Η Υπέρταση είναι θανατηυόρος νόσος

Η Υπέρταση είναι θανατηυόρος νόσος Δ.Καξπάλνπ-Βπζζνύιε Καξδηνιόγνο Υπεξηαζηθό Ιαηξείν ΩΚΚ Οκάδεο εξγαζίαο ΔΚΔ Θεζζαινλίθε, 18/2/12

HYPERTENSION An American Society of Hypertension definition Η ππέξηαζε είλαη έλα πξννδεπηηθά εμειηζζόκελν θαξδηαγγεηαθό ζύλδξνκν πνπ πξνθύπηεη από πνιύπινθεο αιιά θαη αιιεινζρεηηδόκελεο αηηηνινγίεο νη νπνίεο ζπρλά εκθαλίδνληαη πξηλ ηελ άλνδν ηεο αξηεξηαθήο πίεζεο. ASH Writing Group 2005 Giles TD. The new definition of hypertension. 20 th Annual Scientific Meeting of the American Society of Hypertension, 2005; San Francisco

Residual lifetime risk of Hypertension in women and men aged 65 years 100 80 Men Risk of hypertension (%) 60 40 Women 20 0 0 2 4 6 8 10 12 14 16 18 20 Follow-up (years) Vasan RS et al. JAMA. 2002;287:1003-1010.

Awareness of Hypertension in US adults: NHANES 2005-2006 18-59 Men Total Women 60 years and over Total Men Women Mexican American Non-Hispanic White Non-Hispanic Black 0 20 40 60 80 100 Percent of hypertensives Centers for Disease Control and Prevention/National Centre for Health Statistics. (CDC/NCHS). Data Brief no. 3; National Health and Nutrition Examination Survey. 2008.

Global mortality 2000 Impact of Hypertension High mortality, developing region Lower mortality, developing region Developed region 0 1000 2000 3000 4000 5000 6000 7000 8000 Attributable mortality (in thousands; total 55,861,000) BMI = body mass index. Adapted with permission from Ezzati M, et al. Lancet. 2002;360:1347-1360.

Deaths attributed to 19 leading factors, by country income level, 2004

Attributable mortality Leading causes of attributable global mortality and burden of disease, 2004 % 1. High blood pressure 12.8 2. Tobacco use 8.7 3. High blood glucose 5.8 4. Physical inactivity 5.5 5. Overweight and obesity 4.8 6. High cholesterol 4.5 7. Unsafe sex 4.0 8. Alcohol use 3.8 9. Childhood underweight 3.8 10. Indoor smoke from solid fuels 3.3 59 million total global deaths in 2004

Deaths attributed to Hypertension (%) The European hypertension critical situation 35% of deaths attributable to hypertension 40 35 30 20 16.5 13.6 13 9.6 13.5 10 0 Europe & Central Asia Middle East & North Africa East Asia Latin America South Asia World Lawes et al. Lancet 2008;371:1513-8

Mortality Rate, % Mortality From High Blood Pressure Higher in African Americans Overall Mortality Rates From Causes Related to Hypertension, 2003* 60 50 40 30 20 10 0 49.7 40.8 14.9 14.5 Male Female Male Female African American White In hypertensive African Americans, 30% and 20% of all deaths in men and women, respectively, may be due to high blood pressure. *High blood pressure listed as a primary or contributing cause of death. High blood pressure=systolic 140 mmhg or diastolic 90 mmhg, taking antihypertensive medicine, being told 2 times by a physician that you have high blood pressure. Adapted from Thom T et al. Circulation. 2006;113:e85 e151.

Global mortality and burden of disease attributable to CVD and their major RF CVD=cardiovascular disease.vd people aged 30 years Ezzati M, et al. PLoS Med. 2005;2(5):e133.

CV mortality risk Cardiovascular mortality risk doubles with each 20/10 mmhg BP increment* 8 7 6 5 4 3 2 1 0 115/75 135/85 155/95 175/105 Systolic/Diastolic Blood Pressure (mmhg) Lewington S, et al. Lancet. 2002;360:1903-1913 * Individuals aged 40-69 years, starting at BP 115/75 mm Hg

Hypertension commonly clusters with other Risk Factors Kaiser Permanente Northwest database; N=57,573 aged 35 years with HTN and no CVD HTN + 3 other risk factors 3 14 HTN + 2 other risk factors 44 HTN only 39 HTN + 1 other risk factor Other risk factors: obesity, hyperlipidemia, and diabetes Weycker D et al. Am J Hypertens. 2007;20:599-607 Obesity : Body mass index >30 kg/m 2

Consequences of Hypertension Organ damage Hypertension Transient ischemic attack, stroke LVH, CHD, CHF Retinopathy Peripheral arterial disease Chronic kidney disease CHF=congestive heart failure; CHD=coronary heart disease; LVH=left ventricular hypertrophy. Chobanian AV et al. JAMA. 2003;289:2560-2572.

Complications 1 Η αξηεξηαθή ππέξηαζε είλαη κείδσλ παξάγσλ θηλδύλνπ γηα πξώηκε θαξδηνπάζεηα Η θαξδηαθή αλεπάξθεηα ζε όιεο ηηο ειηθίεο ζρεηίδεηαη κε ηελ αύμεζε ηεο ΑΠ Η ππεξηξνθία ηεο αξηζηεξήο θνηιίαο από ππέξηαζε ζπζρεηίδεηαη κε επίπησζε ζπκθνξεηηθήο θαξδηαθήο αλεπάξθεηαο, θνηιηαθέο αξξπζκίεο, ζαλαηεθόξν έκθξαγκα ηνπ κπνθαξδίνπ, θαη αηθλίδην θαξδηαθό ζάλαην

Complications 2 Εγθεθαιηθό επεηζόδην Η ςπέπηαζη είναι ο πιο κοινόρ και ζημανηικόρ παπάγονηαρ κινδύνος Ελδνθξαληαθή αηκνξξαγία ςπέπηαζη Φξόληα λεθξηθή αλεπάξθεηα πος καηαλήγει ζε ηεσνηηό νεθπό Η ζημανηική αύξηζη ηηρ ΑΠ μποπεί να πποκαλέζει ςπεπηαζική κπίζη, μια επείγνπζα θαη δπλεηηθά ζαλαηεθόξν θαηάζηαζε

Hypertension co-morbidities % of patients with BP >140/90 mm Hg: 69% of patients with 1 st MI 77% of patients with 1 st stroke 74% of patients with HF Hypertension precedes HF in 91% of cases Hypertension is associated with a 2- to 3-times higher risk for HF BP, blood pressure; HF, heart failure; MI, myocardial infarction. Thom T et al. Circulation. 2006;113:e85-e151.

Hypertensive patients are at increased risk for cardiovascular events Biennial Age-Adjusted rate per 1000 Framingham Heart Study : Risk of cardiovascular events by hypertensive status in patients aged 35-64 years. A 36-year follow-up. 50 40 30 20 10 22,7 45,4 Kannel WB, JAMA 1996;275(24):1571-1576 0 Coronary Disease 9,5 21,3 Stroke 12,4 6,2 3,3 2,4 Peripheral Artery Disease Normotensive Hypertensive 5 9,9 2 7,3 3,5 Cardiac failure 13,9 6,3 2,1 Men Women Men Women Men Women Men Women Risk Ratio 2.0 2.2 3.8 2.6 2.0 3.7 4.0 3.0 Excess Risk 22.7 11.8 9.1 3.8 4.9 5.3 10.4 4.2

Effects of Hypertension on the Heart Left Ventricular Hypertrophy Vascular Disease: -Atherosclerosis -Arteriosclerosis

ΥΑΚ: Οξηζκόο ΥΑΚ είλαη ε θύξηα θαξδηαθή κεηαβνιή πνπ ζρεηίδεηαη κε ηελ ππέξηαζε. Η κάδα θαη ην πάρνο ησλ ηνηρσκάησλ ηεο αξηζηεξήο θνηιίαο απμάλνπλ ζαλ πξνζαξκνγή ζηελ πξννδεπηηθή ππεξθόξηηζε θαη απμαλόκελε ηνηρσκαηηθή ηάζε πνπ επέξρνληαη από ηελ πςειή ΑΠ θαη πςειέο πεξηθεξηθέο αληηζηάζεηο. Adapted from: Frohlich ED, Re RN Hurst s the Heart. 1998:1635-1650

Prevalence of LVH in hypertension Stage 3: SBP 180; DBP 110 90% Stage of HTN 12% 30% Stage 2: BP = 160 179/100 110 3% 8% Stage 1: SBP = 140 159; DBP = 90 99 10 20 30 80 90 100 Hypertensive patients (%) Tedesco MA et al. Clin Cardiol 2001;24:603 7. Schmieder RE et al. J Hum Hyperten 2000;14:597 604. Kahan T. J Hypertens 1998;16(suppl 7):23 29.

Determinants for LV hypertrophy Υπόβαζξν Ηιηθία Φύιν Φπιή Παρπζαξθία Αιάηη Αιθνόι Λνηπέο παζήζεηο Αηκνδπλακηθέο παξάκεηξνη Αξη. Πίεζε Φόξηηζε όγθνπ Αξηεξηαθή δνκή Γινηόηεηα αίκαηνο Με-αηκνδπλακηθέο παξάκεηξνη Τξνθηθνί παξάγνληεο: -Σπκπαζεηηθό ΝΣ -RAAS -Ιλζνπιίλε Γελεηηθνί παξάγνληεο θαη άιια ελδνθπηηάξηα ζήκαηα

Age-adjusted prevalence of LVH Prevalence of LVH as a function of 30- year average Systolic Blood Pressure 0.4 Women Men 0.2 0 <120 120-129 130-139 140+ 30-year average Systolic Blood Pressure Lauer MS et al. J Am Coll Cardiol. 1991;18:1287-1294.

Epidemiology of LVH Prevalence varies widely depending on method of assessment and hypertension severity Electrocardiographic LVH: 1 to 8% Echocardiographic LVH: up to 60% Vasan RS, Levy D. Arch Intern Med. 1996:156:1789-1796. Mitchell GF et al Med Clin N. Am 1997:81(5);1247-1271

Left Ventricular hypertrophy Independent predictor of: Myocardial infarction Stroke Heart Failure Total Mortality Sudden Death

Progression from Hypertension to Heart Failure Obesity Diabetes LVH Diastolic Dysfunction Hypertension CHF Smoking Dyslipidemia Diabetes MI Systolic Dysfunction Normal LV Structure and Function LV Remodeling Subclinical LV Dysfunction Overt Heart Failure Vasan RS and Levy D. Arch Intern Med. 1996;156:1789-1796.

Cumulative incidence of Heart Failure by baseline Hypertension status Cumulative Incidence (%) 25 20 15 10 Men aged 60-69 y Stage 2+ Stage 1 Normotensive 25 20 15 10 Women aged 60-69 y Stage 2+ Stage 1 5 5 Normotensive Cumulative Incidence (%) 0 40 30 20 10 2 4 6 8 10 12 14 16 Men aged 70-79 y Stage 2+ Stage 1 Normotensive 0 40 30 20 10 2 4 6 8 10 12 14 16 Women aged 70-79 y Stage 2+ Stage 1 0 2 4 6 8 10 12 14 0 Normotensive 2 4 6 8 10 12 14 Time (years) Levy D et al. JAMA. 1996;275:1557-1562.

Αξηεξηαθή ππέξηαζε θαη θαξδηαθή αλεπάξθεηα MALES The Rotterdam Study FEMALES 8% 4% 5% 2% 60% 8% 10% 62% 11% 3% 5% 9% 10% 3% Hypertension Diabetes mellitus Other Myocardial infarction ECG-LVH Angina pectoris Valvulopathy Lips DJ et al, Eur Heart J 2003;24:883-869

FROM HYPERTENSION TO HEART FAILURE IN SHEP HEART FAILURE about 85% about 15% Kostis et al, JAMA 1997

Effects of Hypertension on the Heart Left Ventricular Hypertrophy Vascular Disease: - Atherosclerosis - Arteriosclerosis

ATHERO- SCLEROSIS Focal, Occlusive Inflammatory Endothelial dysfunction Related to LDL cholesterol oxidation Inside-out Sensitive to A II and other substances ARTERIO- SCLEROSIS (Increased vascular stiffness Decreased vascular compliance) Diffuse, Dilatory Fibrotic (elastin breakdown, collagen increase) Adventitial and medial hypertrophy Related to age and BP Outside-in Sensitive to A II and other substances

Hypertension increases atherogenic lipoprotein content of arterial vessel walls BP Atherogenic VLDL, VLDL-R, IDL, LDL VBWG Pressure-driven convection Intima- Enhanced LP penetration media LP retention Intimamedia Pressure-induced distension Stretching LP = lipoprotein Sposito AC. Eur Heart J Suppl. 2004;6(suppl G):G8-G12.

Integrated Perspective on CV Risk Factors and Vascular Disease Endothelial Dysfunction Oxidative Stress & Inflammation CV Disease Ross. N Engl J Med. 1999;340:115-126. Ross. N Engl J Med. 1999;340:115-126. 35

Blood Pressure and Risk for Coronary Heart Disease in Men Age-adjusted Annual Incidence per 1000 60 50 40 30 20 10 Age 35-64 Age 65-94 Age-adjusted Annual Incidence per 1000 60 50 40 30 20 10 Age 35-64 Age 65-94 0 <120 140-159 180+ 120-139 160-179 0 <75 75-84 85-94 95-104 105+ Systolic Blood Pr essur e (m m Hg) Diastolic Blood Pr essur e (m m Hg) Based on 30 year follow-up of Framingham Heart Study Subjects free of CHD at base line but not adjusted for other risk factors.

Effect of systolic BP & diastolic BP on CHD mortality: MRFIT screenees Death rate per 10,000 person-years 100 21 24 90-99 10 31 17 80-89 Diastolic BP (mmhg) 12 48 26 14 75-79 9 37 25 13 9 70-74 N=316,099 35 44 25 13 9 25 <70 <120 12 38 120-139 25 140-159 81 160 Systolic BP (mmhg) *Men aged 35 to 57 years followed up for a mean of 12 years. Adapted from: Neaton et al. Arch Intern Med. 1992;152:56-64. 39

Mortality (Floating Absolute Risk and 95% CI) 256 128 64 32 16 8 Stroke and IHD mortality vs usual Systolic BP by age Stroke Age at risk: 80-89 years 256 70-79 years 128 60-69 years 64 50-59 years 32 16 8 IHD Age at risk: 80-89 years 70-79 years 60-69 years 50-59 years 40-49 years 4 4 2 2 1 1 0 120 140 160 180 0 120 140 160 180 Usual Systolic BP (mmhg) Usual Systolic BP (mmhg) IHD=ischemic heart disease Prospective Studies Collaboration. Lancet. 2002;360:1903-1913. 40

Κύξηνη παξάγνληεο θηλδύλνπ γηα ΑΕΕ Παξάγνληαο Κηλδύλνπ Σρεηηθόο Κίλδπλνο Σπρλόηεηα Νόζνπ Υπέξηαζε 6X 35% Καξδηαθή πάζεζε 2-6X 10-20% Πξνεγ. Εγθεθαιηθό 10X 2% Νόζνο Καξσηίδσλ 3X 4% Δηαβήηεο 2-4X 4-6% Κάπληζκα 2X 25% Stroke: Clinical Updates 1991;I(5):17-20 41

Risk Ratio Ο θύξηνο παξάγνληαο θηλδύλνπ γηα ΑΕΕ 4 3 2 1 Stroke 76 84 91 98 105 Diastolic BP (mmhg) Εκπιέθεηαη σο παξάγνληαο θηλδύλνπ ζε 70% ησλ ΑΕΕ. Κάζε αύμεζε θαηά 10 mm Hg ηεο ζπλήζνπο ΑΠ ζπλεπάγεηαη 80% αύμεζε ζηε πηζαλόηεηα ΑΕΕ Υςειή ΑΠ (ζηάδην >2) έρεη ζαλ απνηέιεζκα 10x-12x απμεκέλν θίλδπλν ΑΕΕ. Απμεκέλα επίπεδα ηόζν ηεο ΣΑΠ όζν θαη ηεο ΔΑΠ ζπλδένληαη κε απμεκέλα επίπεδα ηόζν ηζραηκηθνύ όζν αηκνξξαγηθνύ ΑΕΕ. Η ππέξηαζε πξνθαιεί ΑΕΕ επηδεηλώλνληαο ηελ αζεξνζθιήξσζε ζην ανξηηθό ηόμν θαη ζηηο απρεληθέο θαη εγθεθαιηθέο αξηεξίεο. J Hypertens 1990;8:239-244 Lancet 1995; 346:1647-1653 NEJM 1995; 333(21):1392-1400

Stroke is now more common than myocardial infarction in arterial hypertension Meta-analysis of drug trials in 1990 reported 773 strokes and 1442 heart attacks in 37,000 patients. In trials since 1990 in 59,650 patients there were 2233 strokes and 1627 heart attacks. If the Oriental trials are excluded, there were 2507 strokes and 1603 heart attacks. This trend was seen in both middle-aged and elderly trial participants. The reasons for this apparent change are unknown. Kjeldsen et al, Blood Pressure 2001;10:190-2

Annual incidence per 10000 Risk of atherothrombotic brain infarction in isolated systolic hypertension 320 240 160 80 Women Men 0 45-54 55-64 65-74 75-84 45-54 55-64 65-74 75-84 Age at biennial examination (years) The Framingham Study : 24 years of follow-up Kannel WB, Cardiovasc Pharmacol 1993;21(suppl 2):27-37 Hypertensives Normotensives

Systolic vs diastolic BP & stroke in MRFIT screenees 10 8 Systolic BP Diastolic BP Stroke Adjusted relative risk of stroke 6 4 2 0 1 2 3 4 5 6 7 8 9 10 BP decile SBP DBP <112 <71 112-118- 121-125- 129-132- 137 142-151 71-76- 79-81- 84-86- 89-92- 98 Stamler et al, Arch Int Med 1993;153:598-615 He & Whelton, J Hypertens 1999;17 (Suppl 2):7-13

Life time risk of Stroke The Framingham Study Adapted from: Lloyd-Jones, Hypertension Primer, Fourth Edition, 2007

Annual rate per 1000 Stroke rates according to baseline LVH Women Men 100 75 50 25 0 Levy D et al, Circulation 1994;90:1786-1793 35-64 65-94 35-64 65-94 Age at biennial examination (years) The Framingham Study : 36 years of follow-up with LVH without LVH

Stroke Mortality : 5 million/year world-wide - second cause of death Morbidity : > 15 million world-wide/year - severe impact on cost for care - severe impairment quality of life and independence - much greater fear for stroke than MI - the most common diagnosis for Medicine Clinics (ranked according to number of hospital days) Epidemiological risk relation : SBP fall by 10 mmhg produces a RRR 28% (SE 8)

ΕΓΚΕΦΑΛΙΚΟ επακόλοσθα Σύμφωνα με τη μελέτη Framingham, από όσους επέζησαν : 31% δελ είλαη απηόλνκνη. 20% ζέινπλ βνήζεηα γηα λα πεξπαηήζνπλ. 71% έρνπλ βιάβε ζηελ νκηιία 7 ρξόληα κεηά ην εγθεθαιηθό. 16% πξέπεη λα λνζειεπζνύλ ζε ίδξπκα. 1998 Heart and Stroke Statistical Update, American Heart Association.

Επηπνιαζκόο Οη επηπηώζεηο ηνπ Εγθεθαιηθνύ ζηnλ Ειιάδα Πεξηζζόηεξνη από 19,000 ζάλαηνη θάζε ρξόλν* Δπηπνιαζκόο: από ηνπο κεγαιύηεξνπο ζηελ Δπξώπε** Εγθεθαιηθά επεηζόδηα: Επηπνιαζκόο ζηελ Επξώπε 9 8 7 6 5 4 3 *Σηοισεία 1998 2 ** Acute neurological stroke care in Europe: results of the European Stroke Care Inventory 2000 EFNS European Journal of Neurology 7 1 0 Βέιγην Διβεηία Σνπεδία Τζερία Γεξκαλία Σινβαθία Γαλία Χώξα Απζηξία Διιάδα Πνξηνγαιία Κξναηία Βνπιγαξία

Stroke Recurrence Putative predictors of early Stroke recurrence Hypertension Elevated blood glucose Putative predictors of late Stroke recurrence Age Hypertension Heart disease Atrial fibrillation Heavy alcohol use CHF Diabetes mellitus Hyperglycemia Prior stroke or TIA

Επίπησζε ΚΜ (%) Αξηεξηαθή ππέξηαζε & θνιπηθή καξκαξπγή 30 Έλληνες Υπερτασικοί 28.1 25 n = 24.000 20 18.9 15 11.8 10 5 2.6 3.3 3.5 5.7 6.6 0 <55 55-59 60-64 65-69 70-74 75-80 80-84 85+ Ηλικία (έτη)

Risk factors for progression of renal disease Can be modified Hypertension Albuminuria/Proteinuria Dyslipidemia Cannot be modified Age Ethnicity Gender Hemoglobin A 1C Smoking Anemia Ca P0 4

Chronic kidney disease CKD and hypertension Common pathway in disease progression RENAL INJURY SYSTEMIC HYPERTENSION Nephron mass Glomerular capillary hypertension Glomerular permeability to macromolecules Filtration of plasma proteins Proteinuria Excessive tubular protein reabsorbtion Tubulo-interstitial inflammation RENAL SCARRING

Microalbuminuria : a marker of endothelial dysfunction Hypertension Hypertension is common in diabetics and is associated with endothelial dysfunction, through increase of the intra-arterial pressure. The severity of endothelial dysfunction is linked to the prognosis in both hypertension and diabetes. Pericone F, Circulation 2002;104:191

Cumulative incidence of cardiovascular disease (%) Proteinuria predicts cardiovascular morbidity 40 Proteinuria (n=41) 37% 30 20 10 No proteinuria (n=643) 13% 1 2 3 4 5 6 7 8 9 10 time (years) Samuelsson O, Wilhelmson L, Elmfeldt D et al, J Hypertens 1985;3:167-176

Risk of cardiovascular events in the presence of renal or coronary artery disease 17 RR (95% CI) Renal insufficiency and microalbuminuria Coronary artery disease 0.5 1 1.25 1.5 2.0 2.5 Increased risk Mann JFE, et al. Ann Intern Med 2001; 134: : 629-36.

High Risk Hypertension and Mild Renal Disease How many patients present with minor alterations of renal function in high-risk hypertension? Up to 40% Ruilope LM, J Am Soc Nephrol 2002;13:S165-S168

Years of life Consequences of Untreated Hypertension Historical Data Malignant Hypertension 5-year mortality : 95%! Years of life remaining at 35 years old M.I. 11 % Stroke 5 % Other 5 % Uremia 14 % 40 30-9.1 years -16.5 years 20 10 CHF 65 % 0 <140/95 140/95 150/100 Blood pressure (mmhg) Causes of death Flaxman N. Ann Intern Med 1936;10:748

Η ππέξηαζε παξακέλεη ζησπεξόο δνινθόλνο. Λόγσ ηεο ηαρπηάηεο αύμεζεο ηεο ειηθίαο ηνπ πιεζπζκνύ, ν αξηζκόο ησλ ζαλάησλ πνπ ζα ζρεηίδνληαη κε ηελ ππέξηαζε ζα ζπλερίδεη λα απμάλεηαη παγθόζκηα. Mortality patterns in hypertension, J Hypertens 2011;23:S3