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High and Rising Mortality Rates Among Working-Age Adults (2021)

Chapter: 4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults

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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Page 104
Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Page 108
Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Page 109
Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Suggested Citation:"4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults." National Academies of Sciences, Engineering, and Medicine. 2021. High and Rising Mortality Rates Among Working-Age Adults. Washington, DC: The National Academies Press. doi: 10.17226/25976.
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Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

4 U.S. Trends in Cause-Specific Mortality among Working-Age Adults The previous chapter establishes that among most working-age adults (aged 25–64), the recent increase in all-cause mortality rates in the United States was due less to a break from earlier trends than to the accumulation and acceleration of long-term slowdowns and reversals of progress in mortality. These all-cause mortality trends demonstrate that there were important differences in where and among whom mortality rates increased between 1990 and 2017; however, they cannot establish which factors contributed to these mortality trends over time. In this chapter, the committee begins to examine how these trends were produced by presenting them by cause of death (cause-specific mortality) to determine which causes contributed most to the overall trends reviewed in Chapter 3. The comparison of working-age mortality rates in the United States and 16 peer countries presented in Chapter 2 indicates that the U.S. rates exceeded those of the peer countries across a wide range of causes of death. However, the United States also performed better than its peers on some causes of death, such as lung cancer and HIV/AIDS. International disparities in cause- specific mortality are the result of complex systemic interactions among historical economic, demographic, and policy contexts that differ across countries. Although they may point to areas in which policy changes could lead to improvements within the United States, long-standing differences across countries in mortality from some causes of death may not explain recent within-country mortality trends. Knowing whether recent rises in U.S. working-age mortality were due to increases in a small number of specific causes of death or a broad range of causes can provide insight into the underlying explanations for the recent troubling trends and may help inform policy strategies for combating and reversing these trends. This chapter presents U.S. cause-specific mortality trends in five sections. The first reviews the leading causes of death in the United States in the first and last periods of the time span addressed by this study (1990–1993 and 2015–2017) and the changes in cause-specific mortality rates over this period. This review identifies which causes contributed most to the changes in all-cause mortality over time. The second section examines the findings from previous research on disparities in cause-specific mortality by socioeconomic status to highlight what is known about the causes of death that have contributed most to the growing socioeconomic disparities in mortality. The third section explores how the changes in each cause of death contributed to changes in all-cause mortality by metropolitan status. The fourth section decomposes the overall changes that occurred between 1990 and 2017 into three time periods (roughly representing decades) to show whether the causes of death that drove overall increases or decreases in mortality during this period represent long-term trends or are a more recent phenomenon. The final section of the chapter summarizes these findings, identifying the specific causes of death that have been the most important drivers of the changes in mortality in the United States since 1990. 4-1 Prepublication copy, uncorrected proofs

An overview of the data and analytical methods used in these analyses is presented in Chapter 5. Causes of death are based on the underlying causes of death identified on death certificates. The underlying causes of death were classified into one of 20 nonoverlapping categories, which are exhaustive of all possible causes. Causes of death were coded according to the International Classification of Diseases, 9th Revision (ICD-9) for 1990–1998 and 10th Revision (ICD-10) for 1999–2017. More information regarding the specific ICD codes included in each of the 20 cause-of-death categories, as well as the process for coding underlying cause of death, is provided in Chapter 5. Two of these categories, noted in the tables that follow, could not be made comparable over the 1990–2017 period because of a change in ICD coding. Mortality rates are presented separately by sex and age group for non-Hispanic (NH) White (White), NH Black (Black), and Hispanic adults. Although concerns about the quality of race reports on death certificates for the American Indian and Alaska Native and Asian and Pacific Islander populations prevented the presentation of similar comparisons for these groups, results are included for these groups where possible. When available, this information also was drawn from published research using alternative data sources, and therefore may not be directly comparable to the findings presented for the White, Black, and Hispanic populations. As was done for Chapter 3, deaths were pooled across 3-year periods (1990–1993, 2000–2002, 2009– 2011, and 2015–2017), with the exception that the first period (1990–1993) includes 4 years. The findings presented in this chapter demonstrate that the recent trends in all-cause mortality among working-age adults were the result of the confluence of two important trends: (1) rising mortality from drug poisoning and other causes of death, such as nervous system diseases; hypertensive heart disease; endocrine, nutritional, and metabolic (ENM) diseases; and, among Whites, alcohol use and suicide; and (2) slower progress in lowering mortality from heart diseases and other leading causes of death that drove improvements in all-cause mortality rates before 2010. Mortality due to drug poisoning increased throughout the 1990–2017 period among working-age White, Black, and Hispanic adults of both sexes, with the largest increases occurring among younger (aged 25–44) White adults and older (aged 55–64) Black adults, and was the largest contributor to increases in mortality among all but older Hispanics. Despite their early onset and alarming magnitude, the large increases in mortality from drug poisoning did not lead to corresponding increases in all-cause mortality until the 2010s among most working-age adults because prior to this period, working-age adults experienced large reductions in mortality from ischemic heart disease and other circulatory diseases and most cancers. The dramatic decreases in mortality from these causes of death more than offset the large increases in mortality from drug poisoning and smaller increases in other causes of death during the 1990s and 2000s. The largest reductions occurred among working-age Blacks, leading to dramatic declines in Black–White mortality disparities during this period. In the 2010s, mortality from ischemic heart disease and other circulatory diseases continued to decrease among working-age Blacks, though at a slower pace, but stalled among Whites and Hispanics. TRENDS IN U.S. WORKING-AGE MORTALITY BY CAUSE OF DEATH To identify the key underlying causes of death responsible for the changes in all-cause mortality over the 1990–2017 period, this section presents mortality rates (in deaths per 100,000 population) at the beginning (1990–1993) and end (2015–2017) of the period and the changes in cause-specific mortality rates over the period for working-age White, Black, and Hispanic adults in three age groups—24–44, 45–54, and 55–64. The changes over time are presented in terms of 4-2 Prepublication copy, uncorrected proofs

both absolute change in mortality rates (in deaths per 100,000 population) and the percentage contribution of each cause-specific change in mortality to the total increase or decrease in all- cause mortality. The latter percentages were calculated by dividing the increase (or decrease) in the cause-specific mortality rate by the total increase (or decrease) across all causes of death that increased (or decreased) between 1990–1993 and 2015–2017. The results presented in this section reveal dramatic reductions in mortality from the most common (leading) causes of death in 1990–1993, including ischemic heart disease and other circulatory diseases,1 cancers (excluding liver cancer), and HIV/AIDS. These improvements occurred among both sexes and each of the three racial/ethnic groups the committee examined. However, mortality also increased across a wide range of causes of death, offsetting some, and in some cases all, of these gains. Although there were racial/ethnic differences in which causes of death increased over the period, mortality due to drug poisoning and diseases of the nervous system2 increased across all working-age adults, regardless of sex, age group, or race/ethnicity. Although working-age Black adults maintained the highest mortality throughout the period, they also experienced the largest decreases in mortality across the widest range of causes of death, narrowing the racial gap in mortality between the 1990–1993 and 2009–2011 periods. Working-age Hispanic adults also experienced (comparatively) large reductions in mortality across many causes of death. In contrast, working-age White adults experienced increases in mortality across the widest range of causes of death, and for this reason had higher mortality than working-age Hispanic adults at the end of the period. Although similarly detailed cause-specific trends in mortality for Asians and Pacific Islanders and American Indians and Alaska Natives could not be included here because of concerns about the quality of racial data on death certificates, Boxes 4-1 (Asians and Pacific Islanders) and 4-2 (American Indians and Alaska Natives) briefly review cause-specific mortality for these populations. BOX 4-1 Trends in Cause-Specific Mortality among Asians and Pacific Islanders (APIs) As noted in Chapter 3 and discussed in greater detail in Chapter 5, the development of valid estimates of age-specific mortality rates has been challenging for the API population because of misclassification of race on some death certificates. As a result, the committee’s detailed original analyses of cause-specific mortality trends for APIs are not presented in this report. Instead, the trends we observed for this group are briefly summarized here.                                                         1 “Other diseases of the circulatory system” include all circulatory diseases besides ischemic heart disease and hypertensive heart disease. Major contributors to working-age deaths in this category include stroke, cardiomyopathy, congestive heart failure, intracerebral hemorrhage, cardiac arrest, and pulmonary embolism. Each of these causes contributed to at least 5 percent of working-age deaths in this category, 1999–2017. 2 Diseases of the nervous system include, but are not limited to, meningitis and other inflammatory diseases, encephalitis, myelitis, and encephalomyelitis, Huntington’s disease, spinal muscular atrophy and related syndromes, Parkinson’s disease, movement disorders, Alzheimer’s disease and other degenerative diseases of the nervous system, multiple sclerosis and other demyelinating diseases of the central nervous system, epilepsy and other episodic and paroxysmal disorders, sleep disorders, cerebral palsy and other paralytic syndromes, and other disorders of the brain. In 2017, the most common causes of death within the working-age population were anoxic brain damage, not elsewhere classified; motor neuron disease; multiple sclerosis; infantile cerebral palsy; and Alzheimer’s disease (CDC WONDER, 2020). 4-3 Prepublication copy, uncorrected proofs

As was the case with Whites, Blacks, and Hispanics, drug poisoning was the largest contributor to increases in all-cause mortality among APIs during 1990–2017 for males and females in all age groups except males aged 55–64, for whom increased mortality from endocrine and metabolic diseases surpassed the increase in deaths from drug poisoning. These increases were small, however, particularly when compared with those experienced by Whites. Besides drug poisoning, only a handful of other causes increased by more than 1 death per 100,000 between 1990 and 2017, and these increases were very small. Among males, they included endocrine, nutritional, and metabolic diseases; hypertensive heart disease; mental and behavioral disorders (only among those aged 45–64); diseases of the nervous system (only among those aged 45–64); diseases of the genitourinary system (only among those aged 45– 64); alcohol-induced causes (only among those aged 45–64); and suicide (only among those aged 24–54). Among females, the only cause of death besides drug poisoning to increase by more than 1 death per 100,000 over the period was diseases of the nervous system (only among those aged 45–64). At all ages, any increases observed over the study period were more than offset by mortality declines from other causes of death, yielding declines in all-cause mortality between 1990 and 2017 for both males and females in all age groups. For more detail on the challenges with mortality data for APIs and important considerations for readers in interpreting trends, see the annex to Chapter 3 and Chapter 5. BOX 4-2 Trends in Cause-Specific Mortality among American Indians and Alaskan Natives (AI/ANs) There are considerable data quality concerns related to calculating cause-specific mortality rates for AI/ANs because of errors in race reports on vital statistics records (see the annex to Chapter 3 and the discussion of the quality of death certificate data in Chapter 5 for more information). Given these data concerns, the committee’s original analyses on trends for this group are not presented in this report. The table below shows the 10 leading causes of death for the AI/AN population compared with Whites, Blacks, and Hispanics in 2017. Because these results are based on vital statistics reports that do not correct for errors in race reporting, these tables do not include the estimated mortality rates for these populations; however, other research has demonstrated that the AI/AN population has the highest mortality rates for more causes of death relative to any racial/ethnic group (Espey et al., 2014; Sancar, Abbasi, and Bucher, 2017). AI/AN individuals are more likely to die from diabetes, chronic liver disease, and suicide than are Whites, Blacks, and Hispanics. These cause-of-death rankings are very similar to those found in the 1999–2009 period for AI/AN populations living in 637 Contract Health Service Delivery Areas (CHSDAs) using data that were corrected for misclassification of AI/AN identity on death certificates (Annex Figure 4-1). Additional efforts are needed to better document the health and mortality of all AI/AN individuals and to address the pressing needs of this important population subgroup. 4-4 Prepublication copy, uncorrected proofs

10 Leading Causes of Death among the American Indian and Alaska Native (AI/AN) Population Compared with Whites, Blacks, and Hispanics, 2017 Cause of Death AI/AN White Black Hispanic Heart diseases 1 1 1 2 Malignant neoplasms 2 2 2 1 Accidents (unintentional injuries) 3 4 3 3 Diabetes mellitus 4 7 5 5 Chronic liver disease and 5 11 14 7 cirrhosis Chronic lower respiratory disease 6 3 6 8 Cerebrovascular diseases 7 5 4 4 Suicide 8 9 16 9 Influenza and pneumonia 9 8 12 11 Alzheimer disease 10 6 9 6 SOURCE: Heron, 2019. Non-Hispanic White Adults Among working-age White males and females (Table 4-1), an important takeaway is that mortality rates from several causes of death—including liver cancer; ENM diseases3; hypertensive heart disease; drug poisoning; alcohol-induced causes; suicide4; mental and behavioral disorders; diseases of the nervous system; and diseases of the genitourinary system— increased in all three age groups over the study period. Drug poisoning was responsible for the largest mortality increases by far, particularly among younger White adults (aged 25–44). Even so, the consistency of increases in mortality across such a wide range of causes of death that span multiple disease categories and body systems is cause for concern and suggests that recent increases in working-age mortality rates go beyond increases in drug poisoning. Among older working-age Whites (aged 45–64), these mortality increases were largely offset over the period by substantial decreases in the two leading causes of death in 1990–1993: ischemic heart disease and other circulatory diseases, and cancer. Because mortality from these two causes often results from long-term exposures and chronic disease, it plays a less prominent (though still important) role in mortality among many younger working-age adults (aged 25–44), who therefore experienced much smaller improvements in mortality from these causes over the period. In fact, among younger working-age White women, mortality due to ischemic heart                                                         3 ENM diseases include, but are not limited to, diabetes mellitus, disorders of the thyroid gland, hypoglycemia, disorders of other endocrine glands, malnutrition, obesity, disorders of lipoprotein metabolism and other lipidemias, cystic fibrosis, amyloidosis, and other metabolic disorders. In 2017, the most common cause of death within this category was diabetes mellitus, which was responsible for most of deaths in this category, followed by obesity and hyperlipidaemia (CDC Wonder, 2020). The committee initially examined trends in diabetes and obesity separately from those for other ENM diseases but decided that these trends did not differ substantively from those of the rest of the causes within this category. 4 In this analysis, the category of suicide excludes suicides due to drug poisoning, which are classified with other drug poisoning deaths. 4-5 Prepublication copy, uncorrected proofs

disease and other circulatory diseases actually increased slightly over the period,5 although their mortality from cancers other than liver cancer decreased. Moreover, while mortality from these causes declined between 1990–1993 and 2015–2017, their importance as two of the leading causes of death held over the period. In contrast, HIV/AIDS was the leading cause of death among working-age White men in 1990–1993, but by 2015–2017, mortality rates from this cause had declined by more than 95 percent so that it ranked 19th out of the 20 causes of death.                                                         5 Among younger working-age White females, mortality due to ischemic heart disease was very low and did not change over the period. This increase was driven by increasing mortality due to other circulatory diseases. 4-6 Prepublication copy, uncorrected proofs

TABLE 4-1 Cause-Specific Mortality (deaths per 100,000 population), 1990–1993 and 2015–2017: Non-Hispanic White Adults Aged 25–64 Non-Hispanic White Males Age group: Ages 25–44 Ages 45–54 Ages 55–64 All-Cause Mortality Rate 1990–1993 212.29 520.80 1345.21 All-Cause Mortality Rate 2015–2017 222.62 493.39 1085.81 Change 1990–1993 to 2015–2017 10.33 –27.41 –259.40 (Change as % of 1990–1993 mortality) 4.87 –5.26 –19.28 Mortality Rate Change Mortality Rate Change Mortality Rate Change % of 1990– 2015– Abs % of Total 1990– 2015– Abs Total +/– 1990– 2015– Abs % of Total Cause of Death 1993 2017 Chg +/– Chg 1993 2017 Chg Chg 1993 2017 Chg +/– Chg Infectious and Parasitic Diseases HIV/AIDS 35.83 1.05 –34.78 –56.7 25.76 3.81 –21.95 –15.4 10.16 3.49 –6.67 –1.6 Non-HIV/AIDS 3.62 2.57 –1.05 –1.7 6.54 11.03 4.49 3.9 13.68 29.26 15.59 9.5 Cancers Liver Cancer 0.49 0.52 0.03 0.0 2.54 5.03 2.50 2.2 8.75 25.79 17.04 10.3 – Lung Cancer 4.34 1.61 –2.73 –4.5 52.60 21.22 –31.37 –22.0 198.91 90.90 108.02 –25.5 All Other Cancers 20.90 15.55 –5.35 –8.7 91.52 70.23 –21.29 –14.9 271.79 206.16 –65.63 –15.5 Cardio and Metabolic Diseases Endocrine, Nutritional, & Metabolic 5.12 7.00 1.88 2.6 14.95 24.93 9.97 8.6 36.03 56.26 20.23 12.3 Hypertensive Heart Disease 1.08 3.86 2.78 3.9 5.61 16.00 10.39 9.0 15.20 32.61 17.40 10.6 Ischemic & Other Circulatory System 30.76 24.52 –6.25 –10.2 177.57 110.92 –66.65 –46.7 517.49 279.65 –237.84 –56.1 Substance Use and Mental Health Drug Poisoning 9.55 62.43 52.88 73.7 4.39 47.73 43.34 37.6 2.58 31.42 28.84 17.5 Alcohol-Induced* 4.81 6.70 1.89 2.6 13.33 21.83 8.50 7.4 20.73 31.58 10.85 6.6 Suicide 23.09 32.30 9.21 12.8 22.36 35.21 12.85 11.1 24.75 32.79 8.03 4.9 Mental & Behavioral Disorders 3.84 5.10 1.26 1.8 7.35 12.69 5.34 4.6 11.37 21.01 9.64 5.9 Other Body System Diseases Nervous System 3.11 4.63 1.53 2.1 7.01 11.98 4.98 4.3 15.71 28.44 12.74 7.7 Genitourinary System 1.01 1.29 0.28 0.4 3.18 5.62 2.44 2.1 10.42 16.02 5.59 3.4 Respiratory System 4.49 4.23 –0.27 –0.4 18.32 20.26 1.94 1.7 85.70 81.10 –4.60 –1.1 Digestive System* 5.50 4.59 –0.91 –1.5 17.23 19.94 2.72 2.4 39.05 44.79 5.74 3.5 Other Causes of Death Homicide 8.12 5.66 –2.46 –4.0 6.26 4.78 –1.48 –1.0 4.76 3.42 –1.34 –0.3 4-7 Prepublication copy, uncorrected proofs

Transport Accidents 27.21 22.22 –4.99 –8.1 20.37 22.13 1.77 1.5 20.00 23.30 3.30 2.0 Other External Causes of Death 12.69 10.43 –2.26 –3.7 14.19 15.99 1.80 1.6 19.63 25.58 5.95 3.6 All Other Causes of Death 6.72 6.38 –0.34 –0.6 9.74 12.04 2.31 2.0 18.49 22.24 3.76 2.3 Total Change: Increase (+) 71.74 115.33 164.70 Total Change: Decrease (–) –61.40 –142.74 –424.09 Non-Hispanic White Females Age group: Ages 25–44 Ages 45–54 Ages 55–64 All-Cause Mortality Rate 1990–1993 88.93 295.15 767.20 All-Cause Mortality Rate 2015–2017 121.90 314.97 659.91 Change 1990–1993 to 2015–2017 32.97 19.82 –107.29 (Change as % of 1990–1993 mortality) 37.07 6.72 –13.98 Mortality Rate Change Mortality Rate Change Mortality Rate Change % of % of % of 1990– 2015– Abs Total +/– 1990– 2015– Abs Total +/– 1990– 2015– Total +/– Cause of Death 1993 2017 Chg Chg 1993 2017 Chg Chg 1993 2017 Abs Chg Chg Infectious and Parasitic Diseases HIV/AIDS 2.09 0.37 –1.72 –13.3 1.07 0.71 –0.36 –0.6 0.67 0.58 –0.08 0.0 Non-HIV/AIDS 1.43 2.41 0.98 2.1 3.79 8.45 4.66 5.8 9.40 19.68 10.28 11.0 Cancers Liver Cancer 0.24 0.39 0.14 0.3 1.37 2.14 0.77 1.0 3.79 7.52 3.74 4.0 Lung Cancer 3.07 1.48 –1.59 –12.3 33.42 19.34 –14.08 –23.1 104.57 67.85 –36.72 –18.3 All Other Cancers 26.62 19.19 –7.43 –57.6 111.06 76.40 –34.67 –57.0 248.27 173.33 –74.95 –37.3 Cardio and Metabolic Diseases Endocrine, Nutritional, & Metabolic 3.06 4.92 1.86 4.0 10.04 14.76 4.72 5.9 28.45 32.24 3.78 4.0 Hypertensive Heart Disease 0.33 1.65 1.32 2.9 2.34 7.30 4.96 6.1 7.93 15.27 7.34 7.8 Ischemic & Other Circulatory System 11.88 13.09 1.21 2.6 60.58 49.74 –10.84 –17.8 207.31 120.51 –86.80 –43.2 Substance Use and Mental Health Drug Poisoning 4.10 30.36 26.26 57.2 4.14 33.26 29.12 36.1 3.45 22.56 19.12 20.4 Alcohol-Induced* 1.71 3.83 2.12 4.6 4.21 11.73 7.52 9.3 6.52 12.65 6.13 6.5 Suicide 4.64 7.85 3.21 7.0 5.48 9.10 3.62 4.5 5.16 7.59 2.44 2.6 Mental & Behavioral Disorders 1.24 3.08 1.84 4.0 2.25 5.92 3.67 4.5 3.81 8.86 5.06 5.4 Other Body System Diseases 4-8 Prepublication copy, uncorrected proofs

Nervous System 2.28 3.53 1.25 2.7 6.03 9.70 3.68 4.6 12.82 24.01 11.20 12.0 Genitourinary System 0.71 1.18 0.47 1.0 2.54 4.51 1.97 2.4 7.80 12.16 4.37 4.7 Respiratory System 3.03 4.18 1.15 2.5 14.45 20.87 6.41 7.9 60.25 68.84 8.58 9.2 Digestive System* 2.68 3.75 1.06 2.3 9.47 13.70 4.22 5.2 24.41 29.13 4.72 5.0 Other Causes of Death Homicide 3.36 2.59 –0.77 –5.9 2.48 2.10 –0.38 –0.6 1.72 1.57 –0.16 –0.1 Transport Accidents 9.60 8.22 –1.39 –10.7 8.54 8.04 –0.51 –0.8 9.29 7.12 –2.17 –1.1 Other External Causes of Death 2.59 3.49 0.89 1.9 4.15 6.64 2.49 3.1 6.97 11.29 4.32 4.6 All Other Causes of Death 4.26 6.38 2.12 4.6 7.70 10.55 2.85 3.5 14.62 17.14 2.52 2.7 Total Change: Increase (+) 45.87 80.66 93.59 Total Change: Decrease (–) –12.90 –60.83 –200.88 *Changes in the International Classification of Diseases (ICD)-10 code for diseases of the digestive system in 2006 affected the comparability of both digestive system deaths and alcohol-induced deaths before and after that year. More information is provided in Chapter 5. LEGEND: The top 3 causes of death for each age group in each period are highlighted in bolded red text. Light orange highlights indicate an absolute increase in the overall mortality rate of ≥5 deaths/100,000 population. Dark orange highlights indicate that a cause of death is responsible for ≥10 percent of the total increase in mortality. Light green highlights indicate an absolute decrease in the overall mortality rate of ≥5 deaths/100,000 population. Dark green highlights indicate that a cause of death is responsible for ≥10 percent of the total decrease in mortality. NOTE: The table shows mortality rates and change in all-cause and cause-specific mortality rates among non-Hispanic White working-age adults by age group (25–44, 45–54, and 55–64) for males (upper table) and females (lower table). Changes in mortality are presented as both the absolute change in mortality rates and the percentage of the total increase (or decrease) in mortality. Mortality rates within each age group are age-adjusted by single-year of age to match the age distribution of the U.S. population in 2000 in order to improve comparability over time. These causes of death are exhaustive of all underlying cause-of-death codes and are based on the ICD-9 (1990–1998) and ICD-10 (1999–2017) codes. More information about the classification of causes of death can be found in Chapter 5. SOURCE: Data from: https://www.cdc.gov/nchs/nvss/nvss-restricted-data.htm. 4-9 Prepublication copy, uncorrected proofs

Previous studies have grouped mortality due to drug poisoning, alcohol, and suicide together and found that this set of causes was responsible for the largest increases in mortality over the period among working-age Whites (Case and Deaton, 2015, 2017). The committee made this same finding: taken together, these causes of death were responsible for between one- third and more than 90 percent of the total increase in mortality that occurred between 1990– 1993 and 2015–2017, depending on age group and sex. Nonetheless, drug poisoning was the single largest contributor to the increase in all-cause mortality rates among White males and females in all three age groups, with its contribution to the increase in all-cause mortality over the period ranging from a low of 17.5 percent among males aged 55–64 to a high of 73.7 percent among males aged 25–44. Moreover, in 2015–2017, drug poisoning was the top cause of death among White males and females aged 25–44, and on its own, the increase in drug poisoning completely offset the declines in other causes of death that occurred among White females in this age group. Suicide was the second largest contributor to the increase in all-cause mortality among White males aged 25–44 (12.8%), males aged 45–54 (11.1%), and females aged 25–44 (7.0%). Along with drug poisoning and suicide, Case and Deaton (2015, 2017) highlight the important contribution of alcohol-induced causes to increasing midlife mortality rates among Whites. The committee likewise found that deaths from alcohol-induced causes increased over this period among White males and females in all three age groups, and that these increases were larger among those aged 45–64 relative to the younger age group. This delayed onset is consistent with the clinical course of alcoholic liver disease (the largest contributor to mortality in this category), which develops over time and often results from years of chronic alcohol consumption. Among White females aged 45–54, deaths from alcohol-induced causes were the second largest contributor to the increase in all-cause mortality (representing 9.3% of the total increase). The committee considered rates of mortality from mental and behavioral disorders in conjunction with those from drug poisoning and alcohol-induced causes because most deaths attributed to mental and behavior disorders involve drugs or alcohol.6 Mortality from mental and behavioral disorders also increased among males and females in all three age groups. These mortality increases were generally similar in magnitude to those due to alcohol-induced causes. Together, the causes of death in the substance use and mental health category made an overwhelming contribution to the increases in mortality among both males and females in all three age groups, contributing to 91 percent of the increase for males aged 25–44, 61 percent for males aged 45–54, 35 percent for males aged 55–65, 73 percent for females aged 25–44, 54 percent for females aged 45–54, and 35 percent for females aged 55–64. Other significant contributors to the overall increase in mortality among working-age White adults were cardiometabolic diseases. Although combined mortality from all of these diseases decreased overall because of large decreases in mortality from ischemic heart disease and other circulatory system diseases, mortality from hypertensive heart disease and ENM diseases increased over the period among both males and females in all three age groups. These causes of death made important contributions to the increase in all-cause mortality in the 45–54 and 55–64 age groups, together contributing 18 percent of the increase for males aged 45–54, 13 percent for males aged 55–64, and 12 percent each for females aged 45–54 and 55–64. Other large contributors to the increase in all-cause mortality included liver cancer for males aged 55–                                                         6 More detail about the relationship between mental and behavioral disorders and drug poisoning and/or alcohol-induced causes is presented later in the chapter.  4-10 Prepublication copy, uncorrected proofs

64 (representing 10% of the increase), non-HIV/AIDS infectious and parasitic diseases among females aged 55–64 (11% of the increase), and diseases of the nervous system among females aged 55–64 (12% of the increase). These widespread mortality increases were offset by remarkable improvements in mortality rates from HIV/AIDS; lung and other cancers,7 excluding liver cancer; and ischemic heart disease and other diseases of the circulatory system. Declines in mortality from HIV/AIDS contributed 57 percent of the decline in all-cause mortality among males aged 25–44, 15 percent among males aged 45–54, and 13 percent among females aged 25–44. Declines in mortality due to lung and other cancers contributed 13 percent of the overall decline in all-cause mortality among males aged 25–44, 37 percent among males aged 45–54, 41 percent among males aged 55–64, 70 percent among females aged 25–44, 80 percent among females aged 45–54, and 56 percent among females aged 55–64. Reductions in mortality from ischemic heart disease and other circulatory system diseases also contributed substantially to declines in all-cause mortality among all sex/age groups except females aged 25–44 (who already had comparatively low rates of mortality from this cause). Ischemic heart disease and other circulatory system diseases represented the single largest contributor to the decline in all-cause mortality among males aged 45–54 (47%), males aged 55–64 (56%), and females aged 55–64 (43%). Working-Age Non-Hispanic Black Adults At the beginning of the period, working-age cause-specific mortality was higher among Blacks than among Whites for nearly all causes of death (Table 4-2)—in many cases, significantly higher. Only suicide rates were consistently higher among working-age White adults, although older White females (aged 45–64) also had higher mortality from drug poisoning relative to similarly-aged Black females. In contrast to changes in mortality rates between 1990–1993 and 2015–2017 among working-age White adults, who saw widespread increases, the changes among working-age Blacks were characterized by dramatic decreases in mortality across a wide range of causes. Declines were larger (both absolutely and as a percentage) among Black males than among Black females, with the largest decreases occurring for mortality due to ischemic heart disease and other circulatory system diseases and cancers other than liver cancer. Younger working-age Blacks also experienced large decreases in homicide rates and mortality from HIV/AIDS. Despite these massive declines in Black mortality rates, however, mortality among Black adults remained much higher than that among White adults for most causes of death in 2015–2017. Despite the above improvements, Black working-age mortality rates did increase for a small number of causes of death, notably drug poisoning and diseases of the nervous system. Although drug poisoning mortality also increased among Black adults, these increases were generally smaller than those among White adults, except among older Black males (aged 55–64). Unlike working-age Whites, working-age Blacks did not experience increases in mortality due to alcohol-induced causes, suicide, or mental and behavioral disorders. For this reason, by 2015– 2017, working-age Whites generally had higher rates of mortality from alcohol-induced causes, suicide, and mental and behavioral disorders relative to similarly aged Black adults. Among Black males and younger Black females, mortality due to ENM diseases and hypertensive heart disease increased. Overall, when cause-specific mortality increased, working-age Blacks                                                         7 “Other cancers” include all cancers besides liver and lung. Large declines in breast cancer are responsible for most of the decline in mortality rates from “other cancers” among females. 4-11 Prepublication copy, uncorrected proofs

experienced smaller mortality increases compared with working-age Whites, and these increases were more than offset by large reductions in mortality across multiple causes of death. 4-12 Prepublication copy, uncorrected proofs

TABLE 4-2 Cause-Specific Mortality (deaths per 100,000 population), 1990–1993 and 2015–2017: Non-Hispanic Black Adults Aged 25–64 Non-Hispanic Black Males Age group: Ages 25–44 Ages 45–54 Ages 55–64 All-Cause Mortality Rate 1990–1993 582.82 1236.32 2466.82 All-Cause Mortality Rate 2015–2017 319.86 697.04 1669.83 Change 1990–1993 to 2015–2017 –262.96 –539.28 –796.99 (Change as % of 1990–1993 mortality) –45.12 –43.62 –32.31 Mortality Rate Change Mortality Rate Change Mortality Rate Change % of % of Total % of 1990– 2015– Abs Total +/– 1990– 2015– Abs +/– 1990– 2015– Abs Total Cause of Death 1993 2017 Chg Chg 1993 2017 Chg Chg 1993 2017 Chg +/– Chg Infectious and Parasitic Diseases – HIV/AIDS 134.82 10.16 124.66 –43.9 98.09 20.96 –77.13 –13.2 44.75 30.07 –14.68 –1.6 Non-HIV/AIDS 16.23 4.78 –11.46 –4.0 30.71 18.09 –12.62 –2.2 45.06 54.76 9.70 7.7 Cancers Liver Cancer 1.84 1.18 –0.66 –0.2 7.90 7.51 –0.39 –0.1 18.95 49.60 30.65 24.4 – Lung Cancer 10.43 2.36 –8.07 –2.8 108.93 23.84 –85.10 –14.6 320.63 119.64 200.99 –21.8 – All Other Cancers 31.45 17.42 –14.03 –4.9 176.23 85.03 –91.21 –15.6 461.08 274.10 186.98 –20.3 Cardio and Metabolic Diseases Endocrine, Nutritional, & Metabolic 13.04 15.39 2.35 11.2 43.04 46.95 3.91 8.7 92.87 103.79 10.92 8.7 Hypertensive Heart Disease 9.98 14.97 5.00 23.8 46.34 48.20 1.87 4.1 91.66 100.22 8.57 6.8 – – Ischemic & Other Circulatory System 76.27 49.51 –26.76 –9.4 357.62 188.32 169.31 –29.0 869.66 474.12 395.54 –42.9 Substance Use and Mental Health Drug Poisoning 19.45 32.54 13.09 62.4 12.92 48.91 36.00 79.8 4.79 55.90 51.11 40.7 Alcohol–Induced* 13.17 3.26 –9.92 –3.5 36.81 12.04 –24.77 –4.2 41.88 25.36 –16.53 –1.8 Suicide 17.11 15.67 –1.44 –0.5 12.65 10.64 –2.00 –0.3 10.50 8.17 –2.33 –0.3 Mental & Behavioral Disorders 14.37 3.53 –10.84 –3.8 32.90 10.69 –22.21 –3.8 38.14 26.84 –11.30 –1.2 Other Body System Diseases Nervous System 6.82 7.36 0.54 2.6 12.75 16.07 3.32 7.4 21.91 33.96 12.05 9.6 Genitourinary System 7.59 4.86 –2.73 –1.0 20.19 18.74 –1.45 –0.2 47.87 50.37 2.50 2.0 Respiratory System 19.29 8.52 –10.77 –3.8 52.38 27.31 –25.07 –4.3 136.43 92.21 –44.22 –4.8 Digestive System* 15.93 4.79 –11.13 –3.9 45.89 19.39 –26.50 –4.5 72.29 54.58 –17.71 –1.9 4-13 Prepublication copy, uncorrected proofs

Other Causes of Death Homicide 92.84 69.24 –23.59 –8.3 45.41 27.69 –17.72 –3.0 29.74 17.05 –12.69 –1.4 Transport Accidents 34.30 30.37 –3.93 –1.4 31.78 27.25 –4.53 –0.8 31.16 29.09 –2.07 –0.2 Other External Causes of Death 23.88 11.50 –12.38 –4.4 31.46 17.58 –13.88 –2.4 43.80 30.69 –13.11 –1.4 All Other Causes of Death 24.03 12.46 –11.57 –4.1 32.33 21.84 –10.49 –1.8 43.67 39.35 –4.32 –0.5 Total Change: Increase (+) 20.98 45.10 125.49 Total Change: Decrease (–) –283.93 –584.38 –922.47 Non-Hispanic Black Females Age group: Ages 25–44 Ages 45–54 Ages 55–64 All-Cause Mortality Rate 1990–1993 243.70 627.87 1367.98 All-Cause Mortality Rate 2015–2017 162.89 455.25 1002.30 Change 1990–1993 to 2015–2017 –80.81 –172.62 –365.68 (Change as % of 1990–1993 mortality) –33.16 –27.49 –26.73 Mortality Rate Change Mortality Rate Change Mortality Rate Change % of Total % of % of 1990– 2015– Abs +/– 1990– 2015– Abs Total +/– 1990– 2015– Abs Total +/– Cause of Death 1993 2017 Chg Chg 1993 2017 Chg Chg 1993 2017 Chg Chg Infectious and Parasitic Diseases HIV/AIDS 32.04 5.89 –26.15 –27.5 15.70 11.37 –4.33 –2.2 7.36 10.70 3.33 5.8 Non-HIV/AIDS 8.75 4.26 –4.49 –4.7 16.04 14.21 –1.83 –0.9 28.04 36.95 8.91 15.4 Cancers Liver Cancer 0.59 0.53 –0.05 –0.1 2.30 3.19 0.90 3.7 6.52 13.48 6.97 12.0 Lung Cancer 4.59 1.19 –3.40 –3.6 39.66 16.35 –23.31 –11.8 108.58 68.08 –40.50 –9.6 All Other Cancers 41.80 27.61 –14.18 –14.9 163.83 107.15 –56.68 –28.8 342.25 242.89 –99.36 –23.5 Cardio and Metabolic Diseases Endocrine, Nutritional, & Metabolic 8.34 11.31 2.97 20.9 35.09 31.95 –3.13 –1.6 92.73 70.97 –21.76 –5.1 Hypertensive Heart Disease 5.65 7.51 1.87 13.1 28.67 27.15 –1.51 –0.8 61.95 53.22 –8.72 –2.1 – Ischemic & Other Circulatory System 42.31 27.90 –14.40 –15.2 180.18 101.56 –78.62 –40.0 476.99 244.29 232.70 –54.9 Substance Use and Mental Health Drug Poisoning 6.72 13.88 7.16 50.3 4.01 22.56 18.55 76.8 1.59 18.80 17.21 29.8 Alcohol-Induced* 5.38 2.15 –3.23 –3.4 11.24 6.58 –4.66 –2.4 12.18 9.26 –2.92 –0.7 Suicide 2.42 2.83 0.41 2.9 1.86 1.70 –0.16 –0.1 1.98 1.57 –0.41 –0.1 4-14 Prepublication copy, uncorrected proofs

Mental & Behavioral Disorders 5.30 1.78 –3.52 –3.7 7.92 4.46 –3.46 –1.8 8.39 9.35 0.96 1.7 Other Body System Diseases Nervous System 4.21 5.93 1.72 12.1 9.31 13.72 4.41 18.3 15.27 27.98 12.71 22.0 Genitourinary System 4.01 4.10 0.10 0.7 12.57 12.86 0.29 1.2 35.72 36.48 0.76 1.3 Respiratory System 11.40 6.47 –4.93 –5.2 29.91 24.42 –5.49 –2.8 67.09 72.12 5.03 8.7 Digestive System* 8.18 4.02 –4.16 –4.4 22.27 14.24 –8.03 –4.1 41.75 31.68 –10.08 –2.4 Other Causes of Death Homicide 19.64 8.11 –11.53 –12.1 7.82 4.67 –3.15 –1.6 5.66 3.50 –2.16 –0.5 Transport Accidents 9.83 8.20 –1.62 –1.7 8.73 7.90 –0.83 –0.4 10.44 7.06 –3.39 –0.8 Other External Causes of Death 5.15 3.36 –1.80 –1.9 8.04 6.53 –1.51 –0.8 12.72 11.22 –1.50 –0.4 All Other Causes of Death 17.41 15.84 –1.57 –1.7 22.73 22.66 –0.07 0.0 30.77 32.72 1.95 3.4 Total Change: Increase (+) 14.23 24.14 57.83 Total Change: Decrease (–) –95.04 –196.76 –423.51 *Changes in the International Classification of Diseases (ICD)-10 code for diseases of the digestive system in 2006 affected the comparability of both digestive system deaths and alcohol-induced deaths before and after that year. More information is provided in Chapter 5. LEGEND: The top 3 causes of death for each age group in each period are highlighted in bolded red text. Light orange highlights indicate an absolute increase in the overall mortality rate of ≥5 deaths/100,000 population. Dark orange highlights indicate that a cause of death is responsible for ≥10 percent of the total increase in mortality. Light green highlights indicate an absolute decrease in the overall mortality rate of ≥5 deaths/100,000 population. Dark green highlights indicate that a cause of death is responsible for ≥10 percent of the total decrease in mortality. NOTE: The table shows mortality rates and change in all-cause and cause-specific mortality rates among non-Hispanic White working-age adults by age group (25–44, 45–54, and 55–64) for males (upper table) and females (lower table). Changes in mortality are presented as both the absolute change in mortality rates and the percentage of the total increase (or decrease) in mortality. Mortality rates within each age group are age-adjusted by single-year of age to match the age distribution of the U.S. population in 2000 in order to improve comparability over time. These causes of death are exhaustive of all underlying cause-of-death codes and are based on the ICD-9 (1990–1998) and ICD-10 (1999–2017) codes. More information about the classification of causes of death can be found in Chapter 5. SOURCE: Data from: https://www.cdc.gov/nchs/nvss/nvss-restricted-data.htm. 4-15 Prepublication copy, uncorrected proofs

In all three age groups, mortality from drug poisoning increased among Black adults and was the single largest contributor to increases in all-cause mortality, just as was the case among working-age Whites. However, the increase in mortality due to drug poisoning was greater among working-age Whites than among working-age Blacks, with the exception of older males (aged 55–64). For this reason, the age patterns of these increases differed among working-age Blacks. Among White males, drug poisoning mortality rates increased most among younger adults (aged 25–44) and least among older adults (aged 55–64), but this pattern was reversed among Black males, so that older Black males (aged 55–64) experienced the largest increase, while younger Black males (aged 25–44) experienced the smallest increase. As with White females, the highest mortality rate and largest mortality increase for drug poisoning among Black females was in the middle age group (45–54). Mortality from alcohol-induced causes, suicide, and mental and behavioral disorders declined among Black adults overall between 1990–1993 and 2015–2017. ENM diseases and hypertensive heart disease were also important contributors to increases in all-cause mortality among Black males and younger Black females, together contributing 13–35 percent of the increase. While increases in cause-specific mortality were more limited among working-age Blacks, three other causes of death—diseases of the nervous system, liver cancer, and non-HIV/AIDS infectious and parasitic diseases—increased substantially for them over the period, although only the first of these causes increased among both sexes and all age groups. The increases in mortality from diseases of the nervous system among Black adults were similar to those among Whites: they were larger among females and increased with age. Among Black females aged 45–54, diseases of the nervous system represented the second largest increase in mortality, after drug poisoning. Non-HIV/AIDS infectious and parasitic diseases and liver cancer were important contributors to the total increase in mortality for Black adults aged 55–64, the former contributing 9.7 percent and 15.4 percent of the increase in all-cause mortality for males and females, respectively, and the latter 24.4 percent and 12 percent of the increase for males and females, respectively. After drug poisoning, liver cancer was the second largest contributor to the increase in mortality among males aged 55–64, and this increase in mortality from liver cancer was larger among Black males aged 55–64 than among similarly aged White males. Relative to working-age Whites, working-age Blacks experienced declines in mortality from a wider range of causes, including HIV/AIDS (except Black females aged 55–64), lung and other nonliver cancers, ischemic heart disease and other diseases of the circulatory system, alcohol-induced causes, mental and behavioral disorders, diseases of the respiratory system, diseases of the digestive system, homicide, transport injuries, other external causes of death, and the category of all other causes. As was true among Whites, the largest improvements in mortality for working-age Blacks involved ischemic heart disease and other circulatory system diseases, lung and other nonliver cancers, and HIV/AIDS. The declines in mortality from these causes of death were remarkable and contributed to a major reduction in the Black–White gap in all-cause mortality. For each of these causes of death, Black adults experienced much larger declines relative to White adults, although their rates began at much higher starting points and remained higher in 2015–2017. The slight increase in HIV/AIDS mortality among Black females aged 55–64 is concerning; this is the only group that experienced an increase in mortality from this cause over the study period. 4-16 Prepublication copy, uncorrected proofs

Hispanic Adults Although cause-specific mortality was much lower among working-age Hispanics than among working-age Blacks over the period, their trends over time, while of smaller magnitude, were similar to those among Blacks (Table 4-3). Hispanic adults experienced large reductions in mortality across a wide range of causes of death, with the largest improvements seen in ischemic heart disease and other circulatory diseases, cancers other than liver cancer, HIV/AIDS, and homicide. These improvements more than offset the small increases in mortality experienced by Hispanics for several causes of death, including drug poisoning, hypertensive heart disease, ENM diseases, liver cancer, and nervous system diseases. Working-age Hispanic females also experienced increased mortality from several causes in the substance use and mental health category, including alcohol-induced causes, suicide, and mental and behavioral disorders, but these increases were mostly negligible. Like Black males, Hispanic males experienced decreases in mortality from these causes; however, rates of mortality from these causes were already much higher among both Black and Hispanic males than among Black and Hispanic females in 1990– 1993, and they remained higher throughout the period. Drug poisoning was the single largest contributor to increasing mortality among working- age Hispanics, except those aged 55–64 (for whom it was the second largest contributor among males and the third largest among females). However, absolute increases in mortality from drug poisoning among Hispanic adults were much smaller than those among White and Black adults. Although younger Hispanic adults (aged 25–44) had higher rates of mortality from drug poisoning in 1990–1993, older Hispanic adults, especially males, experienced larger increases over the period. By 2015–2017, rates of mortality from drug poisoning were similar across age groups among both Hispanic males and females. Mortality rates from alcohol-induced causes, suicide, and mental and behavioral disorders declined among Hispanic males in all three age groups, and while increasing negligibly among Hispanic females, remained relatively low throughout the period. Beyond drug poisoning, mortality increased for very few causes of death among Hispanic adults, particularly in the two younger age groups. Negligible increases in mortality from ENM diseases and hypertensive heart disease occurred for males aged 25–54, and a small increase in diseases of the nervous system was seen among females aged 45–54. Table 4-3 shows large percentage contributions of these causes to changes in all-cause mortality, but this is only because the total increase across all causes of death was small. In the older age group (55–64), relatively large increases occurred in mortality from non-HIV/AIDS infectious and parasitic diseases, liver cancer, hypertensive heart disease, and diseases of the nervous system among males, along with increased mortality from non-HIV/AIDS infectious and parasitic diseases, liver cancer, and diseases of the nervous system among females. 4-17 Prepublication copy, uncorrected proofs

TABLE 4-3 Cause-Specific Mortality (deaths per 100,000 population), 1990–1993 and 2015–2017: Hispanic Adults Aged 25–64 Hispanic Males Age group: Ages 25–44 Ages 45–54 Ages 55–64 All-Cause Mortality Rate 2009–2011 287.25 520.73 1090.13 All-Cause Mortality Rate 2015–2017 144.89 344.90 805.96 Change 1990–1993 to 2015–2017 –142.36 –175.83 –284.17 (Change as % of 1990–1993 mortality) –49.56 –33.77 –26.07 Mortality Rate Change Mortality Rate Change Mortality Rate Change % of % of % of 1990– 2015– Abs Total +/– 1990– 2015– Abs Total +/– 1990– 2015– Abs Total +/– Cause of Death 1993 2017 Chg Chg 1993 2017 Chg Chg 1993 2017 Chg Chg Infectious and Parasitic Diseases HIV/AIDS 70.91 2.38 –68.53 –45.5 57.24 6.36 –50.88 –25.0 30.35 7.86 –22.49 –6.3 Non-HIV/AIDS 6.84 2.32 –4.52 –3.0 11.55 12.28 0.73 2.6 19.35 31.13 11.78 16.5 Cancers Liver Cancer 0.83 0.54 –0.29 –0.2 5.32 8.93 3.61 13.1 16.59 35.64 19.05 26.6 Lung Cancer 2.08 0.73 –1.35 –0.9 18.58 5.51 –13.07 –6.4 77.14 30.51 –46.63 –13.1 All Other Cancers 15.65 11.95 –3.70 –2.5 64.00 48.70 –15.29 –7.5 194.86 143.86 –51.00 –14.3 Cardio and Metabolic Diseases Endocrine, Nutritional, & Metabolic 4.65 5.09 0.44 5.4 18.19 20.72 2.53 9.2 54.32 58.01 3.70 5.2 Hypertensive Heart Disease 1.64 3.07 1.44 17.5 7.92 11.99 4.07 14.7 21.36 29.08 7.72 10.8 – Ischemic & Other Circulatory System 23.58 16.19 –7.39 –4.9 128.06 70.47 –57.59 –28.3 385.36 200.92 184.44 –51.8 Substance Use and Mental Health Drug Poisoning 16.26 22.39 6.13 74.8 10.16 24.45 14.29 51.7 4.25 19.36 15.11 21.1 Alcohol-Induced* 12.60 7.78 –4.82 –3.2 37.36 27.02 –10.34 –5.1 50.36 43.74 –6.62 –1.9 Suicide 14.42 12.94 –1.48 –1.0 14.04 11.59 –2.45 –1.2 16.28 10.78 –5.50 –1.5 Mental & Behavioral Disorders 7.33 2.92 –4.41 –2.9 14.66 8.26 –6.40 –3.1 15.28 13.83 –1.46 –0.4 Other Body System Diseases Nervous System 2.53 2.72 0.19 2.3 5.60 7.13 1.53 5.5 10.49 17.62 7.13 10.0 Genitourinary System 1.46 1.14 –0.33 –0.2 5.28 6.14 0.86 3.1 13.55 19.06 5.51 7.7 Respiratory System 6.30 2.97 –3.33 –2.2 17.25 10.39 –6.86 –3.4 51.06 37.73 –13.33 –3.7 Digestive System* 8.58 3.95 –4.62 –3.1 29.07 18.61 –10.47 –5.1 52.63 44.78 –7.84 –2.2 Other Causes of Death 4-18 Prepublication copy, uncorrected proofs

Homicide 38.69 12.75 –25.94 –17.2 22.98 6.89 –16.10 –7.9 14.04 5.47 –8.56 –2.4 Transport Accidents 30.75 19.41 –11.34 –7.5 27.37 17.55 –9.82 –4.8 27.08 20.08 –6.99 –2.0 Other External Causes of Death 13.90 8.68 –5.22 –3.5 15.85 13.24 –2.62 –1.3 20.54 19.69 –0.86 –0.2 All Other Causes of Death 8.26 4.96 –3.30 –2.2 10.26 8.69 –1.57 –0.8 15.26 16.80 1.54 2.2 Total Change: Increase (+) 8.20 27.62 71.54 Total Change: Decrease (–) –150.56 –203.45 –355.72 Hispanic Females Age group: Ages 25–44 Ages 45–54 Ages 55–64 All-Cause Mortality Rate 1990–1993 89.67 243.72 596.84 All-Cause Mortality Rate 2015–2017 66.32 184.45 440.99 Change 1990–1993 to 2015–2017 –23.35 –59.27 –155.85 (Change as % of 1990–1993 mortality) –26.04 –24.32 –26.11 Mortality Rate Change Mortality Rate Change Mortality Rate Change % of % of % of 1990– 2015– Abs Total +/– 1990– 2015– Abs Total +/– 1990– 2015– Abs Total +/– Cause of Death 1993 2017 Chg Chg 1993 2017 Chg Chg 1993 2017 Chg Chg Infectious and Parasitic Diseases HIV/AIDS 11.74 0.54 –11.20 –37.8 7.38 1.33 –6.05 –8.5 4.38 1.88 –2.50 –1.4 Non-HIV/AIDS 2.57 1.41 –1.16 –3.9 5.38 6.13 0.75 6.2 13.41 16.70 3.29 14.7 Cancers Liver Cancer 0.29 0.39 0.10 1.7 1.90 2.24 0.35 2.9 6.17 9.96 3.79 17.0 Lung Cancer 1.03 0.71 –0.32 –1.1 8.09 4.92 –3.18 –4.4 26.69 18.45 –8.25 –4.6 All Other Cancers 21.79 17.24 –4.56 –15.4 85.51 60.52 –24.99 –35.0 178.44 135.29 –43.15 –24.2 Cardio and Metabolic Diseases Endocrine, Nutritional, & Metabolic 2.50 2.88 0.39 6.2 12.99 11.82 –1.17 –1.6 50.36 35.63 –14.73 –8.3 Hypertensive Heart Disease 0.80 1.00 0.20 3.3 4.06 4.73 0.67 5.5 12.34 13.04 0.70 3.1 Ischemic & Other Circulatory System 10.17 7.07 –3.10 –10.5 53.33 28.78 –24.55 –34.4 175.91 81.51 –94.41 –53.0 Substance Use and Mental Health Drug Poisoning 2.91 7.25 4.34 69.7 2.24 9.05 6.81 55.8 2.15 7.54 5.39 24.2 Alcohol-Induced* 2.00 2.50 0.50 8.1 6.07 6.95 0.88 7.2 8.38 9.27 0.89 4.0 Suicide 2.24 2.66 0.42 6.7 1.78 2.40 0.62 5.1 1.92 1.97 0.05 0.2 Mental & Behavioral Disorders 1.29 0.83 –0.46 –1.5 1.63 2.03 0.40 3.3 3.03 4.02 0.99 4.4 Other Body System Diseases 4-19 Prepublication copy, uncorrected proofs

Nervous System 1.54 1.80 0.26 4.2 3.30 5.00 1.71 14.0 7.38 13.44 6.07 27.2 Genitourinary System 0.98 0.99 0.01 0.2 4.48 4.33 –0.15 –0.2 12.33 12.98 0.66 2.9 Respiratory System 3.47 1.93 –1.54 –5.2 10.53 8.00 –2.53 –3.5 29.20 27.01 –2.19 –1.2 Digestive System* 2.50 2.14 –0.36 –1.2 10.94 8.82 –2.12 –3.0 33.06 26.52 –6.54 –3.7 Other Causes of Death Homicide 6.26 2.75 –3.51 –11.9 3.84 2.02 –1.82 –2.5 2.54 1.24 –1.30 –0.7 Transport Accidents 8.49 5.70 –2.79 –9.4 8.92 5.59 –3.33 –4.7 10.70 6.45 –4.25 –2.4 Other External Causes of Death 1.79 1.41 –0.38 –1.3 2.59 2.55 –0.04 –0.1 5.09 5.56 0.47 2.1 All Other Causes of Death 5.33 5.13 –0.20 –0.7 8.77 7.23 –1.53 –2.1 13.37 12.53 –0.85 –0.5 Total Change: Increase (+) 6.23 12.19 22.29 Total Change: Decrease (–) –29.58 –71.46 –178.14 *Changes in the International Classification of Diseases (ICD)-10 code for diseases of the digestive system in 2006 affected the comparability of both digestive system deaths and alcohol-induced deaths before and after that year. More information is provided in Chapter 5. LEGEND: The top 3 causes of death for each age group in each period are highlighted in bolded red text. Light orange highlights indicate an absolute increase in the overall mortality rate of ≥5 deaths/100,000 population. Dark orange highlights indicate that a cause of death is responsible for ≥10 percent of the total increase in mortality. Light green highlights indicate an absolute decrease in the overall mortality rate of ≥5 deaths/100,000 population. Dark green highlights indicate that a cause of death is responsible for ≥10 percent of the total decrease in mortality. NOTE: The table shows mortality rates and change in all-cause and cause-specific mortality rates among non-Hispanic White working-age adults by age group (25–44, 45–54, and 55–64) for males (upper table) and females (lower table). Changes in mortality are presented as both the absolute change in mortality rates and the percentage of the total increase (or decrease) in mortality. Mortality rates within each age group are age-adjusted by single-year of age to match the age distribution of the U.S. population in 2000 in order to improve comparability over time. These causes of death are exhaustive of all underlying cause-of-death codes and are based on the ICD-9 (1990–1998) and ICD-10 (1999–2017) codes. More information about the classification of causes of death can be found in Chapter 5. SOURCE: Data from: https://www.cdc.gov/nchs/nvss/nvss-restricted-data.htm. 4-20 Prepublication copy, uncorrected proofs

As was true for Black males, Hispanic males experienced widespread improvements across multiple causes of death over the period, although the reductions among Hispanic males were much smaller because they began the period with much lower mortality rates. As with White and Black males, the most important contributors to mortality declines among Hispanic males were HIV/AIDS, lung and other nonliver cancers (ages 45–64), and ischemic heart disease and other diseases of the circulatory system. However, Hispanic males also experienced notable declines in mortality from alcohol-induced causes, suicide, mental and behavioral disorders, homicide, and transport injuries. The trends in cause-specific mortality among Hispanic females resemble more closely those of White females, with increasing mortality across multiple causes of death. However, these increases were generally much smaller than those among White females; Hispanic females maintained a very favorable mortality profile, having experienced notable declines (on top of already low rates) in mortality from HIV/AIDS, nonliver cancers, and homicide (among those aged 25–44). DISPARITIES IN CAUSE-SPECIFIC MORTALITY BY SOCIOECONOMIC STATUS The literature on trends in educational attainment and working-age cause-specific mortality is fairly extensive; however, only a limited number of these studies focused on socioeconomic disparities in cause-specific mortality rates. Despite their limited number, these studies consistently found that increases in mortality due to drug poisoning, alcohol-induced causes, and suicide were the largest contributors to the growing gap in mortality by education among working-age Whites, and that increases in drug poisoning mortality were increasingly concentrated among working-age Whites with a high school degree or less. This group also experienced larger increases in mortality across a wide range of other causes of death, and this was especially true for White women with less education. In contrast, among working-age Black adults, education-based disparities in cause-specific mortality remained steady over time. Sasson (2016) used vital statistics data to demonstrate steep increases in educational disparities in life expectancy for White men and women but little change for Black men and women between 1990 and 2010. He showed that the increases in the education-based mortality gap between working-age White men and women involved largely causes of death associated with smoking, external causes (including drug poisoning),8 and cardiovascular diseases. Case and Deaton (2015) delved into the specific causes of death associated with widening educational disparities in working-age mortality, focusing on adults aged 45–54 between 1999 and 2013. They showed that the death rate from poisoning among U.S. adults aged 45–54— which includes deaths from drug poisoning and alcohol-induced causes, both unintentional and of undetermined intentionality—increased during that period for White adults of all educational levels, as well as for Black and Hispanic adults. However, the increase was especially pronounced for White adults with a high school degree or less; in this group the death rate from poisoning increased more than four-fold over the period, from 14 per 100,000 population in 1999 to 58 per 100,000 population in 2013. Death rates due to poisonings among White adults with some college education and those with a college degree or more in this age group also increased rapidly but started at a lower level in 1999, and the increases across the time period were less pronounced. For example, the poisoning death rate for White adults aged 45–54 with some                                                         8 External causes of death are causes that are due to accidents and violence, including poisonings and environmental events. 4-21 Prepublication copy, uncorrected proofs

college increased from 6 per 100,000 to 21 per 100,000, while the increase for White adults with a college degree or more was from 3 per 100,000 to 8 per 100,000. These findings provided the first clear evidence that mortality from drug poisoning among working-age Whites was increasing more rapidly among those with less versus those with more education. Unfortunately, Case and Deaton (2015) did not break down results for working- age Black or Hispanic adults by educational attainment. Notably, though, mortality from poisoning among Black and Hispanic adults aged 45–54 increased between 1999 and 2013, from 18 to 22 and from 10 to 14 per 100,000 population, respectively. Case and Deaton (2017) later updated these descriptive trends, examining them separately by sex, but the main finding of growing education-based disparities in mortality among working-age White adults did not change. Most recently, Geronimus and colleagues (2019) documented changes in educational disparities in mortality between 1990 and 2015 for working-age (and older) Black and White women and men. They measured educational attainment in quartiles to help account for compositional changes within education categories due to increasing educational attainment across time. Thus, they compared changes in mortality disparities between 1990 and 2015 for those in the bottom 25 percent versus those in the top 25 percent of the educational attainment distribution. Geronimus and colleagues (2019) found that among White adults, increasing drug-related mortality was especially concentrated among those with less education, accounting for 73 percent and 44 percent of the increased educational disparity in working-age mortality for White men and White women, respectively. White men and women also exhibited modest increases in educational disparities in working-age mortality due to suicide and liver disease. Educational disparities in working-age mortality for White women also widened over the period for a range of causes of death, including cardiovascular disease, nonlung cancers, non-HIV infectious diseases, lower respiratory diseases, and other internal causes, and only (very modestly) narrowed for homicide. Among White men, educational disparities in working-age mortality widened for some of the same causes as those seen among White women (e.g., other cancers, other infectious diseases, other internal causes), but narrowed for others (e.g., lung cancer, accidents). Thus in all, one-half (White women) to 80 percent (White men) of the increasing educational disparity in working-age mortality over the 1990–2015 period was due to what some researchers have referred to as “despair-related” causes, with educational differences in mortality from drug poisoning being particularly important for understanding the widening of educational disparities in working-age mortality that occurred among White men and women over the period. Further, and particularly for White women, increasing educational disparities in working-age mortality were also seen for a range of other causes. By contrast, there was virtually no change in educational disparities in working-age mortality for Black men and women between 1990 and 2015. Increasing drug-related mortality among Black women and men differed only modestly by educational attainment and thus had very little influence on changing educational disparities in working-age mortality. Geronimus and colleagues (2019) also found only minor changes in educational disparities in mortality from lung cancer, cardiovascular diseases, diabetes, and a range of other causes for Black men and women across the 25-year time period. In other words, declines in working-age mortality over the period for Black men and Black women unfolded in parallel fashion across educational attainment groupings. 4-22 Prepublication copy, uncorrected proofs

CAUSE-SPECIFIC MORTALITY TRENDS BY METROPOLITAN STATUS All-cause mortality trends were most favorable in large central metropolitan areas (hereafter referred to as “large central metros”) and less favorable in less-populated areas over the period, often leading to a widening mortality gap across these areas (see Chapter 3). The findings reported in this section show that most cause-specific mortality rates followed a similar trend, suggesting that the growing geographic mortality gap was the cumulative result of underlying processes that produced metro status differences for multiple causes of death. In general, when cause-specific mortality rates decreased over the period, they declined the most in large central metros; when they increased, either mortality continued to decline, or the increases were smaller in large central metros. Detailed tables showing the change in cause-specific mortality between 1990–1993 and 2015–2017 by sex, age group, and metropolitan status can be found in the annex at the end of this chapter (Annex Tables 4-1 to 4-3). Cause-specific mortality rates by sex, age group, and metropolitan status are in Appendix A. This pattern was most consistent for working-age Whites, among whom most causes of death contributed to the growing disparities between large central metros and less-populated areas. In contrast, for working-age Black and Hispanic adults, cause-specific mortality rates did not consistently decline the most in large central metros. Although Black and Hispanic adults in large central metros did experience greater improvements in mortality from many causes of death, those in nonmetropolitan areas (hereafter referred to as “nonmetros”) often experienced larger decreases in mortality from the causes of death that were key drivers of reductions in mortality over the period (e.g., cancers other than liver cancer or ischemic heart disease and other circulatory diseases). Nonetheless, Black and Hispanic adults in large central metros, particularly males, saw much larger declines in mortality from HIV/AIDS and homicides that offset these differences and drove the greater overall improvements in mortality in large central metros. Areas outside of large central metros were more likely to experience larger increases in mortality across more causes of death. Often, the largest increases in cause-specific mortality occurred within nonmetros. Mortality due to drug poisoning was a notable exception to this pattern. Among White males and older (aged 45–64) Black males and females, large metros saw the biggest increases in mortality from drug poisoning, while nonmetros experienced smaller increases. Among White males, the largest increases occurred in large fringe metropolitan areas (hereafter referred to as “large fringe metros”), while among older Black adults, the largest increases occurred in large central metros. This meant that drug poisoning did not contribute to, and in fact offset, the growing mortality disparity between large central metros and less- populated areas among White males and older (aged 45–64) Black males and females. In contrast, White females, Hispanics, and younger working-age (aged 25–44) Black adults experienced smaller increases in mortality due to drug poisoning overall, with the smallest increases occurring in large central metros. Younger (aged 25–44) Black adults living in nonmetros also experienced a smaller overall increase in drug poisoning mortality. TEMPORAL PATTERNS IN CAUSE-SPECIFIC MORTALITY TRENDS The changes described above reflect changes in cause-specific mortality rates over the full period (1990–1993 to 2015–2017). In this section, the total change in each cause-specific mortality rate over the period is decomposed into changes within three periods that correspond roughly to decades. This decomposition makes it possible to determine when the changes 4-23 Prepublication copy, uncorrected proofs

occurred for different causes of death and identify the causes of death responsible for those changes. These periods of change are referred to as the 1990s (1990–1993 to 2000–2002), the 2000s (2000–2002 to 2009–2011), and the 2010s (2009–2011 to 2015–2017). Figures 4-1 and 4-2 (showing changes in cause-specific mortality rates by time period for males and females, respectively) reveal 2 main findings beyond those already discussed earlier in this chapter. First, among the causes of death for which mortality rates declined in meaningful ways (i.e., HIV/AIDS, nonliver cancers, ischemic heart disease and other diseases of the circulatory system, and homicides [among young Black and Hispanic males]), most improvements occurred in the 1990s or 2000s and stagnated or even reversed in the 2010s. This pattern appeared most consistently for ischemic heart disease and other circulatory diseases, which saw a slowing rate of improvement in mortality over the period among most working-age adults. Among White females, younger Black males, and younger Hispanic males and females, progress in lowering mortality from ischemic heart disease and other circulatory diseases ceased in the 2010s as all-cause mortality rates began to increase.9 Most of the progress in reducing mortality from HIV/AIDS occurred in the 1990s among White and Hispanic males and younger Black males. However, mortality from HIV/AIDS continued to increase among Black females and older Black males in the 1990s and did not begin to decrease until the 2000s; among Black females aged 55–64, mortality from HIV/AIDS did not begin to decline until the 2010s. By 2015–2017, mortality from HIV/AIDS among White and Hispanic adults was sufficiently low that continued progress in reducing it would not have substantially affected future mortality trends. In contrast, mortality from HIV/AIDS remained high among working-age Black adults in 2015–2017; therefore, efforts to address this cause of death in this population could affect future mortality trends, as well as mortality disparities between Blacks and Whites. Although homicide rates decreased substantially in the 1990s, especially among Black and Hispanic males, progress slowed in the 2000s. By the 2010s, most groups had experienced at least a small increase in the homicide rate; the increases were particularly large among younger working-age Black males. In contrast to other leading causes of death, progress on lung and other nonliver cancers continued into the 2010s, although possibly at a slower rate.                                                         Although reductions in mortality ceased for the category of ischemic heart disease and other circulatory 9 diseases as a whole, some causes of death continued to decrease during this period, though at an attenuated rate. 4-24 Prepublication copy, uncorrected proofs

FIGURE 4-1 Decomposition of changes in cause-specific mortality rates (deaths per 100,000 population) by time period: Males. LEGEND: NOTE: The decomposition of the total change in cause-specific mortality rates between 1990 and 2017 is shown for three periods corresponding roughly to the changes in mortality within the 1990s (1990–1993 to 2000–2002), 2000s (2000–2002 to 2009–2011), and 2010s (2009–2011 to 2015–2017) for males aged 25–64. Each decomposition is shown separately for White (top row), Black (middle row), and Hispanic (bottom row) males in each of three age groups (25–44 [left column], 45–54 [middle column], and 55–64 [right column]). The green bars represent declines in mortality (dark green = decline in the 1990s, medium green = decline in the 2000s, and light green = decline in the 2010s), while the red bars represent increases in mortality (dark red = increase in the 1990s, medium red = increase in the 2000s, pink = increase in the 2010s). Readers should be mindful that the x-axis differs across panels. The causes of death shown are exhaustive of all underlying cause-of-death codes and are based on the International Classification of Diseases (ICD)-9 (1990–1998) and ICD-10 (1999–2017) codes. Mortality rates within each age group are age-adjusted by single-year of age to match the age distribution of the U.S. population in 2000 in order to improve comparability over time. More information about the classification of causes of death can be found in Chapter 5. ENM = endocrine, nutritional, and metabolic diseases. SOURCE: Data from: https://www.cdc.gov/nchs/nvss/nvss-restricted-data.htm. 4-25 Prepublication copy, uncorrected proofs

The second main finding is that mortality rates increased among multiple demographic groups across a wide range of causes. These causes included ENM diseases, hypertensive heart disease, drug poisoning, alcohol-induced causes, mental and behavioral disorders, suicide, and diseases of the nervous system. Some of these causes increased throughout the entire period (1990–1993 to 2015–2017), whereas other causes increased only recently (in the 2010s). For example, mortality from diseases of the nervous system increased in all three periods among most groups, although these increases were generally small among younger working-age adults (aged 25–44). The exception was younger Black males, among whom mortality from diseases of the nervous system decreased slightly in the 1990s and 2000s before increasing in the 2010s. The timing of the increases in mortality from the two cardiometabolic diseases— hypertensive heart disease and ENM diseases—differed between older and younger working-age adults. Mortality for both increased in all three periods among younger working-age adults. Although older working-age adults saw increases in mortality from ENM diseases in the 1990s and 2010s, they also experienced much larger reductions in between (in the 2000s) that were often large enough to offset the much smaller mortality increases in both the earlier and later periods. Mortality from hypertensive heart disease increased in all three periods among older working-age (aged 45–64) White males and females and Hispanic males, but did not start to rise until the 2000s among older Black males, Black females aged 45–54, and Hispanic females aged 45–54. Black and Hispanic females aged 55–64 continued to experience reductions in mortality from hypertensive heart disease until the 2010s, during which it increased. As noted earlier, previous studies have considered mortality from drug poisoning, alcohol-induced causes, and suicide together as a group. However, the timing of the increases in these causes of death differed. Increases occurred in drug poisoning mortality in all three periods among White males and females and Hispanic females, but only White males aged 45–54 also saw concurrent increases in mortality from both alcohol-induced causes and suicide. White females aged 25–44 experienced increasing mortality from alcohol-induced causes in all three periods, their suicide rates did not increase until the 2000s. Neither mortality due to alcohol- induced causes nor suicide rates increased until the 2000s among other working-age White adults, and suicide rates remained flat among Hispanic females in all three periods. Mortality from drug poisoning also increased in each period among older working-age (aged 45–64) Black males and females and older working-age Hispanic males, although none of these groups experienced an increase in mortality from alcohol-induced causes or suicide. The exception was Hispanic males aged 55–64, who saw a small increase in alcohol-induced mortality in the 2010s. In fact, alcohol-induced mortality decreased among Hispanic males in the 1990s and 2000s. Among Black males aged 45–54, mortality from drug poisoning increased in the 1990s but fell in the 2000s before sharply increasing again in the 2010s, while mortality from alcohol-induced causes decreased in each period, and suicide rates decreased in the 1990s and 2000s. Mortality due to drug poisoning and suicide did not increase among younger Black adults and younger Hispanic males (aged 25–44) until the 2010s, except among younger Black females, who saw no change in suicide rates. Mortality from alcohol-induced causes remained flat throughout the period among these younger working-age adults. 4-26 Prepublication copy, uncorrected proofs

FIGURE 4-2 Decomposition of change in cause-specific mortality rates (deaths per 100,000 population) by time period: Females. LEGEND: 4-27 Prepublication copy, uncorrected proofs

NOTE: The decomposition of the total change in cause-specific mortality rates between 1990 and 2017 is shown for three periods corresponding roughly to the changes in mortality within the 1990s (1990–1993 to 2000–2002), 2000s (2000–2002 to 2009–2011), and 2010s (2009–2011 to 2015–2017) for males aged 25–64. Each decomposition is shown separately for White (top row), Black (middle row), and Hispanic (bottom row) males in each of three age groups (25–44 [left column], 45–54 [middle column], and 55–64 [right column]). The green bars represent declines in mortality (dark green = decline in the 1990s, medium green = decline in the 2000s, and light green = decline in the 2010s), while the red bars represent increases in mortality (dark red = increase in the 1990s, medium red = increase in the 2000s, pink = increase in the 2010s). Readers should be mindful that the x-axis differs across panels. The causes of death shown are exhaustive of all underlying cause-of-death codes and are based on the International Classification of Diseases (ICD)-9 (1990–1998) and ICD-10 (1999–2017) codes. Mortality rates within each age group are age-adjusted by single-year of age to match the age distribution of the U.S. population in 2000 in order to improve comparability over time. More information about the classification of causes of death can be found in Chapter 5. ENM = endocrine, nutritional, and metabolic diseases. SOURCE: Data from: https://www.cdc.gov/nchs/nvss/nvss-restricted-data.htm. Taken together, the differing trends in mortality for each of these three causes of death (drug poisoning, alcohol-induced causes, and suicide) suggest that there are limitations to considering these causes of death together, particularly when one is examining younger, female, and non-White working-age adults. Drug poisoning was by far the largest contributor to the overall increase in mortality for most working-age adults during the period, but the comparisons in Figures 4-1 and 4-2 demonstrate, importantly, that the timing of the increase in mortality from drug poisoning (the largest contributor to the overall increase in all-cause mortality for several groups) varied by sex, race/ethnicity, and age group. SUMMARY The recent trends in all-cause mortality among working-age adults are the result of the confluence of two important trends: (1) rising mortality from drug poisoning and other causes of death, such as nervous system diseases, hypertensive heart disease, and ENM diseases; and (2) slower progress in lowering mortality from heart diseases and other leading causes of death that drove improvements in all-cause mortality rates in prior decades. Table 4-4 summarizes the findings for each of the 20 causes of death considered in this chapter, showing how each contributed to changes in mortality over the period by age group, sex, and race/ethnicity. Subsequent chapters examine in greater detail the trends in the key causes of death that have driven the recent increases in mortality among working-age adults, either through increasing mortality or through a reduction or reversal of progress in reducing mortality in the most recent period. These trends are used to assess how consistent the prevailing explanations for recent increases in mortality in the research literature are with these cause-specific mortality trends. Based on the findings presented in this chapter, the key drivers of the increases in working-age mortality since 2010 are grouped into three categories, each of which is addressed in detail in Part II of this report. The first category is drug poisoning and alcohol-induced causes (Chapter 7). In addition to mortality from drug poisoning and alcohol-induced causes, this category also includes mortality due to mental and behavioral disorders, which often involve drugs or alcohol (see Figure 4-3). The second category includes suicides that do not involve drug poisoning (Chapter 8). The third is mortality due to cardiometabolic diseases, which include ENM diseases, hypertensive heart disease, and ischemic heart disease and other circulatory diseases. The results presented in Table 4-4 indicate that in addition to these key causes of death, several other causes—including infectious and parasitic diseases other than HIV/AIDS, liver 4-28 Prepublication copy, uncorrected proofs

cancer, diseases of the nervous system, transport accidents, and homicide—also contributed to rising mortality over the period. TABLE 4-4 Summary of Findings: Cause-Specific Mortality among Working-Age Adults, 1990–2017 Ages 25–44 Ages 45–54 Ages 55–64 Males Females Males Females Males Females Hispanic Hispanic Hispanic Hispanic Hispanic Hispanic White White White White White White Black Black Black Black Black Black Infectious and Parasitic Diseases HIV/AIDS Non-HIV/AIDS Cancers Liver Cancer Lung Cancer All Other Cancers Cardio and Metabolic Diseases Endocrine, Nutritional, & Metabolic Hypertensive Heart Disease Ischemic & Other Circulatory System Substance Use & Mental Health Drug Poisoning Alcohol-Induced* Suicide Mental & Behavioral Disorders Other Body System Diseases Nervous System Genitourinary System Respiratory System Digestive System* Other Causes of Death Homicide Transport Accidents Other External Causes All Other Causes Significant contributor to decreasing LEGEND: Significant contributor to rising mortality mortality Minor contributor to rising mortality Minor contributor to decreasing mortality Mortality is unchanged Progress has stagnated or reversed *Changes in the International Classification of Diseases (ICD)-10 code for diseases of the digestive system in 2006 affected the comparability of both digestive system deaths and alcohol-induced deaths before and after that year. More information is provided in Chapter 5. SOURCE: Data from: https://www.cdc.gov/nchs/nvss/nvss-restricted-data.htm. 4-29 Prepublication copy, uncorrected proofs

The results presented in this chapter demonstrate that drug poisoning mortality rose throughout the study period and was the single largest contributor to the overall increases in mortality among working-age adults, except older (aged 45–64) Hispanics. The largest increases during the period occurred among White adults, particularly White males and older Black males. Among working-age Whites, increases in mortality due to drug poisoning were largest among younger males (aged 25–44), those with a high school degree or less, and those living in large metropolitan areas. In contrast, among Black adults, the largest increases in mortality occurred among older males (aged 55–64) in large central metros, but there was no difference in drug poisoning mortality by educational attainment. Alcohol-induced mortality also increased among working-age Whites throughout the period, while increases among Black and Hispanic adults did not begin until the 2010s. Mortality from alcohol-induced causes declined among working-age Black and Hispanic males throughout the 1990s and early 2000s, but these declines leveled off during the 2000s and began to increase in the 2010s. Moreover, the increases in alcohol-induced mortality among working-age Whites followed different patterns than the increases in mortality from drug poisoning, which could reflect temporal differences in the etiology of these causes of death. Mortality due to alcohol-induced causes increased more among older working-age Whites than among other groups and outside of large central metros. Despite these different trends in drug- and alcohol-induced mortality, there are important reasons to consider the explanations for these trends in concert with each other. For example, Case and Deaton (2015, 2017, 2020) posit that these deaths are the result of an underlying root cause: the erosion of economic and social stability within the White working class has increased physical, emotional, and psychological pain, leading to increases in substance use and mortality, particularly among less-educated White men. Considering these causes of death together allowed the committee to better evaluate the evidence underlying this “deaths of despair” hypothesis. However, a second, more practical, reason to consider these causes of death in parallel is that most substance-induced deaths involve more than one substance. Thus, drug use is often involved in deaths for which the underlying cause is coded as alcohol-induced, and vice versa. As noted earlier and discussed in Chapter 7, most deaths for which the underlying cause of death is classified as a mental or behavioral disorder involve either drug poisoning or alcohol (Figure 4-3). In 1990, more than 70 percent of deaths due to a mental or behavioral disorder were due to alcohol, while nearly 15 percent were due to drug use. Over the 1990s and early 2000s, the percentage of these deaths due to alcohol decreased steadily, reaching a low of 55 percent in 2007. At the same time, the percentage due to drug poisoning increased steadily, reaching 23 percent in 2006. Throughout the period, more than 70 percent of all deaths due to a mental or behavioral disorder were due to either alcohol or drug use. For this reason, the explanations for mortality due to drug poisoning, alcohol-induced causes, and mental and behavioral disorders are discussed together in Chapter 7. 4-30 Prepublication copy, uncorrected proofs

FIGURE 4-3 Percentage of mental and behavioral disorder–related deaths due to alcohol, drugs, and all other causes, ages 25–64, 1990–2017. NOTE: The figure shows the percentage of all deaths for which mental and behavioral disorders are identified as the underlying cause of death and that can be attributed to alcohol use (solid black line), drug use (dashed black line), and any other cause (dotted black line). See Chapter 5 (Table 5–1) for specific International Classification of Diseases (ICD) codes included in each category. SOURCE: Data from CDC WONDER (2020b) https://wonder.cdc.gov/ucd-icd10.html The second key driver of mortality evaluated by the committee in detail is suicide. Arguments can be made for examining suicide alongside mortality due to drugs and alcohol. For one, it can be difficult for medical examiners to distinguish between accidental and intentional drug poisoning, leading some suicides to be misclassified as accidental poisoning and vice versa. However, the committee sidestepped this classification problem by categorizing all mortality due to drug poisoning, both intentional and accidental, as drug poisoning. Moreover, the underlying trends for suicide differ in important ways from those for drug poisoning and alcohol-induced mortality. Unlike increased mortality due to drug poisoning, increases in suicide deaths occurred primarily among working-age Whites, particularly White men. Among White adults, suicide rates were highest in nonmetros and lowest in large central metros—whereas the largest increases in mortality from drug poisoning were within large central metros—and were higher among older (aged 45–64) White adults compared with their younger counterparts. These differences between the trends in suicide and in drug poisoning deaths suggest that the explanations for the two causes may differ. Potential explanations for suicide trends are therefore evaluated separately in Chapter 8. The final category of causes of death evaluated by the committee in detail is mortality due to cardiometabolic diseases. This category encompasses two causes of death that increased among most working-age adults over the study period (hypertensive heart disease and ENM diseases), as well as a cause of death that had previously seen dramatic improvements but on which progress stalled or reversed (the combined category of ischemic heart disease and other circulatory diseases). Although the overall trends in mortality for the three cardiometabolic 4-31 Prepublication copy, uncorrected proofs

causes of death differ in direction, all experienced a common slowdown or reversal of progress in reducing mortality, and there is reason to suspect that they share an underlying proximate cause, such as obesity, that justifies examining them together. Mortality due to hypertensive heart disease and ENM diseases increased among most working-age males and White females. These increases were larger outside of large central metros, particularly among White males and females, contributing to the growing mortality gap between large central metros and less-populated areas. As discussed at length in Chapter 9, although mortality due to the combined category of ischemic heart disease and other circulatory diseases declined dramatically overall during the study period among working-age adults, these gains slowed and, in some cases, reversed in the 2010s. Even among those working-age adults for whom mortality from this cause continued to decrease, such as Black females, it decreased at a slower rate in that period, and it began to increase among many younger (aged 25–44) adults and older (aged 45–64) White females. Trends in metropolitan areas differed by race/ethnicity, but generally contributed to mortality gaps by metropolitan status. Working-age Whites in large central metros continued to see reductions in mortality due to ischemic heart disease and other circulatory diseases, while those in nonmetros were most likely to experience increasing mortality from this set of causes. The combination of these trends contributed to an expanding mortality gap between large central metros and nonmetros among White adults. In contrast, older Black and Hispanic adults in nonmetros experienced larger reductions in mortality relative to those in more populous areas. As noted above, other causes of death—including infectious and parasitic diseases (excluding HIV/AIDS), liver cancer, diseases of the nervous system, transport accidents, and homicide—contributed to increasing working-age mortality during the 1990–2017 period. Although these other causes of death are not addressed in detail in this report, they do merit attention. The committee therefore included detailed tables with cause-specific trends for these causes of death in Appendix A. Although some of these other causes of death did not, on their own, contribute meaningfully to the recent alarming increases in mortality, the results presented in Tables 4-1 to 4-3 demonstrate that their combined influence on working-age mortality trends was not trivial. Moreover, important details about deaths from certain causes shed light on their potential role, or lack thereof, in explaining increases in working-age mortality over the 1990–2017 period or ongoing racial/ethnic disparities in mortality. For example, mortality rates for HIV/AIDS, as well as other infectious and parasitic diseases, increased predominantly in the 1990s and subsequently fell; therefore, they do not help explain the current rise in working-age mortality, although the delayed progress in reducing mortality from HIV/AIDS among older working-age Black males and females has contributed to continuing racial/ethnic disparities in mortality. In a similar vein, mortality due to transport accidents and homicides decreased overall between 1990 and 2017, primarily as a result of large reductions during the 1990s. In the 2010s, however, these gains began to reverse, particularly among younger Black and Hispanic working- age males, who otherwise experienced decreases in overall mortality during this period. Overall, neither transport accidents nor homicides were a significant contributor to the recent increase in mortality among working-age White males and females, but like the slower progress in reducing mortality from HIV/AIDS among older Black males and females compared with Whites, these causes of death contributed to mortality disparities between younger Black and White males. The reasons for these recent changes in transport accidents and homicides are not well understood. Research suggests that a recent increase in fatal police shootings is a leading cause of homicide 4-32 Prepublication copy, uncorrected proofs

among young Black males (Edwards, Lee, and Esposito, 2019), but inconsistency across states in data collection on these shootings makes it difficult to assess whether this increase can explain the rise in homicides among younger Black and Hispanic males. Mortality due to nervous system diseases increased among working-age adults regardless of age, sex, and race/ethnicity, although these increases were often very small. Recent studies have noted that similar increases in mortality due to nervous system diseases occurred internationally (Pritchard et al., 2017), but the committee is not aware of research offering an explanation for this trend. The increase in deaths from neurologic diseases among the elderly is an expected outcome of an aging population, but reasons for the increase among working-age adults, before age 65, are less clear. Many of the cause-of death categories included in this report are broadly defined, often by the body system affected, and encompass a wide range of diseases and disorders. For example, mortality from ischemic heart disease and other circulatory system diseases was examined as a combined group, but “other circulatory system diseases” encompassed all circulatory system diseases besides ischemic heart disease and hypertensive heart disease, including arrhythmias, cardiomyopathy, heart failure, cardiac arrest, stroke, intracerebral hemorrhage, and pulmonary embolism. Because the committee’s purpose was to identify the key drivers of recent changes in working-age mortality rather than to fully explore recent changes in all causes of death, this report focuses on mortality trends for entire body systems, such as the nervous, genitourinary, respiratory, and digestive systems, without detailing more pronounced increases in mortality from specific diseases within these body systems. However, readers should note that within each of the broad cause-of-death categories, there may be heterogeneity in the magnitude—and sometimes the direction—of the changes in cause-specific mortality that occurred between 1990 and 2017, particularly for rare causes of death that result in only a small number of deaths per year among working-age adults. It will be important for future research to seek explanations for the increase in working- age mortality across these conditions. To some extent, increased death rates in working age may be coincidental and reflect independent causal pathways. For example, increases in working-age mortality from cerebral palsy may reflect medical advances that have enabled children with these conditions to survive into adulthood (Woolf et al., 2018). Increased cellphone use could contribute to the increase in transport injuries but would not explain deaths from chronic diseases. Another possibility is that some increases in working-age mortality may be secondary to the primary causes this report examines—drugs, alcohol, suicide, and cardiometabolic diseases. Deaths from other causes that stem from these primary causes might be considered “collateral” deaths. Mortality due to liver cancer, for example, increased among older working-age adults (aged 45–64) regardless of race/ethnicity. This increase could potentially have resulted from several underlying causes, including increasing alcohol and drug use, as well as viral hepatitis, diabetes, and non-alcohol-induced fatty liver disease. This complexity in potential etiology complicates any attempt to use the trends in liver cancer to evaluate potential explanations for the increase in alcohol- and drug-related deaths. However, to the extent that the recent increases in mortality due to liver cancer are linked to drug and alcohol use or diabetes, the explanations for these trends in Chapters 7 and 9, respectively, may be relevant. This “collateral” mortality effect could also have contributed to changes in more detailed causes of death contained within the 20 broad cause-of-death categories examined in this chapter. For example, increased use of injection drugs could explain not only overdose deaths 4-33 Prepublication copy, uncorrected proofs

but also increases in deaths from viral hepatitis, infectious valvular heart diseases, and other drug-related complications. Likewise, alcohol use can increase an individual’s risk of death from atrial fibrillation and other arrhythmias, transport accidents, and other causes for which working- age mortality has increased. People who initially survive a suicide attempt may die in the hospital from secondary complications. And obesity and other contributors to deaths from cardiometabolic diseases could help explain increased mortality from renal failure. It is difficult, however, to identify all of the detailed causes of death that could potentially be considered collateral consequences of the larger trends in substance use, suicide, and cardiometabolic diseases. In addition, because death is the result of complex processes that unfold over the life course, trends in mortality are rarely so simply explained. Despite these complications, the evidence gaps noted above and the loss of life involved provide a strong argument for a research agenda to seek the underlying explanations for the large number of causes of death for which mortality has been increasing. Of necessity, the next chapters focus on the main drivers of increasing working-age mortality—drugs, alcohol, suicide, and cardiometabolic diseases—but the committee encourages the research community to continue the work of exploring the explanations underlying increases in working-age mortality due to the range of other causes of death identified in this report. 4-34 Prepublication copy, uncorrected proofs

ANNEX 4-1 Trends in Cause-Specific Mortality among American Indians and Alaskan Natives The American Indian/Alaska Native (AI/AN) population has the highest mortality rates for more causes of death of all racial/ethnic groups. Epsey and colleagues (2014) (reproduced in Sancar et al., 2017) present leading causes of death for 1999–2009 among AI/ANs living in 637 Contract Health Service Delivery Areas (CHSDAs). These data were taken from death certificates, corrected for misclassification of AI/AN identity and from National Vital Statistics Reports for 2017 for the entire United States, without such correction. Annex Figure 4-1 presents the leading causes of death for the CHDSA counties in 1999–2009. AI/AN individuals are more likely to die from diabetes, chronic liver disease, and suicide than are Whites, and also more likely to die from these causes than are non-Hispanic Blacks and Hispanics. 4-35 Prepublication copy, uncorrected proofs

ANNEX FIGURE 4-1 Leading causes of death in Contract Health Service Delivery Area (CHDSA) counties in 1999–2009. DATA SOURCE: Espey et al., 2014. 4-36 Prepublication copy, uncorrected proofs

Cause-Specific Mortality Trends by Metropolitan Area Status ANNEX TABLE 4-1 Absolute Change in Cause-Specific Mortality and Percentage of Total Increase or Decrease in Mortality by Size of Metropolitan Area, 1990–1993 to 2015–2017: Non-Hispanic White Adults MALES Ages 25–44 Ages 45–64 Large Central Large Fringe Small or Large Central Large Fringe Small or Medium Metro Metro Medium Metro Non-Metro Metro Metro Metro Non-Metro All-Cause Mortality Rate 1990–1993 224.09 196.33 195.06 206.06 838.81 830.48 865.54 878.35 All-Cause Mortality Rate 2015–2017 198.33 238.70 236.00 267.70 643.75 767.65 812.83 872.60 Change 1990–1993 to 2015–2017 –25.76 42.37 40.94 61.63 –195.06 –62.83 –52.71 –5.75 (Change as % of 1990–1993 mortality) –11.50 21.58 20.99 29.91 –23.25 –7.57 –6.09 –0.65 % of % of % of % of % of % of % of % of Total Total Total Total Total Total Total Total Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Cause of death Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Infectious and Parasitic Diseases – – HIV/AIDS –51.60 –57.9 –23.30 –55.5 16.18 –44.9 10.39 –41.1 –27.71 –9.2 –8.42 –3.8 –5.14 –2.4 –3.09 –1.7 Non-HIV/AIDS –2.36 –2.6 0.13 0.1 0.63 0.8 1.58 1.8 6.20 5.8 12.20 7.6 12.17 7.5 14.61 8.4 Cancers Liver Cancer 0.00 0.0 –0.02 0.0 0.18 0.2 0.11 0.1 6.72 6.3 10.02 6.2 9.62 5.9 9.75 5.6 Lung Cancer –2.88 –3.2 –2.55 –6.1 –2.62 –7.3 –2.44 –9.7 –66.59 –22.1 –58.74 –26.3 –61.14 –28.5 –51.07 –28.4 All Other Cancers –7.48 –8.4 –5.33 –12.7 –4.36 –12.1 –3.07 –12.1 –46.97 –15.6 –27.35 –12.2 –22.27 –10.4 –12.66 –7.0 Cardio and Metabolic Diseases Endocrine, Nutritional, & Metabolic 0.24 0.4 3.02 3.6 3.33 4.3 4.53 5.2 9.51 8.9 16.72 10.4 17.55 10.8 21.87 12.6 Hypertensive Heart Disease 2.35 3.7 3.32 3.9 2.73 3.6 3.43 3.9 11.08 10.4 15.28 9.5 14.79 9.1 15.51 8.9 – – – – Ischemic & Other Circulatory System –9.09 –10.2 –5.28 –12.6 –4.12 –11.4 0.42 0.5 146.78 –48.7 126.26 –56.5 124.69 –58.0 112.26 –62.4 Substance Use and Mental Health Drug Poisoning 54.32 85.6 58.84 69.7 46.76 60.7 46.21 53.1 40.15 37.8 42.73 26.6 32.55 20.1 30.68 17.6 Alcohol-Induced * –0.74 –0.8 1.40 1.7 1.91 2.5 1.81 2.1 4.05 3.8 9.82 6.1 11.05 6.8 9.09 5.2 Suicide 4.99 7.9 12.29 14.6 12.73 16.5 16.16 18.6 8.74 8.2 12.04 7.5 14.11 8.7 14.56 8.4 Mental & Behavioral Disorders 0.91 1.4 1.66 2.0 2.43 3.2 1.80 2.1 5.93 5.6 9.53 5.9 10.64 6.6 6.23 3.6 Other Body System Diseases Nervous System 0.63 1.0 2.14 2.5 2.20 2.9 2.41 2.8 6.17 5.8 8.97 5.6 10.37 6.4 10.13 5.8 Genitourinary System –0.13 –0.1 0.48 0.6 0.74 1.0 0.96 1.1 2.30 2.2 4.11 2.6 4.90 3.0 6.27 3.6 4-37 Prepublication copy, uncorrected proofs

Respiratory System –1.49 –1.7 0.34 0.4 0.98 1.3 1.93 2.2 –6.21 –2.1 2.36 1.5 2.41 1.5 9.87 5.7 Digestive System * –2.15 –2.4 –0.06 –0.2 0.10 0.1 1.55 1.8 –1.14 –0.4 6.56 4.1 9.83 6.1 12.49 7.2 Other Causes of Death Homicide –4.01 –4.5 –1.64 –3.9 –0.53 –1.5 –1.40 –5.5 –3.00 –1.0 –0.92 –0.4 –1.64 –0.8 –0.86 –0.5 Transport Injuries –5.05 –5.7 –3.84 –9.1 –6.70 –18.6 –5.52 –21.8 0.85 0.8 3.40 2.1 4.29 2.6 5.03 2.9 Other External Causes of Death –1.30 –1.5 0.25 0.3 –1.54 –4.3 –2.47 –9.8 4.59 4.3 6.72 4.2 5.56 3.4 4.94 2.8 All Other Causes of Death –0.90 –1.0 0.52 0.6 2.28 3.0 4.05 4.7 –2.94 –1.0 –1.60 –0.7 2.33 1.4 3.17 1.8 Total Change: Increase (+) 63.43 84.39 76.99 86.94 106.29 160.47 162.17 174.20 – – – – – – Total Change: Decrease (+) –89.19 –42.01 36.05 25.31 301.35 223.29 214.88 179.94 FEMALES Ages 25–44 Ages 45–64 Large Central Large Fringe Small or Medium Large Central Large Fringe Small or Medium Metro Metro Metro Non-Metro Metro Metro Metro Non–Metro All-Cause Mortality Rate 1990–1993 87.28 87.77 90.17 94.04 483.81 474.45 490.11 485.17 All-Cause Mortality Rate 2015–2017 103.91 132.37 132.61 156.66 396.31 471.08 503.41 557.48 Change 1990–1993 to 2015–2017 16.63 44.60 42.43 62.63 –87.50 –3.37 13.29 72.31 (Change as % of 1990–1993 mortality) 19.05 50.81 47.06 66.60 –18.08 –0.71 2.71 14.90 % of % of % of % of % of % of % of % of Total Total Total Total Total Total Total Tota Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs l +/– Cause of death Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Infectious and Parasitic Diseases HIV/AIDS –2.70 –14.7 –1.18 –10.6 –0.90 –7.6 –0.43 –6.1 –0.69 –0.5 –0.24 –0.2 –0.08 –0.1 0.13 0.1 Non-HIV/AIDS 0.41 1.2 1.20 2.2 1.42 2.6 2.58 3.7 5.08 8.4 7.43 7.4 8.66 7.8 10.59 7.8 Cancers Liver Cancer 0.13 0.4 0.25 0.4 0.08 0.2 0.10 0.1 1.77 2.9 1.96 2.0 2.23 2.0 2.32 1.7 Lung Cancer –1.98 –10.8 –1.52 –13.7 –1.02 –8.5 –0.72 –10.1 –31.63 –21.4 –20.18 –19.5 –17.77 –18.3 –5.75 –9.1 – All Other Cancers –8.72 –47.5 –6.37 –57.3 –7.59 –63.5 –5.66 –79.9 –62.00 –41.9 –45.07 –43.5 –46.05 –47.3 –33.41 53.0 Cardio and Metabolic Diseases Endocrine, Nutritional, & Metabolic 0.84 2.4 2.06 3.7 2.15 4.0 4.51 6.5 1.61 2.6 5.19 5.2 6.75 6.1 9.92 7.3 Hypertensive Heart Disease 0.95 2.7 1.54 2.8 1.57 2.9 1.98 2.8 4.66 7.7 6.68 6.7 6.55 5.9 8.07 6.0 – Ischemic & Other Circulatory System –1.30 –7.1 1.95 3.5 3.20 5.9 6.77 9.7 –50.49 –34.1 –36.65 –35.4 –32.76 –33.7 –23.66 37.6 Substance Use and Mental Health 4-38 Prepublication copy, uncorrected proofs

Drug Poisoning 24.73 70.7 30.63 55.0 25.58 47.0 27.23 39.1 23.64 39.0 27.91 27.8 25.61 23.2 26.92 19.9 Alcohol-Induced * 0.94 2.7 2.12 3.8 2.35 4.3 2.09 3.0 4.68 7.7 7.20 7.2 7.73 7.0 6.58 4.9 Suicide 2.24 6.4 4.48 8.0 4.18 7.7 4.06 5.8 2.42 4.0 3.86 3.9 3.73 3.4 4.26 3.1 Mental & Behavioral Disorders 1.53 4.4 2.25 4.0 2.32 4.3 2.39 3.4 3.90 6.4 4.58 4.6 5.09 4.6 4.77 3.5 Other Body System Diseases Nervous System 0.53 1.5 1.43 2.6 2.06 3.8 2.29 3.3 4.84 8.0 7.53 7.5 8.37 7.6 9.19 6.8 Genitourinary System 0.20 0.6 0.64 1.1 0.34 0.6 1.18 1.7 1.48 2.4 3.55 3.5 4.69 4.2 5.12 3.8 Respiratory System 0.09 0.3 1.48 2.7 2.07 3.8 3.41 4.9 –0.71 –0.5 9.24 9.2 13.49 12.2 23.42 17.3 Digestive System * 0.34 1.0 1.59 2.9 1.66 3.1 2.60 3.7 0.95 1.6 6.10 6.1 7.45 6.7 11.09 8.2 Other Causes of Death Homicide –1.42 –7.7 –0.76 –6.9 –1.07 –8.9 –0.28 –3.9 –0.63 –0.4 –0.52 –0.5 –0.28 –0.3 –0.16 –0.3 Transport Injuries –2.25 –12.2 –1.28 –11.5 –1.37 –11.4 1.17 1.7 –1.92 –1.3 –0.90 –0.9 –0.35 –0.4 0.35 0.3 Other External Causes of Death 0.97 2.8 1.50 2.7 1.61 3.0 1.81 2.6 3.32 5.5 4.40 4.4 4.52 4.1 5.05 3.7 All Other Causes of Death 1.10 3.2 2.61 4.7 3.78 6.9 5.54 7.9 2.23 3.7 4.58 4.6 5.71 5.2 7.49 5.5 Total Change: Increase (+) 35.01 55.71 54.38 69.70 60.58 100.20 110.58 135.28 – – Total Change: Decrease (+) –18.38 –11.12 –11.95 –7.08 148.08 103.57 –97.28 –62.98 *Changes in the International Classification of Diseases (ICD)-10 code for diseases of the digestive system in 2006 affected the comparability of both digestive system deaths and alcohol-induced deaths before and after that year. More information is provided in Chapter 5. LEGEND: The top 3 causes of death for each age group in each period are highlighted in bolded red text. Light orange highlights indicate an absolute increase in the overall mortality rate of ≥5 deaths/100,000 population. Dark orange highlights indicate that a cause of death is responsible for ≥10 percent of the total increase in mortality. Light green highlights indicate an absolute decrease in the overall mortality rate of ≥5 deaths/100,000 population. Dark green highlights indicate that a cause of death is responsible for ≥10 percent of the total decrease in mortality. NOTE: The table shows the change in all-cause and cause-specific mortality rates among non-Hispanic White working-age males (upper table) and females (lower table) by age group (25–44 and 45–64) and size of metropolitan area (large central metropolitan area, large fringe metropolitan area, small/medium metropolitan area, and nonmetropolitan area). These causes of death are exhaustive of all underlying cause-of-death codes and are based on the International Classification of Diseases (ICD)-9 (1990–1998) and ICD-10 (1999–2017) codes. Mortality rates within each age group are age-adjusted by single-year of age to match the age distribution of the U.S. population in 2000 in order to improve comparability over time. More information about the classification of causes of death can be found in Chapter 5. SOURCE: Data from: https://www.cdc.gov/nchs/nvss/nvss-restricted-data.htm.   4-39 Prepublication copy, uncorrected proofs

ANNEX TABLE 4-2 Absolute Change in Cause-Specific Mortality and Percentage of Total Increase or Decrease in Mortality by Size of Metropolitan Area, 1990–1993 to 2015–2017: Non-Hispanic Black Adults MALES Ages 25–44 Ages 45–64 Large Central Large Fringe Small or Medium Large Central Large Fringe Small or Medium Metro Metro Metro Non-Metro Metro Metro Metro Non-Metro All-Cause Mortality Rate 1990–1993 642.70 477.67 430.49 466.44 1728.58 1622.77 1717.77 1809.05 All-Cause Mortality Rate 2015–2017 314.95 336.96 323.99 316.37 1033.27 1128.13 1176.07 1255.89 Change 1990–1993 to 2015–2017 –327.75 –140.71 –106.50 –150.07 –695.31 –494.64 –541.70 –553.16 (Change as % of 1990–1993 mortality) –51.00 –29.46 –24.74 –32.17 –40.22 –30.48 –31.53 –30.58 % of % of % of % of % of % of % of % of Total Total Total Total Total Total Total Total Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Cause of death Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Infectious and Parasitic Diseases – HIV/AIDS 162.04 –47.2 –81.50 –45.7 –45.50 –30.4 –39.25 –22.1 –77.72 –10.1 –26.20 –4.3 –10.06 –1.6 –7.98 –1.2 Non-HIV/AIDS –12.25 –3.6 –4.90 –2.7 –2.80 –1.9 –0.96 –0.5 –4.33 –0.6 12.25 11.2 8.95 10.4 14.35 14.9 Cancers Liver Cancer –0.55 –0.2 –1.18 –0.7 –0.23 –0.2 –0.53 –0.3 9.88 13.9 18.67 17.0 12.89 14.9 12.74 13.2 – – – – Lung Cancer –8.09 –2.4 –7.39 –4.1 –6.04 –4.0 –8.52 –4.8 134.27 –17.5 124.09 –20.5 131.94 –21.0 117.10 –18.0 – – All Other Cancers –14.93 –4.3 –13.49 –7.6 –11.47 –7.7 –13.93 –7.9 111.57 –14.6 –94.25 –15.6 108.05 –17.2 –83.64 –12.9 Cardio and Metabolic Diseases Endocrine, Nutritional, & Metabolic 0.38 2.4 4.81 12.8 10.49 24.3 6.26 22.9 3.58 5.1 13.13 12.0 5.77 6.7 17.77 18.4 Hypertensive Heart Disease 4.18 26.6 7.13 19.0 5.95 13.8 6.00 22.0 1.28 1.8 10.33 9.4 10.95 12.7 14.99 15.5 – – – – Ischemic & Other Circulatory System –28.35 –8.3 –17.41 –9.8 –20.47 –13.7 –30.82 –17.4 256.29 –33.5 235.33 –38.9 254.34 –40.5 299.87 –46.2 Substance Use and Mental Health Drug Poisoning 11.05 70.3 22.90 61.1 24.57 57.0 13.34 48.8 50.97 71.9 39.01 35.6 29.02 33.6 19.22 19.9 Alcohol-Induced * –12.07 –3.5 –9.45 –5.3 –8.81 –5.9 –8.91 –5.0 –26.93 –3.5 –18.42 –3.0 –18.61 –3.0 –13.97 –2.1 Suicide –2.03 –0.6 1.09 2.9 –2.70 –1.8 –1.70 –1.0 –2.65 –0.3 –0.44 –0.1 0.44 0.5 –2.83 –0.4 Mental & Behavioral Disorders –12.03 –3.5 –7.93 –4.4 –6.72 –4.5 –8.77 –4.9 –18.97 –2.5 –13.54 –2.2 –15.63 –2.5 –18.73 –2.9 Other Body System Diseases Nervous System 0.10 0.7 1.06 2.8 1.65 3.8 0.65 2.4 5.14 7.2 8.96 8.2 11.32 13.1 8.96 9.3 Genitourinary System –4.49 –1.3 0.50 1.3 0.44 1.0 0.90 3.3 –3.88 –0.5 7.36 6.7 7.14 8.3 8.48 8.8 4-40 Prepublication copy, uncorrected proofs

Respiratory System –13.85 –4.0 –4.84 –2.7 –4.10 –2.7 –4.51 –2.5 –37.46 –4.9 –24.95 –4.1 –15.87 –2.5 –22.45 –3.5 Digestive System * –12.84 –3.7 –7.46 –4.2 –7.59 –5.1 –6.22 –3.5 –27.37 –3.6 –15.86 –2.6 –11.26 –1.8 –9.43 –1.5 Other Causes of Death Homicide –34.09 –9.9 –0.65 –0.4 –10.80 –7.2 –13.36 –7.5 –19.44 –2.5 –9.25 –1.5 –17.15 –2.7 –17.44 –2.7 Transport Injuries –1.40 –0.4 –3.04 –1.7 –4.82 –3.2 –20.26 –11.4 –2.80 –0.4 –3.50 –0.6 –6.62 –1.1 –6.78 –1.0 Other External Causes of Death –10.21 –3.0 –12.44 –7.0 –16.07 –10.7 –19.66 –11.1 –10.85 –1.4 –11.45 –1.9 –15.20 –2.4 –22.70 –3.5 All Other Causes of Death –14.23 –4.1 –6.54 –3.7 –1.49 –1.0 0.16 0.6 –31.65 –4.1 –27.07 –4.5 –23.44 –3.7 –26.77 –4.1 Total Change: Increase (+) 15.71 37.51 43.10 27.32 70.86 109.71 86.48 96.51 – – – – – – – – Total Change: Decrease (+) 343.46 178.21 149.60 177.39 766.17 604.35 628.18 649.68 FEMALES Ages 25–44 Ages 45–64 Large Central Large Fringe Small or Large Central Large Fringe Small or Medium Metro Metro Medium Metro Non-Metro Metro Metro Metro Non-Metro All-Cause Mortality Rate 1990–1993 252.59 218.15 217.28 231.14 919.69 889.80 948.43 951.95 All-Cause Mortality Rate 2015–2017 150.31 180.52 184.40 217.15 640.65 701.81 762.33 805.23 Change 1990–1993 to 2015–2017 –102.28 –37.62 –32.88 –13.99 –279.04 –187.99 –186.10 –146.71 (Change as % of 1990–1993 mortality) –40.49 –17.25 –15.13 –6.05 –30.34 –21.13 –19.62 –15.41 % of % of % of % of % of % of % of % of Total Total Total Total Total Total Total Total Abs +/– Abs +/– Abs +/– Abs +/– +/– +/– +/– Abs +/– Cause of death Chg Chg Chg Chg Chg Chg Chg Chg Abs Chg Chg Abs Chg Chg Abs Chg Chg Chg Chg Infectious and Parasitic Diseases – HIV/AIDS –35.37 –31.4 16.95 –26.6 –7.03 –10.7 –5.16 –10.4 –6.61 –2.1 2.83 5.1 1.67 2.5 4.64 6.5 Non-HIV/AIDS –4.08 –3.6 –2.00 –3.1 –2.31 –3.5 2.95 8.3 1.79 5.5 8.67 15.5 11.32 16.7 11.65 16.4 Cancers Liver Cancer 0.00 0.0 –0.16 –0.3 –0.01 0.0 –0.22 –0.5 3.11 9.6 4.96 8.9 2.19 3.2 2.84 4.0 Lung Cancer –3.55 –3.2 –3.15 –4.9 –3.52 –5.4 –1.97 –4.0 –34.61 –11.1 –23.38 –9.6 –26.96 –10.6 –12.41 –5.7 – – – All Other Cancers –14.26 –12.7 11.25 –17.7 11.10 –16.9 16.42 –33.2 –77.78 –25.0 –62.91 –25.8 –71.53 –28.2 –41.80 –19.2 Cardio and Metabolic Diseases Endocrine, Nutritional, & Metabolic 0.99 9.7 6.51 25.0 8.44 25.9 9.23 26.0 –11.21 –3.6 –12.12 –5.0 –3.65 –1.4 –3.58 –1.6 Hypertensive Heart Disease 1.13 11.1 3.42 13.1 4.21 12.9 3.45 9.7 –6.99 –2.2 2.71 4.9 –4.48 –1.8 2.93 4.1 – – Ischemic & Other Circulatory System –15.89 –14.1 –7.93 –12.4 16.67 –25.5 –7.11 –14.4 –139.59 –44.8 –130.14 –53.4 –127.93 –50.4 145.76 –67.0 4-41 Prepublication copy, uncorrected proofs

Substance Use and Mental Health Drug Poisoning 6.68 65.5 10.37 39.8 10.66 32.7 6.76 19.0 21.16 65.4 15.30 27.3 14.01 20.7 10.15 14.3 Alcohol-Induced * –4.01 –3.6 –3.28 –5.2 –2.61 –4.0 –3.59 –7.3 –4.97 –1.6 –4.50 –1.8 –4.06 –1.6 –3.26 –1.5 Suicide 0.26 2.5 0.68 2.6 0.84 2.6 0.77 2.2 –0.25 –0.1 0.05 0.1 –0.99 –0.4 –0.31 –0.1 Mental & Behavioral Disorders –3.78 –3.4 –2.51 –3.9 –1.93 –2.9 –3.13 –6.3 –1.45 –0.5 –1.99 –0.8 –3.50 –1.4 –0.79 –0.4 Other Body System Diseases Nervous System 1.15 11.2 2.79 10.7 2.46 7.5 2.82 7.9 6.28 19.4 10.19 18.2 10.24 15.1 11.90 16.8 Genitourinary System –0.70 –0.6 1.43 5.5 1.45 4.4 3.66 10.3 –2.33 –0.7 6.43 11.5 8.74 12.9 6.08 8.6 Respiratory System –6.59 –5.9 –1.25 –2.0 –1.97 –3.0 –0.36 –0.7 –5.20 –1.7 1.77 3.2 13.01 19.2 13.47 19.0 Digestive System * –4.74 –4.2 –2.61 –4.1 –2.08 –3.2 –1.42 –2.9 –10.82 –3.5 –5.08 –2.1 –3.72 –1.5 –1.13 –0.5 Other Causes of Death – – Homicide –12.88 –11.5 10.87 –17.1 10.14 –15.5 –8.63 –17.4 –3.59 –1.2 –3.22 –1.3 –1.59 –0.6 –3.14 –1.4 Transport Injuries –1.61 –1.4 –1.04 –1.6 –2.98 –4.5 0.84 2.4 –1.90 –0.6 –0.58 –0.2 –0.76 –0.3 –3.28 –1.5 Other External Causes of Death –1.56 –1.4 –0.69 –1.1 –3.11 –4.8 –1.50 –3.0 –1.23 –0.4 0.60 1.1 –4.67 –1.8 –2.13 –1.0 All Other Causes of Death –3.45 –3.1 0.89 3.4 4.53 13.9 5.03 14.2 –2.84 –0.9 2.43 4.3 6.54 9.7 7.21 10.2 Total Change: Increase (+) 10.20 26.06 32.58 35.51 32.34 55.93 67.72 70.86 – – – – – Total Change: Decrease (+) 112.48 63.69 65.46 49.51 –311.38 –243.92 –253.82 217.58 *Changes in the International Classification of Diseases (ICD)-10 code for diseases of the digestive system in 2006 affected the comparability of both digestive system deaths and alcohol-induced deaths before and after that year. More information is provided in Chapter 5. LEGEND: The top 3 causes of death for each age group in each period are highlighted in bolded red text. Light orange highlights indicate an absolute increase in the overall mortality rate of ≥5 deaths/100,000 population. Dark orange highlights indicate that a cause of death is responsible for ≥10 percent of the total increase in mortality. Light green highlights indicate an absolute decrease in the overall mortality rate of ≥5 deaths/100,000 population. Dark green highlights indicate that a cause of death is responsible for ≥10 percent of the total decrease in mortality. NOTE: The table shows the change in all-cause and cause-specific mortality rates among non-Hispanic White working-age males (upper table) and females (lower table) by age group (25–44 and 45–64) and size of metropolitan area (large central metropolitan area, large fringe metropolitan area, small/medium metropolitan area, and nonmetropolitan area). These causes of death are exhaustive of all underlying cause-of-death codes and are based on the International Classification of Diseases (ICD)-9 (1990–1998) and ICD-10 (1999–2017) codes. Mortality rates within each age group are age-adjusted by single-year of age to match the age distribution of the U.S. population in 2000 in order to improve comparability over time. More information about the classification of causes of death can be found in Chapter 5. SOURCE: Data from: https://www.cdc.gov/nchs/nvss/nvss-restricted-data.htm. 4-42 Prepublication copy, uncorrected proofs

ANNEX TABLE 4-3 Absolute Change in Cause-Specific Mortality and Percentage of Total Increase or Decrease in Mortality by Size of Metropolitan Area, 1990–1993 to 2015–2017: Hispanic Adults MALES Ages 25–44 Ages 45–64 Large Central Large Fringe Small or Medium Large Central Large Fringe Small or Medium Metro Metro Metro Non-Metro Metro Metro Metro Non-Metro All-Cause Mortality Rate 1990–1993 305.04 245.27 220.74 241.11 743.83 731.25 699.50 783.61 All-Cause Mortality Rate 2015–2017 136.69 165.00 156.08 165.45 493.84 604.94 571.72 614.95 Change 1990–1993 to 2015–2017 –168.35 –80.28 –64.67 –75.66 –249.99 –126.30 –127.78 –168.67 (Change as % of 1990–1993 mortality) –55.19 –32.73 –29.30 –31.38 –33.61 –17.27 –18.27 –21.52 % of % of % of % of % of % of % of % of Total Total Total Total Total Total Total Total Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Cause of death Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Infectious and Parasitic Diseases – – – HIV/AIDS –86.08 –48.9 –31.87 –34.9 20.92 –25.6 14.90 –16.2 –54.30 –18.6 10.18 –5.4 –12.18 –6.4 –5.14 –2.2 Non-HIV/AIDS –5.29 –3.0 –1.42 –1.6 –1.35 –1.6 –0.53 –0.6 3.74 8.9 11.34 18.5 11.98 19.2 13.81 21.4 Cancers Liver Cancer –0.39 –0.2 –0.04 0.0 –0.45 –0.5 0.48 3.0 8.21 19.4 12.74 20.8 13.01 20.9 14.16 22.0 – Lung Cancer –1.59 –0.9 –0.48 –0.5 0.16 1.0 –1.64 –1.8 –26.36 –9.0 24.47 –13.0 –24.03 –12.6 –29.55 –12.7 – All Other Cancers –4.04 –2.3 –3.28 –3.6 –3.93 –4.8 –3.98 –4.3 –25.68 –8.8 27.68 –14.7 –22.46 –11.8 –20.00 –8.6 Cardio and Metabolic Diseases Endocrine, Nutritional, & Metabolic 0.32 4.2 0.37 3.3 2.35 13.8 1.09 6.7 4.87 11.5 0.96 1.6 –9.40 –4.9 –0.75 –0.3 Hypertensive Heart Disease 1.36 17.6 1.68 15.1 1.09 6.4 2.30 14.2 4.52 10.7 9.08 14.8 6.66 10.7 6.79 10.5 – – – Ischemic & Other Circulatory System –8.06 –4.6 –5.16 –5.6 –5.65 –6.9 –4.11 –4.5 108.74 –37.2 94.01 –50.1 –83.15 –43.7 131.73 –56.5 Substance Use and Mental Health Drug Poisoning 6.01 78.2 8.44 75.6 8.30 48.6 11.02 68.1 15.14 35.9 18.98 30.9 18.61 29.9 15.29 23.7 Alcohol-Induced * –7.03 –4.0 –5.04 –5.5 –3.80 –4.6 –6.84 –7.4 –14.79 –5.1 –3.21 –1.7 0.41 0.7 –7.06 –3.0 Suicide –1.79 –1.0 –1.47 –1.6 2.68 15.7 –3.01 –3.3 –4.40 –1.5 –0.14 –0.1 –5.33 –2.8 –3.36 –1.4 Mental & Behavioral Disorders –4.49 –2.5 –3.87 –4.2 –4.88 –6.0 –3.32 –3.6 –4.67 –1.6 –4.85 –2.6 1.08 1.7 –3.13 –1.3 Other Body System Diseases Nervous System –0.16 –0.1 0.56 5.0 2.28 13.4 1.07 6.6 3.00 7.1 5.08 8.3 5.99 9.6 4.28 6.6 Genitourinary System –0.51 –0.3 0.12 1.1 0.18 1.1 0.23 1.4 2.39 5.7 1.28 2.1 4.30 6.9 7.70 12.0 Respiratory System –4.02 –2.3 –1.67 –1.8 0.04 0.2 –1.98 –2.2 –10.84 –3.7 –7.04 –3.8 –5.11 –2.7 –3.46 –1.5 Digestive System * –4.97 –2.8 –4.29 –4.7 –1.89 –2.3 –1.82 –2.0 –13.10 –4.5 0.36 0.6 –6.68 –3.5 2.34 3.6 4-43 Prepublication copy, uncorrected proofs

Other Causes of Death – – Homicide –31.86 –18.1 –13.15 –14.4 11.69 –14.3 13.57 –14.8 –17.63 –6.0 –6.02 –3.2 –4.89 –2.6 –8.28 –3.6 – – – Transport Injuries –8.66 –4.9 –15.28 –16.7 22.63 –27.7 25.82 –28.1 –6.93 –2.4 10.01 –5.3 –15.16 –8.0 –18.44 –7.9 – Other External Causes of Death –3.68 –2.1 –2.99 –3.3 –3.75 –4.6 10.32 –11.2 0.35 0.8 –0.06 0.0 –1.65 –0.9 0.03 0.0 All Other Causes of Death –3.42 –1.9 –1.41 –1.5 –0.83 –1.0 –0.03 0.0 –4.78 –1.6 1.55 2.5 0.25 0.4 –2.14 –0.9 Total Change: Increase (+) 7.69 11.16 17.09 16.20 42.23 61.36 62.28 64.39 – – – – – 187.6 – – Total Change: Decrease (+) 176.04 –91.44 81.76 91.85 292.22 7 190.06 233.06 FEMALES Ages 25–44 Ages 45–64 Small or Large Central Large Fringe Medium Large Central Large Fringe Small or Medium Metro Metro Metro Non-Metro Metro Metro Metro Non-Metro All-Cause Mortality Rate 1990–1993 90.29 84.27 86.95 92.35 368.11 402.60 416.57 450.12 All-Cause Mortality Rate 2015–2017 60.57 77.35 77.73 89.30 266.90 327.26 309.09 364.25 Change 1990–1993 to 2015–2017 –29.71 –6.92 –9.22 –3.05 –101.21 –75.33 –107.49 –85.87 (Change as % of 1990–1993 mortality) –32.91 –8.21 –10.60 –3.30 –27.49 –18.71 –25.80 –19.08 % of % of % of % of % of % of % of % of Total Total Total Total Total Total Total Total Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Abs +/– Cause of death Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Chg Infectious and Parasitic Diseases HIV/AIDS –14.03 –41.0 –5.60 –29.0 –2.97 –12.7 –0.95 –4.9 –6.70 –5.9 –0.61 –0.6 –0.59 –0.4 0.21 0.6 Non-HIV/AIDS –1.68 –4.9 0.42 3.4 0.32 2.3 0.63 3.8 0.69 5.8 4.78 16.6 7.52 28.1 4.00 10.9 Cancers Liver Cancer 0.12 2.7 0.11 0.9 –0.08 –0.3 0.14 0.8 1.89 15.8 1.12 3.9 1.49 5.6 2.15 5.9 Lung Cancer –0.49 –1.4 –0.05 –0.3 0.52 3.7 0.29 1.8 –4.42 –3.9 –6.68 –6.4 –6.39 –4.8 –7.15 –5.8 – – – All Other Cancers –3.71 –10.8 –5.46 –28.3 –5.64 –24.0 –7.28 –37.6 29.93 –26.5 28.06 –27.0 –40.93 –30.5 47.70 –39.0 Cardio and Metabolic Diseases – – Endocrine, Nutritional, & Metabolic 0.18 3.9 0.91 7.4 0.78 5.5 0.72 4.4 –3.86 –3.4 10.14 –9.7 –15.25 –11.4 16.33 –13.3 Hypertensive Heart Disease 0.10 2.1 0.51 4.1 0.57 4.0 0.59 3.6 0.27 2.3 2.14 7.5 0.74 2.7 2.19 6.0 – – – Ischemic & Other Circulatory System –3.24 –9.4 –2.74 –14.2 –1.59 –6.8 –2.08 –10.7 51.57 –45.6 52.02 –50.0 –58.10 –43.3 47.75 –39.0 4-44 Prepublication copy, uncorrected proofs

Substance Use and Mental Health Drug Poisoning 3.75 82.8 6.37 51.5 7.23 50.7 7.91 48.5 5.41 45.2 10.36 36.1 8.15 30.4 7.51 20.5 Alcohol-Induced * –0.11 –0.3 0.36 2.9 0.12 0.8 2.28 14.0 –0.28 –0.2 0.64 2.2 2.31 8.6 5.48 15.0 Suicide 0.23 5.0 0.59 4.8 1.31 9.2 1.62 9.9 –0.06 –0.1 1.50 5.2 1.83 6.8 1.18 3.2 Mental & Behavioral Disorders –0.53 –1.5 0.03 0.3 0.41 2.9 –0.51 –2.6 0.52 4.3 0.82 2.9 0.09 0.3 2.55 7.0 Other Body System Diseases Nervous System 0.15 3.4 0.54 4.4 –0.37 –1.6 –0.37 –1.9 2.83 23.6 4.58 16.0 3.56 13.3 5.54 15.1 Genitourinary System –0.05 –0.1 0.12 1.0 0.53 3.7 0.02 0.1 –0.05 0.0 0.71 2.5 –1.03 –0.8 2.57 7.0 Respiratory System –1.83 –5.3 –0.63 –3.3 –1.76 –7.5 –0.18 –0.9 –3.69 –3.3 0.72 2.5 1.10 4.1 0.09 0.2 Digestive System * –0.56 –1.6 0.43 3.5 –0.76 –3.2 0.62 3.8 –4.21 –3.7 –2.45 –2.4 –6.15 –4.6 1.04 2.8 Other Causes of Death Homicide –4.40 –12.9 –1.78 –9.2 –2.33 –9.9 –4.22 –21.8 –2.38 –2.1 –0.59 –0.6 –0.82 –0.6 –0.65 –0.5 Transport Injuries –2.43 –7.1 –3.04 –15.8 –7.90 –33.7 –3.77 –19.5 –3.76 –3.3 –3.49 –3.4 –3.35 –2.5 –2.85 –2.3 Other External Causes of Death –0.20 –0.6 0.18 1.4 –0.07 –0.3 0.06 0.4 0.35 2.9 1.04 3.6 –0.24 –0.2 0.84 2.3 All Other Causes of Death –0.98 –2.9 1.81 14.6 2.47 17.3 1.43 8.8 –2.24 –2.0 0.30 1.0 –1.43 –1.1 1.22 3.3 Total Change: Increase (+) 4.53 12.38 14.26 16.32 11.95 28.70 26.79 36.57 – – – – – – 113.1 104.0 – 122.4 Total Change: Decrease (+) –34.24 19.30 23.48 19.37 6 3 134.28 3 *Changes in the International Classification of Diseases (ICD)-10 code for diseases of the digestive system in 2006 affected the comparability of both digestive system deaths and alcohol-induced deaths before and after that year. More information is provided in Chapter 5. LEGEND: The top 3 causes of death for each age group in each period are highlighted in bolded red text. Light orange highlights indicate an absolute increase in the overall mortality rate of ≥5 deaths/100,000 population. Dark orange highlights indicate that a cause of death is responsible for ≥10 percent of the total increase in mortality. Light green highlights indicate an absolute decrease in the overall mortality rate of ≥5 deaths/100,000 population. Dark green highlights indicate that a cause of death is responsible for ≥10 percent of the total decrease in mortality. NOTE: The table shows the change in all-cause and cause-specific mortality rates among non-Hispanic White working-age males (upper table) and females (lower table) by age group (25–44 and 45–64) and size of metropolitan area (large central metropolitan area, large fringe metropolitan area, small/medium metropolitan area, and nonmetropolitan area). These causes of death are exhaustive of all underlying cause-of-death codes and are based on the International Classification of Diseases (ICD)-9 (1990–1998) and ICD-10 (1999–2017) codes. Mortality rates within each age group are age-adjusted by single-year of age to match the age distribution of the U.S. population in 2000 in order to improve comparability over time. More information about the classification of causes of death can be found in Chapter 5. SOURCE: Data from: https://www.cdc.gov/nchs/nvss/nvss-restricted-data.htm 4-45 Prepublication copy, uncorrected proofs

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High and Rising Mortality Rates Among Working-Age Adults Get This Book
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The past century has witnessed remarkable advances in life expectancy in the United States and throughout the world. In 2010, however, progress in life expectancy in the United States began to stall, despite continuing to increase in other high-income countries. Alarmingly, U.S. life expectancy fell between 2014 and 2015 and continued to decline through 2017, the longest sustained decline in life expectancy in a century (since the influenza pandemic of 1918-1919). The recent decline in U.S. life expectancy appears to have been the product of two trends: (1) an increase in mortality among middle-aged and younger adults, defined as those aged 25-64 years (i.e., "working age"), which began in the 1990s for several specific causes of death (e.g., drug- and alcohol-related causes and suicide); and (2) a slowing of declines in working-age mortality due to other causes of death (mainly cardiovascular diseases) after 2010.

High and Rising Mortality Rates among Working Age Adults highlights the crisis of rising premature mortality that threatens the future of the nation's families, communities, and national wellbeing. This report identifies the key drivers of increasing death rates and disparities in working-age mortality over the period 1990 to 2017; elucidates modifiable risk factors that could alleviate poor health in the working-age population, as well as widening health inequalities; identifies key knowledge gaps and make recommendations for future research and data collection to fill those gaps; and explores potential policy implications. After a comprehensive analysis of the trends in working-age mortality by age, sex, race/ethnicity, and geography using the most up-to-date data, this report then looks upstream to the macrostructural factors (e.g., public policies, macroeconomic trends, social and economic inequality, technology) and social determinants (e.g., socioeconomic status, environment, social networks) that may affect the health of working-age Americans in multiple ways and through multiple pathways.

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