Transcript Document

Practical Approaches to Managing
Hypertension: Reducing Global
Cardiovascular Risk
Joshua Furman, MD
Staff Cardiologist
Mount Sinai Medical Center
Miami Beach, Florida
Key Question
Which class of agents do you presently
consider first-line treatment for patients
with hypertension?
1. Diuretics
2. β-Blockers (BBs)
3. Calcium channel blockers (CCBs)
4. Angiotensin-converting enzyme inhibitors (ACEIs)
5. Angiotensin receptor blockers (ARBs)
6. All of the above
Use your keypad to vote now!
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Faculty Disclosure
 Dr Furman has no relevant financial relationships
with any commercial interests to disclose.
Learning Objectives
 State the prevalence of hypertension and its role
in the cardiovascular disease continuum
 Formulate hypertension management according
to risk stratification
 Describe the importance of targeting improvement
in vascular function in patients with hypertension
Progression of Cardiovascular Disease:
The Cardiovascular Continuum
Myocardial infarction
Myocardial
ischemia
Endothelial
dysfunction and
atherothrombosis
Sudden death
Peripheral
arterial
disease
Ventricular
dysfunction
Ventricular
dilation and
hypertrophy
Stroke
Hyperlipidemia,
hypertension, diabetes,
smoking, obesity, etc
Adapted from Dzau V, Braunwald E. Am Heart J. 1991;121:1244-1263.
Congestive
heart failure
and death
Development and Progression
of Vascular Disease
RISK FACTORS
LDL
BP
Diabetes
Smoking
Oxidative Stress
Endothelial Dysfunction and
Smooth Muscle Activation
NO •  Local Mediators •  Tissue ACE, AII
Endothelin
Catecholamines
PAI-1, Platelet
Aggregation,
Tissue Factor
Vasoconstriction
Thrombosis
VCAM/ICAM
Cytokines
Proteolysis
Inflammation
Inflammation
Plaque
Rupture
CLINICAL SEQUELAE
Dzau V. Hypertension. 2001;37:1047-1052.
Growth Factors
Cytokines
Matrix
Vascular Lesion
and Remodeling
Progression From Hypertension
to Heart Failure/Sudden Death
Obesity
Diabetes
LVH
Hypertension
Smoking
Dyslipidemia
Risk Factors
Diastolic
dysfunction
ACS
Systolic
dysfunction
Atherothrombosis,
left ventricular
remodeling
Subclinical
left ventricular
dysfunction
HF
Overt heart
failure
Time
ACS = acute coronary syndrome; HF = heart failure; LVH = left ventricular hypertrophy.
Adapted from Vasan RS, Levy D. Arch Intern Med. 1996;156:1789-1796.
Death/
Sudden
Death
JNC 7 Cardiovascular Risk Factors
 Hypertension
 Cigarette smoking
 Obesity (BMI ≥30 kg/m2)
 Physical inactivity
 Dyslipidemia
 Diabetes mellitus
 Microalbuminuria
or estimated GFR
<60 mL/min
 Age (men >55 yr;
women >65 yr)
 Family history of
premature CVD
Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; 2004. NIH Publication No. 04-5230.
Available at: www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
In Nearly 2 Out of 3 Adults With Hypertension,
Hypertension Is Still Not Controlled
100
US Population (%)*
90
30%
80
NHANES
(1999-2000)‡
41%
70
60
70
66%!
59
50
40
30
34
20
10
0
Aware
Treated
Controlled†
*Adults aged 18 to 74 years with hypertension. †Controlled = BP 140/90 mm Hg.
‡Data were computed (M. Wolz, unpublished data, 2003) from the NHLBI.
Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; 2004. NIH Publication No. 04-5230.
Available at: www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
Patients With BP Controlled Worldwide
<160/95 mm Hg
<140/90 mm Hg
Canada2
USA1
22%
27%
England3
6%
Finland5
France4
24%
Australia5
Spain5
20.5%
Germany5
Scotland5
22.5%
19%
20%
17.5%
India5
9%
>65 yr only
1. JNC VI. Arch Intern Med. 1997;157:2413-2446.
2. Joffres et al. Am J Hypertens. 1997;10:1097-1102.
3. Colhoun et al. J Hypertens. 1998;16:747-752.
4. Chamontin et al. Am J Hypertens. 1998;11(6 Pt 1):759-762.
5. Marques-Vidal et al. J Hum Hypertens. 1997;11:213-220.
Adapted from G. Mancia
10-Year NCEP/Framingham Risk Scores
for Fatal or Nonfatal CHD in Men*
Age (y)
Points
Smoking
Age (y)
SBP (mm Hg) Untreated Treated
status
20-39
40-49
50-59 60-69 70-79
20-34
-9
<120
0
0
Nonsmoker
0
0
0
0
0
35-39
-4
120-129
0
1
Smoker
8
5
3
1
1
40-44
0
130-139
1
2
140-159
1
2
45-49
3
Point Total 10-Year Risk (%)
160
2
3
<0
<1
50-54
6
0
1
55-59
8
HDL (mg/dL)
Points
1
1
60-64
10
60
-1
2
1
65-69
11
50-59
0
3
1
4
1
40-49
1
70-74
12
5
2
<40
2
75-79
13
6
2
7
3
Age
Age
Age
Age
Age
8
4
TC (mg/dL) 20-39 y 40-49 y
50-59 y
60-69 y
70-79 y
9
5
<160
0
0
0
0
0
10
6
160-199
4
3
2
1
0
11
8
200-239
7
5
3
1
0
12
10
13
12
240-279
9
6
4
2
1
14
16
280
11
8
5
3
1
15
20
*A separate Framingham risk calculator exists for women.
16
25
NCEP ATP III. 2002. NIH Publication No. 02-5215. Available at:
17
30
http://www.nhlbi.nih.gov/guidelines/cholesterol/.
Key Question
What percentage of patients with hypertension
have 2 or more additional CV risk factors?
1. 20%
2. 30%
3. 40%
4. 50%
5. >50%
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CV Risk Factor Clustering With Hypertension:
Framingham Offspring, Aged 18 to 74 Years
>50% of Hypertension Occurs in Presence
of 2 or More Risk Factors
Men
Women
1 RF
2 RFs
1 RF
25%
26%
12%
3 RFs
4 or
More RFs
20%
17%
8%
No
Additional
RFs
24%
27%
22%
19%
2 RFs
No
Additional
RFs
RF = risk factor.
Adapted from Kannel WB. Am J Hypertens. 2000;13:3S-10S.
3 RFs
4 or
More RFs
10-Year Probability of
Event (%)
Risk of CHD in Mild Hypertension by
Intensity of Associated Risk Factors
Risk Factors
40
42
36
30
21
24
18
10
12
6
4
14
6
0
SBP 150-160 mm Hg
TC 240-262 mg/dL
HDL-C 33-35 mg/dL
Diabetes
Cigarette smoking
ECG-LVH
+
−
−
−
−
−
+
+
−
−
−
−
+
+
+
−
−
−
Adapted from Kannel WB. Am J Hypertens. 2000;13:3S-10S.
+
+
+
+
−
−
+
+
+
+
+
−
+
+
+
+
+
+
JNC Reclassification of BP
Based on Risk
JNC 7
JNC VI
Category
Optimal
Normal
SBP
(mm Hg)
<120
DBP
(mm Hg)
and
120-129 and
<80
Category
Normal
130-139
<120
DBP
(mm Hg)
and
<80
80-84
Prehypertension
Borderline
SBP
(mm Hg)
or
85-89
90-99
120-139 or
80-89
140-159 or
90-99
Hypertension
Stage 1
140-159
or
Stage 2
160-179
or 100-109
Stage 3
≥180
or
Stage 1
Stage 2
≥160
or
≥100
≥110
Arch Intern Med. 1997;157:2413-2446; Chobanian AV et al, for the NHBPEPCC. Bethesda, Md:
NHLBI; 2004. NIH Publication No. 04-5230. Available at:
www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
Nonpharmacologic Interventions
and BP Reduction
Weight Loss
(19.4 lb)
0
Low-Salt
Diet
Exercise
Alcohol
Reduction
BP Decrease
(mm Hg)
1
2
3
4
5
6
SBP
DBP
7
Adapted from: Stevens VJ et al. Ann Intern Med. 2001;134:1-11; Messerli FH et al. In: Griffin BP et al,
eds. 2004. Manual of Cardiovascular Medicine. 2nd ed; Whelton SP et al. Ann Intern Med.
2002;136:493-503; Cutler JA et al. Am J Clin Nutr. 1997;65(suppl):643S-651S; Xin X et al. Hypertension.
2001;38:1112-1117; Whelton PK et al. JAMA. 1997;277:1624-1632.
Study Design: TROPHY
STUDY N = 809
Participants had prehypertension:
SBP 130-139 mm Hg and DBP 89 mm Hg OR
SBP 139 mm Hg and DBP 85-89 mm Hg
n = 409
2 years candesartan +
2 years placebo
n = 400
2 years placebo +
2 years placebo
When a participant reached the study end point of stage 1
hypertension, treatment with antihypertensive agents was initiated
RESULTS
• At 2 years, hypertension had developed in 154 participants in the
placebo group and 53 in the candesartan group (RRR 66%, P <.001)
• At 4 years, hypertension had developed in 240 participants in the
placebo group and 208 in the candesartan group (RRR 15.6%, P <.007)
TROPHY = Trial of Preventing Hypertension. Julius S, et al. N Engl J Med. 2006;354:1685-1697.
TROPHY: Kaplan-Meier Curves
of New Onset Clinical Hypertension
Cumulative Incidence (%)
100
90
Candesartan
80
Placebo
70
60
50
40
30
20
10
0
0
1
2
Years in Study
TROPHY = Trial of Preventing Hypertension.
Julius S et al. N Engl J Med. 2006;354:1685-1697.
3
4
Key Points for Optimal
Hypertension Management
<140/90 mm Hg
JNC 7
BP
Goals
<130/80 mm Hg in
patients with
diabetes or
renal disease
JNC 7 recommends:
If SBP >20 mm Hg or DBP >10 mm Hg over goal,
consider initiating with 2-drug combination
Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; 2004. NIH Publication No. 04-5230.
Available at: www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
Antihypertensive Medications:
Mechanism of Action
Drug Class
Mechanism of Action
Diuretics
 Rid body of excess fluids and sodium
 May enhance effect of other BP medications
ACEIs
 Lower levels of angiotensin II
 Dilate blood vessels
ARBs
 Block angiotensin II receptors
 Dilate blood vessels
BBs
 Decrease heart rate and cardiac output
CCBs
 Interrupt movement of calcium into heart and vessel cells
Aldosterone Receptor
Blockers
 Decrease salt and water retention
Renin Inhibitors
 Block action of renin, decreasing formation of angiotensin I
American Heart Association. December 11, 2006. Available
at:http://www.americanheart.org/presenter.jhtml?identifier=3038158.
JNC 7: Algorithm for Hypertension
LIFESTYLE MODIFICATIONS
Not at Goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients
with diabetes or chronic kidney disease)
INITIAL DRUG CHOICES
Without Compelling Indications
Stage 1 Hypertension
Thiazide-type diuretics
for most; may consider
ACEI, ARB, BB, CCB,
or combo
Stage 2 Hypertension
2-drug combos for most
(usually thiazide-type
diuretics and ACEI,
or ARB, or BB, or CCB)
With Compelling Indications
Compelling Indications
Other drugs
(diuretic, ACEI, ARB,
BB, CCB) as needed
If not at goal BP, optimize dosages or add drugs until
goal BP achieved; consider consultation with hypertension specialist
Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; 2004. NIH Publication No. 04-5230.
Available at: www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
JNC 7 Highlights:
Key Risk-Related Messages
 Certain high-risk conditions are compelling
indications for the initial use of specific
antihypertensive drug classes
Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; 2004. NIH Publication No. 04-5230.
Available at: www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
JNC 7: Compelling Indications
for Antihypertensive Drug Classes
Recommended Drugs
Compelling Indication
Heart failure
Post MI
High coronary
disease risk
Diabetes
Chronic kidney disease
Recurrent stroke
prevention
Diuretic ACEI
•
•
•
•
•
•
•
•
•
•
BB
•
•
Aldo
ARB CCB ANT
•
•
•
•
•
•
•
•
•
Aldo ANT = aldosterone antagonist. Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI;
2004. NIH Publication No. 04-5230. Available at:
www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
Study Design: VALUE
STUDY N = 15,245
Aged 50 years;
With treated or untreated hypertension and high risk of cardiac events
Step 1: valsartan 80 mg/day
Step 2: valsartan 160 mg/day
n = 7649
Step 1: amlodipine 5 mg/day
Step 2: amlodipine 10 mg/day
n = 7596
Both regimens included HCTZ in steps 3 and 4
Further drugs could be given to achieve BP control
Randomized, double-blind, parallel group comparison
RESULTS
• BP  with both treatments
• Primary end point (composite of cardiac mortality and morbidity)
occurred in valsartan 10.6% vs amlodipine 10.4%, HR 1.04
• Amlodipine effects were more pronounced in the early period
• BP  4.0/2.1 mm Hg in the amlodipine group after 1 month
VALUE = Valsartan Antihypertensive Long-term Use Evaluation.
Julius S, et al. Lancet. 2004;363:2022-2031.
VALUE: Hazard Ratios for Prespecified
Analyses in Patients With Hypertension
at High CV Risk
Hazard Ratio
Valsartan/Amlodipine
Primary cardiac composite end point
Cardiac mortality
Cardiac morbidity
All myocardial infarction
All congestive heart failure
All stroke
All-cause death
New-onset diabetes
0.5
1
Favors Valsartan
Patients had hypertension and were at high CV risk.
VALUE = Valsartan Antihypertensive Long-term Use Evaluation.
Julius S et al, for the VALUE trial group. Lancet. 2004;363:2022-2031.
2.0
Favors Amlodipine
Key Question
On average, how many drugs will a patient
need to control hypertension?
1. 1
2. 2
3. 3
4. 4
Use your keypad to vote now!
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Number of Antihypertensive Agents
Needed to Achieve Systolic BP Control
Trial
ALLHAT
IDNT
RENAAL
UKPDS
ABCD
MDRD
HOT
AASK
INVEST
SBP achieved
(mm Hg)
138
138
141
144
132
132
138
128
131
*
1
2
3
Number of BP Medications†
4
*~50% patients required ≥3 medications. †Average per patient.
Bakris et al. Am J Kidney Dis. 2000;36:646-661; ALLHAT. JAMA. 2002;288:2981-2997; Berl et al. Ann Intern Med.
2003;138:542-549; Bakris et al. Arch Intern Med. 2003;163:1555-1565; Wright et al. JAMA. 2002;288:2421-2431;
Pepine et al. JAMA. 2003;290:2805-2816.
Hypertension and Diabetes:
Global CV Risk Reduction With
Evidence-Based Intervention
Diabetes Approximately Doubles CVD
Risk in Patients With Hypertension
Patients With
Patients Without
Diabetes
Diabetes
Study
(events per 1000 pt-yr)
Systolic Hypertension in the Elderly Program (SHEP)
Ratio
CV events
Stroke
63.0
28.8
36.8
15.0
1.71
1.92
CHD events
32.2
15.2
2.12
28.9
1.90
Systolic Hypertension in Europe (Syst-Eur)
CV events
55.0
Stroke
26.6
12.3
2.16
CHD events
23.1
12.4
1.87
Hypertension Optimal Treatment (HOT) (DBP <90 mm Hg)
CV events
24.0
9.8
Adapted from Curb JD et al. JAMA. 1996;276:1886-1892; Hansson L et al. Lancet.
1998;351:1755-1762; Tuomilehto J et al. N Engl J Med. 1999:340:677-684.
2.45
HOT Study: Fewer Major CV Events in Patients
With Diabetes Randomized to Lower BP Goal
P = .005
(per 1000 patient-years)
Stroke, MI, or CV Death
25
20
15
10
5
0
80
85
90
Target DBP (mm Hg)
Patients with hypertension and diabetes were given baseline felodipine, plus other agents in
a 5-step regimen. Study N = 18,790; diabetes n = 1501.
HOT = Hypertension Optimal Treatment; MI = myocardial infarction.
Adapted from Hansson L et al, for the HOT Study Group. Lancet. 1998;351:1755-1762.
Relative Risk Reduction (%)
UKPDS: Tight Glucose Versus Tight
BP Control and CV Outcomes
0
-10
Tight glucose control (goal <6.0 mmol/L or 108 mg/dL)
Tight BP control (average 144/82 mm Hg)
Any Diabetic
DM
Microvascular
Stroke
End Point
Deaths
Complications
5%
10%
12%
-20
24%
*
-30
32%
*
-40
-50
44%
*
32%
*P <.05 compared to tight glucose control
37%
*
Patients had hypertension and Type 2 diabetes. N = 1148.
UKPDS = United Kingdom Prospective Diabetes Study.
Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.
Antihypertensive Medications:
Mechanism of Action
Drug Class
Mechanism of Action
Diuretics
 Rid body of excess fluids and sodium
 May enhance effect of other BP medications
ACEIs
 Lower levels of angiotensin II
 Dilate blood vessels
ARBs
 Block angiotensin II receptors
 Dilate blood vessels
BBs
 Decrease heart rate and cardiac output
CCBs
 Interrupt movement of calcium into heart and vessel cells
Aldosterone Receptor
Blockers
 Decrease salt and water retention
Renin Inhibitors
 Block action of renin, decreasing formation of angiotensin 1
American Heart Association. December 11, 2006. Available at:
http://www.americanheart.org/presenter.jhtml?identifier=3038158.
The Renin-Angiotensin-Aldosterone
System (RAAS)
Angiotensinogen
Kininogen
Kallikrein
Renin
Bradykinin
Angiotensin I
ACE
Inactive Peptides
 Blood Pressure
 Vascular Proliferation
 Oxidative Stress
 Vascular Inflammation
 Thrombogenesis
 Aldosterone
Angiotensin II
AT1
Adapted with permission from Brown NJ et al. Circulation. 1998;97:1411-1420; Endemann DH.
J Am Soc Nephrol. 2004;15:1983-1992.
The Renin-Angiotensin-Aldosterone
System (RAAS)
Angiotensinogen
Kininogen
Renin
Inhibitors
Renin 
Kallikrein
Bradykinin
Angiotensin I
ACE
Inactive Peptides
Angiotensin II
ARBs
 Blood Pressure
 Vascular Proliferation
 Oxidative Stress
 Vascular Inflammation
 Thrombogenesis
 Aldosterone
AT1
Adapted with permission from Brown NJ et al. Circulation. 1998;97:1411-1420; Endemann DH.
J Am Soc Nephrol. 2004;15:1983-1992.
The Renin-Angiotensin-Aldosterone
System (RAAS)
Angiotensinogen
Kininogen
Kallikrein
Renin
Bradykinin
Angiotensin I
ACE
Angiotensin II
Inactive Peptides
AT2
AT2
 Blood Pressure
 Vascular Proliferation
 Oxidative Stress
 Vascular Inflammation
 Thrombogenesis
 Aldosterone

ARBs
ARBs
AT1
Adapted with permission from Brown NJ et al. Circulation. 1998;97:1411-1420; Endemann DH.
J Am Soc Nephrol. 2004;15:1983-1992.
The Renin-Angiotensin-Aldosterone
System (RAAS)
Angiotensinogen
Kininogen
Kallikrein
Nitric
Oxide
Bradykinin
Kininase II
Inactive Peptides
Renin
ACEIs
 ACE
 Blood Pressure
 Vascular Proliferation
 Oxidative Stress
 Vascular Inflammation
 Thrombogenesis
 Aldosterone
Angiotensin I
Angiotensin II
AT1
Adapted with permission from Brown NJ et al. Circulation. 1998;97:1411-1420; Endemann DH.
J Am Soc Nephrol. 2004;15:1983-1992.
EUROPA: CV Death/MI/Cardiac Arrest
Placebo
20% Risk Reduction
HR = 0.80 (0.71–0.91)
P = .0003
Perindopril
8 mg
Time (years)
Percent
15
10
5
Time (years)
0
0
30
25
20
15
10
5
0
HOPE: CV Death/MI/Stroke
Placebo
22% Risk Reduction
HR = 0.78 (0.70–0.86)
Ramipril
P <.001
10 mg
20
Percent
14
12
10
8
6
4
2
0
1
2
3
4
5
0
PEACE: CV Death/MI/CABG/PCI
4% Risk Reduction Placebo
HR = 0.96 (0.88–1.06)
P = .43
Trandolapril
4 mg
Time (years)
1
2
3
4
5
6
1
2
3
QUIET: All CV Events
4% Risk Increase
HR = 1.04 (0.89–1.22)
P = .6
50
Percent
Percent
ACEI Trials in CAD Without HF:
Primary Outcomes
40
30
4
Quinapril
20 mg
Placebo
20
10
Time (years)
0
0
1
2
EUROPA Investigators. Lancet. 2003;362:782-788; HOPE Study Investigators. N Engl J Med.
2000;342:145-153; PEACE Trial Investigators. N Engl J Med. 2004;351:2058-2068; Pitt B, et al.
Am J Cardiol. 2001;87:1058-1063.
3
Primary Outcome (%)
MICRO-HOPE, PERSUADE:
CV Events in Patients With Diabetes
MICRO-HOPE
(n = 3577)
CV death/MI/stroke
25
25
PERSUADE
(n = 1502)
CV death/MI/cardiac arrest
Placebo
20
Placebo
20
25% RRR
P = .0004
15
19% RRR
P = .13
15
10
5
Perindopril
8 mg
10
Ramipril
10 mg
5
0
0
0
1
2
3
4
Follow-Up (years)
5
0
1
2
3
4
Follow-Up (years)
5
MICRO-HOPE = Microalbuminuria, Cardiovascular, and Renal Outcomes (Heart Outcomes Prevention
Evaluation); PERSUADE = Perindopril Substudy in Coronary Artery Disease and Diabetes.
HOPE Study Investigators. Lancet. 2000;355:253-259; Daly CA et al. Eur Heart J. 2005;26:1369-1378.
Impact of ACE Inhibitors on the Risk of
Developing New-Onset Diabetes Mellitus
RR = 0.66 (0.51-0.85)
P <.001
New Diagnosis of
Diabetes (%)
10
8
6
5.4
3.6
4
2
0
Placebo
Ramipril
HOPE Trial: Ramipril 10 mg QD vs placebo; 9297 patients with vascular disease or diabetes
plus 1 other CV risk factor, 4355 with hypertension; BP: baseline (139/79 mm Hg); 2 years:
ramipril (135/76 mm Hg), placebo (138/78 mm Hg).
Yusuf S et al. N Engl J Med. 2000;342:145-153.
HOPE Study:
Prevention of Diabetes With Ramipril
Kaplan-Meier Rates
0.10
Placebo
Ramipril
0.08
0.06
0.04
0.02
0
200
400
600
800
1000
1200
1400
1600
Days of Follow-Up (no diabetes at baseline)
The occurrence of self-reported diabetes was reduced by 34% (95% CI, 15%-49%; P <.001) in the HOPE
study. This effect was observed early and maintained consistently throughout the trial.
HOPE Study Investigators. Lancet. 2000;355:253-259.
MICRO-HOPE: Albuminuria in Patients
With Diabetes
Mean Albumin/Creatinine
Ratio (urine)
3.0
Placebo
2.5
Ramipril
2.0
P = .02
1.5
P = .001
1.0
0.5
0.0
0
1
2
Time (y)
HOPE Study Investigators. Lancet. 2000;355:253-259.
3
4-5
LIFE: Secondary End Points
End Points
No. of
Events
Total Mortality
814
Angina Pectoris
301
CHF
314
Revascularization
545
New-Onset Diabetes
562
Hazard Ratio (95% CI)
0.5
Favors Losartan
Dahlof B et al. Lancet. 2002;359:995-1003.
1
2
Favors Atenolol
Proportion of Patients With
First Event (%)
LIFE: New-Onset Diabetes
Intention-to-Treat
10
9
Atenolol
8
7
6
5
Losartan
4
3
2
Adjusted Risk Reduction 25%, P = .001
Unadjusted Risk Reduction 25%, P = .001
1
0
0
6
12
18
24
30
36
42
Study Month
Dahlof B et al. Lancet. 2002;359:995-1003.
48
54
60
66
Reduction of New Diabetes (%)
CV Pharmacotherapy:
Impact on Newly Diagnosed Diabetes
0
10
20
30
100
ACEI or ARB
CA + ACEI or ARB
CA
Randomized active treatment vs control (eg, placebo, diuretic, β-blocker  diuretic)
CA = calcium antagonist.
Pepine CJ, Cooper-DeHoff RM. J Am Coll Cardiol. 2004;44:509-512. Sever PS et al. Lancet.
2003;361:1149-1158.
Multiple Mechanisms of ACEI
in Cardiovascular Disease
Blood pressure lowering
Cardioprotective effects
  Preload and afterload
  LV mass
  Sympathetic stimulation
  Reperfusion injury
 Improved myocardial
remodeling
Metabolic syndrome
 Lipid neutral
 Improved glucose metabolism
 Increases adiponectin
 Decreased insulin resistance
Vasculoprotective effects
 Direct antiatherogenic
 Enhance endogenous
fibrinolysis
 Inhibit platelet aggregation
 Antimigratory for mononuclear
cells
  Matrix formation
 Improve endothelial function
 Antioxidant
 Anti-inflammatory
 Protection from plaque rupture
 Improved arterial compliance
and tone
Modified from: Lonn E et al. Eur Heart J Suppl. 2003;5:A43-A48.
Summary: The Case for Global
CV Risk Management
 CV disease remains the leading cause of death
in both men and women in the United States
 Data from the Framingham Heart Study have
demonstrated clustering of risk factors—and that risk
of death from CHD and stroke increases further with
each added risk factor
 Hypertension, a pivotal risk factor for CV disease,
should prompt the search for the presence of additional
risk factors
 Recent clinical trials have provided evidence supporting
a standard of care for the management of global CV risk
Case Study
Case Study: 55-Year-Old Man From India
With Hypertension and Type 2 Diabetes
 The patient is in for a checkup
 History




Hypertension
Type 2 diabetes
Nonsmoker
No symptoms
 Physical examination
 BP: 148/96 mm Hg
 Height: 64"
 Weight: 178 lb
 BMI: 30 kg/m2
 Waist circumference: 38"
 Cardiac dysfunction status:
normal ventricular function
(LVEF 68%)
 Laboratory values

Glucose: 148 mg/dL
(fasting)
 A1C: 8.8%
 Creatinine: 1.5 mg/dL
 Urinalysis: 1+ proteinuria
 Lipid profile (mg/dL):
TC: 268; LDL-C: 168;
HDL-C: 42; TG: 296
 Medications
 HCTZ 25 mg/d
 Glyburide 5 mg/d
10-Year NCEP/Framingham Risk Scores
for Fatal or Nonfatal CHD in Men*
Age (y)
Points
Smoking
SBP (mm Hg) Untreated Treated
Age (y)
20-34
-9
status
<120
0
0
20-39 40-49 50-59 60-69 70-79
35-39
-4
120-129
0
1
Nonsmoker
0
0
0
0
0
Smoker
8
5
3
1
1
40-44
0
130-139
1
2
140-159
1
2
45-49
3
Point Total 10-Year Risk (%)
160
2
3
50-54
6
<0
<1
55-59
8
0
1
HDL (mg/dL)
Points
1
1
60-64
10
60
-1
2
1
65-69
11
50-59
0
3
1
40-49
1
70-74
12
4
1
5
2
<40
2
75-79
13
6
2
Age
Age
Age
Age
Age
7
3
TC (mg/dL) 20-39 y 40-49 y
50-59 y
60-69 y
70-79 y
8
4
9
5
<160
0
0
0
0
0
10
6
160-199
4
3
2
1
0
11
8
200-239
7
5
3
1
0
12
10
240-279
9
6
4
2
1
13
12
280
11
8
5
3
1
14
16
15
20
*A separate Framingham risk calculator exists for women.
16
25
NCEP ATP III. 2002. NIH Publication No. 02-5215. Available at:
17
30
http://www.nhlbi.nih.gov/guidelines/cholesterol/.
Decision Point
What is the JNC 7 goal for this patient who has
hypertension, diabetes, and renal disease?
1. <120/80 mm Hg
2. <130/80 mm Hg
3. <140/80 mm Hg
4. <140/90 mm Hg
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Decision Point
The patient’s BP is 148/96 mm Hg while
taking HCTZ 25 mg/d and glyburide 5 mg/d.
To further lower BP, you would add a(n):
1. BB
2. CCB
3. ARB
4. ACE
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Q&A
PCE Takeaways
PCE Takeaways
1. Patients with hypertension often present with
multiple cardiac risk factors
2. Be vigilant in your investigation of all clinical
indicators
3. Creatively address patient adherence; not
everyone responds to the same interventions
4. Clinical inertia is the enemy—don't settle for
"close enough"
Key Question
How important is using an antihypertensive
agent with proven risk reduction (reducing
morbidity and mortality) when choosing
medications for your patients with hypertension?
1. Not important
2. Slightly important
3. Somewhat important
4. Extremely important
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