Luminal Diameter Stenosis Research Articles

Peripheral-blood gene expression profiling studies for coronary artery disease and its severity in Xinjiang population in China

BackgroundAlterations in gene expression in peripheral blood cells play a curtail role in the presence and extent of coronary artery disease (CAD), but its severity reflected by gene expression alterations in peripheral blood cells is still unknown in Xinjiang population in China.MethodsGlobal gene expression profiling in peripheral blood was used to explore differentially expressed genes in coronary artery stenosis patients. RNA was extracted from peripheral blood of 9 controls without coronary stenosis and 21 cases with angiographically CAD. The extent of CAD severity was categorized angiographically as no CAD, mild CAD (20 to 50% luminal diameter stenosis [LDS]), moderate CAD (50 to 75% LDS) and severe CAD (≥75% LDS). Differentially expressed genes related with CAD severity from peripheral blood cells were screened by linear mixed effects analysis using the lme4 package in R. Then the differentially expressed genes that gradually up-regulated or down-regulated were enriched by Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.ResultsThe most significantly enrichments were toll-like receptor signaling pathway, immune responses, translational processes, cellular growth, inflammation and metabolic processes. Combined with NCBI-GeneRIF and PubMed analysis, we focused on the 12 genes associated with toll-like receptor signaling pathway in the extent of coronary artery stenosis patients. Receiver operating characteristic (ROC) analysis of 12 genes associated with toll-receptor signaling pathway in the 236 CAD patients from GEO database demonstrated that 12 genes expression could predict severe CAD with an area under the curve of 0.67, sensitivity of 77.65% and specificity of 51.52%.ConclusionThese results suggest that 12 genes associated with toll-like receptor signaling pathway in peripheral-blood cells reflect the presence and extent of CAD severity in Xinjiang population in China.

CT morphological index provides incremental value to machine learning based CT-FFR for predicting hemodynamically significant coronary stenosis

AimsTo study the diagnostic performance of the ratio of Duke jeopardy score (DJS) to the minimal lumen diameter (MLD) at coronary computed tomographic angiography (CCTA) and machine learning based CT-FFR for differentiating functionally significant from insignificant lesions, with reference to fractional flow reserve (FFR). Methods and resultsPatients who underwent both coronary CTA and FFR measurement at invasive coronary angiography (ICA) within 2 weeks were retrospectively included in our study. CT-FFR, DJS/MLDCT ratio, along with other parameters, including minimal luminal area (MLA), MLD, lesion length (LL), diameter stenosis, area stenosis, plaque burden, and remodeling index of lesions, were recorded. Lesions with FFR ≤0.8 were considered to be functionally significant. One hundred and twenty-nine patients with 166 lesions were ultimately included for analysis. The LL, diameter stenosis, area stenosis, plaque burden, DJS and DJS/MLDCT ratio were all significantly longer or larger in the group of FFR ≤ 0.8 (p < 0.001 for all), while smaller MLA, MLD and CT-FFR value were also noted (p < 0.001 for all). CT-FFR and DJS/MLDCT ratio showed the largest AUC among all single parameters (AUC = 0.85 and AUC = 0.83, respectively; p < 0.001 for both) for diagnosing functionally significant stenosis. Combining CT-FFR and DJS/MLDCT ratio provided incremental value for discrimination between flow-limiting and non-flow-limiting coronary lesions and yielded the best diagnostic performance (accuracy of 83.7%). ConclusionsThe combination of ML-based CT-FFR and DJS/MLDCT allows accurate non-invasive discrimination between flow-limiting and non-flow-limiting coronary lesions.

Local Low Shear Stress and Endothelial Dysfunction in Patients With Nonobstructive Coronary Atherosclerosis

BackgroundLocal hemodynamic factors are important determinants of atherosclerotic plaque development and progression. ObjectivesThe goal of this study was to determine the association between low endothelial shear stress (ESS) and microvascular and epicardial endothelial dysfunction in patients with early atherosclerosis. MethodsSixty-five patients (mean age 52 ± 11 years) with nonobstructive coronary atherosclerosis (luminal diameter stenosis <30%) were included. Microvascular and epicardial coronary endothelial function was assessed by using intracoronary acetylcholine infusion. Vascular profiling, using 2-plane coronary angiography and intravascular ultrasound, was used to reconstruct the three-dimensional anatomy of the left anterior descending artery. Each reconstructed artery was divided into sequential 3-mm segments and analyzed for local ESS with computational fluid dynamics; that is, lower ESS levels at both a 3-mm regional level (average ESS and low ESS) and at a vessel level (lowest ESS per artery) and for plaque characteristics (plaque area, plaque thickness, and plaque burden). ResultsCoronary segments in arteries with abnormal microvascular function exhibited lower ESS compared with segments in arteries with normal microvascular function (average ESS: 1.67 ± 1.04 Pa vs. 2.03 ± 1.72 Pa [p = 0.050]; lowest ESS: 0.54 ± 0.25 Pa vs. 0.72 ± 0.32 Pa [p = 0.014]). Coronary segments in arteries with abnormal epicardial endothelial function also exhibited significantly lower ESS compared with segments in arteries with normal epicardial function (average ESS: 1.49 ± 0.89 Pa vs. 1.93 ± 1.50 Pa [p < 0.0001]; low ESS: 1.26 ± 0.81 Pa vs. 1.56 ± 1.30 Pa [p = 0.001]; lowest ESS: 0.51 ± 0.27 Pa vs. 0.65 ± 0.29 Pa [p = 0.080]). Patients with abnormal microvascular endothelial function exhibited a progressive decrease in average and low ESS, starting from patients with normal epicardial endothelial function to those with both microvascular and epicardial endothelial dysfunction (p < 0.0001 and p = 0.004, respectively). ConclusionsThese data indicate an association between dysfunction of the microvascular and epicardial endothelium and local ESS at the early stages of coronary atherosclerosis in humans.

Thrombogenicity and central pulse pressure to enhance prediction of ischemic event occurrence in patients with established coronary artery disease: The MAGMA-ischemia score

Background and aimsConventional cardiovascular risk estimators based on clinical demographics have limited prediction of coronary events. Markers for thrombogenicity and vascular function have not been explored in risk estimation of high-risk patients with coronary artery disease. We aimed to develop a clinical and biomarker score to predict 3-year adverse cardiovascular events. MethodsFour hundred eleven patients, with ejection fraction ≥40% undergoing coronary angiography, and found to have a luminal diameter stenosis ≥50%, were included in the analysis. Thrombelastography indices and central pulse pressure (CPP) were determined at the time of catheterization. ResultsWe identified predictors of death, myocardial infarction (MI) or stroke and developed a numerical ischemia risk score. The primary endpoint of cardiovascular death, MI or stroke occurred in 22 patients (5.4%). The factors associated with events were age, prior PCI or CABG, diabetes, CPP, and thrombin-induced platelet-fibrin clot strength, and were included in the MAGMA-ischemia score. The MAGMA-ischemia score showed a c-statistic of 0.85 (95% Confidence Interval [CI] 0.80–0.87; p<0.001) for the primary endpoint. In the subset of patients who underwent revascularization, the c-statistic was 0.90 (p<0.001). Patients with MAGMA-ischemia score greater than 5 had highest risk to develop clinical events, hazard ratio for the primary endpoint: 13.9 (95% CI 5.8–33.1, p<0.001) and for the secondary endpoint: 4.8 (95% CI 2.3–9.6, p<0.001). When compared to previous models, the MAGMA-ischemia score yielded a higher discrimination. ConclusionsInclusion of CPP and assessment of thrombogenicity in a novel score for patients with documented CAD enhanced the prediction of events.

Low-density lipoprotein 4: a novel predictor of coronary artery disease severity

Background: Hyperlipidemia is a well established risk factor for coronary artery disease (CAD). Severe CAD has been observed in patients with normal levels of total and low-density lipoprotein (LDL) cholesterol. Small dense LDL particle subtypes (LDL3 and LDL4) have been observed to be more oxidizable and atherogenic. We aimed to identify the role of cholesterol particle subtypes in predicting CAD severity.Methods: Blood samples were obtained immediately before cardiac catheterization in 179 consecutive patients with suspected CAD. Detailed lipid profiling was performed using a VAP cholesterol test. CAD severity was categorized angiographically as no/minor CAD (<20% luminal diameter stenosis [LDS]), moderate CAD (20% to 74% LDS) and severe CAD (>75% LDS of any major coronary vessel).Results: Patients with severe CAD had significantly higher LDL4 and triglycerides, and lower total HDL, HDL2, HDL3, LDL2 and LDL3 compared to patients with no/minor CAD (p < .05 for all). Multivariate analysis showed high LDL4 as an independent predictive of severe CAD. ROC analysis showed an area under the curve of 0.62 (p < .0001) with a cut-point of >16.9 mg/dL to predict severe CAD with a sensitivity of 53% and specificity of 79%.Conclusion: Elevated LDL4 levels are associated with severe CAD. Further large-scale investigations are required to evaluate the utility of LDL4 in predicting CAD severity.

Abstract 214: A Blood-based Precision Medicine Test Score is Additive in Determining a Patient’s Risk of Obstructive Coronary Artery Disease After Positive Myocardial Perfusion Imaging: Results From the PREDICT and COMPASS Studies

Background: Myocardial perfusion imaging (MPI) is the predominant diagnostic tool for evaluating outpatients with typical and atypical symptoms suggestive of obstructive coronary artery disease (CAD) and is commonly followed by invasive coronary angiography in patients with abnormal findings. Despite this paradigm, a significant proportion of patients do not need intervention, suggesting better diagnostic methods are needed to identify appropriate patients who would benefit from the risks, resource utilization, and healthcare costs incurred after a positive MPI. A previously validated, blood-based test incorporating age, sex and genomic expression score (ASGES) utilizing peripheral blood cell expression has demonstrated clinical validity in assessing the likelihood of obstructive CAD (≥50% luminal diameter stenosis by quantitative coronary angiography) early in the cardiac workup. Objective: The objective of this study is to evaluate if the utilization of the ASGES in conjunction with a positive MPI would assist in the determination of a patient’s risk of obstructive coronary artery disease. Methods: A total of 249 patients (mean age 58, 45% female) from 59 sites in the PREDICT (NCT00500617) and COMPASS (NCT01117506) studies were identified with a positive MPI study, defined as at least one reversible of fixed defect consistent with obstructive CAD and a subsequent invasive coronary angiography. ASGES scores were performed in all patients and were categorized into 3 groups based on score: low (1-15, 25%), mid-range (16-27, 43%) and high (28-40, 32%). Obstructive CAD rates defined by invasive coronary angiography were measured. The association between obstructive CAD and ASGES was evaluated using Cochran-Armitage trend test and area under the receiver-operating characteristics curve (AUC) analyses. Results: The rate of obstructive CAD among patients with a positive MPI was 35% (88/249). There was a net redistribution of risk based on ASGES testing in 52% (49/88) of these patients. The rate of obstructive CAD was 11% (7/63), 37% (39/106), and 53% (42/80) in the low, mid-range, and high score groups respectively (p&lt;0.001). AUC for the ASGES use with a positive MPI was 0.704. Conclusion: The ASGES test, when used in patients after positive MPI, improved the diagnostic accuracy in the assessment of obstructive CAD. The use of this precision medicine test may help minimize unnecessary referral of low-intermediate risk patients as well as improve diagnostic yield among patients with abnormal MPI findings scheduled to undergo invasive coronary angiography.

Abstract 070: A Precision Medicine Test Influenced Costs of Care Among Patients Presenting With Stable Symptoms Suggestive of Obstructive Coronary Artery Disease: Economic Endpoint Analysis From the PRESET Registry

Background: Because of diagnostic uncertainty, patients with symptoms suggestive of obstructive coronary artery disease (CAD) are referred at high rates to cardiologists and advanced cardiac testing. This evaluation process may also expose patients to appreciable costs and health risks. A previously validated, blood-based test incorporating age, sex and genomic expression into an algorithmic score (1-40) has shown clinical validity in assessing the likelihood of obstructive CAD (≥50% luminal diameter stenosis by quantitative coronary angiography) early in the cardiac workup. This test has also shown clinical utility in association with decision making around cardiac referrals and helping clinicians determine the current likelihood of obstructive CAD in symptomatic patients. Hypothesis: We hypothesized that use of the age/sex/gene expression score (ASGES) test would influence cost of care in the diagnosis and management of symptomatic patients with suspected obstructive CAD. Methods: The prospective PRESET Registry (NCT01677156) enrolled stable, non-acute adult patients presenting with symptoms suggestive of obstructive CAD to 21 US primary care practices from September 2012 to August 2014. Primary care clinicians provided pre- and post-ASGES diagnosis and evaluation plans for each patient. Demographics, clinical factors, and ASGES results (predefined as low [ASGES ≤ 15] or elevated [ASGES &gt; 15]) were collected, as were management plans post-ASGES testing, including referrals to cardiology or further functional/anatomic testing. The economic analysis for cost of care after ASGES testing was based on the cost of cardiovascular-related tests, invasive procedures, office visits, emergency room visits, and hospital admissions during 1-year follow-up. Results: This sub-analysis cohort included 560 patients, with 50% females and median age 56 years. Patients had a median ASGES score of 18, with 246 (44%) patients with ASGES &lt; 15. The mean cost of care for patients in the year following ASGES testing was $234 (SD ±$707) in the low ASGES versus $1,296 (SD ±$5230) in the elevated ASGES group (p=0.03 by Wilcoxon rank test). Multivariate analysis incorporating patient demographics and clinical covariates showed that low ASGES was associated with a 51% reduction in cost of follow-up care compared to elevated ASGES group (p&lt;0.001 by log-linear regression). Conclusion: In this community-based cardiovascular registry, the ASGES influenced costs in the evaluation of patients with suspected obstructive CAD. Low score patients had approximately half the cardiovascular costs of elevated score patients in one year follow-up. Our work provides evidence supporting the economic value of using precision medicine in the delivery of cardiovascular care.

Adult height associates with angiographic extent of coronary artery disease

Background and aimsShorter stature is an established risk factor for coronary artery disease (CAD), but less is known about its association with extent of the disease. MethodsWe assessed the relationship between self-reported height and angiographic findings in 7706 men and 3572 women identified from a nationwide coronary angiography registry in Iceland. ResultsAfter adjustment for traditional cardiovascular risk factors, a standard deviation decrease in height associated with a greater likelihood of significant CAD (defined as ≥50% luminal diameter stenosis) both in men (adjusted odds ratio [ORadj]: 1.24, 95% confidence interval [CI]: 1.18, 1.31; p = 3.2 × 10−16) and women (ORadj = 1.10, 95% CI: 1.02, 1.18; p = 0.012). In partial proportional odds logistic regression models, a standard deviation decrease in height was associated with higher odds of having greater extent of CAD in men (ORadj = 1.19, 95% CI: 1.15, 1.25; p = 1.5 × 10−16) and women (ORadj = 1.09, 95% CI: 1.02, 1.16; p = 0.014). When limited to patients with significant CAD, the association was statistically significant in men (ORadj = 1.08, 95% CI: 1.03, 1.14; p = 0.0022) but not in women (p = 0.56). ConclusionsOur findings show that shorter stature is associated with greater extent of coronary atherosclerosis in a large unselected population of individuals undergoing coronary angiography. This relationship appears to be sex-dependent, with stronger effects in men than in women.

Human serum preβ1-high density lipoprotein levels are independently and negatively associated with coronary artery diseases.

BackgroundSerum preβ1-high density lipoprotein (preβ1-HDL) was defined by two-dimensional non-denaturing linear gel electrophoresis and apolipoprotein A-I immuno-blotting. Serum preβ1-HDL seems to play an important role in reverse cholesterol transport, a well-known anti-atherosclerosis process. However, there are still debatable questions for its quantification and coronary artery disease (CAD) relevance.MethodsWe isolated the preβ1-HDL using a new native polyacrylamide gel electrophoresis (PAGE) system and lipid pre-staining serum. We established a two-demensional gel electrophoresis system.ResultsWe measured the preβ1-HDL in Tangier disease patients and subjects with cholesterol ester transfer protein (CETP) mutation. The preβ1-HDL is clearly separated from lipid-free apoA-I monomer and cannot be converted into other HDL particles under lecithin-cholesterol acyltransferase (LCAT) inhibition. This preβ1-HDL is a spheroidal particle with the highest apoA-1/cholesterol ratio and highest density (≥1.21 g/ml), as compared with all other HDLs. Importantly, we found that serum from subjects with Tangier disease or with cholesterol ester transfer protein (CETP) mutation have no detectible preβ1-HDL particles. We recruited a total of 102 subjects underwent diagnostic coronary angiography and measured their preβ1-HDL levels. Among them, 56 had no stenosis of coronary artery and 46 were diagnosed as CAD, which was predefined as the presence of a luminal diameter stenosis ≥50 % in at least 1 major coronary artery territory. We found that preβ1-HDL is independently and negatively associated with the severity of the coronary artery stenosis (Gensini score).ConclusionWe established a novel and simple method for human serum preβ1-HDL quantification. We found that human lower preβ1-HDL is an independent predictor for severer coronary artery stenosis.

Lower Extremity Arterial Calcification as a Predictor of Coronary Atherosclerosis in Patients with Peripheral Arterial Disease.

BackgroundUntil now, there has been no study on the relationship between the calcification of the lower extremity arteries and significant coronary arterial disease (CAD).ObjectivesTo evaluate whether lower extremity calcium scores (LECS) are associated with CAD and whether this can predict multivessel-CAD in patients with peripheral arterial disease (PAD).Patients and MethodsWe retrospectively enrolled 103 PAD patients without cardiac symptoms or known CAD. All patients underwent cardiac computed tomography (CT) and lower extremity CT within 1 month and were categorized as nonsignificant CAD, single-CAD, or multivessel-CAD. The coronary calcium scores (CCS) were quantitatively measured according to the Agatston method and LECS were semi-quantitatively measured according to the presence of lower extremity calcification in the segment. The extent of CAD was evaluated according to the presence of ≥ 50% luminal diameter stenosis in the segment of CAD.ResultsLECS in multivessel-CAD were significantly higher than those in nonsignificant CAD (10.0 ± 5.8 versus 4.0 ± 3.1, P < 0.001). LECS significantly correlated with CCS (r = 0.831, P < 0.001) and the extent of CAD (r = 0.631, P < 0.001). Multivariate regression analysis demonstrated LECS and log-transformed CCS were independent predictors for multivessel-CAD. In receiver operating characteristic curve analysis, the diagnostic performance of LECS was 0.807 (95% confidence interval = 0.724-0.891, P < 0.001) for predicting multivessel-CAD.ConclusionPeripheral arterial calcification is significantly correlated with CAD extent in patients with PAD. Peripheral arterial calcification can be a useful marker for predicting multivessel-CAD.

Thrombin-Induced Platelet-Fibrin Clot Strength Identified by Thrombelastography: A Novel Prothrombotic Marker of Coronary Artery Stent Restenosis.

In-stent restenosis (ISR) is a limitation of percutaneous coronary intervention and has been linked to specific clinical and angiographic variables. We aimed to simultaneously assess thrombosis biomarkers and lipid levels in patients with and without ISR. Consecutive patients (n = 170) with a history of coronary stenting undergoing elective angiography were studied. Blood samples for thrombelastography, light transmittance aggregometry, and lipid levels were obtained prior to cardiac catheterization. Sixty-nine patients (41%) had ISR (>50% luminal diameter stenosis). Among patients with ISR, 40 (58%) had ISR in more than one stent bed. Patients with ISR were more often female (37.7% vs. 21.8%, P = 0.04), had higher thrombin-induced platelet-fibrin clot strength (TIP-FCS) (69.9 mm vs. 65.6 mm, P < 0.001), and a higher ApoB/A1 ratio (0.65 vs. 0.59, P = 0.03). In patients on dual antiplatelet therapy (n = 86), there were no differences in ADP-, arachidonic acid-, and collagen-induced platelet aggregation between groups. The frequency of patients with ISR increased with TIP-FCS quartiles and by ROC analysis, TIP-FCS = 67.0 mm was the cutpoint for identification of ISR (AUC = 0.80 (95%CI 0.73-0.87, P < 0.0001). By multivariate analysis, TIP-FCS ≥67.0 mm strongly associated with ISR (OR = 7.3, P = 0.004). Patients with ISR identified at the time of cardiac catheterization have a prothrombotic phenotype indicated by high TIP-FCS, a novel marker. Studies to confirm the prognostic utility of high TIP-FCS for the development of ISR are ongoing.

Is galectin-3 a biomarker, a player—or both—in the presence of coronary atherosclerosis?

Atherosclerosis is a complex process mediated by leukocytes, macrophages and various inflammatory markers. Galectin-3 is secreted by activated macrophages and is involved in cardiac fibrosis, cardiac remodeling, and inflammation. The...

Number of Blades-up Runs Using JetStream XC Atherectomy for Optimal Tissue Debulking in Patients with Femoropopliteal Artery In-Stent Restenosis

Rotational atherectomy with the use of the JetStream XC device is indicated for treatment of infrainguinal arterial obstructive disease. The number of blades-up (BU) runs needed for optimal tissue debulking in femoropopliteal in-stent restenosis (ISR) is unknown. In the present series, 6 patients (15 lesions) were treated for femoropopliteal ISR with the JetStream XC device. Minimal luminal diameter or percent stenosis improved significantly from baseline after 2 BU runs, but no further gain was seen between 2 and 4 BU runs (P > .05). However, adjunctive balloon angioplasty reduced percent stenosis significantly following BU runs. In conclusion, the JetStream XC device achieved optimal acute angiographic results in treating femoropopliteal ISR following 2 BU runs and adjunctive balloon angioplasty.

Abstract 10115: The Diagnostic Value of Global and Territorial Longitudinal Strain at Rest for the Detection of Coronary Artery Disease in Patients Without Type 2 Diabetes Mellitus

Background: Global longitudinal strain (GLS) at rest aids the detection of coronary artery disease (CAD). However, myocardial strains are affected by both ischemia and diabetes mellitus (DM), and previous studies that evaluated the performance of GLS for detecting ischemia always included a certain DM patients in the study population. Thus, we sought to investigate in patients with no DM the power of GLS for detecting three-vessel CAD, and whether territorial longitudinal strain (TLS) could help identifying individual coronary artery stenosis Methods and results: We retrospectively studied 211 consecutive patients with suspected CAD and normal left ventricular (LV) ejection fraction. The patients with DM were excluded. All patients underwent echocardiography and subsequently coronary angiography. LV global and segmental peak systolic longitudinal strain (PSLS) parameters were quantified by two-dimensional speckle tracking echocardiography (2D STE). Territorial PSLSs were calculated based on the perfusion territories of the 3-epicardial coronary arteries in a 17-segment LV model. Critical CAD was defined as luminal diameter stenosis ≥ 70% in ≥ 1 epicardial coronary artery. Totally 145 patients had critical CAD on coronary angiography. Significant differences were observed in all strain parameters between patients with and without CAD. The AUC for GLS in the detection of three-vessel CAD was 0.875 at a cutoff value of -19.05% with sensitivity 78.1% and specificity 72.7%, which increased to 0.926 after excluding apical segments (cutoff value -18.66%; sensitivity 84.4% and specificity 81.8%). The TLS values were significantly lower in regions supplied by stenotic compared with non-stenotic coronary arteries. It has better power to identify LCX and LAD stenosis than RCA stenosis. An area under the curve (AUC) for the TLS to identify critical LCX, LAD and RCA stenosis, in order of diagnostic accuracy, is 0.818 for LCX, 0.764 for LAD and lastly 0.723 for RCA. Conclusions: In patients with no DM and suspected CAD, GLS is an excellent predictor of three-vessel CAD with high accuracy. A higher cut point than that reported before was obtained and should be used. TLS could identify which coronary artery is stenotic with fair sensitivity and specificity.

Association of elevated apoA-I glycation and reduced HDL-associated paraoxonase1, 3 activity, and their interaction with angiographic severity of coronary artery disease in patients with type 2 diabetes mellitus.

ObjectiveTo investigate whether apolipoprotein A (apoA)-I glycation and paraoxonase (PON) activities are associated with the severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM).MethodsRelative intensity of apoA-I glycation and activities of high-density lipoprotein (HDL)-associated PON1 and PON3 were determined in 205 consecutive T2DM patients with stable angina with (n = 144) or without (n = 61) significant CAD (luminal diameter stenosis ≥ 70 %). The severity of CAD was expressed by number of diseased coronary arteries, extent index, and cumulative coronary stenosis score (CCSS).ResultsThe relative intensity of apoA-I glycation was higher but the activities of HDL-associated PON1 and PON3 were lower in diabetic patients with significant CAD than in those without. The relative intensity of apoA-I glycation increased but the activities of HDL-associated PON1 and PON3 decreased stepwise from 1 - to 3 - vessel disease patients (P for trend < 0.001). After adjusting for possible confounding variables, the relative intensity of apoA-I glycation correlated positively, while the activities of HDL-associated PON1 and PON3 negatively, with extent index and CCSS, respectively. At high level of apoA-I glycation (8.70 ~ 12.50 %), low tertile of HDL-associated PON1 (7.03 ~ 38.97U/mL) and PON3 activities (7.11 ~ 22.30U/mL) was associated with a 1.97− and 2.49− fold increase of extent index and 1.73− and 2.68− fold increase of CCSS compared with high tertile of HDL-associated PON1 (57.85 ~ 154.82U/mL) and PON3 activities (39.63 ~ 124.10U/mL), respectively (all P < 0.01).ConclusionsElevated apoA-I glycation and decreased activities of HDL-associated PON1 and PON3, and their interaction are associated with the presence and severity of CAD in patients with T2DM.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-015-0221-4) contains supplementary material, which is available to authorized users.

Coronary CT angiography for the detection of coronary artery stenosis in patients referred for transcatheter aortic valve replacement

BackgroundCoronary CT has become the foremost noninvasive imaging modality for detecting coronary stenoses in patients with suspected coronary artery disease. Nevertheless, little is known about its performance in patients undergoing transcatheter aortic valve replacement (TAVR). ObjectiveThis study investigates the diagnostic performance of coronary CT angiography in patients referred for TAVR. MethodsOne hundred and fifteen consecutive patients with severe aortic stenosis underwent CT angiography with retrospective electrocardiography triggered acquisition and an iterative reconstruction algorithm, of whom 23 (20%) had prior coronary artery bypass graft (CABG) surgery. Diagnostic accuracy of CT for detecting significant coronary stenosis (≥50% luminal diameter stenosis in segments ≥2 mm) in the left main, proximal, or middle segments of coronary arteries and bypass grafts was compared with that of invasive coronary angiography. ResultsIn the overall study population, the sensitivity, specificity, and positive and negative predictive value of CT angiography for the detection of coronary segment or bypass graft lesions were 96% (47 of 49), 73% (48 of 66), 72% (47 of 65), and 96% (48 of 50), respectively. The per-patient diagnostic yield of CT angiography was consistent among patients without prior CABG (93% [28 of 30], 73% [45 of 62], 62% [28 of 45], and 96% [45 of 47], respectively) and among patients with prior CABG (100% [19 of 19], 75% [3 of 4], 95% [19 of 20], and 100% [3 of 3], respectively). ConclusionAmong patients referred for TAVR, coronary CT angiography with retrospective gating and iterative reconstruction may allow detection of significant stenosis in the proximal or middle segments of coronary arteries and could permit the evaluation of patients after bypass grafts.

Comparison of Diagnostic Value of a Novel Noninvasive Coronary Computed Tomography Angiography Method Versus Standard Coronary Angiography for Assessing Fractional Flow Reserve

Noninvasive fractional flow reserve (FFR) from coronary computed tomography angiography (cCTA) correlates well with invasive FFR and substantially improves the detection of obstructive coronary artery disease. However, with current algorithms, computed tomography (CT)-based FFR is derived off-site in an involved time-consuming manner. We sought to investigate the diagnostic performance of a novel CT-based FFR algorithm, developed for time-efficient in-hospital evaluation of hemodynamically indeterminate coronary lesions. In a blinded fashion, CT-based FFR was assessed in 67 coronary lesions of 53 patients. Pressure guidewire-based FFR <0.80 served as the reference standard to define hemodynamically significant stenosis and assess the diagnostic performance of CT-based FFR compared with standard evaluation of cCTA (luminal diameter stenosis of ≥50%). We recorded the time needed for derivation of CT-based FFR. On a per-lesion and per-patient basis, CT-based FFR resulted in a sensitivity of 85% and 94%, a specificity of 85% and 84%, a positive predictive value of 71% and 71%, and a negative predictive value of 93% and 97%, respectively. The area under the receiver operating characteristic curve on a per-lesion basis was significantly greater for CT-based FFR compared with standard evaluation of cCTA (0.92 vs 0.72, p= 0.0049). Asimilar trend, albeit not statistically significant, was observed on per-patient analysis (0.91 vs 0.78, p= 0.078). Mean total time for CT-based FFR was 37.5 ± 13.8minutes. In conclusion, the CT-based FFR algorithm evaluated here outperforms standard evaluation of cCTA for the detection of hemodynamically significant stenoses while allowing on-site application within clinically viable time frames.

A peripheral blood gene expression score is associated with atherosclerotic Plaque Burden and Stenosis by cardiovascular CT-angiography: Results from the PREDICT and COMPASS studies

ObjectiveWe previously validated a gene expression score (GES) based on age, sex and peripheral blood cell expression levels of 23 genes measured by quantitative real-time PCR (qRT-PCR) for diagnosis of obstructive coronary artery disease (CAD) (≥50% luminal diameter stenosis). In this study we sought to determine the association between the GES and coronary arterial Plaque Burden and Stenosis by CT-angiography. MethodsA total of 610 patients (mean age: 57 ± 11; 50% male) from the PREDICT and COMPASS studies from 59 centers were analyzed. Coronary artery calcium (CAC) scoring, CT angiography (CTA)-based plaque and stenosis and GES measurements were performed. CAC was expressed as Agatston score and CTA evaluated for stenosis severity: 0. None; 1. Minimal, 2. Mild, 3. Moderate, 4. Severe and 5. Occluded. Correlation analysis, one-way analysis of variance (ANOVA) and receiver operating characteristics (ROC) analyses were performed. ResultsGES was significantly associated with plaque burden by CAC (r = 0.50; p < 0.001) and CTA (segment involvement score index: r = 0.37, p < 0.001); a low score (≤15) had sensitivity of 0.71 and a high score (≥28) a specificity of 0.97 for the prediction of zero vs. non-zero CAC. Increasing GES was associated with a greater degree of categorical stenosis by ANOVA (p < 0.001); GES significantly correlated with maximum luminal stenosis (r = 0.41; p < 0.01) and segment stenosis score index (r = 0.38; p < 0.01). A low score had sensitivity of 0.90 and a high score a specificity of 0.87 for ≥70% stenosis. ConclusionsA previously validated GES is significantly associated with Plaque Burden and Stenosis by CT. Clinical trial registration.(PREDICT [NCT00500617] and COMPASS [NCT01117506]), www.clinicaltrials.gov

Circulation : Cardiovascular Imaging

<i>Circulation</i> : <i>Cardiovascular Imaging</i>

Association ofHelicobacter pyloriInfection with Coronary Artery Disease: IsHelicobacter pyloria Risk Factor?

Background. Helicobacter pylori (HP) infection is the most common infection in the world and coronary artery disease (CAD) is probably associated with it. The aim of this prospective study was to evaluate the association between HP infection and CAD in suspected patients referred for coronary angiography. The coronary angiography was performed using Judkins method and patients were assigned to participate in CAD positive (>50% luminal diameter stenosis) and negative groups. The serum HP IgG antibody was checked. Results. Positive and negative CAD groups consisted of 62 and 58 patients, respectively. HP was more prevalent among CAD+ patients, and with increasing the number of coronary arteries with stenosis, the HP seropositivity increased so that 76.3% of patients with multiple vessel diseases (MVD) and 70% of patients with single vessel diseases (SVD) were HP seropositive versus 50% in control group (P = 0.006). Positive CAD was significantly associated with HDL level (P = 0.01) and ESR level (P = 0.006). Also, CAD+ patients had higher CRP levels than controls and it was statistically different between SVD group and controls (P < 0.05). Conclusion. HP infection is more prevalent in CAD positive patients and, in case of proving causal relationship, it can be considered as a reversible risk factor for CAD.