The main findings of our study were: (i) the prevalence of CAC > 0 was lower in the MESA population than in the HNR population. (ii) Differences in how specific risk factors affected either the prevalence of CAC > 0 or the level of CAC pertained to age, male gender, BMI, and blood pressure. Risk factors in MESA were lower than in HNR. The results for these two studies appear to be representative of the underlying populations and so differences may be due to differences in the distribution of modifiable risk factors between the United States and Germany.
The prevalence of participants with CAC > 0 was lower in the MESA than those in the HNR population, which was surprising. Our study showed not only a lower prevalence but also lower median CAC values in MESA compared with HNR for men and women. The fact that a much higher proportion of HNR participants had low CAC scores (rather than zero scores) could be explained if the HNR scanners were detecting more noise than the MESA scanners. However, we determined that the presence of a small amount of CAC in HNR was associated with the standard risk factors, indicating that these small values are unlikely to be due primarily to noise artefacts.
On the other hand, participants with CAC > 400 were found slightly more often in the MESA cohort than in the HNR cohort. CAC represents the long-term effect of risk factor exposure, and the observed risk factor values in MESA and HNR reflect only the current level. Alternatively, there were selected risk factors that had a worse profile in MESA than in HNR, such as BMI and HDL-C.
With respect to cardiovascular risk, chronological age represents a very strong risk factor in current algorithms.5–9
Measures of CAC seem to be related to survival.11,12,28
The mean age, but not the range, was slightly different between MESA and HNR, but this difference in ages was not sufficient to explain the difference in prevalence of CAC that we observed.16,28,29
Women have much lower values of CAC than men and start to develop CAC later.16,19
Therefore, risk assessment for increased risk of cardiac outcomes should consider both age and sex.30,31
Gender was one of the most important variables when tested for RR of CAC being present. In addition, gender was one of the two variables with a significantly different association with CAC between the two studies. Both in men and women, the prevalence of CAC = 0 is higher in MESA compared with HNR. This may in part be attributable to differences in risk factor control in the United States vs. Germany. This is supported by higher use of antihypertensive and lipid-lowering medication in the United States (see below), which is expected to be similarly effective in men and women. Risk factor control using medication or life-style interventions may also have been initiated earlier in lives of United States compared with German participants.
Blood pressure can be regarded as a strong risk predictor for both cardiac and cardiovascular events.5–9
Blood pressure was lower among MESA participants than among HNR participants. This difference in blood pressure levels may be part of the explanation of the lower degree of CAC in the MESA compared with the HNR cohorts. One factor that might explain some of this observed difference in blood pressure could be the different oscillographic systems that were used, but not being able to explain the total difference.21
More participants in MESA compared with those in HNR received antihypertensive treatment (30 vs. 27%, P
< 0.0172), and there was less untreated hypertension (10 vs. 24%, P
< 0.0001). Blood pressure control in Germany is far from the optimal that has been reported for other countries.32,33
The poor control of blood pressure and thereby the wider range may be an explanation for the significant association of blood pressure and CAC amount in HNR study but not in MESA. The importance of blood pressure as a risk factor is, however, underlined by the fact that in both studies antihypertensive medication was a highly significant predictor of CAC.
Previous studies have shown that tobacco use is a major avoidable cause of cardiovascular diseases.34
Strong efforts have been made to ban smoking in the United States, but efforts in Europe began later and have been less effective.35
This may explain why the prevalence of current smoking is lower in MESA than in HNR. MESA had much higher rates of former smokers, and roughly equivalent average pack years of smoking, supporting the success of recent anti-smoking efforts in the United States. The interactions between study and the smoking variables were not significant, however, suggesting that the association between smoking and CAC was similar in both studies.
Total cholesterol (TC) and LDL-C are regarded as traditional risk factors.5–9
In the MESA cohort, mean TC was <200 mg/dL, LDL-C <130 mg/dL, and triglycerides <150 mg/dL, which are regarded as desirable, nearly optimal, and normal.9
The results seem to be in line with general trends in the United States.36
LDL-C was selected as the primary target of cholesterol-lowering therapy,9
resulting in an increased use of lipid-lowering medication.36
In HNR, significantly higher concentrations were observed which is representative for Germany.37,38
The association between TC and CAC was not significantly different between the two studies, though was qualitatively stronger in HNR than in MESA. Similarly, HDL was only significantly protective (for the presence of CAC > 0) in MESA, though the interaction was not statistically significant. The prevalence of cholesterol lipid-lowering medication was different between the two studies. The effect of these medications on CAC should be further investigated prospectively in each of these study populations once longitudinal data become available.
In both studies glucose levels were not related to risk of CAC independent of diabetic status, but treated diabetes was significantly associated with CAC. However, in HNR not all subjects were fasting and glucose tolerance tests were not performed in both studies. The RR of prevalent CAC was 55% higher for treated diabetics compared with others in MESA, and 65% higher in HNR. The interaction between study and diabetes was non-significant.
Limitations of the study
It was not possible to compare the full cohorts of either study. To allow for best possible comparability between the two cohorts, identical inclusion criteria were employed to identify all participants without prevalent cardiovascular disease. Thereby, the selection bias could be minimized, which otherwise may have been caused by differences in recruitment strategies.
The prevalence and levels of cardiovascular risk factors are very different in the two cohorts of ostensibly healthy persons but both seem to be representative for each of the two countries. This is a cross-sectional study and so it is not possible to establish the direction of any association between risk factors and CAC.39
In addition, there is a possibility of unmeasured confounders such as lifestyle and dietary history that could explain some of the observed differences between the cohorts. It is possible that differences between the types of scanners used in both studies could explain a small part of the observed population differences in CAC levels. It has to be taken into account that the MESA performed a calculation to estimate the LDL-C concentration whereas it was directly measured in HNR. The assay used met the requirements for accurate testing even from non-fasting individuals.40
However, the differences between MESA and HNR cannot be attributed to these methodological differences because TC also showed the same magnitude of difference in the same direction.
In the present analysis, a socio-economic comparison has not been included, because socio-economic variables such as income—due to differences in services, conversion in income from Euros to Dollars, etc. and education—given the United States cost structure of higher education, are difficult to compare between the two countries.