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      Coronary Artery Calcium Area by Electron-Beam Computed Tomography and Coronary Atherosclerotic Plaque Area : A Histopathologic Correlative Study

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          Abstract

          Coronary calcium identified by electron-beam computed tomography (EBCT) correlates poorly with luminal atherosclerotic narrowing, but calcium, an intimate part of coronary plaque, may be more directly related to atheromatous plaque area. Thirty-eight coronary arteries from 13 autopsy hearts were dissected, straightened, and scanned with EBCT in 3-mm contiguous increments. Coronary calcium area was defined as one or more pixels with a density > 130 Hounsfield units (0.18 mm2/pixel). Each artery was divided into corresponding 3-mm segments, representative histological sections were stained, and atherosclerotic plaque area per segment (mm2) was quantified. Coronary artery calcium and coronary artery plaque areas were correlated for the hearts as a whole, for individual coronary arteries, and for individual coronary artery segments. The sums of histological plaque areas versus the sums of calcium areas were highly correlated for each heart and for each coronary artery. However, coronary plaque area was on the order of five times greater than calcium area. Furthermore, minimal diffuse segmental coronary plaque could be present despite the absence of coronary calcium detectable by EBCT. This histopathologic study confirms an intimate relation between whole heart, coronary artery, and segmental coronary atherosclerotic plaque area and EBCT coronary calcium area but suggests that there is a threshold value for plaque area below which coronary calcium is either absent or not detectable by this methodology.

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          Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis?

          To assess visual interpretation of the coronary arteriogram as a means of predicting the physiologic effects of coronary obstructions in human beings, we compared caliper measurements of the degree of coronary stenosis with the reactive hyperemic response of coronary flow velocity studied with a Doppler technique at operation, after 20 seconds of coronary arterial occlusion. In 39 patients (44 vessels) with isolated, discrete coronary lesions varying in severity from 10 to 95 per cent stenosis, measurement of the percentage of stenosis from coronary angiograms was not significantly correlated (r = -0.25) with the reactive hyperemic response. Results were the same for obstructions in the left anterior descending, diagonal, and right coronary arteries. Underestimation of lesion severity occurred in 95 per cent of vessels with greater than 60 per cent stenosis of the diameter by arteriography. Both overestimation and underestimation of lesions with less than 60 per cent stenosis were common. These results, together with the high interobserver and intraobserver variability of standard visual analysis of angiograms, suggest that the physiologic effects of the majority of coronary obstructions cannot be determined accurately by conventional angiographic approaches. The need for improved analytical methods for the physiologic assessment of angiographically detected coronary obstructions is apparent.
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            Diffuse calcification in human coronary arteries. Association of osteopontin with atherosclerosis.

            Coronary atherosclerosis is frequently associated with calcification of arterial plaque. To understand the mechanisms responsible for the formation of atherosclerotic calcification, we examined human coronary arteries for the presence and extent of mineral. In sections stained specifically for mineral, staining was diffuse and present in all atherosclerotic plaques. Hydroxyapatite was not detected in normal coronary artery sections. Distribution of hydroxyapatite coincided with a similar distribution of calcium detected by a radiodense pattern using contact microradiography of the same sections before cytochemical staining. By energy-dispersive x-ray microanalysis, the chemical composition of calcified sites was identical to hydroxyapatite (Ca10[PO4]6[OH]2), the major inorganic component of bone. Osteopontin is a phosphorylated glycoprotein with known involvement in the formation and calcification of bone and is regulated by local cytokines. Human coronary artery segments (14 normal and 34 atherosclerotic) obtained at autopsy were evaluated immunohistochemically using polyclonal antibodies generated against human osteopontin. Immunohistochemistry for osteopontin indicated intense, highly specific staining in the outer margins of all diseased segments at each calcification front; staining was evident throughout the entire plaque. Conversely, arterial segments free of atheroma and calcification and sections treated with nonimmune serum had no evidence of positive staining. Osteopontin, a protein involved in mineralization is specifically associated with calcific coronary atheroma and may play an important role in the onset and progression of this disease in human coronary arteries. The deposition of noncollagenous proteins such as osteopontin may regulate the presence or absence of calcification and ultimately alter vessel compliance.
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              Comparison of serial quantitative evaluation of calcified coronary artery plaque by ultrafast computed tomography in persons with and without obstructive coronary artery disease.

              Coronary artery calcium indicates atherosclerosis. Ultrafast computed tomography (CT) can noninvasively visualize and quantify coronary calcium, permitting the natural history of calcified plaque to be studied. This pilot study evaluates the ability of ultrafast CT to follow the progression of calcified plaque within the coronary arteries in patients with and without obstructive coronary artery disease (CAD). Twenty-five subjects had serial ultrafast CT scans of the coronary arteries a mean of 406 days apart. Changes in the number of calcific deposits, calcified plaque area and volume, calcium density and total calcium score were measured. In the 20 patients with calcium on the first study, there were statistically significant increases in mean peak CT number, total calcified plaque volume, total calcified plaque area and total calcium score (p less than 0.0001 for all). Subjects with proved obstructive CAD (n = 10) on angiography had a 48% increase in calcified plaque volume compared with 22% in asymptomatic subjects (n = 10). Comparison of serial studies showed that smaller calcific deposits often coalesced into single larger calcific deposits. Ninety-eight percent (235 of 241) of deposits identified on the first study were accounted for on the second study. Patients with obstructive CAD had a higher number of new calcific deposits than did those in the asymptomatic group (55 vs 18, p = 0.058). Serial ultrafast CT accurately tracks the progression of coronary artery calcium. It is a useful technique for assessing changes in calcified plaque formation in both asymptomatic subjects and in patients with obstructive CAD. It may be useful for studying the natural history of CAD and the effects of intervention on the course of CAD.
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                Author and article information

                Journal
                Circulation
                Circulation
                Ovid Technologies (Wolters Kluwer Health)
                0009-7322
                1524-4539
                October 15 1995
                October 15 1995
                : 92
                : 8
                : 2157-2162
                Affiliations
                [1 ]From the Departments of Cardiovascular Diseases and Internal Medicine (J.A.R., D.B.S., R.S.S.), Diagnostic Radiology (P.F.S.), and Endocrinology and Internal Medicine (L.A.F.), Mayo Clinic and Foundation, Rochester, Minn.
                Article
                10.1161/01.CIR.92.8.2157
                7554196
                b06431f3-08cd-4034-99e5-05066d6a0e0f
                © 1995
                History

                Molecular medicine,Neurosciences
                Molecular medicine, Neurosciences

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