Prolonged Leisure Time Spent Sitting in Relation to Cause-Specific Mortality in a Large US Cohort

Abstract

The majority of leisure time is spent in sedentary behaviors such as television viewing. Studies have documented that prolonged leisure-time sitting is associated with higher risk of mortality—total, cardiovascular disease, cancer, and “all other causes”—but few have examined the “other” causes of death in detail. To examine associations of leisure-time sitting with risk of specific causes of death, we analyzed data from the Cancer Prevention Study II (CPS-II) Nutrition Cohort, a prospective US cohort including 127,554 men and women who were free of major chronic disease at study entry, and among whom 48,784 died during 21 years of follow-up (1993–2014; median follow-up, 20.3 years, interquartile range, 4.6 years). After multivariable adjustment, prolonged leisure-time sitting (≥6 vs. <3 hours per day) was associated with higher risk of mortality from all causes, cardiovascular disease (including coronary heart disease and stroke-specific mortality), cancer, diabetes, kidney disease, suicide, chronic obstructive pulmonary disease, pneumonitis due to solids and liquids, liver, peptic ulcer and other digestive disease, Parkinson disease, Alzheimer disease, nervous disorders, and musculoskeletal disorders. These findings provide additional evidence for associations between a broad range of mortality outcomes and prolonged sitting time. Given the pervasive nature of sitting in the contemporary lifestyle, this study further supports the recommendation that encouraging individuals to reduce sedentary time may provide health benefits.

cohort, mortality, physical activity, sedentary behavior, sitting time

With technological advancements, the amount of time spent sitting has increased significantly over the past few decades. In an Australian time-use study, investigators estimated that 90% of total nonoccupational time was spent sedentary and, of that, 53% was spent on screen time (computer or television) (1). Furthermore, as individuals age, physical activity decreases while sedentary behavior and risk of chronic disease increase (2). Regardless of sedentary time metric (i.e., total, leisure time, or television viewing), numerous studies have shown that prolonged time spent sitting is associated with total mortality (3–6), type II diabetes (7), cardiovascular disease (8), and some cancers (9, 10), independent of moderate-to-vigorous intensity physical activity (MVPA). Emerging evidence supports that sitting time is a behavioral risk factor that is distinct from inadequate exercise (i.e., physical inactivity) and could be an important additional target for intervention in the effort to increase daily physical activity in the population (11).

In a large meta-analysis (4), investigators reported a 34% higher total mortality risk for adults sitting 10 hours per day compared with 1 hour, after adjustment for physical activity and other potential confounders. Various studies have examined specific grouped causes of death and found associations with cardiovascular disease mortality and, to a lesser extent, with cancer mortality, as well as a statistically significant excess risk of death from “all other causes” (5, 6). The largest prospective study to date, using data from the NIH-AARP Diet and Health Study, further examined the association with “all other causes” to explore the specific causes of death that were driving the excess risk (12). Prolonged television viewing was associated with a statistically significant higher risk (per 2-hour/day increase in television-viewing time) of death from cancer, coronary heart disease, chronic obstructive pulmonary disease (COPD), diabetes, influenza/pneumonia, Parkinson disease, liver disease, and suicide (12). To our knowledge, no other study has comprehensively examined sitting time in relation to death from specific causes beyond cancer and cardiovascular disease mortality.

In an earlier analysis using data from the American Cancer Society’s Cancer Prevention Study II (CPS-II) Nutrition Cohort (5), leisure time spent sitting (≥6 vs. <3 hours per day) was associated with cardiovascular disease mortality among women (relative risk (RR) = 1.33, 95% confidence interval (CI): 1.17, 1.52) and men (RR = 1.18, 95% CI: 1.08, 1.30) and with cancer mortality among women (RR = 1.30, 95% CI: 1.16, 1.46) but not men (RR = 1.04, 95% CI: 0.94, 1.15). Prolonged leisure time spent sitting was also associated with other causes of death (excluding cardiovascular disease and cancer) among women (RR = 1.41, 95% CI: 1.25, 1.60) and men (RR = 1.33, 95% CI: 1.20, 1.47). To further examine the associations of sitting time with risk of specific causes of death, a detailed analysis was conducted using data from the CPS-II Nutrition Cohort, a large prospective US cohort study of men and women. This cohort provides a tremendous opportunity to add to the singular previous study on the association between sitting time and cause-specific mortality due to its large sample size and number of deaths along with detailed exposure assessment.

METHODS

Study population

Men and women in this analysis were drawn from the 184,185 participants in the CPS-II Nutrition Cohort, a prospective study of cancer incidence and mortality in the United States initiated by the American Cancer Society in 1992 (13). The CPS-II Nutrition Cohort is a subgroup of the approximately 1.2 million men and women in the CPS-II Mortality Cohort, a prospective study established by the American Cancer Society in 1982 (14). CPS-II Mortality Cohort participants, who resided in 21 states with population-based state tumor registries and who were 50–74 years of age in 1992, were invited to participate by completing a 10-page self-administered, mailed questionnaire that included questions on demographic, medical, behavioral, and lifestyle factors. The recruitment and characteristics of the CPS-II Nutrition Cohort are described in detail elsewhere (13), and all aspects of the study were approved by Emory University Institutional Review Board.

Men and women were excluded from this analysis if they reported a personal history of cancer (n = 21,785), heart attack (n = 11,559), stroke (n = 2,513), or emphysema/lung disease (n = 9,321) at the time of enrollment; were missing sitting time (n = 2,953) or recreational physical activity (n = 4,240) data; had extreme (top and bottom 0.1%) or missing body mass index (BMI) (n = 2,121); or were missing smoking status (n = 863). Men and women who reported no physical activity in their daily life (defined as no recreational physical activity, other daily life/household activity, or light housekeeping) were also excluded (n = 871) due to the strong possibility of an underlying condition that might be causing their complete inactivity. Finally, we excluded deaths in the first year of follow-up (n = 405). After exclusions, 127,554 men and women were included in the analysis, among whom 48,784 died between baseline and the end of follow-up on December 31, 2014.

Measures of time spent sitting and physical activity

Time spent sitting was assessed using the baseline question “During the past year, on an average day (not counting time spent at your job), how many hours per day did you spend sitting (watching television, reading, etc.)?” Responses included none, <3, 3–5, 6–8, or >8 hours per day. For the present study, time spent sitting was categorized as <3 hours per day (reference group), 3–5 hours per day, ≥6 hours per day.

Information on recreational MVPA was collected using the question “During the past year, what was the average time per week you spent at the following kinds of activities: walking, jogging/running, lap swimming, tennis or racquetball, bicycling or stationary biking, aerobics/calisthenics, and dancing?” Responses to each individual activity included none, 1–3, 4–6, or ≥7 hours/week. A MET, or metabolic equivalent of task—a measure of energy expenditure—is estimated by dividing the energy cost of a given activity by resting energy expenditure (15); summary MET-hours/week were calculated for each participant. The summary MET score for each participant was calculated by multiplying the lowest number of hours within each category by the general MET level of each activity according to the Compendium of Physical Activities to provide conservative summary measures, addressing the likelihood of overreporting physical activity and the older age of study participants (15). The MET scores assigned for various activities included 3.5 for walking, 7.0 for jogging/running, 7.0 for lap swimming, 6.0 for tennis or racquetball, 4.0 for bicycling/stationary biking, 4.5 for aerobics/calisthenics, and 3.5 for dancing. MVPA MET-hours/week was controlled for as a continuous measure in all analyses.

Mortality endpoints

The primary endpoint was death from any cause occurring between 1 year after the time of enrollment and December 31, 2014. Deaths were identified through biennial automated linkage of the entire cohort with the National Death Index (16). Causes of death were classified by using the International Classification of Diseases, Ninth Revision (17), for deaths occurring from 1992 to 1998 and the Tenth Revision (18) for deaths from 1999 to 2012. The following specific causes of death were examined: cancer, cardiovascular disease (grouped, as well as coronary heart disease, stroke, and other circulatory diseases separately), diabetes, other nutritional/metabolic diseases, kidney disease, other genitourinary diseases, accidents, suicide, COPD, pneumonia and influenza, pneumonitis due to solids and liquids, other respiratory diseases, liver disease, peptic ulcer and other digestive diseases, infectious diseases, dementia/mental disorders, Parkinson disease, Alzheimer disease, nervous disorders, and musculoskeletal disorders. All remaining deaths were collapsed into an “ill-defined” or “all other causes” categories. Table 1 summarizes the classification of grouped cause of death according to International Classification of Diseases codes.

Table 1.

Diagnosis Codes Used to Classify Specific Causes of Death, Cancer Prevention Study II Nutrition Cohort, United States, 1992–2014

Cause of Death	ICD-9	ICD-10
Cancer	140–239	C00–C97, D00–D49
All cardiovascular disease	390–459	I00–I99
Coronary heart disease	410–414	I20–I25
Stroke	430–438	I60–I69
Other circulatory diseases	390–405, 415–429, 440–459	I00–I19, I26–I59, I70–I99
Diabetes	250	E10–E14
Endocrine, nutritional, and metabolic diseases	240–249, 251–289	D50–E09, E15–E88
Kidney disease	580–589	N00–N07, N17–N19, N25–N27
Other genitourinary disease	590–629	N08–N16, N20–N24, N28–N39, N40–N98
Accidents	E800–E929	V01–X59, Y85–Y86
Suicide	950–959	X60–X84, Y87.0
Chronic obstructive pulmonary disease	490–496	J40–J45, J47
Pneumonia and influenza	480–487	J09–J18
Pneumonitis due to solids and liquids	507	J69
Other respiratory diseases	460–466, 470–478, 495, 500–506, 508–519	J00–J08, J20–J39, J60–J68, J70–J99
Liver disease	571	K70, K73–K74
Peptic ulcer and other digestive diseases	520–537, 540–543, 550–553, 555–570, 572–579	K25–K28, K00–K24, K29–K66, K71–K72, K75–K99
Infectious and parasitic diseases (including HIV and pulmonary tuberculosis)	001–139	A00–B99
Dementia/mental disorders	290–319	F00–F99
Parkinson disease	332	G20–G21
Alzheimer disease	331.0	G30
Nervous system and sense disorders	320–330, 331.1–331.9, 333–389	G00–G19, G22–29, G31–H93
Musculoskeletal diseases	710–739	M00–M99
Ill-defined	780–799	R00–R99

Abbreviations: HIV, human immunodeficiency virus; ICD-9, International Classification of Diseases, Ninth Revision; ICD-10, International Classification of Diseases, Tenth Revision.

Statistical analyses

Deaths and person-years were calculated according to category of leisure time spent sitting and 5-year attained-age groups, and mortality rates were then standardized to the age distribution of the CPS-II Nutrition Cohort population. Cox proportional hazards regression modeling (19) was used to compute relative risks and 95% confidence intervals, with follow-up time in days as the time axis. For leisure time spent sitting, we assessed risk in 3 models: 1) adjusted only for age (single year of age) and sex; 2) adjusted for age, sex, and other potential confounding factors; and 3) additionally adjusted for MVPA MET-hours per week. The potential confounders included were race (white, black, other/unknown), education (less than high school graduate, high school graduate or some college, college graduate or higher, unknown), smoking status (never, current, former, ever but status unknown), frequency and duration of smoking among current smokers (<20 cigarettes per day and smoking ≤35 years, <20 cigarettes per day and smoking >35 years, ≥20 cigarettes per day and smoking ≤35 years, ≥20 cigarettes per day and smoking >35 years), years since quitting among former smokers (<10, 10–19, ≥20), body mass index (calculated as weight (kg)/height (m)²) (continuous), marital status (married, widowed or divorced, never married, unknown), aspirin use (pills per month: 0, >1 and <15, 15 to <30, ≥30), alcohol consumption (drinks per day: 0, >0 and <1, 1, ≥2, unknown), occupational status (not employed/retired, employed, unknown), American Cancer Society dietary guidelines adherence score (20) (<3, 3 to <6, ≥6, unknown), and comorbidity score (0, 1, or ≥2 comorbidities; includes high blood pressure, diabetes, and high cholesterol). For some causes of death, categories of covariates were sometimes collapsed due to small numbers.

Secondary analyses were conducted to test for effect modification between leisure time spent sitting and sex, MVPA, BMI, and employment status (retired/homemaker vs. employed). We also conducted a sensitivity analysis among men and women who were lifelong nonsmokers or former smokers who quit more than 15 years prior to baseline. We also examined associations for diabetes mortality, excluding prevalent diabetes at baseline, and for kidney disease mortality, excluding prevalent diabetes and history of kidney stones at baseline. While sitting time was queried on some subsequent follow-up surveys, we did not update this exposure because of the possibility of reverse causation given that individuals might become more sedentary with age and/or development of disease, leading to a potential bias away from the null. However, to further address the possibility of reverse causality, we examined the association between baseline sitting time and mortality stratified by follow-up time. Weighted Schoenfeld residuals were used to test the Cox proportional hazards assumption (21). All tests for statistical significance were 2-sided, and P < 0.05 was considered statistically significant. All analyses were conducted using R (R Foundation for Statistical Computing, Vienna, Austria) (22).

RESULTS

Over 2,293,860 person-years of follow-up (median, 20.3 years, interquartile range, 4.6 years), we observed 48,784 total deaths. The most common cause of death was cardiovascular disease (n = 16,083), followed by cancer (n = 14,550), dementia/mental disorders (n = 2,406), Alzheimer disease (n = 2,248), COPD (n = 1,642), accidents (n = 1,339), Parkinson disease (n = 1,153), peptic ulcer and other digestive diseases (n = 1,148), and pneumonia/influenza (n = 1,034). Participants who spent the most leisure time sitting were slightly older, had a higher BMI, and were more commonly retired/unemployed (Table 2). Additionally, the most sedentary participants more commonly had ever smoked or had more comorbidities (diabetes, hypertension, or hyperlipidemia) and less commonly followed American Cancer Society dietary guidelines.

Table 2.

Selected Baseline Characteristics According to Hours of Leisure Time Spent Sitting for Men and Women, Cancer Prevention Study II Nutrition Cohort, United States, 1992

Characteristic	Leisure Time Spent Sitting
	<3 hours/day (n = 58,910)		3–5 hours/day (n = 54,742)		≥6 hours/day (n = 13,902)
	No.	%a	No.	%a	No.	%a
Age, yearsb	61.5 (6.3)		63.4 (6.2)		64.2 (6.3)
BMIb,c	25.5 (4.0)		26.2 (4.2)		26.8 (4.6)
MVPA, MET-hours/weekb	13.1 (13.2)		12.4 (12.5)		12.8 (13.1)
Male sex	24,300	41.2	24,951	45.6	7,356	52.9
Employment status
Not employed or retired	20,935	35.5	27,880	50.9	8,103	58.3
Employed	35,035	59.5	23,816	43.5	4,970	35.8
Race
White	57,339	97.3	53,328	97.4	13,528	97.3
Black	770	1.3	748	1.4	183	1.3
Other	801	1.4	666	1.2	191	1.4
Education
Less than high school	3,270	5.6	3,245	5.9	937	6.7
High school graduate	31,387	53.3	30,954	56.5	7,280	52.4
College graduate or higher	23,886	40.5	20,167	36.8	5,598	40.3
Smoking status
Never	29,990	50.9	24,004	43.8	5,524	39.7
Current	4,142	7.0	5,190	9.5	1,692	12.2
Former	24,540	41.7	25,368	46.3	6,631	47.7
Ever or unknown status	238	0.4	180	0.3	55	0.4
Alcohol intake, no. of drinks/day
0	23,208	39.4	21,103	38.5	5,502	39.6
<1	23,357	39.6	21,430	39.1	5,003	36.0
1	5,861	9.9	5,662	10.3	1,403	10.1
≥2	4,281	7.3	4,669	8.5	1,431	10.3
Marital status
Married	52,601	89.3	48,415	88.4	12,115	87.1
Widowed or divorced	4,963	8.4	5,001	9.1	1,363	9.8
Never married	828	1.4	847	1.5	252	1.8
Comorbidity scored
0	28,317	48.1	22,752	41.6	5,475	39.4
1	21,626	36.7	21,264	38.8	5,392	38.8
≥2	8,967	15.2	10,726	19.6	3,035	21.8
Diet scoree
0–2	11,933	20.3	13,502	24.7	3,757	27.0
3–5	25,836	43.9	24,600	44.9	5,996	43.1
6–9	16,228	27.5	12,441	22.7	2,881	20.7
Aspirin use, no. of pills/month
0	33,896	57.5	30,235	55.2	7,444	53.5
1–14	8,361	14.2	7,527	13.7	1,798	12.9
15–29	4,997	8.5	4,736	8.7	1,207	8.7
≥30	10,176	17.3	10,858	19.8	3,070	22.1

Abbreviations: BMI, body mass index; MET, metabolic equivalent of task; MVPA, recreational moderate-to-vigorous physical activity.

^a Percentages may not sum to due to rounding or missing values for exposure.

^b Values are expressed as mean (standard deviation).

^c Weight (kg)/height (m)².

^d Based on self-reported diabetes, hypertension, and high cholesterol.

^e Calculated based on intake of fruits and vegetables, whole/refined grains, and red and processed meat, with a score of 9 representing optimal dietary adherence.

Results with or without adjustment for MVPA did not differ (Web Table 1, available at https://academic.oup.com/aje). After multivariable adjustment including MVPA, leisure time spent sitting was positively associated with all-cause mortality (RR = 1.19, 95% CI: 1.15, 1.22 for ≥6 vs. <3 hours per day) among men and women combined (Table 3). Longer leisure time spent sitting also was associated with higher risks of cardiovascular disease mortality (RR = 1.19, 95% CI: 1.13, 1.25); when further examining specific types of cardiovascular disease, associations were slightly stronger for coronary heart disease mortality (RR = 1.26, 95% CI: 1.17, 1.35) than for death from stroke or other circulatory disease (Table 3). Prolonged time spent sitting was also associated with higher risk of death from cancer (RR = 1.11, 95% CI: 1.05, 1.17) as well as from diabetes, kidney disease, suicide, COPD, pneumonitis due to solids and liquids, liver, peptic ulcer and other digestive disease, Parkinson disease, Alzheimer disease, nervous disorders, and musculoskeletal disorders (Table 3).

Table 3.

Associations Between Leisure Time Spent Sitting and Cause-Specific Mortality Among Men and Women in the Cancer Prevention Study II Nutrition Cohort, United States, 1992–2014

	Leisure Time Spent Sitting in 1992
	<3 hours/day (n = 1,093,303 person-years)				3–5 hours/day (n = 967,808 person-years)				≥6 hours/day (n = 232,749 person-years)
Cause of Death	No. of Deaths	Ratea	RRb	95% CI	No. of Deaths	Ratea	RRb	95% CI	No. of Deaths	Ratea	RRb	95% CI
All causes	18,906	1,893.10	1.00	Referent	22,938	2,279.86	1.07	1.05, 1.09	6,940	2,722.97	1.19	1.15, 1.22
Cancer	5,929	584.67	1.00	Referent	6,714	679.79	1.06	1.02, 1.09	1,907	762.98	1.11	1.05, 1.17
All CVDc	6,037	612.72	1.00	Referent	7,647	760.78	1.06	1.02, 1.10	2,399	935.75	1.19	1.13, 1.25
CHD	2,728	281.90	1.00	Referent	3,535	357.61	1.07	1.02, 1.13	1,187	462.95	1.26	1.17, 1.35
Stroke	1,286	127.53	1.00	Referent	1,510	146.06	1.04	0.96, 1.12	443	173.01	1.15	1.03, 1.28
Other circulatory disease	2,023	203.29	1.00	Referent	2,602	257.12	1.06	1.00, 1.13	769	299.79	1.13	1.03, 1.23
Diabetes	338	34.38	1.00	Referent	480	47.96	1.13	0.98, 1.30	169	66.30	1.31	1.09, 1.59
Other nutrition/metabolic disease	244	24.42	1.00	Referent	335	32.58	1.19	1.01, 1.41	84	34.31	1.12	0.87, 1.44
Kidney disease	269	28.27	1.00	Referent	392	38.49	1.15	0.99, 1.35	142	54.70	1.43	1.16, 1.77
Other genitourinary disease	124	12.39	1.00	Referent	144	14.11	0.99	0.78, 1.27	45	17.32	1.09	0.77, 1.55
Accidents	564	56.54	1.00	Referent	629	62.90	1.03	0.92, 1.16	146	56.37	0.91	0.76, 1.10
Suicide	70	7.46	1.00	Referent	67	7.37	0.93	0.66, 1.31	34	13.65	1.66	1.09, 2.54
COPD	544	54.68	1.00	Referent	814	80.08	1.16	1.04, 1.30	284	110.12	1.38	1.19, 1.60
Pneumonia and influenza	386	39.24	1.00	Referent	496	48.91	1.09	0.95, 1.24	152	58.28	1.20	0.99, 1.46
Pneumonitis due to solids and liquids	121	12.60	1.00	Referent	190	18.94	1.30	1.03, 1.64	56	21.49	1.41	1.02, 1.95
Other respiratory disease	340	34.53	1.00	Referent	394	39.18	1.02	0.88, 1.18	118	45.41	1.13	0.91, 1.40
Liver disease	95	9.32	1.00	Referent	122	12.56	1.16	0.88, 1.53	54	23.18	1.80	1.27, 2.54
Peptic ulcer and other digestive disease	425	42.10	1.00	Referent	546	53.16	1.10	0.97, 1.25	177	68.64	1.31	1.09, 1.57
Infectious diseases	374	37.55	1.00	Referent	408	40.14	0.92	0.79, 1.06	131	51.86	1.05	0.85, 1.28
Dementia/mental disorders	964	94.73	1.00	Referent	1,142	108.12	1.05	0.97, 1.15	300	114.86	1.11	0.97, 1.26
Parkinson disease	456	48.10	1.00	Referent	528	52.93	1.12	0.99, 1.27	169	63.90	1.37	1.15, 1.64
Alzheimer disease	923	90.17	1.00	Referent	1,032	97.91	1.02	0.94, 1.12	293	112.01	1.18	1.03, 1.35
Nervous disorders	331	32.78	1.00	Referent	376	37.45	1.16	1.00, 1.35	127	51.13	1.54	1.25, 1.90
Musculoskeletal disorders	140	13.36	1.00	Referent	150	14.28	1.03	0.82, 1.31	56	22.08	1.58	1.15, 2.18
Ill-defined	161	16.20	1.00	Referent	244	23.39	1.36	1.11, 1.66	70	27.12	1.49	1.12, 1.99
Other	71	6.89	1.00	Referent	88	8.84	1.17	0.85, 1.61	27	11.49	1.32	0.84, 2.09

Abbreviations: CHD, coronary heart disease; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; RR, relative risk.

^a Age and sex-standardized rate per 100,000 person-years.

^b Multivariable models adjusted for sex, race, education, employment status, alcohol intake, marital status, smoking status (including smoking duration and frequency among current smokers and years since quit among former smokers), number of comorbidities, American Cancer Society diet score, aspirin use, body mass index, and recreational moderate-to-vigorous physical activity.

^c All CVD includes coronary heart disease, stroke, and other circulatory diseases.

Cancer and kidney disease mortality were the only outcomes where associations differed according to sex (interaction P = 0.04 and 0.01, respectively), with stronger associations among women for both cancer (for ≥6 vs. <3 hours per day sitting time, RR = 1.20, 95% CI: 1.11, 1.30) and kidney disease (RR = 1.97, 95% CI: 1.40, 2.77) compared with men (for cancer, RR = 1.06, 95% CI: 0.99, 1.13; for kidney disease, RR = 1.18, 95% CI: 0.90, 1.54). MVPA modified the association between leisure time spent sitting and death from all cardiovascular disease (for <8.75 MET-hours/week, RR = 1.24, 95% CI: 1.16, 1.33; for ≥8.75 MET-hours/week; RR = 1.13, 95% CI: 1.05, 1.21; P for interaction = 0.003) and stroke with associations stronger in those who were less (for <8.75 MET-hours/week, RR = 1.27, 95% CI: 1.10, 1.48) compared with more active (for ≥8.75 MET-hours/week, RR = 1.01, 95% CI: 0.86, 1.20; P for interaction = 0.01). No other associations differed when stratified by sex, physical activity level, or BMI.

When stratifying by occupational status, there was significant effect modification for all-cause mortality (P for interaction = 0.02) but not for any specific causes of death (data not shown). Participants who were employed at baseline had a higher risk of all-cause mortality (for ≥6 vs. <3 hours per day of leisure time spent sitting, RR = 1.23, 95% CI: 1.16, 1.29) compared with those who were unemployed or retired (for ≥6 vs. <3 hours per day of leisure time spent sitting, RR = 1.17, 95% CI: 1.13, 1.21). There was a statistical violation (global P < 0.0001) of the Cox proportional hazards assumption observed for all-cause mortality and some of the more common specific causes of death (cancer, cardiovascular disease, COPD, accidents, Parkinson disease, and Alzheimer disease). However, visual review of log-log survival curves did not show strong evidence of nonparallelism. When results were then stratified by follow-up time, associations were similar but attenuated in the second period. To further examine whether reverse causation explained any of the observed associations in the earlier years of follow-up, we also conducted an analysis with a 5-year lag, and associations were similar with very slight attenuation (e.g., overall RR = 1.38, 95% CI: 1.19, 1.60; with a 5-year lag for COPD mortality, RR = 1.37, 95% CI: 1.18, 1.59; additional data shown in Web Table 2).

Results were similar to those in the overall population in the sensitivity analysis restricted to men and women who were lifelong nonsmokers or long-term (≥15 years) former smokers (data not shown). For diabetes mortality, excluding individuals with diabetes at baseline resulted in an attenuation of the association and loss of statistical significance (for ≥6 hours per day spent sitting vs. <3 hours per day among individuals with no history of diabetes at baseline, RR = 1.23, 95% CI: 0.91, 1.68). Associations among those with no personal history of diabetes or kidney stones were virtually identical to those for the overall population in relation to deaths due to kidney disease (data not shown).

DISCUSSION

In this large prospective study of adults who were free of major chronic diseases at baseline, prolonged leisure time spent sitting for more than 6 hours per day was associated with a 19% higher all-cause death rate when compared with sitting less than 3 hours per day. Risk was significantly higher for 14 of the 22 specific causes of death examined and, importantly, for 8 of the top 10 leading causes of death in the United States (23), including cancer, coronary heart disease, stroke, diabetes, kidney disease, suicide, COPD, pneumonitis due to solids and liquids, liver disease, peptic ulcer and other digestive disease, Parkinson disease, Alzheimer disease, nervous disorders, and musculoskeletal disorders.

Our findings are consistent with previous studies that examined associations between prolonged sitting time and all-cause, cardiovascular disease, and cancer mortality (3–6), including an earlier report from the CPS-II Nutrition Cohort where leisure time spent sitting (≥6 vs. <3 hours per day) was associated with all-cause and cardiovascular disease mortality among women and men, and with cancer mortality among women but not men (5). In that study, sitting time was associated with mortality from other causes combined among women (RR = 1.41, 95% CI: 1.25, 1.60) and men (RR = 1.33, 95% CI: 1.20, 1.47). To better understand individual, less-studied cardiovascular disease mortality outcomes, we expanded the present study to examine specific types of cardiovascular disease and found that sitting time was more strongly associated with coronary heart disease mortality than with stroke or death from other circulatory diseases. These findings were similar to those from the NIH-AARP Diet and Health Study, a prospective cohort of approximately 220,000 healthy adults, in which investigators found positive associations between prolonged sitting while watching television and subsequent mortality risk from cancer and coronary heart disease but not for stroke (12). In another prospective cohort of 12,608 men and women, investigators also found that prolonged sitting was associated with incident coronary heart disease and a (statistically not significant) higher risk of incident stroke (24). Thus, these results require additional replication in other large prospective cohorts.

The NIH-AARP study also found prolonged television time to be associated with higher risk of death from COPD, diabetes, influenza/pneumonia, Parkinson disease, liver disease, and suicide (12). Our findings are largely consistent with a higher risk of mortality from all of these causes of death with the exception of influenza/pneumonia. In addition, we found prolonged sitting to be associated with death from kidney disease, pneumonitis due to solids and liquids, peptic ulcer and other digestive diseases, Alzheimer disease, nervous disorders, and musculoskeletal disorders, with risk estimates ranging from 18% to 58% higher risk for ≥6 versus <3 hours per day spent sitting during leisure time. However, risk estimates in the NIH-AARP study for kidney disease and Alzheimer disease were suggestive of a positive association (RR = 1.22 and 1.46, respectively, for ≥7 hours vs. <1 hour/day of television viewing) but did not reach statistical significance (12). To our knowledge, the other causes of death associated with sitting time included in the present study have not been previously studied in relation to time spent sitting, and those findings require replication in other large prospective studies.

Several possible factors could explain the positive associations between time spent sitting and higher mortality risk from various chronic diseases. Time spent sitting displaces time spent in physical activity and is associated with lower total physical activity levels (11). Adjustment for MVPA did not change results, but it is unclear whether other forms of activity might have (e.g., daily-life light activities). Alternatively, it is possible that time spent sitting, especially when engaged in specific activities such as television viewing, is associated with other unhealthy behaviors, such as excess snacking (25). This could explain why associations with time spent watching television are generally stronger in magnitude than those for leisure time spent sitting (3, 12). However, the relative contributions of poor diet and inactivity linked to prolonged television viewing and poor health are not well understood. Prolonged time spent sitting has also been shown to have important metabolic consequences, including a detrimental influence on various cardiometabolic factors (triglycerides, fasting plasma glucose, blood pressure, and insulin) and the promotion of obesity-related systemic inflammation (24, 26, 27). These pathways may explain why associations were observed with death from cardiovascular disease, cancer, diabetes, liver disease, kidney disease, and COPD, all of which have been shown to be associated with poor metabolic function and obesity. Regardless of the underlying mechanism, results from observational studies consistently suggest that reducing leisure time spent sitting could be beneficial for many health outcomes. Nevertheless, additional studies are essential to better understand how reductions in sitting time affect mortality and other outcomes. Ideally, randomized controlled trials should be conducted, but they would be costly and lengthy and thus may not be feasible.

Other associations—including death from suicide, Parkinson disease, Alzheimer disease, nervous disorders, and musculoskeletal disorders—are less clearly understood. For these causes of death, it is plausible that underlying conditions that would result in excess time spent sitting may explain associations. For example, individuals who are clinically depressed may be more likely to spend time sitting and more likely to commit suicide; however, we are unable to adjust for depression in the present study. Similarly, we were unable to exclude individuals with prevalent Parkinson disease or Alzheimer disease at baseline because we did not capture this information; thus, it is possible that individuals with these conditions are sitting longer as a result of the disease, rather than sitting being a cause of death from these conditions. More research is needed to better understand the relationship between prolonged sitting and death from these outcomes.

The strengths of our study include the large sample size, prospective design, and ability to control for many potential confounders. The lack of information on some prevalent diseases is a limitation of the study. While we adjusted for a wide range of potential confounders, it is possible that there is some residual confounding by another unmeasured factor. Another limitation is the lack of information on occupational physical activity and sedentary time; however, when we stratified our analyses by employment status, results for all-cause mortality were slightly stronger among employed participants compared with those who were unemployed/retired at baseline. This may be due to a higher amount of total sitting time. For all individual causes of death, results were virtually unchanged. Another limitation is the use of self-reported data, including sitting time and physical activity information, which may lead to some nondifferential misclassification. Although these questions are subject to misreporting, the sitting time and physical activity measures are very similar to those validated in the Nurses’ Health Study II, a prospective cohort with similar participant characteristics, which found a correlation of 0.79 between reported behavior on questionnaires and recalls (28). Finally, another limitation to note is that we were unable to differentiate among types of leisure-time sitting activities (i.e., sitting while watching television, reading, or driving).

In conclusion, prolonged leisure time spent sitting was associated with all-cause mortality and with 14 of 22 specific causes of death—including 8 of the 10 most common—independent of moderate-to-vigorous intensity physical activity. Given the increase in leisure time spent sitting in westernized countries over the past several decades, this report broadens our understanding of the array of negative health effects associated with prolonged sitting time and again highlights the importance of sedentary behavior, in addition to exercise, as a health behavior that may be modified in our ongoing efforts to improve public health.

ACKNOWLEDGMENTS

Author affiliations: Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia (Alpa V. Patel, Maret L. Maliniak, Erika Rees-Punia, Susan M. Gapstur); and Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland (Charles E. Matthews).

The American Cancer Society funded all aspects of the data collection and analysis.

We thank all the Cancer Prevention Study II participants and each member of the study and biospecimen management group.

Conflict of interest: none declared.

Abbreviations

 
• BMI

  body mass index

 
• CI

  confidence interval

 
• COPD

  chronic obstructive pulmonary disease

 
• CPS-II

  Cancer Prevention Study II

 
• MET

  metabolic equivalent of task

 
• MVPA

  moderate-to-vigorous physical activity

 
• RR

  relative risk