Table Of ContentHurst's the Heart; Chapter 1: CARDIOVASCULAR DISEASES IN THE UNITED STATES AND PREVENTION APPROACHES, Page 1
Part 1: BASIC FOUNDATIONS OF CARDIOLOGY
Chapter 1:
CARDIOVASCULAR DISEASES IN THE UNITED STATES AND PREVENTION
APPROACHES
Authors: Thomas J. Thom, William B. Kannel, Halit Silbershatz, Ralph B. D'Agostino, Sr.
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The large and long-term decline in mortality from the cardiovascular diseases accounted for
almost 4 of the 5.6-year increase in life expectancy in the United States attained between 1965 and
1995.1 The 55 percent decline in the age-corrected death rate for total cardiovascular disease
between 1950 and 1996 indicates the extent to which these leading causes of death are subject to
Search Hurst's
preventive and therapeutic measures. These diseases, however, still account for 41 percent of all
Search Drug List deaths and are leading causes of morbidity and health care utilization. Control of these diseases
should focus on prevention because of its inherent benefits, its apparent role in the mortality
reductions, and its potential given the presence of modifiable risk factors in millions of
Americans.
CARDIOVASCULAR DISEASES
Major Cause of Morbidity and Mortality
The most common cardiovascular diseases are hypertension and heart disease, but the basis for
most cardiovascular diseases is atherosclerosis, which is almost universally present in U.S. adults
and is manifest clinically as coronary heart disease (CHD), cerebrovascular disease (stroke), or
peripheral arterial disease. The likelihood of developing one of these diseases is high, and they
affect the health of nearly 59 million Americans.2 In 1999, these diseases were projected to
account for $178 billion in health care expenditures in the United States-2 percent of the gross
domestic product (Fig. 1-1). These diseases also account for an estimated $108 billion in lost
productivity due to illness and premature mortality. These expenditures and indirect costs are by
far the largest for any diagnostic group.
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Figure 1-1: Health expenditures for cardiovascular diseases, United States, 1999 (includes
expenditures for hospital, home, and nursing home care; physician and other professionals; and
drugs). (From the American Heart Association and National Heart, Lung, and Blood Insitute.2)
During the past 30 years, there have been major reductions in mortality rates for the various forms
of cardiovascular disease (Fig. 1-2). Cardiovascular diseases, however, continue to be the most
common threat to life and health. The lifetime risk of developing CHD after age 40 is 49 percent
in men and 32 percent in women.3 Even at age 70, the risk is 35 percent for men and 24 percent
for women. CHD is the leading or second leading cause of death beginning at age 45 in men and
in women.4 An estimated 8 percent of the U.S. population, 20 million persons, have some form of
heart disease.5 About 50 million, 20 percent of the total population and one-fourth of the adult
population, have hypertension, defined as a systolic blood pressure of 140 mmHg or greater, a
diastolic blood pressure of 90 mmHg or greater, or normal blood pressure levels maintained by
use of antihypertensive medication.1,2 Thirty-two percent of persons with heart disease and 36
percent of those with stroke are limited in their usual activity by the condition.6 Heart disease and
hypertension, respectively, are the third and fourth most common chronic conditions causing
limitation of activity.1 Almost 60 percent of those with hypertension are under 65 years of age,
and about 50 percent of persons with heart disease are under that age.5 The prevalence and
mortality from the cardiovascular diseases increase with decreasing levels of family income and
education.5,7 Between 1990 and 1992 in the United States, heart disease and hypertension
accounted for an estimated 542 million days of restricted activity and 206 million bed days.6 In
1997, there were an estimated 33 million days in short-stay hospitals, 60 million visits to
physicians' offices, 5 million outpatient visits, and 616,000 patients receiving home health care (in
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1996) for the cardiovascular diseases.8-11
Figure 1-2: Age-adjusted death rates for selected causes of death; United States,1950-1997
(adjusted to U.S. population 2000) CVD, cardiovascular disease; CHD, coronary heart disease.
(From Vital Statistics of the United States, National Center for Health Statistics.)
In 1997, cardiovascular diseases accounted for 41 percent of all deaths in the United States, a total
of 952,000.1 Largely because there are many more older women than older men in the U.S.
population, the analogous percentage is higher in women (42 percent) than in men (39 percent),
and the number of deaths from cardiovascular diseases is greater in women than in men.4 Of all
cardiovascular disease deaths, 36 percent occurred "prematurely," i.e., before 75 years of age.
Atherosclerosis, when manifested as CHD, cerebrovascular disease, or peripheral arterial disease,
accounted for 71 percent of all deaths from the cardiovascular diseases in 1997.1 Heart disease is
the leading cause of death in all racial groups.4 Stroke ranks third highest in whites, blacks, and
Asians in the U.S. population; fourth in Hispanics; and fifth in Native Americans.12 Age-adjusted
death rates for cardiovascular disease in 1997 were highest in black males, next highest in white
males, and then followed by black females and white females.2 Rates are not quite as high in
Native Americans, Asian Americans, and Hispanic Americans.
Unfortunately, national incidence and case fatality data for the cardiovascular diseases do not
exist. Data from the Framingham (Massachusetts) Heart Study, which began in 1948, and the
Framingham Offspring Study provide reliable estimates for 44 years of follow-up of a defined
population sample of men and women aged 35 to 94, the original cohort, and for 20 years of
follow-up of their offspring. The average annual rates of first major cardiovascular events rose
from 7 per 1000 men at ages 35 to 44 years to 68 per 1000 at ages 85 to 94 ( Table 1-1). For
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women, comparable rates are achieved 10 years later in life, with the gap narrowing with
advancing age. CHD is the predominant cardiovascular event, comprising more than one-half of
all such events in men and in women under age 75 ( Table 1-2). The proportions of
cardiovascular events due to CHD decline with age, as the proportions due to stroke and
congestive heart failure (CHF) increase with age. Under age 75, there is a higher proportion of
cardiovascular events due to CHD in men than in women and a higher proportion due to CHF in
women than in men (see Tables 1-1 and 1-2).
Secular Trends
The trend in mortality from total cardiovascular disease has been downward since about 1940,
with long-term declines for the three subgroups-rheumatic, cerebrovascular, and hypertensive
diseases-and a decline for CHD since the mid-1960s.1 The coronary decline antedates effective
antithrombolytic and antihypertensive treatment. Prior to 1940, cardiovascular mortality increased
and became the predominant cause of death because of control of infectious and parasitic diseases
and an epidemic increase in fatal coronary attacks. Cardiovascular mortality declined just less than
1 percent per year in the 1950s and 1960s. The decline became more precipitous in the 1970s,
with the rate falling 3 percent per year since then. For CHD, there has been more than a 58 percent
decline in the age-adjusted death rate between the peak of mortality in 1963 and 1997; the current
decline is 2 to 3 percent per year. For stroke, the rate of decline was 4 to 6 percent per year in the
1970s and early 1980s, but the decline slowed and has been less than 1 percent per year between
1990 and 1996.
The decline in cardiovascular mortality, including the steep rise and fall in CHD mortality,
indicates that the major cause of mortality is controllable. Whether attributable more to beneficial
changes in disease-promoting lifestyle or to better medical care of those already afflicted, it is
clear that cardiovascular disease in most patients is not an inevitable burden of aging or genetic
makeup. Although the causes of the decline in cardiovascular mortality are uncertain, the decline
has been substantial, sustained, and real. The decline has coincided with increased efforts to
achieve healthier living habits and with improvements in the ambient burden of cardiovascular
risk factors.
Unfortunately, there are very few statistics on trends in morbidity, particularly incidence. Some,
but not all, studies suggest that there have been declines in incidence and case fatality of CHD and
stroke.13,14 For myocardial infarction (MI), de- clines have been reported from most international
sites in the MONICA (Monitoring Trends in Cardiovascular Diseases) studies.15 This is important
because reduction in mortality without a decline in the incidence rate would indicate that better
medical care were responsible, whereas a reduction in both incidence and mortality would suggest
that environmental influences and/or preventive measures have improved. If reduction in mortality
continues, the size of the elderly population will continue to increase over and above increases due
to demographic effects.
Risk Factors and Subclinical Disease
Observational studies in populations such as the Framingham Study have documented factors that
increase the risk of cardiovascular diseases.16,17 These include atherogenic attributes such as
dyslipidemia, hypertension, glucose intolerance, and elevated fibrinogen; living habits that
promote them; indicators of unstable lesions; and signs of compromised circulation, e.g., measures
of subclinical arterial disease. Risk factors can be classified into the lipids, metabolic factors,
hemostatic factors, blood pressure, and lifestyle factors. Some are modifiable. They promote
cardiovascular disease in both sexes at all ages but with different strengths. Diabetes and high-
density lipoprotein (HDL) cholesterol operate with greater power in women. Cigarette smoking is
particularly influential in men, is noncumulative, and loses some of its adverse impact shortly
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after quitting. Some risk factors, such as blood lipids, impaired glucose tolerance, uric acid, and
fibrinogen, have smaller risk ratios in advanced age, but this lower relative risk is offset by a high
absolute risk. In fact, most of the major risk factors remain relevant in the elderly. Obesity or
weight gain promotes or aggravates all the atherogenic risk factors, and physical indolence
worsens some of them and predisposes to cardiovascular events at all ages. Systolic blood
pressure and isolated systolic hypertension are major risk factors at all ages in both sexes. The
ratio of total to HDL cholesterol is used by many as a convenient lipid risk factor profile (see also
Chap. 53).
Beyond age 65, women become nearly as vulnerable to cardiovascular mortality as men.4 The
predisposing modifiable risk factors for CHD, stroke, peripheral arterial disease, and cardiac
failure are similar in the young and old in men and women.16 An attenuated risk ratio for some
risk factors at advanced age is offset by a greater incidence of cardiovascular disease.
Consequently, the attributable risk and the potential benefit of treatment rise with age. In old age,
average atherogenic total and low-density lipoprotein (LDL) cholesterol levels are considerably
higher in women than in men. Cardiovascular risk profiles comprising the major risk factors
predict CHD as efficiently in the elderly as in the young. This, and the fact that the decline in
cardiovascular mortality has included the elderly, suggests the potential for intervention.
Evidence from the Framingham Study suggests that the presence of certain risk factors in women
can attenuate their advantage in cardiovascular risk over that in men. The male-female gap in
incidence closes with advancing age. After menopause, risk escalates two- to threefold, with more
infarction and sudden death. A high total to HDL cholesterol ratio of 7.5 or greater virtually
eliminates the female advantage. Diabetes has twice the relative impact on risk in women, almost
canceling the female advantage. Electrocardiographic evidence of left ventricular hypertrophy has
a greater relative impact on risk in women. The residual effect of triglycerides after consideration
of HDL cholesterol appears to be greater in women than in men.
The major modifiable risk factors that contribute powerfully to cardiovascular disease are highly
prevalent in the population. Trends in their prevalence and differences in their impact on the
various atherosclerotic sequelae are noteworthy. Despite 30 years of appreciable decline in the
percentage of persons who smoke cigarettes, one-fourth of adults, 49 million, still smoke.2
Despite declining trends in mean total serum cholesterol level, more than 50 percent of American
adults, 98 million, have blood cholesterol levels of 200 mg/dL or greater, and of these, 39 million
have levels of 240 mg/dL or greater. Fifty million have hypertension, but fortunately, treatment
and control of this condition improved considerably since the early 1970s.1,2 Not improving is
obesity. One-third of adults, 106 million, are overweight, defined as a body mass index greater
than 25 kg/m2. An estimated 10 million persons are at increased risk of cardiovascular disease
because they have diabetes.2 Another highly prevalent risk factor is sedentary lifestyle. It plays a
role in the prevalence of overweight, dyslipidemia, and hypertension and, thus, cardiovascular
disease. There also are persons under 18 years of age who have one or more modifiable risk
factors.1,12
More recent additions to the list of risk factors include homocystinemia. In the general population,
29 percent have deficient enough vitamin B intake to elevate homocystine to more than 14
mol/L.18 Inadequate intake of vitamins B and B and folate account for 67 percent of the
12 6
elevated homocystine encountered in the general population. An estimated 25 percent of the
population have Lp(a) lipoprotein cholesterol values greater than 20 mg/dL.19 Small, dense LDL
(pattern B) occurs in 11.1 percent of the population and in 50 percent of patients with CHD.20
Fibrinogen greater than 300 mg/dL occurs in 30 percent of the population. Other novel risk factors
are leukocyte count, estrogen deficiency, factor VII, endogenous tissue plasminogen activator,
plasminogen activator inhibitor type 1, D-dimer, C-reactive protein, and possibly Chlamydia
pneumoniae.16,17
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Very early asymptomatic cardiovascular disease can be diagnosed by noninvasive testing, such as
magnetic resonance imaging (MRI) and computed tomographic (CT) scanning. Well-established
clinical indicators include left ventricular hypertrophy, audible vascular bruits, a positive exercise
electrocardiogram (ECG), absent arterial pulses in the limbs and neck, regional wall motion
abnormality on the echocardiogram, reduced ankle-arm blood pressure ratio, sonographic
evidence of carotid wall thickness, reduced left ventricular ejection fraction, and presence of
coronary calcium.
No individual risk factor is essential or sufficient in the causation of cardiovascular disease;
causation is multifactorial. Indeed, the risk posed by one factor is generally enhanced in the
presence of another. Thus multivariate risk factor assessment gives the most useful measure of the
joint effect of the risk factors.16 Multivariate analyses help provide a better understanding of the
pathogenesis of the disease and guidelines for prevention. Based on the absolute, relative, and
attributable risks imposed by the various risk factors, the older concepts of normal have evolved
to optimal values associated with long-term freedom from disease. As a consequence, acceptable
blood pressures, blood glucose levels, and lipid values have been revised downward.16
Multifactorial risk functions based on the Framingham Study data, composed of the major
identified risk factors, have been shown to predict the rate of occurrence of coronary disease in a
variety of U.S. population samples, suggesting that much of the cardiovascular disease in the
population is attributable to these factors21 (see also Chap. 41).
Department of Preventive Medicine and Epidemiology, Evans Department of Clinical Research,
Boston University School of Medicine, Boston, Massachusetts, and the Framingham Heart Study.
Framingham Study research is supported by NIH/NHLBI Contract N01-HC-38038 and the
Visiting Scientist Program that is supported by Servier Amerique.
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Chapter 1: CARDIOVASCULAR DISEASES IN THE UNITED STATES AND PREVENTION
APPROACHES
CORONARY HEART DISEASE
CHD kills and disables people in their most productive years and in 1999 was estimated to account for $53
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billion in medical care costs and $47 billion in indirect economic costs.2 Each year there are more
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hospitalizations for CHD than for any broad diagnostic group, with the exceptions of births, all respiratory
diseases, all digestive diseases, and all injuries.8
Prevalence
Search Hurst's
Search Drug List In the United States, an estimated 12 million people have CHD, about one-half of whom have acute MI and
half have angina pectoris.2 For men, prevalence of MI is 1 percent at ages 35 to 44 years and 16 percent at
age 75 and over (Fig. 1-3). In women, the prevalence is less than 1 percent at ages 35 to 44 years and 13
percent at age 75 and over.
Figure 1-3: Prevalence of MI and angina pectoris by age and sex, United States, 1988-1994 (self-reported
myocardial infarction and Rose angina from health interviews). MI, myocardial infarction. (From the
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National Health and Nutrition Examination Survey, 1988-1994, National Center for Health Statistics.)
Incidence
In the United States, CHD causes about 650,000 new heart attacks each year and 450,000 recurrent
attacks.2 The incidence in women lags behind that in men by 10 years for total CHD and by 20 years for
more serious clinical manifestations such as MI and sudden death ( Tables 1-1 and 1-3). Male
predominance is least striking for uncomplicated angina pectoris. The first coronary presentation for
women is more likely to be angina, whereas in men it is more likely to be MI ( Table 1-4). In men,
more angina occurs after MI than before. Only 20 percent of coronary attacks are preceded by long-
standing angina; the percentage is lower if the infarction is silent or unrecognized. In premenopausal
women, serious manifestations of CHD such as infarction or sudden death are relatively rare. The incidence
and severity of CHD increase with age in both sexes (see Table 1-3 and Table 1-4). There
seems to be a more precipitous increase for women after menopause, with CHD rates in postmenopausal
women two to three times those of women the same age who remain premenopausal.21 This applies
whether the menopause is natural or surgical and, in the latter case, whether or not the ovaries are removed.
The sex ratio in incidence narrows progressively with advancing age.
Unrecognized MIs are common in the Framingham Study, numbering at least one in three infarctions
( Fig. 1-4). Half the unrecognized infarctions are silent, and the rest are atypical so that neither the
patient nor the physician entertains the possibility.22 More than half these persons eventually develop some
overt clinical manifestations of CHD and hence come under medical care. Angina is less frequent in
individuals with unrecognized MI than in those with recognized symptomatic MI, either before or after the
infarction occurs. Despite the apparent mild nature of unrecognized MI, t risk of subsequent mortality is
nearly the same as in patients with recognized infarction. Diabetic men and hypertensive persons of both
sexes are particularly susceptible to silent or unrecognized MIs.
Prognosis
In patients who survive the acute stage of an MI, the morbidity and mortality range from 1.5 to 15 times
that of the general population, depending on the person's sex and clinical outcome (Table 1-5). The rates of
occurrence of reinfarction, sudden death, angina pectoris, cardiac failure, and stroke are all substantial. The
relative and absolute risks of these events are as great in women as in men after MI. Within 6 years
following a recognized MI, 18 percent of men and 35 percent of women have a recurrent infarction, and 27
percent of men and 14 percent of women develop angina. About 22 percent of men and 46 percent of
women are disabled with cardiac failure; 8 percent of men and 11 percent of women will have a stroke.
Sudden death will be experienced by 7 percent of men and 6 percent of women. The prognosis is nearly as
bad, sometimes worse, following an unrecognized MI (see Table 1-5).
Table 1-5: Six-Year Prognosis Following Myocardial Infarction: Framingham Study, 44-Year Follow-
Up of Cohort and 20-Year Follow-Up of Offspringa
MEN WOMEN
Percent Risk Ratiob Percent Risk Ratiob
Recognized
Death 37 2.5 60 5.1
Sudden death 7 2.2 6 4.4
Myocardial infarction 18 2.2 35 9.6
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Angina pectoris 27 4.1 14 2.3
Cardiac failure 22 5.4 46 15.4
Stroke/TIA 8 2.4 11 3.1
Unrecognized
Death 46 2.5 34 2.4
Sudden death 5 1.7 2 2.1
Myocardial infarction 19 2.0 18 3.6
Angina pectoris 11 1.6 17 3.2
Cardiac failure 27 5.8 21 6.2
Stroke/TIA 13 3.5 7 1.5
aSurviving 30 days.bStandardized morbidity and mortality ratios (times 0.01).
SOURCE: The Framingham Study.
Mortality
CHD is the leading single cause of death in adults in the United States, accounting for 1 in 5 deaths.4 In
1997, there were 466,000 coronary deaths. Mortality from this disease increases with age, but CHD is also
a prominent cause of death in adults at the peak of their productive lives. Heart disease is the leading cause
of death in men and women in every racial or ethnic group except Asian-American females.2 The CHD
death rate is almost three times higher in men than in women at ages 25 to 34, but this ratio declines to 1.6
by ages 75 to 84. The coronary death rate is more than 50 percent higher in blacks than in whites at ages 25
to 34, and this difference disappears by age 75. CHD mortality is not as high among the Hispanic
population as it is among blacks and whites.
In a substantial number of CHD deaths, the progression from inapparent clinical disease to death is swift.
Much of the premature mortality from CHD comes with little warning in a population prone to this disease.
Sudden, unexpected, out-of-hospital coronary deaths that occur too rapidly to allow arrival alive at the
hospital account for one-half of all coronary fatali- ties. The proportion of coronary deaths that are sudden
deaths is lower in women than in men and lower in elderly men than in the young ( Fig. 1-5). The
percentage of sudden coronary deaths that occur without prior CHD, however, is much greater in women
than in men ( Fig. 1-6). In 50 percent of men and 63 percent of women who died suddenly, there was
no prior overt evidence of coronary disease (see also Chap. 36).
There is a higher risk of death in patients with a prior coronary attack, yet most CHD deaths arise from the
population who are still free of symptomatic CHD.23 Hence primary prevention ultimately appears to offer
more to society than secondary prevention. After MI, sudden death occurs at four to six times the rate in the
general population. The first year following a recognized MI is especially dangerous, with 25 percent of
men and 38 percent of women succumbing ( Fig. 1-7). Long-term survival following unrecognized
MI is only slightly better than for recognized MIs, and survival is better for women than for men (
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Table 1-6). In men under age 65 with uncomplicated angina pectoris, the survival picture is nearly the same
as it is for recognized MI and is much worse than the survival in women (see also Chap. 38).
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