Patterns of Sedentary Behavior and Mortality in U.S. Middle-Aged and Older Adults

Adults are sedentary for an alarming 9 to 10 hours per day (1). Accordingly, the popular press has coined the phrase sitting is the new smoking to describe a current epidemic of developed nations (24). Evidence indicates that sedentary time is associated with incident cardiovascular disease, incidence of cardiovascular diseaserelated risk factors, and mortality (5, 6). Of note, the risk conferred by prolonged sedentariness is eliminated only by high levels of moderate- to vigorous-intensity physical activity (MVPA) (about 60 to 75 min/d), which exceed physical activity recommendations (7, 8). As such, sedentary behavior is now believed to represent a clinically important aspect of a person's physical activity profile and is no longer considered simply the extreme low end of the physical activity continuum (5). Studies linking sedentary behavior to health outcomes have relied almost exclusively on self-reported sedentary time, which is subject to reporting bias and measurement error (9). A 2015 systematic review (5) identified only 1 study (NHANES [National Health and Nutrition Examination Survey]) that examined the association between objectively measured sedentary time and health outcomes, a study limited by a small event rate (10). New studies using NHANES data have since been published, with longer follow-up and higher event rates (1115). However, some of these studies have reported an association between objectively measured sedentary time and mortality (11, 14, 15), but others have not (12, 13). Additional cohort studies are thus needed to rectify evidence gaps. Furthermore, studies using accelerometers to objectively measure sedentary behavior conventionally operationalize sedentary time as the total number of sedentary minutes per day. This approach ignores patterns of accumulated sedentary behavior over time. For example, accumulation of sedentary time in a few long bouts or many short bouts represents 2 distinct patterns of sedentary time accrual. Experimental studies have shown that acute periods of prolonged, uninterrupted sedentary behavior cause greater detrimental cardiometabolic effects than sedentary behavior that is periodically interrupted (1618), suggestive that it is not just total sedentary time that is relevant to health outcomes, but also the manner in which it is accumulated. Few longitudinal studies, however, have explored the association between prolonged, uninterrupted sedentary behavior and mortality to corroborate these findings. To inform guidelines on reducing sedentary behavior (target reductions in overall sedentary time or target interruption of prolonged sedentary bouts), evidence from prospective studies is needed to 1) confirm the association between total sedentary time and mortality using objective measures, 2) determine whether prolonged sedentary bouts confer risk for death, and 3) elucidate whether the total volume of sedentary time and its pattern of accumulation individually or jointly contribute to risk for death. The purpose of this study, therefore, was to examine the association between objectively measured sedentary time (both total volume and accrual in prolonged bouts) and all-cause mortality in a national cohort of U.S. middle-aged and older adults enrolled in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study. Methods Study Population REGARDS is a population-based study designed to examine racial and regional disparities in stroke. It comprises 30239 white and black adults aged 45 years or older enrolled between 2003 and 2007 from across the contiguous United States (19, 20). Detailed design and methods for REGARDS are described elsewhere (21). Briefly, demographic and cardiovascular risk factor data were collected by telephone interview and an in-home physical assessment on enrollment. A detailed summary of baseline measures is provided in the Supplement. Participants (or their proxies) were then followed for 6-month intervals to ascertain vital status. Objective measurements of sedentary behavior were collected from active REGARDS participants from 2009 to 2013 (mean time from study enrollment, 5.7 years [SD, 1.5]; range, 1.9 to 9.5 years) (22). A total of 7985 participants adhered to accelerometer wear requirements (4 days with accelerometer wear 10 hours), provided follow-up data, and were available for the current analyses (Supplement Figure 1). Supplement Table 1 shows the characteristics of included versus excluded REGARDS participants. The REGARDS study protocol was approved by the institutional review boards of participating institutions. All participants provided informed consent. Supplement. Supplementary Material Accelerometer Data Collection Methods for accelerometer data collection are described elsewhere (22). Briefly, participants were fitted with an Actical (Philips Respironics) accelerometer secured to their right hip using a nylon belt and were instructed to wear the device during waking hours for 7 consecutive days. The Actical had been validated formeasurement of physical activity and sedentary behavior and was shown to have acceptable reliability (2325). Activity counts were summed over 1-minute epochs. Nonwear periods were defined as at least 150 consecutive minutes of 0 activity counts. This nonwear algorithm was previously validated against daily log sheets in REGARDS participants (26). Measurements of 0 to 49, 50 to 1064, and at least 1065 counts per minute were defined as sedentary behavior, light-intensity physical activity, and MVPA, respectively, as determined in a laboratory-based calibration study (27). A sedentary bout was defined as consecutive minutes in which the accelerometer registered fewer than 50 counts per minute. A sedentary break was defined as at least 1 minute in which 50 or more counts per minute were registered after a sedentary bout. Both sedentary bouts and breaks were exclusively continuous periods, with no interruptions or nonwear intervals allowed in the definition. Outcome Ascertainment All-cause mortality was the primary outcome, defined as any death after completion of the accelerometer protocol regardless of cause. Dates of death were confirmed through review of death certificates, medical records, and administrative databases. Deaths through 4 September 2015 were included in the current analysis. Statistical Analysis Sedentary and physical activity variables were averaged across compliant days (10 hours of wear). Because of a high correlation between total sedentary time and wear time (Supplement Figure 2), we corrected for the influence of wear time by standardizing total sedentary time to 16 hours of wear time per day using the residuals obtained when regressing total sedentary time on wear time (see Methods section of the Supplement) (2830). Participants were stratified into quartiles according to total sedentary time and, separately, mean sedentary bout duration (a measure of overall prolonged, uninterrupted sedentary behavior). Cox proportional hazards regression modeling was used to calculate the hazard ratio (HR) for all-cause mortality associated with quartiles of total sedentary time (and separately, mean sedentary bout length). Crude HRs were initially calculated. Subsequent HRs were calculated after adjustment for age, race, sex, region of residence, education, and season the accelerometer was worn (model 1), with further adjustment for current smoking, alcohol use, body mass index (BMI), diabetes, hypertension, dyslipidemia, estimated glomerular filtration rate less than 60 mL/min/1.73 m2, atrial fibrillation, history of coronary heart disease, and history of stroke (model 2). Models were additionally adjusted for MVPA expressed continuously (model 3). Tests for linear trend across quartiles were conducted by including the quartile for each participant as an ordinal variable in regression models. Proportional hazards assumptions were confirmed with a Kolmogorov-type supremum test (31). The above analyses were then repeated in a fully adjusted model, testing interactions for age (<65 and 65 years), sex (male and female), race (black and white), BMI category (normal weight and overweight or obese), and MVPA category (<150 min/wk and 150 min/wk). As a secondary analysis, we examined the continuous doseresponse relationship between each sedentary characteristic and all-cause mortality in a fully adjusted model (model 3) using restricted cubic splines (32). Cubic polynomials were fitted with the mean of each sedentary characteristic set as the reference and knots placed at the 5th, 35th, 65th, and 95th percentiles (33). Nonlinear associations were evaluated using the likelihood ratio test. For nonlinear associations, spline models were used to describe the associations and when the association was determined to be linear, a linear model was used. Because of multicollinearity between total sedentary time and mean sedentary bout duration (r= 0.61), both variables were not included in the same model. Alternatively, to examine the individual and joint associations of total sedentary time and prolonged, uninterrupted sedentary behavior with mortality, participants were classified into 4 categories: low total sedentary time (<750 min/d) and low prolonged sedentary bout time (<10 min/bout), low total sedentary time and high prolonged sedentary bout time (10 min/bout), high total sedentary time (750 min/d) and low prolonged sedentary bout time, and high total sedentary time and high prolonged sedentary bout time. Hazard ratios for all-cause mortality were calculated for each joint category in comparison with the lowlow group in a fully adjusted model (model 3). Thresholds for total sedentary time (750 min/d) and mean sedentary bout duration (10 min/bout) were selected on the basis of the restricted cubic splines and were confirmed using a method described by Contal and O'Quigley (see Methods section of the Supplement) (34). To allow for the possibility that sedentary bouts of