7
adequately reflect an individual’s cumulative inflammatory burden. Transgenic
studies of over-expression of human CRP have demonstrated no influence on the
development of atherosclerosis in mice. In prospective studies in humans the asso-
ciation between polymorphisms of the CRP gene and incident CVD have produced
conflicting findings. For example, although CRP genotype was strongly associated
with plasma CRP concentration, there was little association between CRP genotype
and risk of CVD events in the Physician’s Heath Study, the Framingham Heart
Study, or the Rotterdam Study. This contrasts with the Cardiovascular Health Study
where a strong independent association between CRP genotype and fatal CVD
events was observed [ 23 ]. Confirmation of these findings in other large population
studies of older adults with large numbers of fatal events will be important for clari-
fying the role of the CRP gene and risk of CVD. Further research is also required to
determine the clinical utility of apolipoproteins, adiponectin and other biomarkers
because the existing evidence is largely equivocal [ 24 , 25 ].
3.4 Risk Factor Clustering
The presence of two or more risk factors dramatically increases CVD risk. For
example, there are 43 CVD deaths per 10,000 person-years in middle-aged men
who smoke, have high blood pressure, and high cholesterol compared to three CVD
deaths per 10,000 person-years in middle-aged men without these risk factors [ 26 ].
Accordingly, modern treatment regimes have focussed on risk factor clustering to
identify those individuals at greatest risk.
4 Physical Activity and Cardiovascular Disease:
The Evidence
4.1 Population Based Studies
Prospective cohort designs allow groups of individuals with differing levels of phys-
ical activity to be followed for a period of time to determine the relationship between
physical activity and CVD risk. Since the early work of Jerry Morris and Ralph
Paffenbarger, the role of regular physical activity in the prevention of CVD has been
well established. In the 1950s, Morris and colleagues [ 27 ] demonstrated that the
CHD death rates of bus conductors and postmen were half those of comparably
inactive bus drivers and telephonists. Since then, the assessment of physical activity
exposure has become more refined with the use of validated self-reported physical
activity questionnaires. In the Harvard Alumni Health Study, for example,
Paffenbarger and colleagues [ 28 ] questioned 16,936 alumni about the daily number
of blocks walked and flights of stairs climbed, and about the frequency and duration
1 Physical Inactivity and the Economic and Health Burdens Due to Cardiovascular...