4. Discussion
4
.
1
. Pre6alence of femoral plaque and coexistent cardio6ascular disease
This paper is the first report of the prevalence of femoral plaque identified by ultrasound in the general
population. Almost two-thirds of the subjects who were scanned showed evidence of femoral plaque. This is
almost three times higher than the proportion expected to show evidence of disease on testing with the ankle
brachial pressure index [7], and therefore suggests that ultrasound is able to detect much less severe disease.
Most epidemiological studies of intermittent claudica- tion demonstrate higher prevalences of disease in men
than women, and increasing prevalence with age [1], a pattern reflected in this study.
There are no other reports of the prevalence of femoral plaque in the general population, but ultra-
sound studies in carotid arteries indicate plaque occurs in 16 [12] to 45 [13] of middle-aged to elderly
women and 25 [12] to 57 of men [13]. Reasons for these lower estimates may reflect differences due to
anatomical site, true differences in population preva- lence, or variation in measurement technique. Using
ultrasound measurement, the prevalence of carotid plaque in this BRHS population was also found to be
very common, affecting 57 of men and 58 of women [22]. This suggests that there is less difference between
the prevalence of disease in the lower limb and the carotid arteries than might be predicted from other
studies. Previous estimates of the population prevalence of lower limb atherosclerosis have relied on autopsy
studies, which demonstrated similar high levels of dis- ease. A study of 293 unselected adult autopsy cases
carried out in Oxford found 15 of men and 5 of women had more than 50 stenosis of at least one
artery [23], and none of the men and only one of the women was completely free of atherosclerotic plaques
in their common iliac arteries. Similar results have also been found in autopsy studies in Pittsburgh, USA [24],
and Malmo¨, Sweden [25].
Subjects with peripheral arterial disease defined by intermittent claudication or a low ABPI have a greater
risk of death from other cardiovascular diseases, partic- ularly coronary heart disease [1,9]. Studies of patients
presenting with intermittent claudication indicate that almost 50 have evidence of coronary artery disease on
clinical history or electrocardiogram [26], and 90 have evidence of disease on angiogram [27]. The subjects in
this study with less severe disease might therefore be expected to have a lower risk of cardiovascular disease,
and indeed only 16.6 of those with plaque had a history of ischaemic heart disease. The odds of having
previous ischaemic heart disease in this group was significantly greater than in those without plaque.
There was no significant difference in the prevalence of stroke in those with and without femoral plaque, prob-
ably reflecting the weaker association between lower limb atherosclerosis and cerebrovascular disease [1].
There were, however, more people on anti-hypertensive therapy in the group with plaque.
The stronger association between femoral plaque and heart disease than stroke is reflected in the stronger
association between plaque and the British Regional Heart Study score than the stroke score. Those in the
top quintiles of both scores have a greatly increased risk of heart disease or a stroke in the next 5 years
[20,21], and therefore the associations between plaque and these scores suggest that plaque identified by ultra-
sound may have clinical significance.
Intermittent claudication is the main symptom of peripheral arterial disease, and therefore subjects with
femoral plaque might be expected to experience more leg pain than those without. Indeed in men there was a
significantly higher prevalence of leg pain in those with plaque, but not in women. This sex difference may have
arisen because the men had more severe disease, or because the women had a higher prevalence of other
causes of leg pain such as arthritis or varicose veins. The questionnaire in this study did not include all the
questions from the WHO claudication questionnaire, but it did contain the question concerning the presence
on calf pain relieved at rest, which is particularly spe- cific in diagnosing pain of claudication [28]. It is there-
fore more likely that the men had more severe disease than the women.
4
.
2
. Association between plaque and cardio6ascular risk factors
Cigarette smoking is known to be the strongest risk factor for intermittent claudication [5], and these results
confirm that smoking is also the most powerful risk factor for femoral atherosclerosis. Interestingly, current
smokers in this study had a higher odds ratio for femoral plaque than other studies have reported for
intermittent claudication [29,30] or a low ABPI [31,32]. This probably reflects the greater accuracy of ultra-
sound compared with other techniques for defining peripheral arterial disease, thus enabling all those with
significant disease to be identified.
Infrequent exercise is also an important risk factor for peripheral arterial disease, and several epidemiolog-
ical studies demonstrate that claudication is more likely to occur in those with sedentary habits [33,34]. This
study confirmed that undertaking frequent exercise was associated with a significantly lower risk of femoral
plaque, but it is difficult to estimate the true effect of exercise in a cross-sectional study, as debilitating dis-
ease may restrict the amount of physical activity that can be performed. To demonstrate the true effect of
exercise on disease, a prospective period of observation on these subjects is required.
Blood pressure generally shows only a small or weak association with intermittent claudication [1], so the
lack of a statistically significant association between femoral plaque and either systolic or diastolic blood
pressure was not surprising. This lack of association may also have been produced by the high prevalence of
treated hypertensives in the group with plaque.
Most, but not all, studies [30,35] demonstrate that raised total cholesterol is a significant risk factor for
intermittent claudication, but the risk is much lower than that associated with smoking [1]. There was a clear
association between raised cholesterol and femoral plaque in this study, however again possibly because of
the greater accuracy of ultrasound in detecting disease. Higher levels of HDL cholesterol were also associated
with a reduced risk of femoral plaque, but not follow- ing adjustment for other risk factors. This was a sur-
prising finding, as previous studies have suggested that HDL cholesterol has a protective effect in relation to
intermittent claudication [1].
This study also demonstrated a significant associa- tion between raised fibrinogen levels and femoral
plaque, confirming other studies which have shown elevated fibrinogen concentrations in those with inter-
mittent claudication [36]. Fibrinogen levels are known to be influenced by other risk factors including age,
obesity, social class, cholesterol, diabetes and smoking [1], and in this study the risk of femoral plaque associ-
ated with fibrinogen was lost on adjusting for smoking, exercise, blood pressure and cholesterol.
In this study, the subject’s home town might also be considered as a risk factor. The prevalence of femoral
plaque was significantly greater in those living in Dews- bury compared with Maidstone, even after adjusting
for age and sex. The prevalence of ischaemic heart disease was similarly higher in Dewsbury, but it is
difficult to determine whether town had more effect on the development of heart disease than lower limb dis-
ease. This is partly because of the different prevalence of disease, and because of the different sensitivity and
specificities of the tests used to define disease. Further adjustment of the risk factors given in Table 4 for town
had no effect on the significance levels.
5. Conclusions
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