Μαρία Μαρκέτου Επιμ. Α Καρδιολογική Κλινική ΠαΓΝΗ

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1 Μαρία Μαρκέτου Επιμ. Α Καρδιολογική Κλινική ΠαΓΝΗ

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3 Ischemic Heart Disease Mortality Rate in Each Decade of Age IHD mortality (floating absolute risk and 95% CI) SBP DBP Age at risk: y y y y y Usual SBP (mm Hg) Usual DBP (mm Hg) IHD, ischemic heart disease. Prospective Studies Collaboration. Lancet ;360:

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5 Most Hypertensive Patients Have Additional Risk Factors: REACH Registry Relation of BP and age to ischemic heart disease mortality Σχετικός κίνδυνος στεφανιαίας νόσου σε συνύπαρξη παραγόντων κινδύνου N=67,888 Meta-analysis patients of 61 observational studies, 12.7 million person-years 10-year probability (%) aged 45 years or Systolic BP Diastolic BP older 50from Hypertension 44 is Age defined at risk as (y): a SBP of mm Hg, 44 Age at risk (y): countries 256 Hypercholesterolaemia = serum cholesterol 81.8% patients of with mg/dl and atherothrombosis have IHD 30 mortality (floating absolute 20 risk) % hypertensive patients have 3 risk factors IHD = ischemic heart disease HDL cholesterol of mg/dl HTN aemia HTN=hypertension; 0 REACH=Reduction of Atherothrombosis for 0 Continued Health. Risk factors include: Hypertension treated diabetes Hypertension mellitus, diabetic nephropathy, Hypertension pathy, asymptomatic carotid Hypertension stenosis?70%, Systolic blood only 120 pressure [SBP], + hypercholesterol- 180?150 mm Hg, treated + hypercholesterol hypercholesterolaemia,, current smoking, men?55 y, women?70 Usual y. SBP (mm Hg) Usual DBP (mm Hg) aemia + smoking + hypercholesterolaemia+ smoking + diabetes + LVH Prospective Studies Bhatt Collaboration. DL et al. JAMA. Lancet. 2006;295: ;360:

6 High-Normal Blood Pressure and CVD Risk: Framingham Study High normal /85-89 mm Hg Normal /80-84 mm Hg Optimal <120/80 mm Hg Prehypertension Men 12 P< Cumulative Incidence (%)14 Time (years) Vasan et al. N Engl J Med. 2001;345: Women P< Time (years)

7 Mechanisms of Hypertension and CAD increased myocardial oxygen demand diminished coronary blood flow Increase of LV pressure load and cardiac work. angina pectoris and LV hypertrophy. Endothelial dysfunction increased vascular wall tension thinning, fragmentation, fracture of elastin fibers, as well as increased collagen deposition in arteries, Oxidative stress Humoral and metabolic factors

8 Treatment of Hypertension and CVD Outcomes Placebo Controlled Trials 0 Heart failure Fatal/nonfatal strokes CVD deaths Fatal/nonfatal CHD events -10 Risk reduction (%) randomized, placebo-controlled trials (48,000 subjects) 14 diuretic and 3 beta blocker based trials. All differences are statistically significant. CVD, cardiovascular disease; CHD, coronary heart disease. Herbert PR et al. Arch Intern Med. 1993;153: Moser M, Herbert PR. J Am Coll Cardiol. 1996;27:

9 CAD is 2 to 3 fold more frequent in hypertensive than in normotensive patients in a general population of patients with angina pectoris, a history of hypertension is present in 60% of patients Pepine et al. Am J Cardiol 1994; 74:226±231

10 Diagnosis 30 40% have a positive electrocardiogram (ECG) exercise test The specificity of ECG stress testing is low in hypertensives, with or without left ventricular hypertrophy (30 50%) 50% of hypertensive patients with normal coronary arteries and electrocardiographic signs of ischemia during stress testing have no evidence of left ventricular hypertrophy the accuracy of stress echocardiography is high

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12 There is no question that treatment of Hypertension will prevent CV Complications Does it Matter How We Do it?

13 When to initiate antihypertensive treatment? the level of systolic and diastolic blood pressure the level of total cardiovascular risk

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15 Box 8 Position statement: Goals of treatment ESH ESC guidelines 2007

16 BP and Treatment Goals On the basis of this huge cohort and prospective studies such as the intravascular ultrasound substudy of CAMELOT, it appears reasonable to propose that the target BP for individuals at risk for the development of CAD should be lower than that for low risk individuals. Specifically, we recommend a target BP of 130/80 mm Hg for individuals with demonstrated CAD, or CAD risk equivalents (carotid artery disease, peripheral arterial disease, abdominal aortic aneurysm), and for high risk patients, defined as those with diabetes mellitus,chronic renal disease, or a 10 year Framingham risk score of 10% AHA scientific statement. Circulation. 2007;115:

17 lower blood pressure gradually avoid tachycardia

18 Properties of antihypertensives that might provide additional antiatherogenic effect No adverse metabolic effect Increased insulin sensitivity Regression of left ventricular mass Beneficial endothelial effect Anti atherogenic effect Prevention of reinfarction Reduction of myocardial ischemia injury

19 Αναστολή ΡΑΑΣ στη στεφανιαία νόσο Σκεπτικό Αντιαθηρωματική δράση Μείωση του κινδύνου ρήξης της πλάκας Βελτίωση της λειτουργίας του ενδοθηλίου Ενίσχυση ινωδόλυσης Ρύθμιση νευρο ορμονικής αγγειοσύσπασης Μείωση ΥΑΚ Υποστροφή της αναδιαμόρφωσης

20 QUIET 2001 HOPE 2000 Στεφανιαία πλάκα ΣΝ* Αθηροσκλήρυνση Ρήξη πλάκας ΕΜ ISIS-IV IV 1993 SAVE 1992 AIRE 1993 GISSI SMILE 1995 ΣΔΑΚ* SOLVD prevention 1991 Αναδιαμόρφωση Ενδοθηλ ιακή Δυσ/γία Παράγοντες κινδύνου Καρδ. ανεπάρκεια CONSENSUS-1987 V- HeFT I και II 1991 SOLVD-treatment 1991 *ΣΝ=ΣτεφανιαίαΣτεφανιαία νόσος, ΣΔΑΚ: Συστολική Δυσλειτουργία θάνατ

21 B BLOCKER do not have any protective effect with regard to coronary artery disease Wiysonge et al. Cochrane Database Syst Rev 2007:1 47. Reduced antihypertensive effect Unfavorable hemodynamic effect Reduced compliance adverse effects Reduced effect on LVH regression Unfavorable metabolic effects Lack of vascular effects endothelial function

22 Newer Blocking Agents: Are They Different? more favorable hemodynamic and metabolic profile

23 HYPERTENSION AMD MI b blockers and ACE inhibitors and ARBs have been tested with significant reductions in cardiovascular morbidity or mortality

24 Box 11 Position statement: Antihypertensive treatment: Preferred drugs ESH ESC guidelines 2007

25 Treatment of Hypertension in the Prevention and Management of Ischemic Heart Disease AHA scientific statement. Circulation. 2007;115:

26 CV Disease risk 0 mmhg Blood Pressure 200 mmhg

27 CV Disease risk 0 mmhg Blood Pressure 200 mmhg

28 J shaped relationship between in high risk patients old having LVH coronary heart disease wide PP

29 INVEST (CAD pts) J - CURVE ONTARGET (high risk pts, mainly with CAD) 30 3 CV events (%) CV events (%) Adjusted HR >110 to 120 to > to > to > to > >160 On-treatment SBP (mmhg) On-treatment SBP (mmhg) 0 Cardiac events (%) VALUE (High risk pts) CV events (%) TNT (CAD pts) Adjusted HR 0 < 120 >120 to 130 to > to > to > to > to > On-treatment SBP (mmhg) > 100 On-treatment DBP (mmhg) 0

30 J curve effect between DBP and hazard ratio for cardiovascular complications in patients with revascularization and in those without. Revascularized patients have lower hazard ratios for cardiovascular complications

31 Get systolic BP < 120 mmhg and don t worry about diastolic BP CAMELOT- IVUS substudy n=274 Entry BP 130/77 Sipahi I, et al., JACC :

32 J curve may be an epiphenomenon of a more severe and debilitating underlying chronic condition (including cancer) and the low pressure maybe a mere marker of this illness thereby increasing mortality. low pressure may be an epiphenomenon of impaired cardiac function. may represent an epiphenomenon of increased arterial stiffness, i.e. a low DBP might be simply a marker for high pulse pressure and hence the increase in mortality. low DBP may compromise coronary perfusion. Since coronary perfusion occurs in diastole, diastolic hypotension could lead to coronary hypoperfusion in patients with compromised coronary flow reserve such as those with CAD

33 Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document The recommendation of previous guidelines to aim at a lower goal SBP (<130mmHg) in patients at very high cardiovascular risk (previous cardiovascular events) may be wise, but it is not consistently supported by trial evidence. In trials in which SBP was lowered to below 130mmHg in patients with previous cardiovascular events have given controversial results. Journal of Hypertension 2009, 27:

34 2007 AHA Guidelines: Treatment of Hypertension in the Prevention and Management of Ischemic Heart Disease In achieving a target BP < 130/80 mmhg for secondary prevention, the BP should be lowered slowly and caution is advised in inducing falls of diastolic BP below 60mmg. Rosendorff C et al., Circulation 2007,115:

35 AHA SCIENTIFIC STATEMENT Lowering SBP improves cardiac function and outcomes, probably through reduction in cardiac work and improved myocardial oxygen balance. it is theoretically possible that lowering of DBP improves cardiovascular outcomes only when coronary perfusion is maintained above the lower limit of coronary autoregulation. AHA scientific statement. Circulation. 2007;115:

36 For now. Optimal CV risk reduction includes antihypertensive Rx to attain BP targets protect against MI and stroke Antiplatelet Rx Lipid-lowering Rx Polypill?