Transcript Dr. Shahbaz Ahmed Kureshi

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
Destination <120/80
Lower is Better !
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
Thus, hypertension management is a public health priority
1. WHO, 2002; 2. AHA, 2004
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
Potentially Preventable Causes of Death
BP and increasing age
Kearney et al, Lancet 2005
Prevalence of hypertension is
high
Prevalence of hypertension in people aged 20 years and older
2000
50
45
Prevalence of hypertension (%)
40
37.4 37.2
40.7
39.1
35.3
34.8
35
30
26.9
25
22
20.6 20.9
23.7
28.3
Men
22.6
Women
19.7
20
17
14.5
15
10
5
0
2025
50
45.9
44.5
45
41.6
42,50
40.2
39.1
40
35
30
27
25
22.9
27.7
27
27
28.2
24
23.6
18.8
20
17.1
15
10
5
0
Established
market
countries
Former
socialist
economies
India
Latin America
and the
Carribean
Middle
eastern
crescent
China
Other Asia
and islands
Sub-Saharan
Africa
Kearney PM et al.,Lancet. 2005;365:217-223.
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
Hypertension is a leading cause
for cardiovascular morbidity
36-Year Follow-up in Patients Aged 35-64 Years1,2
Biennial Age-Adjusted Rate
per 1,000
50
Coronary Disease
45.4
Peripheral Arterial
Disease
Stroke
Heart Failure
40
Normotensive
Hypertensive
30
22.7
21.3
20
13.9
12.4
9.9
9.5
10
6.2
3.3
2.4
7.3
5.0
2.0
6.3
3.5
2.1
0
Men
Women
Men
Women
Men
Women
Men
Women
1. Kannel W.B. et al., JAMA 1996; 275: 1571-1576
2. Kannel W.B. et al., J Hum Hypertens 2000; 14: 83-90
High-Normal BP and CVD Risk
High normal 130-139/85-89 mm Hg
Normal 120-129/80-84 mm Hg
Optimal <120/80 mm Hg
Men
Cumulative Incidence (%)
14
Prehypertension
Women
12
P<.001
10
10
8
8
6
6
4
4
2
2
0
0
0
2
4
6
8
10
12
14
P<.001
0
2
Time (years)
4
6
8
10
Time (years)
Vasan et al. N Engl J Med. 2001
12
14
Blood pressure, heart disease
and age correlate closely
256
128
64
32
Age at risk:
80–89 years
70–79 years
60–69 years
50–59 years
16
40–49 years
8
4
2
1
b
Age at risk:
256
80–89 years
Ischaemic heart disease mortality
(floating absolute risk and 95% CI)
Ischaemic heart disease mortality
(floating absolute risk and 95% CI)
a
128
70–79 years
64
60–69 years
32
50–59 years
16
40–49 years
8
4
2
1
120 140 160
180
Usual SBP (mmHg)
70
80 90 100 110
Usual DBP (mmHg)
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; 360:1903-1913.
CV Mortality Risk Doubles with Each
20/10 mm Hg BP Increment*
8
7
6
CV
mortality
risk
5
4
3
2
1
0
115/75
135/85
155/95
175/105
SBP/DBP (mm Hg)
*Individuals aged 40-70 years, starting at BP 115/75 mm Hg.
CV, cardiovascular; SBP, systolic blood pressure; DBP, diastolic blood pressure
Lewington S, et al. Lancet. 2002; 60:1903-1913.
JNC 7. JAMA. 2003;289:2560-2572.
Absolute Risk Of Coronary Artery Disease And
Stroke Mortality
Curvilinear Relation Of Blood Pressure And
Cardiovascular Risk
Geographical Variation In Hypertension Prevalence In
Population Of African And European Ancestry
Age- Dependent Changes In Systolic and
Diastolic Blood Pressure In USA
Vascular Remodeling Of Small And Large Arteries
The Renin- Angiotensin- Aldosterone System
Schematic Representation Of The Central Role
Played By Angiotensin 1 Receptor (AT1R)
Superiority Of Ambulatory Over Office
Blood Pressure Measurements
24-Hour Ambulatory Blood Pressure Recording
Relation Between Systolic Blood Pressure And
The Rate Of Progression Of Coronary Atheroma
Blood Pressure Risk
Stratification (ESH/ESC
2007)
Mancia G et al., J Hypertens 2007;25:1105–87
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
2 mmHg decrease in
mortality
mean systolic blood
pressure
10% reduction
in risk of stroke
mortality
1. Lewington S et al. Lancet. 2002;360:1903–1913.
Effective blood pressure control
reduces cardiovascular morbidity
and mortality
Systolic–diastolic hypertension
Relative Risk Reduction (%)
10
0
Fatal and nonfatal events
Stroke
CHD
Fatal and nonfatal events
Mortality
All
Causes
CV
Isolated systolic hypertension
Non CV
Stroke
CHD
Mortality
All
Causes CV
NS
Non CV
NS
-10
<0.01
-20
0.02
<0.01
<0.001
<0.001
0.01
-30
<0.001
-40
-50
ESH/ESC guidelines consider systolic values of <139 mmHg and
diastolic values of <89 mmHg to be normal
<0.001
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.
Relations Between Achieved Blood Pressure Control
And Declines In Glomerular Filtration Rate
Absolute Benefits For The Prevention Of Fatal
Nonfatal Cardiovascular Events
Odds Ratio For Cardiovascular Events And Systolic
Blood Pressure
Trials Comparing The Effect On Primary End
Point Of Treatment Based On Different
Antihypertensive Drugs
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)
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;36:646-661; Bakris et al. Arch Intern Med. 2003;163:15551565; Lewis et al. N Engl J Med. 2001;345:851-860.
An Algorithm For The decision To Manage
Patients With Different Average Blood
Pressure Levels
Algorithm For Therapy Of Hypertension
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
46
47
48
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.
Treatment Enables Retardation of
the Progression of Renal Disease
Benedict
study
Prevention
Protection
IRMA 2
IDNT
MARVAL
RENAAL
Microalbuminuria
Macroalbuminuria
ESRD
Cardiovascular morbidity and mortality
Early stage
Late stage
Severity of renal disease
Terminal stage
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
“First do no harm”
The Mechanisms By Which Chronic Diuretic Therapy
May Lead TO Various Complications
Theoretical Therapeutic And Toxic Logarithmic And
Linear Dose Response Curve
Classification Of Beta- Adrenoreceptor Blockers
On The Basic Of Cardioselectivity And Intrinsic
Sympathomimetic Activity
Worldwide blood pressure
control rates in treated
hypertensive patients are low
Germany
33.6
Canada
41.0
Japan*
55.7
England
29.2
USA
53.1
Greece
49.5
China
28.8
Turkey
19.8
Mexico
21.8
Taiwan
18.0
Egypt
33.5
South Africa*
47.6
Kearney P.M. et al., J Hypertens 2004; 22: 11–19; * Data for men on
Simplified Schematic View Of The Adrenergic Nerve
RAA system targets multiple
receptor sites
Na+
Angiotensinogen
K+
Aldosterone
Renin
Other
ACTH
Chymase
Angiotensin I
CE
Bradykinin
Angiotensin II
Inactive
Adapted from Unger T. Am J Cardiol 2002; 89 (suppl):3A-10A.
•
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=αadrenergic stimulation.
AII=angiotensin II.
Kaplan NM & Opie LH. Lancet 2006; 367:168-176.
Angiotensin (AT1) receptor blockade
provides vascular protection
Angiotensinogen
Renin
Angiotensin I
ACE
Non-ACE
Pathways*
Angiotensin II
*not affected
by ACE
inhibitors
ARB Blockade
AT1 receptor
• Vasoconstriction
• Hypertrophy and
Proliferation
• Oxidation and
Inflammation
• PAI-1 expression and
release
Blockade of
AT1 receptor
Activation of
AT2 receptor
Vascular
Protection
AT2 receptor
• Vasodilation
• Nitric Oxide release
• Antiproliferation
Adapted from:
Kaschina E and Unger T. Blood Press 2003;12:7088.
Unger T. J Hypertens 1999;17:1775-1786.
Renin profile correlates with
CV risk
18.8
Events
per 1000
person-years
13.3
10.6
5.0
2.8
High
2.0
Yes
Normal
No
Low
48.5
34.5
Events
per 1000
person-years
Events
per 1000
person-years
10.2
8.4
6.3
8.4
3.2
High
0.9
6.3
24.4
Normal
Low
7.8
12.4
4.6
2.1
7.8
11.7
High
Normal
Low
Alderman MH et al. N Engl J Med. 1991;324:1098-1104.