1. No category

MNT in Cardiovascular
Disease
Prevalence and Incidence



The United States ranks 14th and 16th,
among industrialized nations for the
prevalence of CVD in women and men,
respectively.
More than 61 million Americans have at least
one form of CVD (i.e., hypertension, CHD,
stroke, rheumatic heart disease, or
congestive heart failure).
The incidence of CHD is high; an American
experiences a coronary event almost every
29 seconds.
Leading Causes of Death
U.S. 2000
From http://www.nhlbi.nih.gov/resources/docs/02_chtbk.pdf; accessed 3-05
Percentage Breakdown of Deaths From
Cardiovascular Diseases
United States:2002 Preliminary
Coronary Heart Disease
13%
Stroke
0%
4%
Congestive Heart Failure
5%
High Blood Pressure
6%
53%
Diseases of the Arteries
18%
Rheumatic Fever/Rheumatic
Heart Disease
Congenital Cardiovascular
Defects
Other
Source: CDC/NCHS.
Prevalence of Coronary Heart Diseases
by Age and Sex
Percent of Population
NHANES :1999-2002
20
16.8
15
11.6
10.3
11.5
10
6.3
5
0.0 0.3
1.4
3.0
0.2
3.6
1.6
0
20-34
35-44
45-54
55-64
Ages
Men
Source: CDC/NCHS and NHLBI.
Women
65-74
75+
New and Recurrent Attacks
Annual Number of Americans Having
Diagnosed Heart Attack by Age and Sex
ARIC: 1987-2000
500,000
410,000 372,000
400,000
300,000
250,000
200,000
88,000
100,000
34,000
10,000
0
29-44
45-64
65+
Ages
Men
Women
Source: Extrapolated from rates in the NHLBI’s ARIC surveillance
study, 1987-2000. These data don’t include silent MIs.
Prevalence of Stroke by Age and Sex
NHANES: 1999-2002
Percent of Population
14
12.0 11.5
12
10
8
6.6 6.3
6
4
2
0.4
0.3
1.1 0.8
0
20-34
35-44
2.1
1.2
3.1 3.0
`
45-54
55-64
Ages
Men
Source: CDC/NCHS and NHLBI.
Women
65-74
75+
Percent of Population
Prevalence of High Blood Pressure
in Americans by Age and Sex
NHANES: 1999-2002
100
74.0
80
55.5
60
69.2
46.6
34.1 34.0
40
20
60.9
83.4
11.1
21.3 18.1
5.8
0
20-34
35-44
45-54
55-64
Ages
Men
Source: CDC/NCHS and NHLBI.
Women
65-74
75+
Percent of Population
Prevalence of Congestive Heart
Failure by Age and Sex
NHANES: 1999-2002
9.8 10.9
10
8
6
4.1
4
1.8
2
6.2
5.8
0.3 0.3
0.5
2.3
1.5
0.4
0
20-34
35-44
45-54
55-64
Ages
Men
Source: CDC/NCHS and NHLBI.
Women
65-74
75+
Cardiovascular Disease Mortality Trends
for Males and Females
Years
Males
Source: CDC/NCHS.
Females
01
99
97
95
93
91
89
87
85
83
81
520
500
480
460
440
420
400
380
79
Deaths in Thousands
United States: 1979-2002
CVD in Men and Women



CVD mortality in men is holding
steady; in women it is increasing
Women have comparable CVD rates
about 10-15 years later than men, but
the gap diminishes with age
82% of coronary events in women are
attributable to unhealthy diet, lack of
activity, cigarette use, and overweight
CVD in Women


Women post MI are less likely to receive
aspirin, beta-blockers, intravenous heparin,
or nitrate therapies within the first 24 hours
of hospital admission
They were less likely to undergo coronary
angiography, angioplasty, or bypass surgery,
but they were more likely to die in the
hospital.
CVD in Women



Women have a higher prevalence of
white-coat hypertension than men.
Women may have atypical symptoms
when suffering a heart attack or
angina
When they are sent home from the
hospital, they are more than twice as
likely to die as those who are admitted
A Nation at Risk





49 million Americans smoke
42 million have total cholesterols >240
mg/dl
63 million have total cholesterols 200239
17 million Americans have diabetes
61 million Americans are obese; 68
million are overweight
There is Encouraging
News!
Framingham Milestones




1960: cigarette smoking found to increase
the risk of heart disease
1961: Cholesterol level, blood pressure, and
EKG abnormalities found to increase the risk
of heart disease
1967: physical activity found to reduce the
risk of heart disease; obesity found to
increase the risk of heart disease
1970: High blood pressure found to increase
the risk of stroke
Framingham Milestones





1976: Menopause found to increase the risk
of heart disease
1978: Psychosocial issues found to affect
the risk of heart disease
1988: High levels of HDL found to reduce
risk of death
1994: Enlarged left ventricle found to
increase the risk of stroke
1996: Progression from hypertension to
heart failure described
Favorable Trends


Over past 30 years, mortality and inhospital case fatality has declined 50%
Prevalence of risk factors of smoking,
hypertension, high cholesterol has
declined 25 to 46%
Cigarette smoking among men, women, high school students,
and mothers during pregnancy: United States, 1965-2003
60
50
Men
40
Percen
t
High school students
Women
30
20
Mothers during pregnancy
10
0
1965
1970
1975
1985
1980
1990
1995
Year
NOTES: Percents for men and women are age adjusted. See
Data Table for data points graphed, standard errors, and
additional notes. Cigarette smoking is defined as: (for men and
women 18 years of age and older) at least 100 cigarettes in
lifetime and now smoke every day or some days; (for students
in grades 9-12) 1 or more cigarettes in the 30 days preceding
the survey; and (for mothers with a live birth) during pregnancy.
SOURCES: Centers for Disease Control and Prevention,
National Center for Health Statistics, National Health Interview
Survey (data for men and women); National Vital Statistics
System (data for mothers during pregnancy); National Center
for Chronic Disease Prevention and Health Promotion, Youth
Risk Behavior Survey (data for high school students).
Centers for Disease Control and Prevention, National Center for Health Statistics. Health, United States, 2004
2003
Percent of Population 20-74 with
High Serum Cholesterol by Race
and Sex 1971-74 to 1988-94
http://www.nhlbi.nih.gov/resources/docs/02_chtbk.pdf accessed 3-05
THE BAD NEWS: Overweight and obesity by
age: United States, 1960-2002
Overweight including obese, 20-74 years
Overweight, but not obese, 20-74 years
Obese, 20-74 years
Overweight, 6-11 years
Overweight, 12-19 years
1960-62 1963-65
1966-70
1971-74
1976-80
1988-94
Year
NOTES: Percents for adults are age adjusted. For adults: "overweight
including obese" is defined as a body mass index (BMI) greater than or equal
to 25, "overweight but not obese" as a BMI greater than 25 but less than 30,
and "obese" as a BMI greater than or equal to 30. For children: "overweight" is
defined as a BMI at or above the sex- and age-specific 95th percentile BMI cut
points from the 2000 CDC Growth Charts: United States. "Obese" is not
defined for children. See Data Table for data points graphed, standard errors,
and additional notes. Data are for the civilian noninstitutionalized population
and are age adjusted. See Data Table for data points graphed and additional
notes.
19992002
SOURCES: Centers for Disease Control and Prevention,
National Center for Health Statistics, National Health
Examination Survey and National Health and Nutrition
Examination Survey.
Centers for Disease Control and Prevention, National Center for Health Statistics. Health, United States, 2004
The Decrease in CVD
Mortality


25% is due to primary prevention
75% is due to behavioral changes
affecting risk factors or improvements
in treatment
Benefits of Risk Factor
Reduction




50-70% lower risk in former vs current
smokers within 5 years of cessation
2-3% decline in risk for each reduction
of 1% serum cholesterol
2-3% decline in risk for each reduction
of 1 mm Hg in diastolic blood pressure
35-55% lower risk for those who
maintain desirable body weight as
compared to those 20%+ above
Benefits of Risk Factor
Reduction


45% lower risk for those who maintain
an active lifestyle compared with a
sedentary lifestyle
35% lower risk in aspirin users
compared with nonusers
Coronary Heart Disease (CHD) or
Coronary Artery Disease (CAD)



Disease involves impeded blood flow to the
network of blood vessels surrounding and
serving the heart
Major cause is atherosclerosis; structural and
compositional changes in the inner wall of the
arteries
Manifested in clinical end points of myocardial
infarction (MI) and sudden death
Pathophysiology of
Atherosclerosis



Vessel lining is injured (often at branch
points) →
Plaque is deposited to repair injured
area →
Plaque thickens, incorporating
cholesterol, protein, muscle cells, and
calcium (rate depends partly on level
of LDL-C in the blood) →
Pathophysiology of
Atherosclerosis (cont)



Arteries harden and narrow as plaque
builds, making them less elastic →
Increasing pressure causes further
damage →
A clot or spasm closes the opening,
causing a heart attack
Pathophysiology of
Atherosclerosis



Proliferation of smooth-muscle cells,
macrophages, and lymphocytes
Formation of smooth muscle cells into
a connective tissue matrix
Accumulation of lipid and cholesterol
in the matrix around the cells
Endothelial Injury Caused
by








Hypercholesterolemia
Oxidized low-density lipoprotein
Hypertension
Cigarette smoking
Diabetes
Obesity
Homocysteine
Diets high in saturated fat and cholesterol
Natural Progression of
Atherosclerosis
(From Harkreader H. Fundamentals. Philadelphia: W.B. Saunders, 2000)
Plaque or Atheroma

Lipid deposits and other materials
(cellular waste products, calcium, fibrin)
that build up in the intimal layer
Heart Attack (Myocardial
Infarction)
Heart Attack (Myocardial
Infarction)



When blood supply to the heart is
disrupted, the heart is damaged
May cause the heart to beat irregularly
or stop altogether
25% of people do not survive their
first heart attack
Symptoms of a Heart
Attack








Intense, prolonged chest pain or
pressure
Shortness of breath
Sweating
Nausea and vomiting (especially
women)
Dizziness (especially women)
Weakness
Jaw, neck and shoulder pain
(especially women)
Irregular heartbeat
Factors That May Bring On
Heart Attack (in at-risk)





Dehydration
Emotional stress
Strenuous physical activity when not
physically fit
Waking during the night or getting up
in the morning
Eating a large, high-fat meal
(increases risk of clotting)
Cerebrovascular Accident
(CVA) or Brain Attack
Brain Attack (Stroke) or
Cerebrovascular Accident
Symptoms of Stroke
(Brain Attack)





Sudden numbness or weakness of the face,
arm or leg, especially on one side of the
body
Sudden confusion, trouble speaking or
understanding
Sudden trouble seeing in one or both eyes
Sudden trouble walking, dizziness, loss of
balance or coordination
Sudden severe headache
Functions of Lipoproteins




Lipids are transported in the blood bound to
protein
Lipoproteins vary in composition, size, and
density
Consist of varying amounts of triglyceride,
cholesterol, phospholipid, and protein
The ratio of protein to fat determines the
density (HDLs have more protein than LDLs)
Lipoproteins combine
Lipids (triglycerides,
cholesterol)
 Protein
 Phospholipids

Functions of the Plasma
Lipoproteins





Chylomicron—Transport of dietary
triglyceride
VLDL—Transport of endogenous
triglyceride
IDL—LDL precursor
LDL—Major cholesterol transport
lipoprotein
HDL—Reverse cholesterol transport
Lipoprotein Summary
Lipoprotein Assessment

Includes measurement of total
cholesterol, LDL cholesterol, HDL
cholesterol, and triglyceride level after
fasting
Total Cholesterol




Captures cholesterol contained in all
lipoprotein fractions
60%-70% is carried on LDL
20%-30% is carried on HDL
10%-15% on VLDL
Total Cholesterol




Direct, positive association between TC and
CHD risk
Diets high in saturated fats raise total
cholesterol and CHD incidence and mortality
ATP-III Guidelines: lowering total
cholesterol and LDL-C reduces CHD risk
10% reduction in TC decreases CHD risk by
about 30%
Factors Affecting Total
Cholesterol





Age
Diets high in fat,
saturated fat,
cholesterol
Genetics
Endogenous sex
hormones (premenopause)
Exogenous steroids






Drugs (beta
blockers, thiazide
diuretics)
Body weight
Glucose tolerance
Physical activity
Season of the year
Diseases
Prevalence of High Total
Cholesterol



Serum cholesterol levels in the U.S.
population have been declining since 1960
More than half that decline occurred
between 1976 and 1991, when national
preventive education efforts were begun
Proportion of adults with TC>240 mg/dl fell
from 27% to 19%, while HDL and VLDL
remained unchanged
Total Triglycerides




Triglyceride-rich lipoproteins include
chylomicrons, VLDL, remnants or
intermediary products
Are atherogenic
At very high levels, ↑ risk of
pancreatitis
Can be evidence of metabolic
syndrome
Chylomicrons






Largest particles
Transport dietary fat and cholesterol from
the small intestine to the liver
In the bloodstream, triglycerides are
hydrolyzed by lipoprotein lipase (LPL) in
muscle and adipose tissue
When 90% of triglyceride is hydrolyzed,
released into blood as a remnant
Liver metabolizes remnants, but some
deliver cholesterol to the arterial wall
Absent in fasting studies
Very-Low-DensityLipoproteins





Manufactured in the liver to transport
endogenous triglyceride and
cholesterol
60% is triglyceride
Large VLDL may be nonatherogenic
VLDL remnants or IDL appear to be
atherogenic
Not routinely measured, but TG in
them is measured in total triglyceride
Intermediate-Density
Lipoprotein




Formed with catabolism of VLDL, a
precursor of LDL
Rich in cholesterol and apo E
High concentrations of IDL and VLDL
remnants directly related to lesion
progression and coronary events
Not routinely measured, though
components can be
Low-Density Lipoprotein





Primary cholesterol carrier in blood
Total cholesterol and LDL-cholesterol are
strongly correlated
95% of apolipoproteins in LDL are apo-B100
LDL is formed in VLDL catabolism, 60% is
taken up by LDL receptors in liver, adrenals,
other tissues; rest is metabolized via
alternative pathways
Number and activity of receptors determines
LDL cholesterol levels in the blood
LDL-C



Particles heterogeneous in size, density,
lipid components
Phenotype A: large particles, not
associated with disease risk
Phenotype B typified by small, dense
LDL particles; triglyceride rich,
cholesterol depleted; predictive of
CHD risk in men and women
High Density Lipoproteins
(HDL)



Contain more protein than
the other lipoproteins
Apo A-1 is involved in tissue
cholesterol removal
High HDL is associated with
low levels of chylomicrons,
VLDL remnants, and small,
dense LDL
Lipoprotein Profile



Measures total cholesterol, LDLcholesterol, HDL-cholesterol, and
triglycerides
8-12 hour fast allows chylomicrons to
clear
Friedenwald formula for calculating
LDL-C = (TC) – (HDL-C) – (TG/5)
ATP III Guidelines




Adult Treatment Panel for the
Detection, Evaluation, and Treatment
of High Blood Cholesterol in Adults
convened by the National Heart, Lung
& Blood Institute of the NIH
Published 2002
Updated in 2004
Next revision expected in 2009 (panel
convened 2/08)
Lipoprotein Profile


If nonfasting, can measure total and
HDL cholesterol
If TC>200 mg/dl or HDL-C is <40
mg/dl, get fasting analysis
Evaluating Blood Lipids:
Total Cholesterol
<200 mg/dL
Desirable
200-239 mg/dL Borderline high
≥240 mg/dL
High
Source: ATP-III Guidelines, NHLBI, accessed 2-2005
Evaluating Blood Lipids:
Triglycerides
<150 mg/dL
Normal
150-199
Borderline high
200-499
High
>500 mg/dl
Very high
Source: ATP-III Guidelines, NHLBI, accessed 4-2005
Evaluating Blood Lipids:
LDL
<100 mg/dL
Optimal
100-129
Near optimal
130-159
Borderline high
160-189
High
≥190
Very high
Source: ATP-III Guidelines, NHLBI, accessed 2-2005
Evaluating Blood Lipids:
HDL
< 40 mg/dL
Low
≥ 60 mg/dL
High
Source: ATP-III Guidelines, NHLBI, accessed 2-2005
Risk Factors affect Lipid
Targets



Major, independent risk factors
Life-habit risk factors
Emerging risk factors
Major Risk Factors That
Modify LDL Goals




Cigarette smoking
Hypertension (BP 140/90 mmHg or on
antihypertensive medication)
Low HDL cholesterol (<40 mg/dL)†
Family history of premature CHD
– CHD in male first degree relative <55
– CHD in female first degree relative <65
– Age (men 45 years; women 55 years)
†
Life-Habit Risk Factors



Obesity (BMI  30)
Physical inactivity
Atherogenic diet
Emerging Risk Factors






Lipoprotein (a)
Homocysteine
Prothrombotic factors
Proinflammatory factors
Impaired fasting glucose
Subclinical atherosclerosis
Risk Assessment
Count major risk factors*

For patients with multiple (2+) risk factors
– Perform 10-year risk assessment

For patients with 0–1 risk factor
– 10 year risk assessment not required
– Most patients have 10-year risk <10%

*HDL cholesterol 60 mg/dL counts as a “negative” risk
factor; its presence removes one risk factor from the total
count.
CHD Risk Equivalents


Risk for major coronary events equal
to that in established CHD
10-year risk for hard CHD >20%
Hard CHD = myocardial infarction + coronary
death
Diabetes
In ATP III, diabetes is regarded
as a CHD risk equivalent.
Diabetes as a CHD Risk
Equivalent


10-year risk for CHD  20%
High mortality with established CHD
– High mortality with acute MI
– High mortality post acute MI
CHD Risk Equivalents



Other clinical forms of atherosclerotic
disease (peripheral arterial disease,
abdominal aortic aneurysm, and
symptomatic carotid artery disease)
Diabetes
Multiple risk factors that confer a 10year risk for CHD >20%
Calculate Your 10-Year
Risk of Heart Attack


Risk Calculation
http://hp2010.nhlbihin.net/atpiii/calcul
ator.asp?usertype=pub
At-A-Glance treatment guidelines:
http://www.nhlbi.nih.gov/guidelines/c
holesterol/atglance.htm
Three Categories of Risk
that Modify LDL-C GOALS
Risk Category
CHD and CHD risk
equivalents
Multiple (2+) risk
factors
Zero to one risk
factor
LDL Goal
(mg/dL)
<100
<130
<160
ATP III Guidelines
Goals and Treatment
Overview
Primary Prevention With
LDL-Lowering Therapy
Public Health Approach



Reduced intakes of saturated fat and
cholesterol
Increased physical activity
Weight control
Causes of Secondary
Dyslipidemia





Diabetes
Hypothyroidism
Obstructive liver disease
Chronic renal failure
Drugs that raise LDL cholesterol and
lower HDL cholesterol (progestins,
anabolic steroids, and corticosteroids)
Secondary Prevention W/
LDL-Lowering Therapy




Benefits: reduction in total mortality,
coronary mortality, major coronary
events, coronary procedures, and
stroke
LDL cholesterol goal: <100 mg/dL
Includes CHD risk equivalents
Consider initiation of therapy during
hospitalization
(if LDL 100 mg/dL)
LDL-C Goals in Different Risk
Categories
Risk Category
LDL Goal
(mg/dL)
CHD or CHD
Risk
Equivalents
(10-year risk
>20%)
<100;
optional goal
<70 mg/dL
Moderately
high risk
2+ Risk Factors
(10-year risk
10-20%)
<130
LDL for Total
Lifestyle Change
(TLC) (mg/dL)
LDL for
Drug Therapy
(mg/dL)
100
100
(<100:
consider drug
options
130
>130 mg/dL
(100-129
mg/dL,
consider drug
options)
ATP-3 update, Circulation, 2004
LDL-C Goals in Different
Risk Categories
Risk Category
LDL Goal
(mg/dL)
LDL for Total
Lifestyle Change
(TLC) (mg/dL)
LDL for
Drug Therapy
(mg/dL)
Moderate risk:
2+ risk factors
(10 year
risk<10%)
<130 mg/dL
>130 mg/dL
>160 mg/dL
Lower risk (0-1
risk factors)
<160 mg/dL
>160 mg/dL
>190 mg/dL
(160-189
mg/dL, drug
optional)
ATP-3 update, Circulation, 2004