原创 毛毛弟 一起学科研 2022-04-28 10:00
“护”说科研
Mechanisms of sitting-related risk
与久坐有关的风险机制
Biological systems related to the adverse health consequences of physical inactivity have been reviewed extensively but less is known about the pathways that underlie the risks of too much sitting. Experimental evidence is beginning to accumulate that elucidates some of the crucial biological associations between sitting time and decreased cardiovascular health. Laboratory studies with healthy and unhealthy adults have experimentally identified the effect of prolonged periods of sitting, with or without brief, physically active interruptions, on cardiovascular risk factors. The scientific rationale for these experimental approaches is underpinned by the crucial principle that, by definition, physical activity (that is, any bodily movement produced by skeletal muscles that requires energy expenditure) must be the countermeasure to sitting during waking hours. The relevant pathways are multifaceted, function across major biological systems and interact to increase the overall risk of cardiovascular disease (Fig. 3).
与缺乏体力活动的不良健康后果有关的生物系统已被广泛审查，但对过多坐着的风险所依据的途径知之甚少。实验证据开始积累，阐明了坐着的时间和心血管健康下降之间的一些重要的生物学联系。对健康和不健康的成年人进行的实验室研究已经确定了长时间坐着，无论是否有短暂的体力活动中断，对心血管风险因素的影响。这些实验方法的科学依据是一个重要的原则，即根据定义，体力活动（即任何由骨骼肌产生的、需要能量消耗的身体运动）必须是清醒时间内坐着的对策。相关的途径是多方面的，在主要的生物系统中发挥作用，并相互作用，增加心血管疾病的总体风险（图3）。
Vascular function
血管功能
Vascular function is affected during prolonged periods of sitting, particularly in the lower limbs (Fig. 3). A meta-analysis of 17 studies showed that prolonged sitting led to an acute impairment of vascular function as measured by flow-mediated dilation (standardized mean difference (SMD) –0.84). By contrast, breaking up prolonged periods of sitting with physically active interruptions significantly improved lower-limb vascular function (SMD 0.57). Reductions in blood flow and shear stress have been attributed to acute, sitting-induced vascular dysfunction. Indeed, a lower blood flow and shear stress decrease the availability of nitric oxide and increase the production of vasoconstrictors, such as endothelin 1, that impair vascular function. Evidence to support these mechanisms comes from trials of interventions that attenuate the reduction in blood flow and shear stress during sitting via lowerlimb heating, increasing metabolic flow via fidgeting or introducing regular activity interruptions. All interventions preserved vascular function.
长时间坐着时，血管功能会受到影响，特别是在下肢（图3）。对17项研究的Meta分析显示，长时间坐着会导致血管功能的急性损伤，这是通过血流介导的扩张来衡量的（SMD:-0.84）。相比之下，用体力活动打断长期坐着的时间，可显著改善下肢血管功能（SMD:0.57）。血流和剪切应力的减少被归因于急性、坐着引起的血管功能障碍。事实上，较低的血流和剪切应力减少了一氧化氮的可用性，增加了血管收缩剂的产生，如内皮素1，从而损害了血管功能。支持这些机制的证据来自于对干预措施的试验，这些干预措施通过下肢加热减轻坐着时血流和剪切应力的减少，通过坐立不安增加代谢流量或引入定期活动中断。所有的干预措施都保留了血管功能。
The mechanisms underlying the reduction in blood flow and shear stress during sitting are probably multifaceted. The diminished muscular activity when sitting, particularly in the large, lower-limb, weight-bearing muscles, and the subsequent reduction in energy demand lead to decreased peripheral blood flow, resulting in reduced shear stress. Additionally, decreases in blood flow and shear stress might relate to prolonged gravitational forces increasing the hydrostatic pressure within the lower limbs, a mechanism supported by observations of increased calf circumference after prolonged sitting, which indicates venous pooling. Sitting-induced increases in muscle sympathetic nerve activity and blood viscosity might also contribute to altered blood flow and shear stress.
坐着时血流和剪切应力减少的机制可能是多方面的。坐着时肌肉活动减少，特别是大块的下肢负重肌肉，以及随后能量需求的减少导致外周血流减少，导致剪切应力减少。此外，血流和剪切应力的减少可能与长时间的重力增加了下肢的静水压力有关，这种机制得到了久坐后小腿周长增加的观察结果的支持，这表明静脉积水。坐着引起的肌肉交感神经活动和血液粘度的增加也可能有助于改变血流和剪切应力。
Blood pressure
血压
The reduction in metabolic demand and blood flow during prolonged sitting is likely to contribute to acute increases in blood pressure, with several, but not all, studies reporting reductions in blood pressure when sitting time is interrupted by regular brief bouts of physical activity (Fig. 3). The magnitude of the effect of prolonged sitting in increasing blood pressure or the blood pressure-lowering effect of regular physically active interruptions seem to be greater in individuals with existing cardiovascular disease risk factors such as obesity and type 2 diabetes mellitus. The lower metabolic demand of sitting, coupled with reduced levels of vasodilatory metabolites, might lead to vasoconstriction in inactive muscles and, consequently, to increased peripheral resistance and mean arterial pressure. However, these mechanisms underlying the blood pressure-lowering effects of interrupting sitting time remain hypothetical given the current lack of relevant experimental evidence.
长时间坐着时新陈代谢需求和血流的减少可能会导致血压的急性升高，一些（但不是全部）研究报告称，当坐着的时间被定期的短暂体力活动打断时，血压会降低（图3）。对于已有心血管疾病危险因素（如肥胖和2型糖尿病）的人来说，长期坐着对血压升高的影响或定期进行体力活动中断的降压效果似乎更大。坐着的代谢需求较低，加上血管扩张代谢物的水平降低，可能会导致不活动的肌肉血管收缩，并因此导致外周阻力和平均动脉压增加。然而，鉴于目前缺乏相关的实验证据，中断坐着的时间所产生的降压效果的这些机制仍然是假设性的。
Elevated sympathetic nervous system activity might also contribute to acute increases in blood pressure during prolonged sitting. In patients with type 2 diabetes mellitus, prolonged sitting increased plasma noradrenaline levels, with a concurrent increase in blood pressure; interrupting sitting with regular brief bouts of physical activity resulted in blood pressure reductions. These blood pressure variations might be caused by changes in total peripheral resistance owing to the vasoconstricting influence of noradrenaline.
交感神经系统活动的增强也可能导致长时间坐着时血压的急性升高。在2型糖尿病患者中，长时间坐着会增加血浆去甲肾上腺素的水平，同时血压也会升高；通过定期的短暂体力活动来中断坐着，会导致血压下降。这些血压变化可能是由于去甲肾上腺素的血管收缩影响导致的总外周阻力的变化。
In the blood pressure context, the biomechanics of sitting itself might increase the risk of cardiovascular disease. Sitting causes bending and angulation of lowerlimb arteries owing to hip and knee flexion, which in addition to contributing to decreased blood flow, can also induce turbulent blood flow and shear-stress patterns (Fig. 3). Importantly, low and oscillatory shear stress can increase oxidative stress and decrease vascular function. Consistent with this perspective, blood flow and shear stress can be lower when lying supine with a bent leg compared with a straight leg. Under these experimental conditions, only the prolonged leg bending resulted in an impairment in vascular function. Furthermore, 3 hours of standing, thereby avoiding arterial bending in the legs, can preserve leg vascular function compared with prolonged sitting. Arterial angulation during sitting might also increase peripheral vascular resistance, contributing to sitting-induced elevations in blood pressure.
在血压方面，坐着的生物力学本身可能增加心血管疾病的风险。由于髋关节和膝关节的屈曲，坐着会导致下肢动脉的弯曲和成角，这除了导致血流减少外，还可能诱发紊乱的血流和剪切应力模式（图3）。重要的是，低的和震荡的剪切应力可以增加氧化应激，降低血管功能。与这一观点相一致的是，与直腿相比，仰卧时的血流和剪切应力会更低。在这些实验条件下，只有长时间的腿部弯曲会导致血管功能受损。此外，3小时的站立，从而避免了腿部的动脉弯曲，与长时间坐着相比，可以保护腿部血管功能。坐着时的动脉弯曲也可能增加外周血管阻力，导致坐着引起的血压升高。
Blood glucose levels
血糖水平
Postprandial glucose, insulin and triacylglycerol levels in blood are acutely elevated after periods of prolonged sitting (Fig. 3), which might also contribute to the previously described effects of sitting on vascular function because insulin resistance and hyperglycaemia are associated with vascular dysfunction. This sitting-induced metabolic dysfunction is attenuated by regular interruptions with physical activity. A metaanalysis of 37 studies showed that regular interruptions with physical activity during prolonged sitting had a significant beneficial effect by acutely reducing glucose (SMD –0.54) and insulin (SMD –0.56) levels compared with continuous sitting. Furthermore, individuals at higher risk of cardiovascular disease (physically inactive, type 2 diabetes mellitus and impaired fasting glucose) had greater reductions in glucose levels (SMD –0.62) with regular active interruptions. Although most studies have investigated the acute changes in glycaemic control during a single day of sitting, with or without brief, physically active interruptions, some studies have shown that the improved glycaemic regulation induced by regular active interruptions to sitting persists overnight.
长时间坐着之后，血液中的餐后葡萄糖、胰岛素和三酰甘油水平会急性升高（图3），这可能也是之前描述的坐着对血管功能的影响，因为胰岛素抵抗和高血糖与血管功能障碍有关。这种坐着引起的代谢功能紊乱会被定期中断的体力活动所削弱。一项对37项研究的Meta分析显示，与持续坐着相比，在长时间坐着时定期中断体力活动具有显著的有益效果，可急性降低葡萄糖（SMD:-0.54）和胰岛素（SMD:-0.56）水平。此外，心血管疾病风险较高的人（身体不活跃、2型糖尿病和空腹血糖受损）在定期活动中断时，葡萄糖水平的降低幅度更大（SMD:-0.62）。尽管大多数研究调查了单日坐着时血糖控制的急性变化，无论是否有短暂的体力活动中断，一些研究表明，定期主动中断坐着所引起的血糖调节的改善会持续一晚。
The primary mechanism potentially explaining the influence of sitting on glucose metabolism relates to glucose uptake by skeletal muscle via insulin-mediated and contraction-mediated pathways. Both pathways result in glucose transporter 4 translocation to the plasma membrane, facilitating glucose uptake and thereby reducing blood glucose levels. Experimental evidence from skeletal muscle biopsy samples has shown that interrupting prolonged sitting with regular active bouts for 1 or 3 days increased the expression of proteins involved in both pathways compared with 1 or 3 days of uninterrupted sitting. Furthermore, physically active interruptions during prolonged sitting lead to the increased expression, in skeletal muscle, of genes related to the regulation of carbohydrate metabolism compared with uninterrupted sitting. Therefore, frequent muscular contractions resulting from physically active interruptions in prolonged sitting might promote increased muscle cell glucose uptake via the increased expression of glucose transporter 4.
可能解释坐姿对葡萄糖代谢影响的主要机制与骨骼肌通过胰岛素介导和收缩介导的途径吸收葡萄糖有关。这两种途径都会导致葡萄糖转运体4转运到质膜上，促进葡萄糖的摄取，从而降低血糖水平。来自骨骼肌活检样本的实验证据表明，与1或3天不间断的坐着相比，用有规律的活动中断长时间的坐着，会增加参与这两种途径的蛋白质的表达。此外，与不间断地坐着相比，在长期坐着期间，体力活动的中断导致与碳水化合物代谢调节有关的基因在骨骼肌中的表达增加。因此，长时间坐着时的体力活动中断导致的频繁的肌肉收缩可能会通过葡萄糖转运体4的表达增加而促进肌肉细胞的葡萄糖摄取。
Regular, physically active interruptions during prolonged sitting had a small significant beneficial effect by acutely reducing triacylglycerol levels (SMD –0.26) compared with uninterrupted sitting. The smaller effect of physically active interruptions during sitting on triacylglycerol levels compared with the effects on glucose and insulin levels might relate to the delayed activation of lipoprotein lipase after physical activity. Consequently, studies assessing acute effects (single day designs) do not capture the long-term beneficial effect of physically active interruptions during sitting time that have been observed in 2-day or multi-day study designs. Studies in animals have shown that prolonged muscle inactivity lowers lipoprotein lipase activity. Therefore, muscle inactivity while sitting might attenuate the muscle-mediated uptake of fatty acids. Experimental research in humans is required to further explore the cardiovascular-health relevance of this hypothesis. Studies in humans have investigated alternative mechanisms underlying the beneficial effects of physically active interruptions during prolonged sitting on triacylglycerol levels. Lipidomic analysis in patients with type 2 diabetes mellitus showed that regular interruptions to sitting reduced the plasma levels of pro-inflammatory lipids and increased the concentrations of lipids associated with antioxidant capacity compared with prolonged sitting. However, in those who are overweight, physically active interruptions to sedentary time reduced postprandial insulinaemic responses but did not affect adipose tissue gene expression compared with uninterrupted sitting.
与不间断的坐着相比，在长时间坐着时定期进行体力活动的中断有一个小的明显的有益影响，即急性降低三酰甘油水平（SMD:-0.26）。与对葡萄糖和胰岛素水平的影响相比，坐着的时候进行体力活动中断对三酰甘油水平的影响较小，这可能与体力活动后脂蛋白脂肪酶的延迟激活有关。因此，评估急性效应的研究（单日设计）不能捕捉到在2日或多日研究设计中观察到的坐着时体力活动中断的长期有益效应。对动物的研究表明，长时间的肌肉不活动会降低脂蛋白脂肪酶的活性。因此，坐着时肌肉不活动可能会减弱肌肉介导的脂肪酸的吸收。需要对人类进行实验研究，以进一步探索这一假设的心血管健康相关性。在人类中的研究已经调查了在长期坐着的时候中断体力活动对三酰甘油水平的有益影响的替代机制。对2型糖尿病患者的脂质体分析显示，与长时间坐着相比，定期中断坐姿可降低血浆中促炎症的脂质水平，并增加与抗氧化能力有关的脂质浓度。然而，在那些超重的人中，与不间断的坐着相比，体力活动中断久坐时间减少了餐后胰岛素血症反应，但不影响脂肪组织的基因表达。
Cerebral blood flow
脑血流
Sitting-induced impairments in blood glucose regulation might also affect cerebrovascular function (Fig. 3). Cerebrovascular function encompasses mechanisms that maintain constant cerebral perfusion, preventing ischaemic brain injury and damage. Importantly, impaired cerebrovascular function is involved in diseases such as vascular dementia and stroke. Acute hyperglycaemia has been suggested to reduce regional cerebral blood flow and increase insulin secretion, promoting glucose clearance and creating a glucose nadir. This glucose nadir can impair endocrine counter-regulation to subsequent decreases in glucose, exacerbating hypoglycaemia and impairing vascular function. Given that uninterrupted sitting can induce hyperglycaemia, this process might occur during prolonged sitting periods, leading to vascular dysfunction of cerebral arteries. However, this mechanism, while biologically plausible, requires support from relevant human experimental evidence.
坐着引起的血糖调节障碍也可能影响脑血管功能（图3）。脑血管功能包括维持大脑持续灌注的机制，防止大脑缺血性损伤和损害。重要的是，脑血管功能受损与血管性痴呆和中风等疾病有关。有人认为，急性高血糖会减少区域性脑血流，增加胰岛素分泌，促进葡萄糖的清除，形成一个葡萄糖低谷。这种葡萄糖低谷会影响内分泌对随后的葡萄糖下降的对抗调节，加剧低血糖症并损害血管功能。鉴于不间断的坐姿可以诱发高血糖，这一过程可能发生在长时间的坐姿期间，导致脑动脉的血管功能障碍。然而，这种机制虽然在生物学上是合理的，但需要相关人类实验证据的支持。
Increases in blood pressure after prolonged sitting might also affect cerebral blood flow. Cerebral autoregulation maintains a constant blood flow despite changes in blood pressure. Increased blood pressure might evoke cerebral vasoconstriction to increase cerebral resistance, maintaining a constant flow of blood. Indeed, in older adults (mean age 78 years), 3 hours of sitting increased blood pressure and cerebrovascular resistance. Increased vascular resistance causes arterial remodelling, reducing lumen size, which over time, might reduce cerebral blood flow. Experimental investigations in healthy adults have shown that interrupting prolonged sitting with regular, brief, physical activity bouts can attenuate the reductions in cerebral blood flow velocity induced during prolonged sitting. This benefit might be caused, in part, by alterations in the neural control of the cerebrovasculature. Cerebral blood vessels are innervated by cholinergic fibres, which are stimulated during physical activity, contributing to increased cerebral blood flow. Therefore, frequent physically active interruptions might increase cholinergic activity, thereby maintaining cerebral blood flow. By contrast, the cerebral vasculature is also innervated by sympathetic fibres, which cause vasoconstriction. Given that sitting elevates muscle sympathetic nerve activity, prolonged sitting might induce cerebral vasoconstriction, thereby reducing cerebral blood flow. Despite these potential mechanisms, studies in older adults (mean age 78 years) showed no change in cerebral blood flow after prolonged sitting. Age-related decreases in cerebral blood flow attenuating absolute blood flow reductions might explain the lack of cerebral blood change after sitting in older adults. Importantly, however, chronic exposure to acute sitting-induced reductions in cerebral blood flow might contribute to this age-related decline. Further human experimental studies are now needed to elucidate these potential mechanisms.
长时间坐着后血压升高也可能影响脑血流。尽管血压发生了变化，但脑部自动调节功能仍能保持恒定的血流。血压升高可能会唤起脑血管收缩以增加脑部阻力，从而保持恒定的血流。事实上，在老年人中（平均年龄78岁），坐了3个小时会增加血压和脑血管阻力。血管阻力增加导致动脉重塑，减少管腔大小，随着时间的推移，可能会减少脑血流量。对健康成年人的实验调查表明，用定期的、短暂的体力活动来中断长时间的坐姿可以减弱长时间坐着时引起的脑血流速度的下降。这种好处可能部分是由脑血管的神经控制的改变引起的。大脑血管由胆碱能纤维支配，这些纤维在体力活动中受到刺激，有助于增加脑血流量。因此，频繁的体力活动中断可能会增加胆碱能的活动，从而维持脑血流。相比之下，脑血管也受到交感神经纤维的支配，交感神经纤维会导致血管收缩。鉴于坐着会提高肌肉交感神经的活动，长时间坐着可能会诱发脑血管收缩，从而减少脑血流量。尽管有这些潜在的机制，对老年人（平均年龄78岁）的研究显示，久坐后脑血流量没有变化。与年龄有关的脑血流减少减弱了绝对血流的减少，这可能解释了老年人坐着后缺乏脑血的变化。然而，重要的是，长期暴露于急性坐位引起的脑血流减少可能有助于这种与年龄有关的下降。现在需要进一步的人体实验研究来阐明这些潜在的机制。
Inflammation
炎症
Increased systemic inflammation caused by prolonged sitting might broadly contribute across different systems to factors that can increase the risk of cardiovascular disease. For example, chronic low-grade systemic inflammation is associated with the development of cardiovascular disease. Cross-sectional studies have shown that increased amounts of sitting time are detrimentally associated with levels of C-reactive protein and IL-6 in the plasma. Furthermore, as mentioned above, prolonged sitting time can induce postprandial hyperglycaemia and postprandial spikes in glucose have been shown to increase the levels of circulating markers of inflammation. Although experimental research to date on prolonged sitting and inflammation is limited, one study showed that interrupting sitting with highintensity exercise lowered the acute increase in salivary IL-8 levels induced by uninterrupted sitting.
长时间坐着引起的全身性炎症的增加可能在不同的系统中广泛地促成了可增加心血管疾病风险的因素。例如，慢性低级别的系统性炎症与心血管疾病的发展有关。横断面研究显示，坐着的时间增加与血浆中的C反应蛋白和IL-6水平有不利的关系。此外，如上所述，长时间坐着会诱发餐后高血糖，而餐后血糖的飙升已被证明会增加循环中的炎症标志物的水平。尽管迄今为止关于久坐和炎症的实验研究是有限的，但一项研究显示，用高强度的运动来打断久坐，可以降低不间断的久坐所引起的唾液IL-8水平的急性增加。
Inflammation might also contribute to sittinginduced impairments in vascular function given that inflammatory markers are associated with reduced nitric oxide availability and activate the vascular production of reactive oxygen species (Fig. 3). However, research on this link remains unclear. The oral administration of vitamin C, a reactive oxygen species scavenger, prevented vascular dysfunction after 3 hours of sitting but blood markers of oxidative stress were not measured. Moreover, in another study, the same sitting duration impaired vascular function but no concomitant changes in plasma markers of systemic oxidative stress were observed, suggesting that oxidative stress-independent mechanisms were responsible for the change in vascular function. Finally, the possibility that chronic low-grade inflammation and oxidative stress, resulting in arterial stiffening, might contribute to chronic elevations in blood pressure owing to prolonged sitting remains open to question.
鉴于炎症标志物与一氧化氮的减少有关，并激活血管产生的活性氧（图3），炎症也可能导致久坐引起的血管功能损害。然而，对这种联系的研究仍不清楚。口服维生素C，一种活性氧清除剂，可以防止坐3小时后的血管功能障碍，但血液中的氧化应激标志物没有被测量。此外，在另一项研究中，同样的坐立时间损害了血管功能，但没有观察到系统氧化应激的血浆标志物的伴随变化，这表明氧化应激无关的机制是血管功能变化的原因。最后，慢性低度炎症和氧化应激导致动脉僵化，可能有助于因久坐而导致的血压长期升高，这种可能性仍有待商榷。
Sitting-induced ‘exercise resistance’.
坐着引起的“运动阻力”。
Prolonged, uninterrupted sitting might further increase the risk of cardiovascular disease by promoting the development of sitting-induced ‘exercise resistance’, involving reductions in the typical responses observed after acute exercise. Acute exercise lowers plasma glucose, insulin and triglyceride levels. However, 4 days of prolonged sitting prevents these expected beneficial postprandial responses to acute exercise. Furthermore, despite the known blood pressure-lowering effects of acute exercise, when this activity is followed by prolonged sitting, the benefits are attenuated. Alternatively, the blood pressurelowering response to acute exercise is increased if sitting is interrupted with brief bouts of physical activity. In this context, sitting might contribute to the risk of cardiovascular disease in two ways: through the adverse processes described above that occur during sitting and by blunting the cardioprotective benefits of exercise.
长期不间断的坐着可能会进一步增加心血管疾病的风险，因为它促进了坐着引起的“运动抵抗”的发展，包括急性运动后观察到的典型反应的减少。急性运动可降低血浆葡萄糖、胰岛素和甘油三酯水平。然而，4天的长期坐着会阻止这些预期的对急性运动的有益餐后反应。此外，尽管已知急性运动有降低血压的作用，但当这种活动之后又长期坐着，其好处就会减弱。另外，如果坐着的时候有短暂的体力活动，那么急性运动的降压反应会增加。在这种情况下，坐着可能以两种方式导致心血管疾病的风险：通过上述坐着时发生的不利过程，以及通过削弱运动的心脏保护性益处。
Future directions
未来研究方向
Experimental evidence relevant to understanding the mechanisms by which sedentary behaviour affects the major pathways implicated in cardiovascular disease is, at present, largely restricted to the acute effects of prolonged sitting. Extension of this work to longer-term mechanistic investigations is warranted. Furthermore, the majority of studies have been conducted in healthy populations and often include only male participants. Therefore, sex-specific differences are unclear, although some differences are evident for vascular function and blood pressure. Women have demonstrated a greater protection from acute sittinginduced vascular dysfunction86 and an improved acute blood pressure-lowering response to physically active interruptions to prolonged sitting. Given the links between the biological pathways underlying the influence of sitting on cardiovascular risk factors (Fig. 3), experimental research also needs to consider an integrated approach that will enable the identification of potential adverse synergies.
目前，与了解久坐行为影响与心血管疾病有关的主要途径的机制有关的实验证据主要限于长期坐着的急性影响。有必要将这项工作扩展到长期的机制调查。此外，大多数研究都是在健康人群中进行的，而且往往只包括男性参与者。因此，尽管在血管功能和血压方面有一些明显的差异，但性别差异还不清楚。女性已经证明了对急性久坐引起的血管功能障碍有更大的保护作用，并且对体力活动中断久坐的急性降压反应有改善。鉴于坐着对心血管危险因素影响的生物途径之间的联系（图3），实验研究还需要考虑一种综合的方法，以便能够识别潜在的不利的协同作用。
Sedentary behaviour reduction trials
减少久坐行为的试验
The heightened interest in sedentary behaviour as a public-health issue has stimulated the conduct of >30 controlled trials of interventions to reduce sedentary behaviour in adult populations since 2003 (ref. 87). These interventions can be categorized into three types: environmental interventions designed to make changes to a particular behavioural setting (for example, sit–stand workstations in workplaces), educational and motivational interventions that target the behaviour of the individual (for example, smartphone apps and educational programmes), and multicomponent interventions that incorporate both environmental and educational or motivational components.
对久坐行为这一公共健康问题的高度关注，促使自2003年以来进行了超过30项干预措施的对照试验，以减少成年人群的久坐行为（参考文献87）。这些干预措施可分为三种类型：旨在改变特定行为环境的环境干预措施（例如，工作场所的坐姿工作站），针对个人行为的教育和激励干预措施（例如，智能手机应用程序和教育方案），以及同时包含环境和教育或激励成分的多成分干预措施。
A meta-analysis of the findings of trials of sedentary behaviour reduction interventions has identified the high feasibility of changing sedentary behaviour in adults, reporting that the pooled effect of the intervention groups was a significant reduction in daily sitting time of –30.4 minute per day. Environmental interventions yielded the largest reduction (–40.6 minutes per day), followed by multicomponent (–35.5 minutes per day) and behavioural (–23.8 minutes per day) interventions. This new evidence updates and builds on an earlier meta-analysis that reported a high feasibility of change and that interventions that focus solely on sedentary behaviours yield much greater reductions in sedentary time than physical activity interventions or combined physical activity and sedentary behaviour interventions.
一项对减少久坐行为干预试验结果的Meta分析确定了改变成年人久坐行为的高度可行性，报告说干预组的综合效果是每天坐的时间显著减少-30.4 min。环境干预产生了最大的减少量（每天-40.6 min），其次是多成分（每天-35.5 min）和行为干预（每天-23.8 min）。这项新的证据更新并建立在早期的Meta分析上，该分析报告了变化的高度可行性，而且只关注久坐行为的干预措施比体力活动干预措施或体力活动和久坐行为联合干预措施产生的久坐时间的减少要大得多。
The observed reductions in sedentary behaviour, particularly for environmental and multicomponent interventions, are clinically relevant because sedentary time has a high inverse correlation with light-intensity physical activity (Spearman’s ρ=0.98). Modelling the effect of reallocating just 30 minutes of sitting time to light-intensity physical activity suggests a potential 2–4% improvement in major cardiovascular risk factors. This improvement is supported by the findings of a meta-analysis of free-living interventions targeting sedentary behaviour reductions alone or in combination with increases in physical activity. Pooled effects showed small but significant beneficial effects of the interventions on body mass (~–0.6 kg), waist circumference (~–0.7 cm), percentage of body fat (~–0.3%), systolic blood pressure (~–1.1mmHg), plasma insulin level (~–1.4pmol/l) and plasma HDL-cholesterol level (~ 0.04 mmol/l). The effects observed for sedentary behaviour reduction interventions are generally inferior to those reported after exercise training interventions. However, to date, most of the evidence comes from sedentary behaviour reduction interventions conducted in the workplace setting. By comparison, a meta-analysis revealed that workplace physical activity interventions have yielded modest pooled effects on body mass (~–2.6kg) and waist circumference (~–1.9cm), whereas reductions in blood pressure and blood lipid and glucose levels were not significant.
观察到的久坐行为的减少，特别是环境和多成分干预的减少，在临床上是有意义的，因为久坐时间与轻强度的体力活动有很高的反相关性（Spearman's ρ=0.98）。将30 min的坐着的时间重新分配给轻强度的体力活动的效果建模表明，主要的心血管风险因素可能会有2-4%的改善。这项改善得到了自由生活干预措施的Meta分析结果的支持，这些干预措施的目标是单独减少久坐行为或与增加体力活动相结合。汇总效应显示，干预措施对体重（~-0.6 kg）、腰围（~-0.7 cm）、身体脂肪百分比（~-0.3%）、收缩压（~-1.1mmHg）、血浆胰岛素水平（~-1.4pmol/l）和血浆高密度脂蛋白胆固醇水平（~0.04mmol/l）有小而显著的有益影响。减少久坐行为的干预措施所观察到的效果通常不如运动训练干预后的报告。然而，到目前为止，大多数证据来自于在工作场所进行的减少久坐行为的干预。相比之下，一项Meta分析显示，工作场所的体力活动干预对体重（约2.6 kg）和腰围（约1.9 cm）产生了适度的集合效应，而对血压、血脂和葡萄糖水平的降低并不显著。
However, the findings supporting interventions to target sedentary behaviour reductions are from studies with limited representation of individuals with clinical conditions pertinent to cardiovascular health (for example, those with cardiovascular disease or type 2 diabetes mellitus), different racial/ethnic groups and older populations (that is, non-working age adults). Furthermore, as is the case for trials of physical activity interventions, a need exists for studies intervening for ≥12 months and including maintenance evaluations from which to consider sustainability and longer-term effectiveness.
然而，支持以减少久坐行为为目标的干预措施的研究结果，对患有与心血管健康有关的临床疾病的人（例如，患有心血管疾病或2型糖尿病的人）、不同种族/民族群体和老年人群（即非工作年龄的成年人）的代表性有限。此外，就像体力活动干预试验一样，需要进行干预时间≥12个月的研究，并包括维持性评价，以便考虑可持续性和长期有效性。
As a consequence of the emerging evidence described above, intriguing possibilities arise for future research and clinical innovation. Technological advances in consumer devices provide particular opportunities. Data from wrist-worn activity trackers now deliver feedback on interruptions to sedentary time and on light-intensity activity and moderate–vigorous-intensity activity. These data can already provide clinical starting points to address reductions in sitting time and increase total physical activity, along with relevant goal setting and objective feedback for the individual. Evidence from randomized trials to determine the feasibility and cardiovascular health benefits of the relevant behavioural changes might provide a future basis for specific clinical recommendations.
由于上述新出现的证据，未来的研究和临床创新出现了令人好奇的可能性。消费设备的技术进步提供了特别的机会。来自腕带式活动追踪器的数据现在可以提供关于中断久坐时间以及轻度强度活动和中度强度活动的反馈。这些数据已经可以提供临床起点，以解决减少坐着的时间和增加总的体力活动，以及相关的目标设置和对个人的客观反馈。通过随机试验确定相关行为改变的可行性和心血管健康益处的证据可能为未来的具体临床建议提供基础。
Sitting less and moving more
少坐多动
An increased understanding of the effects of sedentary behaviour and physical activity on cardiovascular outcomes and mortality has augmented the interest in understanding the interaction between these behaviours to optimize behavioural-based strategies designed to reduce the risk of cardiovascular disease. Specifically, the interactions between sedentary behaviour and physical activity on the risk of cardiovascular disease have received intense scrutiny in a series of prospective epidemiological studies; the crucial conclusions relating to this interaction are summarized below.
对久坐行为和体力活动对心血管疾病结果和死亡率影响的进一步了解，增强了人们对了解这些行为之间相互作用的兴趣，以优化旨在减少心血管疾病风险的基于行为的策略。具体来说，在一系列前瞻性流行病学研究中，久坐行为和体力活动对心血管疾病风险的相互作用得到了严格的审查；与这种相互作用有关的关键结论总结如下。
First, physical inactivity and sedentary behaviour are both associated with an increased risk of cardiovascular disease incidence and death. Replacing sedentary behaviour with any intensity of physical activity (that is, movement) will have health benefits, with greater benefits seen when sedentary behaviour is replaced with moderate–vigorous-intensity physical activity. Finally, the effects of sedentary behaviour on the risk of cardiovascular disease are most pronounced in individuals who are physically inactive. Furthermore, high levels of moderate-intensity physical activity can ameliorate the increased risk of cardiovascular disease associated with excessive sedentary behaviour. This benefit was revealed in a meta-analysis that included individual-level data from >1 million participants95. Higher levels of self-reported sitting time were associated with increased all-cause mortality across categories of moderate-intensity physical activity. However, this correlation did not exist in the highest category of physicalactivity (>35.5 MET-hours per week, equivalent to ~60–75 minutes per day of moderate-intensity physical activity) in which the risks of sitting are mitigated95. Similarly, amelioration of the excess risk associated with high levels of sitting for cardiovascular death (>8 hours per day) and incident cardiovascular disease (≥10 hours per day) is evident only in individuals with higher physical activity levels (~40 to >60 minutes per day). Consistently across all the studies to date, the detrimental associations between excessive sitting and adverse cardiovascular outcomes are particularly evident among physically inactive individuals (that is, those not meeting the minimum recommendations of >150 minutes per week of moderate-intensity activity).
首先，缺乏体力活动和久坐行为都与心血管疾病的发病和死亡风险增加有关。用任何强度的体力活动（即运动）取代久坐行为都会对健康有益，当用中等强度的体力活动取代久坐行为时，会看到更大的益处。最后，久坐行为对心血管疾病风险的影响在不爱运动的人身上最为明显。此外，高水平的中等强度的体力活动可以改善与过度久坐行为相关的心血管疾病风险的增加。一项包括100多万参与者的个体层面数据的Meta分析显示了这种好处。自我报告的坐着的时间水平越高，与各种中等强度体力活动的全因死亡率增加有关。然而，这种相关性并不存在于最高类别的体力活动（每周>35.5 MET-小时，相当于每天约60-75 min的中等强度体力活动），在这种情况下，坐的风险会得到缓解。同样，与高坐位相关的心血管死亡（每天>8 h）和心血管疾病（每天≥10 h）的超额风险只有在具有较高体力活动水平（每天约40至>60 min）的人中才会明显改善。迄今为止的所有研究一致表明，过度坐立和不良心血管结果之间的有害联系在不从事体力活动的人（即那些没有达到每周>150 min中等强度活动的最低建议）中特别明显。
Although the joint associations between prolonged sitting, physical inactivity and other health outcomes (for example, cardiovascular events and type 2 diabetes mellitus) are beginning to be elucidated, we can nevertheless consider how the evidence for all-cause mortality can be utilized to create a mortality ‘matrix’. This matrix will uniquely combine sitting time and physical activity in a way that has relevance to the application of novel management approaches in clinical practice. Despite the widespread use of prediction matrices for the total risk of cardiovascular disease in clinical practice, little attention has been given to similar risk matrix approaches for both of these behaviours; it is now possible to begin doing so through the findings of meta-analyses of studies that have measured both sitting time and physical activity in relation to the risk of death.
尽管久坐、缺乏体力活动和其他健康结果（例如心血管事件和2型糖尿病）之间的联合关系开始被阐明，但我们还是可以考虑如何利用全因死亡率的证据来创建一个死亡率“矩阵”。这个矩阵将独特地结合坐着的时间和体力活动，与临床实践中应用新的管理方法有关。尽管在临床实践中广泛使用心血管疾病总风险的预测矩阵，但很少有人关注这两种行为的类似风险矩阵方法；现在有可能通过对测量坐姿时间和体力活动与死亡风险关系的研究进行Meta分析，开始这样做。
A SIT-ACT all-cause death risk matrix can assist clinicians to develop treatment decisions for patients who are living with or at risk of developing cardiovascular disease (Fig. 4). Responses to two separate questions that ascertain daily sitting time and physical activity time are fundamental to the application of this risk prediction model. With the use of relevant hazard ratios for all-cause death, the estimates for sitting time and physical activity can be applied to directly compare the percentage of risk increment from the combined sitting and physical activity status against the reference category used in the harmonized meta-analysis (individuals who sat the least (<4 hours per day) and those who had the most physical activity (top quartile equivalent to >60 minutes per day of moderate-intensity activity)). The potential clinical utility of considering the interaction between sitting time and physical activity for risk reduction, particularly in physically inactive patients, is provided in Fig. 5, which also describes how to achieve a reduction from a high-risk to a medium-risk of death. This transition could be achieved through two distinct means. One strategy is to increase physical activity to recommended levels (>150 minutes per week or ~30 minutes per day) without changes to sitting time (that is, sitting time remains at >8 hours per day). Another method is to substantially reduce sitting time (reduce from >8 hours per day to <4 hours per day) without changes in physical activity. A further risk reduction (that is, from high risk to low–medium risk) could be achieved through the combination of an increase in physical activity to recommended levels and a substantial reduction in sitting time (to <4 hours per day).
SIT-ACT全因死亡风险矩阵可以帮助临床医生为心血管疾病患者或有风险的患者制定治疗决策（图4）。对确定每日坐立时间和体力活动时间的两个独立问题的回答是应用该风险预测模型的基础。在使用全因死亡的相关危险比的情况下，坐着的时间和体力活动的估计值可以应用于直接比较综合坐着和体力活动状态的风险增量百分比与统一的Meta分析中使用的参考类别（坐着最少的人（每天<4 h）和体力活动最多的人（最高四分之一相当于每天>60 min的中等强度活动））。图5提供了考虑坐着的时间和体力活动之间的相互作用以减少风险的潜在临床效用，特别是在体力不活跃的病人中，该图还描述了如何实现从高风险到中等死亡风险的减少。这种转变可以通过两种不同的手段实现。一种策略是在不改变坐着的时间（即坐着的时间保持在每天>8 h）的情况下，将体力活动增加到建议的水平（每周>150 min或每天~30 min）。另一种方法是在不改变体力活动的情况下，大幅度减少坐的时间（从每天>8 h减少到<4 h）。进一步降低风险（即从高风险到中低风险）可以通过增加体力活动到推荐水平和大幅减少坐着的时间（到每天<4 h）相结合来实现。
However, the available evidence that can currently be used to populate the SIT-ACT matrix is from all-cause death findings. Therefore, extrapolations to more specific outcomes, such as cardiovascular disease events or type 2 diabetes mellitus, require caution. Nevertheless, the SIT-ACT matrix provides a framework to consider how different combinations of time spent being physically active and time spent sitting might determine particular health risks. As evidence from large-scale epidemiological studies with cardiovascular disease and other specific health outcomes becomes available, it will be possible to use this framework with a greater degree of specificity with a more disease-specific focus.
然而，目前可用于填充SIT-ACT矩阵的现有证据是来自全因死亡的研究结果。因此，推断出更具体的结果，如心血管疾病事件或2型糖尿病，需要谨慎对待。然而，SIT-ACT矩阵提供了一个框架来考虑体力活动时间和坐着时间的不同组合如何决定特定的健康风险。随着对心血管疾病和其他特定健康结果的大规模流行病学研究证据的出现，将有可能以更具体的疾病为重点，更大程度地使用这一框架。
Implications for clinical practice
对临床实践的影响
Although regular, structured physical activity (exercise) effectively reduces cardiovascular risk and improves relevant outcomes, adherence to exercise, even within structured cardiac rehabilitation programmes, can be suboptimal. Furthermore, sitting-induced ‘exercise resistance’ (as described above) might attenuate the benefits of exercise among those performing suboptimal levels throughout the day. Multimorbidity is pervasive among individuals with cardiovascular disease risk factors and negatively affects health outcomes and mortality, thereby complicating treatment strategies. Given the physical complications and pain often associated with multimorbidity, particularly in patients with angina or arthritis, the reduction in sedentary time could be a feasible starting point to improve cardiovascular risk factors in these individuals. Given that physically inactive individuals are at a greater total risk of acute cardiac events than physically active counterparts, the American College of Sports Medicine recommends light–moderate-intensity exercise in the first instance, especially for individuals who are habitually inactive. Specifically, among inactive adults, reducing sedentary time and thereby increasing light-intensity activity might provide sufficient stimulus and progressive overload that lead to worthwhile improvements in cardiorespiratory and musculoskeletal function.
尽管定期的、有组织的体力活动（运动）能有效地降低心血管风险并改善相关的结果，但对运动的坚持，即使是在有组织的心脏康复计划中，也可能是次优的。此外，坐着引起的“运动阻力”（如上所述）可能会减弱那些全天进行次优水平运动的好处。多病症在具有心血管疾病风险因素的人中普遍存在，并对健康结果和死亡率产生负面影响，从而使治疗策略复杂化。考虑到通常与多病症相关的身体并发症和疼痛，尤其是心绞痛或关节炎患者，减少久坐时间可能是改善这些人的心血管风险因素的一个可行的起点。鉴于身体不活跃的人比身体活跃的人发生急性心脏事件的总风险更大，美国运动医学会建议首先进行轻中度强度的运动，尤其是对习惯不运动的人。具体来说，在不活动的成年人中，减少静坐时间，从而增加轻度强度的活动，可能会提供足够的刺激和渐进的超负荷，导致心肺功能和肌肉骨骼功能值得改善。
A ‘staircase’ approach can be applied that focuses initially on reducing and interrupting sitting time (Fig. 5). This approach initially increases standing and stepping time, progressing to increasing light intensity physical activity volumes and then to increasing moderate–vigorous-intensity physical activity. The staircase approach contrasts with the salutary but formidable primary goal of transitioning from a chronic inactive state to regular engagement in moderate– vigorous-intensity activity and improved cardiorespiratory fitness. In many patients with cardiovascular disease, this approach might seem unrealistic and includes practical challenges and risks, especially for older adults (≥65 years) and those with multiple morbidities. Nevertheless, for individuals who are young (≤45 years) and have an athletic or fitness-training history or who might otherwise be so inclined, starting with increasing moderate–vigorous activity and cardiorespiratory fitness could be appropriate and most beneficial.
可以采用“阶梯式”方法，首先注重减少和中断坐的时间（图5）。这种方法最初是增加站立和踏步的时间，进而增加轻度强度的体力活动量，然后再增加中度-剧烈强度的体力活动。阶梯式方法与从长期不活动的状态过渡到经常从事中等强度的活动和改善心肺功能的主要目标形成对比。对于许多心血管疾病患者来说，这种方法似乎是不现实的，包括实际的挑战和风险，特别是对于老年人（≥65岁）和有多种疾病的人。然而，对于那些年轻的（≤45岁）、有运动或健身训练史的人，或者那些可能有此倾向的人，从增加中等强度的活动和心肺功能开始可能是合适的，也是最有益的。
Although the conclusions of the meta-analysis described above suggest that total sitting time should be limited to 4 hours per day for individuals who are inactive95, this goal is likely to be too ambitious for most patients who have a compromised cardiovascular health. Consequently, the optimal prescription should build on the interaction between sitting time and physical activity. This combined approach is particularly relevant in light of findings on sitting-induced ‘exercise resistance’ because focusing on physical activity alone might not lead to the desired outcomes.
尽管上述Meta分析的结论表明，对于不活动的人来说，每天的总坐时间应限制在4 h以内，但对于大多数心血管健康受到影响的病人来说，这个目标可能过于雄心勃勃。因此，最佳处方应该建立在坐着的时间和体力活动之间的互动上。考虑到关于坐着引起的“运动阻力”的研究结果，这种综合方法尤其重要，因为仅仅关注体力活动可能无法达到预期的效果。
A first step towards integrating more movement into patients’ daily lives could include goals of reducing total sitting time by 30 minutes per day or interrupting prolonged bouts of sitting throughout the day. This approach can enable a simultaneous reduction in sitting time and an increase in total physical activity. Although initial interruptions in sitting time might be limited to standing or light-intensity activities, this added movement could increase functional capacity or physical conditioning, thereby preparing individuals for higher intensities of physical activity. An older adult with cardiovascular disease might, for example, be able to increase their leg strength by simply adding several sit-to-stand transitions throughout their day. This added movement might increase their capacity for more physical activity such as walking the stairs. Indeed, several individual-specific and disease-specific factors should be considered when providing advice to patients with cardiovascular disease. However, the message to sit less and move more might be more effective at integrating more movement into the day of an individual than a primary focus of accumulating at least 150 minutes per week of exercise. A focus on sitting time reduction has considerable potential for clinical settings in which some patients with cardiovascular disease are likely to require supervised sessions to engage safely in moderate–vigorous-intensity physical activity. Focusing on reducing sitting time (Fig. 5) might be an important first step in making sustainable changes to movement patterns that will support a higher level of overall physical activity for the benefit of cardiovascular health.
将更多的运动融入病人的日常生活的第一步可以包括将每天的总坐时间减少30 min的目标，或者打断一天中长时间的坐姿。这种方法可以同时减少坐着的时间和增加总的体力活动。虽然最初中断坐着的时间可能仅限于站立或轻度强度的活动，但这种额外的运动可以增加功能能力或身体条件，从而为个人进行更高强度的体力活动做好准备。例如，患有心血管疾病的老年人可能会通过在一天中增加几次从坐到站的过渡来增加他们的腿部力量。这种额外的运动可能会增加他们进行更多体力活动的能力，如走楼梯。事实上，在向心血管疾病患者提供建议时，应该考虑一些针对个人和疾病的因素。然而，少坐多动的信息可能比每周积累至少150分钟的运动的主要重点更有效地将更多的运动融入个人的一天。在临床上，一些心血管疾病患者可能需要在监督下才能安全地进行中等强度的体力活动，因此关注减少坐着的时间有很大的潜力。注重减少坐着的时间（图5）可能是持续改变运动模式的重要第一步，这将支持更高水平的整体体力活动，以利于心血管健康。
Conclusions
结论
Prolonged, uninterrupted periods of sitting contribute to the risk of cardiovascular disease. Time spent sitting also reduces the total physically active time, resulting in diminished overall skeletal muscle activity and leading to detrimental effects on cardiorespiratory fitness and multiple metabolic processes related to cardiovascular health. Observational evidence shows interactions between sitting time, physical inactivity, and all-cause and cardiovascular death. High volumes of sitting can be particularly harmful in individuals who are also physically inactive. In this context, active interruptions to sedentary time have an important role, with evidence from laboratory studies showing beneficial glycaemic, vascular and other changes consistent with lower cardiovascular risk. The findings from real-world intervention trials show that changing sedentary behaviours can be feasible and acceptable and that modest improvements in cardiovascular risk factors can be achieved. However, this evidence is fairly new and requires further confirmatory findings. Taken on balance, both the epidemiological and experimental evidence suggest that less sitting will lead to a cardiovascular health benefit. In clinical practice, a combined approach emphasizing sitting less and moving more could amplify the transition to more physically active lifestyles with cardiovascular health benefits. In this Review, we have considered the current strengths and limitations of the available evidence, highlighting some of the emerging opportunities for further research and suggesting initial implications for clinical practice. The body of evidence needs to be developed and further consolidated to inform future clinical guidelines on sedentary behaviour and cardiovascular health, particularly on dose–response relationships and on appropriate quantitative change targets. However, as we have illustrated in our concluding sections, novel implications arise from the evidence already available, which can help to inform realistic, acceptable and beneficial innovations in clinical practice.
长时间、不间断的坐着会导致心血管疾病的风险。坐着的时间也减少了总的体力活动时间，导致整体骨骼肌活动减少，并导致对心肺功能和与心血管健康有关的多种代谢过程的不利影响。观察性证据显示，坐着的时间、身体不活动与所有原因和心血管死亡之间存在相互作用。高量的坐姿对那些不爱运动的人来说可能特别有害。在这种情况下，积极中断久坐时间具有重要作用，实验室研究的证据显示，有益的血糖、血管和其他变化与较低的心血管风险一致。现实世界的干预试验结果表明，改变久坐行为是可行的、可接受的，并且可以实现心血管风险因素的适度改善。然而，这些证据是相当新的，需要进一步的确认结果。总的来说，流行病学和实验证据都表明，少坐会带来心血管健康的好处。在临床实践中，强调少坐和多动的综合方法可以扩大向更多体力活动的生活方式的转变，从而对心血管健康有益。在本综述中，我们考虑了现有证据的优势和局限性，强调了进一步研究的一些新机会，并提出了对临床实践的初步影响。证据体系需要发展和进一步巩固，以便为未来关于久坐行为和心血管健康的临床指南提供信息，特别是关于剂量-反应关系和适当的量化变化目标。然而，正如我们在结论部分所说明的，从已有的证据中产生了新的影响，这有助于为临床实践中现实的、可接受的和有益的创新提供依据。
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