DISEASES, CHRONIC AND DEGENERATIVE

Chronic and degenerative diseases (CDDs) are morbid pathological processes characterized by slow development, long duration, and gradual deterioration in the functioning of the affected tissue, organ, or

TABLE 1

organ system. These diseases generally involve asymptomatic preclinical stages, gradual progression to manifest symptoms, and terminal stages ranging from mild discomfort to lethality. Their incidence is correlated with age and in many cases is approximately proportional to the fifth, sixth, or seventh power of age. Their durations typically extend from the time of the initial symptoms to the time of death. Their prevalence reflects the cumulative effects of incidence and duration. They can kill afflicted individuals in a variety of ways. For example, persistent high blood pressure (hypertension, a chronic condition) is a risk factor for stroke (an acute manifestation of cerebrovascular disease), which may be lethal if it is not treated immediately.

CDDs are generally noncommunicable (noninfectious). There are numerous exceptions, however, including AIDS, which is caused by human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2); stomach ulcers/cancers caused by the bacterium Helicobacter pylori; liver cancers caused by hepatitis B virus; and cervical cancers caused by human papillomaviruses. Other significant pathogens include herpes simplex virus types 1 and 2 (possibly linked to Alzheimer's disease and schizophrenia), human herpes virus 6 (possibly linked to multiple sclerosis), and Chlamydia pneumoniae (possibly linked to Alzheimer's disease and heart disease).

Classification of Diseases

The International Classification of Diseases (ICD) is a statistical classification system for mortality and morbidity that is maintained and updated every one or two decades by the World Health Organization (WHO). The periods covered by the last five revisions and their adaptations for use in the United States are listed in Table 1.

The ICD-9-CM (clinical modification) adapts the ICD for hospital indexing and other clinical uses, adding codes for factors that influence health status and contact with health services. The alphabetical indexes of the ICD-9 and ICD-9-CM contain approximately 60,000 and 75,000 distinct diagnostic entries, respectively. In practice, however, 1998 U.S mortality files indicate that the ICD-9 describes approximately 5,600 causes of death.

Causes of Death

Estimates of the incidence and prevalence of major CDDs are limited by the progressive nature of those diseases and the lack of disease registries covering the population. Consequently, substantial use is made of cause of death data from national vital statistics files. These data are coded according to WHO protocols embodied in the ICD's underlying cause selection rules, where the underlying cause of death is defined as "(a) The disease or injury which initiated the train of events leading directly to death, or (b) the circumstances of the accident or violence which produced the fatal injury" (WHO 1975).

An important limitation is that each tabulated underlying cause of death is an aggregation of etiologically distinct diseases. For example, the top 15 underlying causes of death at age 65 and older in the United States in 1998, with the range of ICD-9 codes indicated in parentheses, were:

1. Heart diseases (390–398, 402, 404–429)
2. Malignant neoplasms (140–208)
3. Cerebrovascular diseases (430–438)
4. Chronic obstructive pulmonary diseases (490–496)
5. Pneumonia and influenza (480–487)
6. Diabetes mellitus (250)
7. Accidents and adverse effects (E800–E949)
8. Nephritis, nephrotic syndrome, and nephrosis (580–589)
9. Alzheimer's disease (331.0)
10. Septicemia (038)
11. Aortic aneurysm (441)
12. Atherosclerosis (440)
13. Hypertension (with or without renal disease) (401 and 403)
14. Chronic liver disease and cirrhosis (571)
15. Suicide (E950–E959)

These 15 causes accounted for 87 percent of deaths among the elderly in 1998. Only pneumonia/influenza and septicemia (numbers 5 and 10) are clearly infectious in nature, accidents and adverse effects (number 7) may involve chronic debilitation and treatment (e.g., hip fracture), and suicide (number 15) is associated with depression and chronic mental illness. The remaining 11 causes represent predominantly noninfectious CDDs, accounting for 79 percent of deaths. All 15 "causes" are aggregations of distinct elementary disease/injury components.

Another limitation is that each death can have only one tabulated underlying cause–the one cause that supposedly initiated the train of events leading directly to death. To the extent that there are other, nonunderlying ("contributory") causes indicated on the medical condition field of the death certificate, there is additional information on the impact of CDDs over time and across populations. For example, the top five nonunderlying causes of death at age 65 and older in the United States in 1998 were heart diseases (number 1 above), hypertension (number 13), chronic obstructive pulmonary diseases (number 4), diabetes mellitus (number 5), and cerebrovascular diseases (number 3). Malignant neoplasms (number 2) were ranked ninth. Furthermore, the joint three-way occurrence of heart diseases, hypertension, and diabetes mellitus on the death certificates was 3.3 times higher than expected, assuming independent causes. Combined with cerebrovascular diseases, the joint four-way occurrence was 11.8 times higher than expected under conditions of independence. Similar results for other cause combinations demonstrate that nonunderlying causes reflect complex processes and distinctive patterns of joint dependence. Conversely, these results indicate that analytic models based on independent causes (e.g., multiple decrement life tables) may be substantially biased.

A third limitation relates to the accuracy of reported causes of death. Autopsy and medical record studies show that accuracy decreases across the categories of malignant neoplasms, heart diseases, and cerebrovascular diseases, with substantial variation within each category. Most errors are due to incorrect diagnoses and incorrect sequencing of the underlying cause when multiple and possibly interacting diseases are operating at the time of death.

TABLE 2

Mortality Statistics

Seventy-five percent of deaths in the United States in 1998 occurred at age 65 and older, and this rate is gradually increasing. Most deaths involved CDDs as underlying or contributory causes. The average reported number of causes was 2.0 per 1998 U.S. death at ages 65 to 94, 1.9 at ages 95 to 99, and 1.8 at ages 100 and older. When stratified by underlying cause, the averages ranged from 1.8 for malignant neoplasms to 2.9 for diabetes mellitus. Different causes exhibited different patterns of change over age and time and unique multiway associations consistent with their nature as distinct, related physiological processes.

Quantification of temporal changes in CDDs presents major challenges because of the lack of comprehensive models. Summary measures based on total and cause-specific life tables generally are used for public policy planning. For example, recorded life expectancies at age 65 in the United States and in Japan since the middle of the twentieth century for selected years are shown in Table 2.

Life expectancy at age 65 increased significantly after 1950 in both countries, but the relative increases in Japan were more than double those in the United States, with the largest differences being for females in the period 1980–1998. Comparisons of age and cause patterns of mortality in the United States, Japan, and Sweden have shown that the U.S. cause, but not age, pattern was similar to Sweden's. In a 1988 study Machiko Yanagishita and Jack Guralnik identified declines in cerebrovascular and heart diseases as the primary reasons for Japan's surpassing Sweden in the mid-1970s as the top-ranked country in life expectancy. The top three causes of death in Japan during 1965–1980 were cerebrovascular diseases, malignant neoplasms, and

TABLE 3

heart diseases. Japanese statistics through 1999 show that malignant neoplasms have replaced cerebrovascular diseases as the top-ranked cause of death and that heart diseases have replaced cerebrovascular diseases in the second-place ranking.

Comparisons of mortality patterns within and between countries must consider changes in incidence, prevalence, duration, severity, and treatment of the various CDDs. Each one exhibits unique patterns consistent with the complex and heterogeneous nature of the underlying disease processes. For example, the temporal changes in agestandardized underlying cause death rates (per 100,000 population) for the top four causes identified above for the U.S. are shown in Table 3.

The table clearly shows that the patterns of change differ significantly by cause, with large relative declines for cerebrovascular and heart diseases, a trend reversal for malignant neoplasms, and large relative increases for chronic obstructive pulmonary diseases.

Morbidity Measures

Recognition of the complex nature of CDDs has led to the development of procedures for summarizing the population health impact of these diseases in ways that do not require full specification of the relevant physiological processes. These procedures generally employ age-specific prevalence estimates from national health surveys and epidemiological studies that are combined with life-table statistics, using the method developed by Daniel Sullivan in 1971. For example, Diane Wagener and her colleagues used this method in a 2001 study to estimate that 17 percent of male life expectancy and 19 percent of female life expectancy at birth in the United States in 1995 was lived with some degree of activity limitation as a result of chronic health conditions.

In a 1996 study Christopher Murray and Alan Lopez presented comprehensive analyses of the morbidity and mortality burden of lethal and nonlethal diseases for developed and developing countries worldwide. Those authors extended Sullivan's method to measure disease burden two ways: (1) using disability-adjusted life expectancy (DALE), which is the expected number of years of life lived in full health, and (2) using disability-adjusted life years (DALYs), which are additive, time-weighted measures of the severities of specific diseases, including years of life lost to premature deaths from lethal diseases.

Murray and Lopez reported that 86 percent of deaths in developed countries in 1990 were due to noncommunicable diseases (i.e., noninfectious CDDs), with 22 to 25 percent of remaining life expectancy at age 60 spent disabled. Corresponding results for developing countries indicated that 47 percent of deaths were due to noncommunicable diseases, with 31 to 48 percent of remaining life expectancy at age 60 spent disabled. Murray and Lopez projected that the global fraction of deaths from noncommunicable diseases would rise from 55 percent in 1990 to 73 percent in 2020 (from 86 percent to 89 percent in developed and from 47 percent to 70 percent in developing countries). They provided quantitative estimates of the impact on DALYs of a range of disease risk factors, including alcohol, tobacco, illicit drugs, air pollution, inadequate sanitation, physical inactivity, and malnutrition.

In a 2000 study Colin Mathers and his colleagues estimated DALEs for 191 countries: Japanese females and males were both top ranked within the respective sex, followed by French females and Swedish males, respectively.

Morbidity/Mortality Pathways

Studies of monozygotic and dizygotic twins indicate that 25 to 30 percent of variability in the length of life is heritable. Heritable single-gene defects produce 1,500 distinct, rare diseases, 98 percent of which emerge by age 50. Natural selection accounts for their rarity; existing equilibriums may be altered by effective medical treatments.

Factors contributing to the nonheritable 70 to 75 percent of length of life variability include environmental, nutritional, behavioral, and lifestyle influences beginning with fetal, postnatal, and childhood development; socioeconomic and demographic factors such as race/ethnicity, gender, education, income, occupation, stress, social support, and other social conditions; and epidemiologic risk factors such as diet, exercise, weight, tobacco, alcohol, cholesterol, and blood pressure.

Continued progress against major CDDs can be expected to result from improved understanding of the pathways through which CDDs develop, innovative forms of primary prevention, and medical diagnostic and pharmaceutical treatment protocols that permit disease detection and treatment at successively earlier stages in the morbid process.

See also: Cancer; Cardiovascular Disease; Disease, Burden of; Epidemiological Transition; Mortality Decline.

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Eric Stallard