13
might best be explained by disparity in the exercise interventions and insufficient
training periods, poor adherence levels, differences between characteristics of par-
ticipants and genetic influences. Indeed, evidence from the Heritage Family study
suggests that exercise training only has significant anti-inflammatory effects in sed-
entary adults with initially elevated CRP levels [ 83 ]. Thus, further studies are
required to resolve these issues.
4.3 Biological Mechanisms
Given the range of factors that are altered by exercise it seems likely that multiple
biological mechanisms are responsible for alterations in CVD risk. Some of these
mechanisms are well-understood and supported by empirical evidence, and others
are biologically plausible but unsubstantiated. The reductions in blood pressure
associated with regular exercise are likely to be due to a combination of nervous
system adaptations and vascular adaptations [ 84 ], including decreased activation of
sympathetic nervous system and increased vasodilation which decreases peripheral
resistance. Various mechanisms have been associated with these vascular adapta-
tions [ 85 ], for example, exercise induced enhancement of the synthesis and release
of nitric oxide and endothelin-1. The favourable alterations in blood lipids as a
consequence of exercise are likely to be due an alteration in the activity of key
enzymes involved in lipoprotein metabolism. For example, increased lipoprotein
lipase activity and decreased hepatic TG lipase activity have been noted after a
single bout of exercise [ 86 ]. In addition, reductions in cholesterol ester transfer
protein concentrations have been reported [ 87 ], which might allow slowed catabo-
lism of HDL particles with endurance training. Increases in cardiorespiratory fitness
with exercise result from a combination of improvements in cardiac function, oxy-
gen transport, muscle perfusion and alterations in the activity of key enzymes
involved in aerobic metabolism. Numerous mechanisms have been connected with
the anti-inflammatory effects of exercise. One key mechanism might be related to
nuclear factor-κB activation, given that this is a redox sensitive and oxidant- activated
transcription factor that regulates inflammation related gene expression. Heat shock
proteins that are released during exercise may be a viable mechanism that could
explain the training induced changes in toll like receptor 4, which is thought to play
an important role in inflammatory pathways [ 88 ]. Changes in leukocyte telomere
dynamics, which progressively change with age, may also be involved although the
current evidence remains equivocal [ 89 ]. The anti-inflammatory effects of exercise
may also be mediated by increased insulin sensitivity and oxidative capacity, HDL
cholesterol, and improved endothelial and autonomic nervous system functioning.
Thus, it is clear that exercise induced reduction in CVD risk is related to multiple
mechanisms that are unlikely to operate in isolation. Recent advances in metabolo-
mics platforms may help to further elucidate biological signatures associated with
physical activity [ 90 ].
1 Physical Inactivity and the Economic and Health Burdens Due to Cardiovascular...