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.
Adiponectin; High-molecular-weight adiponectin; Coronary artery plaque; Coronary low-attenuation plaque
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.
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.
Biomarkers; Atherosclerosis; Cardiac CT; Imaging; Coronary artery disease
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.
atherosclerosis; computed tomography; coronary artery disease; risk factors; progression
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.
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.
Aortic valve calcification; coronary artery disease; multi-detector computed tomography; calcified plaque; non-calcified plaque; mixed plaque
To compare the influence of different iodinated contrast media with several dilutions on plaque attenuation in an ex vivo coronary model studied by multislice CT coronary angiography.
In six ex vivo left anterior descending coronary arteries immersed in oil, CT (slices/collimation 64×0.625 mm, temporal resolution 210 ms, pitch 0.2) was performed after intracoronary injection of a saline solution, and solutions of a dimeric isosmolar contrast medium (Iodixanol 320 mgI ml−1) and a monomeric high-iodinated contrast medium (Iomeprol 400 mgI ml−1) with dilutions of 1/80 (low concentration), 1/50 (medium concentration), 1/40 (high concentration) and 1/20 (very high concentration). Two radiologists drew regions of interest in the lumen and in calcified and non-calcified plaques for each solution. 29 cross-sections with non-calcified plaques and 32 cross-sections with calcified plaques were evaluated.
Both contrast media showed different attenuation values within lumen and plaque (p<0.0001). The correlation between lumen and non-calcified plaque values was good (Iodixanol r=0.793, Iomeprol r=0.647). Clustered medium- and high-concentration solutions showed similar plaque attenuation values, signal-to-noise ratios (SNRs) (non-calcified plaque: medium solution SNR 31.3±15 vs 31.4±20, high solution SNR 39.4±17 vs 37.4±22; calcified plaque: medium solution SNR 305.2±133 vs 298.8±132, high solution SNR 323.9±138 vs 293±123) and derived contrast-to-noise ratios (p>0.05).
Differently iodinated contrast media have a similar influence on plaque attenuation profiles.
Advances in knowledge
Since iodine load affects coronary plaque attenuation linearly, different contrast media may be equally employed for coronary atherosclerotic plaque imaging.
It is generally well-known that smoking has a substantial impact on general health, and cardiovascular health in particular. The purpose of this study was to analyze the effects of different smoking status on the burden and characteristics of coronary artery plaques in Chinese men.
Our study enrolled 1920 individuals with suspected coronary artery disease undergoing 256-detector-row computed tomography scan after clinical assessment. These study participants were stratified into three groups: never smoker, current smoker, and former smoker, according to their smoking status. Thereafter, the associations of different smoking status with the coronary artery plaques were assessed using both univariable and multivariable logistic regression.
The prevalences of any plaque, significant stenosis and coronary artery calcium score (CACS) ≥ 10 were highest in the current smokers (all p < 0.05). The proportion of calcified plaques was the lowest and the prevalence of non-calcified plaques was the highest in current smokers (p = 0.004). The higher pack-years group had significantly elevated percentages of any plaque, significant stenosis, ≥ 2/LM vessel disease and CACS ≥ 10 than the lower pack-years group (all p < 0.001). The percent of calcified plaques was lower and the percent of non-calcified plaques was higher in the higher (> 20) pack-years group than in the lower pack-years group (≤ 20) (p = 0.024). Current smoking with higher pack-years was the independent risk factor for any plaque, significant stenosis, CACS ≥ 10, non-calcified and mixed plaques (all p < 0.05) after multivariate adjustments.
The current smokers had the most serious burden of coronary artery plaques and the highest percentage of non-calcified plaques. Current smoking with higher pack-years was a significant risk factor for coronary artery plaque burden and non-calcified and mixed plaques.
Chinese men; Cigarette smoking; Coronary artery calcium score; Coronary artery plaques; Non-calcified plaques
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.
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.
Computed tomography; Microparticles; Low density lipoprotein; Lysine; Coronary artery disease
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.
Coronary artery disease; Coronary atherosclerotic plaque; Plaque progression; Cardiac biomarker; Coronary CT angiography
Coronary computed tomographic angiography (CCTA) facilitates comprehensive evaluation of coronary artery disease (CAD), including plaque characterization, and can provide additive diagnostic value to single-photon emission computed tomography (SPECT). However, data regarding the incremental prognostic value of CCTA to SPECT remain sparse. We evaluated the independent and incremental prognostic value of CCTA, as compared with clinical risk factors and SPECT.
Materials and methods
A total of 1,077 patients with suspected CAD who underwent both SPECT and cardiac CT between 2004 and 2012 were enrolled retrospectively. Presence of reversible or fixed perfusion defect (PD) and summed stress score were evaluated on SPECT. Presence, extent of coronary atherosclerosis and diameter stenosis (DS) were evaluated on CCTA. Plaque composition was categorized as non-calcified, mixed, or calcified according to the volume of calcified component (>130 Hounsfield Units). Patients were followed up for the occurrence of adverse cardiac events including cardiac death, non-fatal myocardial infarction, unstable angina, and late revascularization (>90 days after imaging studies).
During follow-up (median 23 months), adverse cardiac events were observed in 71 patients (6.6%). When adjusted for clinical risk factors and SPECT findings, the presence of any coronary plaque, any plaque in ≥3 segments, coronary artery calcium score (CACS) ≥400, a plaque ≥50% DS, presence of non-calcified plaque (NCP) or mixed plaque (MP), and NCP/MP in ≥2 segments were independent predictors of adverse cardiac events; however, the presence of calcified plaque (CP) was not. Conventional CCTA findings, including CACS ≥400 and a plaque ≥50% DS, demonstrated incremental prognostic value over clinical risk factors and SPECT (χ² 54.19 to 101.03; p <0.001). Addition of NCP/MP in ≥2 segments resulted in further significantly improved prediction (χ² 101.03 to 113.29; p <0.001).
Comprehensive CCTA evaluation of coronary atherosclerosis provides independent and incremental prognostic value in relation to SPECT evaluation of myocardial ischemia. Specifically, segmentally-analyzed plaque composition with CCTA provides further risk stratification in addition to CACS and DS.
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.
Adipokines; adiponectin; leptin; heart; subclinical coronary atherosclerosis; metabolic side effects of HIV infection; coronary CT angiography; cardiac CT
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
NHLBI and NIAID
The aim of the present study was to explore the association between the levels of serum N-terminal pro-B-type natriuretic peptide (NT-pro BNP) and the characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography (CCTA), in patients with unstable angina (UA). A total of 202 patients (age range, 47–82 years) were divided into the following three groups: Non-cardiac disease group (57 patients); stable angina pectoris (SAP) group (62 patients); and UA group (83 patients). There were significant differences between the serum NT-pro BNP levels among the three groups (P=0.007). However, in multivariant diagnoses, NT-pro BNP level was not an independent risk factor for UA. The levels of serum NT-pro BNP were observed to be positively correlated with the number of vessels involved (r=0.462; P<0.001), SIS (r=0.475; P<0.001), segment-stenosis score (r=0.453; P<0.001), coronary calcification score (r=0.412; P=0.001), number of obstructive diseases (r=0.346; P<0.001), and the number of segments with non-calcified plaque (r=0.235; P=0.017), mixed plaque (r=0.234; P=0.017) and calcified plaque (r=0.431; P<0.001). The levels of serum NT-pro BNP were significantly higher in patients with UA and left main-left anterior descending (LM-LAD) disease, compared with UA patients without LM-LAD disease (P<0.001). In addition, serum NT-pro BNP was significantly higher in patients with obstructive disease and UA than in those without obstructive disease (P<0.001). The area under the curve of log(NT-pro BNP) was 0.656 (P=0.006; optimal cut-off value, 1.74; sensitivity, 77.6%; specificity, 51.9%). In conclusion, the levels of serum NT-pro BNP are associated with the burden and severity of coronary artery atherosclerotic disease in patients with UA, and may be helpful in risk stratification of patients with UA.
N-terminal pro-B-type natriuretic peptide; coronary atherosclerotic plaque; unstable angina
Little data are available regarding coronary plaque composition and semi-quantitative scores in individuals with diabetes; the extent to which diabetes may affect the presence and extent of Coronary Artery Calcium (CAC) needs more evaluation. Considering that this information may be of great value in formulating preventive interventions in this population, we compared these findings in individuals with diabetes to those without.
Multi-Detector Computed Tomographic (MDCT) images of 861 consecutive patients with diabetes who were referred to Los Angeles Biomedical Research Institute from January 2000 to September 2012, were evaluated using a 15–coronary segment model. All 861 patients underwent calcium scoring and from these; 389 had coronary CT angiography (CTA). CAC score was compared to 861 age, sex and ethnicity matched controls without diabetes after adjustment for Body Mass Index (BMI), family history of coronary artery disease, hyperlipidemia, hypertension and smoking. Segment Involvement Score (SIS; the total number of segments with any plaque), Segment Stenosis Score (SSS; the sum of maximal stenosis score per segment), Total Plaque Score (TPS; the sum of the plaque amount per segment) and plaque compositionwere compared to 389 age, sex and ethnicity matched controls without diabetes after adjustment for BMI, family history of coronary artery disease, hyperlipidemia, hypertension and smoking.
Diabetes was positively correlated to the presence and extent of CAC (P<0.0001 for both). SIS, SSS and TPS were significantly higher in those with diabetes (P<0.0001). Number of mixed and calcified plaques were significantly higher in those with diabetes (P = 0.018 and P<0.001 respectively) but there was no significant difference in the number of non-calcified plaques between the two groups (P = 0.398).
Patients with diabetes have higher CAC and semi-quantitative coronary plaque scores compared to the age, gender and ethnicity matched controls without diabetes after adjustment for cardiovascular risk factors. Since mixed plaque is associated with worse long-term clinical outcomes, these findings support more aggressive preventive measures in this population.
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.
Coronary artery disease; pericoronary fat; epicardial fat; adipose tissue; inflammation; computed tomography
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.
Non-calcified plaque; sinogram-affirmed iterative reconstruction (sinogram-affirmed IR); coronary computed tomography angiography (CCTA)
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.
aortic distensibility; coronary atherosclerosis; thoracic atherosclerosis; peripheral vascular disease; computed tomography; cardiovascular aging
Studies have demonstrated a consistent relationship between white blood cell (WBC) counts and coronary artery disease (CAD). The neutrophil/lymphocyte ratio (NLR) has been considered as a potential marker for identifying individuals under risk of CAD and associated events. In this study, we aimed to evaluate whether NLR was associated with the severity and morphology of coronary atherosclerotic plaques shown by multidetector computed tomography (MDCT).
Our study population consisted of 684 patients who underwent dual-source 64 slice MDCT for the assessment of CAD. Coronary arteries were evaluated on a 16-segment basis and critical coronary plaque was described as luminal narrowing > 50%, whereas plaque morphology was assessed on a per segment basis. Total WBC, neutrophil and lymphocyte counts were determined using commercially available assay kits.
WBC count [7700 (6400-8800) vs. 6800 (5700-7900), p < 0.05] and NLR [2.40 (1.98-3.07) vs. 1.86 (1.50-2.38), p < 0.001] were found to be higher in patients with critical stenosis than in those without. In the binary logistic regression analysis, NLR was a predictor of critical stenosis (odds ratio, 1.68; 95% confidence interval, 1.39-2.03, p < 0.001). NLR levels differed among plaque morphology subtypes (p < 0.05) and was significantly higher in non-calcified plaque (NCP) compared to mixed plaque (MP) and calcified plaque (CP) (p < 0.05). In the multinomial logistic regression analysis, NLR was found to be an independent predictor of NCP, MP and CP (p < 0.001).
These data show that NLR is associated with both the severity and morphology of coronary atherosclerotic disease.
Atherosclerosis; Coronary plaque; Inflammation; Multidetector computerized tomography
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.
Epidemiology; plaque; coronary angiography; coronary artery disease; HIV
Determine plaque subtype and volume difference in male and female patients with obstructive and non-obstructive CAD using 320-row MDCTA.
Materials and methods
128 patients with suspected CAD underwent MDCTA. All studies were divided into two groups based on disease severity. 0–70% stenosis (non-obstructive CAD) & >70% (obstructive). All were compared for plaque quantity and subtypes by gender. Main arteries, RCA, LM, LAD and LCX were analyzed using Vitrea 5.2 software to quantify fatty, fibrous and calcified plaque. Thresholds for coronary plaque quantification (volume in mm3) were preset at 35 ± 12 HU for fatty, 90 ± 24 HU for fibrous and >130 HU for calcified/mixed plaque and analyzed using STATA software.
Total plaque burden in 118 patients [65M: 53F] was significantly higher in all arteries in males compared to females with non-obstructive disease. Total plaque volume for males vs. females was: RCA: 10.10 ± 5.02 mm3 vs. 6.89 ± 2.75 mm3, respectively, p = 0.001; LAD: 7.21 ± 3.38 mm3 vs. 5.89 ± 1.93 mm3, respectively, p = 0.04; LCX: 9.13 ± 3.27 mm3 vs. 7.16 ± 1.73 mm3, respectively, p = 0.002; LM 15.13 ± 4.51 mm3 vs. 11.85 ± 4.03 mm3, respectively, p = 0.001. In sub-analyses, males had significantly more fibrous and fatty plaque in LM, LAD & LCX than females. However in the RCA, only fibrous plaque was significantly greater in males. Calcified plaque volume was not significantly different in both genders. Only 8% of patients had obstructive CAD (>70% stenosis); there was no significant difference in plaque volume or subtypes.
In patients with non-obstructive CAD, males were found to have significantly higher total coronary plaque volume with predominance of fibrous and fatty subtypes compared to females of the same age and BMI. There was no significant difference in plaque subtype or volume in patients with obstructive disease.
Coronary plaque subtypes; Coronary artery disease; 320-row MDCTA
We investigated the relationship of quantitative plaque features from coronary CT Angiography (CTA) and coronary vascular dysfunction by impaired myocardial flow reserve (MFR) by 13N-Ammonia Positron Emission Tomography (PET).
Methods and Results
Fifty-one patients (32 men, 62.4±9.5 years) underwent combined rest-stress 13N-ammonia PET and CTA scans by hybrid PET/CT. Regional MFR was measured from PET. From CTA, 153 arteries were evaluated by semi-automated software, computing arterial non-calcified plaque (NCP), low-density NCP (NCP<30 HU), calcified and total plaque volumes, and corresponding plaque burden (plaque volumex100%/vessel volume), stenosis, remodeling index, contrast density difference (maximum difference in luminal attenuation per unit area in the lesion), and plaque length. Quantitative stenosis, plaque burden and myocardial mass were combined by boosted ensemble machine-learning algorithm into a composite risk score to predict impaired MFR (MFR≤2.0) by PET, in each artery. Nineteen patients (37%) had impaired regional MFR in at least one territory, (41/153 vessels). Patients with impaired regional MFR had higher arterial NCP (32.4 vs.17.2 %), low-density NCP (7 vs 4 %) and total plaque burden (37 vs 19.3 %, p<0.02). In multivariable analysis with 10-fold cross-validation, NCP burden was the most significant predictor of impaired MFR (Odds Ratio 1.35, p=0.021). For prediction of impaired MFR with 10-fold cross-validation, receiver-operating-characteristics-area-under-the-curve for the composite score was 0.83 (95%CI:0.79–0.91), greater than for quantitative stenosis (0.66, 95%CI:0.57–0.76, p = 0.005).
Compared to stenosis, arterial NCP burden and a composite score combining quantitative stenosis and plaque burden from CTA significantly improves identification of downstream regional vascular dysfunction.
noncalcified plaque; plaque volume; plaque burden; stenosis; coronary CT angiography; impaired myocardial flow reserve; vascular dysfunction; 13N-Ammonia PET; Nuclear Cardiology and PET; Computerized Tomography (CT)
Background and Objectives
Non-calcified carotid plaques are more unstable than calcified plaques, and they are associated with a higher risk of rupture, thromboembolism, and consequently, stroke. The purpose of the present study is to compare calcified and non-calcified plaques that cause intermediate carotid artery stenosis with respect to neutrophil/lymphocyte ratio (NLR).
Subjects and Methods
A total number of 139 asymptomatic patients with 50-70% stenosis of the carotid artery were included in this study. Carotid Doppler ultrasound imaging and computed tomography angiography were performed to divide the carotid artery plaques into two groups as calcified and non-calcified. Patients included in the calcified (n=73) and non-calcified (n=66) plaque groups were compared with respect to total neutrophil count, lymphocyte count and NLR.
Total lymphocyte count was statistically significantly lower in the non-calcified plaque group compared to the calcified plaque group (total lymphocyte count in non-calcified/calcified plaque groups [103/mm3]: 2.1/2.3, respectively) (p=0.002). NLR was statistically significantly higher in the non-calcified plaque group compared to the calcified plaque group (NLR in non-calcified/calcified plaque groups: 2.6/2.1, respectively) (p<0.001). The cut-off value for NLR was found to be >2.54. Multivariate regression analysis showed that NLR was independently associated with non-calcified carotid artery plaques (odds ratio 5.686, 95% CI 2.498-12.944, p<0.001).
NLR is increased in the presence of non-calcified carotid artery plaques that cause asymptomatic intermediate stenosis. Increased NLR can be used as a marker to assess the risk of rupture of non-calcified carotid artery plaques.
Atherosclerosis; Carotid artery stenosis; Neutrophil, lymphocyte, ratio; Atherosclerotic plaque; Stroke
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.
Statin; Plaque composition; Coronary CTA; Coronary artery disease; Lipid profile