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Sitting Less and Moving More

2018; Lippincott Williams & Wilkins; Volume: 72; Issue: 5 Linguagem: Inglês

10.1161/hypertensionaha.118.11190

1524-4563

Paddy C. Dempsey, Robyn N. Larsen, David W. Dunstan, Neville Owen, Bronwyn A. Kingwell,

Urban Transport and Accessibility

HomeHypertensionVol. 72, No. 5Sitting Less and Moving More Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplementary MaterialsFree AccessReview ArticlePDF/EPUBSitting Less and Moving MoreImplications for Hypertension Paddy C. Dempsey, Robyn N. Larsen, David W. Dunstan, Neville Owen and Bronwyn A. Kingwell Paddy C. DempseyPaddy C. Dempsey Correspondence to Paddy C. Dempsey, Physical Activity, Metabolic & Vascular Physiology, and Behavioural Epidemiology Laboratories, Baker Heart and Diabetes Institute, Level 4, 99 Commercial Rd, Melbourne, Victoria 3004, Australia. Email E-mail Address: [email protected] From the Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (P.C.D., R.N.L., D.W.D., N.O., B.A.K.) MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge Biomedical Campus, United Kingdom (P.C.D.) Centre for Urban Transitions, Swinburne University of Technology, Melbourne, Victoria, Australia (P.C.D., N.O.) , Robyn N. LarsenRobyn N. Larsen From the Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (P.C.D., R.N.L., D.W.D., N.O., B.A.K.) , David W. DunstanDavid W. Dunstan From the Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (P.C.D., R.N.L., D.W.D., N.O., B.A.K.) Mary MacKillop Institute of Health Research, Australian Catholic University, Melbourne, Victoria (D.W.D.). , Neville OwenNeville Owen From the Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (P.C.D., R.N.L., D.W.D., N.O., B.A.K.) Centre for Urban Transitions, Swinburne University of Technology, Melbourne, Victoria, Australia (P.C.D., N.O.) and Bronwyn A. KingwellBronwyn A. Kingwell From the Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (P.C.D., R.N.L., D.W.D., N.O., B.A.K.) Originally published17 Sep 2018https://doi.org/10.1161/HYPERTENSIONAHA.118.11190Hypertension. 2018;72:1037–1046Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: September 17, 2018: Ahead of Print On the basis of recent changes to blood pressure (BP) guidelines,1 some 46% of Americans (a further 31 million people) are now classified as having hypertension (BP ≥130/80 mm Hg). This new classification recognizes the recent clinical trial evidence on the benefits of lower BP targets2 and, among other factors, emphasizes the importance of considering how nonpharmacological strategies (ie, lifestyle modification) can be better incorporated into broader prevention messages.3 In this context, and with conventional guidelines focusing on moderate-vigorous physical activity, there is unrealized potential for benefitting a large proportion of the at-risk population through broadening the range of physical activity options in ways that might be more amenable to lifetime adherence.Although the benefits of a physically active lifestyle for overall cardiometabolic health, including BP control, are well known,4–7 a large and growing proportion of the global population is physically inactive.8,9 Worksites, schools, homes, and public spaces are physically engineered and socially arranged in ways that minimize regular movement and muscular activity and maximize the time spent sitting. This is against a background of unprecedented demographic shifts associated with the aging of populations, with higher proportions experiencing more years of frailty, a range of chronic noncommunicable diseases and risk factors, and poorer physical function and quality of life. Aside from contributing significantly to increases in healthcare costs, these combined factors represent a formidable set of clinical and public health challenges.The contribution of low rates of participation in moderate-vigorous physical activity to the chronic disease burden has provided the impetus to explore the efficacy of physical activity options that are more amenable to lifetime adherence and that have broader population reach. In this regard, emerging strategies focusing on reducing and changing the patterns of sedentary behaviors (put simply, too much sitting) may have potential for lowering the incidence and prevalence of hypertension, as well as minimizing medication use in those already treated.Through a hypertension lens, this review focuses on the potential health implications and some of the plausible countermeasures for the high volumes of prolonged sitting that now characterize modern lifestyles. We synthesize findings on the specific relationships of sedentary behavior with BP, which primarily are from observational and acute experimental studies, including a discussion on the relevant cardiovascular mechanisms. We also consider what will need to be better understood as a basis for evidence-based recommendations on sedentary time in the context of BP control and identify evidence gaps for future research.Sedentary Behavior: a Newly Identified Element for Chronic Disease Risk and a Target for ManagementRegular moderate-vigorous physical activity is well established as an effective tool in the prevention and management of multiple chronic diseases, including hypertension.4,7 However, in recent years, sedentary behavior, defined as any waking behavior characterized by an energy expenditure ≤1.5 metabolic equivalents while in a sitting or reclining posture, has received increasing attention as a clinical and population health problem that is additional to insufficient moderate-vigorous physical activity.10 Reasons for this new perspective around sedentary behavior largely stem from 3 key points (expanded below). For clarity and distinction, we refer to recommended amounts of moderate- to vigorous-intensity physical activity as exercise and utilize the terms sitting and sedentary behavior interchangeably throughout this article.7Modest uptake and adherence to exercise guidelines: despite the multitude of potential health benefits derived from regular physical activity, population uptake is low. One-third of many adult populations (about 1.5 billion people globally) and four-fifths of adolescents do not adhere to minimum recommended levels of moderate-vigorous physical activity.8 Although leisure-related physical activity levels have tended to remain relatively steady over time, physical activity at work, in the domestic environment and in transportation, has all decreased in recent decades.8,9 Sustained and growing concerns also exist around the limited uptake and adherence to exercise guidelines in longer term trials11 and in accordance with national/global activity guidelines, particularly for older adults and in deconditioned/clinical populations.8,12–15High volume of waking hours spent sedentary: in developed countries, and in the rapidly urbanizing populations of developing countries, sedentary behaviors have become the primary default behavioral option, inextricably embedded in work, school, transport, and leisure time. Data obtained from studies using accelerometers, mainly from America and Australia, indicate that adults spend on average 55% to 70% of their waking hours (or >8–10 hours/day) engaged in sedentary behaviors.16–18 Furthermore, recent Australian-based data suggest that just under half of the ≈9 hours of total sitting time (as measured by posture-sensitive accelerometers)19 is spent in prolonged unbroken bouts of >30 minutes and that just over half of all adults accumulated >4 hours per day of their sitting time in this manner (Figure 1).Evidence on the associations of total sedentary time, and its pattern of accumulation, with cardiometabolic risk: prospective epidemiological evidence suggests that high volumes of sedentary time are associated with premature mortality and cardiometabolic risk biomarkers for type 2 diabetes mellitus, cardiovascular disease, and certain cancers. These deleterious associations are partly moderated by time spent in moderate-vigorous physical activity but are particularly evident in those who undertake insufficient or no moderate-vigorous physical activity.7,20,21 Furthermore, accumulating observational and experimental evidence indicates that specific patterns of sedentary time (ie, whether sitting is undertaken in prolonged or regular intermittent bouts) may be differentially associated with a number of cardiometabolic risk biomarkers and premature mortality.19,22–25 For example, a recent large-scale observational study found that both total sedentary time and prolonged uninterrupted sedentary bouts were associated with an increased risk for all-cause mortality, after controlling for moderate-vigorous physical activity and traditional cardiovascular risk factors.24 Another recent cross-sectional study, using inclinometer data from a subset of Australian-based participants (also see Figure 1 from the same cohort), showed that both greater amounts of sitting time and prolonged sitting time were deleteriously associated with waist circumference, body mass index, HDL cholesterol, triglycerides, 2-hour postload glucose, and fasting plasma glucose.23Download figureDownload PowerPointFigure 1. Unpublished data showing how a subsample of Australian adults (n=717; aged 36–80 y) allocated their physically active and sitting time behaviors on average during waking hours (derived from both ActiGraph and ActivPAL activity monitors and normalized to 16 h/d). These data highlight the high volumes of sitting time typically observed and the proportion of people who accumulated sitting time in prolonged unbroken bouts (≥30 min). Note that moderate-vigorous–intensity activity is calculated based on every minute of activity accumulated during the day (ie, not just in exercise bouts of ≥10 min).As a result, leading health agencies, such as the American Heart Association26 and the American Diabetes Association,27 have begun to acknowledge the likely clinical and population health impact of changing sedentary behaviors. Consideration of the mechanistic linkages of reducing and breaking up prolonged sitting with BP control and hypertension is highly relevant in this context. Indeed, evidence from epidemiological observational studies and a new body of findings from acute experimental trials can provide helpful insights.Sedentary Behavior and BP ControlMeasurement ChallengesThere are significant challenges in objective quantification of both physical activity patterns and BP, which make relational investigations difficult.28,29 Most observational studies examining associations of sedentary behavior with BP and hypertension have typically relied on self-reported daily sitting or television/screen viewing time—methods that are susceptible to recall and response bias, social desirability, and underreporting or overreporting.28 Accelerometer-derived measures of movement and posture have been used recently to more "objectively" characterize sedentary and active behaviors because they are less subject to the biases that are inherent to self-report. However, they are not without limitations. For example, these newer methods cannot determine the behavioral contexts (ie, the location and purpose of these behaviors), and results may be influenced by wear-time differences, some activity misclassification (depending on device type/location), and data analysis approaches.Particularly under conditions of normal daily living, BP measurement is associated with additional challenges. BP is an inherently labile parameter, with considerable temporal variation from heart beat to heart beat and across the 24-hour day. Thus, interpretation of a single time-of-day BP must be in a behavioral context that considers additional factors, such as dietary and fluid intake, physical activity, emotions, stress, and drugs (including caffeine and nicotine). In addition, BP measurements can be dramatically affected by the white coat or masked effects in clinic/office settings and is often measured under a variety of conditions (eg, postures) with differing preceding rest periods. Although not without limitations, 24-hour ambulatory BP has better prognostic value than single office BP measurements and is thus considered the reference standard to diagnose hypertension according to certain groups.29The above measurement challenges likely contribute to variability in observational evidence on the associations of sedentary behavior with BP and hypertension (almost always assessed via resting office BP). Indeed, such evidence to date has been quite heterogeneous and inconsistent,30–34 with relatively small mean effect sizes.Observational EvidenceIn a recent systematic review and meta-analysis, Lee and Wong35 examined the associations of time spent in sedentary behaviors with BP in both adults and children. Of the 28 studies included in the meta-analysis (8 longitudinal and 20 cross-sectional), 10 assessed sedentary behavior via accelerometry, and the remainder used self-report measures (ie, television/screen viewing time, sitting time, or both). Results from this meta-analysis revealed that for each hour increase in self-reported sedentary behavior, there was an associated small increase in systolic and diastolic BP of 0.06 (95% CI, 0.01–0.11) and 0.20 (95% CI, 0.10–0.29) mm Hg, respectively. Additionally, for each hour increase in sedentary behavior, there was a 2% elevation in risk for hypertension (odds ratio, 1.02; 95% CI, 1.003–1.03).Interestingly, no statistically significant associations were observed when sedentary time was assessed via accelerometry, although systolic BP trended at 0.10 (95% CI, −0.001 to 0.21; P=0.06) mm Hg.35 These discrepancies between the self-report and device-based exposure measures suggest either differences in measurement variability, validity, and reliability (for both the sedentary behavior exposures and the resting BP outcomes), poorer compliance with the use of the accelerometers (which has been shown to be lower in those with hypertension36), or that the disparity in timing of office BP measurements in relation to the active/sedentary behaviors and other factors (as mentioned previously) may also be important.In one of the few observational studies to utilize both 7-day accelerometry and ambulatory BP measures, Hamer et al37 showed in a sample of 216 middle-aged black and white-African school teachers with or at high risk of hypertension that the positive associations of sedentary time with 24-hour BP (but not daytime or resting office BP) were primarily driven by the nighttime readings. Further analyses showed that participants in the highest sedentary tertile were also more likely to be nighttime nondippers (odds ratio, 2.11; 95% CI, 0.99–4.46; P=0.052) compared with those in the lowest sedentary tertile. These nighttime-specific BP findings for the more sedentary participants are intriguing because ambulatory BP-derived sleep BP (presence/absence of dipping) tends to be a more stable BP measure and is a stronger predictor of cardiovascular risk, independent of office BP or wake-time BP.38 The findings could be because of elevated nighttime sympathetic activation, which is consistent with the findings from 1 experimental study demonstrating higher plasma noradrenaline levels during prolonged sitting.39 Alternatively, BP readings are generally more stable nocturnally. However, there is also the potential for measurement issues because study participants were required to sleep in unfamiliar surroundings at the overnight clinical facility. Importantly, the study also showed that those who spent less daily time in light-intensity physical activity (the corollary of spending more time sedentary) had significantly higher 24-hour ambulatory and daytime systolic and diastolic BP, as well as higher resting systolic BP.It is thus difficult to draw any firm conclusion from the observational evidence to date. The question of whether sedentary behavior is an acute BP stressor, as distinct from other conventional risk factors that contribute to sustained BP elevation (eg, age, obesity, and diabetes mellitus), is difficult to disentangle. Ambulatory BP measures may be better suited for studying the patterning of BP on days characterized by periods of prolonged sitting. Thus, further prospective study evidence using ambulatory BP methods, and with more detailed sensor-assessed measures of actual sitting patterns/postures and their context/setting, would be highly informative. Consideration of the specific population (eg, normotensive and uncomplicated hypertension and medication) in these contexts will also be important.Experimental EvidenceFew studies have examined the effects of prolonged sitting on BP (see Table S1 in the online-only Data Supplement for a summary of the relevant acute studies published to date). Most studies,39–45 but not all,46,47 have observed significant systolic or diastolic BP-lowering effects when prolonged sitting time has been reduced or interrupted (mostly with walking breaks but also some with standing breaks), ranging from 1 to 16 mm Hg in magnitude. However, the majority of studies have generally included BP as a secondary end point, which may limit the rigor and interpretability of the BP findings.Although not an entirely consistent phenomenon, reductions in BP with activity breaks in prolonged sitting have tended to be more modest in the physically active healthy younger populations, but most pronounced in older/at-risk populations and those with overt or prehypertension. For example, in inactive overweight/obese adults (over half of whom were classed as having prehypertension or hypertension), interrupting sitting time with brief bouts of either light- or moderate-intensity walking significantly lowered resting systolic and diastolic BP by ≈2 to 3 mm Hg.43 Similarly, reductions in resting systolic and diastolic BP of significantly greater magnitude (mean, ↓14–16 and ↓8–10 mm Hg, respectively) were shown when sitting was interrupted with either light-intensity walking or with simple resistance activities in adults with type 2 diabetes mellitus (of whom 88% were also hypertensive).39 These latter 2 laboratory-based studies support the contention that the magnitude of BP lowering by interrupting sitting time, or the BP increase with prolonged uninterrupted sitting, may be greater in hypertensive compared with normotensive groups. Moreover, BP reductions in these 2 studies were established on top of standard antihypertensive medications.To further explore the hypothesis that those with hypertension may be more susceptible to BP elevation with prolonged sitting exposures, or derive more benefit from reducing and breaking up sitting time, we pooled data from 4 separate laboratory-based randomized crossover trials. These studies examined the BP responses to prolonged uninterrupted sitting versus sitting interrupted by regular 2- to 3-minute walking breaks (Figure 2A) or by regular 3-minute simple resistance activity breaks (half squats, calf raises, gluteal contractions, and knee raises; Figure 2B) in overweight/obese adults with and without hypertension. Figure 2 and accompanying Table S2 illustrate 2 key points:Download figureDownload PowerPointFigure 2. Temporal changes in systolic and diastolic blood pressure (BP) of pooled data from 4 separate crossover trials39,43,73,85 employing similar experimental protocols in individuals with and without hypertension. A, Lines represent line of best fit (with 95% CI, dotted lines) for uninterrupted sitting (red line) and sitting interrupted with short 2–3-min walking breaks (blue line) every 20–30 min after a 1-h steady-state period. B, Lines represent line of best fit (with 95% CI, dotted lines) for uninterrupted sitting (red line) and sitting interrupted with short 3-min simple resistance activities (green line) every 30 min after a 1-h steady-state period. Hypertensive individuals defined by a combination of clinical diagnosis/medication use or BP ≥130/80 mm Hg at screening visit. Solid dashed line represents new US clinical thresholds for hypertension (>130/80 mm Hg).1 Difference in slopes according to a linear mixed effects model adjusted for age, sex, body mass index, treatment order, and baseline values, ***P<0.001, **P=0.002 (see Table S2 for further details on the statistical models/results).Prolonged uninterrupted sitting appears to evoke increases in both systolic and diastolic BP in a manner proportional to the length of time spent sitting, and the magnitude of these changes is generally greater and more clinically relevant in those with hypertension compared with normotensives andRegular interruptions in prolonged sitting with either light-walking breaks or simple resistance activity breaks reduce both systolic and diastolic BP, but by a greater magnitude for simple resistance activity breaks, in both normotensive and hypertensive populations.The simple resistance activity breaks incorporated into these recent trials were designed to provide an alternative option to walking breaks, which usually obliges a person to leave their immediate workspace/location. They require no specialized equipment and only small amounts of floor space. In addition, the compound/multijoint nature of these activities engages a significant muscle mass in contractile activity and when performed regularly, could increase functional capacity and insulin sensitivity through maintenance or increases in muscle mass and adaptations in metabolic enzymes. These factors may be particularly relevant for overweight and aging populations with hypertension,48 the vast majority of whom do not engage in sufficient moderate-vigorous or muscle-strengthening activities, in accordance with national activity guidelines.7,49 If these findings are corroborated by further studies and in a chronic context, there are potential implications for future targeting and optimization of physical activity/sedentary behavior interventions in these population groups.Recent studies have also started to include more detailed ambulatory BP measures over consecutive days and while simulating free-living scenarios, which is providing insight into the sustained effects of sitting-reduction interventions. For example, Zeigler et al44,45 showed that prehypertensive, overweight/obese adults accumulating 2.5 hours of standing or light-intensity physical activity across the day equally reduced systolic and diastolic ambulatory BP both during and after working hours by ≈3 to 4 mm Hg and ≈2 to 13 mm Hg, respectively, compared with a simulated 8-hour seated workday. Using a comparable design and measures, Bhammer et al41 also showed similar reductions in systolic, diastolic, and mean arterial BP (≈5–6 mm Hg) with moderate- but not vigorous-intensity walking breaks, but these effects were only observed in the evening after the intervention period (outside of the laboratory).The accumulation of the experimental findings described above is congruent with previous literature on the similarly beneficial impact of fractionized vs continuous exercise bouts,50–54 and the potential for a light-intensity physical activity threshold for BP lowering,55,56 which may even be related to simple postural changes (ie, sit-to-stand transitions) across the day. Further prospective and longer duration intervention studies of this nature, in more free-living settings and with ambulatory BP measures, will be important in elucidating whether prolonged sitting per se induces BP elevation. They will also assist in determining the efficacy and specificity of interventions that reduce and break up prolonged sitting time using a range of light- to moderate-intensity activities.Teasing apart the impact of other confounding and interacting factors of everyday living, such as dietary, stress, and sleep patterns, will continue to be a challenge and may require more tailored study designs and advanced measurement and analytical approaches. The timing of BP measurements relative to activity and dietary factors will also be important, with a combination of parallel ambulatory BP measurements to determine BP reactivity in real-time, and well-standardized resting and ambulatory BP measures taken after the intervention period, to determine chronic BP changes.Potential Physiological MechanismsTheoretical ConsiderationsThe potential underlying biological mechanisms by which a bout of prolonged sitting may acutely modulate BP are multiple but ultimately must result from alterations in cardiac output or total peripheral resistance. In this context, mechanisms are likely to predominantly affect total peripheral resistance and to include metabolic, autonomic, and direct vascular mechanisms (Figure 3).Download figureDownload PowerPointFigure 3. Hypothesized mechanisms by which prolonged sitting may influence risk for hypertension and cardiovascular complications. Systemic reductions in metabolic demand and blood flow, and elevated sympathetic nervous system (SNS) activity, may evoke concurrent decrements in insulin sensitivity and vascular function, promoting oxidative stress and low-grade inflammatory cascades. When prolonged sitting is habitual, these factors likely contribute to the development of hyperglycemia, dyslipidemia, and hypertension, promoting vascular damage and progression toward serious cardiovascular complications. GFR indicates glomerular filtration rate; and NOS, nitric oxide synthase.The concept that metabolism controls blood flow and thus drives pressure is a potentially important consideration with respect to understanding how prolonged sitting might modulate BP. Prolonged sitting is characterized by low energy expenditure or metabolic demand, as measured by indirect57,58 and whole-room calorimetry,59 where the average energy cost of common sedentary behaviors (reclining, watching television, reading, and typing on a computer) is narrowly banded around ≈1.0 metabolic equivalent, even in the postprandial state.59 Metabolic demand is the key determinant of blood flow in all tissues, with multiple mechanisms linking the metabolic requirements of tissues in terms of oxygen and substrates (glucose and fatty acids), to blood supply.Since metabolic demand is low during prolonged sitting, vasodilatory metabolites—including adenosine—are correspondingly low, and the caliber of capillaries is therefore minimized. It would be expected that low metabolic demand would result in closure of precapillary sphincters and the shutdown of nutritive capillary beds (Figure 4). Capillary closure as a result of low metabolic demand within muscles reduces the pressure differential with upstream feed arteries, thus reducing blood flow via simple hemodynamics. As a consequence, vascular shear stress is reduced, promoting vasoconstriction through associated endothelial mediators (ie, reduced NO [nitric oxide] and increased ET-1 [endothelin-1]). Low metabolic demand, therefore, has the potential to increase peripheral resistance and drive BP up through effects at multiple levels of the vascular tree. A seated posture creates bends and constrictions in major blood vessels of the lower limbs, particularly under the thighs.60 Such effects may result in simple mechanical increases in peripheral resistance but also promote turbulent blood flow patterns, which may have acute and chronic consequences for blood flow and pressure regulation.61,62Download figureDownload PowerPointFigure 4. Hypothesized vascular mechanisms by which prolonged sitting may impact on blood pressure (BP) in contrast to sitting interrupted by regular active breaks. During prolonged sitting (left), (a) low metabolic/ATP demand within muscles results in low levels of vasodilator metabolites, constriction of precapillary arterioles, and closure of precapillary sphincters. This in turn results in blood being shunted through metarterioles. (b) Reduced pressure differential between capillaries and upstream muscular (distributing) arteries reduces blood flow and endothelial shear stress, promoting vasoconstriction through associated endothelial mediators (ie, reduced NO [nitric oxide] and increased ET-1 [endothelin-1]) and (c) reduced caliber of resistance arterioles, increasing peripheral resistance and BP. During brief 2–3-min activity bouts during prolonged sitting (right), (d) increased metabolic/ATP demand within muscles results in upregulation of vasodilator metabolites, dilation of precapillary arterioles, and relaxation of precapillary sphincters, promoting flow through nutritive capillaries. (e) The greater pressure differential between capillaries and upstream muscular (distributing) arteries increases blood flow and endothelial shear stress, promoting vasodilation through associated endothelial mediators and (f) increased caliber of resistance arterioles, reducing peripheral resistance and BP. Previously observed alterations in circulating noradrenaline (NA) during these 2 states are also depicted, along with ET-1 and NO bioavailability, for which the evidence is only preliminary.A further consideration is that increased hydrostatic pressure and reduced venous return (ie, via insufficient calf muscle pump activity) while being seated also leads to fluid accumulation in the lower limbs that is proportional to the time spent sitting.63–65 This fluid accumulation during the day likely shifts rostral overnight and is hypothesized to predispose or exacerbate obstructive sleep apnea, particularly in those with congestive heart failure or at increased risk for obstructive apnea,66–68 which has been associated with nocturnal hypertension and nondipping BP patterns.67 Significant peripheral edema may also have implications for nighttime BP elevation via carotid baroreceptor unloading (because of increased interstitial pressure), reduced baroreceptor afferent activity, and, therefore, a reflex increase in efferent sympathetic ac