Search tips
Search criteria

Results 1-25 (1056188)

Clipboard (0)

Related Articles

1.  Lower ratio of high-molecular-weight adiponectin level to total may be associated with coronary high-risk plaque 
BMC Research Notes  2013;6:83.
Although high-molecular-weight (HMW) adiponectin is believed to protect against atherosclerosis, the association between HMW adiponectin and the composition of coronary plaques is unknown. We evaluated whether the HMW to total adiponectin ratio was associated with the presence of coronary plaque and its composition using multi-slice computed tomography coronary angiography (MSCTCA).
Serum total and HMW adiponectin levels were measured in 53 consecutive patients (age, 71) with >50% coronary artery stenosis detected by MSCTCA. A low-attenuation coronary plaque was defined as a plaque with a mean CT density <50 Hounsfield units. Multivariate logistic regression analyses were performed to evaluate the predictors of the presence of low-attenuation coronary plaques, which is thought to be high risk, on CT.
Decreased serum levels of total as well as HMW adiponectin were significantly associated with the presence of at least one calcified or non-calcified coronary artery plaque (total adiponectin level: odds ratio 0.76, 95% CI 0.58–0.99, P = 0.048; HMW adiponectin level: odds ratio 0.65, 95% CI 0.42–0.99, P = 0.047). A low ratio of HMW to total adiponectin was significantly associated with the presence of low-attenuation coronary plaques (4.55, 1.94–21.90, P = 0.049). However, neither the total adiponectin nor the HMW adiponectin level was associated with the presence of low-attenuation coronary plaques.
Lower total or HMW adiponectin levels are associated with the presence of calcified and non-calcified coronary plaques, whereas a lower ratio of HMW to total adiponectin associated with the presence of low-attenuation coronary plaques (thought to be high risk). Measurement of total and HMW adiponectin levels and the HMW to total adiponectin ratio may be useful for risk stratification of coronary artery plaques.
PMCID: PMC3599310  PMID: 23497474
Adiponectin; High-molecular-weight adiponectin; Coronary artery plaque; Coronary low-attenuation plaque
2.  MMP-1 serum levels predict coronary atherosclerosis in humans 
Myocardial infarction results as a consequence of atherosclerotic plaque rupture, with plaque stability largely depending on the lesion forming extracellular matrix components. Lipid enriched non-calcified lesions are considered more instable and rupture prone than calcified lesions. Matrix metalloproteinases (MMPs) are extracellular matrix degrading enzymes with plaque destabilisating characteristics which have been implicated in atherogenesis. We therefore hypothesised MMP-1 and MMP-9 serum levels to be associated with non-calcified lesions as determined by CT-angiography in patients with coronary artery disease.
260 patients with typical or atypical chest pain underwent dual-source multi-slice CT-angiography (0.6-mm collimation, 330-ms gantry rotation time) to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed or non-calcified.
In multivariable regession analysis, MMP-1 serum levels were associated with total plaque burden (OR: 1.37 (CI: 1.02-1.85); p < 0.05) in a model adjusted for age, sex, BMI, classical cardiovascular risk factors, hsCRP, adiponectin, pericardial fat volume and medication. Specification of plaque morphology revealed significant association of MMP-1 serum levels with non-calcified plaques (OR: 1.16 (CI: 1.0-1.34); p = 0.05) and calcified plaques (OR: 1.22 (CI: 1,03-1.45); p < 0.05) while association with mixed plaques was lost in the fully adjusted model. No associations were found between MMP9 serum levels and total plaque burden or plaque morphology.
MMP-1 serum levels are associated with total plaque burden but do not allow a specification of plaque morphology.
PMCID: PMC2754422  PMID: 19751510
3.  Differential associations between blood biomarkers of inflammation, oxidation, and lipid metabolism with varying forms of coronary atherosclerotic plaque as quantified by coronary CT angiography 
Although epidemiologic data link biomarkers of cardiovascular risk with incident and prevalent coronary artery disease, exact anatomic relationships between biomarkers and coronary atherosclerosis as measured by coronary CT angiography remain unclear. Patients with acute chest pain who ultimately had no evidence of acute coronary syndrome underwent contrast-enhanced 64-slice coronary CT angiography to determine presence, extent and composition of coronary atherosclerotic plaque. We determined the differences in levels of blood biomarkers measured at the time of the CT scan between different CT-based atherosclerotic plaque groups. Among 313 patients (mean age: 51.6 ± 11 years, 62% male) high-sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-2 were associated with the extent of calcified plaque (P = 0.03 and P<0.001), while hs-CRP and apolipoprotein A1 were associated with the extent of non-calcified plaque (P = 0.03 and P = 0.004; respectively). Despite a generally lower risk profile, subjects with exclusively non-calcified plaque had significantly higher levels of hs-CRP and oxidized low-density lipoprotein (P = 0.01 and P = 0.03; respectively) and lower levels of adiponectin (P = 0.03) when compared to subjects with calcified plaque (n = 130, 42%). Biomarkers reflecting inflammation, vascular remodeling, oxidation, and lipoprotein metabolism maybe associated with different patterns of coronary atherosclerosis as quantified by coronary CT angiography.
PMCID: PMC3099253  PMID: 21222039
Biomarkers; Atherosclerosis; Cardiac CT; Imaging; Coronary artery disease
4.  Assessment of Coronary Plaque Progression in Coronary CT Angiography Using a Semi-Quantitative Score 
JACC. Cardiovascular imaging  2009;2(11):1262-1270.
To describe progression of coronary atherosclerotic plaque over time by computed tomography (CT) angiography stratified by plaque composition and its association with cardiovascular risk profiles.
Data on the progression of atherosclerosis stratified by plaque composition using non-invasive assessment by CT are limited and hampered by high measurement variability.
This analysis included patients who presented with acute chest pain to the emergency room but had initially no evidence for acute coronary syndrome. All patients underwent contrast enhanced 64-slice CT at baseline and after 2-years using a similar protocol. CT datasets were co-registered and assessed for presence of calcified and non-calcified plaque at 1mm cross-sections of the proximal 40mm of each major coronary artery. Plaque progression over time and its association to risk factors were determined. Measurement reproducibility and correlation to plaque volume was performed in a subset of patients.
We included 69 patients (mean age 55±12years, 59% male) and compared 8,311 co-registered cross-sections at baseline and follow-up. At baseline, any plaque, calcified plaque, and non-calcified were detected in 12.5%, 10.1%, and 2.4% of cross-sections per patient. There was significant progression in the mean number of cross-sections containing any plaque (16.5±25.3 versus 18.6±25.5, p=0.01) and non-calcified plaque (3.1±5.8 versus 4.4±7.0, p=0.04), but not calcified plaque (13.3±23.1 versus 14.2±22.0, p=0.2). In longitudinal regression analysis, the presence of baseline plaque, number of cardiovascular risk factors and smoking were independently associated with plaque progression after adjustment for age, gender and follow-up time interval. The semi-quantitative score based on cross-sections correlated close with plaque volume progression (r=0.75, p<0.0001) and demonstrated an excellent intra- and inter-observer agreement (κ=0.95 and κ=0.93, retrospectively).
Coronary plaque burden of patients with acute chest pain significantly increases over two years. Progression over time is dependent on plaque composition and cardiovascular risk profile. Larger studies are needed to confirm these results and to determine the effect of medical treatment on progression.
PMCID: PMC2796339  PMID: 19909929
atherosclerosis; computed tomography; coronary artery disease; risk factors; progression
5.  Neutrophil/Lymphocyte Ratio Is Associated with Non-Calcified Plaque Burden in Patients with Coronary Artery Disease 
PLoS ONE  2014;9(9):e108183.
Elevations in soluble markers of inflammation and changes in leukocyte subset distribution are frequently reported in patients with coronary artery disease (CAD). Lately, the neutrophil/lymphocyte ratio has emerged as a potential marker of both CAD severity and cardiovascular prognosis.
The aim of the study was to investigate whether neutrophil/lymphocyte ratio and other immune-inflammatory markers were related to plaque burden, as assessed by coronary computed tomography angiography (CCTA), in patients with CAD.
Twenty patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and 30 patients with stable angina (SA) underwent CCTA at two occasions, immediately prior to coronary angiography and after three months. Atherosclerotic plaques were classified as calcified, mixed and non-calcified. Blood samples were drawn at both occasions. Leukocyte subsets were analyzed by white blood cell differential counts and flow cytometry. Levels of C-reactive protein (CRP) and interleukin(IL)-6 were measured in plasma. Blood analyses were also performed in 37 healthy controls.
Plaque variables did not change over 3 months, total plaque burden being similar in NSTE-ACS and SA. However, non-calcified/total plaque ratio was higher in NSTE-ACS, 0.25(0.09–0.44) vs 0.11(0.00–0.25), p<0.05. At admission, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios, CD4+ T cells, CRP and IL-6 were significantly elevated, while levels of NK cells were reduced, in both patient groups as compared to controls. After 3 months, levels of monocytes, neutrophils, neutrophil/lymphocyte ratios and CD4+ T cells remained elevated in patients. Neutrophil/lymphocyte ratios and neutrophil counts correlated significantly with numbers of non-calcified plaques and also with non-calcified/total plaque ratio (r = 0.403, p = 0.010 and r = 0.382, p = 0.024, respectively), but not with total plaque burden.
Among immune-inflammatory markers in NSTE-ACS and SA patients, neutrophil counts and neutrophil/lymphocyte ratios were significantly correlated with non-calcified plaques. Data suggest that these easily measured biomarkers reflect the burden of vulnerable plaques in CAD.
PMCID: PMC4182451  PMID: 25268632
6.  Association of Aortic Valve Calcification to the Presence, Extent, and Composition of Coronary Artery Plaque Burden: ROMICAT Study 
American heart journal  2009;158(4):562-568.
Aortic valve calcification (AVC) is associated with cardiovascular risk factors and coronary artery calcification. We sought to determine whether AVC is associated with the presence and extent of overall plaque burden, as well as to plaque composition (calcified, mixed, and non-calcified).
We examined 357 subjects (mean age: 53 ± 12 years, 61% male) who underwent contrast-enhanced ECG-gated 64-slice multi-detector computed tomography from the ROMICAT trial for the assessment of presence and extent of coronary plaque burden according to the 17-coronary segment model and presence of AVC.
Patients with AVC (n=37, 10%) were more likely than those without AVC (n=320, 90%) to have coexisting presence of any coronary plaque (89% vs. 46%, p<0.001) and had a greater extent of coronary plaque burden (6.4 segments vs. 1.8 segments, p<0.001). Those with AVC had over 3-fold increase odds of having any plaque (adjusted odds ratio [OR] 3.6, p=0.047) and an increase of 2.5 segments of plaque (p<0.001) as compared to those without AVC. When stratified by plaque composition, AVC was associated most with calcified plaque (OR 5.2, p=0.004), then mixed plaque (OR 3.2, p=0.02), but not with non-calcified plaque (p=0.96).
AVC is associated with the presence and greater extent of coronary artery plaque burden and may be part of the later stages of the atherosclerosis process, as its relation is strongest with calcified plaque, less with mixed plaque, and nonsignificant with non-calcified plaque. If AVC is present, consideration for aggressive medical therapy may be warranted.
PMCID: PMC2764241  PMID: 19781415
Aortic valve calcification; coronary artery disease; multi-detector computed tomography; calcified plaque; non-calcified plaque; mixed plaque
7.  HMGB1 Is Associated with Atherosclerotic Plaque Composition and Burden in Patients with Stable Coronary Artery Disease 
PLoS ONE  2012;7(12):e52081.
The role of inflammation in atherosclerosis is widely appreciated. High mobility group box 1 (HMGB1), an injury-associated molecular pattern molecule acting as a mediator of inflammation, has recently been implicated in the development of atherosclerosis. In this study, we sought to investigate the association of plasma HMGB1 with coronary plaque composition in patients with suspected or known coronary artery disease (CAD).
HMGB1, high sensitive troponin T (hsTnT) and high sensitive C-reactive protein (hsCRP) were determined in 152 consecutive patients with suspected or known stable CAD who underwent clinically indicated 256-slice coronary computed tomography angiography (CCTA). Using CCTA, we assessed 1) coronary calcification, 2) non-calcified plaque burden and 3) the presence of vascular remodeling in areas of non-calcified plaques.
Using univariate analysis, hsCRP, hsTnT and HMGB1 as well as age, and atherogenic risk factors were associated with non-calcified plaque burden (r = 0.21, p = 0.009; r = 0.48, p<0.001 and r = 0.34, p<0.001, respectively). By multivariate analysis, hsTnT and HMGB1 remained independent predictors of the non-calcified plaque burden (r = 0.48, p<0.01 and r = 0.34, p<0.001, respectively), whereas a non-significant trend was noticed for hs-CRP (r = 0.21, p = 0.07). By combining hsTnT and HMGB1, a high positive predictive value for the presence of non-calcified and remodeled plaque (96% and 77%, respectively) was noted in patients within the upper tertiles for both biomarkers, which surpassed the positive predictive value of each marker separately.
In addition to hs-TnT, a well-established cardiovascular risk marker, HMGB1 is independently associated with non-calcified plaque burden in patients with stable CAD, while the predictive value of hs-CRP is lower. Complementary value was observed for hs-TnT and HMGB1 for the prediction of complex coronary plaque.
PMCID: PMC3524090  PMID: 23284878
8.  Procoagulant activity of circulating microparticles is associated with the presence of moderate calcified plaque burden detected by multislice computed tomography 
Circulating microparticles (MPs) have been reported to be associated with coronary artery disease (CAD). In this study, we explored the relationship between MPs procoagulant activity and characteristics of atherosclerotic plaque detected by 64-slice computed tomography angiography (CTA).
In 127 consecutive patients with CAD but without acute coronary syndrome and who underwent 64-slice CTA, MPs procoagulant activity in plasma (by a thrombin generation test), soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and N(epsilon)-(carboxymethyl) lysine (CML) circulating levels (by ELISA) were measured. A quantitative volumetric analysis of the lumen and plaque burden of the vessel wall (soft and calcific components), for the three major coronary vessels, was performed. The patients were classified in three groups according to the presence of calcium volume: non-calcified plaque (NCP) group (calcium volume (%) = 0), moderate calcified plaque (MCP) group (0 < calcium volume (%) < 1), and calcified plaque (CP) group (calcium volume (%) ≥ 1).
MPs procoagulant activity and CML levels were higher in MCP group than in CP or NCP group (P = 0.009 and P = 0.027, respectively). MPs procoagulant activity was positively associated with CML (r = 0.317, P < 0.0001) and sLOX-1 levels (r = 0.216, P = 0.0025).
MPs procoagulant activity was higher in the MCP patient group and correlated positively with sLOX-1 and CML levels, suggesting that it may characterize a state of blood vulnerability that may locally precipitate plaque instability and increase the risk of subsequent major cardiovascular events.
PMCID: PMC3981978  PMID: 24748876
Computed tomography; Microparticles; Low density lipoprotein; Lysine; Coronary artery disease
9.  Lower Adiponectin is Associated with Subclinical Cardiovascular Disease among HIV-infected Men 
AIDS (London, England)  2014;28(6):901-909.
To examine if altered levels of adipokines, adipose-derived peptides associated with myocardial infarction in the general population, may contribute to subclinical coronary atherosclerosis in HIV-infected persons.
Nested cohort study.
We studied HIV-infected(HIV+) and HIV-uninfected(HIV−) men in the Multicenter AIDS Cohort Study with noncontrast CT to measure coronary artery calcium and regional adiposity; 75% additionally underwent coronary CT angiography to measure plaque composition and stenosis. Adiponectin and leptin levels were assessed. Multiple regression models were used to assess associations between adipokine levels and HIV disease parameters, regional adiposity, and plaque adjusted for age, race, HIV serostatus and CVD risk factors (RFs).
Significant findings were limited to adiponectin. HIV+ men (n=493) had lower adiponectin levels than HIV− men (n=250) after adjusting for CVD RFs (p<0.0001), which became non-significant after adjustment for abdominal visceral and thigh subcutaneous adipose tissue. Among HIV+ men, lower adiponectin levels were associated with higher CD4+ T cell counts (p= 0.004), longer duration of antiretroviral therapy (p= 0.006) and undetectable HIV RNA levels (p = 0.04) after adjusting for age, race and CVD RFs; only CD4+ cell count remained significant after further adjustment for adipose tissue. In both groups, lower adiponectin levels were associated with increased odds of coronary stenosis > 50% (p <0.007). Lower adiponectin levels were associated with increased extent of plaque in HIV+ and of mixed plaque in HIV− men.
Adiponectin levels were lower in HIV-infected men and related to the severity of subclinical atherosclerosis, independent of traditional CVD risk factors.
PMCID: PMC3967406  PMID: 24401646
Adipokines; adiponectin; leptin; heart; subclinical coronary atherosclerosis; metabolic side effects of HIV infection; coronary CT angiography; cardiac CT
10.  Correlation of concentrations of high-sensitivity troponin T and high-sensitivity C-reactive protein with plaque progression as measured by CT coronary angiography 
Elevated levels of inflammatory biomarkers are associated with increased cardiovascular morbidity and mortality.
We sought to determine whether elevated concentrations of high-sensitivity troponin T (hs-TnT) and high-sensitivity C-reactive protein (hs-CRP) predict progression of coronary artery disease (CAD) as determined by coronary CT angiography (coronary CTA).
Patients presenting to the emergency department with acute chest pain who initially showed no evidence of an acute coronary syndrome underwent baseline and follow-up coronary CTA (median follow-up, 23.9 months) using identical acquisition and reconstruction parameters. Coronary CTA data of each major coronary artery were co-registered. Cross-sections were assessed for the presence of calcified and noncalcified plaques. Progression of atherosclerotic plaque and change of plaque composition from noncalcified to calcified plaque was evaluated and correlated to levels of hs-TnT and hs-CRP at the time of the baseline CT.
Fifty-four patients (mean age, 54.1 years; 59% male) were included, and 6775 cross-sections were compared. CAD was detected in 12.2 ± 21.2 cross-sections per patient at baseline. Prevalence of calcified plaque increased by 1.5 ± 2.4 slices per patient (P < .0001) over the follow-up period. On average, 1.6 ± 3.6 slices with new noncalcified plaque were found per patient (P < .0001) and 0.7 ± 1.7 slices with pre-existing noncalcified plaque had progressed to calcified plaque (P < .0001). After multivariate adjustment, change of overall CAD burden was predicted by baseline hs-TnT and hs-CRP (r = 0.29; P = .039 and r = 0.40; P = .004). Change of plaque composition was associated with baseline hs-TnT (r = 0.29; P = .03).
Concentrations of hs-TnT and hs-CRP are weakly associated with a significant increase in CAD burden and change in plaque composition over 24 months independent of baseline risk factors.
PMCID: PMC4487607  PMID: 25467832
Coronary artery disease; Coronary atherosclerotic plaque; Plaque progression; Cardiac biomarker; Coronary CT angiography
11.  Associations between HIV Infection and Subclinical Coronary Atherosclerosis: The Multicenter AIDS Cohort Study (MACS) 
Annals of internal medicine  2014;160(7):458-467.
Coronary artery disease (CAD) has been associated with HIV infection; however data are not consistent.
We performed cardiac CT to determine whether HIV-infected men have more coronary atherosclerosis than uninfected men.
Cross-sectional study within the Multicenter AIDS Cohort Study(MACS).
HIV-infected (n=618) and –uninfected (n=383) men who have sex with men (MSM) had non-contrast and contrast enhanced cardiac CT if they were between 40–70 years, weighed <300 pounds, and had no history of coronary revascularization.
Presence and extent, for those with plaque, of coronary artery calcium (CAC) on non-contrast CT, and of any plaque, non-calcified, mixed or calcified plaque and stenosis on CT angiography.
1001 men underwent non-contrast CT of whom 759 had coronary CT angiography. After adjusting for age, race, center, and cohort, HIV-infected men had a greater prevalence of CAC [Prevalence ratio(PR)=1.21, 95% confidence interval (CI) 1.08–1.35, p=0.001], and any plaque [PR=1.14(1.05–1.24),p=0.001], including non-calcified plaque [PR=1.28(1.13–1.45),p<0.001) and mixed plaque [PR=1.35(1.10–1.65),p=0.004] than HIV-uninfected men. Associations between HIV-infection and any plaque and non-calcified plaque remained significant (p<0.005) after CAD risk factor adjustment. HIV-infected men also had a greater extent of non-calcified plaque after CAD risk factor adjustment (p=0.026). HIV-infected men had a greater prevalence of coronary artery stenosis>50% than HIV-uninfected men [PR=1.48(1.06–2.07),p=0.020), but not after CAD risk factor adjustment. Longer duration of highly active antiretroviral therapy [PR=1.09(1.02–1.17), p=0.007,per year] and lower nadir CD4+ T-cell count [PR=0.80(0.69–0.94),p=0.005, per 100 cells] were associated with coronary stenosis>50%.
Coronary artery plaque, especially non-calcified plaque, is more prevalent and extensive in HIV-infected men, independent of CAD risk factors.
Cross-sectional observational study design and inclusion of only men.
Primary Funding Source
PMCID: PMC4143766  PMID: 24687069
12.  Influence of Pericoronary Adipose Tissue on Local Coronary Atherosclerosis as Assessed by a Novel MDCT Volumetric Method 
Atherosclerosis  2011;219(1):151-157.
Pericoronary adipose tissue (PCAT) may create a pro-inflammatory state, contributing to the development of coronary artery disease (CAD). We sought to evaluate the feasibility of avolumetric PCAT quantification method using a novel threshold based computed tomography approach. In addition we determined the relation between PCAT volumes and CAD.
In 51 patients (49.5±5.1 years, 64.8% male) who underwent 64-slice MDCT, we measured threshold-based PCAT volumes using distance and anatomic-based methods. Using the most reproducible method, we performed the proximal 40-mm distance measurement in three groups as stratified by coronary plaque and high-sensitivity C-reactive protein (hs-CRP) levels: Group 1 (presence of coronary plaque, hs-CRP >2.0 mg/L); an intermediate group (Group 2, no plaque, hs-CRP >2.0 mg/L); and Group 3 (no plaque, hs-CRP<1.0 mg/L). We compared PCAT volumes to the presence of coronary plaque on a patient (n=51) and vessel (n=153) basis. On a subsegment basis (n=1224), we compared PCAT volume to the presence of plaque as well as plaque morphology.
Distance-based PCAT volume measurements yielded excellent reproducibility with intra-observer intraclass correlation (ICC) of 0.997 and inter-observer ICC of 0.951. On a both a per-patient and per-vessel analysis, adjusted PCAT volume was greater in patients with plaque (Group 1) than without plaque (Group 2 and 3, p<0.001). No difference in PCAT volume was seen between high and low hs-CRP groups without plaque (p=0.51). Adjusted PCAT volumes were higher in subsegments with plaque as compared without (p<0.001). Additionally, adjusted PCAT volume was greatest in subsegments with mixed plaque followed by non-calcified plaque, calcified plaque, and the lowest volume in segments with no plaque (p<0.001).
In this proof-of-concept study, threshold based PCAT volume assessment is feasible and highly reproducible. PCAT volume is increased in patients and vessels with coronary plaques. Surrounding vessel subsegments with coronary plaque, particularly mixed plaques, have greatest PCAT volume and highlight the effect of local PCAT in the development of coronary atherosclerosis.
PMCID: PMC3203345  PMID: 21782176
Coronary artery disease; pericoronary fat; epicardial fat; adipose tissue; inflammation; computed tomography
13.  Segmental heterogeneity of vasa vasorum neovascularization in human coronary atherosclerosis and role of intraplaque hemorrhage in plaque calcification 
JACC. Cardiovascular imaging  2010;3(1):32-40.
To investigate the role of coronary vasa vasorum (VV) neovascularization in the progression and complications of human coronary atherosclerotic plaques.
Accumulating evidence supports an important role of VV neovascularization in atherogenesis and lesion location determination in coronary artery disease. VV neovascularization can lead to intraplaque hemorrhage, which has been identified as a promoter of plaque progression and complications like plaque rupture. We hypothesized that distinctive patterns of VV neovascularization and associated plaque complications can be found in different stages of human coronary atherosclerosis.
Hearts from 15 patients (age 52±5, mean±SEM) were obtained at autopsy, perfused with Microfil™ and subsequently scanned with micro-computed tomography (micro-CT). Two-cm-segments (n=50) were histologically classified as either normal (n=12), nonstenotic plaque (<50% stenosis, n=18), or calcified (n=10) or non-calcified (n=10) stenotic plaque. Micro-CT images were analyzed for VV density (#/mm2), VV vascular area fraction (mm2/mm2) and VV endothelial surface fraction (mm2/mm3). Histological sections were stained for Mallory’s (iron), von Kossa (calcium) and glycophorin-A (erythrocyte fragments) as well as endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α).
VV density was higher in segments with non-stenotic and non-calcified stenotic plaques as compared to normals (3.36±0.45, 3.72±1.03 vs. 1.16±0.21, P<0.01). In calcified stenotic plaques VV spatial density was lowest (0.95±0.21, P<0.05 vs. non-stenotic and non-calcified stenotic plaque). The amount of iron and glycophorin A was significantly higher in non-stenotic and stenotic plaques as compared to normals, and correlated with VV density (Kendall-Tau correlation-coefficient 0.65 and 0.58 respectively, P<0.01). Moreover, relatively high amounts of iron and glycophorin A were found in calcified plaques. Further immunohistochemical characterization of VV revealed positive staining for eNOS and TNF-α but not VEGF.
Our results support a possible role of VV neovascularization, VV rupture and intraplaque hemorrhage in the progression and complications of human coronary atherosclerosis.
PMCID: PMC2872563  PMID: 20129528
vasa vasorum; human coronary atherosclerosis; micro-CT; calcification; intraplaque hemorrhage
14.  Aortic Distensibility and its Relationship to Coronary and Thoracic Atherosclerosis Plaque and Morphology by MDCT: Insights from the ROMICAT Trial 
International journal of cardiology  2012;167(4):1616-1621.
Multi-detector cardiac computed tomography (CT) allows for simultaneous assessment of aortic distensibility (AD), coronary atherosclerosis, and thoracic aortic atherosclerosis.
We sought to determine the relationship of AD to the presence and morphological features in coronary and thoracic atherosclerosis.
In 293 patients (53±12 years, 63% male), retrospectively-gated MDCT were performed. We measured intraluminal aortic areas across 10 phases of the cardiac cycle (multiphase reformation 10% increments) at pre-defined locations to calculate the ascending, descending, and local AD (at locations of thoracic plaque). AD was calculated as maximum change in area/(minimum area × pulse pressure). Coronary and thoracic plaques were categorized as calcified, mixed, or non-calcified.
Ascending and descending AD were lower in patients with any coronary plaque, calcified or mixed plaque than those without (all p<0.0001) but not with non-calcified coronary plaque (p≥0.46). Per 1 mmHg−110−3 increase in ascending and descending AD, there was an 18–29% adjusted risk reduction for having any coronary, calcified plaque, or mixed coronary plaque (ascending AD only) (all p≤0.04). AD was not associated with non-calcified coronary plaque or when age was added to the models (all p>0.39). Local AD was lower at locations of calcified and mixed thoracic plaque when compared to non-calcified thoracic atherosclerosis (p<0.04).
A stiffer, less distensible aorta is associated with coronary and thoracic atherosclerosis, particularly in the presence of calcified and mixed plaques, suggesting that the mechanism of atherosclerosis in small and large vessels is similar and influenced by advancing age.
PMCID: PMC3419779  PMID: 22578738
aortic distensibility; coronary atherosclerosis; thoracic atherosclerosis; peripheral vascular disease; computed tomography; cardiovascular aging
15.  Improved non-calcified plaque delineation on coronary CT angiography by sonogram-affirmed iterative reconstruction with different filter strength and relationship with BMI 
To prospectively compare non-calcified plaque delineation and image quality of coronary computed tomography angiography (CCTA) obtained with sinogram-affirmed iterative reconstruction (IR) with different filter strengths and filtered back projection (FBP).
A total of 57 patients [28.1% females; body mass index (BMI) 29.2±6.5 kg/m2] were investigated. CCTA was performed using 128-slice dual-source CT. Images were reconstructed with standard FBP and sinogram-affirmed IR using different filter strength (IR-2, IR-3, IR-4) (SAFIRE, Siemens, Germany). Image quality of CCTA and a non-calcified plaque outer border delineation score were evaluated by using a 5-scale score: from 1= poor to 5= excellent. Image noise, contrast-to-noise ratio (CNR) of aortic root, left main (LM) and right coronary artery, and the non-calcified plaque delineation were quantified and compared among the 4 image reconstructions, and were compared between different BMI groups (BMI <28 and ≥28). Statistical analyses included one-way analysis of variance (ANOVA), least significant difference (LSD) and Kruskal-Wallis test.
There were 71.9% patients in FBP, 96.5% in IR-2, 96.5% in IR-3 and 98.2% in IR-4 who had overall CCTA image quality ≥3, and there were statistical differences in CCTA exam image quality score among those groups, respectively (P<0.001). Sixty-one non-calcified plaques were detected by IR-2 to IR-4, out of those 11 (18%) were missed by FBP. Plaque delineation score increased constantly from FBP (2.7±0.4) to IR-2 (3.2±0.3), to IR-3 (3.5±0.3) up to IR-4 (4.0±0.4), while CNRs of the non-calcifying plaque increased and image noise decreased, respectively. Similarly, CNR of aortic root, LM and right coronary artery improved and image noise declined from FBP to IR-2, IR-3 and IR-4. There were no significant differences of image quality and plaque delineation score between low and high BMI groups within same reconstruction (all P>0.05). Significant differences in image quality and plaque delineation scores among different image reconstructions both in low and high BMI groups (all P<0.001) were found. I4f revealed the highest image quality and plaque delineation score.
IR offers improved image quality and non-calcified plaque delineation as compared with FBP, especially if BMI is increasing. Importantly, 18% of non-calcified plaques were missed with FBP. IR-4 shows the best image quality score and plaque delineation score among the different IR-filter strength.
PMCID: PMC4420677  PMID: 25984450
Non-calcified plaque; sinogram-affirmed iterative reconstruction (sinogram-affirmed IR); coronary computed tomography angiography (CCTA)
16.  Non-invasive evaluation of atherosclerosis with contrast enhanced 16 slice spiral computed tomography: results of ex vivo investigations 
Heart  2004;90(12):1471-1475.
Objective: To evaluate the diagnostic accuracy of 16 slice computed tomography (CT) in determining plaque morphology and composition in an experimental setting. The results were compared with histopathological analysis as the reference standard.
Methods: Nine human popliteal arteries derived from amputations because of atherosclerotic disease were investigated with multislice spiral CT (MSCT). Atherosclerotic lesions were morphologically classified (completely or partially occlusive, concentric, eccentric), and tissue densities were determined within these plaques. In addition, vessel dimensions were quantitatively measured.
Results: The results were compared with histological analysis. The concordance index κ for morphological classification was 0.88. Plaque density (n  =  51 lesions) was significantly different (p < 0.0001) between lipid rich, fibrotic, and calcified lesions (Stary stage III: n  =  2, 58 (8) Hounsfield units (HU); Stary V: n  =  11, 50 (21) HU; Stary VI: n  =  14, 96 (42) HU; Stary VII: n  =  6, 858 (263) HU; Stary VIII: n  =  18, 126 (99) HU). The concordance index κ for the classification of plaques based on density was 0.51. Vessel dimensions had a good correlation (r  =  0.98).
Conclusions: 16 slice CT was found to be a reliable non-invasive imaging technique for assessing atherosclerotic plaque morphology and composition. Although calcified lesions can be differentiated from non-calcified lesions, the diagnostic accuracy in further subclassifying non-calcified plaques as lipid rich and fibrotic is low, even under experimental conditions.
PMCID: PMC1768560  PMID: 15547032
atherosclerosis; coronary artery disease; multislice spiral computed tomography; non-calcified plaques
17.  Comparison of Racial Differences in Plaque Composition and Stenosis among HIV Positive and Negative Men from the Multicenter Aids Cohort Study (MACS) 
The American journal of cardiology  2014;114(3):369-375.
Previous studies demonstrated that blacks have less coronary artery calcification (CAC) than whites. We evaluated racial differences in plaque composition and stenosis in the Multicenter AIDS Cohort Study (MACS). HIV positive and negative men completed non-contrast cardiac CT if they were 40–70 years, weighed <300 pounds, and had no prior history of cardiac surgery or revascularization, and if eligible, coronary CT angiography (CTA). There were 1001 men who underwent CT scans and 759 men had CTA. We measured CAC on non-contrast CT, and total plaque, non-calcified, calcified, and mixed plaque, and identified coronary stenosis >50% on CTA. The association of presence and extent of plaque with race was determined after adjustment for HIV serostatus, cardiovascular risk factors and measures of socioeconomic status. The prevalences of any plaque on CTA and non-calcified plaque were not different between black and white men; however, black men had lower prevalences of CAC (Prevalence ratio (PR)=0.79, p=0.01), calcified plaque (PR=0.69, p=0.002), and stenosis >50% (PR=0.59, p=0.009). There were no associations between black race and extent of plaque in fully adjusted models. Using log-linear regression, black race was associated with a lower extent of any plaque on CTA in HIV positive men (estimate=−0.24, p=0.051) but not in HIV negative men (0.12, p=0.50, HIV interaction p=0.005). In conclusion, a lower prevalence of CAC in black compared to white men appears to reflect less calcification of plaque and stenosis rather than a lower overall prevalence of plaque.
PMCID: PMC4143765  PMID: 24929623
Epidemiology; plaque; coronary angiography; coronary artery disease; HIV
18.  Statins use and coronary artery plaque composition: Results from the International Multicenter CONFIRM Registry 
Atherosclerosis  2012;225(1):148-153.
The effect of statins on coronary artery plaque features beyond stenosis severity is not known. Coronary CT angiography (CCTA) is a novel non-invasive method that permits direct visualization of coronary atherosclerotic features, including plaque composition. We evaluated the association of statin use to coronary plaque composition type in patients without known coronary artery disease (CAD) undergoing CCTA.
From consecutive individuals, we identified 6673 individuals (2413 on statin therapy and 4260 not on statin therapy) with no known CAD and available statin use status. We studied the relationship between statin use and the presence and extent of specific plaque composition types, which was graded as non-calcified (NCP), mixed (MP), or calcified (CP) plaque.
The mean age was 59 ± 11 (55% male). Compared to the individuals not taking statins, those taking statins had higher prevalence of risk factors and obstructive CAD. In multivariable analyses, statin use was associated with increased the presence of MP [odds ratio (OR) 1.46, 95% confidence interval (CI) 1.27–1.68), p < 0.001] and CP (OR 1.54, 95% CI 1.36–1.74, p < 0.001), but not NCP (OR 1.11, 95% CI 0.96–1.29, p = 0.1). Further, in multivariable analyses, statin use was associated with increasing numbers of coronary segments possessing MP (OR 1.52, 95% CI 1.34–1.73, p < 0.001) and CP (OR 1.52, 95% CI 1.36–1.70, p < 0.001), but not coronary segments with NCP (OR 1.09, 95% CI 0.94–1.25, p = 0.2).
Statin use is associated with an increased prevalence and extent of coronary plaques possessing calcium. The longitudinal effect of statins on coronary plaque composition warrants further investigation.
PMCID: PMC4277888  PMID: 22981406
Statin; Plaque composition; Coronary CTA; Coronary artery disease; Lipid profile
19.  Mechanism of lumen enlargement with direct stenting versus predilatation stenting: influence of remodelling and plaque characteristics assessed by volumetric intracoronary ultrasound 
Heart  2003;89(1):84-90.
Objective: To compare the effects of arterial remodelling and plaque characteristics on the mechanisms of direct stenting and predilatation stenting. Direct stenting has become routine in some laboratories and differs technically from predilatation stenting.
Methods: Pre- and post-interventional volumetric intravascular ultrasound (IVUS) was undertaken in 30 patients with direct stenting and in 30 with predilatation stenting of non-calcified native coronary lesions, using the same stent design and stent length. Lumen, vessel (external elastic membrane (EEM)), and plaque (plaque + media) volumes were calculated. Remodelling was determined by comparing the EEM area at the centre of the lesion with the EEM areas at proximal and distal reference sites. Plaque eccentricity was defined as the thinnest plaque diameter to the thickest plaque diameter ratio. Plaque composition was characterised as soft, mixed, or dense.
Results: All volumetric IVUS changes were similar in the two groups. Pre-intervention remodelling remained uninfluenced after direct stenting, but was neutralised after predilatation stenting. Eccentric lesions responded to intervention by a greater luminal gain owing to greater vessel expansion in direct stenting. Plaque composition influenced luminal gain in direct stenting, the gain being greatest in the softest plaques; in predilatation stenting, luminal gain was equivalent but vessel expansion was greater for “dense” plaque and plaque reduction greater for “soft” plaque.
Conclusions: In non-calcified lesions, the mechanisms of lumen enlargement after direct or predilatation stenting are significantly influenced by atherosclerotic remodelling, plaque eccentricity, and plaque composition.
PMCID: PMC1767502  PMID: 12482801
stents; intravascular ultrasound; angioplasty; remodelling
20.  The Association of Brachial Artery Diameter with Noncalcified Coronary Plaque Burden in Apparently Healthy Individuals 
Coronary artery disease  2013;24(8):657-662.
Coronary atherosclerosis has been associated with systemic arterial remodeling even in non-atherosclerotic vessels. However it is not known whether systemic remodeling is differentially associated with the cumulative atherosclerotic process, reflected by putatively quiescent calcified plaque (CP) or with active atherosclerosis consisting of non-calcified plaque (NCP). We thus examined the association of brachial artery diameter (BAD), an artery which does not suffer clinical atherosclerosis, with the presence and the extent of coronary CP and NCP.
We studied 688 apparently healthy, asymptomatic participants from 350 families with a history of early-onset coronary artery disease (<60 years of age) measuring CAD risk factors and coronary plaque using dual-source CT angiography. Plaque volumes were quantified using a validated automated method. BAD was measured during diastole using B-mode ultrasound. The association of resting BAD with any detectable plaque, and log-transformed CP and NCP volumes if detectable, was tested using Generalized Estimating Equations (GEE) adjusted for age, sex, race, current smoking, diabetes, hypertension, body mass index, non-HDL and HDL-cholesterol.
Higher quintiles of BAD were associated with greater age and male sex (both p <0.001). In fully adjusted analysis, CP volume was not associated with BAD (p=0.65) but 1 ml greater NCP volume was associated with 0.65 mm larger BAD (p=0.027).
Our results suggest that systemic arterial remodeling of non-atherosclerotic arteries is a dynamic process that is correlated with the extent of putatively active atherosclerotic processes in distant beds, but not inactive accumulated plaque burden.
PMCID: PMC4476290  PMID: 24077324
Brachial Artery; Remodeling; CT Angiography
21.  Relationship among coronary plaque compliance, coronary risk factors and tissue characteristics evaluated by integrated backscatter intravascular ultrasound 
The purpose of the present study was to evaluate the mechanical properties of coronary plaques and plaque behavior, and to elucidate the relationship among tissue characteristics of coronary plaques, mechanical properties and coronary risk factors using integrated backscatter intravascular ultrasound (IB-IVUS).
Non-targeted plaques with moderate stenosis (plaque burden at the minimal lumen site: 50-70%) located proximal to the site of the percutaneous coronary intervention target lesions were evaluated by IB-IVUS. Thirty-six plaques (less calcified group: an arc of calcification ≤10°) in 36 patients and 22 plaques (moderately calcified group: 10° < an arc of calcification ≤60°) in 22 patients were evaluated. External elastic membrane volume (EEMV) compliance, lumen volume (LV) compliance, plaque volume (PV) response (difference between PV in systole and diastole), EEM area stiffness index were measured at the minimal lumen site. Relative lipid volume (lipid volume/internal elastic membrane volume) was calculated by IB-IVUS.
In the less calcified group, there was a significant correlation between EEMV compliance and the relative lipid volume (r = 0.456, p = 0.005). There was a significant inverse correlation between EEM area stiffness index and the relative lipid volume (p = 0.032, r = −0.358). The LV compliance and EEM area stiffness index were significantly different in the diabetes mellitus (DM) group than in the non-DM group (1.32 ± 1.49 vs. 2.47 ± 1.79%/10 mmHg, p =0.014 and 28.3 ± 26.0 vs. 15.7 ± 17.2, p =0.020). The EEMV compliance and EEM area stiffness index were significantly different in the hypertension (HTN) group than in the non-HTN group (0.77 ± 0.68 vs. 1.57 ± 0.95%/10 mmHg, p =0.012 and 26.5 ± 24.3 vs. 13.0 ± 16.7, p =0.020). These relationships were not seen in the moderately calcified group.
The present study provided new findings that there was a significant correlation between mechanical properties and tissue characteristics of coronary arteries. In addition, our results suggested that the EEMV compliance and the LV compliance were independent and the compliance was significantly impaired in the patients with DM and/or HTN. Assessment of coronary mechanical properties during PCI may provide us with useful information regarding the risk stratification of patients with coronary heart disease.
PMCID: PMC3489794  PMID: 22846428
Coronary artery disease; Intravascular ultrasound; Plaque; Stiffness; Tissue
22.  Characteristics of coronary artery disease in symptomatic type 2 diabetic patients: evaluation with CT angiography 
Coronary artery disease (CAD) is a common and severe complication of type 2 diabetes mellitus (DM). The aim of this study is to identify the features of CAD in diabetic patients using coronary CT angiography (CTA).
From 1 July 2009 to 20 March 2010, 113 consecutive patients (70 men, 43 women; mean age, 68 ± 10 years) with type 2 DM were found to have coronary plaques on coronary CTA. Their CTA data were reviewed, and extent, distribution and types of plaques and luminal narrowing were evaluated and compared between different sexes.
In total, 287 coronary vessels (2.5 ± 1.1 per patient) and 470 segments (4.2 ± 2.8 per patient) were found to have plaques, respectively. Multi-vessel disease was more common than single vessel disease (p < 0.001), and the left anterior descending (LAD) artery (35.8%) and its proximal segment (19.1%) were most frequently involved (all p < 0.001). Calcified plaques (48.8%) were the most common type (p < 0.001) followed by mixed plaques (38.1%). Regarding the different degrees of stenosis, mild narrowing (36.9%) was most common (p < 0.001); however, a significant difference was not observed between non-obstructive and obstructive stenosis (50.4% vs. 49.6%, p = 0.855). Extent of CAD, types of plaques and luminal narrowing were not significantly different between male and female diabetic patients.
Coronary CTA depicted a high plaque burden in patients with type 2 DM. Plaques, which were mainly calcified, were more frequently detected in the proximal segment of the LAD artery, and increased attention should be paid to the significant prevalence of obstructive stenosis. In addition, DM reduced the sex differential in CT findings of CAD.
PMCID: PMC2992482  PMID: 21067585
23.  The diagnostic and prognostic value of coronary CT angiography in asymptomatic high-risk patients: a cohort study 
Open Heart  2014;1(1):e000096.
To prospectively assess the value of coronary CT angiography (CTA) in asymptomatic patients with high ‘a priori’ risk of coronary artery disease (CAD).
711 consecutive asymptomatic patients (61.8 years; 40.1% female) with high ‘a priori’ risk of CAD were prospectively examined with a coronary calcium score (CCS) and CTA. Coronary arteries were evaluated for atherosclerotic plaque (non-calcified and calcified) and stenosis (mild <50%, intermediate 50–70% or high-grade >70%). Coronary Segment Involvement Score (SIS, total number of segments with plaque) and nc (non-calcified) SIS were calculated. Primary end points were major adverse cardiac events (ST-elevation MI, non-ST-elevation MI and cardiac death); secondary end points were coronary revascularisation and >50% stenosis by invasive angiography.
Of 711 patients, 28.3% were negative for CAD and 71.7% positive (CAD+) by CTA (15.6% had plaques without stenosis, 23.9% mild, 10.7% intermediate and 21.5% high-grade stenosis). CCS zero prevalence was 306 (43%), out of those 100 (32.7%) had non-calcified plaque only. Mean follow-up period was 2.65 years. MACE rate was 0% in CAD negative and higher (1.2%) in CAD positive by CTA. Coronary revascularisation rate was 5.5%. Patients with SIS ≥5 had an HR of 6.5 (95% CI 1.6 to 25.8, p<0.013) for MACE, patients with ncSIS ≥1 had an HR of 2.4 (95% CI 1.2 to 4.6, p<0.01) for secondary end point. The sensitivity of CTA for stenosis >50% compared with invasive angiography was 92.9% (95% CI 83.0% to 98.1%). Negative predictive value of CTA was 99.4% (95% CI 98.3% to 99.8%) for combined end points.
CAD prevalence by CTA in asymptomatic high-risk patients is high. CCS zero does not exclude CAD. CTA is highly accurate to exclude CAD. Total coronary plaque burden and nc plaques, even if only one segment is involved, are associated with an increased risk of adverse outcome.
PMCID: PMC4189305  PMID: 25332810
24.  Noninvasive assessment of the carotid and cerebrovascular atherosclerotic plaques by multidetector CT in type-2 diabetes mellitus patients with transient ischemic attack or stroke 
The cerebrovasuclar artery disease as a common complication of type-2 diabetes mellitus (T2DM) caused huge economic burden and lives threatening to patients. We evaluated the prevalence and morphology of carotid and cerebrovascular atherosclerotic plaques in T2DM patients with transient ischemic attack (TIA) or stroke using multidetector CT (MDCT).
64-MDCT and dual-source CT (DSCT) angiographies were performed in 195 T2DM patients with TIA or stroke (mean age 65.7+/-12.8 years; 118 men) between January 2009 to August 2011. During the process, plaque type, its distribution, extensive and obstructive natures were determined for each segment derived from the patients.
Atherosclerotic plaques were detected in 183 (93.8%) patients. A total of 1056 segments with plaque were identified, of which 450 (42.6%) were non-calcified, 192 (18.2%) were mixed and 414 (39.2%) calcified ones. Among them, 562 (53.2%) resulted in mild stenosis, 291 (27.6%) moderate stenosis, 170 (16.1%) severe stenosis and 33 (3.1%) occlusion. Non-calcified plaques contributed 91.8% to non-obstructive lumen narrowing, while mixed and calcified plaques contributed 89.0% and 65.0% respectively.
MDCT angiography detected a high prevalence of plaques in T2DM patients with TIA or stroke. A relatively high proportion of plaques were non-calcified, as well as with non-obstructive stenosis. MDCT angiography might further enhance the detection and management of carotid and cerebrovascular atherosclerosis in T2DM patients with TIA and stroke
PMCID: PMC3598273  PMID: 23443053
25.  Association of Adiponectin Gene Polymorphism with Adiponectin Levels And Risk for Insulin Resistance Syndrome 
Adiponectin is an abundant adipose tissue–derived protein with anti-atherogenic, anti-inflammatory and antidiabetic properties. Plasma adiponectin levels are decreased in obesity, type 2 diabetes, and coronary artery disease and low adiponectin levels also predict insulin resistance (IR).
Case-control study in which 642 male and female subjects were participated from the North Indian population. Lipid, insulin, leptin and adiponectin level were estimated using standard protocols by commercially available test kits. Single nucleotide polymorphisms +45T>G and +276G>T of the AMP1 (adiponectin) gene was genotyped by polymerase chain reaction restriction fragment length polymorphism method.
Levels of adiponectin, insulin, homeostasis model assessment-IR index (HOMA-IR index), systolic blood pressure and fat mass showed significant differences between male and female subjects. Serum adiponectin level showed highly significant association with both the +45 and the +276 genotypes. The common haplotype triglyceride (TG) showed a significantly lower adiponectin value than other haplotypes (P = 0.0001). A clear trend of decreasing adiponectin levels per copy of the common haplotype was observed. Nonobese insulin sensitive subjects showed a higher adiponectin value (P = 0.0006) than nonobese insulin resistant subjects. The values of blood pressure, adiponectin, insulin, HOMA-IR, total-cholesterol, and low-density lipoprotein-cholesterol significantly associated with TG haplotype.
We observed the very strong association of the adiponectin 45-276 genotypes and haplotypes with adiponectin levels in healthy north Indian population and TG haplotypes also associated with metabolic parameters of the IR syndrome.
PMCID: PMC4410438  PMID: 25949781
Adiponectin; AMP1; haplotype; insulin resistance; polymorphism

Results 1-25 (1056188)