cause (per 100 person-yr) 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 0.76 1.08 No. of Events 25,803 11,569 7802 4408 1842 GFR = glomerular filtration rate. 6x 4.76 15x 11.36 Estimated GFR (ml/min/1.73 m 2 ) Go AS, et al. N Engl J Med. 2004;351:1296-1305. ~20x 14.14 60 45-59 30-44 15-29 <15
Renal Dysfunction Predicts Increased Mortality After Acute Stroke 1.0 N = 2042, 7 ys follow -up Cumulative Survival 0.8 0.6 0.4 0.2 0 0 1 2 3 4 5 6 7 >66 ml/min 51 66 ml/min 39 51 ml/min <39 ml/min CrCl <51 ml/min predicted significantly worse outcome, even after adjustment for confounders* Time to Death (years) *Adjusted for age, neurologic score, high BP or ischemic heart disease, smoking, and diuretic use; Kaplan-Meier survival analysis (log-rank test, P<.0001). MacWalter RS, et al. Stroke. 2002;33:1630-1635.
Albuminuria and Proteinuria as risk factor of CVD in CKD
63 The increase of proteinuria is associated with increased CV morbidity and mortality in patients with type 2 diabetes Incidence of cardiovascular events (% of patients per year) 16 14 12 10 8 6 4 2 0 1,9x * 4,1x Normoalbuminuria Microalbuminuria Macroproteinuria * *p < 0.05 versus normoalbuminuria after adjusting for other risk markers Gimeno Orna et al. Rev Clin Esp 2003;203:526 531
Proteinuria and mortality risk from Stroke and atherosclerotic CV events in type -2 DM A: U-Prot <150 B: U-Prot 150 300 C: U-Prot >300 mg/l Survival curves for CV mortality 1. 0 0. 9 0.8 0.7 0.6 0. 5 Overall: P<0.001 A B C Incidence (%) P<0.001 0 0 10 20 30 40 50 60 70 80 90 Stroke Cardiovasc 40 30 20 10 0 Months U-Prot, urinary protein concentration. Miettinen H et al. Stroke. 1996;27:2033 2039. events
Increased Mortality in HTN with Proteinuria in DM type-2 1,000 Standardized Mortality Ratio 500 0 P- H- P- H+ Men P+ H- P+ H+ Status of hypertension (H) and proteinuria (P) in type 2 diabetes P- H- P- H+ P+ H- Women P+ H+ Wang SL et al. Diabetes Care 1996;19:305-312.
66 Definition, classification, and prognosis of CKD KDIGO controversy report: Kidney International (2011) 80, 17 28
Νεότερες απόψεις (ESH/ESC-2013) Πότε αρχίζουμε τη θεραπεία, δηλαδή σε ποια επίπεδα της ΑΠ; Ποιος είναι ο στόχος της ΣΑΠ/ΔΑΠ; Με ποια φάρμακα;
T27_1 Copyright 2013 Journal of Hypertension. Published by Lippincott Williams & Wilkins. 68
Συμπεράσματα Υπάρχει αύξηση της επίπτωσης του ΣΔ τύπου 2 παγκοσμίως (πανδημία παχυσαρκίας) - Yψηλή συχνότητα συνυπάρχουσας υπέρτασης (ιδίως ως ΜΣ) Oι ασθενείς με υπέρταση και ΣΔ -2 διατρέχουν υψηλό κίνδυνο καρδιαγγειακής και νεφρικής νόσου, ενώ τη στιγμή της διάγνωσης του διαβήτη, πολλοί ασθενείς πάσχουν ήδη από υπέρταση, νεφροπάθεια (μικρολευκωματινουρία) και άρα διατρέχουν και υψηλό κίνδυνο καρδιαγγειακού θανάτου H πρωτεϊνουρία είναι ισχυρός προγνωστικός δείκτης καρδιαγγειακής νοσηρότητας και θνητότητας Η θεραπεία, συνήθως με συνδυασμό 2 ή και περισσότερων φαρμάκων, από τα οποία πρωταρχικό ρόλο έχουν οι ΑΜΕΑ και οι ΑΥΑ, ρυθμίζει την ΑΠ, βελτιώνει την πρόγνωση και παρέχει οργανοπροστασία (όσον αφορά την καρδιά, εγκέφαλο, νεφρούς και αγγεία). Στόχος της αγωγής, μετά τις σύγχρονες μελέτες, συνιστάται να είναι η ΣΑΠ 140-130 και η ΔΑΠ<85-80 mmhg
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