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.

United Hearts Homecare
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.!,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.! 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

1996) for the cardiovascular diseases.8-!!

Coronary Artery Disease Statistics
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 (&H0; Table 1-1). For 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 0-H0; Tables 1-1 and Q-hB; 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.! 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.!3!4 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.1617 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 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.!6 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.142

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 I bol/L.l8 Inadequate intake of vitamins B12 and B6 and folate account for 67 percent of the 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

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.!6 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.!6 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 factors^! (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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