Calcification of Coronary Intima and Media

Abstract

Coronary calcification is a potent predictor of cardiac events. In patients with chronic renal disease, both prevalence and intensity of coronary calcification are increased. It has remained uncertain whether it is the intima of the coronaries or the media that is calcified and whether the morphologic details of calcified plaques differ between renal and nonrenal patients. Autopsy samples of coronaries were obtained from standard sites in 23 renal and 23 age- and gender-matched nonuremic patients. Specimens were examined using light and electron microscopy, immunohistochemistry, backscatter imaging, and x-ray analysis. In coronaries, calcified plaques occupied a similar proportion of the intima area in renal versus nonrenal patients (17.3 +/- 11.9 versus 18.1 +/- 11.9%) but occupied a significantly higher proportion of the media (16.6 +/- 10.6 versus 3.8 +/- 2.31%). Expression of the proteins osteocalcin, C-reactive protein, TGF-beta, and collagen IV was significantly more intensive around coronary plaques of renal compared with nonrenal patients. The non-plaque-bearing intima of renal patients showed minimal staining for fetuin, but fetuin staining was seen surrounding calcified plaques. In addition, more pronounced deposition of C5b-9 was found around coronary plaques of renal patients, and glycophorin deposition pointed to more past intraplaque hemorrhage in renal patients. Calcification by electron backscatter analysis is more intense in the coronary media, but not if the intima is more intense in renal compared with nonrenal patients. A more marked inflammatory response in renal patients is suggested by more frequent presence and greater intensity of markers of inflammation.

Media Calcification and Intima Calcification Are Distinct Entities in Chronic Kidney Disease

“…This finding obviously differs from the findings in muscular arteries, where both granular and well-formed, patchy media calcification can be seen (16). When Gross et al (15) investigated more distal parts of the coronary arteries using backscatter imaging analysis, they found significantly more medial calcification in patients with CKD compared with nonrenal control subjects as well as significantly more deposition of Ca but not of P only in the arterial media. The discrepancies with respect to findings made in a previous autopsy study (8) could be explained by the striking heterogeneity between different vascular regions; therefore, it is almost impossible to draw conclusions pertaining to the changes in the coronary arteries on the basis of findings in peripheral arteries.…”

“…Using x-ray diffraction analysis, two autopsy studies revealed deposits of hydroxyapatite crystals (Ca and P) in coronary plaques of patients with CKD (8,15). In addition, smaller crystalline granules were found in the plaques but not consistently in the vascular media.…”

“…The histologic definition of MS sometimes differs in that some authors also included calcification of the internal lamina elastica (22). In patients with CKD, however, MS-type calcification restricted to the arterial media has been documented in coronary arteries and peripheral arteries (epigastric and radial arteries) (15,16,23). Using plain x-ray analysis, heavy medial calcification of peripheral arteries (the cubital and radial arteries and their branches) can also be demonstrated in patients with CKD and in particular in those with hyperparathyroidism (Figure 1H) (24).…”

25-Hydroxyvitamin D Levels Inversely Associate with Risk for Developing Coronary Artery Calcification

“…Calcitriol concentrations across the range of GFR may help in the evaluation of this possibility but were not available for analysis. It is also possible that CAC includes medial calcification among patients with CKD, 30 with low vitamin D concentrations associated more strongly with medial calcification than with intimal calcification. That risk associated with lower 25(OH)D concentrations does not increase until GFR is Ͻ50 ml/min per 1.73 m 2 may reflect misclassification of eGFR in the 50-to 60-ml/min per 1.73 m 2 range or may reflect a threshold effect of declining calcitriol production.…”

Ultrastructural Analysis of Vascular Calcifications in Uremia

“…To assess the degree of calcification, we applied a semiquantitative score according to the study of Gross et al 30 : Grade 0, no staining; grade 1, minimal positive staining; grade 2, positive staining involving up to 50% of the field of view; grade 3, positive staining involving Ͼ50%; grade 4, positive staining of all structures within the field of view.…”