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Beta-Blocker For Reducing Cardiovascular Disease

Beta-Blocker For Reducing Cardiovascular Disease. Dr Suryono, SpJP. FIHA. Elevated HR Predicts Excessive Male CV Mortality. Heart Rate. 30 20 10 0. 30-67 68-75 76-83 84-91 > 92. Age-adjusted incidence of CV mortality/1000. 35-64 (p < 0.001). 65-94 (p < 0.01).

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Beta-Blocker For Reducing Cardiovascular Disease

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  1. Beta-Blocker For Reducing Cardiovascular Disease Dr Suryono, SpJP. FIHA

  2. Elevated HR Predicts Excessive Male CV Mortality Heart Rate 30 20 10 0 30-67 68-75 76-83 84-91 > 92 Age-adjusted incidence of CV mortality/1000 35-64 (p < 0.001) 65-94 (p < 0.01) Men initially free of CV disease Adapted from Kannel, Am. Heart. J., 1987

  3. Elevated HR is an Important Risk Factor Elevated HR is linked to or predicts : • Higher hypertensive risk • Ischaemia in coronary disease • Coronary heart disease • Cardiovascular mortality Palatini & Julius; J. Hypertens., 1997

  4. Increased Heart Rate Means Increased Hypertensive Risk (Data adjusted for standard risk factors) HR quintiles Relative Risk 0.5 1.0 1.5 2.0 2.5 Low 1 2 3 4 High 5 1.04 1.34 1.57 1.66 p = 0.014 Adapted from Selby et al., Am. J. Epidemiol., 1990

  5. Coronary Disease : Ischaemia is Closely Linked to HR 60 50 40 30 20 10 0 Magnitute of HR increase > 8 bpm > 10 bpm > 15 bpm > 20 bpm Likelihood of Ischaemia (%) n = 50 <10 10-19 20-29 30-39 40-49 Duration of period of HR increase (min) Andrews et al., Circulation, 1993

  6. Elevated Heart Rate Increased Likelihood of CHD 2.00 1.75 1.50 1.25 1.00 0.75 MEN WOMEN 1.49 Relative Risk 1.40 1.25 1.10 < 74 74-84 > 84 < 74 74-84 > 84 Heart Rate Adapted from Gillum, Am. Heart. J., 1991

  7. Elevated HR Predicts Male Sudden Death 6 5 4 3 2 1 0 MEN 2-year age-adjusted mortality rate WOMEN < 65 66-73 74-79 80-87 > 88 Quintile of heart rate Adapted from Kannel et al., Am Heart J., 1985

  8. Elevated HR : Connection With Insulin Resistance  Heart Rate  SNS tone Beta-receptors Alpha-receptors Acute effects Chronic effect Vasoconstriction Low nutritional flow  Fast twitch fibers  Muscle glucose uptake Insulin resistance Dyslipidemia

  9.  Cholest  Glucose  HDL-Ch  Insulin Heart Rate  Triglycer  Blood pressure  Haemato- crit  B.M.I. HR is a Marker for Coronary Risk  p < 0.0001  p < 0.01  p < 0.05 Palatini & Julius; J. Hypertens., 1997

  10. Correlation between heart rate and male’s death Singh AHJ suppl. 2003;5(G);G3-G9

  11. Lower HR can Prolong Life 1.8 1.6 1.4 1.2 1.0 MEN Adjusted Odds Ratio 1.39 1.39 (n = 747) 1.38  HR  Smoking  SBP Adapted from Gillum, Am. Heart. J., 1991

  12. Why does heart rate increase ?

  13. Causes of Sympathetic Nervous System (SNS) Activation Diet Genetic Factors SNS Activation Psychosocial Stress Acute Physical Stressors Catecholamine levels  Heart rate Cardiac output Blood pressure Platelet aggregation

  14. Awareness of the Sympathetic Nervous System Cardiovascular risks associated with elevated levels of plasma catecholamines • Left Ventricular Hypertrophy • Vascular Hypertrophy • Arteriosclerosis • Platelet Aggregability • Sudden Cardiac Death • Myocardial Infarction

  15. Role of BB

  16. Cardiovascular Continuum

  17. BB are equally effective? NO • ISA(+) lessen anti-HT action • B2 blockade properties lessen anti-HT action • Non selective < selective

  18. Effect of Beta-Blockers on Haemodynamic Response to an Acute Stressor Without ISA With ISA Heart Heart STRESS  HR HR controlled  CO BP controlled  BP Catecholamines Catecholamines Vessels Vessels TPR reduced  TPR Blood Platelets Blood Platelets  Coagulation  Coagulation ?

  19. Hypothesis for the Action of Bisoprolol Sympathetic Nervous System Higher Centers Sympathetic Ganglia  Synaptic Transmission Neuromuscular Synapse  NE Release SA node  HR Cardiac Muscle Adrenal Medulla Vascular Muscle  NE Storage  Catecholamine Production Vasodilation  BP Adapted from Kailasam et al., Hypertension, 1995; 26: 143-149

  20. The use of BB in clinical practice

  21. 1. Anti Hypertensive Properties • Established • since 2006 : CONTROVERSIAL

  22. British Hypertension Society Guidelines–2004; based on renin levels Younger (< 55 years)and non-black Older (≥ 55 years)and black C or D A or B Step 1 A or B plus C or D Step 2 A or B + C + D Step 3 Add either  blocker or spironolactone or other diuretic Step 4(Resistant hypertension) A = ACE inhibitor or angiotensin receptor blocker, B = Beta-blocker, C = Calcium channel blocker, D = Duiretic (thiazide or thiazide – like)

  23. Young Hypertensive • Diastolic HT ~ BMI> • Central obesity • Stimulate sympathomimetic activity

  24. Mech of action BB in young hypertensive ISA (-) ISA (+) • Depends on renin level • High renin or normal renin : effective • Low renin: not effective • Fall of systemic vascular resistance (b2) through NO release • Fall in Plasma Nor-adr • Renin little effect

  25. GOOD ANTIHYPERTENSIVE EFFECT -Antagonist may be either 1-cardioselective or non-cardioselective (1- 2 antagonism). Sinus rate Renin inhibiton Bradycardia Negative inotropy Less bronchopasm 1-SELECTIVE Metabolic Fewer peripheral effects Circulatory Similar cardiac and antihypertensive effects More marked pulmonary and peripheral effects NONSELECTIVE (1-2)

  26. 2. Anti Heart Failure Properties • New • NOT all beta blockers are EQUAL • NON-ISA is vital component • Bisoprolol, Carvedilol, Metoprolol: Mort <35% Xamoterol Bucindolol Nevibolol Mortality >25% Mortality n.n. <10% ISA + Mortality n.s.<12% (elderly)

  27. Mechanism of anti heart failure • Bradycardia-prolonged diastolic coronary filling time • Anti-ischaemia-decreased oxyg. requirement • Anti-arrhythmic( sudden death) • Inhibition of catecholamine-induced necrosis and apoptosis (beta-1) • Up-regulation of B-1 receptors • Inhibition of renin-angiotensin-aldosterone system • Increase in atrial natriuretic factor

  28. 6 months 24 months week week week week week week week week week week week week 12 0 2 4 6 8 10 28 30 32 34 36 20 10 enalapril (mg/d) 5 10 7.5 5 3.75 2.5 bisoprolol (mg/d) 1.25 10 7.5 5 Random 3.75 2.5 1.25 bisoprolol (mg/d) -isation 20 10 enalapril (mg/d) 5 Monotherapy Combination therapy 6 months 6 to 18 months CIBIS III Dose titration

  29. 3. BB and metabolic changes • B2-blockage: HbA1-c, BS, FFA, insulin sensitivity, TG, VLDL, HDL • Non selective (propranolol, timolol, nadolol) or partially selective (atenolol, metoprolol) : the offenders • Highly B1-selective(bisoprolol), a-b1 (carvedilol) • Non selective may also block B3 receptor: increased obesity and “diabesity”

  30. 1-blockade benefits in central obesity/insulin resistance/DM2 with hypertension DM2/obese :1-blockade Insulin resistance Insulin/leptin Noradrenaline Release  PRA  Angiotensin II Ventriculararrhythmias  BP + non-dipping at night  Intra-glomerular pressure + nephropathy B1 stimulation-induced cardiac and coronary artery damage (atheroma)

  31. HEPARIN or LMWH Aspirin -BLOCKADE Hypertension tachycardia O2 wastage Increased O2 demand 4. UNSTABLE ANGINA AT REST PLATELET AGGREGATION Subendocardial ischemia LV end-diastolic pressure  • Gp IIb/IIIa blockers • If troponin • High risk group NITRATES (intravenous) Increased sympathetic drive Increasing ischemic damage LV failure pain Diltiazem in selectec cases Regional ischemia

  32. Secondary prevention of myocardial infarction with different types of b - blockers b -30 1 - selective y t without ISA i l a t r non-selective o m without ISA f -20 o b 1 - selective n o with ISA i t c u non-selective d with ISA -10 e R b b - blockers - blockers without ISA with ISA - Yusuf S et al. Progress Cardiovasc. Diseases 1985; 5: 335-371

  33. 100 75 / 1 75 50 35 B1/B2 35 / / 1 1 20 Selectivity / 1 25 1 Ratios / 2 0 Propranolol Atenolol Bisoprolol Metoprolol Betaxolol 1 / 2 5 1 / 1 300 / 50 ICI 118,551 1 / 300 Beta1 and Beta2 Selectivity Ratios Wellstein et al Europ Heart J 1987

  34. Efektif, Aman, TerjangkauLodoz2,5 & Lodoz5(Bisoprolol 2,5 & 5 mg + HCT 6,25)Concor 2,5 &Concor 5(Bisoprolol 2,5 & 5 mg)

  35. Thank You

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