Search

Background: Genome-wide association studies have identified many genetic loci that are robustly associated with coronary artery disease (CAD). However, the underlying biological mechanisms are still unknown for most of these loci, hindering the progress to medical translation. Evidence suggests that the genetic influence on CAD susceptibility may act partly through vascular smooth muscle cells (VSMCs).Methods: We undertook genotyping, RNA sequencing, and cell behavior assays on a large bank of VSMCs (n>1499). Expression quantitative trait locus and splicing quantitative trait locus analyses were performed to identify genes with an expression that was influenced by CAD-associated variants. To identify candidate causal genes for CAD, we ascertained colocalizations of VSMC expression quantitative trait locus signals with CAD association signals by performing causal variants identification in associated regions analysis and the summary data-based mendelian randomization test. Druggability analysis was then performed on the candidate causal genes. CAD risk variants were tested for associations with VSMC proliferation, migration, and apoptosis. Collective effects of multiple CAD-associated variants on VSMC behavior were estimated by polygenic scores.Results: Approximately 60% of the known CAD-associated variants showed statistically significant expression quantitative trait locus or splicing quantitative trait locus effects in VSMCs. Colocalization analyses identified 84 genes with expression quantitative trait locus signals that significantly colocalized with CAD association signals, identifying them as candidate causal genes. Druggability analysis indicated that 38 of the candidate causal genes were druggable, and 13 had evidence of drug-gene interactions. Of the CAD-associated variants tested, 139 showed suggestive associations with VSMC proliferation, migration, or apoptosis. A polygenic score model explained up to 5.94% of variation in several VSMC behavior parameters, consistent with polygenic influences on VSMC behavior.Conclusions: This comprehensive analysis shows that a large percentage of CAD loci can modulate gene expression in VSMCs and influence VSMC behavior. Several candidate causal genes identified are likely to be druggable and thus represent potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Keywords: coronary artery bypass grafting; coronary artery disease; radial artery; smartphone EN coronary artery bypass grafting coronary artery disease radial artery smartphone 1183 1185 3 04/10/23 20230411 NES 230411 Use of the radial artery (RA) as a conduit in coronary artery bypass grafting (CABG) has been associated with improved long-term cardiovascular outcomes when compared with other conduit options.[1],[2] To mitigate risk of postoperative hand ischemia, assessment of collateral circulation before RA harvesting remains the current standard of care. Footnotes 1 Nonstandard Abbreviations and Acronyms CABG coronary artery bypass grafting MAT modified Allen test RA radial artery SP smartphone photoplethysmography 2 S. Parlow and P. Di Santo contributed equally. [Extracted from the article]

Aim: The executive summary of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guideline provides the top 10 items readers should know about the guideline. In the full guideline, the recommendations replace the 2011 coronary artery bypass graft surgery guideline and the 2011 and 2015 percutaneous coronary intervention guidelines. This summary offers a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization, as well as the supporting documentation to encourage their use.Methods: A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. Structure: Recommendations from the earlier percutaneous coronary intervention and coronary artery bypass graft surgery guidelines have been updated with new evidence to guide clinicians in caring for patients undergoing coronary revascularization. This summary includes recommendations, tables, and figures from the full guideline that relate to the top 10 take-home messages. The reader is referred to the full guideline for graphical flow charts, supportive text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in the development of this guideline. [ABSTRACT FROM AUTHOR]

Coronary artery anomalies (CAAs) are a group of congenital conditions characterized by abnormal origin or course of any of the 3 main epicardial coronary arteries. Although CAAs have been identified as a common underlying condition in young athletes with sudden cardiac death, the widespread use of invasive and noninvasive coronary imaging has led to increased recognition of CAAs among adults. CAAS are often discovered as an incidental finding during the diagnostic workup for ischemic heart disease. The clinical correlates and prognostic implication of CAAs remain poorly understood in this context, and guideline-recommended therapeutic choices are supported by a low level of scientific evidence. Several studies have examined whether assessment of CAA-related myocardial ischemia can improve risk stratification in these patients, suggesting that multimodality imaging and functional tests may be key in the management of CAAs. The aim of this review is to outline definitions, classification, and epidemiology of the most relevant CAAs, highlighting recent advances and the potential impact of multimodality evaluation, and to discuss current therapeutic opportunities. [ABSTRACT FROM AUTHOR]

Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk. [ABSTRACT FROM AUTHOR]

Background: Measuring fractional flow reserve (FFR) with a pressure wire remains underutilized because of the invasiveness of guide wire placement or the need for a hyperemic stimulus. FFR derived from routine coronary angiography (FFRangio) eliminates both of these requirements and displays FFR values of the entire coronary tree. The FFRangio Accuracy versus Standard FFR (FAST-FFR) study is a prospective, multicenter, international trial with the primary goal of determining the accuracy of FFRangio.Methods: Coronary angiography was performed in a routine fashion in patients with suspected coronary artery disease. FFR was measured in vessels with coronary lesions of varying severity using a coronary pressure wire and hyperemic stimulus. Based on angiograms of the respective arteries acquired in ≥2 different projections, on-site operators blinded to FFR then calculated FFRangio using proprietary software. Coprimary end points were the sensitivity and specificity of the dichotomously scored FFRangio for predicting pressure wire-derived FFR using a cutoff value of 0.80. The study was powered to meet prespecified performance goals for sensitivity and specificity.Results: Ten centers in the United States, Europe, and Israel enrolled a total of 301 subjects and 319 vessels meeting inclusion/exclusion criteria which were included in the final analysis. The mean FFR was 0.81 and 43% of vessels had an FFR≤0.80. The per-vessel sensitivity and specificity were 94% (95% CI, 88% to 97%) and 91% (86% to 95%), respectively, both of which exceeded the prespecified performance goals. The diagnostic accuracy of FFRangio was 92% overall and remained high when only considering FFR values between 0.75 to 0.85 (87%). FFRangio values correlated well with FFR measurements ( r=0.80, P<0.001) and the Bland-Altman 95% confidence limits were between -0.14 and 0.12. The device success rate for FFRangio was 99%.Conclusions: FFRangio measured from the coronary angiogram alone has a high sensitivity, specificity, and accuracy compared with pressure wire-derived FFR. FFRangio has the promise to substantially increase physiological coronary lesion assessment in the catheterization laboratory, thereby potentially leading to improved patient outcomes.Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique Identifier: NCT03226262. [ABSTRACT FROM AUTHOR]

Backgound: The inability to detect premature atherosclerosis significantly hinders implementation of personalized therapy to prevent coronary heart disease. A comprehensive understanding of arterial protein networks and how they change in early atherosclerosis could identify new biomarkers for disease detection and improved therapeutic targets.Methods: Here we describe the human arterial proteome and proteomic features strongly associated with early atherosclerosis based on mass spectrometry analysis of coronary artery and aortic specimens from 100 autopsied young adults (200 arterial specimens). Convex analysis of mixtures, differential dependent network modeling, and bioinformatic analyses defined the composition, network rewiring, and likely regulatory features of the protein networks associated with early atherosclerosis and how they vary across 2 anatomic distributions.Results: The data document significant differences in mitochondrial protein abundance between coronary and aortic samples (coronary>>aortic), and between atherosclerotic and normal tissues (atherosclerotic<Conclusions: The human arterial proteome can be viewed as a complex network whose architectural features vary considerably as a function of anatomic location and the presence or absence of atherosclerosis. The data suggest important reductions in mitochondrial protein abundance in early atherosclerosis and also identify a subset of plasma proteins that are highly predictive of angiographically defined coronary disease. [ABSTRACT FROM AUTHOR]

In patients with stable coronary artery disease, percutaneous coronary intervention is associated with improved outcomes if the lesion is deemed significant by invasive functional assessment using fractional flow reserve. Recent studies have shown that a revascularization strategy using instantaneous wave-free ratio is noninferior to fractional flow reserve in patients with intermediate-grade stenoses. The decision to perform coronary artery bypass grafting surgery is usually based on anatomic assessment of stenosis severity by coronary angiography. The data on the role of invasive functional assessment in guiding surgical revascularization are limited. In this review, we discuss the diagnostic and prognostic significance of invasive functional assessment in patients considered for coronary artery bypass grafting. In addition, we critically discuss ongoing and future clinical trials on the role of invasive functional assessment in surgical revascularization. [ABSTRACT FROM AUTHOR]

Background: Extracellular matrix (ECM) remodeling contributes to in-stent restenosis and thrombosis. Despite its important clinical implications, little is known about ECM changes post-stent implantation.Methods: Bare-metal and drug-eluting stents were implanted in pig coronary arteries with an overstretch under optical coherence tomography guidance. Stented segments were harvested 1, 3, 7, 14, and 28 days post-stenting for proteomics analysis of the media and neointima.Results: A total of 151 ECM and ECM-associated proteins were identified by mass spectrometry. After stent implantation, proteins involved in regulating calcification were upregulated in the neointima of drug-eluting stents. The earliest changes in the media were proteins involved in inflammation and thrombosis, followed by changes in regulatory ECM proteins. By day 28, basement membrane proteins were reduced in drug-eluting stents in comparison with bare-metal stents. In contrast, the large aggregating proteoglycan aggrecan was increased. Aggrecanases of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family contribute to the catabolism of vascular proteoglycans. An increase in ADAMTS-specific aggrecan fragments was accompanied by a notable shift from ADAMTS1 and ADAMTS5 to ADAMTS4 gene expression after stent implantation. Immunostaining in human stented coronary arteries confirmed the presence of aggrecan and aggrecan fragments, in particular, at the contacts of the stent struts with the artery. Further investigation of aggrecan presence in the human vasculature revealed that aggrecan and aggrecan cleavage were more abundant in human arteries than in human veins. In addition, aggrecan synthesis was induced on grafting a vein into the arterial circulation, suggesting an important role for aggrecan in vascular plasticity. Finally, lack of ADAMTS-5 activity in mice resulted in an accumulation of aggrecan and a dilation of the thoracic aorta, confirming that aggrecanase activity regulates aggrecan abundance in the arterial wall and contributes to vascular remodeling.Conclusions: Significant differences were identified by proteomics in the ECM of coronary arteries after bare-metal and drug-eluting stent implantation, most notably an upregulation of aggrecan, a major ECM component of cartilaginous tissues that confers resistance to compression. The accumulation of aggrecan coincided with a shift in ADAMTS gene expression. This study provides the first evidence implicating aggrecan and aggrecanases in the vascular injury response after stenting. [ABSTRACT FROM AUTHOR]

Introduction/Purpose: Many male marathon runners have elevated coronary artery calcium (CAC) scores despite high physical activity. We examined the association between CAC scores, cardiovascular risk factors, and lifestyle habits in long-term marathoners. Methods: We recruited men who had run one or more marathons annually for 25 consecutive years. CAC was assessed using coronary computed tomography angiography. Atherosclerotic cardiovascular disease risk factors were measured with a 12-lead ECG, serum lipid panel, height, weight, resting blood pressure and heart rate, and a risk factor questionnaire. Results: Fifty males, mean age 59 T 0.9 yr with a combined total of 3510 marathons (median = 58.5, range = 27-171), had a mean BMI of 22.44 T 0.4 kg⋅m-2, HDL and LDL cholesterols of 58 T 1.6 and 112 T 3.7 mg⋅dL-1, and CAC scores from 0 to 3153. CAC scores varied from 0 in 16 runners to 1-100 in 12, 101-400 in 12, and >400 in 10. There was no statistical difference in the number of marathons run between the four groups. Compared with marathoners with no CAC, marathoners with moderate and extensive CAC were older (P = 0.002), started running at an older age (P = 0.003), were older when they ran their first marathon (P = 0.006), and had more CAD risk factors (P = 0.005), and marathoners with more CAC had higher rates of previous tobacco use (P = 0.002) and prevalence of hyperlipidemia (P = 0.01). Conclusion: Among experienced males who have run marathons for 26-34 yr and completed between 27 and 171 marathons, CAC score is related to CAD risk factors and not the number of marathons run or years of running. This suggests that among long-term marathoners, more endurance exercise is not associated with an increased risk of CAC. [ABSTRACT FROM AUTHOR]

Background: Coronary artery calcium (CAC) is an established predictor of future major adverse atherosclerotic cardiovascular events in asymptomatic individuals. However, limited data exist as to how CAC compares with functional testing (FT) in estimating prognosis in symptomatic patients.Methods: In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain (or dyspnea) and intermediate pretest probability for obstructive coronary artery disease were randomized to FT (exercise electrocardiography, nuclear stress, or stress echocardiography) or anatomic testing. We evaluated those who underwent CAC testing as part of the anatomic evaluation (n=4209) and compared that with results of FT (n=4602). We stratified CAC and FT results as normal or mildly, moderately, or severely abnormal (for CAC: 0, 1-99 Agatston score [AS], 100-400 AS, and >400 AS, respectively; for FT: normal, mild=late positive treadmill, moderate=early positive treadmill or single-vessel ischemia, and severe=large ischemic region abnormality). The primary end point was all-cause death, myocardial infarction, or unstable angina hospitalization over a median follow-up of 26.1 months. Cox regression models were used to calculate hazard ratios (HRs) and C statistics to determine predictive and discriminatory values.Results: Overall, the distribution of normal or mildly, moderately, or severely abnormal test results was significantly different between FT and CAC (FT: normal, n=3588 [78.0%]; mild, n=432 [9.4%]; moderate, n=217 [4.7%]; severe, n=365 [7.9%]; CAC: normal, n=1457 [34.6%]; mild, n=1340 [31.8%]; moderate, n=772 [18.3%]; severe, n=640 [15.2%]; P<0.0001). Moderate and severe abnormalities in both arms robustly predicted events (moderate: CAC: HR, 3.14; 95% confidence interval, 1.81-5.44; and FT: HR, 2.65; 95% confidence interval, 1.46-4.83; severe: CAC: HR, 3.56; 95% confidence interval, 1.99-6.36; and FT: HR, 3.88; 95% confidence interval, 2.58-5.85). In the CAC arm, the majority of events (n=112 of 133, 84%) occurred in patients with any positive CAC test (score >0), whereas fewer than half of events occurred in patients with mildly, moderately, or severely abnormal FT (n=57 of 132, 43%; P<0.001). In contrast, any abnormality on FT was significantly more specific for predicting events (78.6% for FT versus 35.2% for CAC; P<0.001). Overall discriminatory ability in predicting the primary end point of mortality, nonfatal myocardial infarction, and unstable angina hospitalization was similar and fair for both CAC and FT (C statistic, 0.67 versus 0.64). Coronary computed tomographic angiography provided significantly better prognostic information compared with FT and CAC testing (C index, 0.72).Conclusions: Among stable outpatients presenting with suspected coronary artery disease, most patients experiencing clinical events have measurable CAC at baseline, and fewer than half have any abnormalities on FT. However, an abnormal FT was more specific for cardiovascular events, leading to overall similarly modest discriminatory abilities of both tests.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550. [ABSTRACT FROM AUTHOR]

Background: Despite the reduced incidence of coronary heart disease with intensive risk factor management, people with diabetes mellitus and prediabetes remain at increased coronary heart disease risk. Diabetes prevention interventions may be needed to reduce coronary heart disease risk. This approach was examined in the DPP (Diabetes Prevention Program) and the DPPOS (Diabetes Prevention Program Outcome Study), a long-term intervention study in 3234 subjects with prediabetes (mean±SD age, 64±10 years) that showed reduced diabetes risk with lifestyle and metformin compared with placebo over 3.2 years.Methods: The DPPOS offered periodic group lifestyle sessions to all participants and continued metformin in the originally randomized metformin group. Subclinical atherosclerosis was assessed in 2029 participants with coronary artery calcium (CAC) measurements after an average of 14 years of follow-up. The CAC scores were analyzed continuously as CAC severity and categorically as CAC presence (CAC score >0) and reported separately in men and women.Results: There were no CAC differences between lifestyle and placebo intervention groups in either sex. CAC severity and presence were significantly lower among men in the metformin versus the placebo group (age-adjusted mean CAC severity, 39.5 versus 66.9 Agatston units, P=0.04; CAC presence, 75% versus 84%, P=0.02), but no metformin effect was seen in women. In multivariate analysis, the metformin effect in men was not influenced by demographic, anthropometric, or metabolic factors; by the development of diabetes mellitus; or by use/nonuse of statin therapy.Conclusions: Metformin may protect against coronary atherosclerosis in prediabetes and early diabetes mellitus among men.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00038727. [ABSTRACT FROM AUTHOR]

Background: We previously described a strong association between fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection. Angiographic manifestations of coronary FMD aside from dissection were considered rare. However, we observed several coronary FMD angiographic abnormalities with corresponding optical coherence tomography abnormalities. Methods and Results: Baseline demographics and imaging of patients with suspected coronary FMD at Vancouver General Hospital were reviewed. Presence of multifocal (string-of-beads) extracoronary FMD was confirmed by 2 specialists. In these patients, coronary angiographic findings (excluding dissected segments) were reviewed and classified by 2 experienced angiographers for irregular stenosis, that is, stenosis with irregular borders in a focal or diffuse pattern with/without systolic accentuation; smooth stenosis, diffuse or focal; segmental dilatation/ectasia; and tortuosity. Optical coherence tomography was performed in a subset of patients. Of 32 patients with extracoronary FMD and suspected coronary involvement, 28 were women (88%), and their mean age was 59.4±9.9 years. Nineteen presented with myocardial infarction (13 caused by spontaneous coronary artery dissection), and 13 had stable symptoms. The observed coronary angiographic abnormalities included tortuosity in all cases (91% were moderate to severe), irregular stenosis in 59%, smooth stenosis in 19%, and segmental dilatation/ectasia in 56%. Fifteen patients had optical coherence tomography of the abnormal segments showing abnormalities, including multiple areas of patchy or diffuse intimal, medial or adventitial abnormalities with thickening/accumulation of varied reflectivities, macrophage infiltration, loss/duplication of elastic membranes, and cavitation. Conclusions: This is the first case series describing findings suggestive of angiographic and intracoronary manifestations of coronary FMD. Future studies should prospectively review these features in patients with extracoronary FMD. [ABSTRACT FROM AUTHOR]

Background: A well-developed coronary collateral circulation provides a potential source of blood supply in coronary artery disease. However, the prognostic importance and functional relevance of coronary collaterals is controversial with the association between exercise training and collateral growth still unclear.Methods and Results: This prospective, open-label study randomly assigned 60 patients with significant coronary artery disease (fractional flow reserve ≤0.75) to high-intensity exercise (group A, 20 patients) or moderate-intensity exercise (group B, 20 patients) for 4 weeks or to a control group (group C, 20 patients). The primary end point was the change of the coronary collateral flow index (CFI) after 4 weeks. Analysis was based on the intention to treat. After 4 weeks, baseline CFI increased significantly by 39.4% in group A (from 0.142±0.07 at beginning to 0.198±0.09 at 4 weeks) in comparison with 41.3% in group B (from 0.143±0.06 to 0.202±0.09), whereas CFI in the control group remained unchanged (0.7%, from 0.149±0.09 to 0.150±0.08). High-intensity exercise did not lead to a greater CFI than moderate-intensity training. After 4 weeks, exercise capacity, Vo2 peak and ischemic threshold increased significantly in group A and group B in comparison with group C with no difference between group A and group B.Conclusions: A significant improvement in CFI was demonstrated in response to moderate- and high-intensity exercise performed for 10 hours per week.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01209637. [ABSTRACT FROM AUTHOR]

The article discusses coronary artery calcification (CAC), a direct measure of coronary atherosclerosis, as well as cardiorespiratory fitness (CRF) as strong predictors of future cardiovascular events. Other information about higher levels of CRF which are linked with decreased cardiovascular events across the spectrum of CAC scores is presented.

Background--Impaired vasodilator function is an early manifestation of coronary artery disease and may precede angiographic stenosis. It is unknown whether noninvasive assessment of coronary vasodilator function in patients with suspected or known coronary artery disease carries incremental prognostic significance. Methods and Results--A total of 2783 consecutive patients referred for rest/stress positron emission tomography were followed up for a median of 1.4 years (interquartile range, 0.7-3.2 years). The extent and severity of perfusion abnormalities were quantified by visual evaluation of myocardial perfusion images. Rest and stress myocardial blood flows were calculated with factor analysis and a 2-compartment kinetic model and were used to compute coronary flow reserve (coronary flow reserve equals stress divided by rest myocardial blood flow). The primary end point was cardiac death. Overall 3-year cardiac mortality was 8.0%. The lowest tertile of coronary flow reserve (<1.5) was associated with a 5.6-fold increase in the risk of cardiac death (95% confidence interval, 2.5-12.4; P<0.0001) compared with the highest tertile. Incorporation of coronary flow reserve into cardiac death risk assessment models resulted in an increase in the c index from 0.82 (95% confidence interval, 0.78-0.86) to 0.84 (95% confidence interval, 0.80-0.87; P = 0.02) and in a net reclassification improvement of 0.098 (95% confidence interval, 0.025-0.180). Addition of coronary flow reserve resulted in correct reclassification of 34.8% of intermediate-risk patients (net reclassification improvement=0.487; 95% confidence interval, 0.262-0.731). Corresponding improvements in risk assessment for mortality from any cause were also demonstrated. Conclusion--Noninvasive quantitative assessment of coronary vasodilator function with positron emission tomography is a powerful, independent predictor of cardiac mortality in patients with known or suspected coronary artery disease and provides meaningful incremental risk stratification over clinical and gated myocardial perfusion imaging variables. [ABSTRACT FROM AUTHOR]

Objectives: Inflammation has been reported as an important component of vascular aneurysm formation, as found in obstructive vascular disorder. Neopterin is produced by activated macrophages and is thought to represent a marker of immune activation and macrophage activity. The plasma neopterin levels were investigated .in coronary artery ectasia (CAE) patients to investigate the role of inflammation. Study Design: The study population consisted of three groups: the first consisted of 28 patients with isolated CAE without stenotic lesion; the second of 27 patients with obstructive coronary artery disease (O-CAD) without CAE; and the third group of 15 control subjects with normal coronary arteries (NCA). Plasma soluble neopterin levels were measured in all patients and control subjects using commercially available enzyme-linked immunosorbent assay kits. Results: Plasma neopterin levels were found to be significantly higher in patients with isolated CAE compared with control subjects with angiographically NCA (18.5 ± 8.8 versus 8.7 ± 2.6 nmol/L, respectively, P = 0.006). Although neopterin levels were higher in patients with CAE than in patients with O-CAD, they did not reach the statistically significant levels (18.5 ± 8.8 versus 16.8 ± 8.2 nmol/L, respectively, P = 0.77). Patients with O-CAD had significantly higher levels of neopterin compared with subjects with angiographically NCA (16.8 ± 8.2 versus 8.7 ± 2.6 nmol/L, respectively, P = 0.03). The mean serum neopterin levels in patients with single-vessel, two-vessel, and diffuse ectasia were as follows: 17.4 ± 9.9 nmol/L, 19.5 ± 8.9 nmol/L, and 20 ± 5.5 nmol/L, respectively (P = 0.4). Conclusion: Patients with isolated CAE have raised levels of neopterin compared with patients with NCA, showing the possible role of inflammatory processes (monocyte/macrophage activity) in the higher levels of neopterin in patients with O-CAD. [ABSTRACT FROM AUTHOR]

Objectives: Adverse behavioral profiles, particularly depression and hostility, increase the risk of coronary artery disease (CAD) and affect recovery after CAD events. We sought to determine the effects of outpatient phase II cardiac rehabilitation and exercise training (CRET) programs in CAD patients with high levels of psychological distress. Methods: We studied 500 consecutive patients both before and after phase II CRET programs and compared 109 patients with the highest quintile of psychological distress (HD) with 115 patients with the lowest quintile of psychological distress (LD). Results: At baseline, patients with HD were younger (P < 0.00 1), had higher weight (+ 11%; P < 0.00 1), body mass indices (BMI) (+9%; P < 0.01), triglycerides (+66%; P < 0.0001), and glycosylated hemoglobin (+ 9%; P = 0.03), and had higher scores for depression, hostility, anxiety, and somatization (all P < 0.0001), but had lower values for exercise capacity(- 15%; P = 0.02), high-density lipoprotein (HDL) cholesterol (- 10%; P < 0.01), and total quality of life (QoL) (-26%; P < 0.0001), and all 6 major components of QoL compared with LD. After CRET, patients with HD had significant reductions in weight (-2%; P < 0.01), % fat (-6%; P < 0.001), BMI (-2%, P < 0.01), and scores for anxiety (-49%), depression (-47%), somatization (-34%) and hostility (-38%) (all P < 0.000 1), and increases in exercise capacity (+54%; P <0.0001), HDL cholesterol (+ 10%; P < 0.0001), and total Q0L (+23%; P < 0.000 1), and the 6 components of QoL studied. Compared with patients with LD, those with HD had statistically greater improvements in HDL (P = 0.03), triglycerides (P = 0.03), BMI (P = 0.02), as well as all behavioral characteristics and QoL (P < 0.0001), and had similar improvements in all other factors assessed. Conclusions: These data support the routine assessment of high-risk behavioral characteristics in patients with CAD and demonstrate the marked improvements that occur after phase IT CRET programs in CAD patients with high psychological distress. [ABSTRACT FROM AUTHOR]

Coronary artery disease is the number 1 killer of Americans. There are many efforts underway to prevent and treat this life-threatening disease. One such treatment is the placement of drug-eluting stents. However, recent reports that show an increased risk of potentially life-threatening complications associated with drug-eluting stents have surfaced. This article provides a brief overview of research performed concerning the risks of drug-eluting stents. [ABSTRACT FROM AUTHOR]

The article discusses a study by De Rosa and colleagues, which examined whether or not circulating miRNAs associated with cardiovascular disease (CVD) remains unclear in many cases. The research found that circulating levels of cardiomyocyte-enriched miR-499, miR-133a, and miR-208 are elevated. They were also found to correlate with troponin level in patients with troponin-positive acute coronary syndrome (ACS) compared with patients with coronary artery disease.

Introduction: Sudden cardiac arrest (SCA) is often associated with coronary artery disease (CAD). However, the specific nature and patterns of coronary lesions and ischemia require more investigation. Objective: In this case control study, we evaluated coronary artery lesion characteristics associated with SCA from a novel digital coronary angiography archive of consecutive SCA cases. Methods: From a large, prospective ongoing community-based study of SCA in the Northwestern United States, we identified 58 cases with CAD who had digital angiograms (81% in the peri-arrest period, age ≥18, 2002 to 2014). These cases were compared to angiograms in control subjects with a history of CAD without SCA, from the same population. We performed quantitative coronary analysis (QCA) in these angiograms and defined significant CAD as a vessel diameter stenosis of ≥50% and severe CAD as a vessel diameter stenosis ≥70%. Anatomic location was reported using the AHA 15 segment coronary model, with TIMI flow grade assessed for each stenosis. Results: We analyzed 317 angiograms: 58 SCA cases and 259 controls. CAD burden was higher in cases as assessed by the total number of segments with disease ≥70% (p=0.04). Left anterior descending artery (LAD) disease was more prevalent in cases with ≥50% LAD stenosis in 37 (64%) cases and 118 (46%) controls (p=0.01). This also held true with severe LAD disease with LAD stenosis ≥70% in 25 (43%) cases and 65 (25%) controls (p=0.006). Proximal LAD disease was also more common in cases, being present in 14 (24%) cases and 36 (14%) of controls (p=0.053). LAD flow limiting lesions were more common in cases as demonstrated by reduced TIMI flow in 17 (29%) cases and 36 (14%) controls (p=0.005). Flow limiting lesions in the left circumflex artery were present in more cases as well with reduced TIMI flow in 9 (16%) cases and 17 (7%) of controls (p=0.03). There were no significant differences in left main or RCA disease. Conclusion: CAD is common in SCA. In our study, we show that in particular, LAD disease by multiple measures is involved in SCA pathophysiology. Further investigation is needed to clarify mechanisms behind these findings and identify the highest risk coronary lesions that should undergo pre-emptive management to avert SCA. [ABSTRACT FROM AUTHOR]

Introduction: Guidelines recommend using pretest probability risk assessment to direct the diagnostic approach for coronary artery disease (CAD), but the best model for routine clinical use is unclear and national organizations provide different recommendations on which model to use. We sought to externally validate prediction models for obstructive CAD in a contemporary, real world population. Methods: Between June 2014 and June 2016, 727 symptomatic subjects (age 40-90 years without known CAD) referred for CAD evaluation underwent calcium scoring and coronary computed tomography angiography (CCTA). Obstructive CAD was defined as ≥50% stenosis on CCTA. Pretest probabilities for obstructive CAD were calculated using published coefficients for modified Diamond-Forrester (DF; age, sex, angina characteristic), CAD Consortium Basic (age, sex, angina characteristic), Clinical (Basic + diabetes, hypertension, dyslipidemia, smoking), and Extended (Clinical + coronary artery calcium score) models. Models were evaluated using C-statistics, calibration plots, and reclassification. Results: Median (5-95th percentile) age was 59.0 (44.9-76.0) years with 54% males. C-statistics were modified DF 0.677 (95% confidence interval: 0.617-0.734), CAD Basic 0.692 (0.632-0.747), Clinical 0.723 (0.669-0.774), and Extended 0.851 (0.813-0.886). Calibration was similar for the Clinical and Extended models. The Extended model classified the most subjects as low risk (390 with 9 having obstructive CAD) followed by Clinical (305 with 15 having obstructive CAD) and Basic (287 with 17 having obstructive CAD). The Extended model had comparable sensitivity and higher specificity (91% and 60%, respectively) to the Clinical (85% and 46%), Basic (82% and 43%), and modified DF (98% and 5%) models. Conclusions: The CAD Consortium Extended model incorporating coronary artery calcium score demonstrated improved discrimination and specificity for obstructive CAD, with comparable calibration and sensitivity. As compared to the Basic and Clinical models, the Extended model also classified the largest percentage of individuals as low risk, potentially sparing similar patients from further noninvasive and invasive testing. [ABSTRACT FROM AUTHOR]

Introduction: Atherosclerosis is a chronic inflammatory disease in the arterial wall. The ratio of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) to total fatty acids (FA), termed omega-3 FA index, predicts cardiovascular outcomes. EPA and DHA are precursors of specialized pro-resolving lipid mediators (SPMs) - resolvins (Rv) and maresins (MaR) - which resolve chronic inflammation. Objective: To examine the relationship between levels of EPA, DHA, SPMs and proinflammatory lipid mediators (LM) and coronary plaque progression. Methods: A total of 240 subjects with CAD on statins were randomized to 3.36 g of EPA and DHA daily or control for 30 months. Coronary plaque volume was measured by coronary computed tomographic angiography. Levels of SPMs and LMs - leukotriene B4(LTB4) and prostaglandin E2and D2- were measured with liquid chromatography-tandem mass spectrometry in the top and bottom 6% of subjects stratified by omega-3 FA index. Results: Levels of two SPMs, RvE1 and MaR1, were significantly higher in those with a high omega-3 FA index (median 8.4%) compared to a low index (median 2.4%). Those with a low omega-3 FA index had a low ratio of MaR1/LTB4and significant progression of all plaque subtypes (Table). Those with a high omega-3 FA index fell into two groups based on regression or progression of coronary plaque. Those with a high omega-3 FA index and low MaR1/LTB4ratio (median, 0.2 [IQR, 0.1 - 0.4]) had significant progression of fatty, fibrous, noncalcified and total plaque whereas those with a high omega-3 index and high MaR1/LTB4ratio (median, 2.3 [IQR, 0.5 - 2.7]) had significant regression of fatty, fibrous and noncalcified plaque. The MaR1/LTB4ratio was the strongest predictor of plaque change (r= -0.606, p = 0.001). Conclusions: A deficiency of SPMs and low ratio of MaR1/LTB4predict coronary plaque progression and suggest that an imbalance of proinflammatory to pro-resolving lipid mediators contributes to progression of coronary plaque. [ABSTRACT FROM AUTHOR]

Introduction: When patients present with anginal symptoms, functional stress testing (FST) is often used to detect myocardial ischemia and to guide treatment. However, because FST is not perfect, patients with high prior probabilities of disease may not benefit from it. Coronary artery calcium scores (CAC) indicate atherosclerosis burden and predict future major adverse cardiovascular events (MACE). Whether very high CAC may affect the utility of FST is unknown. Methods: We studied symptomatic patients with no history of coronary artery disease (CAD) sent for a functional stress PET/CT who had a CAC >1000 (n=279). Baseline demographics and clinical characteristics were collected, and patients were stratified between those with a low versus a medium or high PET/CT functional risk assessment (FRA). Patients were followed for 1 year for the endpoints of coronary angiography within 60 days, high-grade CAD (HGCAD), all-cause death, MACE (myocardial infarction or cardiovascular death), and the composite endpoint of HGCAD/MACE. Results: FRA for all patients (age = 69.8±10.0 years, males = 73.5%, diabetes = 43.4%, smoking history = 39.4%) was low, medium, and high-risk in 203 (72.8%), 53(19.0%) and 23 (8.2%), respectively. Overall one-year HGCAD/MACE was 66 (23.7%). Baseline clinical characteristics did not differ between those with and without HGCAD/MACE. Functional PET/CT results, including stress EF, myocardial blood flow, and ischemic burden, differed significantly between those with and without HGCAD/MACE. While a majority of those with HGCAD/MACE were assessed as medium/high risk, still 29% of all HGCAD/MACE, and 58% of all cardiovascular deaths came from the low risk group, and 12/14 (86%) of the patients with low FRA who received coronary angiography had HGCAD. Conclusions: Almost one quarter of all symptomatic patients with CAC score >1000 were found to have high-grade obstructive CAD or a MACE within 1-year, and nearly one third of those had an initial low-risk assessment through functional PET/CT. The very high prior probability of HGCAD/MACE among those with extremely high CAC scores may render functional testing less effective. Direct referral to coronary arteriography in this high-risk group, when appropriate, may perhaps be considered. [ABSTRACT FROM AUTHOR]

Background: Coronary artery calcification (CAC) is a major limitation of the diagnostic performance of coronary computed tomography angiography (CCTA). Coronary computed tomography derived fractional flow reserve (CT-FFR) is a novel noninvasive and diagnostic modality to diagnose coronary artery disease (CAD). However, little is known about the extent to which the severity of CAC affects the diagnostic performance of CT-FFR. We investigated the diagnostic accuracy of CT-FFR for detecting CAD by CAC severity. Methods: We enrolled consecutive 64 patients (mean age: 74 ± 8 years, 38 male) suspected CAD who received 320-row CCTA and coronary angiography (CAG) and evaluated 169 major vessels. CCTA was scanned at diastole in 70-99% of the R-R interval. CT-FFR was analyzed by Vitrea workstation (Canon Medical Systems). Experienced cardiologists assessed all scans and evaluated major vessels with a diameter > 2mm. CCTA > 50% stenosis or CT-FFR < 0.80 were considered obstructive. CAD was defined as quantitative CAG (QCA) > 50% stenosis. Furthermore, CAC was assessed by non-contrast enhanced cardiac CT using the total Agatston score (median, 392; interquartile range, 128 -1068). The study population was divided into 3 groups based on tertiles of Agatston scores (mild, <171; moderate, 171-653; severe, >653). Results: There was no significant difference of the diagnostic accuracy for the detection of CAD between CCTA and CT-FFR in the mild and moderate CAC groups. In the severe CAC group, the sensitivity, specificity, accuracy, positive predict value and negative predict value of CCTA and CT-FFR were 94%, 37%, 56%, 42% and 93% versus 94%, 69%*, 77%*, 59%* and 96% (* P <0.05), respectively. The area under the ROC curve for CT-FFR was significantly higher compared with that for CCTA (0.87 vs 0.67; P = 0.02). Conclusions: In the patients with severe CAC, novel CT-FFR provided a high diagnostic accuracy for the detection of CAD. [ABSTRACT FROM AUTHOR]

Introduction: Our group has shown the Wnt-pathway to be a key regulator of SMC function and to be expressed in human coronary atheroma. Dickkopf-related protein 1 (DKK-1) is a member of the Wingless (Wnt) signaling pathway molecules and has recently been shown to improve GRACIE-risk factor score prediction of coronary events in chest pain patients and to predict restenosis post coronary stenting. We tested its association with coronary plaque burden and cardiovascular risk factors in comparison with CRP-1; Hypothesis: DKK-1 may be associated with coronary artery plaque burden and cardiovascular risk factors and play a role in coronary artery disease through modulation of SMC. Methods: 218 patients with angiographic evidence of CAD (mildly obstructive CAD, n=35; obstructive stable CAD, n=154; unstable CAD, n=29) were enrolled in this study at the time of cardiac catherization. DKK-1 and CRP-1 were measured by ELISA. Data are shown as Mean p SEM. Values of DKK-1 and CRP1 were skewed, so non-parametric tests were used to determine the associations between DKK-1 and CRP-1 with Syntax Score, age, BMI, LDL, HDL, and HgbA1c.. Spearman's Rank Order Correlation, Wilcoxon Rank Sum Test, and analysis of variance (ANOVA) were used to assess associations. Results: Data are shown as Mean p SEM.Variables were as follows: DKK-1 736 pg/ml p 129, CRP-1 0.108 mg/ml p 0.01, age 66 years p 1, BMI 32 p 0.5, LDL 97 p 3, HDL 46 p 2, HgbA1C 6.5 p 0.2, Syntax score 11 p 0.7. With DKK-1 the only statistically significant correlation observed was between DKK-1 and HgbA1c (r=0.18, P<0.05). There was no association between DKK-1 and CRP-1, Syntax Score, Age, BMI, LDL, and HDL. With CRP-1, however, we observed significant positive correlations with Syntax Score (r=0.2, P<0.05), BMI (r=0.18, P<0.05), LDL (r=0.18, P<0.05) and significant negative correlation with age (r= -0.19, P<0.05) and with HDL (r=-0.18, P<0.05). There was no association between CRP-1 and HDL as well as HgbA1c. Conclusions: In patients with angiographically established CAD DKK-1 in contrast to CRP-1 is not a predictor of coronary plaque burden and has as only significant association a positive correlation with HgbA1c. Our data suggest that the reported role of DKK-1 in coronary event risk and in restenosis might be related to Diabetes mediated effects. [ABSTRACT FROM AUTHOR]

Aim: To investigate if estimation of the amount of calcium in the coronary system utilizing a visual coronary artery calcium scoring (CACS) system (Kirsch et al. Detection of coronary calcium during standard chest computed tomography correlates with multi-detector computed tomography coronary artery calcium score) in non - electrocardiogram (ECG) gated chest computed tomography (CT) scans maintains its strong correlation with the Agatston CACS on dedicated ECG gated cardiac CT exams across two or more points in time per patient. Methods: A visual scoring system (Weston score, WCS) was previously developed assigning a score (0-3, total score 0-12) for each coronary vessel including the left main trunk. Predetermined score cutoffs in both Agatston and Weston scoring methods were designated for risk stratification. Following institutional review board approval, we retrospectively analyzed 127 total body CT scans on 53 low-risk patients referred by executive health who had received repeat CT scans between 2007 and 2018 and compared the traditional Agatston CACS with the Weston score. Analysis: The data were gathered from a total of 53 executive health patients ages 33 to 71, with an average age of 51. 83.6% were male and 16.4% were female. 118 scans were examined, taken between 307 and 2,792 days apart, with an average of 937 days between scans. The Weston and Agatston scores predicted the same risk classification for 79.7% of the first set of scans, with 10.2% uprisked and 10.2% downrisked by their Weston scores. For the second set of scans, 78.0% had the same classification, with 10.2% uprisked and 11.9% downrisked by their Weston scores. Weston scores predicted 100% of scans within one risk classification of the corresponding Agatston score across all pairs of scans.The average CACS utilizing the Agatston scoring method was 54.3, with a standard deviation of 148.6 due to a large positive skew in the data. The corresponding Weston scores had an average of 1.1, with a standard deviation of 2.14. Conclusion: A visual CACS system (WCS) performed on non-gated CT scans allows risk stratification for cardiac events in a similar manner as the Agatston CACS on ECG-gated CT scans even at separate points in time. [ABSTRACT FROM AUTHOR]

Background: Coronary computed tomography angiography (CCTA) is a noninvasive imaging modality to detect coronary artery disease (CAD), however, the diagnostic accuracy of CCTA is constrained because of high false-positive rates. Recently, fractional flow reserve derived CCTA has been reported feasible for CAD detection. We investigated the diagnostic accuracy of computed tomography fractional flow reserve (CT-FFR) using fluid structure interactions for CAD compared with CCTA. Methods: Consecutive 174 major vessels in 64 patients (mean age: 74 ± 8 years, 38 male) with suspected CAD who received 320-row CCTA and coronary angiography (CAG) within 90 days were enrolled. The vessels with stent were excluded from the analysis. CCTA was scanned at diastole in 70-99% of the R-R interval. CT-FFR was analyzed by Vitrea workstation (Canon Medical Systems). Experienced cardiologists assessed all scans and evaluated major vessels with a diameter >2mm. CCTA > 50% stenosis or CT-FFR < 0.80 were considered obstructive. CAD was defined as quantitative CAG (QCA) > 50% stenosis. Results: CT-FFR was successfully calculated in 169 of 174 vessels (97%). Of 169 vessels, CT-FFR was calculated of all vessels in the proximal segment, 148 (88%) in the mid segment, and 77 (46%) in the distal segment. Overall, the sensitivity, specificity, and accuracy of CCTA and CT-FFR to detect CAD were 96%, 71% and 75% versus 92%, 83%* and 85%* (* P <0.05), respectively. There was no significant difference of the diagnostic performance for CAD between CCTA and CT-FFR in the right coronary artery (100%, 74% and 77% versus 100%, 85% and 87%), left anterior descending artery (100%, 60% and 70% versus 92%, 78% and 81%), and left circumflex artery (80%, 76% and 77% versus 80%, 86%, and 86%), respectively. Conclusion: CT-FFR improved the specificity and accuracy of detecting for CAD compared with CCTA. [ABSTRACT FROM AUTHOR]

Introduction: Optical coherence tomography (OCT) is thought to be capable of identifying lipid-rich plaque (LRP). However, several histopathological correlative studies have shown that LRP assessment by OCT alone may be indecisive for identifying advanced plaque containing a necrotic core. This study aims to investigate the feasibility of multi-modality OCT-near-infrared autofluorescence (NIRAF) imaging to identify advanced necrotic-core LRP. Methods: We constructed a new fully integrated multi-modality OCT-NIRAF imaging system and catheter that allows simultaneous and co-registered acquisition of OCT and NIRAF data. NIRAF excitation was 635nm and emission was collected between 690-750nm. OCT-NIRAF pullback imaging was performed with excised human cadaver coronary arteries during saline perfusion. Subsequently, H&E sections were obtained and co-registered (longitudinally and azimuthally) with corresponding OCT-NIRAF images, using the known pullback distances, and anatomic landmarks and features such as calcium nodules seen in the OCT and histopathology images. In addition, a bench top confocal microscope was used to obtain images of NIRAF on corresponding unstained, formalin-fixed, paraffin-embedded slides. Results: A total of 187 histopathological sections and corresponding OCT-NIRAF images from 13 cadaver coronary arteries from 5 patients were imaged and analyzed. Several LRP that were identified by histopathology in these arteries showed regions with evidence of necrotic core with hemosiderin granules that had significantly higher catheter-based NIRAF than regions without hemosiderin granules. Confocal NIRAF microscopy also showed that regions of high NIRAF were associated with accumulation of hemosiderin in corresponding histological sections. Conclusions: This study provides suggestive data that an integrated OCT-NIRAF imaging system and catheter may be able to be used to identify advanced LRP that contains a necrotic core with hemosiderin granules. Future investigation of NIRAF from cadaver arteries from additional patients is merited to robustly confirm these findings. [ABSTRACT FROM AUTHOR]

Introduction: Data-driven guidelines for the optimal medical and interventional management of cancer patients according to the primary malignancy are absent. Hypothesis: We aimed to assess whether specific malignancies and their treatments (chemotherapy, radiation) can modify the natural progression of coronary artery disease (CAD) and lesion location. Methods: From April 2008 to February 2018, cancer and non-cancer patients from a high-volume onco-cardiology center and a tertiary cardiology center, respectively, who underwent coronary angiography (CA) for any indication were enrolled. Baseline demographics, current and prior CA findings, and cancer status and treatment were collected. Neural network machine learning supported multivariable regression of CAD (left main [LM], left anterior descending [LAD], right coronary artery [RCA], and left circumflex [LCx]) according to the primary malignancy. Results: We included 480 patients who underwent coronary angiography, of which 240 (50%) had cancer. Mean age was 63.87 ± 11.69 years and 34.79% of patients were women. The main indications for CA were chest pain (30.00%), abnormal stress test (23.96%), and prior coronary artery disease (18.75%), with 35.08% having a prior percutaneous coronary intervention (PCI) and 5.63% having post-PCI referral for CABG. In multivariable regression, patients with lung cancer compared to those without this malignancy had higher odds of significant LAD (OR 5.19, 95%CI 1.13-23.80, p=0.034) and RCA (OR 9.92, 95% CI 1.99-49.32, p=0.005) stenoses, but not of LM or LCx stenoses, even after controlling for age, peripheral artery disease, dyslipidemia, diabetes, platelet number, and triglycerides. Hematological malignancies, breast cancer, and prostate cancer did not have independent associations with any particular vessel. Conclusions: This innovative machine learning and statistical analysis suggests that particular cancer types can impact lesion severity in specific coronary vessels, potentially altering management. [ABSTRACT FROM AUTHOR]

Background: Larger epicardial plaque burden (PB) and coronary microvascular endothelial dysfunction (CMED) have both been associated with major adverse cardiovascular events (MACE). However, the relationship between PB and CMED remains unknown. Methods: 148 patients with chest pain, referred for evaluation of coronary vasomotion and found to have angiographically normal coronary arteries or mild coronary artery disease (CAD) [<40% stenosis], underwent acetylcholine (Ach) assessment of CMED (defined as coronary blood flow [CBF] change <50% post ACh) and gray-scale intravascular ultrasound (IVUS) imaging of the left anterior descending artery for evaluation of vessel-averaged epicardial plaque area (PA) and PB (PB: PA/vessel area x 100). Results: Baseline clinical characteristics were not significantly different between patients with (n=87, 58.8%) vs. those without CMED (n=61, 41.2%). We observed a significant inverse linear relationship between both IVUS segment-level PA and PB with CBF (Figure). Patients with CMED had significantly higher averaged epicardial PA and PB (Figure). Hypertension (β=0.179, p=0.027 for PA and β=0.166, p=0.036 for PB), hyperlipidemia (β=0.26, p=0.001 for PA and β=0.311, p<0.001 for PB), and CMED (β=0.189, p=0.017 for PA and β=0.20, p=0.01 for PB) were independent predictors of larger PA and higher PB after adjusting for age, sex, hypertension, hyperlipidemia, diabetes mellitus, smoking and CMED. Conclusion: Coronary microvascular endothelial dysfunction is an independent predictor of larger epicardial PA and higher PB in patients with non-obstructive CAD. [ABSTRACT FROM AUTHOR]

Introduction: Coronary artery calcium (CAC) is considered as an adverse cardiovascular events predictor. However, its prognostic impact on heart failure with preserved ejection fraction (HFpEF) patients in the absence of coronary artery disease history (CAD Hx) remains unclear and that is what we aimed to evaluate. Methods: In this cohort, we queried our institutional HF database and identified 249 patients with a new HFpEF diagnosis during 2006 who had CT coronary calcium score within 12 months of admission. Average follow up was 10 years (10.2±2.3). CAC Agatston score of >100 was considered significant. Measured outcomes were cardiovascular disease (CVD) mortality and HF re-admissions (poor outcome was defined as ≥2 HF re-admissions in 12 months) Results: Women constituted 56.6%. CAD Hx was documented in 124 patients , 70 patients had neither CAD Hx nor CAC, and 55 patients had no CAD Hx but demonstrated CAC score >100 on CT. Mean age was 72.1±13.4 years. The CVD mortality rate for patients with CAD Hx was relatively similar to those without CAD Hx but significant CAC, 25% and 23.6%, respectively. However, the CVD mortality rate for those with neither CAC nor CAD Hx was only 7.1% (p=0.008). Poor outcome was identified in 54.5% of patients with CAC and in 44.3% of those with no CAC (p=0.25). Only 36.4% of patients with CAC and no CAD Hx were on optimal therapy. Conclusions: In HFpEF patients, the presence of CAC >100 is significantly associated with CVD mortality despite the absence of CAD hx. Accordingly, screening for CAC in HFpEF patients should be considered for detecting those at risk for CVD mortality and to aid in optimizing medical therapy. [ABSTRACT FROM AUTHOR]

Introduction: Kawasaki disease (KD), which is the most common multisystem vasculitis with unknown causes in childhood, causes coronary artery aneurysms (CAAs). Infliximab (IFX), anti-human TNF-α monoclonal antibody, is one of the additional treatment of severe KD patients who are resistant to intravenous immunoglobulin (IVIG). However, the newly developed CAAs still occur in 10% of IFX treated patients. Nuclear factor (NF)-kappa B activation is strongly involved with the source of inflammatory substances production, including TNF-α, interleukins, chemokines, and the receptors for these cytokines, in vascular endothelial cells. Hypothesis: A NF-kappa B inhibitor prevents coronary arteritis (CA) in KD patients through the tests on an animal model. Methods: A Candida albicans cell wall extract (CAWE)-induced KD-like vasculitis model was established in DBA/2 mice. Custom-made Peptide YMAPdEV (Tyr-Met-Ala-Pro-dGlu-Val) 0.25mg/0.5ml was injected intraperitoneally on the first, third, and fifth days (NF-kappa B group, n=6). We compared the incidence of CA between the NF-kappa B group and the placebo group (n=6) four weeks after insertion of the NF-kappa B inhibitor. Histological analysis was performed by using a quantified scoring system: grade 1; &lt20 cells /HPF, grade 2; &lt100cells/HPF, grade 3; &gt100cels/HPF, grade 4; distraction of elastic lamina, grade 5; neointimal proliferation. Results: One mouse in the placebo group died within two days after CAWE administration. Therefore, histological analyses were performed in the eleven remaining mice (six in the NF- kappa B group, five in the placebo group). Four of five mice in placebo group (80%) had the infiltration more than grade 3. In contrast, only one mouse of six mice (17%) in NF- kappa B group had the infiltration more than grade 3. Treatments utilizing the NF-kappa B inhibiter significantly suppressed vasculitis induced by CAWE (p &lt0.01). Conclusions: A NF-kappa B inhibitor prevents the development of CA in a Candida -induced KD mouse model. NF-kappa B may be a therapeutic target for preventing coronary artery inflammation in all cascades and controlling the formation of CAAs in KD patients. [ABSTRACT FROM AUTHOR]

Introduction: Breast arterial calcification (BAC), seen on mammograms, has emerged as a potential risk stratification tool and surrogate marker of cardiovascular disease (CVD) that comes with no additional cost or radiation. However, measurement of BAC can be imprecise and time consuming. Hypothesis: We measured BAC using an automated, quantitative method developed by CureMetrix, Inc. and assessed the hypothesis that BAC is significantly associated with coronary artery calcium (CAC). Methods: This single-center, retrospective study included 293 women (mean age 62 ± 11 years) who had both digital mammography and CAC assessment by coronary computed tomographic (CT) scan within one year of each other. BAC scores were computed by an algorithm and compared with CAC, defined by Agatston score. Results: Among the 293 women, 23% had diabetes, 29% were current or former smokers, 54% had hypertension, 53% had hyperlipidemia, and 15% had a family history of premature CVD. BAC was detectable in 79 women (27%), and CAC was present in 143 (49%). BAC scores were significantly correlated with CAC Agatston scores (r=0.38, p<0.001). Overall, BAC had a positive predictive value (PPV) of 77% for presence of CAC and a specificity of 88%. Among women under 60 years of age, the PPV was 75% with a specificity of 95% (TABLE). BAC score was independently associated with the presence of CAC after adjusting for age, HTN, diabetes, smoking, LDL and HDL-cholesterol, and renal function (odds ratio per standard deviation increase in lgBAC 1.66 [1.18-2.23], p=0.04). Conclusions: BAC is significantly associated with CAC with a high specificity, especially among younger women in whom the presence of CAC may be more concerning. BAC may be useful for identifying women at increased risk of CVD who merit aggressive prevention measures. Clinical application will require prospective studies with hard cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Acute myocardial ischemia and infarction diagnosis is traditionally based on clinical (e.g. pain) and ECG criteria. Other advanced diagnostic techniques have limitations including invasiveness, radiation exposure, time to receive and analyze data, or cost. We recently showed (Pahlevan et al. Critical Care Medicine ,2017 PMID: 28441235) that the intrinsic frequency (IF) method (a systems-based approach), can be used to monitor left ventricle (LV) ejection fraction from a standard iPhone. Utilizing the IF method, one can extract two intrinsic frequencies (ω1 and ω2) from an arterial pressure waveform. ω1 is IF of the coupled LV-arterial system during systole. Since one of the first hemodynamic abnormalities to occur within seconds of coronary artery occlusion is a sudden decrease in LV contractile performance, we propose that ω1 (measured from the carotid waveforms) captures the changes in the dynamics of LV shortly after acute myocardial infarction (MI). Methods: We used animal models of Female Sprague Dawley rats (n=9, body weight ≈200 g). Catheters were inserted into carotid artery for pressure waveform measurement. Proximal left coronary occlusions were performed for 30 minutes to ensure infarction and necrosis. The coronaries were then reperfused for several hours hour. ω1 values were computed from carotid waveforms 2 hours after reperfusion. Results: Our results (figure) show a significant and acute change in ω1 (50 bpm reduction) before and after imposed myocardial infarctions (p= 0.0001). Conclusions: Our results suggest that ω1, which can also be obtained instantaneously from an iPhone, can detect acute changes in the dynamic of LV contraction after acute MI, and has the potential to provide noninvasive assessment of LV function using an iPhone in the setting of acute MI. This can be clinically significant since the first few hours of an acute MI is critical as mortality can be significantly reduced if therapy is initiated in this acute window. [ABSTRACT FROM AUTHOR]

Background: Optimal treatment approach for spontaneous coronary artery dissection (SCAD) remains unclear. Objectives: The study aims to compare in-hospital and long-term clinical outcomes of SCAD patients initially managed with medical therapy (conservative approach) versus percutaneous coronary intervention or coronary artery bypass grafting (revascularization approach) based on published data. Methods: We identified relevant studies by performing a systematic search in the Ovid MEDLINE® and Embase database. Studies that report in-hospital outcomes (death, myocardial infarction [MI], and urgent revascularization) or long-term outcomes (death, MI, target vessel revascularization [TVR], SCAD recurrence, and heart failure [HF]) were included and case reports were excluded. Risk difference (RD) between conservative and revascularization approach was estimated with the inverse variance-weighted method in a fixed-effect model. Results: The analysis includes 25 non-randomized studies totaling 1351 SCAD patients. The risk of in-hospital death or MI was comparable between two strategies. Conservative approach was associated with a lower risk of urgent revascularization compared with initial stenting or bypass surgery (RD=-6.32% [95% CI: -10.95 to -1.69%]; P=0.007). There was no significant difference in long-term mortality (RD=-0.47% [-2.80 to 1.87%]; P=0.70), MI (RD=-0.08% [-3.54 to 3.38%]; P=0.96), TVR (RD=-4.01% [-8.72 to 0.70%]; P=0.09), SCAD recurrence (RD=3.21% [-3.46 to 9.88%]; P=0.35), or HF (RD=0.33% [-2.84 to 3.50%]; P=0.84). Conclusions: Pooled results suggest that conservative and revascularization strategy may have similar in-hospital and long-term outcomes, except that SCAD patients managed conservatively had a lower risk of urgent revascularization. Prospective registries and randomized trials are required to validate these findings. Figure. In-hospital and long-term clinical outcomes of conservative (Rx) versus revascularization (Revasc) approach for SCAD [ABSTRACT FROM AUTHOR]

Introduction: Racial differences in cardiovascular outcomes have been observed in prior studies. However, the racial difference of major adverse cardiovascular events (MACEs) and major bleeds after receiving coronary artery stenting have not been explored. Objective: The objective of this study was to evaluate the risk of MACEs and major bleeds after receiving coronary artery stenting between African Americans (AAs) and European Americans (EAs). Methods: We recruited 767 patients receiving coronary artery stenting at the UAB Hospital. Demographics, socioeconomic status, previous medical history, comorbidities, characteristics of percutaneous coronary intervention (PCI), and medications usage at discharge were appraised. Patients were followed for up to 1 year. Rate of MACEs and major bleeds were assessed by race. Results: AAs accounted for 21.0 % of the cohort. AAs were more likely to be younger, female, physical inactive, have a lower annual income and higher prevalence of end stage renal disease. Compared to EAs, AAs were more likely to have urgent PCI due to myocardial infarction. Ninety-six MACEs (rate 17.6/100 person-years) and 66 major bleeds (12.1/100 person-years) occurred during 545.6 person-years follow-up. The rates of MACEs (24.76 % vs 15.72 %) and major bleeds (18.57 % vs 10.4 %) were higher in AAs versus EAs, and the incident risk ratio of MACEs was 1.58 (95 % CI: 1.00-2.43, P = 0.048) and major bleeds was 1.79 (95 % CI: 1.05-2.97, P = 0.03), respectively. Conclusion: Compared to EAs, AAs had higher rate of MACEs and major bleeds. Ongoing research should aim to identify reasons for the disparities and develop interventions to improve outcomes and reduce disparities. [ABSTRACT FROM AUTHOR]

Introduction: An standardized definition of myocardial infarction with non-obstructive coronary arteries has recently been published by the European Society of Cardiology. The aim of this study is to analyse clinical profile and prognosis of these patients during a twelve-month follow up Methods: Analytical and observational study developed in a University Hospital, which is the only hospital in an area of 220.000 individuals. We analysed data of all consecutive MINOCA patients (pts) admitted during a three-years period, a total of 118 pts. We compared them with 269 consecutive pts admitted for myocardial infarction with obstructive lesions. We used the definitions and clinical management of 2016 ESC Working Group position paper on MINOCA. We used Chi-square test or Fisher's exact to compare categorical variables. The predicting analysis was made with Kaplan-Meier and Cox regression. Results: A 11.6% of pts with myocardial infarction during that period where MINOCA pts. They were younger (61.8±15.7 vs 67.1±12.9 years, p<0.01) and more frequently women (50.8 vs 22.3% p<0.01) than the obstructive group. MINOCA group also had a better cardiovascular risk profile than the pts with obstructive coronary lesions: hypertension (56.8 vs 62.2%, p 0.37), dyslipidemia (41.9 vs 56.9%, p 0.08), diabetes (18.6 vs 36.6%, p<0.01) and tobacco (45.2 vs 65.1%). MINOCA pts had more frequently a previous history of psychiatric illnesses (29.1 vs 12.6%, p<0.01), and more inflammatory conditions: autoimmune disorders (19.5 vs 10.0%, p 0.014), cancer (10.2 vs 3.7%, p<0.01) and connective tissue diseases (7.6% vs 1.5%, p<0.01).At twelve months follow, MINOCA pts showed less all-cause mortality (8 vs 26%, p<0.01) and cardiovascular mortality (5 vs 20% p<0.01), as well as less rate of MACE (11 vs 17%, p 0.02). However, once adjusted by age and cardiovascular risk factors with Cox regression, being MINOCA has no impact on the prognosis. Conclusions: According to this study, MINOCA has an important prevalence and a special profile, with less traditional risk factors, more proinflammatory conditions and more psychiatric illnesses. This study shows that MINOCA pts have less mortality and rate of MACE during the follow up, although after a multivariable adjust the prognosis was similar to the obstructive group. [ABSTRACT FROM AUTHOR]

Introduction: Single photon emission computed tomography myocardial perfusion (SPECT-MPI) is increasingly being acquired with non-contrast CT for attenuation correction, which allows coronary artery calcium (CAC) scoring. We investigated the value of CAC scanning for identifying patients with obstructive coronary artery disease (CAD) in the absence of myocardial perfusion abnormalities. Methods: From the CORE320 multicenter study, we studied 188 patients with suspected CAD who were referred for invasive coronary angiography (ICA) and had normal SPECT-MPI. Cardiac CT and SPECT-MPI were obtained separately. Patients were stratified based on pretest probability and history of CAD into two groups: low/intermediate risk (N=96) and high risk/history of CAD (N=92). The area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic accuracy of CAC scoring for identifying patients with obstructive CAD defined as at least one ≥50% stenosis by quantitative ICA. Other endpoints were: multi-vessel CAD (≥2 vessels with ≥50% stenosis) and high-risk anatomy (left main stenosis of ≥50%, 3-vessel CAD, or 2-vessel CAD with involvement of the proximal LAD artery). Results: The median age was 63 years and 59% were male. Despite the absence of perfusion abnormalities by SPECT-MPI, 28% in the low/intermediate risk group and 64% in high risk group had obstructive CAD. AUC (95% CI) of CAC scoring for detecting obstructive CAD was 81 (71-88) in the low/intermediate risk group and 72 (61-81) in the high risk group (Table). Six percent (2 of 34) in the low/intermediate risk group and 43% (3 of 7) in the high risk group had obstructive CAD despite absence of CAC. Conclusion: CAC scanning yields good accuracy for detecting obstructive CAD in symptomatic patients who have normal SPECT-MPI results. A CAC score >400 was strongly suggestive of high-risk coronary anatomy in our cohort. Routine integration of the CAC score with SPECT-MPI interpretation may be valuable. [ABSTRACT FROM AUTHOR]

Background: The prognostic determinants of coronary artery disease (CAD) include luminal obstruction severity, plaque burden and components, which can be assessed by coronary artery computed tomography angiography (CTA) scores. The role of CTA scores in the long-term prognosis of patients with stable symptoms is unknown. Hypothesis: To evaluate the long-term prognosis value of CTA scores for cardiovascular events in symptomatic patients with suspected CAD referred for coronary CTA in two studies: CORE 64 and CORE 320. Methods: Two hundred and twenty-two participants from Heart Institute for suspected or known CAD. Coronary CTA were categorized as non-obstructive or obstructive CAD, presence and extent of calcified, non-calcified and partially calcified plaques, using coronary CTA modified scores including all plaques or specific plaque types scores (SIS, SSS, Gensini and CTA modified Leaman). The primary endpoint was MACE. Results: During a median follow-up of 6.8 (6.3-9.1) years, 73 patients met the composite end points of MACE. Cardiovascular death occurred in 9 (4.5%), non-fatal ACS in 14 (7.0%), revascularization in 31 (15.5%) patients. When individually added to clinical model on multivariate analysis, all CTA features remained significant, with the exception of SIS of calcified and mixed plaque (SISCalc, SICMixed) and Gensini score. Compared to the clinical model, the highest model improvement was observed when added obstructive CAD (χ2 35.6 vs 21.2, p<0.001). After further adjustment for the presence of obstructive CAD, SISNoncalcremained independently associated with MACE, presenting incremental prognostic value over clinical data and CAD severity (χ2 39.5 vs 21.2, p<0.001 for comparison with clinical model). Patients with obstructive CAD and SISNoncalc>3 were likely to experience events (HR 4.27, 95% CI 2.17-4.40, p<0.001). Conclusions: Coronary CTA scores predict cardiovascular events in long-term follow-up in symptomatic patients. Among patients with obstructive CAD, the presence of more than 3 non-calcified plaques is associated with increased cardiovascular risk in the long term. [ABSTRACT FROM AUTHOR]

Background: Coronary arteries are covered by a thin layer of endothelial cells (ECs). Impairment of ECs is at the origin of coronary atherosclerosis. More recently, endothelial erosion has emerged as the second most prevalent pathological finding in acute coronary syndrome (ACS). However, the study of ECs in humans remains elusive because of a lack of an imaging tool with sufficient resolution. We have recently developed a novel, light-based 1-μm-resolution microscopic imaging technology termed micro-optical coherence tomography (μOCT) that can potentially be implemented in a coronary catheter. Here, we investigated the capability of μOCT to visualize EC morphology. Methods: We stripped the endothelium from 36 fresh swine coronary segments with cyanoacrylate glue. Coronary segments were imaged in 3D with μOCT, and were processed for histology and scanning electron microscopy (SEM). μOCT images of stripped vs. intact sites were volume rendered in 3D and visually compared. ECs visualized by μOCT were validated with those seen by SEM. Surface roughness was calculated for both stripped and intact sites by computing root mean squared error (RMSE). μOCT was also applied to identify ECs of human cadaver coronary arteries. Results: Histology showed the stripping procedure with glue successfully removed ECs from the swine coronary arteries. 3D-μOCT allowed visualization of EC pavementing on intact artery surfaces that was strongly correlated to that seen by SEM (Fig B). EC pavementing disappeared (Fig A) and RMSE diminished significantly at the sites with stripped EC compared with intact sites (P<0.05). μOCT was also capable of identifying EC morphology of human coronary plaque harboring leukocyte adhesion (Fig C), EC stent strut tissue coverage, and lack of ECs at a lesion with superficial nodular calcification. Conclusions: μOCT enables EC visualization in coronary arteries, suggesting that it could be useful in patients with coronary artery disease to better understand the role of ECs in the pathogenesis of ACS. [ABSTRACT FROM AUTHOR]

Introduction: Acute myocardial infarction and chronic ischemic cardiomyopathy are major etiologies leading to implantation of left ventricular assist devices (LVAD). Persistent coronary artery disease (CAD) that goes unaddressed at LVAD implant may pose adverse clinical impact after implant. Objective/Hypothesis: To evaluate the impact of CAD incidence, manifestations and subsequent interventions after LVAD implantation. Patients and Methods: Between February 2007 and December 2017, 388 patients (314 male) underwent primary LVAD implantation in our hospital. Retrospective data from VAD registry were retrieved. Pre-operative myocardial infarction (MI) was present in 191 patients (48%), percutaneous intervention (PCI) was performed in 147 (37%), and prior bypass grafting (CABG) in 95 (24%). Results: Out of 388 total LVAD patients, 223 (57%) were ischemic in etiology. Concomitant CABG was performed in 19 patients (8.5%). Follow-up was available in all early survivors for a total of 791 patient-years of support. Clinical manifestations of recurrent CAD while on support included angina pectoris in 5 patients (2.2%) and 4 patients (1.7%) had MI. Interventions for coronary artery disease included PCI in 3 (1.3%). No late deaths were directly attributable to coronary artery pathology. Conclusions: Despite a high prevalence of ischemic heart disease requiring many pre-LVAD coronary artery procedures and persistent uncorrected CAD after LVAD implantation, the incidence of clinically relevant coronary artery events and subsequent interventions after LVAD implant was exceedingly low. CABG may be required in some patients during LVAD implant. This data increase understanding of natural history of CAD in these patients and enhance the ability to counsel these patients preoperatively. Key Words: Coronary artery disease (CAD), Left Ventricular Assist Device (LVAD) [ABSTRACT FROM AUTHOR]

Nesfatin-1 is a recently identified anorexigenic peptide derived from nucleobindin 2, which is mainly secreted from brain and adipose tissue. Although nesfatin-1 was suggested to have anti-inflammatory and anti-apoptotic properties, the association between plasma nesfatin-1 levels and atherosclerotic disease, such as coronary artery disease (CAD), has not been elucidated. We investigated plasma nesfatin-1 levels by ELISA in 302 patients (pts) undergoing elective coronary angiography for suspected CAD. Pts with ACS, heart failure, malignancy or a history of PCI were excluded. The severity of CAD was represented as the numbers of >50% stenotic vessels and segments, and the severity score of stenosis. The degree of coronary stenosis in each segment was scored 0 to 4 points (0, ≤25%; 1, 26-50%; 2, 51-75%; 3, 76-90%; 4, >90% stenosis), and the severity score was defined as the sum of scores of all segments. Results: Of the 302 study pts, CAD was present in 172 (57%), of whom 67 had 1-vessel, 49 had 2-vessel, 56 had 3-vessel disease (3-VD). Compared with 130 pts without CAD, 172 with CAD more often had hypertension, hyperlipidemia and DM (P<0.05). Plasma nesfatin-1 levels were higher in pts with CAD than without CAD (median 0.21 vs. 0.17 ng/mL, P<0.01). A stepwise increase in nesfatin-1 levels was found depending on the number of >50% stenotic coronary vessels: 0.17 in CAD(-), 0.20 in 1-VD, 0.21 in 2-VD and 0.22 ng/mL in 3-VD (P<0.05). High nesfatin-1 level (>0.19 ng/mL) was found in 43% of pts with CAD(-), 55% of 1-VD, 55% of 2-VD and 68% of 3-VD (P<0.05). Nesfatin-1 levels also correlated with the number of stenotic segments and the severity score (r=0.14 and r=0.13, P<0.02), but they did not correlate with body mass index or HbA1c level. In multivariate analysis, nesfatin-1 levels were a significant factor associated with CAD, especially 3-VD, independent of atherosclerotic risk factors. The odds ratios for CAD and 3-VD were 1.71 (95%CI=1.01-2.91) and 1.96 (95%CI=1.02-3.76) for high nesfatin-1 level of >0.19 ng/mL (P<0.05). Conclusions: Plasma nesfatin-1 levels were found to be associated with the presence and severity of CAD independent of atherosclerotic risk factors. High nesfatin-1 levels in CAD pts may be aimed at preventing the progression of coronary atherosclerosis. [ABSTRACT FROM AUTHOR]

Betatrophin, also called angiopoietin-llike protein 8, is a recently identified adipokine, mainly produced in liver and adipose tissue, which is recognized to play a dual role in lipid and glucose metabolism. However, any association between plasma betatrophin levels and atherosclerotic diseases, such as coronary artery disease (CAD) and peripheral artery disease (PAD), has not been elucidated yet. We investigated plasma betatrophin levels by ELISA in 457 patients (pts) undergoing elective coronary angiography who also had ankle-brachial index (ABI) test for PAD screening. Pts with ACS or a history of PCI were excluded. Results: Of the 457 study pts, CAD was present in 241 (53%), of whom 99 had 1-vessel, 71 had 2-vessel, 71 had 3-vessel disease (3-VD). Plasma betatrophin levels were higher in 241 pts with CAD than in 216 without CAD (median 1120 vs. 909 pg/mL, P<0.001). A stepwise increase in betatrophin levels was found depending on the number of >50% stenotic coronary vessels: 909 in CAD(-), 962 in 1-VD, 1097 in 2-VD and 1393 pg/mL in 3-VD (P<0.001). Betatrophin levels also correlated with the numbers of >50% and >25% stenotic coronary segments (r=0.22 and r=0.24, P<0.001). Moreover, betatrophin levels correlated with HbA1c (r=0.18, P<0.001) but not with FPG and triglyceride levels. In multivariate analysis, betatrophin levels were not a factor for CAD but were a significant factor for 3-VD independent of atherosclerotic risk factors. Odds ratio for 3-VD was 1.06 (95%CI=1.01-1.11, P<0.02) for a 100 pg/mL increase in betatrophin levels. Of the 457 pts, PAD (ABI<0.9) was found in 41 (9%). Betatrophin levels were also higher in 41 pts with PAD than in 416 without PAD (median 1354 vs. 981 pg/mL, P<0.001). Notably, pts with PAD more often had CAD (85% vs. 65%), especially 3-VD (46% vs. 13%) (P<0.001). In multivariate analysis, betatrophin levels were a significant factor for PAD independent of atherosclerotic risk factors and CAD. Odds ratio for PAD was 1.08 (95%CI=1.01-1.14, P<0.02) for a 100 pg/mL increase in betatrophin levels. Conclusions: Plasma betatrophin levels were found to be associated with the presence and severity of CAD as well as PAD independent of atherosclerotic risk factors. Betatrophin may play a role in the development of atherosclerotic diseases. [ABSTRACT FROM AUTHOR]

Background: Smooth muscle cell (SMC) phenotypic modulation, a process by which quiescent SMCs in the arterial wall de-differentiate, proliferate and migrate into the atherosclerotic lesion, has recently been shown to play a major role in disease development. However, the phenotype of modulated SMCs in vivo and the influence of this process on coronary artery disease (CAD) risk are poorly understood. Methods: We used single cell RNA sequencing (scRNAseq) in the atherosclerotic aortic root of SMC lineage-tracing, ApoE-/- mice to characterize the in vivo transcriptional phenotype of modulated SMCs. We also studied the effect of SMC-specific knockout of Tcf21 , a transcription factor causally associated with CAD in human genetic studies, on SMC phenotypic modulation in these mice. We performed scRNAseq in atherosclerotic arteries from heart transplant recipients in order to study SMC phenotypic modulation and TCF21 expression in humans. We explored the relationship between TCF21 expression and CAD risk using human expression quantitative trait locus (eQTL) and CAD association data. Results: We comprehensively characterized the transcriptomic phenotype of modulated SMCs in vivo in mouse and human for the first time. We found that SMC phenotypic modulation leads to a specific fibroblast-like phenotype characterized by production of collagens and extracellular matrix-organizing proteoglycans as well as inhibitors of Wnt/B-catenin signaling. In the mouse, we found that SMC-specific Tcf21 knockout dramatically inhibited SMC phenotypic modulation, leading to fewer modulated SMCs within the lesion and the protective fibrous cap area. We also found that TCF21 expression is strongly associated with SMC phenotypic modulation in diseased human coronary arteries. Human eQTL analysis revealed that TCF21 expression is associated with decreased CAD risk, suggesting a protective role for both TCF21 and SMC phenotypic modulation. Conclusions: We have described the comprehensive in vivo transcriptomic phenotype of modulated SMCs for the first time in mouse and humans, revealing their development of a specific fibroblast-like phenotype. The CAD-associated gene TCF21 promotes this process, leading to decreased risk of CAD and myocardial infarction. [ABSTRACT FROM AUTHOR]

Introduction: Patients with renal impairment are considered a coronary artery disease (CAD) equivalent. Repeated coronary artery calcium (CAC) scoring has been recognized as a robust tool for tracking progression of atherosclerosis. Further, CAC progression is an important marker of future adverse event. However, the evidence for an independent association of renal function with CAC progression remains unclear. Hypothesis: To examine the cross-sectional association between renal function and CAC progression. Methods: From a 6-center, single ethnicity observational registry, a total of 10,033 asymptomatic adults (mean age: 51.1±8.5 years, 84.9% men) without prior history of CAD and stroke underwent 2 examinations, including CAC screening as part of a broader health study with an average of 3.3±1.9 years between baseline scan and follow-up scan. Estimated glomerular filtration rate (eGFR; mL/min/1.73 m2) was ascertained using the modified MDRD formula, and was categorized as: ≥90 (normal), 60-89 (mildly decreased), and <60 (moderate-to-severely decreased) based on current guidelines. CAC progression was calculated as the difference between the square root of baseline and square root of follow-up CAC score ≥2.5. Results: During an 8.7-year follow-up (IQR, 6.4-10.6 years), CAC progression was found in 766 subjects (7.6%). The patients with more impaired renal function were older, likely to be women and higher prevalence of hypertension, diabetes mellitus, and dyslipidemia. Among patients with normal or mildly decreased renal function, no difference of the proportion was found according to the presence or absence of CAC progression. Yet, patients with moderate-to-severely decreased renal function of eGFR <60 had higher prevalence of CAC progression (7.3% vs. 4.5%) (Figure). Notably, multivariate logistic regression model revealed that impaired renal function was associated with the progression of CAC (Odds ratio [OR]: 1.11, 95% confidence interval [CI]: 1.00-1.33 for eGFR 60-89 and OR: 1.80, 95% CI: 1.31-2.42 for eGFR <60). Conclusions: Impaired renal function evoked a strong relationship with a higher risk of the progression of subclinical atherosclerosis as measured by CAC scoring. [ABSTRACT FROM AUTHOR]

Background: Epicardial coronary endothelial dysfunction is associated with development and progression of local coronary atherosclerotic lesion. However, the role of coronary microvascular endothelial function in the development of coronary atherosclerosis is largely unknown. The aim of the present study was to test the hypothesis that coronary microvascular endothelial dysfunction (CMED) is associated with epicardial atherosclerotic coronary artery disease (CAD). Methods and Results: 148 patients with chest pain, referred for the evaluation of coronary vasomotion and found to have angiographically normal coronary arteries or mild CAD (<40% stenosis), underwent invasive coronary endothelial function testing and virtual-histology intravascular ultrasound (VH-IVUS) of the left anterior descending coronary artery. Endothelium-dependent coronary vascular reactivity was evaluated by graded administration of intracoronary acetylcholine. CMED was defined as percent increase in coronary blood flow of ≤50% in response to a maximum dose of acetylcholine. Patients with CMED (n=87), as compared to those with normal microvascular endothelial function (n=61), had higher averaged epicardial plaque necrotic core area [0.07 (0.01-0.34) vs. 0.03 (0.00-0.17) mm2, p=0.016] and higher frequency of imaged arteries containing at least one VH-IVUS-derived thin-cap fibroatheroma (TCFA) [n=22 (25.3%) vs. 5 (8.2%), p=0.008] (Figure). After adjusting for age, gender and CAD risk factors, CMED was an independent predictor of VH-IVUS-derived larger averaged necrotic core area (β=0.176, p=0.033) and TCFA frequency (β=0.180, p=0.028). Conclusions: CMED is an independent predictor of larger necrotic core plaque area and higher TCFA frequency, both of which are characteristics of rupture-prone plaques. [ABSTRACT FROM AUTHOR]

Background: Forward Projected Model-based Iterative Reconstruction SoluTion (FIRST) is a new reconstruction technique using computed tomography (CT) providing successful reconstruction of high quality CT images. Hypothesis: Diagnostic accuracy of the detection of significant coronary artery stenosis using 2nd generation 320-slice CT with FIRST may be improved. Methods: This is a retrospective study of 200 patients (141 males; mean age 66±14 years) without past histroy of coronary artery bypass surgery who underwent coronary CT and invasive coronary angiography (ICA) within 3 months. The first 100 consecutive patients (Group 1) underwent 1st generation 320-slice CT (Aquilion One, Cannon Medical) without FIRST. The next consecutive 100 patients (Group 2) underwent 2nd generation 320-slice CT (Aquilion One/ Vision, Cannon Medical) with FIRST. Diagnostic accuracy of detection of significant coronary artery stenosis ≥75% on CT, regarded ICA as gold standard, was compared between the 2 groups, in both patient-based and segment-based analysis (defined by the AHA). Results: In a patient-based analysis, sensitivity, specificity, positive and negative predictive values (PPV and NPV), and overall accuracy of detection of significant stenosis on CT against ICA were 96, 86, 92, 90, and 91%, respectively in Group 1, and 93, 80, 88, 89, and 88%, respectively, in Group 2. No significant differences were observed between the 2 groups both in a patient-based and segment-based analysis. However, in cases with severe coronary artery calcifications (Agatston calcium score (ACS) >400, 31 cases in Group 1 and 62 cases in Group 2), in a segment-based analysis, specificity and accuracy were significantly higher (all P < 0.05) in Group 2 than in Group 1 (Figure). Conclusion: The diagnostic accuracy of the detection of coronary artery stenosis on CT compared with ICA has been improved with the use of 2nd generation 320-slice CT with FIRST in cases with severe calcified coronary arteries. [ABSTRACT FROM AUTHOR]