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  • Canadian Neighbor Pharmacy: Enhanced Coronary Calcification Determined by Electron Beam CT Is Strongly Related to Endothelial Dysfunction

Electron beam CTCoronary artery calcification has been shown to play an important role in the development of atherosclerosis and is strongly associated with the total plaque burden proved in previous histopathologic studies. The use of electron beam CT (EBCT) for accurate quantitative measurements has led to an increased interest in understanding the clinical importance of coronary calcium. The coronary calcium score (CCS) determined by EBCT could provide useful prognostic information regarding subsequent coronary events in high-risk subjects with no clinical coronary artery disease (CAD), as well as in patients with the presence of CAD.> EBCT has also been demonstrated to be a useful technique for assessing the progression or regression of CAD in response to treatment of cardiovascular risk factors.

Endothelial dysfunction is thought to be an early sign of vascular endothelium injury and is the first critical step in the pathogenesis of atherosclerosis. Endothelial function plays a key role in determining the clinical manifestations of established atherosclerotic lesions and was proved predictive of further cardiovascular events.’ However, no previous study has shown the relationship between the extent of coronary artery calcification and endothelial function. Therefore, in this study we test the hypothesis that enhanced CCSs determined by EBCT would be associated with endothelial dysfunction assessed by brachial ultrasonography. In addition, although conflicting results were shown about the relationship between C-reactive protein (CRP) and coronary calcification in asymptomatic patients, in this study the associations of CRP and monocyte che-moattractant protein-1 (MCP-1) with coronary calcification and endothelial function were also evaluated in patients with suspected CAD.

Coronary artery calcificationStudy Population

The study population was composed of 124 consecutive patients with symptoms of typical or atypical chest pain who were referred for EBCT to determine coronary calcification between July 2002 and August 2003. We included patients who agreed to undergo brachial ultrasonography for endothelial function evaluation and blood sampling. Patients were excluded if they had history of previous cardiac surgery, myocardial infarction, heart failure, congenital heart disease, valvular heart disease, malignant hypertension, or significant endocrine, hepatic, or renal diseases. Before the study, a detailed review of each patient chart and an interview were conducted to gather data on symptoms, medications, coronary risk factors, previous cardiac events, smoking status, exercise habits, family history of CAD, and other systemic diseases. Blood biochemistry testing analyzed for lipid profiles, fasting sugar, uric acid, and creatinine. The latest news from Canadian Neighbor Pharmacy is collected on its official website.

EBCT Scanning and Image Analysis

EBCT scanning was performed (Imatron C-150XP Ultrafast CT scanner; Imatron; South San Francisco, CA) in the singleslice mode with an image-acquisition time of 100 ms and a section thickness of 3 mm. ECG triggering was used so that the image acquisition occurred after 80% of the R-R interval. Transverse image slices of the heart were obtained contiguously beginning 1 cm below the carina and progressing caudally through the apex to cover the whole heart. All obtained sections of the EBCT scan were then reviewed by an experienced radiologist who was blinded to all clinical data. The CCS for each artery was calculated by the radiologist using the methods of Agatston et al, as previously described.

Endothelium-Dependent Flow-Mediated VasodilationEndothelium-Dependent Flow-Mediated Vasodilation

Endothelium-dependent flow-mediated vasodilation (FMD) was assessed using a 7.5-MHz linear array transducer (Sonos 5500; Hewlett-Packard; Andover, MA) to scan the brachial artery in longitudinal section, as published previously. All subjects were asked to fast, refrain from smoking, and withhold all medications for 12 h before the endothelial function test. To minimize mental stress, care was taken to make the patients as comfortable as possible, and the procedure was performed in a quiet air-conditioned room (22 to 25°C). The left arm was stabilized with a cushion, and a sphygmomanometric cuff was placed on the forearm. A baseline image was acquired, and blood flow was estimated by time averaging the pulsed Doppler velocity signals obtained from a midartery sample volume. Then the cuff was inflated to at least 50 mm Hg above systolic pressure to occlude arteries for 5 min and released abruptly. Postocclusion diameters were obtained at 60, 80, 100, and 120 s after deflation. FMD was calculated as the maximal postocclusion diameter relative to the averaged preocclusion diameters. A midartery pulsed Doppler signal was obtained immediately on cuff release and no later than 15 s after cuff deflation to assess hyperemic velocity.

Endothelium-Independent Nitroglycerine-Mediated Vasodilation

At least 10 min of rest was given after the reactive hyperemia before another image was acquired to reflect the reestablished baseline conditions. Diameter measurements were taken at least three times at 3- to 4-min intervals after 0.6-mg sublingual nitroglycerine administration. The maximal FMD and nitroglycerine-mediated vasodilation (NMD) diameters were determined as the average of the three consecutive maximal-diameter measurements after reactive hyperemia and nitroglycerine use, respectively. The FMD and NMD were then calculated as the percentage change in diameter compared with baseline.

Serum Levels of High-Sensitivity CRP and MCP-1

After 12-h overnight fasting, blood samples were collected for measurement of high-sensitivity CRP (hsCRP) and MCP-1. The blood samples were centrifuged at 3,000 revolutions per minute for 10 min immediately after collection, and then the serum samples were kept frozen at — 70°C until analysis. Determination of hsCRP levels was performed with use of latex-enhanced immunophelometric assay (Dade Behring; Marburg, Germany). MCP-1 in serum was quantified by a sandwich enzyme immunoassay technique (human MCP-1) [Quantikine TM; R&D Systems; Wiesbaden-Nordenstadt, Germany] according to the protocol of the manufacturer. Each standard and each serum sample were analyzed two times. The mean value was used for all subsequent analysis.

Statistical Analysis

All data are expressed as mean ± SEM; p < 0.05 was considered to indicate statistical significance. Differences in baseline characteristics of underlying diseases, smoking status, exercise habits, medications were compared with the x2 test or Fisher Exact Test. Comparison among the three groups with FMD, NMD, hsCRP, and MCP-1 were performed with analysis of variance and Scheffe test (post hoc test). Correlations between FMD, NMD, hsCRP, and MCP-1 were calculated by Pearson correlation test. Multivariable analysis was analyzed by multiple linear regression method, and the variables included in the multivariate model were age, sex, body mass index, hypertension, diabetes mellitus, total cholesterol levels, high-density Lipoproteins, and smoking status.

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