Non-calcified Coronary Plaque Burden Research Articles

Abstract 588: Glyc-A, a Novel Inflammatory Biomarker, is Associated With Total and Non-Calcified Coronary Plaque Burden Beyond Traditional Cardiovascular Risk Factors

Introduction: Recent studies suggest that hsCRP may inaccurately predict coronary heart disease (CHD) in patients with chronic inflammatory disorders. GlycA, a novel inflammatory biomarker measured by nuclear magnetic resonance, was associated with future cardiovascular events in a large cohort study. Whether GlycA predicts CHD beyond hsCRP in chronic inflammatory patients is unknown. Psoriasis (PSO), a chronic inflammatory disease associated with increased cardiovascular risk, provides a clinical human model to assess the utility of GlycA as a risk marker of CHD. Hypothesis: We hypothesized that GlycA would associate with CHD, by total (TB) and non-calcified burden (NCB) assessed by coronary CT angiography, beyond traditional risk factors in PSO. Methods: 151 consecutive PSO patients and 40 controls underwent coronary CT angiography (320 detector row) as part of a large cohort study (NCT01778569). Coronary plaque burden was assessed by QAngio (Medis). We measured GlycA by nuclear magnetic resonance (LabCorp). A physician ascertained clinical parameters. Labs were measured in a certified clinical research facility. Statistical analyses include multivariate regression and ROC modeling. Results: PSO patients were older, at low Framingham risk, but had significant cardiometabolic dysfunction and increased CHD by TB and NCB (Table). While hsCRP significantly associated with CHD in controls, it showed no relationship in PSO. GlycA, however, strongly associated with TB (β=0.14, p=0.01) and NCB (β=0.12, p=0.01) beyond traditional risk factors in PSO. Finally, ROC analyses demonstrated greater AUC for GlycA in predicting TB and NCB (Figure), suggesting GlycA adds incremental value to traditional cardiovascular risk factors. Conclusion: In conclusion, GlycA associates with coronary plaque burden in PSO. Our study suggests a role for GlycA beyond hsCRP in assessing CHD in inflammatory states. Larger prospective studies are needed to confirm these findings.

HIV infection is associated with an increased prevalence of coronary noncalcified plaque among participants with a coronary artery calcium score of zero: Multicenter AIDS Cohort Study (MACS).

HIV-infected individuals bear increased cardiovascular risk even in the absence of traditional cardiovascular risk factors. In the general population, coronary artery calcium (CAC) scanning is of value for cardiovascular risk stratification, but whether a CAC score of zero implies a low noncalcified coronary plaque burden in HIV-infected persons is unknown. We assessed the prevalence of noncalcified coronary plaque and compared noncalcified coronary plaque burden between HIV-infected and HIV-uninfected participants who had CAC scores of zero in the Multicenter AIDS Cohort Study (MACS) using coronary computed tomography (CT) angiography. HIV infection was associated with the presence of noncalcified coronary plaque among these men with CAC scores of zero. In a model adjusted only for age, race, centre, and pre- or post-2001 cohort, the prevalence ratio for the presence of noncalcified plaque was 1.27 (95% confidence interval 1.04-1.56; P = 0.02). After additionally adjusting for cardiovascular risk factors, HIV infection remained associated with the presence of noncalcified coronary plaque (prevalence ratio 1.31; 95% confidence interval 1.07-1.6; P = 0.01). Among men with CAC scores of zero, HIV infection is associated with an increased prevalence of noncalcified coronary plaque independent of traditional cardiovascular risk factors. This finding suggests that CAC scanning may underestimate plaque burden in HIV-infected men.

Reproducibility of Noncalcified Coronary Artery Plaque Burden Quantification From Coronary CT Angiography Across Different Image Analysis Platforms

The objective of our study was to evaluate the reproducibility of noncalcified coronary artery plaque burden quantification from coronary CT angiography (CTA) across different commercial analysis platforms. For this study, 47 patients (36 men, 11 women; mean age ± SD, 62 ± 13 years) with noncalcified plaques on coronary CTA were included. Automated quantification of noncalcified coronary artery plaque volume was performed on identical datasets using three commercially available image analysis software platforms (software platforms 1-3). Identical tissue attenuation ranges between 0 and 50 HU for low-attenuation plaques and 50-130 HU for medium-attenuation plaques were consistently applied. Log volume data were compared with the Pearson correlation coefficient and Bland-Altman analysis. Differences in plaque volume measurements on intraplatform repeat measurements were statistically insignificant (p = 0.923). At the low-attenuation threshold, software platform 3 had significantly higher log volumes (p < 0.001) than both software platforms 1 and 2 and software platform 1 had significantly higher log volumes than software platform 2 (p < 0.001). The results at the medium-attenuation level were identical except that the log volumes for software platforms 1 and 2 were not significantly different (p > 0.05) in the left anterior descending artery and left circumflex artery. The Pearson correlation coefficient was found to be 0.677 (p < 0.001; 95% CI, 0.608-0.735) between software platforms 1 and 2, 0.672 (p < 0.001; 95% CI, 0.603-0.732) between software platforms 1 and 3, and 0.550 (p < 0.001; 95% CI, 0.463-0.627) between software platforms 2 and 3. Currently available noncalcified plaque quantification software provides good intraplatform reproducibility but poor interplatform reproducibility. Serial or comparative assessments require evaluation using the same software. Industry standards should be developed to enable reproducible assessments across manufacturers.

The association of brachial artery diameter with noncalcified coronary plaque burden in apparently healthy individuals

Coronary atherosclerosis has been associated with systemic arterial remodeling even in nonatherosclerotic 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 noncalcified plaque (NCP). We thus examined the association of brachial artery diameter (BAD), an artery that 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) by measuring coronary artery disease risk factors and coronary plaque using dual-source computed tomographic 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 adjusted for age, sex, race, current smoking, diabetes, hypertension, BMI, and non-HDL and HDL cholesterol. Higher quintiles of BAD were associated with greater age and male sex (both P<0.001). In the fully adjusted analysis, CP volume was not associated with BAD (P=0.65) but a 1 ml greater NCP volume was associated with a 0.65 mm larger BAD (P=0.027). Our results suggest that systemic arterial remodeling of nonatherosclerotic arteries is a dynamic process that is correlated with the extent of putatively active atherosclerotic processes in distant beds but not with inactive accumulated plaque burden.

Abstract 19480: Non-Calcified Coronary Plaque (NCCP) Burden &amp; its Correlation with Left Ventricular Mass (LVM) in Diabetic vs Non-Diabetic Patients

Determine Non-Calcified Coronary Plaque (NCCP) burden &amp; its correlation with Left Ventricular Mass (LVM) in Diabetic vs Non-diabetic patients. Methods : IRB approved, retrospective review of 190 patients imaged with 320-row MDCTA [89 Diabetics (mean age 62.5 ± 8.73 Yrs &amp; BMI 31.49 ± 5.13) &amp; 101 Non-diabetic (mean age 61.15±14.6 Yrs &amp; BMI 27.47 ± 5.47)]. Measurements were taken for plaque subtypes and total plaque burden (TPB) using Vitrea 5.2. RCA, LM, LAD and LCX were analyzed to quantify fatty, fibrous and calcified plaque in mm 3 . LVM was calculated from left ventricular inner diameter (LVID), posterior wall thickness (PWD) and Septal wall thickness (SWT) measured in diastolic phase from 4 and 2 chamber views using ASE formula. STATA was used for analyses. Results: TPB &amp; LVM for diabetic vs. non-diabetic were: RCA: 10.00±3.80 mm 3 vs 8.69±4.2 mm 3 , p = 0.029; LM 16.66±5.24 mm 3 vs 13.74±4.58 mm 3 ,p = &lt;0.001, LAD: 7.41±2.67 mm 3 vs 6.55±2.72 mm 3 , p = 0.034; LCX: 9.69±2.93 mm 3 vs 8.30±2.76 mm 3 ,p = 0.002 &amp; LVM: 175.29 ± 53.8 vs 173.92 ± 71.6 gm, p = 0.0881 respectively Diabetic had significantly ↑ TPB in all arteries compared to non-diabetics. Diabetics had significantly ↑ fibrous and fatty plaque in LM, LAD &amp; LCX and fatty plaque only in RCA. Calcified plaque volume and LVM were same in both groups (Table 1). Adjusting for demographic and clinical variables, linear regression showed no difference in TPB in all vessels. In sub analyses LAD had significantly ↑ fibrous (p = 0.050), fatty (p =0.042) and calcified plaque (p = 0.031) whereas LM had ↑ fibrous (p =0.039) and LCX had ↑ calcified plaque (p =0.039) in diabetics. Linear regression showed significantly ↑ PWT (p =0.017), LVID (p =&lt;0.001) and LVM (p =&lt;0.001) in diabetics. Conclusion: Diabetes is associated with higher non-calcified plaque burden with increase in LVM which may provide a reason for increased risk of adverse cardiac events in diabetics. Timely screening and appropriate medical therapy may reduce coronary events in this specific group.

Combined evaluation of myocardial perfusion and coronary morphology in the identification of subclinical CAD

Summary Purpose: To evaluate the mean effective radiation dose of 13N-ammonia PET/CT and ECGpulsing CT angiography (CTA) in the evaluation of myocardial perfusion, myocardial blood flow (MBF) and coronary morphology for the identification of subclinical CAD. Patients, material, methods: Following rest-stress 13N-ammonia PET/CT perfusion imaging and MBF quantification, ECG-pulsing CTA at a pulse window of 70% of the R-R cycle was performed in ten healthy controls and in sixteen individuals with cardiovascular risk factors. Individual radiation dose exposure for ECG-pulsing CTA was estimated from the dose-length product. Results: PET demonstrated normal perfusion in all study individuals, while hyperemic MBFs during dipyridamole stimulation and the myocardial flow reserve (MFR) in cardiovascular risk individuals were significantly lower than in healthy controls (1.34 ± 0.26 vs. 2.28 ± 0.47 ml/g/min and 1.48 ± 0.39 vs. 3.24 ± 0.81, both p . 0.0001). Further, ECG-pulsing CTA identified mild calcified and non-calcified coronary plaque burden in 7 (43%) individuals of the cardiovascular risk group. Rest-stress 13N-ammonia PET/CT perfusion study yielded a mean effective radiation dose of 3.07 ± 0.06 mSv (2.07 ± 0.06 mSv from the rest-stress 13N-ammonia injections and 1.0 mSv from the 2 CT transmission scans), while ECG-pulsing CTA was associated with 5.57 ± 2.00 mSv. The mean effective radiation dose of the combined 13N-ammonia PET/CT and ECG-pulsing CTA exams in the evaluation of myocardial perfusion and coronary morphology was 8.0 ± 1.5 mSv. Conclusion: 13N-ammonia PET/CT and ECG-pulsing CTA affords cardiac hybrid imaging studies in the evaluation of subclinical CAD with a relatively low mean effective radiation exposure of 8.0 ± 1.5mSv.

Reproducibility of Automated Noncalcified Coronary Artery Plaque Burden Assessment at Coronary CT Angiography

To evaluate the accuracy and effect on interreader reproducibility of automated versus manual volumetric quantification of noncalcified coronary artery plaque burden at coronary computed tomography angiography. Thirty-seven patients underwent 64-slice coronary computed tomography angiography. Two experienced observers in consensus evaluated each study and identified 40 noncalcified coronary artery plaques. Also in consensus, they performed manual, 3-dimensional planimetric measurements on each plaque as the reference standard. The same 2 observers then performed volumetric measurements on each plaque using a threshold-based automated volumetry automated plaque analysis algorithm. Two different, less experienced observers also performed both, manual and automated measurements of each plaque, first independently and then in consensus. Spearman rank correlation was used to determine association between variables. Automated volumetry was successfully performed on each plaque. There was excellent (R=0.920) correlation between the expert manual measurements (average plaque burden=33.58 mm(3)+/-18.16) and automated plaque volumetry (35.64 mm(3)+/-16.42). For the less experienced observers, there was better correlation with expert manual measurements using automated plaque volumetry (R=0.885) than with manual measurements (R=0.854). Interreader correlation for volume measurements by the 2 less experienced observers without and with use of the automated plaque analysis algorithm significantly (P<0.001) increased from R=0.781 to R=0.919. Compared with expert manual measurements, automated plaque volumetry enables accurate quantification of noncalcified plaque burden. Reproducibility of plaque measurements between different observers is improved. Use of such automated plaque analysis algorithms should facilitate fast, objective and reproducible assessment of noncalcified plaque burden for risk stratification and therapeutic monitoring.

Low Adiponectin Levels Are an Independent Predictor of Mixed and Non-Calcified Coronary Atherosclerotic Plaques

BackgroundAtherosclerosis is the primary cause of coronary artery disease (CAD). There is increasing recognition that lesion composition rather than size determines the acute complications of atherosclerotic disease. Low serum adiponectin levels were reported to be associated with coronary artery disease and future incidence of acute coronary syndrome (ACS). The impact of adiponectin on lesion composition still remains to be determined.Methodology/Principal FindingsWe measured serum adiponectin levels in 303 patients with stable typical or atypical chest pain, who underwent dual-source multi-slice CT-angiography to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed or non-calcified. In bivariate analysis adiponectin levels were inversely correlated with total coronary plaque burden (r = −0.21, p = 0.0004), mixed (r = −0.20, p = 0.0007) and non-calcified plaques (r = −0.18, p = 0.003). No correlation was seen with calcified plaques (r = −0.05, p = 0.39). In a fully adjusted multivariate model adiponectin levels remained predictive of total plaque burden (estimate: −0.036, 95%CI: −0.052 to −0.020, p<0.0001), mixed (estimate: −0.087, 95%CI: −0.132 to −0.042, p = 0.0001) and non-calcified plaques (estimate: −0.076, 95%CI: −0.115 to −0.038, p = 0.0001). Adiponectin levels were not associated with calcified plaques (estimate: −0.021, 95% CI: −0.043 to −0.001, p = 0.06). Since the majority of coronary plaques was calcified, adiponectin levels account for only 3% of the variability in total plaque number. In contrast, adiponectin accounts for approximately 20% of the variability in mixed and non-calcified plaque burden.Conclusions/SignificanceAdiponectin levels predict mixed and non-calcified coronary atherosclerotic plaque burden. Low adiponectin levels may contribute to coronary plaque vulnerability and may thus play a role in the pathophysiology of ACS.

Abstract 4223: Low Adiponectin Levels Are an Independent Predictor of Mixed and Non-Calcified Coronary Atherosclerotic Plaques

We sought to examine the relationship of adiponectin with coronary atherosclerotic plaque morphology in patients with stable typical or atypical chest pain. There is increasing recognition that lesion composition rather than size determines the acute complications of atherosclerotic disease. Low serum adiponectin levels are associated with coronary artery disease and future incidence of acute coronary syndrome. The impact of adiponectin on lesion composition still remains to be determined. Serum adiponectin levels were determined in 303 patients with stable typical or atypical chest pain, who underwent dual-source multi-slice CT-angiography to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed or non-calcified plaques. In bivariate analysis adiponectin levels were inversely correlated with total coronary plaque burden (r=−0.22, p&lt;0.0001), mixed (r=−0.20, p=0.0007) and non-calcified plaques (r=−0.18, p=0.003). No correlation was seen with calcified plaques (r=−0.05, p=0.39). In a fully adjusted multivariate model containing age, sex, body mass index, hypertension, diabetes mellitus, smoking, family history of coronary artery disease, LDL-cholesterol, HDL-cholesterol, triglycerides, hsCRP levels, medication and pericardial adipose tissue volume, adiponectin levels remained predictive of total plaque burden (estimate: −0.035, 95% CI: −0.051 to −0.019, p&lt;0.0001), mixed (estimate: −0.083, 95% CI: −0.127 to −0.039, p=0.0002) and non-calcified plaques (estimate: −0.076, 95% CI: −0.114 to −0.038, p=0.0001). Since the majority of coronary plaques were calcified plaques, adiponectin levels account for only 3% of the variability in total plaque number. In contrast, adiponectin accounts for approximately 20% of the variability in mixed and non-calcified plaque burden. Adiponectin levels predict mixed and non-calcified coronary atherosclerotic plaque burden. Low adiponectin levels may contribute to coronary plaque vulnerability and may thus play a role in the pathophysiology of acute coronary syndrome.