Implications Of Coronary Artery Disease Research Articles

Coronary Artery Disease in Patient with An Anomalous Origin of Right Coronary Artery

Coronary artery disease (CAD) remains a leading cause of mortality and morbidity in developed countries. CAD is a pathological process characterized by the accumulation of atherosclerotic plaques in the epicardial arteries, both obstructive and non-obstructive. This study aims to investigate rare cases of anomalous right coronary artery arising from the left main coronary artery and its clinical implications for coronary artery disease (CAD). The research methodology involved clinical examinations, echocardiography, diagnostic coronary angiography, and computed tomography angiography (CCTA) to obtain a comprehensive understanding of this case. The research findings indicate severe stenosis in the proximal-mid left main coronary artery (LAD) and an anomalous origin of the right coronary artery (RCA) leading to lower-level stenosis. Percutaneous coronary intervention (PCI) on the proximal-mid LAD lesion resulted in significant improvement in the patient's condition. The implications of this research underscore the importance of a deep understanding of coronary artery anatomical variations for accurate diagnosis and appropriate management of CAD patients, especially in rare cases like this.

Prognostic value of plasma adipokine chemerin in patients with coronary artery disease

BackgroundAdipokine chemerin was proven to be associated with coronary artery disease (CAD), but its prognostic implications in CAD remain unclear.MethodsThis study consists of two parts, one is a basic study and the other is a clinical cohort study. First, we investigated the differential expression of six adipokines in the atherosclerotic mice model compared to mice with milder degrees of atherosclerosis and mice without atherosclerosis using microarray data. We then examined the potential of chemerin as a diagnostic and prognostic indicator in a CAD cohort. A total of 152 patients were enrolled in our study, including 77 patients with angiographically proven CAD and 75 control subjects without cardiovascular disease. Plasma adipokine chemerin levels were measured in all patients, and major adverse cardiovascular events (MACEs) were followed up, including ischemic stroke, non-fatal myocardial infarction, revascularization, and cardiovascular death.ResultsIn the aortas of atherosclerotic mice, chemerin expression was up-regulated compared to control mice. The plasma chemerin levels of CAD patients were higher than those of non-CAD patients (128.93 ± 37.06 vs. 109.85 ± 27.47 mmol/L, respectively, P < 0.001). High chemerin levels were an independent predictor of CAD (β = 2.702, 95% CI, 1.344–5.431, P = 0.001). We followed up with patients for a median duration of 5.5 years (3.9–5.6). The Kaplan–Meier curves showed that patients in the high chemerin group had a significantly higher risk of MACEs than the low chemerin group in patients with CAD (log-rank P = 0.003), not with non-CAD (Log-rank P = 0.120). Furthermore, Cox multivariate analysis revealed that high chemerin levels were an independent predictor of MACEs (HR 2.267; 95% CI, 1.139–4.515; P = 0.020). Finally, the cellular study showed that chemerin is predominantly expressed in PBMC-derived macrophages.ConclusionPlasma chemerin levels were increased in the CAD patients, and a high chemerin level increased the risk of MACEs in CAD patients.

Noncanonical Role of Telomerase in Regulation of Microvascular Redox Environment With Implications for Coronary Artery Disease.

Telomerase reverse transcriptase (TERT) (catalytic subunit of telomerase) is linked to the development of coronary artery disease (CAD); however, whether the role of nuclear vs. mitchondrial actions of TERT is involved is not determined. Dominant-negative TERT splice variants contribute to decreased mitochondrial integrity and promote elevated reactive oxygen species production. We hypothesize that a decrease in mitochondrial TERT would increase mtDNA damage, promoting a pro-oxidative redox environment. The goal of this study is to define whether mitochondrial TERT is sufficient to maintain nitric oxide as the underlying mechanism of flow-mediated dilation by preserving mtDNA integrity.Immunoblots and quantitative polymerase chain reaction were used to show elevated levels of splice variants α- and β-deletion TERT tissue from subjects with and without CAD. Genetic, pharmacological, and molecular tools were used to manipulate TERT localization. Isolated vessel preparations and fluorescence-based quantification of mtH2O2 and NO showed that reduction of TERT in the nucleus increased flow induced NO and decreased mtH2O2 levels, while prevention of mitochondrial import of TERT augmented pathological effects. Further elevated mtDNA damage was observed in tissue from subjects with CAD and initiation of mtDNA repair mechanisms was sufficient to restore NO-mediated dilation in vessels from patients with CAD. The work presented is the first evidence that catalytically active mitochondrial TERT, independent of its nuclear functions, plays a critical physiological role in preserving NO-mediated vasodilation and the balance of mitochondrial to nuclear TERT is fundamentally altered in states of human disease that are driven by increased expression of dominant negative splice variants.

Prognostic implications of coronary artery disease and stress tests in patients with elevated left ventricular filling pressure and preserved ejection fraction.

BackgroundThe prognostic role of myocardial ischemia in patients with heart failure with preserved ejection fraction (HFpEF) has not been fully elucidated. Therefore, we investigated the change in echocardiographic parameters and clinical outcomes based on the presence of epicardial coronary artery disease (CAD) and positive stress tests in HFpEF patients.MethodsSymptomatic patients with left ventricular end diastolic pressure ≥15 mmHg who underwent coronary angiography were analyzed between January 2000 and August 2019 after exclusion of patients with acute coronary syndrome.ResultsA total of 555 HFpEF patients were invasively confirmed, 285 (51%) had angiographically-proven CAD. HFpEF patients with CAD displayed greater deterioration in left ventricular ejection fraction (p = 0.002) over time but this was not observed in those without CAD (p = 0.99) on follow-up echocardiography; however, the mitral annulus early diastolic velocity (e') was significantly decreased in both groups (p < 0.001 and p = 0.003, respectively). Among 274 patients that received stress tests, those with positive stress tests showed a decline in e' (p 0.001), but this was not found in subjects with negative stress tests (p = 0.44). There was no significant difference in all-cause mortality between patients with CAD and without CAD (p = 0.26) with a median follow-up of 10.6 years.ConclusionIn HFpEF patients, CAD was associated with greater deterioration in the left ventricular systolic function but not with mortality during the follow-up. In addition, myocardial ischemia with a positive stress test may contribute to greater deterioration of diastolic dysfunction.

Preexisting coronary artery disease among coronavirus disease 2019 patients: a systematic review and meta-analysis.

The prevalence and prognostic implications of coronary artery disease (CAD) in patients infected by the novel coronavirus 2019 (COVID-19) disease remain unclear. We conducted a systematic review and meta-analysis to investigate the prevalence and mortality risk in COVID-19 patients with preexisting CAD. We searched Medline and Scopus to locate all articles published up to December 8, 2021, reporting data of COVID-19 survivors and nonsurvivors with preexisting CAD. Data were pooled using the Mantel-Haenszel random effects models with odds ratio (OR) as the effect measure with the related 95% confidence interval (CI). Thirty-eight studies including 27 435 patients (mean age 61.5 and 70.9 years) were analysed. The pooled prevalence of preexisting CAD was 12.6% (95% CI: 11.2-16.5%, I2 : 95.6%), and resulted as higher in intensive care unit patients (17.5%, 95% CI: 11.9-25.1, I2 : 88.4%) and in European cohorts (13.1%, 95% CI: 7.8-21.6%, P < 0.001, I2 : 98.4%). COVID-19 patients with preexisting CAD had a two-fold risk of short-term mortality (OR 2.61, 95% CI 2.10-3.24, P < 0.001, I2 = 73.6%); this risk was higher among Asian cohorts (OR: 2.66, 95% CI: 1.79-3.90, P < 0.001, I2 : 77.3%) compared with European (OR: 2.44, 95% CI: 1.90-3.14, P < 0.001, I2 : 56.9%) and American (OR: 1.86, 95% CI: 1.41-2.44, P < 0.001, I2 : 0%) populations. The association between CAD and poor short-term prognosis was influenced by age, prevalence of hypertension (HT), DM and CKD. Preexisting CAD is present in approximately 1 in 10 patients hospitalized for COVID-19 and significantly associated with an increased risk of short-term mortality, which is influenced by age, HT, DM and CKD.

C90 PRE–EXISTING CORONARY ARTERY DISEASE AMONG COVID–19 PATIENTS: A SYSTEMATIC REVIEW AND META–ANALYSIS

BackgroundThe prevalence and prognostic implications of coronary artery disease (CAD) in patients infected by the novel coronavirus 2019 (COVID–19) disease remain unclear.MethodsWe conducted a systematic review and meta–analysis to investigate the prevalence and mortality risk in COVID–19 patients with pre–existing CAD. We searched Medline and Scopus to locate all articles published up to December 8, 2021, reporting data of COVID–19 survivors and non–survivors with pre–existing CAD. Data were pooled using the Mantel–Haenszel random effects models with odds ratio (OR) as the effect measure with the related 95% confidence interval (CI). ResultsThirty–eight studies including 27.435 patients [mean age 61.5 and 70.9 years] were analysed. The pooled prevalence of pre–existing CAD was 12.6% (95% CI: 11.2–16.5%, I2:95.6%), and resulted higher in ICU patients (17.5%, 95% CI: 11.9–25.1, I2: 88.4%) and in European cohorts (13.1%, 95% CI: 7.8–21.6%, p < 0.001, I2: 98.4%). COVID–19 patients with pre–existing CAD had a twofold risk of short–term mortality (OR 2.61, 95% CI 2.10–3.24, p < 0.001, I2=73.6%) (Figure 1); this risk was higher among Asian cohorts (OR: 2.66, 95% CI: 1.79–3.90, p < 0.001, I2: 77.3%) compared to European (OR: 2.44, 95% CI: 1.90–3.14, p < 0.001, I2:56.9%) and American (OR: 1.86, 95% CI: 1.41–2.44, p < 0.001, I2: 0%) populations (Figure 2). The association between CAD and poor short–term prognosis was influenced by age, prevalence of HT, DM and CKD. ConclusionsPre–existing CAD is present in approximately 1 in 10 patients hospitalised for COVID–19 and significantly associated with an increased risk of short–term mortality, which is influenced by age, HT, DM and CKD.

Homophilic Interaction Between Transmembrane-JAM-A and Soluble JAM-A Regulates Thrombo-Inflammation: Implications for Coronary Artery Disease

Genetic predisposition through F11R-single-nucleotide variation (SNV) influences circulatory soluble junctional adhesion molecule-A (sJAM-A) levels in coronary artery disease (CAD) patients. Homozygous carriers of the minor alleles (F11R-SNVs rs2774276, rs790056) show enhanced levels of thrombo-inflammatory sJAM-A. Both F11R-SNVs and sJAM-A are associated with worse prognosis for recurrent myocardial infarction in CAD patients. Platelet surface-associated JAM-A correlate with platelet activation markers in CAD patients. Activated platelets shed transmembrane-JAM-A, generating proinflammatory sJAM-A and JAM-A-bearing microparticles. Platelet transmembrane-JAM-A and sJAM-A as homophilic interaction partners exaggerate thrombotic and thrombo-inflammatory platelet monocyte interactions. Therapeutic strategies interfering withthis homophilic interface may regulate thrombotic and thrombo-inflammatory platelet response in cardiovascular pathologies where circulatory sJAM-A levels are elevated.

COVID-19 patients with coronary artery disease have a higher mortality risk: a meta-analysis

Abstract Background The prevalence and prognostic implications of coronary artery disease (CAD) in patients infected by the novel coronavirus 2019 disease (COVID-19) remain unclear. Purposes We conducted a systematic review and meta-analysis to investigate the prevalence and mortality risk in COVID-19 patients with pre-existing CAD. PRISMA. guidelines were followed in abstracting data and assessing validity. We searched Medline, Scopus and Web of Science to locate all articles published up to December 8, 2020 reporting data of COVID-19 survivors and non-survivors with pre-existing CAD. Data were pooled using the Mantel-Haenszel random effects models with odds ratio (OR) as the effect measure with the related 95% confidence interval (CI). Statistical heterogeneity between groups was measured using the Higgins I2 statistic. Results Twenty-four studies, enrolling 22744 patients [mean age 58.2 and 70.9 years for survivors and non-survivors (p&amp;lt;0.0001), respectively], met the inclusion criteria and were included into the final analysis. The pooled prevalence of pre-existing CAD in COVID-19 patients was 11.5% (95% CI 0.097–0.136) and resulted significantly higher in non-survivors compared to survivors (16.7% vs 7.1%, respectively, p&amp;lt;0.0001). A random-effect model confirmed a significant higher risk of death in COVID- 19 patients with pre-existing CAD in the short-term period (OR 2.96, 95% CI 2.18–4.03, p&amp;lt;0.0001, I2=79%) (Figure 1). A meta-regression, using age as moderator, did not identify any statistical significance (Coeff: −0.046, 95% CI −0.101–0.009, p=0.104). The Egger's regression test (t=0.596; p=0.06) confirmed that there were not statistically evidences of publication bias Conclusions Pre-existing CAD in COVID-19 patients significantly increased the risk of death during the infection. Funding Acknowledgement Type of funding sources: None. Figure 1. Forest plot investigating the COVID-19 patients mortality risk in relation to pre-existing coronary artery disease.

Characterization of cholesteryl ester-loaded human coronary vascular smooth muscle cell secretome. A source of potential biomarkers of coronary artery disease

Background and Aims: Human coronary vascular smooth muscle cells (hcVSMC) become foam cells by the selective uptake of cholesteryl ester (CE) from aggregated LDL (agLDL). We developed peptides that specifically inhibited agLDL formation and intracellular CE accumulation. Despite the relevance of CE-loaded hcVSMC for atherothrombosis, knowledge about their clinical implications for Coronary Artery Disease (CAD) diagnosis is limited. The objective of this work was to identify the proteins released by CE-loaded hcVSMC to identify potential new circulating CAD biomarkers.

Changes in left ventricle myocardial volume during stress test using cadmium-zinc-telluride cardiac imaging: Implications in coronary artery disease

BackgroundCadmium-zinc-telluride (CZT) SPECT allows the estimation of left ventricle myocardial volume (LVMV). We tested the clinical relevance of rest-stress LVMV changes (Δ LVMV) in detecting coronary artery disease (CAD, coronary stenosis > 70%), using CZT-SPECT. MethodsWe prospectively enrolled 512 consecutive patients with known or suspected CAD (mean age: 70.3 ± 9.2 years, 72% male) for stress-rest myocardial perfusion imaging (MPI, single-day stress-rest protocol). We quantified summed stress scores (SSS), summed rest scores, and summed difference scores, together with LVMV and ejection fraction (EF) after stress and at rest. All patients underwent coronary angiography within 30 days. ResultsTwo hundred seventy-two patients had CAD at coronary angiography. ΔLVMV ≤ 5 mL, corresponding to 6% of change from rest LVMV, was the best predictor of CAD (AUC = 0.831, 79% sensitivity, 82% specificity), irrespective of the stress protocol (dipyridamole or exercise stress) and independently of MPI-SSS, LV EF, and clinical history (P = 0.004). Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were significant for the addition of ΔLVMV ≤ 5 mL (IDI = 6.1%, P < 0.0001; NRI = 29.7%, P = 0.02) to MPI-SSS, whereas the other parameters were not. ConclusionsThe evaluation of ΔLVMV using CZT-SPECT can improve the diagnostic accuracy in predicting the presence of CAD when added to conventional MPI.

New endothelial markers: implications for coronary artery disease and chronic periodontitis

Abstract Funding Acknowledgements Type of funding sources: None. Introduction There is an association between chronic periodontitis (CP) and coronary artery disease (CAD). Endothelial function is increasingly used as an important outcome measure in cardiovascular diseases. But the data on early markers endothelial dysfunction in patients with CP is limited. Aim. To determine whether there are differences in parameters of tissue endothelial markers in gingiva between patients with CP, CAD or CAD and concomitant CP. Methods We examined 30 patients with CAD, 75 patients with CP and 35 patients with CAD and concomitant CP and 25 healthy control. There were no differences between the groups of patients with CP, CAD and co-morbidity in age, gender, smoking and obesity. In marginal gingiva NO-synthase-like cells (NOs-cells) and marker of endothelial progenitor cells (CD34+ cells) by immunohistochemical and morphometric analyses were assessed. Endothelium-dependent vasodilation (EDV) of the brachial artery was evaluated. Results Immunoreactivity to NOs and the CD34+ cells was found mainly in the vascular. In patients with average and severe CP significant decrease of expression of NOs–cells (6.2 ± 2.4% vs 7.9 ± 1.9%, p &amp;lt; 0.05) and of CD34+ -cells (6.3%±1.8 vs 8.9 ± 2.6%, p &amp;lt; 0.05) in gingiva was detected. There were no differences of endothelial immunohistochemical markers between the groups of patients with mild CP and healthy person. In patients with CAD also significant decrease of expression of NOs–cells (5.0 ± 2.1%) and of CD34+ -cells (4.9%±2.0%) in gingiva was found. The most significance changes of gingival expression of NOs–cells (4.3 ± 1.4%) and of CD34+ -cells (3.8%±1.7%) in patients with CAD and concomitant CP were observed. In the control group EDV 15.4 ± 6.5%, in patients with mild CP 13.9 ± 6.5, in patients with average and severe CP 10,9 ± 5,1% (p = 0.02 between healthy person). There were associations between the decrease of EDV of the brachial artery with gingival expression of NOs–cells and of CD34+ -cells (Spearman"s R = 0.575 and R = 0.578). Conclusion Average and severe periodontitis is associated with vascular effects outside the oral cavity. Periodontitis also as CAD are associated with changes in the cell expression of NOs and endothelial progenitor cells in the periodontal tissue. Immunohistochemical assessment of endothelial markers in periodontium is a promising method of early assessment of endothelial dysfunction in cardiovascular disease.

Interaction between the apelinergic system and ACE2 in the cardiovascular system: therapeutic implications.

The apelinergic system is widely expressed and acts through autocrine and paracrine signaling to exert protective effects, including vasodilatory, metabolic, and inotropic effects on the cardiovascular (CV) system. The apelin pathway's dominant physiological role has delineated therapeutic implications for coronary artery disease, heart failure (HF), aortic aneurysm, pulmonary arterial hypertension (PAH), and transplant vasculopathy. Apelin peptides interact with the renin-angiotensin system (RAS) by promoting angiotensin converting enzyme 2 (ACE2) transcription leading to increased ACE2 protein and activity while also antagonizing the effects of angiotensin II (Ang II). Apelin modulation of the RAS by increasing ACE2 action is limited due to its rapid degradation by proteases, including ACE2, neprilysin (NEP), and kallikrein. Apelin peptides are hence tightly regulated in a negative feedback manner by ACE2. Plasma apelin levels are suppressed in pathological conditions, but its diagnostic and prognostic utility requires further clinical exploration. Enhancing the beneficial actions of apelin peptides and ACE2 axes while complementing existing pharmacological blockade of detrimental pathways is an exciting pathway for developing new therapies. In this review, we highlight the interaction between the apelin and ACE2 systems, discuss their pathophysiological roles and potential for treating a wide array of CV diseases (CVDs).

Changes in Pericardial Fat Composition after Radiotherapy: Implications for Coronary Artery Disease?

Changes in Pericardial Fat Composition after Radiotherapy: Implications for Coronary Artery Disease?

A novel study to examine the association of PCSK9 rs505151 polymorphism and coronary artery disease in north Indian population

There is a drastic increase in the number of people suffering from coronary artery disease (CAD) worldwide with Indians being no exception. Being a developing country and experiencing a dramatic shift in lifestyle and eating habits, urbanization and industrialization, all these factors have collectively predisposed the Indian population towards CAD and the prevalence data arequite alarming. Genetic studies have disclosed the role of genes in CAD susceptibility and severity. One such gene is proprotein convertase subtilisin/kexin type 9 (PCSK9) which is sought to modulate the cholesterol levels and hence, has implications in CAD. We aim to explore the association of PCSK9 A/G (rs505151) polymorphism and hence, the susceptibility towards CAD in the north Indian population. Five-hundred angiographically confirmed CAD patients and 500 healthy individuals as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis revealed a significant association with the G allele with odds ratio (OR)=1.50, 95% confidence interval (CI)=1.22-1.85 and P=0.000. Also, a strong association was observedfor CAD risk with OR=1.590, 95% CI=1.106-2.284 and P=0.012. However, the homozygous GG mutant genotype was found to be completely absent from our population. Analysis of the dominant model also revealed an association with CAD risk. Our work demonstrated for the first time the association of PCSK9 A/G (rs505151) polymorphism with CAD risk in the north Indian population.

The effects of cigarette smoking and smoking cessation on high-density lipoprotein functions: implications for coronary artery disease.

Smoking cessation was associated with improved prognosis of coronary artery disease. This study was designed to investigate the effect of smoking cessation on high-density lipoprotein functionality in coronary artery disease patients. In this prospective, randomized and parallel controlled study, coronary artery disease smokers ( n = 28) and healthy smokers ( n = 30) were divided into smoking cessation group and continuous smoking group, respectively. Blood samples were collected before and after three-month smoking cessation. Plasma high-density lipoprotein was isolated by density gradient centrifugation. The ability of high-density lipoprotein against copper-induced oxidation of lipoprotein was determined to evaluate the antioxidative property of high-density lipoprotein, and the macrophage migration inhibited by high-density lipoprotein was tested to identify the antichemotactic property of high-density lipoprotein. High-density lipoprotein-induced macrophage cholesterol efflux was measured by fluorescence spectrometry using NBD cholesterol analogue. Healthy non-smoking volunteers were enrolled as the baseline control. The baseline antioxidative, antichemotactic ability of high-density lipoprotein and high-density lipoprotein-induced cellular cholesterol efflux in coronary artery disease smokers and healthy smokers were significantly attenuated when compared with those in healthy non-smokers. After three-month smoking cessation, both the antioxidative ability and antichemotactic ability of high-density lipoprotein were improved significantly in coronary artery disease smokers. However, high-density lipoprotein-induced cellular cholesterol efflux was not increased by smoking cessation. In in vitro experiments, carbon monoxide reduced the antioxidative ability and nicotine enhanced the antichemotactic ability of high-density lipoprotein. Smoking cessation is an effective measure to improve high-density lipoprotein functions in coronary artery disease smokers. Our study re-emphasizes the importance of smoking cessation in the secondary prevention of coronary artery disease.

Clinical Relevance of Functionally Insignificant Moderate Coronary Artery Stenosis Assessed by 3-Vessel Fractional Flow Reserve Measurement.

BackgroundUnderstanding of the risk conferred by functionally insignificant lesions in multiple coronary vessels is limited. We investigated the prognostic implications of coronary artery disease (CAD) based on 3‐vessel fractional flow reserve (FFR).Methods and ResultsA total of 1,136 patients underwent FFR measurement in the 3 major epicardial arteries. We defined vessels with “Moderate CAD” as vessels with FFR, 0.81 to 0.87. Patients were classified into Group 1: No apparent CAD (FFR>0.87 in all 3‐vessels); Group 2: Single‐vessel moderate CAD; Group 3: Multivessel moderate CAD; and Group 4: Functionally significant CAD (FFR≤0.80) in any vessel. The primary end point was 2‐year major adverse cardiac events, a composite of cardiac death, myocardial infarction, and ischemia‐driven revascularization. Forty‐three percent of patients had moderate CAD (Group 2: 403/1136, 35.5%; Group 3: 84/1136, 7.4%). The 2‐year risk of major adverse cardiac events was not significantly different between patients with single‐vessel moderate CAD and no apparent CAD (2.6 versus 2.6%; HR, 1.1; 95% confidence interval, 0.4%–2.8%; P=0.89). However, patients with multivessel moderate CAD were at significantly higher risk than Group 1 (7.4 versus 2.6%; hazard ratio, 3.3; 95% confidence interval, 1.1%–9.8%; P=0.03). The risk of major adverse cardiac events in patients with multivessel moderate CAD was comparable to that of patients with functionally significant CAD (hazard ratio, 1.2; 95% confidence interval, 0.5%–3.0%; P=0.67). In a multivariable regression model, multivessel moderate CAD was an independent predictor of greater risk of 2‐year major adverse cardiac events.ConclusionsGlobal physiologic assessment with FFR measurement of 3 vessels can identify multivessel moderate CAD. The prognostic implication of multivessel moderate CAD appears comparable to that of functionally significant CAD.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01621438.

Regulation of oxidized platelet lipidome: implications for coronary artery disease.

Hyperlipidaemia enhances susceptibility to thrombosis, while platelet oxidixed LDL (oxLDL) binding in acute coronary syndrome (ACS) correlates with activation status. This study explores the platelet lipidome in symptomatic coronary artery disease (CAD) patients and the functional consequences of the chemokine CXCL12 and its receptors CXCR-4/-7 on lipid uptake in platelets. Platelet-oxLDL detected by flow cytometry was enhanced (P = 0.04) in CAD patients, moderately correlated with platelet CXCR7 surface expression (ρ = 0.39; P < 0.001), while inversely with CXCR4 (ρ = 0.35; P < 0.001). Platelet-oxLDL was elevated (P = 0.01) in ACS patients with angiographic evidence of intracoronary thrombi. Ex vivo analysis of intracoronary thrombi sections revealed oxLDL deposition in platelet-enriched areas verified by immunofluorescence confocal microscopy. LDL-oxLDL uptake enhanced reactive oxygen species, mitochondrial superoxide generation, intraplatelet LDL to oxLDL conversion, and lipid peroxidation, counteracted by SOD2-mimetic MnTMPyP. Lipidomic analysis revealed enhanced intraplatelet-oxidized phospholipids, cholesteryl esters, sphingomyelin, ceramides, di- and triacylglycerols, acylcarnitines in CAD patients compared with age-matched controls as ascertained by liquid chromatography hyphenated to high-resolution mass spectrometry. LDL-oxLDL induced degranulation, αIIbβ3-integrin activation, apoptosis, thrombin generation estimated by calibrated automated thrombinoscopy, and shape change verified by live imaging using scanning ion conductance microscopy. Further, LDL-oxLDL enhanced thrombus formation ex vivo and in vivo in mice (ferric chloride-induced carotid artery injury). LDL-oxLDL enhanced platelet CXCL12 release, differentially regulated CXCR4-CXCR7 surface exposure, while CXCL12 prompted LDL-oxLDL uptake and synergistically augmented the LDL-oxLDL-induced pro-oxidative, thrombogenic impact on platelet function. An altered platelet lipidome might be associated with thrombotic disposition in CAD, a mechanism potentially regulated by CXCL12-CXCR4-CXCR7 axis.

Implications of Coronary Artery Disease in Heart Failure With Preserved Ejection Fraction

This study investigated the characteristics, evaluation, prognostic impact, and treatment of coronary artery disease (CAD) in patients with heart failure and preserved ejection fraction (HFpEF). CAD is common in patients with HFpEF, but it remains unclear how CAD should be categorized, evaluated for, and treated in HFpEF. Clinical, hemodynamic, echocardiographic, treatment, and outcome characteristics were examined in consecutive patients with previous HFpEF hospitalizations who underwent coronary angiography. Of the 376 HFpEF patients examined, 255 (68%) had angiographically-proven CAD. Compared with HFpEF patients without CAD, patients with CAD were more likely to be men, to have CAD risk factors, and to be treated with anti-ischemic medications. However, symptoms of angina and heart failure were similar in patients with and without CAD, as were measures of cardiovascular structure, function, and hemodynamics. Compared with patients without CAD, HFpEF patients with CAD displayed greater deterioration in ejection fraction and increased mortality, independent of other predictors (hazard ratio: 1.71, 95% confidence interval: 1.03 to 2.98; p= 0.04). Complete revascularization was associated with less deterioration in ejection fraction and lower mortality compared with patients who were not completely revascularized, independent of other predictors (hazard ratio: 0.56, 95% confidence interval: 0.33 to 0.93; p= 0.03). CAD is common in patients with HFpEF and is associated with increased mortality and greater deterioration in ventricular function. Revascularization may be associated with preservation of cardiac function and improved outcomes in patients with CAD. Given the paucity of effective treatments for HFpEF, prospective trials are urgently needed to determine the optimal evaluation and management of CAD in HFpEF.

Incidence and implications of coronary artery disease in patients undergoing valvular heart surgery: The Indian scenario

We evaluated the incidence and implications of coronary artery disease (CAD) in patients above 40 years presenting for valve surgery. Between January 2009 and December 2010, coronary angiography (CAG) was performed in all such patients ( n = 140). Coronaries were normal in 119 (Group I), and diseased in 21 (Group II). In Group II, 11 patients were < 50 years, 3 were between 51 and 60 years and 7 were > 61 years. In 8 of these, only valve replacement was performed. Coronary artery bypass grafting (CABG) and aortic valve replacement was performed in 10, CABG and mitral valve replacement in 2 and CABG with mitral and aortic valve replacement in one. The number of vessels grafted in these 13 patients was 1.54 ± 0.66. Hypertension and diabetes were significant ( P < 0.05) in this group. The mortality was significant in Group II (11 vs. 6, P < 0.05). Six patients died in Group II, 5 had severe aortic stenosis and severe left ventricular hypertrophy; the sixth patient had severe mitral stenosis and was in CHF. The predominant cause of death was congestive heart failure (CHF). Fifteen percentage of these patients had CAD. CAG should be performed routinely in these patients while presenting for valve surgery. Combined CABG and valve replacement carries high mortality (28.5%), especially in patients with aortic stenosis. The study suggests that the cardio-protective measures should be applied more rigorously in this subset of patients.

Epicardial Fat: Definition, Measurements and Systematic Review of Main Outcomes

Epicardial fat (EF) is a visceral fat deposit, located between the heart and the pericardium, which shares many of the pathophysiological properties of other visceral fat deposits, It also potentially causes local inflammation and likely has direct effects on coronary atherosclerosis. Echocardiography, computed tomography and magnetic resonance imaging have been used to evaluate EF, but variations between methodologies limit the comparability between these modalities.We performed a systematic review of the literature finding associations of EF with metabolic syndrome and coronary artery disease. The summarization of these associations is limited by the heterogeneity of the methods used and the populations studied, where most of the subjects were at high cardiovascular disease risk.EF is also associated with other known factors, such as obesity, diabetes mellitus, age and hypertension, which makes the interpretation of its role as an independent risk marker intricate. Based on these data, we conclude that EF is a visceral fat deposit with potential implications in coronary artery disease. We describe the reference values of EF for the different imaging modalities, even though these have not yet been validated for clinical use. It is still necessary to better define normal reference values and the risk associated with EF to further evaluate its role in cardiovascular and metabolic risk assessment in relation to other criteria currently used.