In this study we report the use of MRI to directly and noninvasively measure coronary artery wall thickness as a measure of atherosclerotic disease burden. Our objective in this study was to assess the potential utility of coronary artery wall thickness as a marker of atherosclerotic burden in a population free of clinical cardiovascular disease. In this study, participants with 2 or more cardiovascular risk factors had significantly greater maximum coronary wall thickness than those with 1 or no risk factors. This relationship was also present even in subjects without coronary calcification by CT scan. Coronary artery wall thickness overall showed better correlation with carotid intimal-medial thickness than coronary calcium score.
The extent of coronary calcium correlates with overall plaque burden.(8
) Calcium is a minor component of total plaque and is not present in early plaque on autopsy specimens.(8
) Despite a strong correlation between coronary calcium and coronary atherosclerosis, there is substantial interindividual variation in calcium deposition that is apparently due to differences in the tendency for plaque to calcify. (24
) For example, a “zero” calcium score is associated with mild to moderate coronary narrowing in 15% of patients.(26
) The role of coronary calcium scoring seems to be greatest for detection of advanced atherosclerosis in individuals at intermediate risk.(14
We found that there was a trend toward greater coronary wall thickness for increasing levels of calcium but overall this relationship was not statistically significant. Reasons for lack of correlation between calcium score and MRI wall thickness may be related to the threshold method for calcium scoring used for computed tomography, low spatial resolution of the MRI, or both. The calcium scoring method defines a threshold level of x-ray density (130 Hounsfield units), below which calcium (and therefore atherosclerosis) is defined to be absent. We noted that some individuals with a calcium score of zero had increased coronary wall thickness above the mean value. When we evaluated only participants with zero calcium score, we found that participants with 2 or more risk factors had significantly increased coronary wall thickness compared to those with 1 or no risk factors. The ability of MRI to identify coronary artery wall abnormalities in subjects without clinical cardiovascular disease and with zero calcium scores suggests that MRI could be used as an early marker of subclinical coronary atherosclerosis.
Indeed, carotid IMT overall showed better correlation with coronary wall thickness than did calcium score. Carotid IMT is abnormal in individuals with coronary heart disease;(29
) and the relationship between IMT and CHD severity is constant but not strong.(14
) In the Cardiovascular Health Study, carotid IMT greater than 80th percentile had a sensitivity of 47% for predicting coronary artery calcium (CAC) score equal to or greater than 400.(32
) In the present study, participants with IMT values higher than one standard deviation above the mean (greater than the 68th
percentile) had thicker coronary artery walls compared to those with lower IMT values. Since atherosclerosis is a systemic disease, these results confirm the expected co-development of atherosclerosis in multiple vascular territories.
The results of this study show that asymptomatic individuals with increased risk factors for cardiovascular disease have thicker coronary walls than those one or no risk factors. Our results support prior studies using echocardiography, which can interrogate the left anterior descending coronary artery.(33
) Risk factor reduction, including statin therapy,(35
) can reverse the adverse cardiovascular effects of atherosclerosis, but currently there is no noninvasive method that can reliably quantify the anatomic correlate of risk factor reduction in the coronary arteries. Most studies demonstrating the benefit of medical intervention have targeted a population with advanced stages of atherosclerosis because of the inability to detect earlier disease, but a greater reduction in risk is expected if an earlier stage of vascular disease can be identified and quantitatively monitored for response to preventive interventions. Modest reductions in coronary plaque burden after intervention have been reported with intravascular ultrasound,(39
) but the technique is invasive and not easily repeated nor performed on asymptomatic individuals.
There were several limitations of this study. The coronary MRI technique is technically challenging, and only approximately 80% of participants who completed the protocol had interpretable images. As indicated, the sample size was small, limiting the ability to detect graded responses of wall thickness over multiple categories. The spatial resolution of MRI is limited and overestimates the wall thickness of normal coronary arteries.(40
) The spatial resolution used in this study was similar to other studies for MRI of coronary plaque(10)
that have also noted correlation with measures of coronary wall thickness. Focal deposits of calcium may cause loss of signal on the coronary wall images. The MRI readers were blinded to the CT images for calcium, so the mean wall thickness in particular could be reduced if heavy deposits of calcium were present. Despite these issues, the multiple associations between coronary wall thickness by MRI and other subclinical measures of atherosclerosis that were detected in this and other studies thus relates to the identification of abnormal coronary walls by the method. Another limitation of this study is its cross-sectional nature, which prevented us from assessing the temporal sequence between MRI-defined coronary wall thickness and the other variables.
In conclusion, coronary artery wall thickness appears to be related to the coronary artery disease risk factors and carotid IMT, a general marker of atherosclerosis. Further studies are needed to determine the relationship of coronary artery wall thickness to the subsequent development of luminal narrowing and ultimately to the development of cardiovascular events.