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Actual Causes of Death in the United States, 2000 Ali H. Mokdad, PhD James S. Marks, MD, MPH Donna F. Stroup, PhD, MSc Julie L. Gerberding, MD, MPH

I N A S E M I N A L 1 9 9 3 A R T I C L E , McGinnis and Foege1 described the major external (nongenetic) modi- fiable factors that contributed to

death in the United States and labeled them the “actual causes of death.” Dur- ing the 1990s, substantial lifestyle pat- tern changes may have led to variations in actual causes of death. Mortality rates from heart disease, stroke, and cancer have declined.2 At the same time, behav- ioral changes have led to an increased prevalence of obesity and diabetes.3

Most diseases and injuries have mul- tiple potential causes and several fac- tors and conditions may contribute to a single death. Therefore, it is a chal- lenge to estimate the contribution of each factor to mortality. In this ar- ticle, we used published causes of death reported to the Centers for Disease Con- trol and Prevention (CDC) for 2000, relative risks (RRs), and prevalence es- timates from published literature and governmental reports to update actual causes of death in the United States—a m e t h o d s i m i l a r t o t h a t u s e d b y McGinnis and Foege.

METHODS Our literature review used a MEDLINE database search of English-language ar- ticles that identified epidemiological, clinical, and laboratory studies link- ing risk behaviors and mortality. Our search criteria were to include all ar-

ticles including the following key words: mortality, smoking, physical ac- tivity, diet, obesity, alcohol, microbial agents, toxic agents, motor vehicle, fire- arms, sexual behavior, illicit drug use. Our search allowed for words with simi- lar meaning to be included (ie, exer- cise as well as physical activity). The search was initially restricted to ar- ticles published during or after 1990, but we later included relevant articles published in 1980 to December 31, 2002 (search strategies are available from the authors on request). For each risk factor, we used the prevalence and RR identified by the literature search. To identify the causes and number of

deaths, we used mortality data re- ported in 2000 to the CDC.4 We used no unpublished information or data.

We used the following formula to cal- culate attributable fractions for each dis- ease: [(P0 + �Pi (RRi)) − 1]/[P0 + �Pi (RRi)], in which P0 is the percentage of individuals in the United States not en- gaging in the risk behavior, Pi is the per-

Author Affiliations: Division of Adult and Commu- nity Health (Dr Mokdad), Office of the Director (Drs Marks and Stroup), National Center for Chronic Dis- ease Prevention and Health Promotion and Office of the Director (Dr Gerberding), Centers for Disease Con- trol and Prevention, Atlanta, Ga. Corresponding Author: Ali H. Mokdad, PhD, Divi- sion of Adult and Community Health, 4770 Buford Hwy, NE, Mailstop K66, Atlanta, GA 30341 ([email protected]).

Context Modifiable behavioral risk factors are leading causes of mortality in the United States. Quantifying these will provide insight into the effects of recent trends and the implications of missed prevention opportunities.

Objectives To identify and quantify the leading causes of mortality in the United States.

Design Comprehensive MEDLINE search of English-language articles that identified epidemiological, clinical, and laboratory studies linking risk behaviors and mortality. The search was initially restricted to articles published during or after 1990, but we later included relevant articles published in 1980 to December 31, 2002. Prevalence and relative risk were identified during the literature search. We used 2000 mortality data reported to the Centers for Disease Control and Prevention to identify the causes and number of deaths. The estimates of cause of death were computed by multiply- ing estimates of the cause-attributable fraction of preventable deaths with the total mortality data.

Main Outcome Measures Actual causes of death.

Results The leading causes of death in 2000 were tobacco (435 000 deaths; 18.1% of total US deaths), poor diet and physical inactivity (400 000 deaths; 16.6%), and alcohol consumption (85 000 deaths; 3.5%). Other actual causes of death were mi- crobial agents (75 000), toxic agents (55 000), motor vehicle crashes (43 000), inci- dents involving firearms (29 000), sexual behaviors (20 000), and illicit use of drugs (17 000).

Conclusions These analyses show that smoking remains the leading cause of mor- tality. However, poor diet and physical inactivity may soon overtake tobacco as the leading cause of death. These findings, along with escalating health care costs and aging population, argue persuasively that the need to establish a more preventive ori- entation in the US health care and public health systems has become more urgent. JAMA. 2004;291:1238-1245 www.jama.com

For editorial comment see p 1263.

centage engaging in separate catego- ries of the risk behavior, and RRi is the RR of death for each separate cat- egory relative to none. For instance, in the case of smoking, P0 is the percent- age of persons who never smoked, P1 is the percentage of former smokers, P2 is the percentage of current smok- ers, RR1 is the RR of a certain type of death for former smokers compared with those who never smoked, and RR2 is the RR of death for current smokers compared with those who never smoked. We then multiplied estimates of the cause-attributable fraction of preventable deaths by total mortality data. Whenever pos- sible, we used RRs of death and mor- tality data by other variables such as age, sex, and race.

We estimated ranges for our esti- mated number of deaths by using the smallest and highest RRs and their boundaries when available. When data were available, we used specific under- lying causes of death in deriving some of our estimates (ie, firearms, motor ve- hicles, and illicit drug use). Further de- tails of these methods may vary due to availability of data and are presented in each section below. We used SAS (ver- sion 8.2, SAS Institute Inc, Cary, NC) and SUDAAN (version 8.0, Research Triangle Institute, Research Triangle Park, NC) statistical software.

RESULTS The number of deaths in the United States in 2000 was 2.4 million, which is an increase of more than 250 000 deaths in comparison with the 1990 total, due largely to population growth and increasing age.2,4 Leading causes of death were diseases of the heart (710 760), malignant neoplasms (553 091), and cerebrovascular dis- eases (167 661) (TABLE 1).

Tobacco We used methods and software used in previous CDC reports to compute the annual smoking-attributable mortality for 2000.5,6 As in previous reports, we used RRs for each cause of death from the American Cancer Society’s Cancer

Prevention Study II7 and included deaths due to secondhand smoking.

We used data from the Behavioral Risk Factor Surveillance System (BRFSS), a cross-sectional telephone survey con- ducted by state health departments with the CDC’s assistance, to determine changes in US smoking prevalence from 1995-1999 to 2000. A detailed descrip- tion of survey methods is available else- where.8 A slight decline in smoking was observed from 1995-1999 to 2000. The prevalence of smoking in 1995-1999 was 22.8% for current smokers (males: 25.1%; females: 20.6%), 24.1% for former smokers (males: 28.3%; females: 20.3%), and 53.1% for never-smokers (males: 46.5%; females: 59.2%). In 2000, these estimates were 22.2% for current smok- ers (males: 24.1%; females: 20.5%), 24.4% for former smokers (males: 28.3%; females: 20.7%), and 53.4% for never- smokers (males: 47.6%; females: 58.8%).

We estimate that approximately 435 000 deaths were attributable to smoking in 2000, which is an increase of 35 000 deaths from 1990 (TABLE 2). This increase is due to the inclusion of 35 000 deaths due to secondhand smok- ing and 1000 infant deaths due to ma- ternal smoking, which were not in- cluded in the article by McGinnis and Foege.1

Poor Diet and Physical Inactivity To assess the impact of poor diet and physical inactivity on mortality, we com- puted annual deaths due to over-

weight.9 Recent articles have reported that overweight increased in all seg- ments of the US population.10,11 To de- rive the attributable number of deaths due to overweight, we used estimates from the CDC’s 1999 and 2000 Na- tional Health and Nutrition Examina- tion Surveys.12 We used the same pro- cedure reported by Allison et al13 to estimate annual overweight-attribut- able deaths. We used the body mass in- dex (BMI) range of 23 to 25 as our ref- erence category to match the method used by Allison et al. Body mass index is calculated as weight in kilograms di- vided by the square of the height in me- ters. Using data from the 1999 and 2000 National Health and Nutrition Exami- nation Surveys, the percentages for BMI cut points were less than 23 (22.3%), 23 to less than 25 (15.09%), 25 to less than 26 (7.49%), 26 to less than 27 (7.36%), 27 to less than 28 (6.23%), 28 to less than 29 (6.30%), 29 to less than 30 (5.94%), 30 to 35 (16.95%), and more than 35 (12.62%).

We used hazard ratios reported pre- viously13 to recompute annual deaths for 6 major population-based studies. The mean estimate of the total num- ber of overweight-attributable deaths in 2000 was 494 921. For the Alameda County Health Study, the estimated number of overweight-attributable deaths in 2000 was 567 683; Framing- ham Heart Study, 543 981; Tecumseh Community Health Study, 462,005; American Cancer Society Cancer Pre-

Table 1. Leading Causes of Death in the United States in 2000*

Cause of Death No. of Deaths Death Rate per

100 000 Population

Heart disease 710 760 258.2

Malignant neoplasm 553 091 200.9

Cerebrovascular disease 167 661 60.9

Chronic lower respiratory tract disease 122 009 44.3

Unintentional injuries 97 900 35.6

Diabetes mellitus 69 301 25.2

Influenza and pneumonia 65 313 23.7

Alzheimer disease 49 558 18

Nephritis, nephrotic syndrome, and nephrosis 37 251 13.5

Septicemia 31 224 11.3

Other 499 283 181.4

Total 2 403 351 873.1

*Data are from Minino et al.4

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vention Study I, 451 708; Nurses Health Study, 504 602; and the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study, 439 548.14-19

As in the study by Allison et al, the estimate for the attributable number of deaths for nonsmokers or never- smokers was higher than the estimate for the total because smoking is asso- ciated with both lower body weight and higher mortality. Also in 2000, the mean estimate of the total number of overweight-attributable deaths among nonsmokers or never-smokers was 543 797. For the Alameda County Health Study, the estimate of over- weight-attributable deaths among non- smokers or never-smokers was 639 026; Framingham Heart Study, 583 913; Te- cumseh Community Health Study, 457 460; American Cancer Society Can- cer Prevention Study I, 466 729; Nurses Health Study, 570 855; and the Na- tional Health and Nutrition Examina- tion Survey I Epidemiologic Fol- low-up Study, 544 798. Our estimates indicate an increase of 76.6% over the 1991 estimate of overweight-attribut- able deaths, with more than 80% of ex- cess deaths occurring among individu- als with class 2 and 3 obesity.

The prevalence of overweight used in this study is based on data from 1999- 2000. Because the effects of overweight on mortality may not appear until some years after a person becomes over- weight, it is likely that the increase in prevalence of overweight in the 1990s overestimates the current actual num- ber of deaths. However, the total num-

ber of deaths from the 1999-2000 data may well be the expected number of deaths in the next few years. Thus, we believe a more accurate and conserva- tive estimate for overweight mortality in 2000 such as 385 000, which is the rounded average of 2000 and 1991 es- timates (494 921 and 280 184).

Overweight would account for the major impact of poor diet and physi- cal inactivity on mortality.20 Diet may have a minor additional effect on mor- tality mainly from lack of certain es- sential nutrients.21,22 Consumption of fruits and vegetables increased in the 1990s,23 and fat intake as a percentage of calories declined.24 Physical activ- ity has increased slightly.25 We esti- mate that poor diet and physical inac- tivity will cause an additional 15 000 deaths a year, although this too may be conservative. Nutritional deficiencies alone (International Classification of Dis- eases, 10th Revision [ICD-10] codes E40- E64) were reported as the causes of 4242 deaths in 2000.

We estimate that 400 000 deaths were attributable to poor diet and physical inactivity, an increase of one third from 300 000 deaths estimated by McGinnis and Foege,1 and the largest increase among all actual causes of death. How- ever, poor diet and physical inactivity could account for even more deaths (�500 000) when the 1999-2000 preva- lence estimates of overweight have their full effect.

Alcohol Consumption We used 2 large nationally representa- tive surveys to determine US alcohol

consumption. The National Health In- terview Survey, a household survey that measured alcohol intake in 1999 and 2000, and the BRFSS, a telephone sur- vey that measured alcohol intake in 1999.8,26

We used RRs from the Australian Na- tional Drug and Safety Report that were based on mortality rates derived from pooled data of several studies.27,28 The RR values were 1.33 for hazardous drinking (4.01-6.00 drinks/d for males and 2.01-4.00 for females) and 1.47 for harmful drinking (�6.01 drinks/d for males and �4.01 for females) in con- trast to low levels of drinking (0.26- 4.00 drinks/d for males and 0.26-2.00 for females) and abstinence (0-0.25 drinks/d for both males and females).

We used BRFSS data to compute the number of alcohol-attributable deaths for the US population aged 18 years or older. The BRFSS also asked ques- tions about binge drinking (ie, �5 drinks per occasion). To account for the effect that respondents appeared not to include binge drinking in their re- ported regular drinking, we reran our analyses, adding 5 drinks per binge oc- casion to average drinks per day. The total number of deaths attributable to alcohol was 103 350.

We also used 3 other recent studies to estimate alcohol-attributable mor- tality. Two studies were based on the National Health Interview Survey29,30

and the National Alcohol Survey.31 Us- ing all-cause mortality and RRs from these studies, we estimated approxi- mately 60 000 deaths per year. This dif- ference in number of deaths is mainly due to the fact that BRFSS respon- dents report a higher percentage of heavy drinking than do respondents in a household survey such as the Na- tional Health Interview Survey.

In another approach, we aggregated alcohol-related deaths from specified ICD codes that were summed to pro- vide an overall estimate of deaths. In 2000, 18 539 deaths were reported as al- cohol-induced (ICD-10 codes F10, G31.2, G62.1, I42.6, K29.2, K70, R78.0, X45, X65). In addition, 16 653 persons were killed in alcohol-related crashes.32

Table 2. Actual Causes of Death in the United States in 1990 and 2000

Actual Cause No. (%) in 1990* No. (%) in 2000

Tobacco 400 000 (19) 435 000 (18.1)

Poor diet and physical inactivity 300 000 (14) 400 000 (16.6)

Alcohol consumption 100 000 (5) 85 000 (3.5)

Microbial agents 90 000 (4) 75 000 (3.1)

Toxic agents 60 000 (3) 55 000 (2.3)

Motor vehicle 25 000 (1) 43 000 (1.8)

Firearms 35 000 (2) 29 000 (1.2)

Sexual behavior 30 000 (1) 20 000 (0.8)

Illicit drug use 20 000 (�1) 17 000 (0.7)

Total 1 060 000 (50) 1 159 000 (48.2)

*Data are from McGinnis and Foege.1 The percentages are for all deaths.

CAUSES OF DEATH

We estimate another 34 797 deaths in 2000 using BRFSS alcohol consump- tion data and disease-specific RRs from the Australian study for oropharyn- geal, esophageal, liver, laryngeal, and fe- male breast cancers; stroke; hyperten- sive heart disease; and other chronic liver disease and cirrhosis (ICD-10 code K73-74). This totals to 69 989 deaths in 2000 from these factors alone. In the Australian study, all-cause mortality was also higher than the summation of cause- specific mortality.

Total alcohol-attributable deaths would reach about 140 000 if mortal- ity among previous alcohol drinkers were included. It is unclear whether ex- cess mortality among former alcohol drinkers is due to damage or illness from past alcohol consumption.

Taking these various numbers into ac- count, our best estimate for total alcohol- attributable deaths in 2000 is approxi- mately 85000, based on the conservative estimate from cause-specific deaths and the high estimate using all-cause mor- tality. This is a reduction of 15 000 deaths from the 1990 estimates.

Microbial Agents We excluded human immunodefi- ciency virus (HIV) from this category and included it with sexual behaviors to be consistent with the analysis by McGinnis and Foege.1 In the past, in- fectious agents were the leading cause of mortality.33 These agents still pre- sent a major threat to the nation’s health and are associated with high mor- bidity.34 Several improvements in the health system have led to a decline in mortality from infectious diseases. The increase in US immunization rates led to a decline in mortality from many vac- cine-preventable diseases.35-37 Several laws ensure this high immunization rate for children by requiring vaccination for school and day-care enrollment.38 There also have been substantial improve- ments in sanitation and hygiene, anti- biotics and other antimicrobial medi- cines, and hospital-infection control.35

In 2000, influenza and pneumonia accounted for 65 313 deaths, septice- mia for 31 224, and tuberculosis for

776.4 In general, mortality from infec- tious and parasitic diseases has de- clined since 1990.33 Because pneumo- nia and septicemia occur at higher rates among patients with cancer, heart dis- ease, lung disease, or liver disease, some of these deaths really are attributable to smoking, poor diet, and alcohol con- sumption.39-43 We estimate that ap- proximately 75 000 deaths were attrib- utable to microbial agents in 2000 from all ICD-10 codes for infectious and para- sitic mortality. The major cause of the decline was a decrease in deaths from influenza and pneumonia probably re- flecting at least in part an increase in immunization in older adults against vaccine-preventable diseases. This con- trasts with 90 000 deaths attributed to microbial agents in 1990 estimates.

Toxic Agents Estimating the number of deaths due to toxic agents is more challenging than any of the other risk factors due to limited published research and the challenges of measuring exposure and outcome. In the 1990s, many improvements were made in controlling and monitoring pol- lutants.44 There is more systematic moni- toring of pollutants at state and county levels, and exposure to asbestos, ben- zene, and lead have declined.44 In fact, the US Environmental Protection Agency reported a decline of 25% from 1970 to 2001 in 6 principal air pollut- ants: carbon monoxide, lead, ozone, ni- trogen dioxide, sulfur dioxide, and par- ticulate matter.45

Toxic agents are associated with in- creased mortality from cancer, respira- tory, and cardiovascular diseases.46-49 We used the National Morbidity, Mortal- ity, and Air Pollution Study to estimate mortality due to air pollution.50 The study assessed the association between air pollution and mortality and morbid- ity in 90 cities in the United States. Only particulate matter (PM) was associated with a significant increase in mortal- ity—an approximate 0.5% increase in total mortality for each 10-µ/m3 in- crease in PM10. Previous studies re- ported a range of 0.4% to 1% for that as- sociation.51,52 We used 23.8 µ/m3 as the

daily average of PM10 concentration in 2000,45 which results in an estimate of 24 000 deaths per year (range, 22 000- 52 000 deaths) from air pollution alone.

The National Institute for Occupa- tional Safety and Health (NIOSH) esti- mates that about 113 000 deaths are due to occupational exposure from 1968 to 1996.53 The number of deaths caused by occupational exposure has declined dur- ing that period. In 1996, NIOSH esti- mated 3119 deaths from pneumoconio- sis and 1176 from asbestosis. Although, particulate air pollution accounts for the majority (about 60%) of mortality re- lated to toxic agents,54 indoor air pollu- tion, environmental tobacco smoke, ra- don, lead in drinking water, and food contamination are associated with in- creased mortality.55,56 We estimate that toxic agents (excluding environmental tobacco exposure) were associated with 2% to 3.5% of total mortality in 2000. We estimate approximately 55000 deaths at- tributable to toxic agents in 2000. This estimate is our least certain of the vari- ous causes.

Motor Vehicles Motor-vehicle crashes involving pas- sengers and pedestrians resulted in 43 354 deaths in 2000.4 This decline from 47 000 deaths in 1990 represents successful public health efforts in motor- vehicle safety.57,58 Deaths from alcohol- related crashes declined from 22 084 in 1990 to 16 653 in 2000.32 Major con- tributing factors include the use of child safety seats and safety belts,59,60 de- creases in alcohol-impaired driving,61

changes in vehicle and highway de- sign,62,63 and national goals to reduce mo- tor-vehicle–related mortality and in- jury.64 We estimate that approximately 26 500 deaths in 2000 were attribut- able to motor-vehicle crashes in which alcohol was not a factor. This is an in- crease of 1500 from the 1990 report be- cause both estimates were not adjusted for the number of registered vehicles, number of crashes, nor miles of travel. We included alcohol-related deaths to stress that efforts to educate the public and enforce laws against driving while intoxicated have accounted for most of

CAUSES OF DEATH

the decline in deaths related to motor- vehicle crashes.

Firearms Firearm-related incidents resulted in 28 663 deaths among individuals in the United States in 2000.4 This is a de- cline from approximately 36 000 deaths in 1990. The largest declines were in deaths from homicides and uninten- tional discharge of firearms. In 2000, 16 586 deaths were due to intentional self-harm (suicide) by discharge of fire- arms (ICD-10 codes X72-X74). Assault (homicide) by discharge of firearms (ICD-10 codes X93-X95) resulted in 10 801 deaths. Unintentional dis- charge of firearms (ICD-10 codes W32- W34) resulted in 776 deaths, while dis- charge of firearms, undetermined intent (ICD-10 codes Y22-Y24), resulted in 230 deaths. The remaining 270 deaths were due to legal intervention (ICD-10 code Y35). These numbers were ascertained from death certificate reports.

Sexual Behavior Sexual behavior is associated with an in- creased risk of preventable disease and disability.65 An estimated 20 million per- sons are newly infected with sexually transmitted diseases each year in the United States.66,67 Mortality from sexu- ally transmitted diseases is declining due to the availability of earlier and better treatment, especially for HIV.67,68 In 2000, HIV disease (ICD-10 codes B20- B24) resulted in 14 578 deaths. In 1990, HIV was the cause of 27 695 deaths for persons older than 13 years, indicating about a 48% decline in HIV mortality during the decade. Based on the sexual behavior–attributable fraction from the literature,69-71 we estimate that 20 000 deaths (range, 18 000-25 000 deaths) in 2000 were due to sexual behavior— mainly HIV; other contributors were hepatitis B and C viruses and cervical cancer. The decline of 10 000 deaths from the 1990 estimates1 was due to the decline in HIV mortality.

Illicit Use of Drugs Illicit drug use is associated with sui- cide, homicide, motor-vehicle injury,

HIV infection, pneumonia, violence, mental illness, and hepatitis.27,28,72-77 An estimated 3 million individuals in the United States have serious drug prob- lems.7 8 , 7 9 Several studies have re- ported an undercount of the number of deaths attributed to drugs by vital sta- tistics80; however, improved medical treatments have reduced mortality from many diseases associated with illicit drug use. In keeping with the report by McGinnis and Foege,1 we included deaths caused indirectly by illicit drug use in this category. We used attribut- able fractions to compute the number of deaths due to illicit drug use.27,28,81

Overall, we estimate that illicit drug use resulted in approximately 17 000 deaths in 2000, a reduction of 3000 deaths from the 1990 report.

Other Factors Several other factors contribute to an increased rate of death. There are fac- tors that we do not know of such as un- known pollutants or perhaps expo- sures that may cause a considerable number of deaths. Poverty and low edu- cation levels are associated with in- creased mortality from many causes,82,83

partly due to differential exposure to the risks described above. However, con- trolling for differential exposure to risk factors is unlikely to explain the en- tire impact on mortality. Lack of ac- cess to proper medical care or preven- tive services is associated with increased mortality.84 Biological characteristics and genetic factors also greatly affect risk of death.85 In most studies we re- viewed, low education levels and in- come were associated with increased risk of cardiovascular disease, cancer, diabetes, and injury. The Healthy People 2010 initiative has made the elimination of health disparities, espe- cially racial and ethnic disparities, a pri- mary goal.86

COMMENT We found that about half of all deaths that occurred in the United States in 2000 could be attributed to a limited number of largely preventable behav- iors and exposures. Overall, we found

relatively minor changes from 1990 to 2000 in the estimated number of deaths due to actual causes. Our findings in- dicate that interventions to prevent and increase cessation of smoking, im- prove diet, and increase physical activ- ity must become much higher priori- ties in the public health and health care systems.

The most striking finding was the substantial increase in the number of estimated deaths attributable to poor diet and physical inactivity. We esti- mate that roughly 400 000 deaths now occur annually due to poor diet and physical inactivity. The gap between deaths due to poor diet and physical in- activity and those due to smoking has narrowed substantially. Because rates of overweight increased rapidly dur- ing the 1990s, we used a conservative approach to make our estimates, ac- counting for the delayed effects of over- weight on mortality. In addition, over- weight lessens life expectancy.87,88

However, it is clear that if the increas- ing trend of overweight is not re- versed over the next few years, poor diet and physical inactivity will likely over- take tobacco as the leading prevent- able cause of mortality.

The most disappointing finding may be the slow progress in reducing to- bacco-related mortality. A few states, notably California, have had major suc- cess in programs that led to reducing deaths from heart disease and can- cer.89 However, efforts in most other states are too recent or short-term to have a similar effect. In response to the increase in tobacco use among youth in the early 1990s, state and national tobacco-control efforts increased their focus on prevention of initiation and recognized the importance of cessa- tion on reducing smoking-related deaths. Thus, most national and state efforts now address comprehensive pro- gram strategies.90 Current tobacco- control efforts will also need strong ces- sation components to show a decline in tobacco deaths in a future assess- ment. Recent reports on the effects of telephone quit lines for smokers are en- couraging.91 On the other hand, large

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state budget shortfalls are leading to large cuts in public health, with a cor- responding diversion of resources from tobacco taxes and settlement dollars to cover deficits instead of tobacco- control programs.

Despite the call to action on these risk factors a decade ago, there has been little progress in reducing the total number of deaths from these causes. The progress that has occurred primarily in- volves actual causes of death that are less prominent. With the shift in the age distribution of the population, more adults now are in the age group at high- est risk because of the cumulative ef- fects of their behavior. The net effect is that both total deaths and total burden due to the actual causes have increased.

Our analyses have several limita- tions. Our study reported actual causes of mortality in the United States. How- ever, these causes are also associated with a large morbidity burden. In ad- dition to premature death, years of lost life, diminished productivity, and high rates of disability, decreased quality of life is also strongly associated with these actual causes. A recent World Health Organization report finds these actual causes of death to be the leading causes of total disease burden, not just mor- tality, in the developed world.92 Be- cause we used self-reported estimates for some risk behaviors, (ie, preva- lence of alcohol intake) they may have been underestimated. Finally, using all-cause mortality may result in over- estimates of the number of deaths from specific causes. In addition, if the effect of the risk factor is age-dependent, then age- and sex-specific estimates are preferable.

Our analyses did not assess the effect of genetics. Genetic factors have been associated with several diseases dis- cussed herein.85 Much of the impact of genetics is likely mediated through in- creased physical susceptibility to these behavioral and other modifiable risks. However, increases in obesity and dia- betes cannot be due to widespread changes in the human genome over the last 10 years. Nevertheless, genetics of-

fers great potential for treating and ame- liorating risk. Identifying individuals at higher risk for a disease through ge- netic testing may promote lifestyle changes that can help prevent the on- set of that disease.93

In this study we also did not exam- ine the effects of high blood pressure and cholesterol or lipid profile on mor- tality, although some of the effects of these factors are meditated through poor diet and physical inactivity. These risk factors are common among adults in the United States. More than 30% of US adults have high blood pressure or high cholesterol.94,95 Monitoring and controlling blood pressure and choles- terol is crucial to preventing prema- ture mortality and morbidity.

One of the most difficult aspects of this analysis is that the attribution of the actual cause that led to death var- ies depending on perspective. We used similar methods to those used by McGinnis and Foege1 to allow com- parisons. We tried when possible to use RRs that are fully adjusted for other risk factors in our analyses, but possibly not eliminating duplicate attribution of causes. We also explicitly included some deaths in more than 1 category (eg, alcohol and motor vehicle crashes) when choosing another category seemed as though it might artificially constrain interpretation for future pre- vention programs.

In summary, smoking and the deaths attributed to the constellation of poor diet and physical inactivity currently ac- count for about one third of all deaths in the United States. The rapid in- crease in the prevalence of overweight means that this proportion is likely to increase substantially in the next few years. The burden of chronic diseases is compounded by the aging effects of the baby boomer generation and the concomitant increased cost of illness at a time when health care spending con- tinues to outstrip growth in the gross domestic product of the United States. In ancient times, Hippocrates stated that “the function of protecting and devel- oping health must rank even above that of restoring it when it is impaired.” The

findings in this study argue persua- sively for the need to establish a more preventive orientation in health care and public health systems in the United States.

Author Contributions: Dr Mokdad had full access to the data in this study and takes full responsibility for the scientific integrity of the data and the accuracy of the analysis and content of the manuscript. Study concept and design: Mokdad, Marks, Stroup, Gerberding. Acquisition of data: Mokdad, Stroup, Gerberding. Analysis and interpretation of data: Mokdad, Marks, Stroup, Gerberding. Drafting of the manuscript: Mokdad, Marks, Stroup, Gerberding. Critical revision of the manuscript for important intellectual content: Mokdad, Marks, Stroup, Gerberding. Statistical expertise: Mokdad, Stroup. Obtained funding: Marks, Gerberding. Administrative, technical, or material support: Mokdad, Marks, Stroup, Gerberding. Study supervision: Marks, Gerberding. Funding/Support: There was no external funding for this work. Acknowledgment: We acknowledge the valuable con- tributions of Barbara A. Bowman, PhD, Robert D. Brewer, MD, MSPH, Earl S. Ford, MD, MPH, Wayne H. Giles, MD, James M. Mendlein, PhD, Cheryl Pel- lerin, Susan Y. Chu, PhD, and Eduardo J. Simoes, MD, MPH. Role of the Sponsor: The Centers for Disease Con- trol and Prevention reviewed and approved this re- port before submission.

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