In recent years, a substantial literature has identified sedentary behaviour as an independent risk factor for a wide range of health outcomes. [1], [2], [3], [4], [5] It has been postulated that there is something about sedentary behaviour in itself — i.e. other than the fact that it displaces other types of physical activity — which causes cardio-metabolic deficits. For example, postural stasis, triggering a chain of unhealthy molecular sequelae, may be a critical mechanism. [6]

The persistent relationship between sedentary behaviour and cardio-metabolic deficits, even when adjusted for physical activity, has been cited as evidence of sedentary behaviour's unique health effects. [1], [2] However, intriguingly, epidemiological studies on which these assertions are based have adjusted only for limited measures of physical activity, such as duration of moderate-to-vigorous physical activity (MVPA), [3] or even subcomponents of MVPA, such as leisure time MVPA. [4], [5] This approach has a number of limitations. It treats MVPA as a homogeneous entity, whereas moderate physical activity and vigorous physical activity are recognized to have distinct physiologic effects. [7] Furthermore, light physical activity (eliciting between 1.5 and 3 METs) has been overlooked, and there is a growing body of literature that light physical activity has health benefits. [8], [9] This is important, particularly when considering that light physical activity constitutes a relatively large part of the day for most adults when compared to MVPA. [10]

In the largest epidemiological study to date based upon the National Health and Nutrition Examination Survey (NHANES) dataset, Healy and colleagues stated that their analyses could not be controlled for light physical activity because light physical activity and sedentary behaviour were almost perfectly inversely associated (Spearman's rho = −0.98), and thus would have caused collinearity in the regression models. [11] However, if these variables are virtually the inverse of one another, then the detrimental associations identified between sedentary time and various cardio-metabolic biomarkers might, in fact, be markers of favourable associations between light physical activity and the biomarkers.

To truly ascertain whether sedentary behaviour and cardio-metabolic markers are related independent of physical activity, studies are needed which control for total physical activity (i.e. light, moderate and vigorous activity). If associations between sedentarism and health outcomes disappear, or are largely attenuated, when corrected for total physical activity, then displacement would appear to be the most likely mechanism.

Accounting for all types of physical activity (light, moderate and vigorous) is not possible if analyses are based on duration derivatives of accelerometry (e.g. minutes of sedentary time, minutes of light physical activity and so on); collinearity will necessarily occur, given that time in all bands will add up to 24 hours per day (adjusted for wear time). However, counts-based derivatives of accelerometry (e.g. total daily accelerometer counts) might alleviate the issue of collinearity, since total daily accerelometer counts do not have a fixed upper limit, and will vary from person to person, and day to day.

This study aimed to investigate the associations between sedentary behaviour and cardio-metabolic biomarkers when corrected for total physical activity (including light, moderate and vigorous physical activity). In addition, we aimed to compare the associations between sedentary behaviour and cardio-metabolic biomarkers when adjusting for total physical activity to those identified when adjusting for a more conventional measure of physical activity, namely MVPA minutes. Analyses were undertaken using a large, representative sample of US adults from the 2003/4 and 2005/6 waves of NHANES.

A total of 4,618 NHANES participants met the inclusion criteria; their socio-demographic and behavioural characteristics are provided in Table 1.

A series of linear regression models were built, to determine the presence and magnitude of associations between mean daily sedentary time and each cardio-metabolic biomarker (Table 2). In the simplest model (Model 1 – in which the only covariate was accelerometer wear time), sedentary time was significantly associated with all 11 cardio-metabolic biomarkers. In all cases with the exception of diastolic blood pressure, higher sedentary time was associated with detrimental levels of the biomarkers. However, the relationship between sedentary time and each biomarker was very small, as indicated by the adjusted R² values (0.003 to 0.038), showing that just 0.3 to 4% of the variability in cardio-metabolic biomarkers was explained by the model.

Models 2, 3 and 4 involved further covariates being added to the regression models (socio-demographic, plus medical history, plus dietary and smoking behaviour). Looking across these models in Table 2, a pattern for the R² values to gradually increase is apparent, indicating that the more complex models better explained the variability in cardio-metabolic biomarkers. By Model 4, sedentary time was still significantly associated with 10 of the 11 cardio-metabolic biomarkers, although there was a clear pattern for the sedentary time metric regression coefficient to reduce in magnitude across the models, indicating that the relationship between sedentary time and cardio-metabolic biomarkers weakened as confounders were accounted for.

Model 5 was similar to the linear regression model previously reported in the literature, [11] where the relationship between sedentary time and cardio-metabolic biomarkers was adjusted for duration of MVPA behaviour, in addition to socio-demographic, medical history, and dietary and smoking behaviour variables. In this model, the sedentary time metric regression coefficient further reduced in magnitude, so that sedentary time was significantly associated with 8 of the 11 cardio-metabolic biomarkers. In all cases in which a significant association was present, higher sedentary time was associated with detrimental differences in the cardio-metabolic biomarkers.

Finally, Model 6 examined the relationship between sedentary time and cardio-metabolic biomarkers, adjusting for total physical activity (total daily accelerometer counts, excluding sedentary counts), in addition to socio-demographic, medical history, and dietary and smoking behaviour variables. In this model, sedentary time is significantly associated with 2 of the 11 cardio-metabolic biomarkers: C-reactive protein and triglycerides. In both cases, the magnitude of the relationship is very small, as indicated by metric regression coefficient values of −0.06 and 0.04, respectively. Interestingly, in the case of C-reactive protein, the direction of the relationship was reversed, so that higher sedentary time was associated with favourable differences in C-reactive protein. There were no significant interactions between sedentary time and sex, ethnicity or age for either triglycerides or C-reactive protein.

In order to determine the relative magnitude of the association between the cardio-metabolic outcomes and sedentary time and total physical activity, the standardized β for sedentary time was compared with the standardized β for total physical activity (Table 3). Total physical activity was most strongly and consistently associated with the biomarkers (significant associations in 9 out of 11 biomarkers, absolute standardized β = 0.04–0.30). In all cases, higher physical activity was associated with favourable levels of the biomarkers. There were, however, few and weak associations between sedentary time and biomarkers (significant association in 2 out of 11 biomarkers, absolute standardized β = 0.02–0.12). As previously noted, in one of these two cases (C-reactive protein), higher sedentary time was associated with favourable differences in the biomarker.

In an effort to understand the clinical significance of the relationships between sedentary time and cardio-metabolic biomarkers, and how these apparent relationships differed depending on whether analyses were corrected for MVPA minutes or total physical activity, we undertook one further analysis. We divided sedentary time into quartiles, as has been done by previous investigators, [11] and calculated the adjusted means (95% CI) for the biomarkers, using the same covariates used in Table 2 Model 5 (MVPA minutes) and Model 6 (total physical activity). Sedentary time quartile cutpoints were 6.88, 8.14 and 9.43 hours/day. As can be seen from Figure 1, when analyses were corrected for MVPA minutes, 8 out of 11 biomarkers showed significant detrimental relationships with sedentary time (all biomarkers except systolic blood pressure, diastolic blood pressure and C-reactive protein). However, when analyses were corrected for total physical activity, the associations were no longer statistically significant for any of these 8 biomarkers. Once total activity counts were accounted for, only one biomarker had a significant relationship with sedentary time, C-reactive protein, and this biomarker showed a favourable relationship, that is, as sedentary time increased, C-reactive protein significantly decreased (P = 0.02).

This study showed that while there are weak relationships between cardio-metabolic biomarkers and sedentary behaviour when analyses are adjusted for MVPA minutes, the associations effectively disappear when analyses are adjusted for total physical activity. The exceptions to this are C-reactive protein, which show a minute, favourable association with sedentary time, and triglycerides, which show a minute, detrimental association with sedentary time.

While previous studies have found statistically significant relationships between sedentary behaviour and biomarkers of cardio-metabolic risk, [11], [18], [19] few have drawn attention to the fact that these relationships are very weak, and may not be of major clinical significance. It is possible that the relationships between sedentary behaviour and biomarkers are due to residual confounding. Accelerometry-based measures of physical activity (such as MVPA minutes and total physical activity counts) are quite crude. As such, residual confounding may account for associations between sedentary time and health parameters even after adjustment for physical activity.

Alternatively, it is possible that they are true associations, albeit of very small magnitude. We produced Figure 1 to aid interpretability of the relationships between sedentary behaviour and health biomarkers. Looking at triglycerides (the only biomarker that maintained a detrimental association with sedentary time once corrected for total physical activity in Table 2), there was a very small difference between the triglyceride levels in the most sedentary versus the least sedentary segments of the population – just 0.15 mmol per liter variation occurred across the sedentary behaviour spectrum. It is difficult to argue that such a difference is of clinical significance considering that a change of 0.28 mmol/L is required to shift someone from one risk band to another (e.g. from “high” to “borderline”, or from “borderline” to “normal”; based on the definitions of <1.69 mmol/L =  normal, 1.69−2.25 =  borderline, >2.25 mmol/L =  high. [20]). Furthermore, the small difference in triglycerides association with quite marked variation in sedentary behaviour (4.5 h difference in sedentary time between the median values for the least sedentary and most sedentary quartiles) suggests the relationship is of minimal population health significance.

The study has two main implications. Firstly, further research is needed in other cross-sectional datasets, and using other research designs, to replicate our findings. Appropriately designed experimental studies will help our understanding of potential mechanisms underpinning the link between sedentary behaviour and health risk. Such studies could definitively answer the question of whether overall activity level is the underlying factor, or alternatively, whether physical activity and sedentary behaviour are indeed two independent entities. In recent years public health messages have increasingly encouraged people to reduce sitting behaviour (and often, replacing it with stationary standing); our findings suggest that a better message would be to encourage movement at a low intensity. Secondly, our study has important methodological implications for future research examining the health effects of physical activity and sedentary behaviour. Focussing on MVPA ignores a large part of the intensity spectrum of physical activity, and a part which can have a significant impact on health. Failure to account for the full spectrum of physical activity may inadvertently attribute health effects to sedentary behaviour which may in fact be due to lower total physical activity.

A strength of the current study was the use of a large, nationally representative dataset. Physical activity and sedentary behaviour were measured objectively using accelerometers, which minimized the bias associated with recall. [21] Accelerometer data handling ensured that sedentary time and physical activity were estimated with greatest accuracy possible. In particular, the censoring of consecutive minutes of zero counts allowed the proper estimation on non-wear time; these minutes were removed from total activity, thus preventing the overestimation of time spent in sedentary.

Furthermore, the comprehensive nature of the NHANES dataset allowed us to statistically control for numerous covariates, including ethnicity, socioeconomic status, medical history and diet (including saturated fat and alcohol intake), which if not included, may have confounded the results. Limitations of the study should also be acknowledged. This study is cross-sectional, therefore only associations, and not causation, can be determined.

Some may argue that a correlation of Spearman's rho = −0.78 between sedentary minutes and total activity counts less sedentary represents collinearity, threatening the validity of findings. Collinearity diagnostic tests were undertaken to explore this issue. The Variance Inflation Factor (VIF) for total physical activity and sedentary time in our models was 5.2, which is well below the threshold of VIF >10 generally accepted to indicate collinearity [22], [23], [24]. Furthermore, we examined the stability of the regression coefficients by running statistical models using sedentary time and total physical activity separately, and together. Should collinearity have been present, we would have expected the regression estimates to change erratically in the combined model compared with the separate models. However, the model outputs were remarkably consistent across the separate and combined models, indicating that the analyses presented within this paper are robust. The results of these analyses are presented in the Table S2.

In conclusion, while there are significant (albeit weak) relationships between sedentary behaviour and cardio-metabolic risk factors with or without adjustment for MVPA minutes, these relationships dissipate when adjusted for overall physical activity. Thus it appears that sedentary behaviour may not have health effects independent of physical activity.