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Coronary artery calcium (CAC) is a marker of atherosclerosis, and CAC progression is independently associated with all-cause mortality in the general population but not convincingly in subjects with diabetes mellitus (DM). The aim of this study was to ascertain the differences in the rates of CAC progression, the effect of statin therapy, and all-cause mortality in subjects with and without DM. The study group consisted of 296 asymptomatic subjects with type 2 DM and 300 controls (mean age 59 ± 6 years, 29% women) who underwent baseline and follow-up CAC scans within a 2-year interval. Absolute annual CAC score change, percentage annual CAC progression(ΔCAC%), event-free survival, and the effect of statin therapy on survival were all assessed. The mean follow-up duration was 56 ± 11 months. Absolute annual CAC score change was 81 ± 10 in subjects with DM and 34 ± 5 in controls (p = 0.0001). Percentage annual CAC progression was 29 ± 9% in subjects with DM and 10 ± 7% in controls (p = 0.0001). The hazard ratios of death in 3 groups of subjects with DM compared to controls without DM were 1.88 (95% confidence interval [CI] 1.51 to 2.36, p = 0.0001) for ΔCAC of 10% to 20%, 2.29 (95% CI 1.56 to 3.38, p = 0.0001) for ΔCAC of 21% to 30%, and 6.95 (95% CI 2.23 to 11.53, p = 0.0001) for ΔCAC >30%, all compared to ΔCAC <10%. The adjusted hazard ratios of all-cause mortality in subjects receiving compared to those not receiving statin therapy were 0.29 (95% CI 0.13 to 0.56, p = 0.001) in those without DM and without CAC progression, 0.51 (95% CI 0.21 to 0.73, p = 0.001) in those with DM and without CAC progression, and 0.71 (95% CI 0.25 to 0.91, p = 0.003) in those without DM and with CAC progression, with all 3 groups compared to 1.0 (reference) in those with DM, with CAC progression and without statin therapy. In conclusion, CAC progression was greater and event-free survival lower in patients with DM compared to controls in proportion to the extent of CAC progression. These results suggest that CAC progression is an independent predictor of all-cause mortality in patients with DM., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Previous studies have shown that increase in carotid wall thickness (CWT) is associated with cardiovascular risk factors. However, simultaneous systemic and local involvement of atherosclerosis in subjects with high risk of coronary atherosclerosis is not well studied. This study investigates the relation of carotid subclinical atherosclerosis assessed by CWT with the presence and severity of coronary artery calcium(CAC)., Methods: One hundred and twenty nine subjects (age of 69±10 years, 72% male) underwent CAC, carotid CT angiography, and their metabolic status was evaluated. CAC was defined as 0, 1-100, 101-400, 401-1000 and 1000+. CWT (mm) was calculated as: [mean of both right and left CT-measured CWT 10-mm below the common carotid bifurcation]., Results: Modest correlation between CWT and CAC was noted (r=0.48, p=0.0001). CWT increased substantially with the severity of CAC from CAC 0 to CAC 1000+ (p<0.05). Increased CWT (1.0 mm+) was more prevalent in subjects with significant CAC (100+) as compared to CAC 0 (44.7% vs. 3.3%, p<0.05). Increase in CWT was associated with increased rates of metabolic syndrome and diabetes mellitus. After adjustment for cardiovascular risk factors, the risk of metabolic syndrome and DM was 1.7 and 2.3 respectively for each standard deviation (SD) increase in CWT. Similarly, the risk for each SD increase in CWT increased with severity of CAC as compared to CAC 0 (RR:CAC 1-100:1.2, CAC 101-400:1.5, CAC 400-1000:2.1, and CAC 1000+:3.4, respectively)., Conclusion: Increased CWT is associated with the presence and severity of CAC, metabolic syndrome and DM independent of conventional cardiovascular risk factors; highlighting the important role of comprehensive carotid and coronary atherosclerotic assessment to identify at-risk individuals., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: Ventricular dysfunction in asymptomatic patients is directly linked to the eventual development of symptomatic congestive heart failure. This study investigates whether subclinical left ventricular (LV) and right ventricular (RV) dysfunctions measured by computed tomography angiography is associated with the severity of coronary artery disease (CAD)., Methods and Results: We studied 1608 consecutive patients with suspected CAD (age 62 ± 10 years, 64% male), who underwent coronary artery calcium (CAC) scanning and computed tomography angiography. RV and LV volumes at end systole and end diastole were measured, and stroke volume and ejection fraction were calculated using the Simpson method and piecewise smooth subdivision surface (PSSS) method. Analysis by Simpson was performed on short axis and apical four-chamber views. Axial images were used to measure RV and LV volumes by the PSSS method. CAD was defined as normal, nonobstructive, and obstructive (0% stenosis, luminal stenosis 1-49 and 50%+, respectively). There was a strong agreement between PSSS and Simpson method RV ejection fraction (RVEF) and LV ejection fraction (LVEF) measurement. RVEF and LVEF decreased proportionally from CAC 0 to CAC 100+, also from normal-to-diseased coronaries (P=0.001). After adjustment for cardiovascular risk factors, the mean LVEF and RVEF decreased 2.8 and 2.4%, respectively in CAC 100+ compared with CAC 0. Similarly, LVEF and RVEF decreased significantly in nonobstructive CAD (-3.5 and -3.1%, respectively) and obstructive CAD (-5.9 and -4.5%, respectively) compared with normal coronaries, respectively (P<0.05). The relative risk of each 5% decrease in LVEF and RVEF was 1.33 and 1.29 for nonobstructive CAD and 1.54 and 1.33 for obstructive CAD, respectively., Conclusion: The presence and severity of coronary atherosclerosis is significantly associated with subclinical RV and LV dysfunctions.

Rationale and Objectives: Epicardial adipose tissue (EAT), pericardial adipose tissue (PAT), and subcutaneous adipose tissue (SAT) are mediators of metabolic risk and may be involved in the pathogenesis of coronary artery disease. The aim of this study was to investigate the association of visceral and subcutaneous fat depots with the presence and severity of coronary artery calcium (CAC) in asymptomatic individuals., Materials and Methods: One hundred eleven consecutive subjects underwent CAC assessment, and their Framingham risk scores were measured. EAT, total thoracic adipose tissue, and SAT volumes were measured from slice level 15 mm above to 30 mm below the ostium of the left main coronary artery. PAT was calculated as thoracic adipose tissue - EAT. SAT was defined as the volume of fat depot anterior to the sternum and posterior to the vertebra. CAC was defined as 0, 1 to 100, 101 to 400, or ≥ 400. Relative risk regression analysis was used to assess the association between fat depots and CAC., Results: There were modest correlations between EAT (r = 0.58), PAT (r = 0.47), SAT (r = 0.34), and CAC (P < .01). EAT, PAT, and SAT increased proportionally with the severity of CAC in both genders (P < .05). After adjustment for cardiovascular risk factors and body mass index, the relative risks for each standard deviation increase in EAT, PAT, and SAT were 3.3 (95% confidence interval, 1.9-5.6), 2.7 (95% confidence interval, 1.6-3.9), and 2.6 (95% confidence interval, 1.5-4.4) for CAC ≥ 100 compared to CAC 0, respectively (P < .05). The area under the receiver-operating characteristic curve to predict CAC ≥ 100 was higher in each fat depot compared to Framingham risk score, and addition of fat depots to Framingham risk score provided maximum prognostication value to detect CAC ≥ 100., Conclusions: Increased EAT, PAT, and SAT are associated with the severity of CAC independent of risk factors., (Published by Elsevier Inc.)

Aims: In individuals with chronic kidney disease (CKD), including those undergoing maintenance hemodialysis (MHD), coronary artery calcification (CAC) is common. We hypothesized that, in MHD patients, intake of the calcium-free phosphate binder sevelamer is associated with lower CAC compared to calcium-based phosphate binders (CBPB)., Material and Methods: This is a cross-sectional study of MHD patients, who underwent computerized tomography to assess coronary artery calcium scores (CACS). Patients were stratified into two mutually exclusive groups based on taking only a CBPB vs. sevelamer. Logistic regression was used to calculate adjusted odds ratio (OR) of CACS > or = 400, CACS 100 < or =; CACS < 400, 10 < or =; CACS < 100 vs. CACS < 10., Results: 117 MHD patients were either on a CBPB alone (n = 60) or sevelamer alone (n = 57). Despite increased prevalence of DM in the sevelamer group (58%) as compared to the CBPB group (35%), CACS was significantly lower with sevelamer use (283 + or - 83 vs. 494 + or - 94, p = 0.02). The OR of significant CACS > or =; 400 vs. CAC < 10 was 4.35 (95% confidence interval: 1.5 - 9.9, p = 0.008) for CBPB compared with sevelamer, after controlling for case-mix, cholesterol-lowering medication, DM, and inflammatory markers., Conclusion: In our cohort, significant CAC was significantly more prevalent among MHD patients taking CBPB as compared to sevelamer monotherapy.

Introduction: Multidetector computed tomographic angiography (MDCTA) has emerged as a promising noninvasive tool to rule out significant coronary artery disease (CAD). In addition, MDCTA also provides additional information about atherosclerotic plaque composition. In this study, we aim to assess whether differences in plaque composition exist across patients with varying degree of stenotic CAD disease., Methods: Four hundred and sixteen patients with chest pain or shortness of breath thought to be related to CAD (64% males, mean age: 61+/-13 years), with 61 (15%) reporting type 2 diabetes mellitus, who underwent contrast-enhanced MDCTA were studied. Enrolled patients had an intermediate pretest probability of obstructive disease., Results: Overall 51 patients (12%) had normal coronaries without evidence of plaque. In the remaining 365 patients, 45 (12%) and 83 (23%) were found to have stenosis 50-70% and at least 70% in at-least one coronary artery segment, respectively. Those with a higher degree of stenotic CAD showed significantly more coronary segments with exclusively calcified and mixed plaques. With increasing severity of CAD (<50 vs. 50-70% vs. >70% stenosis), the overall proportion of plaque burden was more likely to be mixed (18 vs. 38% vs. 44%) in nature as well less likely to be exclusively noncalcified (39 vs. 20 vs. 16%). Only two of 108 (2%) patients without any underlying calcification had significant CAD (stenosis> or =50%)., Conclusion: Significant differences in plaque composition according to severity of CAD were observed in our study. Individuals with a higher likelihood of stenotic CAD were more likely to have higher underlying burden of exclusively calcified and mixed plaque. These findings should stimulate further investigations to assess the prognostic value of plaque according to their underlying composition.

Background: Atherosclerotic changes within the coronary artery wall can affect vessel distensibility., Objective: This study evaluated the relationship between the coronary distensibility index (CDI) and the severity of coronary artery disease (CAD) measured by computed tomographic angiography (CTA)., Methods: One hundred thirteen subjects, age 63 +/- 10 years, 32% women, who underwent coronary artery calcium (CAC) scanning and CTA, were studied. Early diastolic and mid diastolic (MD) cross-section area (CSA) of the left anterior descending (LAD) artery were measured 5 mm distal to the left main bifurcation. CDI was defined as Deltalumen CSA/[lumen CSA in MD x estimated central pulse pressure (eCPP)] x 10(3) {eCPP = 0.77 x peripheral pulse pressure}. LAD diameter measured by CTA and quantitative coronary angiography (QCA) was compared in 19 subjects without CAD. CAD was defined as normal (no stenosis and CAC 0), mild (stenosis or= 70%) on CTA., Results: Excellent correlation was observed between CTA and QCA measured by CDI (r(2) = 0.96, P = 0.0001). CDI decreased from normal coronaries (6.75 +/- 1.43) to arteries with mild (5.78 +/- 1.45), moderate (3.96 +/- 1.06), and severe (3.31 +/- 1.06) disease (P = 0.004). The risk factor adjusted odds ratio of lowest versus 2 upper tertiles of CDI was 1.28 for mild, 8.47 for moderate, and 10.59 for severe CAD compared with the normal cohort. The area under the ROC curve to predict obstructive CAD (stenosis >or= 50%) increased significantly from 0.71 to 0.84 by addition of CDI to CAC (P < 0.05)., Conclusion: CTA-measured CDI is inversely related to the severity of CAD independent of age, sex, cardiovascular risk factors, and CAC., (Copyright 2010 Society of Cardiovascular Computed Tomography. All rights reserved.)

The relation between oxidative stress and coronary artery calcium (CAC) progression is currently not well described. The present study evaluated the relation among the biomarkers of oxidative stress, vascular dysfunction, and CAC. Sixty asymptomatic subjects participated in a randomized trial evaluating the effect of aged garlic extract plus supplement versus placebo and underwent measurement of CAC. The postcuff deflation temperature-rebound index of vascular function was assessed using a reactive hyperemia procedure. The content of oxidized phospholipids (OxPL) on apolipoprotein B-100 (apoB) particles detected by antibody E06 (OxPL/apoB), lipoprotein(a), IgG and IgM autoantibodies to malondialdehyde-low-density lipoprotein and apoB-immune complexes were measured at baseline and after 12 months of treatment. CAC progression was defined as an annual increase in CAC >15%. Vascular dysfunction was defined according to the tertiles of temperature-rebound at 1 year of follow-up. From baseline to 12 months, a strong inverse correlation was noted between an increase in CAC scores and increases in temperature-rebound (r(2) = -0.90), OxPL/apoB (r(2) = -0.85), and lipoprotein(a) (r(2) = -0.81) levels (p <0.0001 for all). The improvement in temperature-rebound correlated positively with the increases in OxPL/apoB (r(2) = 0.81, p = 0.0008) and lipoprotein(a) (r(2) = 0.79, p = 0.0001) but inversely with autoantibodies to malondialdehyde-low-density lipoprotein and apoB-immune complexes. The greatest CAC progression was noted with the lowest tertiles of increases in temperature-rebound, OxPL/apoB and lipoprotein(a) and the highest tertiles of increases in IgG and IgM malondialdehyde-low-density lipoprotein. In conclusion, the present results have documented a strong relation among markers of oxidative stress, vascular dysfunction, and progression of coronary atherosclerosis. Increases in OxPL/apoB and lipoprotein(a) correlated strongly with increases in vascular function and predicted a lack of progression of CAC., (Copyright 2010 Elsevier Inc. All rights reserved.)

Type 2 diabetes mellitus (DM) is associated with a higher risk of cardiovascular disease and atherosclerotic burden. However little data exists in regards to plaque distribution and plaque composition in these patients. To assess for differences in the coronary plaques burden and composition among symptomatic patients with and without type 2 DM using multidetector computed tomography angiography (MDCTA). The 416 symptomatic patients (64% males, mean age: 61 +/- 13 years) with 61 (15%) reporting type 2 DM, who underwent contrast-enhanced MDCTA were studied. Enrolled patients had an intermediate to high pre-test probability of obstructive coronary artery disease. Multivariate analysis was used to correct for differences in age and gender. Patients with type 2 DM were more likely to have significant stenosis >or=70% in at least one coronary segments (33% in type 2 DM vs. 18% in non diabetic, P = 0.013), whereas 11% of both type 2 DM and non diabetics had stenosis of 50-70% (P = NS). Also type 2 DM patients had a higher number of coronary segments with mixed plaques compared to nondiabetic patients (1.67 +/- 2.01 vs. 1.23 +/- 1.61, P = 0.05), whereas no such differences were observed for non-calcified or calcified plaques. Nearly half (43%) of type 2 DM had coronary artery calcium scores (CACS) >or=400 vs. 29% in non diabetic patients (P = 0.03). Patients with type 2 DM tend to have atherosclerotic plaques which are more likely to be mixed in nature. Future studies need to elucidate the prognostic value of differences in plaque characteristics observed according to type 2 diabetic status.

Previous studies showed strong correlations between low fingertip temperature rebound measured by digital thermal monitoring (DTM) during a 5 min arm-cuff induced reactive hyperemia and both the Framingham Risk Score (FRS), and coronary artery calcification (CAC) in asymptomatic populations. This study evaluates the correlation between DTM and coronary artery disease (CAD) measured by CT angiography (CTA) in symptomatic patients. It also investigates the correlation between CTA and a new index of neurovascular reactivity measured by DTM. 129 patients, age 63 +/- 9 years, 68% male, underwent DTM, CAC and CTA. Adjusted DTM indices in the occluded arm were calculated: temperature rebound: aTR and area under the temperature curve aTMP-AUC. DTM neurovascular reactivity (NVR) index was measured based on increased fingertip temperature in the non-occluded arm. Obstructive CAD was defined as >or=50% luminal stenosis, and normal as no stenosis and CAC = 0. Baseline fingertip temperature was not different across the groups. However, all DTM indices of vascular and neurovascular reactivity significantly decreased from normal to non-obstructive to obstructive CAD [(aTR 1.77 +/- 1.18 to 1.24 +/- 1.14 to 0.94 +/- 0.92) (P = 0.009), (aTMP-AUC: 355.6 +/- 242.4 to 277.4 +/- 182.4 to 184.4 +/- 171.2) (P = 0.001), (NVR: 161.5 +/- 147.4 to 77.6 +/- 88.2 to 48.8 +/- 63.8) (P = 0.015)]. After adjusting for risk factors, the odds ratio for obstructive CAD compared to normal in the lowest versus two upper tertiles of FRS, aTR, aTMP-AUC, and NVR were 2.41 (1.02-5.93), P = 0.05, 8.67 (2.6-9.4), P = 0.001, 11.62 (5.1-28.7), P = 0.001, and 3.58 (1.09-11.69), P = 0.01, respectively. DTM indices and FRS combined resulted in a ROC curve area of 0.88 for the prediction of obstructive CAD. In patients suspected of CAD, low fingertip temperature rebound measured by DTM significantly predicted CTA-diagnosed obstructive disease.

Background: Digital thermal monitoring (DTM) of vascular function was shown to correlate with the presence of known coronary artery disease (CAD)., Objective: We evaluated whether DTM can identify at-risk, asymptomatic patients with significant coronary artery calcium (CAC) or increased Framingham risk score (FRS)., Methods: Two hundred thirty-three consecutive asymptomatic subjects (58 +/- 11 years; 62% men) without known CAD underwent DTM, CAC, and FRS calculation. DTM measurements were obtained during and after a 5-minute suprasystolic arm-cuff occlusion. After cuff-deflation temperature rebound (TR) and area under the temperature curve (AUC) were measured and correlated with FRS and CAC., Results: TR was lower in patients with FRS > 20% and CAC >or= 100 as compared with FRS < 10% and CAC < 10, respectively (P < 0.05). After adjustment for age, sex, and traditional cardiac risk factors, the odds ratio of the lowest compared with the upper 2 tertiles of TR was 3.96 for FRS >or= 20% and 2.37 for CAC >or= 100 compared with low-risk cohorts. The area under the receiver operating characteristic (ROC) curve to predict CAC >or= 100 increased significantly from 0.66 for FRS to 0.79 for TR to 0.89 for TR + FRS., Conclusions: Vascular dysfunction measured by DTM strongly correlates with FRS and CAC independent of age, sex, and traditional cardiac risk factors and was superior to FRS for the prediction of significant CAC.

Background: Brachial artery measures of arterial distensibility have been demonstrated to be independent risk factors for development of heart disease. These measures have been suggested as reflecting the endothelial function or atherosclerotic burden; however, they have not been compared with levels of subclinical atherosclerosis. This study sought to compare measures of brachial artery distensibility to subclinical atherosclerosis as measured by electron beam tomography (EBT)., Methods: Brachial artery pulse waveform data were collected using the DynaPulse 2000A (Pulse Metric, Inc., San Diego, CA). Distensibility measurements were taken on 201 healthy adults and compared with levels of coronary artery calcification (CAC) as measured by EBT. Laboratory values, risk factors, blood pressure (BP), and heart rate measurements were also obtained. We then compared the results of the brachial artery measurements to measures of standard risk factors and CAC., Results: Multivariate analysis was performed, revealing that brachial artery measures were the strongest predictor of CAC. For women, brachial artery (BA) resistance was the strongest independent predictor of log CAC score (r = 0.373, P =.004). For men, BA distensibility was the only independent predictor of calcium scores (P =.012). We then divided the patients into quintiles of calcium score. Patients in the top quintile had a mean BA distensibility that was significantly higher than those of the lowest quintile (P =.02)., Conclusions: Stiffer vessels with decreased distensibility were seen in subjects with higher levels of coronary artery calcium. Therefore, noninvasive measures of distensibility are useful in measuring subclinical vascular changes related to arteriosclerosis. This noninvasive measure might provide a simple and inexpensive method to identify patients with significant atherosclerotic burden.