Presentation is loading. Please wait.

Presentation is loading. Please wait.

Avoiding End Organ Damage

Similar presentations


Presentation on theme: "Avoiding End Organ Damage"— 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 Hypertension Represents a Significant Burden on Healthcare
Potentially preventable causes of death Hypertension Represents a Significant Burden on Healthcare Worldwide, hypertension is responsible for 62% of strokes1 49% of heart attacks1 Hypertension is the third leading risk factor for disease Causes 7.1 million premature deaths each year1 4.5% of global burden of disease1 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 billion2 The World Health Organization’s (WHO) World Health Report for 2002 states that, worldwide, high blood pressure is estimated to cause 7.1 million deaths, about 13% of the total global fatality and 4.5% of attributable disability adjusted life-years (DALYs).1 Across WHO regions, research indicates that about 62% of strokes and 49% of heart attacks are caused by high blood pressure.1 In 2004, the American Heart Association (AHA) estimated the direct and indirect cost of high blood pressure in the US to be $55.5 billion.2 References Facts and Figures: World Health Report World Health Organization. Available at (last accessed date 10/2006). AHA. Heart Disease and Stroke Statistics Update. Available at: (last accessed date 10/2006). Thus, hypertension management is a public health priority 1. WHO, 2002; 2. AHA, 2004

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

5

6 Potentially preventable causes of death

7 BP and increasing age Kearney et al, Lancet 2005

8 Prevalence of hypertension is high
Potentially preventable causes of death Prevalence of hypertension is high Prevalence of hypertension in people aged 20 years and older 2000 Prevalence of hypertension (%) 2025 GLB.IRB 071022b-Irbe Reference : Kearney PM et al.,Lancet. 2005;365: Kearney PM et al.,Lancet. 2005;365: 8

9 Factors Necessary to Assess the Risk or Target Organ Damage
Risk stratification Target organ damage Systolic / diastolic BP Left ventricular hypertrophy Men > 55; Women > 65 years Ultrasound: Evidence of thickening Tobacco smoking or 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 ESH-ESC guidelines, 2003, J Hypertens

10 Hypertension is a leading cause for cardiovascular morbidity
Potentially preventable causes of death Hypertension is a leading cause for cardiovascular morbidity 36-Year Follow-up in Patients Aged Years1,2 Coronary Disease Stroke Peripheral Arterial Disease Heart Failure 50 45.4 40 Normotensive Hypertensive Biennial Age-Adjusted Rate per 1,000 30 22.7 21.3 20 13.9 12.4 GLB.IRB 071022b-Irbe Reference : 1. Kannel W.B. et al., JAMA 1996; 275: 2. Kannel W.B. et al., J Hum Hypertens 2000; 14: 83-90 9.5 9.9 10 7.3 6.2 6.3 5.0 3.3 3.5 2.4 2.0 2.1 Men Women 1. Kannel W.B. et al., JAMA 1996; 275: 2. Kannel W.B. et al., J Hum Hypertens 2000; 14: 83-90 10

11

12 High-Normal BP and CVD Risk
Potentially preventable causes of death High-Normal BP and CVD Risk High normal /85-89 mm Hg Normal /80-84 mm Hg Optimal <120/80 mm Hg Prehypertension Men Cumulative Incidence (%) 14 12 10 8 6 4 2 Time (years) P<.001 Women 10 8 6 4 2 Time (years) 12 14 P<.001 Studies have shown that risk of CVD is increased even at levels of BP considered to be high-normal. The cardiovascular (CV) event rates of 6589 patients from the Framingham Study who had high-normal, normal, or optimal BP at baseline (as defined above) were recorded over 14 years. Men and women with high-normal BP at baseline had a higher incidence of CVD on follow-up than did those with normal or optimal BP. This relationship was consistent in both men and women, and in middle-aged and elderly subjects. The rate of CV events in persons with normal or optimal BP was low, but a continuous gradient of increasing risk was observed across the 3 BP categories.9 Vasan et al. N Engl J Med. 2001 9. Vasan RS, Larsen MG, Leip EP, et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med. 2001;345: SLIDE 12

13 Blood pressure, heart disease and age correlate closely
Potentially preventable causes of death Blood pressure, heart disease and age correlate closely 256 128 64 32 16 8 4 2 1 80–89 years 70–79 years 60–69 years 50–59 years 40–49 years Age at risk: Usual SBP (mmHg) Usual DBP (mmHg) Ischaemic heart disease mortality (floating absolute risk and 95% CI) a b GLB.IRB 071022b-Irbe Reference : 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. Lewington S et al. Lancet. 2002; 360:

14 Potentially preventable causes of death
CV Mortality Risk Doubles with Each 20/10 mm Hg BP Increment* 8 7 6 CV mortality risk 5 4 3 2 CV Mortality Risk Doubles with Each 20/10 mm Hg BP Increment Slide Summary According to a meta-analysis of over 60 prospective studies, the risk of cardiovascular mortality doubles with each rise of 20 mm Hg in systolic blood pressure (BP) and 10 mm Hg in diastolic BP. Background In a meta-analysis of 61 prospective, observational studies conducted by Lewington et al involving one million adults with no previous vascular disease at baseline, the researchers found that between the ages of years, each incremental rise of 20 mm Hg systolic BP and 10 mm Hg diastolic BP was associated with a twofold increase in death rates from ischemic heart disease and other vascular disease. The researchers also noted that when attempting to predict vascular mortality risk from a single BP measurement, the average of systolic and diastolic BP was “slightly more informative” than either alone, and that pulse pressure was “much less informative.” The seventh report Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) notes this study result as yet more information linking hypertension to high risk for cardiovascular events. Lewington S, Clarke R, Qizilbash H, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2003;361: JNC 7. JAMA. 2003;289: 1 115/75 135/85 155/95 175/105 SBP/DBP (mm Hg) *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:

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 (AT1R)

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 Microalbuminuria and CV Complications inHypertension: Is the Threshold Correct? The Copenhagen City Heart Study 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 4 3 2 1 UAE ³4.8 µg/min UAE ³4.8 µg/min UAE <4.8 µg/min RR of CHD 30 20 10 < –5 5–10 >10 Cumulative mortality (%) 4 3 2 1 RR of death Years from entry < –5 5–10 >10 UAE (µg/min) Klausen et al. Hypertension 2005;46:33–7

28 Microalbuminuria and Incidence of CV events: The Framingham Study
Survival free of CVD According to sex-specific median UACR 100 95 90 Percentage < Median ³ Median Years Arnlov et al. Circulation 2005;112:969–75

29 Blood Pressure Risk Stratification (ESH/ESC 2007)
Potentially preventable causes of death Blood Pressure Risk Stratification (ESH/ESC 2007) GLB.IRB 071022b-Irbe Mancia G et al., J Hypertens 2007;25:1105–87 29

30 2 mmHg decrease in mean systolic blood pressure
Potentially preventable causes of death 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 7% reduction in risk of ischemic heart disease mortality GLB.IRB 071022b-Irbe Methods Data from a meta-analysis of 61 prospective, observational studies has provided powerful evidence that throughout middle and old age, blood pressure (BP) is strongly and directly related to vascular mortality.1 These findings show, for example, that a 10 mmHg lower systolic BP is associated over the long-term with a 40% lower risk of stroke death and a 30% lower risk of death from ischemic heart disease (IHD) or other vascular causes. Importantly, within each decade of life between 40 and 89 years the proportional difference in the risk of vascular death associated with a given absolute difference in mean BP is roughly equivalent down to at least 115 mmHg for systolic BP and 75 mmHg for diastolic BP (below which there is little evidence). Thus, there was no evidence of a J curve across all middle and older age groups. Perhaps most striking is the practical implications of these data: even a small, 2 mmHg fall in mean systolic BP would be associated with large absolute reductions in premature deaths and disabling strokes.1 As shown here, a 2 mmHg lower mean systolic BP could lead to a 7% lower risk of IHD death and a 10% lower risk of stroke death.1 Reference : Lewington S, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360:1903–1913. 2 mmHg decrease in mean systolic blood pressure 10% reduction in risk of stroke mortality 1. Lewington S et al. Lancet. 2002;360:1903–1913. 30

31 Potentially preventable causes of death
Effective blood pressure control reduces cardiovascular morbidity and mortality Systolic–diastolic hypertension Isolated systolic hypertension Fatal and non- fatal events Fatal and non- fatal events Mortality Mortality 10 All Causes All Causes CV Non CV CV Non CV Stroke CHD Stroke CHD NS NS -10 Relative Risk Reduction (%) -20 <0.01 <0.01 0.02 GLB.IRB 071022b-Irbe Methods Meta-analysis of data from trials of active antihypertensive treatment compared with placebo have shown that blood pressure lowering reduces:1 Cardiovascular and total mortality Stroke Coronary events. Benefits have been shown in placebo-controlled trials that have used all major antihypertensive drug classes, including: Diuretics Beta blockers Calcium antagonists Angiotensin-converting enzyme (ACE)-inhibitors Angiotensin receptor antagonists. Benefits have been proven: In patients with systolic-diastolic hypertension In elderly patients with isolated-systolic hypertension. Reference : Cifkova R, et al. for the ESH/ESC Hypertension Guidelines Committee. Practice guidelines for primary care physicians: 2003 ESH/ESC hypertension guidelines. J Hypertens. 2003;21:1011–1053 <0.001 0.01 <0.001 -30 <0.001 -40 ESH/ESC guidelines consider systolic values of <139 mmHg and diastolic values of <89 mmHg to be normal <0.001 -50 Event reduction in patients on active antihypertensive treatment vs placebo or no treatment CHD: coronary heart disease; CV: cardiovascular Cifkova R, et al. J Hypertens. 2003;21:1011–1053.

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 Antihypertensive Therapy: Number of Agents Required to Achieve BP Goal
Potentially preventable causes of death Antihypertensive Therapy: Number of Agents Required to Achieve BP Goal UKPDS (<85 mm Hg, diastolic) MDRD (<92 mm Hg, MAP) HOT (<80 mm Hg, diastolic) AASK (<92 mm Hg, MAP) Polypharmacy may be necessary to reach BP goals in hypertension management.45,47,48 RENAAL (<140/90 mm Hg) IDNT (135/85 mm Hg) 1 2 3 4 Number of BP Medications 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: Trial abbreviations: UKPDS = United Kingdom Prospective Diabetes Study; MDRD = Modification of Diet in Renal Disease; HOT = Hypertension Optimal Treatment; AASK = African American Study of Kidney Disease; RENAAL = Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan; IDNT = Irbesartan Diabetic Nephropathy Trial. 45. Lewis EJ, Hunsicker LG, Clarke WR, et al, for the Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med ;345: 47. Brenner BM, Cooper ME, de Zeeuw D, et al, for the RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345: 48. Bakris GL, Williams M, Dworkin L, et al, for the National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Special report: preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000;36: 49. Bakris GL, Weir MR, Shanifar S, et al, for the RENAAL Study Group. Effects of blood pressure level on progression of diabetic nephropathy. Results from the RENAAL study. Arch Intern Med. 2003;163: SLIDE 40 40

41 Potentially preventable causes of death
41

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

43 Algorithm For Therapy Of Hypertension

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

45 45 45

46 46 46

47 47

48 48

49 Head, Department of Cardiology Federal Govt. Serv. Hospital, Islamabad
VALsartan In Acute myocardial iNfarcTion 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 The Valsartan in Acute Myocardial Infarction Trial –VALIANT. 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. 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 hospital admission for heart failure. Combining valsartan with a proven dose of captopril produced no further reductions in mortality and resulted in more adverse drug events. Implications are that by preserving all the cardiovascular benefits of an ACE inhibitor in this population, valsartan is a clinically effective alternative for high risk patients post-MI. 50

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

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

53 Potentially preventable causes of death
53

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 Potentially preventable causes of death
Worldwide blood pressure control rates in treated hypertensive patients are low Germany 33.6 Canada 41.0 Japan* 55.7 England 29.2 Greece 49.5 USA 53.1 China 28.8 Taiwan 18.0 GLB.IRB 071022b-Irbe Mexico 21.8 Turkey 19.8 Egypt 33.5 South Africa* 47.6 Kearney P.M. et al., J Hypertens 2004; 22: 11–19; * Data for men only

62 Simplified Schematic View Of The Adrenergic Nerve

63 RAA system targets multiple receptor sites
Potentially preventable causes of death RAA system targets multiple receptor sites Na+ K+ Angiotensinogen Aldosterone Renin Other ACTH Chymase CE Angiotensin I Angiotensin II Bradykinin Inactive GLB.IRB 071022b-Irbe Methods The RAAS is stimulated by: Fall in BP Fall in circulating volume Sodium depletion Any of the above stimulate renin release from the juxtaglomerular apparatus Renin converts angiotensinogen to angiotensin I Angiotensin I is converted to angiotensin II by angiotensin converting enzyme (ACE) Angiotensin II is a potent Vasoconstrictor Anti-natriuretic peptide Stimulator of aldosterone release from the adrenal glands Aldosterone is also a potent antinatriuretic and antidiuretic peptide Angiotensin II is also a potent hypertrophic agent which stimulates myocyte and smooth muscle hypertrophy in the arterioles Reference : Adapted from Unger T. Am J Cardiol 2002; 89 (suppl):3A-10A. Adapted from Unger T. Am J Cardiol 2002; 89 (suppl):3A-10A.

64 Hypertension has a multifactorial origin
Potentially preventable causes of death Hypertension has a multifactorial origin 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. GLB.IRB 071022b-Irbe Methods There is still much uncertainty about the pathophysiology of hypertension. A small number of patients (between 2% and 5%) have an underlying renal or adrenal disease as the cause for their raised blood pressure. In the remainder, however, no clear single identifiable cause is found and their condition is labelled “essential hypertension”. A number of physiological mechanisms are involved in the maintenance of normal blood pressure, and their derangement may play a part in the development of essential hypertension. It is probable that a great many interrelated factors contribute to the raised blood pressure in hypertensive patients, and their relative roles may differ between individuals. Among the factors that have been intensively studied are salt intake, obesity and insulin resistance, the renin­angiotensin system, and the sympathetic nervous system. In the past few years, other factors have been evaluated, including genetics, endothelial dysfunction (as manifested by changes in endothelin and nitric oxide), low birth weight and intrauterine nutrition, and neurovascular anomalies. Reference: Kaplan NM & Opie LH. Lancet 2006; 367: Kaplan NM & Opie LH. Lancet 2006; 367:

65 Angiotensin (AT1) receptor blockade provides vascular protection
Potentially preventable causes of death Angiotensin (AT1) receptor blockade provides vascular protection Angiotensinogen Renin Angiotensin I Non-ACE Pathways* ACE Angiotensin II *not affected by ACE inhibitors ARB Blockade AT1 receptor AT2 receptor GLB.IRB 071022b-Irbe Reference : Kaschina E and Unger T. Blood Press 2003;12:70-88. Unger T. J Hypertens 1999;17: Blockade of AT1 receptor Activation of AT2 receptor Vasoconstriction Hypertrophy and Proliferation Oxidation and Inflammation PAI-1 expression and release Vasodilation Nitric Oxide release Antiproliferation Vascular Protection Adapted from: Kaschina E and Unger T. Blood Press 2003;12:70-88. Unger T. J Hypertens 1999;17:

66 Renin profile correlates with CV risk
Potentially preventable causes of death Renin profile correlates with CV risk Smoking Events per 1000 person-years Low Normal High No Yes Renin Profile Cholesterol (mmol/L) Events per 1000 person-years Low Normal High 6.3 6.3 Renin Profile 34.5 8.4 10.2 3.2 0.9 Fasting Blood Glucose (mmol/L) Events per 1000 person-years Low Normal High 7.8 7.8 Renin Profile GLB.IRB 071022b-Irbe Methods The prognostic value of plasma-renin activity was tested in a systematic work-site treatment program in 1717 subjects with mild to moderate hypertension (mean age 53 years). The incidence of myocardial infarction during 8.3 years of follow-up was 14.7 events per 1000 person-years among subjects with a high renin profile, 5.6 among those with a normal renin profile, and 2.8 among those with a low renin profile. The renin profile before treatment remained independently associated with the subsequent risk of myocardial infarction, but not with stroke or noncardiovascular events (after adjustment for race, age at entry, sex, serum cholesterol levels, smoking status, electrocardiographic evidence of left ventricular hypertrophy, blood glucose level, body-mass index, history of cardiovascular disease or treatment, blood pressure, and use of beta-blockers). Reference: Alderman MH et al. N Engl J Med. 1991;324: Alderman MH et al. N Engl J Med. 1991;324:


Download ppt "Avoiding End Organ Damage"

Similar presentations


Ads by Google