We have shown that traditional risk factors for CVD and living in the city centre are independently associated with the presence of CAC in a cohort of asymptomatic middle-aged subjects. Men showed a three-fold increase in the risk of having CAC, compared with women, and the risk almost doubled for 60-year-old compared with 50-year-old subjects, participants with diabetes and smokers. Thus, living in the city centre almost doubles the risk of having CAC when compared to living outside the city centre.
The estimated prevalence of CAC in this study is comparable to reported data from two earlier studies of asymptomatic individuals. In the Multi-Ethnic Study of Atherosclerosis (MESA) cohort from the USA, the prevalence of CAC was slightly lower (41% and 16% of 50-year-old men and women and 68% and 36% of 60-year-old men and women, respectively). By contrast, the prevalence was slightly higher in the German Heinz Nixdorf Recall (HNR) study compared with the present study [15, 16]. Both these studies included the Framingham risk factors in an asymptomatic, nonreferred, gender-balanced cohort. The risk profiles between studies, however, are difficult to compare because the DanRisk cohort included only 50- and 60-year-old men and women, whereas the MESA cohort included individuals aged 45–84 years old and the HNR study included 45- to 75-year-old subjects. The Danish and German cohorts seem to have higher blood pressure and higher cholesterol levels, and more participants were current smokers, compared with the US cohort .
In the MESA study, hyperlipidaemia and hypercholesterolaemia were associated with an increased relative risk of 1.22 for the presence of CAC . Moreover, conventional risk factors were associated with the risk of developing CAC amongst participants free of CAC at baseline . In addition, LDL cholesterol was found to be an explanatory factor for incident cases but not in the model for progression of existing CAC. In a multivariate analysis in the HNR study, male gender, age (per 5-year increase), HDL cholesterol, LDL cholesterol, blood pressure and smoking remained independently associated with the presence of CAC .
Data on the presence of CVD risk factors and their association with CAC from the MESA and the HNR studies were evaluated by Erbel et al. . A relative risk regression model was used to compare the presence of CAC in the two studies. The association between age and CAC was almost identical in the two cohorts with an approximately 47% increase in prevalent cases with each 10-year increase in age. A consistent finding in both the HNR and MESA cohorts as well as the present study is that age and sex were most strongly associated with the presence of CAC.
Living in the city centre
The level of human exposure to general air pollution can be associated with traffic and population density at specific locations; thus, a subject’s place of residence is often used as a surrogate for exposure to air pollution . In the present study, even after adjustment for demographic and clinical variables, residency status was independently associated with the presence of CAC, and the prevalence of CAC was highest in people living in the city centre.
Noise, level of stress and educational or socio-economic factors may also influence CAC. However, in the present study, information on these variables was not available; thus, the possibility that they were differently distributed amongst the three groups (city centre, urban and rural dwellers) cannot be excluded. The most robust of these risk factors is noise. Noise [20, 21] as well as stress  has been shown to increase blood pressure levels. In the present study, however, mean blood pressure was lower for the group living in the city centre compared to those living outside. Accordingly, blood pressure was not significantly associated with the presence of CAC in this study. Furthermore, there were no differences in heart rate (another surrogate for stress) prior to scanning, with a mean (±SD) of 69 (±12) beats per min in those living in city centre and mean (±SD) of 69 (±12) living in the urban or rural, thus suggesting that sympathetic activity was equal in the two groups. However, the influence of various stress confounders on the association between residency and asymptomatic CVD needs delineation in future studies.
The mechanisms by which air pollution may contribute to the incidence of CAC are not well understood; it has previously been reported that traffic exposure or air pollution can trigger an acute cardiovascular event  but the results of the present study suggest the involvement of a different mechanism. In the HNR study, the relation between long-term traffic exposure and subclinical atherosclerosis was investigated [9, 10, 24], defined either by CAC or ankle–brachial index . A validated chemical transport model (European air pollution dispersion) was used to assess exposure, and a specific value was assigned for the annual fine PM concentrations for each individual. The urban PM air pollution was related to both carotid intima–media thicknesses  and Agatston score  with stronger associations with particles <2.5 μm than with larger particles (PM10). Also, an association between air pollution and the risk of having an Agatston score above the age- and gender-specific 75th percentile was described . By contrast, no consistent association between air pollution and CAC was found in the MESA study . In the latter study, slightly different statistical methods were applied, measuring both the relative prevalence of CAC (binomial regression) and the amount of CAC (linear regression). The estimate of air pollution was very similar in the MESA and HNR studies. The lower overall number of participants with Agatston score >0 in the MESA study, compared with the HNR study, might be a reasonable explanation for the differences in association between air pollution and the presence of CAC. However, the differences between the studies may also be explained by variations in living conditions in the USA and Europe. Our results seem to be in line with the German observations, although our focus was on prevalent cases, whereas the exact value of Agatston score was considered in the HNR study. The estimate of traffic pollution used in the HNR and MESA studies may be a more accurate estimate of air pollution. However, the surrogate of air pollution used in this study is commonly applied and easily accessible. Thus, it should be acknowledged that results on air pollution from different studies are not directly comparable. The fact that people living in the city centre are more exposed to pollution as compared to those living outside the city centres is supported by other reports including measurements from the Danish National Environmental Research Institute, showing almost triple the concentration of NOx in city centres as compared to urban districts .
There are some limitations that should be discussed. First, the Agatston score is a precise estimate of the atherosclerotic burden, but CAC only represents part of the atherosclerotic lesion. It should, however, be acknowledged that studies have shown that the presence of coronary plaque may occur in patients with an Agatston score of zero . Nevertheless, an Agatston score of zero is generally associated with an excellent prognosis .
Second, atherosclerosis develops over many years during which some participants may have moved between polluted and nonpolluted areas, leading to misclassification. A detailed recall study of residency over time is needed to examine the existence of a dose–response relation between ‘air pollution’ and the Agatston score. There were too few participants in the present study for subanalyses according to various Agatston score intervals. The retrospective exposure assessment defined by taking the lifetime place(s) of residence of the participants into account inevitably leads to some degree of misclassification, and the lack of residential history is a limitation of our study.
Third, there was an association between residential status and the presence of CAC even after adjustment for traditional CVD risk factors. However, other factors potentially related to place of residence, such as social and educational status, lifestyle and exposure to noise, were not taken into account. Noise is known to cause a disposition towards higher blood pressure ; however, we found a lower average blood pressure amongst people living in city centres. Moreover, continuous surveillance of air pollution is carried out in Denmark and shows that, in major cities that are comparable to the cities included in this study, pollution is related to place of residence with much higher mean values of pollutants in the long term in city centres.
In conclusion, the presence of CAC in asymptomatic ‘healthy’ middle-aged subjects is related to the presence of traditional CVD risk factors and living in a city centre (a surrogate for air pollution). These findings may be relevant from a public health perspective, but should be verified in further studies.