6
aerobic activity, or equivalent combinations [ 8 ]. It has been estimated that, if physi-
cal inactivity were to decrease by 25%, more than a million deaths worldwide would
be avoided each year (the population attributable fraction for all-cause mortality is
9%, ranging from 4% in low-income countries to 11% in high-income countries)
[ 8 ]. Reductions in smoking, blood pressure, and cholesterol have explained approx-
imately 50% of the decline in CVD events over the last 25 years in Britain [ 9 ]. The
relative risk of heart disease per unit change in cholesterol has been shown to
decrease with age and blood pressure, although the positive association persists into
older age [ 10 ]. Pharmacological therapies that have been employed to control ele-
vated cholesterol and blood pressure demonstrate a favourable effect on cardiovas-
cular outcomes. For example, statin therapy was associated with a 12% proportional
reduction in all-cause mortality per mmol⋅l−^1 reduction in LDL-C and a 19% reduc-
tion in the 5-year incidence of coronary events [ 11 ]. The recent implementation of
comprehensive smoking bans in public places has provided an opportunity to exam-
ine the large-scale impact of exposure to tobacco smoke using a natural experiment
design. Hospital admission rates for acute myocardial infarction were reduced by
8% as a result of a comprehensive smoking ban in New York State, which was esti-
mated to result in direct healthcare savings of US$56 million per year [ 12 ]. While
much as been done to tackle smoking, little has been done to tackle physical inactiv-
ity [ 13 , 14 ]. Physical inactivity costs global healthcare systems at least INT$
billion per year [ 15 ] and policy makers have been urged to take physical inactivity
more seriously [ 16 ].
3.3 Novel Modifiable CVD Risk Factors
A variety of novel circulating biomarkers that reflect inflammation, coagulation,
impaired fibrinolysis, and increased blood viscosity have been identified as poten-
tial CVD risk factors [ 17 ]. There is intense inflammatory activity in atherosclerosis,
for example, and inflammatory markers such as interleukin (IL)-6 and C-reactive
protein (CRP) may directly influence plaque vulnerability and rupture [ 18 ].
However, the clinical utility and causal role of novel risk markers remains widely
debated. In several meta-analyses of large scale prospective cohort studies, CRP and
fibrinogen were found to be moderately associated with risk of CHD and other car-
diovascular outcomes after adjustment for traditional risk factors [ 19 , 20 ]. There are
limited data on the predictive value of novel biomarkers beyond that of traditional
risk factors, and existing evidence is equivocal. For example, in the 17-year follow
up of 1592 participants from the Edinburgh Artery Study, a wide range of novel
biomarkers provided very little prognostic information for incident CVD over and
above traditional risk factors [ 21 ]. In contrast, prospective data from the Women’s
Health Study suggested that fibrinogen and CRP provided additive value to tradi-
tional risk factors in predicting incident CVD [ 22 ].
Geneticists have examined if alleles associated with higher CRP increase risk ofCVD because the measurement of plasma CRP at a single point in time may not
M. Hamer et al.