HYPERTENSION AND OBESITY

1

• HYPERTENSION AND OBESITY
• AS CLUSTERED RISK FACTORS CONSIDERATIONS AND
  GOALS FOR SUCCESS IN THE COMPLEX PATIENT
• Henry R. Black, M.D.
• NYU School of Medicine
• Center for the Prevention of Cardiovascular
  Disease
• Oct. 30, 2007

2
Achievements in Public Health, 20th Century
Total cardiovascular diseases
Diseases of the heart
Coronary heart disease
Stroke
Age-adjusted to the 2000 US population. Sources
NHLBI, Morbidity and Mortality Chart Book 2000
CDC, Health, United States 2001
3
Leading Causes of Death for All Ages United
States
SGR
STATINS
VA STUDY DIURETICS
CLRDchronic lower respiratory diseases. Centers
for Disease Control and Prevention. Available at
http//www.cdc.gov/nchs/data/hus/ hus05.pdf.
Accessed July 4, 2006.
4
Cardiovascular disease mortality trends for males
and females (United States 1979-2004). Source
NCHS and NHLBI.

5
Deaths in Thousands
A Total CVD B Cancer C Accidents
D Chronic Lower Respiratory Diseases E Diabetes
Mellitus F Alzheimers Disease
Leading causes of death for all males and
females (United States 2004). Source NCHS and
NHLBI.
6
Leading causes of death both sexes (United
States 2004). Source NCHS and NHLBI.
7
Leading causes of death females (United States
2004). Source NCHS and NHLBI.
8
Impact of Cardiovascular Disease

• CVD No 1 killer in US
• 403.1 billion
• 2500 CVD deaths each day 1 death every 35
  seconds
• CVD claims more lives each year than the next 3
  leading causes of death combined

Deaths per 100,000
CVD
Cancer
Trauma
Respiratory Disease
AHA Statistics Committee and Stroke Statistics
Subcommittee. Circulation. 20061-69.
9
Prevalence of cardiovascular diseases in adults
age 20 and older by age and sex (NHANES
1999-2004). Source NCHS and NHLBI. These data
include coronary heart disease, heart failure,
stroke and hypertension.
10
Percentage breakdown of deaths from
cardiovascular diseases (United States2004)
Source NCHS and NHLBI.
11
Cardiovascular Risk FactorsJNC 7
LDLlow-density lipoprotein HDLhigh-density
lipoprotein GFRglomerular filtration rate
UAEurinary albumin excretion LVHleft
ventricular hypertrophy MImyocardial
infarction CKDchronic kidney disease JNC 7The
Seventh Report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment
of High Blood Pressure. Components of the
metabolic syndrome.Chobanian et al. JAMA.
20032892560-2572 (C) Segura et al. Curr
Cardiol Rep. 20024458-462 (A).
12
Trends in CV Risk Factors, US Adults Aged 20-74
Years (NHES 1960-1962 NHANES 1971-1975 to
1999-2000)
High total cholesterol was defined as 240 mg/dL
hypertension was defined as 140/90 mm Hg.
NHESNational Health Examination Survey.
Gregg EW, et al. JAMA. 20052931868-1874.
13
Multiple Risk Factors Are Prominent in Residents
Across the United States
Risk Factors for Heart Disease and Stroke, 2003
Percentage With ?2 Risk Factors
2029
3039
gt40
Risk factors included high BP, high cholesterol,
diabetes, and smoking.
CDC. MMWR Morbid Mortal Wkly Rep. 200554113-117.
14
Stroke and IHD Mortality vs Usual Systolic BP by
Age
Mortality(Floating absolute risk and 95 CI)
IHD ischemic heart disease.Prospective Studies
Collaboration. Lancet. 20023601903-1913.
15
Prospective Studies Collaboration

• Throughout middle and old age, usual blood
  pressure is strongly and directly related to
  vascular (and overall) mortality, without any
  evidence of a threshold down to at least 115/75
  mm Hg.

Lancet 2002 3601903
16
BP Reductions as Small as 2 mmHg Reduce the Risk
of CV Events by Up to 10

• Meta-analysis of 61 prospective, observational
  studies
• 1 million adults
• 12.7 million person-years

7 reduction in risk of IHD mortality
2 mmHg decrease in mean SBP
10 reduction in risk of stroke mortality
Prospective Studies Collaboration. Lancet.
20023601903-1913.
17
CV Mortality Risk Doubles WithEach 20/10 mm Hg
BP Increment
8
7
6
5
CVmortalityrisk
4
3
2
1
0
115/75
135/85
155/95
175/105
SBP/DBP (mm Hg)
CV, cardiovascular DBP, diastolic blood
pressure SBP, systolic blood pressure. Individua
ls aged 40-69 years, starting at BP 115/75 mm
Hg. Lewington S et al. Lancet. 20023601903-1913.
Chobanian AV et al. JAMA. 20032892560-2572.
18
Global Mortality and Burden of Disease
Attributable to CVD and Major Risk Factorsfor
People Aged ?30 Years
Mortality
Burden of Disease
All CV
16M
128M
High BP
High cholesterol
7.8M
59M
Overweight and obesity
39M
4.3M
2.3M
30M
Mmillion.

• Ezzati M, et al. PLoS Med. 20052e133.

19

• "I see one third of a nation
• ill-housed,
• ill-clad, and
• ill-nourished.
• FDR, Second Inaugural, Jan. 1937

20
Welcome to Cape Cod!
21
Age-adjusted prevalence of obesity (BMI gt 30.0)
in adults ages 20-74 by sex and survey NHES,
1960-62 NHANES, 1971-74, 1976-80, 1988-94 and
2001-2004). Source Health, United States, 2006,
unpublished data. NCHS
22
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23
Prevalence of overweight among students in grades
9-12 by race/ethnicity and sex (YRBS 2005).
Source BMI 95th percentile or higher. MMWR. 2006
55 No. SS-5. NH non-Hispanic.
24
Trends in prevalence of overweight among U.S.
children and adolescents by age and survey
(NHANES, 1971-74, 1976-80, 1988-94 and
2001-2004). Source Health, United States, 2006,
unpublished data. NCHS.
25
Prevalence of Overweight Obesity in
School-Children (10-16 yr-old), Defined by BMI,
2001-2002

• Source International Association for the Study
  of Obesity
• Published in the Br Med J, June 21, 2005

26
Trends in Age-Adjusted Prevalence of Health
Conditions, US Adults Aged 20-74 Years(NHANES
1971-1974 to 1999-2000)
NHANESNational Health and Nutrition Examination
Survey.
Briefel RR, et al. Annu Rev Nutr. 200424401-431.
27
OBESITY AND HYPERTENSION RISKPERCENT OF PATIENTS
WITH SYSTOLIC BP gt 140 mm Hg

BMI Levels
Canadian Guidelines for Healthy Weights. Cat No.
H39-134/1989E 198869
28
PREVALENCE OF OBESITY AND DIABETES AMONG US
ADULTS, 1991 AND 2001
Obesity
Diabetes
Mokdad JAMA 2001, 286 1195-1200 Sacks FM et
al. Am J Cardiol. 200290(suppl 2)165-167
29
Prevalence of Non-Insulin-Dependent (Type 2)
diabetes in Adults age 18 by Race/Ethnicity, and
Years of Education (NHANES 1999-2004). Source
NCHS and NHLBI.
30
NHANES III 1988-1994 Prevalence of Elevated Blood
Pressurein Diabetic Adults
Total Population, Total
Men Women

Non-Hispanic White, Total
Men Women

Non-Hispanic Black, Total
Men Women

Mexican American, Total
Men Women

Percent
NHANES IIIThird US National Health and Nutrition
Examination Survey (1988-1994) ?130/85 mm Hg or
current use of prescription medication for
hypertension
Geiss LS et al. Am J Prev Med. 20022242-48.
31
Association of Systolic BP andCardiovascular
Death in Type 2 Diabetes
250
Non-diabetic patients
Diabetic patients
200
150
Cardiovascular mortalityrate/10,000 person-yr
100
50
0
lt120
120139
140159
160179
180199
³200
Systolic blood pressure (mm Hg)
Stamler J et al. Diabetes Care. 199316434-444.
32
Percent Chance of Cardiovascular Event in 5
Years No Diabetes
Men Women
Nonsmoker Smoker Total Chol.HDL-C
Nonsmoker Smoker Total Chol.HDL-C
BP(mm Hg)
4 5 6 7 8 4 5 6 7 8
4 5 6 7 8 4 5 6 7 8
180/105 160/95 140/85 120/75
Age 70
180/105 160/95 140/85 120/75
Age 60
180/105 160/95 140/85 120/75
Age 50
Jackson R. BMJ. 2000320709-710.
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Percent Chance of Cardiovascular Event in 5
Years Diabetes
Men Women
Nonsmoker Smoker Total Chol.HDL-C
Nonsmoker Smoker Total Chol.HDL-C
BP(mm Hg)
4 5 6 7 8 4 5 6 7 8
4 5 6 7 8 4 5 6 7 8
180/105 160/95 140/85 120/75
Age 70
gt20 15-20 10-15 5-10 2.5-5
180/105 160/95 140/85 120/75
Age 60
180/105 160/95 140/85 120/75
Age 50
Jackson R. BMJ. 2000320709-710.
34
Causes of ESRD in the United States
Primary Diagnosis for Patients Who Start Dialysis
Glomerulonephritis
Other
10
13
No. of patients
700
Projection
600
500
400
No. of dialysis patients (thousands)
520,240
300
281,355
200
243,524
100
r299.8
0
1984
1988
1992
1996
2000
2004
2008
United States Renal Data System. Annual data
report. 2000.
35
Consequences of Obesity
36
Body Mass Index (BMI)
Weight (kg) Height (m2)
BMI
Adapted from the World Health Organization.
Obesity Preventing and Managing the Global
Epidemic. Geneva WHO 2000.
37
Correlation Between Increased Body Mass Index
and Risk of Mortality
3.0
Age at Issue
Digestive and Pulmonary Disease
CV Gallbladder Diabetes Mellitus
2029 y
2.5
3039 y
2.0
1.5
Clinical Obesity
Mortality Ratio
Overweight
1.0
Pre-overweight
Moderate Risk
Very Low Risk
Low Risk
High Risk
Very High Risk
.5
0
15
20
25
30
35
40
BMI (kg/m2)
BMIbody mass index.
Image courtesy of George A. Bray, MD.
38
Comorbid Conditions and BMI
Patients With BMI ?27

• Comorbid conditions that increase as BMI
  increases
• Hypertension (56)
• Dyslipidemia (47)
• Type 2 diabetes (70)

No Comorbidity 35
Comorbidity65
Adapted from NHANES III data.
39
Relation Between BMI and Comorbidities
Women
Men
4
4
Relative Risk
Body Mass Index
Body Mass Index
Willett WC, et al. N Engl J Med. 1999341427434.
40
Relative Risk of Type 2 DiabetesNurses Health
Study(N Engl J Med 2001345790-7)
61 of diabetes cases had BMI of 25 or
higher
Relative Risk
Body Mass Index
41
RELATIONSHIP OF BMI AND MORTALITY
Hu FB et al. N Engl J Med. 20043512694-2703.
42
RELATIONSHIP OF BMI AND MORTALITY
We estimate that excess weight (defined as a BMI
of 25 or higher) and physical inactivity (less
than 3.5 hours of exercise per week) together
could account for 31 of all premature deaths,
59 of deaths from CVD, and 21 of deaths from
cancer among nonsmoking women.
Hu FB et al. N Engl J Med. 20043512694-2703.
43
BMI and risk for Type 2 Diabetes, Hypertension
and CVD
30-39.9 Obesity Very high risk
?40 Extreme Obesity Extremely high risk
25-29.9 Overweight Moderate risk
Weight (lbs)
260
270
280
290
300
190
200
210
220
230
240
250
120
130
150
160
170
180
140
5'0"
5'2"
19-24.9 Normal Low risk
5'4"
5'6"
Height
5'8"
5'10"
15-18.9 Very low risk
6'0"
6'2"
6'4"
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Impact of 5-unit BMI increase on CHD risk
Meta-analysis of 21 studies N 302,296
Adverse effects of overweight on BP and
cholesterol could account for 45 of the ?CHD
risk
RR relative risk CI confidence
interval
Bogers RP et al. Arch Intern Med. 20071671720-8.
45
Discrimination The Pain of Obesity

• Former severely obese patients
• Leg amputation was preferred by 91.5 and
  blindness by 89.4
• 100 preferred to be deaf, dyslexic, diabetic or
  have heart disease or bad acne than to be obese
  again
• 100 preferred to be a normal weight person
  rather than a severely obese multimillionaire

Rand CSW, Macgregor AMC. Int J Obes.
199115577-579.
46
Android (Apple) vs. Gynoid (Pear) Obesity
ATributeto a Pioneer
Jean Vague (1947)
Vague J. Presse Med 194730339340.
47
Intra-abdominal (Visceral) Fat
Visceral adipose tissue
Front
Subcutaneous adipose tissue
Lemieux l, et al. Ann Endocrinol. 200162255-261.
48
Visceral Fat Is an Independent Predictor of
All-Cause Mortality in Men
6 5 4 3 2 1 0
Subject B is at a 2-fold higher risk for
mortality
Risk of Death
1
0
0.5
1.5
Visceral Fat (kg)
Subject A
Subject B
Visceral fat in red
Kuk JL, et al. Obesity (Silver Spring).
200614336-341.
49
Waist Circumferenceas a Surrogate Marker

• Amount of visceral fat, as seen on the computed
  tomography scan of the abdomen, has an excellent
  correlation with waist circumference as shown by
  the adjoining graph
• Correlation coefficient (r0.80)

Despres JP, et al. BMJ. 2001322716-720.
50
Features of the Metabolic Syndrome Commonly Found
among Viscerally Obese Patients
Genetic susceptibility to hypertension, type 2
diabetes, and coronary heart disease ultimately
affects the clinical features of the metabolic
syndrome.
Adapted from Lemieux l , Després JP. In
Management of Obesity and Related Disorders.
200145-63.
51
Abdominal obesity is linked to multiple
cardiometabolic risk factors
Patients with abdominal obesity often present
with one or more additional CV risk factors (NCEP
ATP-III Criteria)
NHANES 19992000 cohort (data on file) National
Cholesterol Education Panel/Adult Treatment Panel
III (2002)
52
Abdominal Obesity Better Predictor of
Development of the Metabolic Syndrome than BMI
Han TS et al. Obes Res. 200210923-931.
Janssen I et al. Arch Intern Med.
20021622074-2079.
53
ATP III The Metabolic Syndrome(?3 risk factors
are required for diagnosis)Modifications as of
10/2005
Defining Level
Risk Factor
Abdominal obesity (Waist circumference)
gt40 in (37-39 gen. predisp 35 for As. Am)gt35 in
(31-35 gen. predisp 31 for As. Am)
MenWomen
?150 mg/dL or Rx
TG
HDL-C
lt40 mg/dL or Rxlt50 mg/dL or Rx
MenWomen
?130 or ?85 mm Hg or Rx for ?BP
Blood pressure
?100 mg/dL
Fasting glucose
Grundy SM et al. Circulation. 2005282289-2304.
54
The Metabolic Syndrome andits Consequences
Visceral obesity ? Insulin resistance Raised
blood pressure Atherogenic dyslipidemia Proinfla
mmatory state Prothrombotic state
Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults.
JAMA. 20012852486-2497.
55
Mortality rates in U.S. adults, age 30-75, with
metabolic syndrome (MetS), with and without
diabetes mellitus (DM) and pre-existing CVD
(NHANES II 1976-80 Follow-up Study). Average of
13 years of follow-up. Source Malik et
al., Circulation. 20041101245-50.
56
Adverse Cardiovascular Prognosis in Metabolic
Syndrome.Population-Based Observational Study in
1209 Men
Cardiovascular Disease Mortality
15
RR (95 Cl), 3.55 (1.98-6.43)
10
Cumulative Hazard,
Metabolic Syndrome Yes No
5
0
0
2
4
6
8
10
12
Follow-up, y
Lakka et al. JAMA 20022882709-2716
57
Abdominal Obesity and Increased Risk of
Cardiovascular Events
The HOPE Study
1.4
1.35
1.29
1.27
1.17
1.16
1.2
1.14
Adjusted relative risk
1
1
1
1
0.8
CVD death
MI
All-cause deaths
Adjusted for BMI, age, smoking, sex, CVD disease,
DM, HDL-C, total-C
Dagenais GR et al. Am Heart J. 200514954-60.
58
Elevated BP One of the Most Prevalent Risk
Factors in Metabolic Syndrome
Prevalence of Selected Risk Factors Among
Patients With Metabolic Syndrome
Patients With Metabolic Syndrome,
Wong ND, et al. Am J Cardiol. 2003911421-1426.
59
Different Components of the NCEP the Metabolic
Syndrome Predict CHD NHANES
Prediction of CHD Prevalence using Multivariate
Logistic Regression
Significant predictors of prevalent CHD.
Alexander CM et al. Diabetes. 2003521210-1214.
60
The Problem
61
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62
Note Currently recommended levels is defined
as activity that increased their heart rate and
made them breathe hard some of the time for a
total of at least 60 minutes/day on 5 or more of
the 7 days preceding the survey.
Prevalence of students in grades 9-12 who met
currently recommended levels of physical activity
during the past 7 days by race/ethnicity and sex
Source MMWR. 200655No. SS-5. NH non-Hispanic.
63
Prevalence of leisure-time physical inactivity
among adults age 18 and older by race/ethnicity,
and sex. Source MMWR, 200554No. 39. NH
non-Hispanic.
64
FitnessFatness and CVD Mortalityin Men
Unfit Fit
5.0
4.5
3.1
Risk for Death
Reference
1.6
1.5
Overweight
Obese
Normal Weight
Wei M et al. JAMA 19992821547-1553.
65
CVD Mortality Risk by Fitness Level in
Individuals with Diabetes
Reference
Risk for CVD Mortality
lt7
7.07.9
8.08.9
9.09.9
10.010.9
11.0 11.9
12.012.9
?13.0
Maximal METs
Church TS et al. Arch Intern Med
20051652114-2120.
66
Cardiovascular Disease and Abdominal Obesity and
Inflammation
?
TNF-?
?
IL-6
?
? Risk of acute coronary syndrome
Atherogenic,insulin resistantdysmetabolicmilie
u
Adipose Tissue
Després JP. Int J Obes Relat Metab Disord.
200327S22-S24.
67
Potential Contribution of Ectopic Fat Deposition
to the Cardiometabolic Risk Profile of Viscerally
Obese Patients
Insulin-resistant subcutaneous adipose tissue
? LPL Insulin resistance
? Visceral adipose tissue
? Systemic FFAs
SKELETAL MUSCLE
?

• PAI-1
• IL-6
• TNF-?
• ?Adiponectin

? Portal FFAs
? Hepatic lipase Lipid deposition
Altered Cardiometabolic Risk Profile
? Insulin
LIVER
? Glucose
? Triglyceride
CORONARY ATHEROSCLEROSISUNSTABLE PLAQUE
? Apolipoprotein B
FFAs Free Fatty Acids
Després JP. Ann Med. 20063852-63.
68
Cardiometabolic Risk
Type 2diabetes
High LDL-C
Inflammatorymarkers
LowHDL-C
High BP
HighTG
CVdisease
Smoking
Insulinresistance
Abdominaladiposity
Dysglycaemia
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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
70
GOAL OF ANTIHYPERTENSIVE THERAPY

• lt 140 mm Hg and lt 90 mm Hg for most patients
• lt 130 mm Hg and lt 80 mm Hg for diabetics,
  patients with HF and those with CRF and any day
  now for those with CAD
• Goal is not dependent on age, gender or
  co-morbidity
• THE GOAL IS THE CEILING, NOT THE FLOOR.

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Appropriate Intensive Risk Factor Management
Today, Protect Patients Against Consequences
Tomorrow
Manage Risk Factors Intensively Today
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Saving and Overconsuming Energy