Arterial calcifications: intimal or medial, does it matter?

Abstract

Cardiovascular diseases are the leading cause of death worldwide. Vascular calcifications are associated with an increased risk of cardiovascular diseases. Vascular calcifications can be present in the intimal or medial layer of the vascular wall. In the past, medial arterial calcifications were considered to be an innocent bystander. However, more recent studies showed that medial arterial calcifications are an independent risk factor for cardiovascular morbidity and mortality. In the breast, medial arterial calcifications have shown to be reversible without interference. In case series and small studies, patients with genetic forms of medial arterial calcifications seem to benefit from etidronate treatment. These findings lead to the hypothesis that medial arterial calcification could be a treatable risk factor in patients with an increased risk of cardiovascular events. However, to be able to treat the patients with medial arterial calcifications, it is important to be able to select these patients in vivo. Therefore, studies are needed on the location of vascular calcification, comparing imaging with histology. In literature, calcifications of the intracranial internal carotid artery (iICA) were found to be an independent risk factor for stroke. Older literature described the presence of both intimal and medial calcification in this artery. We confirmed the presence of calcifications in the intimal layer of the arterial wall, around the internal elastic lamina and in the media. We found that in the majority of arteries, the contribution of internal elastic lamina calcification to the total calcified cross-sectional surface area in the vascular wall was biggest. This suggests that also calcifications of the internal elastic lamina are detected by CT scanning, and that calcifications in that area might therefore be, at least partly, responsible for the observed association between iICA calcification and stroke. This could underline the clinical relevance of non-atherosclerotic calcifications. To be able to study the calcifications in this area in vivo, we created a calcification score based on morphological characteristics of calcifications on Computed Tomography. This score uses thickness, circularity and morphology of the calcifications to determine the dominant type of calcification in the iICA. Older literature suggests that medial calcifications are more regular, diffuse and circumferential, while intimal calcifications are more irregular and discontinuous clumps of calcification. The developed score showed good reproducibility and reasonable ability to differentiate the dominant type of calcification. We applied the calcification score to a cohort suspected acute ischemic stroke patients. We studied whether risk factors would differ between patients with predominant intimal and predominant medial arterial calcification. Although the differences were limited, there were some. Medial arterial calcification is associated with chronic limb threatening ischemia. We studied arterial wall calcifications in the leg. We studied both the popliteal artery and posterior tibial artery and found more atherosclerosis and intimal calcification in the first, and more medial arterial calcification in the latter. We compared the histology data with imaging and tested the previously developed calcification score for the iICA in the peripheral arteries of the lower extremity. We found a reasonable ability to distinguish predominant intimal and predominant medial calcification both with radiography and CT. Given the strong association between CT-detected aortic calcification and aortic stiffness, and the relation between medial arterial calcification and vascular stiffness, we wondered if calcifications in the aortic wall were also mainly medial. We showed that aortic calcifications visible on CT, although sometimes circular, are mainly located in the atherosclerotic intimal lesions, demonstrating that circularity of calcifications (in the developed score used as a feature of medial arterial calcification) not always indicates the presence of medial arterial calcification. This implies that the developed score cannot randomly be applied to every artery in the body.