Total Plaque Volume Research Articles

Acupuncture treatment for carotid atherosclerotic plaques: study protocol for a pilot randomized, single blinded, controlled clinical trial

BackgroundCarotid atherosclerosis disease (CAD) is generally associated with the occurrence of cardiovascular and cerebrovascular accidents. However, CAD has not been taken seriously enough in the clinic, which, coupled with the single treatment and prevention of CAD, has led to a generally low level of patient compliance. Therefore, acupuncture is expected to be a safe and effective therapy that can be maintained in the long term for patients with CAD. The study objective is to evaluate the efficiency and reliability of acupuncture to relieve CAD and provide a new therapeutic idea for the clinical treatment of CAD.MethodsThis is a three-arm randomized clinical trial in China. Three groups (TA, SA, and MC) will be randomly allocated at a 1:1:1 ratio. The study will enrol 105 cervical atherosclerosis plaque patients in total on a voluntary basis, with 35 patients in each group. The treatment will last for 12 weeks, with two treatments per week for twenty-four treatments in total.ResultsTwo 3D ultrasound indicators will be measured as the primary outcomes: the total plaque volume (PV) of the carotid artery on each side and the grey-scale median (GSM). The secondary outcomes will include intima-media thickness (IMT), lipid levels, apolipoprotein A-IV level, platelet count (PLT), fibrinogen (FIB), and platelet aggregation rate (PAR). All the outcomes will be assessed before treatment, after treatment, and after a 12-week follow-up period. This study will utilize per-protocol (PP) and intention-to-treat (ITT) analysis principles.ConclusionsThis trial is to evaluate the efficacy and reliability of acupuncture in relieving carotid atherosclerotic plaques by establishing acupuncture (TA), sham acupuncture (SA), and medication (MC) groups.Ethics and disseminationThis study was approved by the Institutional Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine (no. YF2018-107-01). All data and findings will be provided by the principal investigator via email.Trial registrationChiCTR, ChiCTR1800019259. Registered on 1 November 2018—retrospectively registered, http://www.chictr.org.cn/index.aspx

Coronary flow impairment in asymptomatic patients with early stage type-2 diabetes: Detection by FFRCT.

Purpose:To determine the occurrence of physiological significant coronary artery disease (CAD) by coronary CT angiography (CTA) derived fractional flow reserve (FFRCT) in asymptomatic patients with a new diagnosis (<1 year) of type-2 diabetes mellitus (T2DM).Methods:FFRCT-analysis was performed from standard acquired coronary CTA data sets. The per-patient minimum distal FFRCT-value (d-FFRCT) in coronary vessels (diameter ⩾1.8 mm) was registered. The threshold for categorizing FFRCT-analysis as abnormal was a d-FFRCT ⩽0.75. Total plaque volume and volumes of calcified plaque, non-calcified plaque, and low-density non-calcified plaque (LD-NCP) were assessed by quantitative plaque analysis.Results:Overall, 76 patients; age, mean (SD): 56 (11) years; males, n (%): 49(65), were studied. A total of 57% of patients had plaques. The d-FFRCT was ⩽0.75 in 12 (16%) patients. The d-FFRCT, median (IQR), was 0.84 (0.79–0.87). Median (range) d-FFRCT in patients with d-FFRCT ⩽0.75 was 0.70 (0.6–0.74). Patients with d-FFRCT⩽0.75 versus d-FFRCT >0.75 had numerically higher plaque volumes for all plaques components, although only significant for the LD-NCP component.Conclusion:Every sixth asymptomatic patient with a new diagnosis of T2DM has hemodynamic significant CAD as evaluated by FFRCT. Flow impairment by FFRCT was associated with coronary plaque characteristics.

NGAL Correlates with Femoral and Carotid Plaque Volume Assessed by Sonographic 3D Plaque Volumetry

Background/Objectives: Inflammation represents a cornerstone in the development of atherosclerosis and early detection is essential to avoid cardiovascular events. Biomarkers like interleukin-1 beta, interleukin-6, or high sensitivity CRP (hs-CRP) have been investigated intensively in this field. Since they have several limitations, additional biomarkers are needed for cardiovascular risk stratification. The acute phase protein, neutrophil gelatinase-associated lipocalin (NGAL), modulates inflammation and is elevated in cardiovascular disease (CVD). Moreover, it contributes to plaque destabilization. Methods: In this prospective, single-center study, we included 323 asymptomatic patients with at least one cardiovascular risk factor or established CVD. NGAL levels were measured in plasma samples using a commercially available ELISA. Carotid, femoral, and total atherosclerotic plaque volumes (PV) were measured using a 3D ultrasound system (Philips iU22). Patients were separated into a low (n = 243) and high (n = 80) total PV group. Results: NGAL was significantly higher in patients with high total PV versus patients with low total PV. The NGAL amplitude for the prediction of high total PV was significantly higher when compared with hs-CRP. A high predictive value could also be observed for patients without established CVD. Conclusion: NGAL seems to be a promising biomarker for the identification of asymptomatic patients with atherosclerotic disease.

Serum Cystatin C Level as a Biomarker of Aortic Plaque in Patients with an Aortic Arch Aneurysm.

Aim: During surgery for an aortic arch aneurysm, aortic plaque in the descending aorta should be evaluated, but there are currently no suitable biomarkers for it. Surgeons should be especially aware of cerebral embolism from femoral perfusion and of peripheral embolism from stent graft deployment. Cystatin C is a known useful marker of renal dysfunction with a role as a biomarker for severity of coronary artery disease. In the absence of a suitable biomarker for aortic plaque in the descending aorta, we examine cystatin C as a candidate. Methods: In all, 75 patients who underwent surgery for an aortic arch aneurysm were enrolled. They were divided into two groups, depending on whether they had chronic kidney disease or not. The serum cystatin C value and creatinine value were evaluated preoperatively. The aortic plaque volume ratio and components in the descending aorta were calculated from preoperative enhanced computed tomography. Results: The soft plaque volume ratio was higher in patients with chronic kidney disease than in patients without it. Cystatin C positively correlated with the total aortic plaque volume ratio in all cases, and it positively correlated with the soft plaque volume ratio in both groups. Creatinine had no correlation with any type of plaque volume ratio in either group. In patients without chronic kidney disease, the soft plaque volume ratio was higher in patients with higher cystatin C levels than in patients with normal levels. Conclusion: The preoperative serum cystatin C level could be a biomarker of aortic plaque in the descending aorta in patients with an aortic arch aneurysm.

Sex Differences in Compositional Plaque Volume Progression in Patients With Coronary Artery Disease

ObjectivesThis study sought to explore sex-based differences in total and compositional plaque volume (PV) progression. BackgroundIt is unclear whether sex has an impact on PV progression in patients with coronary artery disease (CAD). MethodsThe study analyzed a prospective multinational registry of consecutive patients with suspected CAD who underwent 2 or more clinically indicated coronary computed tomography angiography (CTA) at ≥2-year intervals. Total and compositional PV at baseline and follow-up were quantitatively analyzed and normalized using the analyzed total vessel length. Multivariate linear regression models were constructed. ResultsOf the 1,255 patients included (median coronary CTA interval 3.8 years), 543 were women and 712 were men. Women were older (62 ± 9 years of age vs. 59 ± 9 years of age; p < 0.001) and had higher total cholesterol levels (195 ± 41 mg/dl vs. 187 ± 39 mg/dl; p = 0.002). Prevalence of hypertension, diabetes, and family history of CAD were not different (all p > 0.05). At baseline, men possessed greater total PV (31.3 mm3 [interquartile range (IQR): 0 to 121.8 mm3] vs. 56.7 mm3 [IQR: 6.8 to 152.1 mm3] p = 0.005), and there was an approximately 9-year delay in women in developing total PV than in men. The prevalence of high-risk plaques was greater in men than women (31% vs. 20%; p < 0.001). In multivariate analysis, after adjusting for age, clinical risk factors, medication use, and total PV at baseline, despite similar total PV progression rates, female sex was associated with greater calcified PV progression (β = 2.83; p = 0.004) but slower noncalcified PV progression (β = –3.39; p = 0.008) and less development of high-risk plaques (β = –0.18; p = 0.049) than in men. ConclusionsThe compositional PV progression differed according to sex, suggesting that comprehensive plaque evaluation may contribute to further refining of risk stratification according to sex. (NCT02803411).

Quantified coronary total plaque volume from computed tomography angiography provides superior 10-year risk stratification.

Automated coronary total plaque volume (TPV) quantification derived from coronary computed tomographic angiography (CTA) datasets provide exact and reliable assessment of calcified and non-calcified coronary atherosclerosis burden. The aim of this analysis was to investigate the long-term predictive value of TPV. TPV was quantified in 1577 patients undergoing coronary CTA and cardiovascular events were collected during 10.5 years (interquartile range 6.0-11.4) of follow-up. The study endpoint comprised cardiac death and acute coronary syndrome and occurred in 59 (3.7%) patients. Coronary TPV provided additive prognostic value over clinical risk assessed with the Morise Score and coronary artery disease severity (rise in C-index from 0.744 to 0.769, P = 0.03). A category-based reclassification approach combining the Morise Score and TPV revealed superior risk stratification (categorical net reclassification improvement: 0.48 with 95% CI 0.13-0.68, P < 0.001) and resulted in reclassification of 800 (51%) patients compared with the Morise Score alone. The 10-year risk for the study endpoint was 0.6% (95% CI 0-1.3) for patients classified as low risk (n = 807), 4.8% (95% CI 2.4-7.2) for patients at intermediate risk (n = 400), and 10.3% (95% CI 6.6-13.9) for patients at high risk (n = 370) using the combined reclassification approach. Quantification of TPV from coronary CTA permits an improved 10-year cardiovascular risk stratification.

Age- and sex-related features of atherosclerosis from coronary computed tomography angiography in patients prior to acute coronary syndrome: results from the ICONIC study.

Although there is increasing evidence supporting coronary atherosclerosis evaluation by coronary computed tomography angiography (CCTA), no data are available on age and sex differences for quantitative plaque features. The aim of this study was to investigate sex and age differences in both qualitative and quantitative atherosclerotic features from CCTA prior to acute coronary syndrome (ACS). Within the ICONIC study, in which 234 patients with subsequent ACS were propensity matched 1:1 with 234 non-event controls, our current subanalysis included only the ACS cases. Both qualitative and quantitative advance plaque analysis by CCTA were performed by a core laboratory. In 129 cases, culprit lesions identified by invasive coronary angiography at the time of ACS were co-registered to baseline CCTA precursor lesions. The study population was then divided into subgroups according to sex and age (<65 vs. ≥ 65 years old) for analysis. Older patients had higher total plaque volume than younger patients. Within specific subtypes of plaque volume, however, only calcified plaque volume was higher in older patients (135.9 ± 163.7 vs. 63.8 ± 94.2 mm3, P < 0.0001, respectively). Although no sex-related differences were recorded for calcified plaque volume, females had lower fibrous and fibrofatty plaque volume than males (Fibrofatty volume 29.6 ± 44.1 vs. 75.3 ± 98.6 mm3, P = 0.0001, respectively). No sex-related differences in the prevalence of qualitative high-risk plaque features were found, even after separate analyses considering age were performed. Our data underline the importance of age- and sex-related differences in coronary atherosclerosis presentation, which should be considered during CCTA-based atherosclerosis quantification.

Per-lesion versus per-patient analysis of coronary artery disease in predicting the development of obstructive lesions: the Progression of AtheRosclerotic PlAque DetermIned by Computed TmoGraphic Angiography Imaging (PARADIGM) study.

To determine whether the assessment of individual plaques is superior in predicting the progression to obstructive coronary artery disease (CAD) on serial coronary computed tomography angiography (CCTA) than per-patient assessment. From a multinational registry of 2252 patients who underwent serial CCTA at a ≥ 2-year inter-scan interval, patients with only non-obstructive lesions at baseline were enrolled. CCTA was quantitatively analyzed at both the per-patient and per-lesion level. Models predicting the development of an obstructive lesion at follow up using either the per-patient or per-lesion level CCTA measures were constructed and compared. From 1297 patients (mean age 60 ± 9years, 43% men) enrolled, a total of 3218 non-obstructive lesions were identified at baseline. At follow-up (inter-scan interval: 3.8 ± 1.6years), 76 lesions (2.4%, 60 patients) became obstructive, defined as > 50% diameter stenosis. The C-statistics of Model 1, adjusted only by clinical risk factors, was 0.684. The addition of per-patient level total plaque volume (PV) and the presence of high-risk plaque (HRP) features to Model 1 improved the C-statistics to 0.825 [95% confidence interval (CI) 0.823-0.827]. When per-lesion level PV and the presence of HRP were added to Model 1, the predictive value of the model improved the C-statistics to 0.895 [95% CI 0.893-0.897]. The model utilizing per-lesion level CCTA measures was superior to the model utilizing per-patient level CCTA measures in predicting the development of an obstructive lesion (p < 0.001). Lesion-level analysis of coronary atherosclerotic plaques with CCTA yielded better predictive power for the development of obstructive CAD than the simple quantification of total coronary atherosclerotic burden at a per-patient level.Clinical Trial Registration: ClinicalTrials.gov NCT0280341.

Measurement of carotid plaque burden.

To describe the uses of measurement of carotid plaque burden, as total plaque area (TPA), total plaque volume (TPV), and vessel wall volume (VWV), which includes plaque burden and wall volume. Measurement of plaque burden is useful for risk stratification, research into the genetics and biology of atherosclerosis, for measuring effects of new therapies for atherosclerosis, and for treatment of high-risk patients with severe atherosclerosis. Measurement of plaque burden is far superior to measurement of carotid intima-media thickness (IMT) in many ways, and should replace it. Vessel wall volume can be measured in persons with no plaque as an alternative to IMT.

Plaque Regression and Endothelial Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen (PREMIER).

Low-density lipoproteins (LDLs) are removed by extracorporeal filtration during LDL apheresis. It is mainly used in familial hyperlipidemia. The PREMIER trial (Plaque Regression and Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen) evaluated LDL apheresis in nonfamilial hyperlipidemia acute coronary syndrome patients treated with percutaneous coronary intervention. We randomized 160 acute coronary syndrome patients at 4 Veterans Affairs centers within 72 hours of percutaneous coronary intervention to intensive lipid-lowering therapy (ILLT) comprising single LDL apheresis and statins versus standard medical therapy (SMT) with no LDL apheresis and statin therapy alone. Trial objectives constituted primary safety and primary efficacy end points and endothelial progenitor cell colony-forming unit mobilization in peripheral blood. Mean LDL reduction at discharge was 53% in ILLT and 17% in SMT groups (P<0.0001) from baseline levels of 116.3±34.3 and 110.7±32 mg/dL (P=0.2979), respectively. The incidence of the primary safety end point of major peri-percutaneous coronary intervention adverse events was similar in both groups (ILLT, 3; SMT, 0). The primary efficacy end point, percentage change in total plaque volume at 90 days by intravascular ultrasound, on average decreased by 4.81% in the ILLT group and increased by 2.31% in the SMT group (difference of means, -7.13 [95% CI, -14.59 to 0.34]; P=0.0611). The raw change in total plaque volume on average decreased more in the ILLT group than in the SMT group (-6.01 versus -0.95 mm3; difference of means, -5.06 [95% CI, -11.61 to 1.48]; P=0.1286). Similar results were obtained after adjusting for participating sites, age, preexisting coronary artery disease, diabetes mellitus, baseline LDL levels, and baseline plaque burden. There was robust endothelial progenitor cell colony-forming unit mobilization from baseline to 90 days in the ILLT group (P=0.0015) but not in SMT (P=0.0844). PREMIER is the first randomized clinical trial to demonstrate safety and a trend for early coronary plaque regression with LDL apheresis in nonfamilial hyperlipidemia acute coronary syndrome patients treated with percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01004406 and NCT02347098.

Uses of ultrasound in stroke prevention.

Ultrasound methods are useful in stroke prevention in several ways. Measurement of carotid plaque burden, as either total plaque area (TPA) or total plaque volume (TPV) are strong predictors of cardiovascular risk: much stronger than intima-media thickness, which does not represent true atherosclerosis, but a biologically and genetically distinct phenotype. Measurement of plaque burden is also useful for the study of genetics, and of new risk factors such as toxic products of the intestinal microbiome. Carotid plaque burden is highly correlated with and as predictive of risk as coronary calcium scores, but is less costly and does not require radiation. Furthermore, because carotid plaques change in time over a period of months, they can be used for a new approach to vascular prevention: "Treating arteries instead of treating risk factors". In high-risk patients with asymptomatic carotid stenosis (ACS), this approach, implemented in 2003 in our clinics, was associated with a >80% reduction of stroke and myocardial infarction over 2 years. "Treating arteries without measuring plaque would be like treating hypertension without measuring blood pressure". Ultrasound methods can also be used to assess plaque vulnerability, by detecting echolucency, ulceration and plaque inhomogeneity on assessment of plaque texture. Transcranial Doppler (TCD) embolus detection is useful for risk stratification in patients with ACS; patients with two or more microemboli in an hour of monitoring have a 1-year risk of 15.6%, vs. 1% without microemboli, so this very clearly distinguishes which patients with ACS could benefit from intervention. TCD saline studies are more sensitive than trans-esophageal echocardiography for detection of patent foramen ovale, and more predictive of recurrent stroke. These methods should be more widely used, to reduce the increasing burden of stroke in our aging populations.

MR imaging of vulnerable carotid plaque.

Current risk stratification for stroke is still based upon percentage of carotid stenosis, despite this measure providing minimal patient-specific information on the actual risk of stroke for both symptomatic individuals without significant carotid artery stenosis as well as asymptomatic carotid stenosis patients. A continuously growing body of literature suggests that the identification and quantification of certain carotid plaque characteristics, including lipid-rich necrotic core (LRNC), thin/ruptured fibrous cap (FC), and intraplaque hemorrhage (IPH), provide a superior means of predicting future stroke. These characteristics are identifiable via magnetic resonance imaging (MRI), with most features detectable using commercially available coils and sequences utilized in routine clinical practice in as little as 4 minutes. The presence of LRNC, a thin/ruptured FC, and IPH is associated with increased risk of future stroke or TIA. Plaques with greater than 40% LRNC with a thin overlying FC are prone to rupture. LRNC is T2 hypointense and lacks enhancement on contrast enhanced T1 weighted images. Increasing LRNC size is associated with the development of new ulceration, FC rupture, increasing plaque burden, as well as fatal and nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome (ACS), and symptom-driven revascularization, allowing for MR biomarkers of carotid plaque vulnerability to be utilized for systemic athero-thrombotic risk and not just stroke/TIA. LRNC typically shrinks with appropriate statin therapy, with PCSK9 inhibitors possibly playing a role in patients with inadequate response. Carotid plaques with IPH represent a more advanced stage of atherosclerotic disease. IPH is detectable with field strengths of both 3.0 T and 1.5 T and will demonstrate high signal on all T1 weighted imaging sequences. The presence of IPH increases the risk of future stroke in both symptomatic and asymptomatic patients, with multivariate analysis identifying IPH as a predictor of stroke, independent of percent stenosis, with no statistical difference in men vs. women, demonstrating that simple carotid stenosis measurements and traditional risk factor analysis may be inadequate in identifying patients at the highest risk for adverse cerebrovascular events. In the evaluation for recurrent stroke in recently symptomatic patients with >50% carotid stenosis, the estimated annual stroke risk is 23.2% in IPH+ patients and only 0.6% in IPH- patients, calling into question the current risk-benefit assessment for CEA. Additionally, a recent meta-analysis suggests that IPH+ plaque in patients with symptomatic <50% stenosis may be the etiology of embolic strokes previously labeled as "embolic stroke of undetermined source" (ESUS). There are no prospective drug trials testing the ability of any lipid-lowering therapies to decrease IPH and/or total plaque volume (TPV). Given the continuously increasing evidence of IPH as a significant predictor of carotid plaque progression and future adverse vascular events, trials aimed at targeted therapy for IPH represents a significant need.

Association of Cardiovascular Disease Risk Factor Burden With Progression of Coronary Atherosclerosis Assessed by Serial Coronary Computed Tomographic Angiography

Several studies have reported that the progression of coronary atherosclerosis, as measured by serial coronary computed tomographic (CT) angiography, is associated with the risk of future cardiovascular events. However, the cumulative consequences of multiple risk factors for plaque progression and the development of adverse plaque characteristics have not been well characterized. To examine the association of cardiovascular risk factor burden, as assessed by atherosclerotic cardiovascular disease (ASCVD) risk score, with the progression of coronary atherosclerosis and the development of adverse plaque characteristics. This cohort study is a subgroup analysis of participant data from the prospective observational Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) study, which evaluated the association between serial coronary CT angiography findings and clinical presentation. The PARADIGM international multicenter registry, which includes 13 centers in 7 countries (Brazil, Canada, Germany, Italy, Portugal, South Korea, and the US), was used to identify 1005 adult patients without known coronary artery disease who underwent serial coronary CT angiography scans (median interscan interval, 3.3 years; interquartile range [IQR], 2.6-4.8 years) between December 24, 2003, and December 16, 2015. Based on the 10-year ASCVD risk score, the cardiovascular risk factor burden was classified as low (<7.5%), intermediate (7.5%-20.0%), or high (>20.0%). Data were analyzed from February 8, 2019, to April 17, 2020. Association of baseline ASCVD risk burden with plaque progression. Noncalcified plaque, calcified plaque, and total plaque volumes (mm3) were measured. Noncalcified plaque was subclassified using predefined Hounsfield unit thresholds for fibrous, fibrofatty, and low-attenuation plaque. The percent atheroma volume (PAV) was defined as plaque volume divided by vessel volume. Adverse plaque characteristics were defined as the presence of positive remodeling, low-attenuation plaque, or spotty calcification. In total, 1005 patients (mean [SD] age, 60 [8] years; 575 men [57.2%]) were included in the analysis. Of those, 463 patients (46.1%) had a low 10-year ASCVD risk score (low-risk group), 373 patients (37.1%) had an intermediate ASCVD risk score (intermediate-risk group), and 169 patients (16.8%) had a high ASCVD risk score (high-risk group). The annualized progression rate of PAV for total plaque, calcified plaque, and noncalcified plaque was associated with increasing ASCVD risk (r = 0.26 for total plaque, r = 0.23 for calcified plaque, and r = 0.11 for noncalcified plaque; P < .001). The annualized PAV progression of total plaque, calcified plaque, and noncalcified plaque was significantly greater in the high-risk group compared with the low-risk and intermediate-risk groups (for total plaque, 0.99% vs 0.45% and 0.58%, respectively; P < .001; for calcified plaque, 0.61% vs 0.23% and 0.36%; P < .001; and for noncalcified plaque, 0.38%vs 0.22% and 0.23%; P = .01). When further subclassified by noncalcified plaque type, the annualized PAV progression of fibrofatty and low-attenuation plaque was greater in the high-risk group (0.09% and 0.02%, respectively) compared with the low- to intermediate-risk group (n = 836; 0.02% [P = .02] and 0.001% [P = .008], respectively). The interval development of adverse plaque characteristics was greater in the high-risk group compared with the low-risk and intermediate-risk groups (for new positive remodeling, 73 patients [43.2%] vs 151 patients [32.6%] and 133 patients [35.7%], respectively; P = .02; for new low-attenuation plaque, 26 patients [15.4%] vs 44 patients [9.5%] and 35 patients [9.4%]; P = .02; and for new spotty calcification, 37 patients [21.9%] vs 52 patients [11.2%] and 54 patients [14.5%]; P = .002). The progression of noncalcified plaque subclasses and the interval development of adverse plaque characteristics did not significantly differ between the low-risk and intermediate-risk groups. Progression of coronary atherosclerosis occurred across all ASCVD risk groups and was associated with an increase in 10-year ASCVD risk. The progression of fibrofatty and low-attenuation plaques and the development of adverse plaque characteristics was greater in patients with a high risk of ASCVD.

Quantitative assessment of coronary plaque volume change related to triglyceride glucose index: The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry

BackgroundThe association between triglyceride glucose (TyG) index and coronary atherosclerotic change remains unclear. We aimed to evaluate the association between TyG index and coronary plaque progression (PP) using serial coronary computed tomography angiography (CCTA).MethodsA total of 1143 subjects (aged 60.7 ± 9.3 years, 54.6% male) who underwent serial CCTA with available data on TyG index and diabetic status were analyzed from The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. PP was defined as plaque volume (PV) (mm3) at follow-up minus PV at index > 0. Annual change of PV (mm3/year) was defined as PV change divided by inter-scan period. Rapid PP was defined as the progression of percent atheroma volume (PV divided by vessel volume multiplied by 100) ≥ 1.0%/year.ResultsThe median inter-scan period was 3.2 (range 2.6–4.4) years. All participants were stratified into three groups based on TyG index tertiles. The overall incidence of PP was 77.3%. Baseline total PV (group I [lowest]: 30.8 (0.0–117.7), group II: 47.2 (6.2–160.4), and group III [highest]: 57.5 (8.4–154.3); P < 0.001) and the annual change of total PV (group I: 5.7 (0.0–20.2), group II: 7.6 (0.5–23.5), and group III: 9.4 (1.4–27.7); P = 0.010) were different among all groups. The risk of PP (odds ratio [OR] 1.648; 95% confidence interval [CI] 1.167–2.327; P = 0.005) and rapid PP (OR 1.777; 95% CI 1.288–2.451; P < 0.001) was increased in group III compared to that in group I. TyG index had a positive and significant association with an increased risk of PP and rapid PP after adjusting for confounding factors.ConclusionTyG index is an independent predictive marker for the progression of coronary atherosclerosis.Clinical registration ClinicalTrials.gov NCT02803411

Association of high-density lipoprotein levels with baseline coronary plaque volumes by coronary CTA in the EVAPORATE trial

Background and aimsDyslipidemia with elevated triglycerides (TGL) and low high-density lipoprotein cholesterol (HDL-C) predicts residual cardiovascular risk, despite goal LDL-C levels and optimal statin therapy. Coronary plaque characterization by CCTA can provide mechanistic understanding of coronary artery disease and associated prognosis. The role of HDL-C in the pathogenesis of atherosclerosis is not well understood in statin-treated patients with elevated TGL. We sought to examine the association of HDL-C levels with baseline coronary plaque volumes, namely total plaque (TP) and total non-calcified plaque (TNCP) volumes by CCTA in participants enrolled in the EVAPORATE trial. MethodsWe analyzed 80 participants who were enrolled in the trial. Linear regression analysis as a univariate and multivariate model adjusted for significant cardiovascular risk factors was performed to evaluate independent association of HDL-C and baseline coronary plaque volumes. In an exploratory analysis, stratified by sex, we compared the association of serum HDL-C levels with baseline coronary plaque volumes in males and females. ResultsMean (SD) age of participants (n = 80) was 57.1 (8.6) years and 43% were male. Median (Inter Quartile Range/IQR) log-TNCP volume was 83.0 (0.1–7.3) mm3 and median (IQR) log-TP volume was 144.8 (0.1–7.1) mm3. After adjustment for relevant clinical covariates including age, gender, BMI, hypertension, diabetes, past smoking and baseline TGL levels, increasing levels of HDL-C remain independently associated with lower baseline log-TNCP volumes (β: 0.043 ± 0.021, p = 0.042) and baseline log-TP volumes (β: 0.046 ± 0.022, p = 0.035) on CCTA. On stratifying by sex in a multivariable regression analysis, HDL-C levels were inversely associated with baseline log-TNCP volumes (β: 0.066 ± 0.026, p = 0.018) and log-TP volumes (β: 0.077 ± 0.025, p = 0.004) in females, but not in males (log-TNCP volumes β: 0.038 ± 0.034, p = 0.282) and log-TP volumes (β: −0.033 ± 0.036, p = 0.364). ConclusionsIn a cohort of statin treated patients with known atherosclerosis and residually elevated TGL, there was a significant inverse relationship between HDL-C levels and baseline coronary plaque, TP and TNCP volumes on CCTA. Our findings provide more detailed mechanistic evidence regarding the protective role of HDL-C in coronary atherosclerosis in a high-risk cohort. Further investigation to evaluate the interaction of HDL-C levels and coronary plaque volumes on differential CVD risk in statin-treated patients with elevated TGL levels is warranted.

Serial change of perivascular fat attenuation index after statin treatment: Insights from a coronary CT angiography follow-up study

BackgroundPerivascular fat attenuation index (FAI) was thought to be an indicator of active vessel inflammation surrounding coronary plaques. However, whether this index can be reduced by statin treatment remains unknown. We aimed to investigate the serial change of lesion-specific perivascular FAI as quantified by coronary computed tomography (CCTA) after statin treatment. MethodsConsecutive patients with chest pain and intermediate likelihood of coronary artery disease were referred for baseline CCTA. Patients were retrospectively included if they were treated medically and underwent follow-up CCTA at 1-year to 1.5-year interval. Lesion-specific perivascular FAI, as well as other plaque features, were measured at baseline and follow-up. ResultsOne hundred and eight patients (mean age 67.7 ± 11.1, 76 males) were included. A significant reduction of the FAI value was found for non-calcified plaques and mixed plaques (−68.0 HU ± 8.5 HU Vs. -71.5 HU ± 8.1 HU, p < .001 and − 70.5 HU ± 8.9 HU Vs. -72.8 HU ± 9.0 HU, p = .014). However, this improvement was not observed for calcified plaques (−70.6 HU ± 9.7 HU Vs. −71.7 HU ± 9.9 HU, p = .258). For non-calcified and mixed plaques, the volumes of non-calcified as well as low attenuation component was significantly reduced whereas total plaque volume and volume of calcified component increased. For calcified plaque, total plaque volume also demonstrated remarkable increase after statin treatment ConclusionsLesion-specific perivascular FAI decreased at mid-term follow-up after statin treatment for non-calcified and mixed plaques. Perivascular FAI can be a potential imaging biomarker to monitor the anti-inflammation response to statin treatments.

Association of high-risk coronary atherosclerosis at CCTA with clinical and circulating biomarkers: Insight from CAPIRE study

BackgroundHigh-risk coronary atherosclerosis features evaluated coronary CT angiography (CCTA) were suggested to have a prognostic role. The present study aimed to evaluate the association of circulating biomarkers with high-risk plaque features assessed by CCTA. MethodsA consecutive cohort of subjects who underwent CCTA because of suspected CAD was screened for inclusion in the CAPIRE study. Based on risk factors (RF) burden patients were defined as having a low clinical risk (0–1 RF with the exclusion of patients with diabetes mellitus as single RF) or an high clinical risk (≥3 RFs). In all patients, measurement of inflammatory biomarkers and CCTA analysis focused on high-risk plaque features were performed. Univariate and multivariate logistic regression analysis were used to evaluate the relationship between clinical and biological variables with CCTA advanced plaque features. Results528 patients were enrolled in CAPIRE study. Older age and male sex appeared to be predictors of qualitative high-risk plaque features and associated with the presence of elevated total, non-calcified and low-attenuation plaque volume. Among circulating biomarkers only hs-CRP was found to be associated with qualitative high-risk plaque features (OR 2.02, p = 0.004 and 2.02, p = 0.012 for LAP and RI > 1.1, respectively) with borderline association with LAP-Vol (OR 1.52, p = 0.076); HbA1c and PTX-3 resulted to be significantly associated with quantitative high-risk plaque features (OR 1.71, p = 0.003 and 1.04, p = 0.002 for LAP-Vol, respectively). ConclusionsOur results support the association between inflammatory biomarkers (hs-CRP, PTX- 3), HbA1c and high-risk atherosclerotic features detected by CCTA. Male sex and older age are significant predictors of high-risk atherosclerosis.

0721 Coronary Atherosclerotic Plaque Burden and Composition in Patients with Obstructive Sleep Apnea by Coronary CT Angiography

Abstract Introduction OSA is closely associated with increased risk of coronary artery disease. Although previous small studies have investigated coronary plaque in OSA patients, limited data are available regarding the association of OSA with plaque morphology and composition. Therefore, we aimed to quantitatively characterize and compare coronary plaque burden and composition between patients with no or mild obstructive sleep apnea (OSA) and moderate-severe OSA using coronary computed tomography angiography (CTA) in a large-scale study. Methods We retrospectively analyzed consecutive patients who underwent sleep monitoring and coronary CTA. Metrics reflecting coronary plaque characteristics were compared between patients with no or mild OSA with apnea hypoxic index (AHI) ≤15 and moderate-severe OSA (AHI&amp;gt;15). The associations of OSA with coronary plaque components were determined by logistic and linear regression analysis. Results A total of 854 patients were enrolled in the study. Of these, 162 did not meet the inclusion criteria and of the remaining 692 patients 400 (57.8%) had moderate-severe OSA and 292 had no or mild OSA. Patients with moderate-severe OSA had a significantly higher total plaque volume, total non-calcified plaque (NCP) volume and total low density non-calcified plaque (LD-NCP) volume, and corresponding burden than those with no or mild OSA (all with p&amp;lt;0.05). Multivariate logistic regression analysis revealed that moderate-severe OSA patients are more likely to have any plaque, NCP and LD-NCP than those without no or mild OSA (p&amp;lt;0.05). In addition, stepwise multivariate linear regression analysis further revealed an independent relationship between moderate OSA (15&amp;lt;AHI≤30) and more so between severe OSA (AHI&amp;gt;30) and, NCP volume, LD-NCP volume, NCP composition, and LD-NCP composition, following adjustment for traditional cardiovascular risk factors, compared to no or mild OSA (AHI&amp;lt;15) (all with a p&amp;lt;0.05). Moderate-severe OSA conferred a similar odds ratio for LD-NCPs (a high-risk plaque) as the usual cardiovascular risk factors. Conclusion In this large cross-sectional study, OSA severity was associated with high-risk plaque features independent of traditional cardiovascular risk factors, suggesting an increased risk for cardiovascular events. Support This study was supported by NSFC (Project 81870335), International Science &amp; Technology Cooperation Program of China (No.2015DFA30160), Beijing Municipal Science &amp; Technology Commission (No. Z141100006014057)

Prognostic Value of Coronary Computed Tomography Angiography-derived Morphologic and Quantitative Plaque Markers Using Semiautomated Plaque Software.

In this study, we analyzed the prognostic value of coronary computed tomography angiography-derived morphologic and quantitative plaque markers and plaque scores for major adverse cardiovascular events (MACEs). We analyzed the data of patients with suspected coronary artery disease (CAD). Various plaque markers were obtained using a semiautomated software prototype or derived from the results of the software analysis. Several risk scores were calculated, and follow-up data concerning MACE were collected from all patients. A total of 131 patients (65±12 y, 73% male) were included in our study. MACE occurred in 11 patients within the follow-up period of 34±25 months.CAD-Reporting and Data System score (odds ratio [OR]=11.62), SYNTAX score (SS) (OR=1.11), Leiden-risk score (OR=1.37), segment involvement score (OR=1.76), total plaque volume (OR=1.20), and percentage aggregated plaque volume (OR=1.32) were significant predictors for MACE (all P≤0.05). Moreover, the difference of the corrected coronary opacification (ΔCCO) correlated significantly with the occurrence of MACE (P<0.0001). The CAD-Reporting and Data System score, SS, and Leiden-risk score showed substantial sensitivity for predicting MACE (90.9%). The SS and Leiden-risk score displayed high specificities of 80.8% and 77.5%, respectively. These plaque markers and risk scores all provided high negative predictive value (>90%). The coronary computed tomography angiography-derived plaque markers of segment involvement score, total plaque volume, percentage aggregated plaque volume, and ΔCCO, and the risk scores exhibited predictive value for the occurrence of MACE and can likely aid in identifying patients at risk for future cardiac events.

HIV May Accelerate Coronary Artery Disease Progression Through Promoting the Adverse Effects of Conventional Cardiovascular Risk Factors and Illicit Drugs

Background: Only the independent effect of human immunodeficiency virus (HIV)-infection on coronary artery disease (CAD) has been investigated in cross-section studies, while rather than directly, HIV-infection may accelerate CAD through promoting the effects of risk factors. Furthermore, there is no information on the potential effects of HIV-infection on coronary plaque volumes. Therefore, we investigated whether HIV-infection directly or indirectly promotes clinical and volumetric characteristics of CAD in a observational longitudinal study. Methods: 300 individuals without cardiovascular symptoms (210 male; age: 48·0±7·2 years; 226 HIV-infected) underwent coronary CT angiography at two time points (mean follow-up: 4·0±2·3 years). We quantified Agatston-score, number of coronary plaques, segment stenosis score, and also segmented the coronary plaques to enumerate total, noncalcified (-100–350HU) and calcified (≥351HU) plaque volumes. Linear mixed models were used to assess the effects of HIV-infection, atherosclerotic cardiovascular disease (ASCVD) risk, years of cocaine use and high-sensitivity C-reactive protein on CT markers of CAD. Findings: There was no significant difference in annual progression rates between HIV-infected and -uninfected (p>0·05 for all). Multivariately, HIV-infection was not associated with any CAD parameter (p>0·05 for all). However, among HIV-infected individuals, each year of cocaine use significantly increased all CAD parameters (p<0·05 for all), while ASCVD risk score was significantly associated with CAD parameters except for Agatston-score (p<0·05). However, these associations were only apparent among HIV-infected individuals. Importantly, none of the HIV-medications were associated with any of the CAD outcomes. Interpretation: HIV-infection is not directly associated with CAD and therefore HIV-infected are not destined to have worse CAD profiles as compared to uninfected individuals. However, more aggressive management of conventional cardiovascular risk factors and abstinence from illicit drugs may be needed to achieve similar CAD status. Funding Statement: Procedures and tests were funded by the National Institute on Drug Abuse, and the National Institutes of Health (NIH R01DA12777, R01DA15020, R01DA25524, R21DA048780 and U01DA040325). Declaration of Interests: None. Ethics Approval Statement: The Committee on Human Research at the Johns Hopkins School of Medicine (Baltimore, MD) approved the study protocol, and all study participants provided written informed consent. All procedures used in this study were in accordance with HIPAA, local and federal regulations, and the Declaration of Helsinki.