Μαρία Μαρκέτου Επιμ. Α Καρδιολογική Κλινική ΠαΓΝΗ

Μαρία Μαρκέτου Επιμ. Α Καρδιολογική Κλινική ΠαΓΝΗ

Ischemic Heart Disease Mortality Rate in Each Decade of Age IHD mortality (floating absolute risk and 95% CI) 256 128 64 32 16 8 4 2 SBP 256 128 64 32 16 8 4 2 DBP Age at risk: 80-89 89 y 70-79 79 y 60-69 69 y 50-59 59 y 40-49 49 y 1 1 120 140 160 180 Usual SBP (mm Hg) 70 80 90 100 110 Usual DBP (mm Hg) IHD, ischemic heart disease. Prospective Studies Collaboration. Lancet.. 2002;360:1903-1913. 1913.

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 150-160mm Hg, 44 Age at risk (y): countries 256 Hypercholesterolaemia 80 89 256= 80 89 40 128 serum cholesterol 81.8% 70 79 patients of 240-262128 with mg/dl and 70 79 atherothrombosis 60 69 have IHD 30 mortality (floating absolute 20 risk) 10 0 64 32 16 8 4 2 1 6 90.3% hypertensive patients have 3 risk factors 2 60 69 50 59 40 49 IHD = ischemic heart disease HDL cholesterol of 33-3564 mg/dl 50 59 HTN 32 19 40 49 16 13 aemia 8 4 1 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 140 160 [SBP], + hypercholesterol- 180?150 mm Hg, treated + hypercholesterol- 70 80 90 100 110 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;295:180-189. 2002;360:1903-13. 6

High-Normal Blood Pressure and CVD Risk: Framingham Study High normal 130-139/85-89 mm Hg Normal 120-129/80-84 mm Hg Optimal <120/80 mm Hg Prehypertension Men 12 P<.001 10 10 8 8 6 6 4 4 2 2 0 0 0 2 4 6 8 10 12 14 Cumulative Incidence (%)14 Time (years) Vasan et al. N Engl J Med. 2001;345:1291-1297. Women P<.001 0 2 4 6 8 10 12 14 Time (years)

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

Treatment of Hypertension and CVD Outcomes Placebo Controlled Trials 0 Heart failure Fatal/nonfatal strokes CVD deaths Fatal/nonfatal CHD events -10 Risk reduction (%) -20-30 -40-38 -21-16 -50-60 -52 17 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;153:578-581. Moser M, Herbert PR. J Am Coll Cardiol. 1996;27:1214-1218.

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

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

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

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

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

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;115:2761-2788

lower blood pressure gradually avoid tachycardia

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

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

QUIET 2001 HOPE 2000 Στεφανιαία πλάκα ΣΝ* Αθηροσκλήρυνση Ρήξη πλάκας ΕΜ ISIS-IV IV 1993 SAVE 1992 AIRE 1993 GISSI-3 3 1994 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

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

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

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

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

Treatment of Hypertension in the Prevention and Management of Ischemic Heart Disease AHA scientific statement. Circulation. 2007;115:2761-2788

CV Disease risk 0 mmhg Blood Pressure 200 mmhg

CV Disease risk 0 mmhg Blood Pressure 200 mmhg

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

60 50 40 INVEST (CAD pts) J - CURVE ONTARGET (high risk pts, mainly with CAD) 30 3 CV events (%) 30 20 10 CV events (%) 20 10 2 1 Adjusted HR 0 110 >110 to 120 to >120 130 to >130 140 to >140 150 to >150 160 >160 On-treatment SBP (mmhg) 0 112 121 126 130 133 136 140 144 149 160 On-treatment SBP (mmhg) 0 Cardiac events (%) 30 20 10 VALUE (High risk pts) CV events (%) 35 30 25 20 15 10 5 TNT (CAD pts) 5 4 3 2 1 Adjusted HR 0 < 120 >120 to 130 to >130 140 to >140 150 to >150 160 to >160 170 to >170 180 180 On-treatment SBP (mmhg) 0 60 61-70 71-80 81-90 91-100 100 > 100 On-treatment DBP (mmhg) 0

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

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 2006 48:833-838.

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

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, 27:2121 2158

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 2007,115:2761-2788.

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;115:2761-2788

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