The Importance of Blood Pressure Control in Preventing Cardiovascular Disease

1
The Importance of Blood Pressure Control in
Preventing Cardiovascular Disease

• Wendy Post, MD, MS
• Associate Professor of Medicine
• and Epidemiology
• Cardiology Division
• Johns Hopkins University

2
Risk of Fatal Coronary Heart Disease by Systolic
Blood Pressure Level

• MRFIT screenees- 356,222 men, age 35-37 yrs at
  baseline with 6 yrs of f/u

Stamler J. Hypertension 198913 (suppl1)12-112.
3
Risk of Fatal Coronary Heart Disease by Systolic
Blood Pressure Level

• MRFIT screenees- 356,222 men, age 35-37 yrs at
  baseline with 6 yrs of f/u

Stamler J. Hypertension 198913 (suppl1)12-112.
4
Risk of Fatal Coronary Heart Disease by Diastolic
Blood Pressure Level
MRFIT screenees- 356,222 men, age 35-37 yrs at
baseline with 6 yrs of f/u
Stamler J. Hypertension 198913 (suppl1)12-112.
5
Risk of Fatal Coronary Heart Disease by Diastolic
Blood Pressure Level
MRFIT screenees- 356,222 men, age 35-37 yrs at
baseline with 6 yrs of f/u
Stamler J. Hypertension 198913 (suppl1)12-112.
6
JNC 7 More-Aggressive Guidelines
Diastolic (mm Hg)
Systolic (mm Hg)
BP Classification
lt80
lt120
and
Normal
120-139
Prehypertension
80-89
or
Stage 1 Hypertension
90-99
140-159
or
Stage 2 Hypertension
100
160
or
Chobanian AV, et al. JAMA. 20032892560-2572.
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Determinants of Progression to Hypertension
Adjusted for age, sex, SBP, DBP, smoking, heart
rate, BMI and weight change
Vasan RS, Lancet 20013581682-6
8
Determinants of Progression to Hypertension
Normal
PreHTN
Adjusted for age, sex, SBP, DBP, smoking, heart
rate, BMI and weight change
Vasan RS, Lancet 20013581682-6
9
Framingham Heart StudyHigh-normal BP Is Not
Benign
CV death, MI, stroke, CHF Adjusted for
concomitant CV risk factors Optimal lt120/lt80
mmHg Normal 120129/8084 mmHg High normal
130139/8489 mmHg
Vasan RS et al. N Engl J Med. 200134512911297.
10
Framingham Heart StudyHigh-normal BP Is Not
Benign
PreHTN
PreHTN
PreHTN
Normal
PreHTN
Normal
CV death, MI, stroke, CHF Adjusted for
concomitant CV risk factors Optimal lt120/lt80
mmHg Normal 120129/8084 mmHg High normal
130139/8489 mmHg
Vasan RS et al. N Engl J Med. 200134512911297.
11
JNC 7 Classification and Management of Blood
Pressure
Considerations for Initial Therapy
DBP mm Hg
Lifestyle modification
SBP mm Hg
Category
With CompellingIndications
Without Compelling Indications
No antihypertensive drug indicated Thiazide-type
diuretics for most. May consider ACEI, ARB, BB,
CCB, or combo 2-drug combo for most (usually
thiazide-type diuretic and ACEI or ARB or BB or
CCB)
Drug(s) for compelling indications Drug(s)
for the compelling indications Other
antihypertensive drugs (diuretics, ACEI, ARB, BB,
CCB) as needed
Encourage Yes Yes Yes
and lt80 or 8089 or 9099 or 100
lt120 120139 140159 160
Normal Prehypertension Stage
1 Hypertension Stage 2 Hypertension
SBP, systolic blood pressure DBP, diastolic
blood pressure ACEI, angiotensin-converting
enzyme inhibitor ARB, angiotensin receptor
blocker BB, beta blocker CCB, calcium channel
blocker. Treatment determined by highest BP
category. Initial combined therapy should be
used cautiously in those at risk for orthostatic
hypotension. Treat patients with chronic kidney
disease or diabetes to BP goal of lt130/80
mmHg. Chobanian AV et al. JAMA.
200328925602572.
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NHANESPrevalence of Hypertension By Sex, Age,
and Race/Ethnicity
Non-Hispanic White
Non-Hispanic Black
Mexican-American
100
100
Men
Women
80
80
60
60
Hypertension Prevalence ()
Hypertension Prevalence ()
40
40
20
20
0
0
18-39
40-59
60
Age
Age
Error bars indicate 95 CI. Data weighted to the
US population. Hajjar I, Kotchen TA. JAMA.
2003290199-206.
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Systolic Hypertension in the Elderly Trial
(SHEP)
For persons over age 50, SBP is a more important
than DBP as CVD risk factor.
4736 subjects, age gt 60 yrs with ISH - SBP gt 160
mmHg and DBP lt 90 mmHg randomized to
chlorthalidone atenolol versus placebo f/u 4.5
yrs
(p NS)
JAMA 19912653255-3264
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Population-Based Strategy
SBP Distributions
Before Intervention
After Intervention
Reduction in BP
Reduction in SBP mmHg 2 3 5
Reduction in Mortality
Stroke CHD Total 6 4 3 8 5 4 14 9 7
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Lifestyle Modification
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The Super-Sizing of America
This year, Americans will spend more money on
fast food than on higher education
Eric Schlosser. Fast Food Nation The Dark Side
of the All-American Meal. HarperCollins. 2002.
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Obesity Trends Among Adults, 1989
Body Mass Index (BMI) 30, or 30 lbs
overweight for 54 woman Mokdad AH, et al.
JAMA.19992821519-22 Mokdad AH, et al. JAMA.
20012861195-200.
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Obesity Trends Among Adults, 1991
Body Mass Index (BMI) 30, or 30 lbs
overweight for 54 woman Mokdad AH, et al.
JAMA.19992821519-22 Mokdad AH, et al. JAMA.
20012861195-200.
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Obesity Trends Among Adults, 1993
Body Mass Index (BMI) 30, or 30 lbs
overweight for 54 woman Mokdad AH, et al.
JAMA.19992821519-22 Mokdad AH, et al. JAMA.
20012861195-200.
20
Obesity Trends Among Adults, 1995
Body Mass Index (BMI) 30, or 30 lbs
overweight for 54 woman Mokdad AH, et al.
JAMA.19992821519-22 Mokdad AH, et al. JAMA.
20012861195-200.
21
Obesity Trends Among Adults, 1997
Body Mass Index (BMI) 30, or 30 lbs
overweight for 54 woman Mokdad AH, et al.
JAMA.19992821519-22 Mokdad AH, et al. JAMA.
20012861195-200.
22
Obesity Trends Among Adults, 1999
Body Mass Index (BMI) 30, or 30 lbs
overweight for 54 woman Mokdad AH, et al. JAMA.
20012861195-200.
23
Obesity Trends Among Adults, 2001
Body Mass Index (BMI) 30, or 30 lbs
overweight for 54 woman Mokdad AH, et al. JAMA.
20012861195-200.
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DASH StudyEffects of Diet on Systolic and
Diastolic Blood Pressure

• Dietary Approaches to Stop Hypertension
• 459 adults with mild hypertension or high-normal
  blood pressure (lt160/80-95) randomized for 8
  weeks to
• 1) Control diet or
• 2) High fruit/vegetable diet or
• 3) DASH combination diet (high fruit/vegetable,
  low saturated fat and cholesterol, high calcium,
  high potassium)
• Sodium intake and body weight remained constant

Appel LJ, et al. N Engl J Med. 19973361117-1124.
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DASH StudyEffects of Diet on Systolic and
Diastolic Blood Pressure
SBP (mm Hg)
DBP (mm Hg)
1
4
7 8
Baseline
2
3
5
6
Base-line
1
3
4
6
7 8
2
5
Intervention Week
Intervention Week
Control diet
Fruit/vegetable diet
Combination diet
Appel LJ, et al. N Engl J Med. 19973361117-1124.
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DASH-Sodium Trial Effects of Diet on Systolic
and Diastolic Blood Pressure

• 412 adults randomized to typical US control diet
  or DASH diet
• Within each group, subjects ate foods with high,
  intermediate, and low sodium for 30 days each in
  random order
• Sodium reduction and the DASH diet both decreased
  SBP and DBP

Sacks FM, et al. N Engl J Med. 20013443-10.
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DASH-Sodium Trial Effects of Diet on Systolic
and Diastolic Blood Pressure
-2
-1
-2
-6
-3
-5
-3
-5
-1
-2
-1
-1
-1
-2
Control diet
DASH diet
Plt0.05 Plt0.01 Plt0.001These symbols indicate
significant differences in BP between groups or
between dietary sodium categories
Sacks FM, et al. N Engl J Med. 20013443-10.
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Algorithm for Treatment of Hypertension
Lifestyle Modifications
Not at Goal Blood Pressure (lt140/90 mmHg)
(lt130/80 mmHg for those with diabetes or chronic
kidney disease)
Initial Drug Choices
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Compelling Indications for Individual Drug
Classes
31
Compelling Indications for Individual Drug
Classes
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BP Control Rates
Trends in awareness, treatment, and control of
high blood pressure in adults ages 1874
Sources Unpublished data for 19992000
computed by M. Wolz, National Heart, Lung, and
Blood Institute JNC 6.
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Get the blood pressure down!
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ALLHAT Study Design
Randomized, double-blind, multicenter
trial 33,357 subjects, aged ?55 y, with stage 1
or stage 2 hypertension and ?1 CHD risk factor
Lisinopril 10-40 mg/d (n9054)
Amlodipine besylate 2.5-10 mg/d (n9048)
Chlorthalidone 12.5-25 mg/d (n15,255)
Primary outcome Fatal CHD or nonfatal
MI Secondary outcomes All-cause mortality
stroke combined CHD combined CVD Mean
follow-up 4.9 years
ALLHAT, Antihypertensive and Lipid-Lowering
Treatment to Prevent Heart attack Trial. CHD,
coronary heart disease CVD, cardiovascular
disease MI, myocardial infarction LVH, left
ventricular hypertrophy. Previous (gt6 mos) MI
or stroke, LVH, type 2 diabetes, current smoker,
HDL-C lt35 mg/dL, other documented CVD. Primary
outcome, coronary revascularization, hospitalized
angina. Combined CHD, stroke, treated angina,
heart failure, peripheral vascular
disease. ALLHAT. JAMA. 200228829812997.
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ALLHATBP Results by Treatment Group
DBP mmHg
SBP mmHg
Compared to chlorthalidone SBP significantly
higher in the amlodipine group (1 mmHg) and the
lisinopril group (2 mmHg).
Compared to chlorthalidone DBP significantly
lower in the amlodipine group (1 mmHg).
ALLHAT. JAMA. 200228829812997.
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ALLHATResults Primary Outcome
Primary outcome fatal CHD or nonfatal MI
combined. ALLHAT. JAMA. 200228829812997.
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Cumulative Event Rates for Stroke
Chlorthalidone Amlodipine Lisinopril
ACEI vs. diuretic RR 1.15 (1.02-1.30) CCB vs.
diuretic RR 0.93 (0.82-1.06)
Cumulative Event Rate,
Time to Event, y
ALLHAT. JAMA. 200228829812997.
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Comments on ALLHAT

• No difference in primary outcome?nonfatal MI or
  CHD death
• BP was lower with diuretics than ACEI (2 mmHg),
  especially in blacks (4 mmHg) and gt65 years (3
  mmHg)
• BP difference might explain the lower incidence
  of CHF and CVAs with diuretic than with ACEI,
  especially in blacks
• much data exists about benefits of ACEI in CHF

ALLHAT. JAMA. 200228829812997.
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Comments on ALLHAT

• Diuretics should be an integral part of HTN
  therapy, especially in the elderly and blacks
• ACEI should be used in optimal combinations with
  adequate BP control, and may still be optimal
  first-line in non-blacks
• CCBs dont increase risk for MI or death

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VALUE Study Design
15,313 high-risk hypertensive patientsage ?50
years
Amlodipine 5 mg
Valsartan 80 mg
? Amlodipine 10 mg
? Valsartan 160 mg
HCTZ 12.5 mg
? HCTZ 25 mg
Free add-on
Primary endpointCV morbidity and mortality
Mann J et al. Blood Press. 19987176183.
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VALUESystolic Blood Pressure in Study
Sitting SBP by Time and Treatment Group
155
Valsartan (N 7649)
Amlodipine (N 7596)
150
mmHg
145
140
135
1
24
48
2
3
4
6
12
18
30
36
42
54
60
66
Baseline
Months
(or final visit)
Difference in SBP Between Valsartan and Amlodipine
5.0
4.0
3.0
mmHg
2.0
1.0
0
1
24
48
2
3
4
6
12
18
30
36
42
54
60
66
1.0
Months
(or final visit)
Julius S et al. Lancet. 200436320222031.
45
VALUE Outcomes and SBP Differences at Different
Time Points Primary Endpoint
Time Interval
PRIMARY ENDPOINT Odds Ratios and 95 CIs
SBP
(months)
mmHg
2.2
Overall study
03
3.8
36
2.3
612
2.0
1224
1.8
2436
1.6
3648
1.4
Study end
1.7
4.0
1.0
2.0
0.5
Favors Amlodipine
Favors Valsartan
Odds ratio
Julius S et al. Lancet. 200436320222031.
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VALUE Outcomes and SBP Differences at Different
Time Points Myocardial Infarction
Time Interval
MYOCARDIAL INFARCTION Odds Ratios and 95 CIs
D
SBP
(months)
(mmHg)
Overall study
2.2
3.8
03
2.3
36
2.0
612
1.8
1224
1.6
2436
1.4
3648
Study end
1.7
4.0
1.0
2.0
0.5
0.25
Favors amlodipine
Favors valsartan
Julius S et al. Lancet. 200436320222031.
47
VALUE Study Summary

• Incidence of stroke was lower, but not
  significantly, in the amlodipine group
• Incidence of fatal and non-fatal MI was
  significantly lower in the amlodipine group
• There was a positive trend in favor of valsartan
  for less heart failure but this did not reach
  significance
• There was a highly significant (23) lower rate
  of new-onset diabetes in the valsartan group

Julius S et al. Lancet. 200436320222031.
48
VALUE Outcomes and SBP Differences at Different
Time Points Primary Endpoint
Time Interval
PRIMARY ENDPOINT Odds Ratios and 95 CIs
SBP
D
(months)
mmHg
2.2
Overall study
03
3.8
36
2.3
612
2.0
1224
1.8
2436
1.6
3648
1.4
Study end
1.7
4.0
1.0
2.0
0.5
Favors Amlodipine
Favors Valsartan
Odds ratio
Julius S et al. Lancet. 20043632022-2031.
49
VALUE Study Summary

• The observed difference in stroke rates appears
  to be strongly related to differences in achieved
  blood pressures
• VALUE highlights the need for aggressive prompt
  BP control to modify acute outcomes (stroke, MI)
  and RAS inhibition to modify long-term outcomes
  (CHF and diabetes)

Julius S et al. Lancet. 200436320222031.