The 24-h activity cycle and cardiovascular outcomes: establishing biological plausibility using arterial stiffness as an intermediate outcome

Abstract

This review proposes a biologically plausible working model for the relationship between the 24-h activity cycle (24-HAC) and cardiovascular disease. The 24-HAC encompasses moderate-to-vigorous physical activity (MVPA), light physical activity, sedentary behavior (SB), and sleep. MVPA confers the greatest relative cardioprotective effect, when considering MVPA represents just 2% of the day if physical activity guidelines (30 min/day) are met. While we have well-established guidelines for MVPA, those for the remaining activity behaviors are vague. The vague guidelines are attributable to our limited mechanistic understanding of the independent and additive effects of these behaviors on the cardiovascular system. Our proposed biological model places arterial stiffness, a measure of vascular aging, as the key intermediate outcome. Starting with prolonged exposure to SB or static standing, we propose that the reported transient increases in arterial stiffness are driven by a cascade of negative hemodynamic effects following venous pooling. The subsequent autonomic, metabolic, and hormonal changes further impair vascular function. Vascular dysfunction can be offset by using mechanistic-informed interruption strategies and by engaging in protective behaviors throughout the day. Physical activity, especially MVPA, can confer protection by chronically improving endothelial function and associated protective mechanisms. Conversely, poor sleep, especially in duration and quality, negatively affects hormonal, metabolic, autonomic, and hemodynamic variables that can confound the physiological responses to next-day activity behaviors. Our hope is that the proposed biologically plausible working model will assist in furthering our understanding of the effects of these complex, interrelated activity behaviors on the cardiovascular system.

Keywords: activity behaviors; biological plausibility; physical activity; pulse wave velocity; sedentary behavior; sleep.

Figure 1.

The 24-h activity cycle (24-HAC). The 24-HAC encompasses sedentary behavior, light-intensity physical activity (LPA), moderate-to-vigorous intensity physical activity (MVPA), and sleep. A: these behaviors are classified according to energy expenditure requirement, expressed as metabolic equivalents (METs). A MET is the ratio of the working metabolic rate relative to resting metabolic rate, which is commonly assumed to be 1.0 MET. B: well-established guidelines exist for MVPA but not the other behaviors. C: for American adults, we have a good understanding of the average total duration spent engaged in each activity behavior. We also know that the day is finite and that activity behaviors share bidirectional physiological and behavioral interactions. At present, we do not know the optimal dose for engaging in or interrupting each behavior.

Figure 2.

Arterial stiffness. A: throughout the arterial tree the vessel wall is composed of 3 layers: inner (intima), middle (media), and outer (adventitia). Collagen and elastin maintain the shape and functional properties of these layers and thus the arterial wall. A major factor regulating the health of arteries is blood flow-induced shear stress. B: biological aging within the vasculature, or vascular aging, manifests as arteriosclerosis (hardening of the artery) and arterial stiffening. The central elastic arteries, including the aorta, are highly susceptible to stiffening. Accelerated vascular aging of the aorta can lead to a cascade of negative hemodynamic effects, which can impair coronary perfusion and damage target organs such as the heart, kidney, and brain. C: arterial stiffness is commonly measured as the pulse wave velocity (PWV) between the carotid and femoral arteries. PWV is the speed at which the forward pressure wave is transmitted between 2 arterial segments, with faster PWV indicative of increased arterial stiffness.

Figure 3.

Hypothesized mechanistic model to establish a biological plausibility relationship between sedentary behavior and cardiovascular disease. We propose that prolonged sitting leads to increased central (aorta) arterial stiffness, likely driven by hemodynamic changes and compounded by several detrimental autonomic, hormonal, metabolic, oxidative, and inflammatory factors. The elastic aorta, which is directly proximal to the heart, plays an important role in regulating cardiac afterload and the transmission of pulsatile forces to the microcirculation. Stiffening of the aorta increases the pulsatile load on the left ventricle and the transmission of pulsatile forces to the microcirculation, which can damage target organs such as the heart, kidney, and brain. Accelerated stiffening of the aorta relative to the periphery can also lead to a physiological impedance mismatching and a subsequent attenuation or reversal of the stiffness gradient. This amplifies and hastens wave reflection, leading to additional cardiac afterload and compromised coronary perfusion.

Figure 4.

The 24-h activity cycle and cardiovascular disease: physiological and behavioral interactions. This simplified biological model places arterial stiffness, a measure of vascular aging, as the key intermediate outcome. Starting with prolonged exposure to sitting or static standing, we propose that the reported transient increases in arterial stiffness are driven by a cascade of negative hemodynamic effects as a function of venous pooling. The autonomic, metabolic, and hormonal changes that follow further impair vascular function. Vascular dysfunction can be offset by using interruption strategies that target the mechanistic pathways and/or by engaging in protective behaviors throughout the day. Physical activity, especially moderate-to-vigorous physical activity, can confer protection by chronically improving endothelial function and associated protective mechanisms. Sleep not only is a complex behavior that is bidirectionally related to physical activity and sedentary behavior but also independently impacts several hormonal, metabolic, autonomic, and hemodynamic variables.