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Avoiding End Organ Damage DR. SHAHBAZ AHMED KURESHI MBBS, MCPS, D. CARD, D. Med.Sc, FACC, FAHA, FACP, FPAMS Consultant Cardiologist, Head Department of.

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Presentation on theme: "Avoiding End Organ Damage DR. SHAHBAZ AHMED KURESHI MBBS, MCPS, D. CARD, D. Med.Sc, FACC, FAHA, FACP, FPAMS Consultant Cardiologist, Head Department of."— Presentation transcript:

1 Avoiding End Organ Damage DR. SHAHBAZ AHMED KURESHI MBBS, MCPS, D. CARD, D. Med.Sc, FACC, FAHA, FACP, FPAMS Consultant Cardiologist, Head Department of Cardiology and Nuclear Cardiology, Federal Government Services Hospital, Islamabad

2 Destination <120/80 Lower is Better !

3 Thus, hypertension management is a public health priority 1. WHO, 2002; 2. AHA, 2004 Hypertension Represents a Significant Burden on Healthcare Worldwide, hypertension is responsible for –62% of strokes 1 –49% of heart attacks 1 Hypertension is the third leading risk factor for disease –Causes 7.1 million premature deaths each year 1 –4.5% of global burden of disease 1 Hypertension represents a high burden on healthcare expenditure –In 2004, the direct and indirect cost of high blood pressure in the US was $55.5 billion; drug costs accounted for $21 billion 2

4 National Health Survey Circulatory diseases account for over 100,000 deaths a year or 12% of all cause mortality. Overall 18% of adults in Pakistan suffer from HBP, 21.5% in urban areas and 16.2% in rural areas. One in every 3 adults over age 45 suffer from hypertension. Very few Pakistanis with hypertension (<3%) have their B.P controlled. PROCOR: 7/25/99 The National Health Survey in Pakistan published in 1998 by (PMRC) 1


6 Potentially Preventable Causes of Death

7 BP and increasing age Kearney et al, Lancet 2005

8 Prevalence of hypertension is high Prevalence of hypertension (%) Kearney PM et al.,Lancet. 2005;365: Prevalence of hypertension in people aged 20 years and older

9 ESH-ESC guidelines, 2003, J Hypertens Factors Necessary to Assess the Risk or Target Organ Damage Risk stratificationTarget organ damage Systolic / diastolic BP Left ventricular hypertrophy Men > 55; Women > 65 yearsUltrasound: Evidence of thickening Tobacco smokingor plaques Dyslipidemia Increased creatininemia Family history + Microalbuminuria (malb/creat ratio) Protein C-reactive > 6 mg/dl men: >2.5 mg/mmol women: >3.5 mg/mmol

10 Hypertension is a leading cause for cardiovascular morbidity MenWomenMenWomenMenWomenMenWomen Normotensive Hypertensive Coronary DiseaseStroke Peripheral Arterial Disease Heart Failure Biennial Age-Adjusted Rate per 1, Year Follow-up in Patients Aged Years 1,2 1. Kannel W.B. et al., JAMA 1996; 275: Kannel W.B. et al., J Hum Hypertens 2000; 14: 83-90


12 Vasan et al. N Engl J Med High-Normal BP and CVD RiskWomen Time (years) P<.001 Men Cumulative Incidence (%) Time (years) P<.001 High normal /85-89 mm Hg Normal /80-84 mm Hg Normal /80-84 mm Hg Optimal <120/80 mm Hg Optimal <120/80 mm Hg Prehypertension

13 Lewington S et al. Lancet. 2002; 360: Relationship between (a) systolic blood pressure (SBP) and (b) diastolic blood pressure (DBP) and ischaemic heart disease mortality in one million individuals in the general population. CI, confidence interval. Blood pressure, heart disease and age correlate closely

14 CV Mortality Risk Doubles with Each 20/10 mm Hg BP Increment* *Individuals aged 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: JNC 7. JAMA. 2003;289: CV mortality risk SBP/DBP (mm Hg) /75135/85155/95175/105

15 Absolute Risk Of Coronary Artery Disease And Stroke Mortality

16 Curvilinear Relation Of Blood Pressure And Cardiovascular Risk

17 Geographical Variation In Hypertension Prevalence In Population Of African And European Ancestry

18 Age- Dependent Changes In Systolic and Diastolic Blood Pressure In USA

19 Sympathetic Nervous System

20 Endothelium-Derived Relaxing And Constricting Factors

21 Vascular Remodeling Of Small And Large Arteries

22 The Renin- Angiotensin- Aldosterone System

23 Schematic Representation Of The Central Role Played By Angiotensin 1 Receptor (AT 1 R)

24 Superiority Of Ambulatory Over Office Blood Pressure Measurements

25 24-Hour Ambulatory Blood Pressure Recording

26 Relation Between Systolic Blood Pressure And The Rate Of Progression Of Coronary Atheroma

27 Klausen et al. Hypertension 2005;46:33– Cumulative mortality (%) RR of death RR of CHD 10 UAE (µg/min) Years from entry UAE  4.8 µg/min UAE <4.8 µg/min Cox-estimated age-adjusted curves of cumulative incidence of coronary heart disease for a 60-year-old person based on 1,734 hypertensive subjects with microalbuminuria and normoalbuminuria Microalbuminuria and CV Complications inHypertension: Is the Threshold Correct? The Copenhagen City Heart Study

28 Arnlov et al. Circulation 2005;112:969– Percentage Years < Median  Median Survival free of CVD According to sex-specific median UACR Microalbuminuria and Incidence of CV events: The Framingham Study

29 Blood Pressure Risk Stratification (ESH/ESC 2007) Mancia G et al., J Hypertens 2007;25:1105–87

30 Blood pressure reductions of as little as 2 mmHg reduce the risk of cardiovascular events by up to 10% 1 Meta-analysis of 61 prospective, observational studies One million adults 12.7 million person-years 2 mmHg decrease in mean systolic blood pressure 10% reduction in risk of stroke mortality 7% reduction in risk of ischemic heart disease mortality 1. Lewington S et al. Lancet. 2002;360:1903–1913.

31 Fatal and non- fatal events Mortality Fatal and non- fatal events Mortality Isolated systolic hypertension StrokeCHD All Causes CVNon CV StrokeCHD All Causes CVNon CV Systolic–diastolic hypertension <0.001 <0.01 NS Event reduction in patients on active antihypertensive treatment vs placebo or no treatment CHD: coronary heart disease; CV: cardiovascular Effective blood pressure control reduces cardiovascular morbidity and mortality Cifkova R, et al. J Hypertens. 2003;21:1011–1053. Relative Risk Reduction (%) ESH/ESC guidelines consider systolic values of <139 mmHg and diastolic values of <89 mmHg to be normal

32 Relations Between Achieved Blood Pressure Control And Declines In Glomerular Filtration Rate

33 Idealized Curves Of Cerebral Blood Flow At Varying levels Of Systemic Blood Pressure

34 Absolute Benefits For The Prevention Of Fatal Nonfatal Cardiovascular Events

35 Odds Ratio For Cardiovascular Events And Systolic Blood Pressure

36 Graphical Representation Of Three Hypothetical Relationships Between Levels Of Blood Pressure And Risk Of Cardiovascular Disease

37 Relationship Between The Net Change In Urinary Sodium Excretion And Systolic Blood Pressure

38 Mean Cerebral Blood Flow Autoregulation Curves

39 Trials Comparing The Effect On Primary End Point Of Treatment Based On Different Antihypertensive Drugs

40 Bakris et al. Am J Kidney Dis. 2000;36: ; Bakris et al. Arch Intern Med. 2003;163: ; Lewis et al. N Engl J Med. 2001;345: Number of BP Medications Antihypertensive Therapy: Number of Agents Required to Achieve BP Goal UKPDS (<85 mm Hg, diastolic) 4321 MDRD (<92 mm Hg, MAP) HOT (<80 mm Hg, diastolic) AASK (<92 mm Hg, MAP) RENAAL (<140/90 mm Hg) IDNT (  135/85 mm Hg)


42 An Algorithm For The decision To Manage Patients With Different Average Blood Pressure Levels

43 Algorithm For Therapy Of Hypertension

44 l Get patients to BP goal l Provides 24 hour BP control l Has good tolerability l Has ‘added’ protection What qualities do you want to see in an effective Anti Hypertensive agent?

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49 Marc A. Pfeffer, M.D., Ph.D. (Chair), John J.V. McMurray, M.D. (Co-Chair), Eric J. Velazquez, M.D., Jean-Lucien Rouleau, M.D., Lars Køber, M.D., Aldo P. Maggioni, M.D., Scott D. Solomon, M.D., Karl Swedberg, M.D., Ph.D., Frans Van de Werf, M.D., Ph.D., Harvey D. White, D.Sc., Jeffrey D. Leimberger, Ph.D., Marc Henis, M.D., Susan Edwards, M.S., Steven Zelenkofske, D.O., Mary Ann Sellers, M.S.N., and Robert M. Califf, M.D., for the VALIANT Investigators VALsartan In Acute myocardial iNfarcTion Dr Shahbaz A. Kureshi Head, Department of Cardiology Federal Govt. Serv. Hospital, Islamabad

50 Conclusion In patients with MI complicated by heart failure, left ventricular dysfunction or both: Valsartan is as effective as a proven dose of captopril in reducing the risk of: –Death –CV death or nonfatal MI or heart failure admission Combining valsartan with a proven dose of captopril produced no further reduction in mortality—and more adverse drug events. Implications: In these patients, valsartan is a clinically effective alternative to an ACE inhibitor.

51 Treatment Enables Retardation of the Progression of Renal Disease Early stage Late stage Terminal stage Severity of renal disease IRMA 2 MARVAL IDNT RENAAL Microalbuminuria Macroalbuminuria ESRD PreventionProtection Benedict study Cardiovascular morbidity and mortality

52 Conclusions In type 2 diabetic pts with microalbuminuria arterial BP was reduced to the same extent in the valsartan and amlodipine groups AER was significantly reduced in the valsartan group compared with the amlodipine group. Significantly more pts regressed to normoalbuminuria in the valsartan group The effect of valsartan on AER was similar in both the normotensive and hypertensive subgroups


54 “First do no harm”

55 Algorithm for Evaluating Patients in whom Renal Artery Stenosis Is Suspected

56 Path physiology Of Primary Aldosteronism

57 Mendelian Forms Of Hypertension That Cause Mineralcorticoid- induced Hypertension

58 The Mechanisms By Which Chronic Diuretic Therapy May Lead TO Various Complications

59 Theoretical Therapeutic And Toxic Logarithmic And Linear Dose Response Curve

60 Classification Of Beta- Adrenoreceptor Blockers On The Basic Of Cardioselectivity And Intrinsic Sympathomimetic Activity

61 USA 53.1 Canada 41.0 Mexico 21.8 Germany 33.6 Greece 49.5 England 29.2 Egypt 33.5 South Africa* 47.6 Japan* 55.7 Taiwan 18.0 China 28.8 Worldwide blood pressure control rates in treated hypertensive patients are low Kearney P.M. et al., J Hypertens 2004; 22: 11–19; * Data for men only Turkey 19.8

62 Simplified Schematic View Of The Adrenergic Nerve

63 Angiotensinogen Angiotensin IAngiotensin II CE Renin Chymase Bradykinin Inactive K+K+ Na + ACTH Other Adapted from Unger T. Am J Cardiol 2002; 89 (suppl):3A-10A. RAA system targets multiple receptor sites Aldosterone

64 Kaplan NM & Opie LH. Lancet 2006; 367: Major mechanisms –(1) increased adrenergic drive, as often found in young people (aged 30– 49 years); –(2) high-renin hypertension, as seen in individuals with renal dysfunction; –(3) low-renin hypertension, as recorded in individuals with inherently raised aldosterone concentrations; –(4) increased peripheral vascular resistance (PVR), as seen in elderly patients. CO=cardiac output. β=β-adrenergic stimulation α=α- adrenergic stimulation. AII=angiotensin II. Hypertension has a multifactorial origin

65 Renin ACE Non-ACE Pathways* Angiotensinogen Angiotensin II Angiotensin I AT 1 receptor ARB Blockade AT 2 receptor *not affected by ACE inhibitors Vasoconstriction Hypertrophy and Proliferation Oxidation and Inflammation PAI-1 expression and release Vasodilation Nitric Oxide release Antiproliferation Blockade of AT 1 receptor Activation of AT 2 receptor Vascular Protection Adapted from: Kaschina E and Unger T. Blood Press 2003;12: Unger T. J Hypertens 1999;17: Angiotensin (AT1) receptor blockade provides vascular protection

66 Renin profile correlates with CV risk Alderman MH et al. N Engl J Med. 1991;324: Smoking Events per 1000 person-years Low Normal High No Yes Renin Profile Fasting Blood Glucose (mmol/L) Events per 1000 person-years Low Normal High 7.8  7.8 Renin Profile Cholesterol (mmol/L) Events per 1000 person-years Low Normal High 6.3  6.3 Renin Profile

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