Unstable CAD Research Articles

Abstract 16467: The Prevalence, Racial Distribution, and In Hospital Outcome of Percutaneous Coronary Intervention in Non ST Elevation Myocardial Infarction With Patients With Wild Type Transthyretin Cardiac Amyloidosis

Introduction: Epicardial coronary arteries are also a target for intramural amyloid deposits in cardiac amyloidosis beyond the myocardium. For patients with restrictive cardiomyopathy and some degree of stable chronic angina, the role of coronary revascularization has not been clearly shown to have additional benefits over medical management. In unstable angina and Non-ST-elevation acute coronary syndrome (NSTE-ACS) population, isolated observations have painted a grimmer prognosis. Hypothesis: We hypothesized that wild-type ATTR-CA patients with NSTEMI undergoing Percutaneous coronary interventions (PCI) had poor outcomes. We sought to establish their prevalence and uncover the determinants of these outcomes. Methods: A five-year retrospective inquiry of the National Inpatient Sample (NIS) database from 2016 to 2020 on all the patients admitted with a matching diagnosis to the ICD-10 code of interest. Results: Over the five-year span of our observation, about 1,116,170 patients were admitted to the hospital in the US with an NSTE-ACS diagnosis, of which 99% underwent PCI during the same hospitalization (1,116,065). Among the latter 1,505 patients (1%) had ATTR-CA. The most represented demographics in that subpopulation were men (69%), elderly about 74 years old on average (80%), and Whites (60%). The cumulative mortality rate among the ATTR-CA PCI group was higher (18%) than the general NSTE-ACS PCI (14%). Factors associated with survival at hospital discharge were female sex (p-value 0.008), and black race (p-value 0.019). Meanwhile, Asian race (p-value 0.0001), being in a teaching hospital (p-value 0.0001), medium to large size hospital (p-value 0.0001) were harbingers of poor outcomes including death (18%), prolonged hospitalization (about 9.5 days), and higher healthcare costs (about $127,319). Conclusions: PCI has mortality benefits in STEMI and unstable CAD. However, in the ATTR-CA with unstable CAD, this might not be the case as seen with the staggering 28% risk increase in mortality rates in our study. Percutaneous revascularization in wild-type ATTR-CA deserves its own category when clinicians are weighing the benefits and a multidisciplinary approach should be preferred.

Abstract 17202: Cross-Species Evaluation of Cellular TNF Receptor-Associated Factor (TRAF) Expression, Regulation and Function in Murine and Human Atherosclerosis

Background: TNF receptor-associated factors (TRAFs) potently modulate immune cell function and activity in a variety of inflammatory diseases. However, due to the limited availability of viable animal models, the roles of TRAF3, TRAF4 and TRAF7 in atherosclerosis remain unknown to date. Here, we present a stepwise multiparametric approach to delineate cellular expression, regulation and implications on cardiovascular outcomes of TRAFs in murine and human atherosclerosis. Methods: To induce atherosclerotic lesion formation, LDLR-/- mice were fed a high cholesterol diet for 20 weeks and expression of TRAF1-7 was determined in whole tissue lysates of the murine aorta as well as on sorted leukocytes. We then performed scRNAseq and bioinformatical integration of leukocytes from human and mouse atherosclerotic plaques to analyze and compare single cell TRAF expression in both species. Finally, potential significance of cellular TRAF3, 4 and 7 expression in human atherosclerosis was assessed in three independent clinical study cohorts. Results: Aortic TRAF3 and TRAF4 expression was 2-fold higher in atherosclerotic mice compared to controls, whereas TRAF7 expression was significantly lower. Between species, humans exhibited higher cellular TRAF3 expression than mice. Further, TRAF7 blood expression was lower in patients with an unstable CAD angiogram than in patients with stable CAD while expression of TRAF3 in human atherosclerotic plaques was significantly higher in unstable compared to stable lesions. Finally, TRAF3 expression on circulating CD16+ monocytes determined by scRNAseq of PBMCs was substantially higher in atherosclerotic patients that died from a cardiovascular cause during 20 years of follow-up compared to survivors from the same study collective, indicating that cellular TRAF expression may predict cardiovascular long-term outcomes. Conclusion: Here, we present the first cross-species assessment of cellular TRAF3, 4 and 7 expression in murine and human atherosclerosis by utilizing a multiparametric approach to circumvent the lack of viable knockout models. Finally, we provide first evidence that cellular TRAF expression assessed by scRNAseq may add to the clinicians armamentarium for MACE prediction in the future.

RNA-sequencing reveals that STRN, ZNF484 and WNK1 add to the value of mitochondrial MT-COI and COX10 as markers of unstable coronary artery disease.

Markers in monocytes, precursors of macrophages, which are related to CAD, are largely unknown. Therefore, we aimed to identify genes in monocytes predictive of a new ischemic event in patients with CAD and/or discriminate between stable CAD and acute coronary syndrome. We included 66 patients with stable CAD, of which 24 developed a new ischemic event, and 19 patients with ACS. Circulating CD14+ monocytes were isolated with magnetic beads. RNA sequencing analysis in monocytes of patients with (n = 13) versus without (n = 11) ischemic event at follow-up and in patients with ACS (n = 12) was validated with qPCR (n = 85). MT-COI, STRN and COX10 predicted new ischemic events in CAD patients (power for separation at 1% error rate of 0.97, 0.90 and 0.77 respectively). Low MT-COI and high STRN were also related to shorter time between blood sampling and event. COX10 and ZNF484 together with MT-COI, STRN and WNK1 separated ACS completely from stable CAD patients. RNA expressions in monocytes of MT-COI, COX10, STRN, WNK1 and ZNF484 were independent of cholesterol lowering and antiplatelet treatment. They were independent of troponin T, a marker of myocardial injury. But, COX10 and ZNF484 in human plaques correlated to plaque markers of M1 macrophage polarization, reflecting vascular injury. Expression of MT-COI, COX10, STRN and WNK1, but not that of ZNF484, PBMCs paired with that in monocytes. The prospective study of relation of MT-COI, COX10, STRN, WNK1 and ZNF484 with unstable CAD is warranted.

Long- and short-term association of low-grade systemic inflammation with cardiovascular mortality in the LURIC study

The present study aimed to evaluate biomarkers representing low-grade systemic inflammation and their association with cardiovascular mortality in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. The included 3134 consecutive patients underwent coronary angiography between June 1997 and May 2001 with a median follow-up of 9.9years. Plasma levels of IL-6, and acute-phase reactants serum amyloid A (SAA) and C-reactive protein (CRP) were measured. SAA and IL-6 polymorphisms were genotyped. During a median observation time of 9.9years, 949 deaths (30.3%) occurred, of these 597 (19.2%) died from cardiovascular causes. High plasma levels of IL-6, CRP and SAA were associated with unstable CAD, as well as established risk factors including type 2 diabetes mellitus, smoking, low glomerular filtration rate, low TGs and low HDL-C. After adjusting for established cardiovascular risk markers and the other two inflammatory markers, SAA was found to be an independent risk factor for cardiovascular mortality after a short-term follow-up (6months-1year) with a HR per SD of 1.41. IL-6 was identified as an independent risk factor for long-term follow-up (3, 5, and 9.9years) with HRs per SD of 1.21, 1.22 and 1.18. CRP lost significance after adjustment. Although 6 out of 27 SAA SNPs were significantly associated with SAA plasma concentrations, the genetic risk score was not associated with cardiovascular mortality. The present findings from the large, prospective LURIC cohort underline the importance of inflammation in CAD and the prognostic relevance of inflammatory biomarkers that independently predict cardiovascular mortality.

The Novel CHA2DS2-VASC-FSH Score is Predictive of Severe Coronary Artery Disease on Coronary Angiography in Patients with Atrial Fibrillation and Unstable Symptoms.

AF may create confusion about the presence of severe or unstable coronary artery disease in cases with unstable symptoms. Novel scores and markers are needed to determine severe coronary artery disease in such patients. We aimed to test the newly developed CHA2DS2-VASc-FSH score, developed by adding family history for coronary artery disease, hyperlipidemia, and smoking to the original CHA2DS2-VASc score, in the prediction of severe CAD in patients with AF and unstable symptoms. We retrospectively analyzed 72 patients presenting to Başkent Universtiy School of Medicine Hospital between April 2011 and January 2016. The CHA2DS2VASc-FSH score was assessed for the prediction of severe CAD. Seventy-two patients aged 65.7±11.2 years were enrolled. Thirty-five (48.6%) patients had severe CAD and 11 (15.3%) had unstable CAD. patients with severe coronary artery disease had a significantly greater CHA2DS2VASC-FSH score (5 (1-8) vs 3(0-7); p<0.05). The CHA2DS2VASC-FSH score independently predicted severe CAD, with a CHA2DS2VASc-FSH score of 3 or greater having a sensitivity of 77.1% and a specificity of 56.8% for severe CAD. Among patients with AF and unstable symptoms, the CHA2DS2VASc-FSH score independently predicts severe CAD.

Trials Comparing Percutaneous And Surgical Myocardial Revascularization: A Review.

Ischemic heart diseases are the major leading cause of death worldwide. Revascularization procedures dramatically reduced the overall risk for death related to acute coronary syndromes. Two kinds of myocardial revascularization can grossly be outlined: percutaneous coronary intervention (PCI) and surgical coronary artery bypass graft intervention (CABG). The net clinical benefit coming from these two kinds of procedures is still under debate. We have traced the state-of-the-art background about myocardial revascularization procedures by comparing the most important trials dealing with the evaluation of percutaneous interventions versus a surgical approach to coronary artery diseases. Both PCI and CABG have become effective treatments for revascularization of patients suffering from advanced CAD. The advance in technology and procedural techniques made PCI an attractive and, to some extent, more reliable procedure in the context of CAD. However, there are still patients that cannot undergo PCI and have to be rather directed towards CABG. CABG still remains the best strategy for the treatment of multiple vessel CAD due to improved results in term of survival and freedom from reintervention. Anyway, a systematic, multidisciplinary approach to revascularization is the fundamental behaviour to be chased in order to effectively help the patients in overcoming its diseases. The creation of the "heart team" seems to be a good option for the correct treatment of patients suffering from stable and unstable CAD.

Abstract 17353: Comparing the Association of DKK-1, a Wingless (Wnt)-Regulatory Molecule, and CRP-1 With Cardiovascular Risk Factor Profile and Coronary Plaque Burden in Patients With Coronary Artery Disease

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&lt;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&lt;0.05), BMI (r=0.18, P&lt;0.05), LDL (r=0.18, P&lt;0.05) and significant negative correlation with age (r= -0.19, P&lt;0.05) and with HDL (r=-0.18, P&lt;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.

Lower Platelet Reactivity Is Associated with Presentation of Unstable Coronary Artery Disease.

In patients with acute coronary syndrome, high platelet reactivity (PR) is associated with an increased risk of secondary thrombotic events. However, in patients undergoing elective percutaneous coronary intervention (PCI), no association between high PR and outcome has been demonstrated. At present, the relation of PR and clinical symptoms is unknown. To examine the association of PR with clinical indication for diagnostic angiography (stable or unstable coronary artery disease [CAD]), taking into account the influence of P2Y12 inhibitors. A platelet function score (PFS) was determined in 195 patients by quantifying fibrinogen binding and P-selectin expression with flow cytometry. We evaluated the PFS with clinical presentation of stable or unstable CAD, angiographic severity of CAD, and the incidence of cardiovascular events during 2 years of follow-up. All data were analyzed stratified by P2Y12 inhibitor use (long-term and preprocedural versus none). Surprisingly, among non-P2Y12 inhibitor users, the PFS was lower in patients with unstable CAD compared with stable CAD (5.6 ± 1.8 vs. 7.4 ± 1.6; p = 0.001). Angiographic CAD severity showed no relation with PFS. The SYNTAX score tended to be inversely related with PFS: low PFS, 13.2 (IQR, 11.9-19.1); median PFS, 10.0 (IQR, 5.0-14.0); and high PFS, 8.0 (IQR, 5.0-13.0), without significance (p = 0.304). Patients with low PFSs required more re-PCIs than those with median and high PFSs (11.1 vs. 4.7 vs. 0.0%, p = 0.004). This association was modified for patients using P2Y12 inhibitors. Among patients without P2Y12 inhibitors undergoing coronary angiography, presentation of unstable CAD is independently associated with lower PR.

TRAIL is Reduced in the Circulation of Patients with CVD, and in Monocytes of Unstable CAD Patients

TRAIL is Reduced in the Circulation of Patients with CVD, and in Monocytes of Unstable CAD Patients

Role of stent type and of duration of dual antiplatelet therapy in patients with chronic kidney disease undergoing percutaneous coronary interventions. Is bare metal stent implantation still a justifiable choice? A post-hoc analysis of the all comer PRODIGY trial

AimChronic kidney disease (CKD) is a powerful predictor of major cardiovascular events and stent thrombosis (ST) in patients undergoing percutaneous coronary interventions (PCI). No randomized data are available to compare, and guide the selection of type of stent between bare metal (BMS) or drug eluting stent (DES) in this population. Methods and resultsWe performed a post-hoc analysis of the PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY (PRODIGY) trial, in which stable or unstable patients with coronary artery disease undergoing PCI were randomized 1:1:1:1 to receive BMS, paclitaxel- (PES), zotarolimus- (ZES-S), or everolimus- (EES) eluting stent. A total of 2003 patients were randomized, and 22 patients were excluded for missing serum creatinine leading to a final population of 1981 patients. Primary outcome was definite or probable ST. We also assessed MACE (myocardial infarction, stroke, or death), and all-cause death, as secondary outcome.CKD, defined with estimated glomerular filtration rate <60ml/min/1.73m2, was found in 373 patients (18.8%). The incidence of ST at 2years was 5.1% in CKD and 2.1% in non-CKD patients (HR 2.57, 95% confidence interval (CI) 1.46 to 4.52, p<0.001). At multivariable regression we found that patients randomized to EES or ZES-S, but not PES, had lower risk of ST at two years as compared with BMS: adjusted HR=0.288, 95% CI [0.107–0.778, p=0.014] and HR=0.394, 95% CI [0.164–0.947, p=0.037] respectively. The number of patients needed to be treated to prevent 1 ST with an EES vs BMS was 20 in CKD and 50 in patients without CKD. EES patients had the lowest incident MACE events 26.4% as compared to BMS 35.1%, ZES-S 33.0%, or PES 35.7% patients, p=0.551. All-cause death was lowest in ZES-S group 10.6% as compared to BMS 18.1%, PES 25.5% and EES 14.9%, p=0.040. We found no significant interaction between DAPT duration (6 vs 24months) and stent type on primary outcome, PINT=0.47 for BMS, PINT=0.57 for PES, PINT=0.41 for ZES-S and PINT=0.28 for EES. ConclusionsIn an all-comer population of patients with stable and unstable CAD, CKD at baseline was associated with a double risk of ST and MACE. CKD patients receiving EES had less than half risk of ST 2years after PCI as compared with BMS and PES. Our analysis suggests that 2nd generation limus-based stent should be favored over paclitaxel-based DES or BMS to reduce ST and MACE in CKD patients.

Abstract 4450: Does the Evidence Support Guideline Recommendations for Clopidogrel Pretreatment?

Although few concrete data exist about the optimal timing and dose of clopidogrel pretreatment, the ACC/AHA &amp; ESC guidelines endorse pretreatment with 300 – 600 mg of clopidogrel at least 2– 6 hours before PCI as Class IA (ACS) and Class IC (elective PCI) recommendation. To evaluate the current evidence base in support for clopidogrel pretreat-ment. Five trials examining the impact of clopidogrel pretreatment in stable and unstable CAD were evaluated: PCI-CURE, PCI-CLARITY, CREDO, PRAGUE-8, ARMYDA-5. Because of substantial clinical heterogeneity in trial design and population, concomitant therapies (glycoprotein 2b/3a inhibitors, thrombolysis, etc), loading dose, pretreatment duration and analysis plan between PCI-CURE, PCI-CLARITY and the rest, a formal meta-analysis was confined only to CREDO, PRAGUE-8, ARMYDA-5. The key data are summarized in the Table . Clopidogrel pretreatment was associated with significant reduction in ischemic outcomes without a significant increase in major bleeding in two out of the 5 trials (PCI-CURE and PCI-CLARITY). Both these trials utilized nonrandomized subgroup comparisons with pretreatment duration longer than that typically encountered in clinical practice (&lt;48h). A meta-analysis of the 3 trials demonstrated a nonsignificant 23% odds reduction in efficacy (P=0.1) and a nonsignificant 29% odds increase in major bleeding (P=0.24). No significant heterogeneity was observed for pooled efficacy (P=0.79) or bleeding (P=0.77) outcomes. Pretreatment hypothesis is currently not validated in rigorous prospective assessments, thereby calling into question the Class I recommendation (benefit &gt;&gt;&gt;risk) endorsed by the guidelines. Clearly, further clinical data regarding dose, time course of pretreatment and associated benefit are warranted to provide unequivocal support. Until then, it is prudent to rule out surgical CAD before pretreatment to avoid bleeding risk. Trials Assessing Clopidogrel Pretreatment

Increased Plasma Concentration of Matrix Metalloproteinase-7 in Patients with Coronary Artery Disease

Plaque rupture is often associated with breakdown of the extracellular matrix in the shoulder region of a plaque. We tested whether plasma concentrations of various matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) could serve as markers for plaque instability as well as relationships between plasma MMPs and inflammatory markers. The study group included 65 men with angiographically verified CAD (45 with stable and 20 with unstable CAD) and 28 healthy controls. Circulating MMP, TIMP-1, C-reactive protein, and cytokine concentrations were measured by ELISA. Leukocyte subtype counts in whole blood were determined, and T-cell subsets and natural killer cells were measured by flow cytometry. Differences in continuous variables between groups were tested by ANOVA with the Scheffé F-test used as a post hoc test, and correlations were analyzed by a linear regression method. The plasma concentration of MMP-7 was increased in patients with stable and unstable CAD, whereas MMP-2 and -3 concentrations were decreased. The plasma concentration of TIMP-1 was significantly increased in patients with unstable CAD. MMP-2, -3, and -7 showed no correlations with established markers of inflammation. However, MMP-2 correlated positively with the number of natural killer cells in patients with stable and unstable CAD. Plasma concentrations of MMPs and TIMPs may be markers of CAD but appear to be differentially regulated.

An early invasive strategy reduced death, myocardial infarction, and hospital readmissions at 2 years in unstable CAD

Source Citation Lagerqvist B, Husted S, Kontny F, et al. A long-term perspective on the protective effects of an early invasive strategy in unstable coronary artery disease: two-year follow-up of t...

Dalteparin warranted for unstable CAD in Sweden

Dalteparin warranted for unstable CAD in Sweden

Dalteparin warranted for unstable CAD in Sweden

Dalteparin warranted for unstable CAD in Sweden

Early Invasive Treatment of Unstable CAD Less Beneficial for Women Than Men

Invasive management has been shown to benefit patients with acute coronary syndrome (JWC Oct 2000, p. 78, accession number 000915006, and Lancet 2000;

Early invasive revascularization strategy was more effective than a non-invasive strategy at one year in patients with unstable CAD

Early invasive revascularization strategy was more effective than a non-invasive strategy at one year in patients with unstable CAD

Troponin T and C-reactive protein levels were useful in predicting cardiac mortality in patients with unstable CAD

Troponin T and C-reactive protein levels were useful in predicting cardiac mortality in patients with unstable CAD

Effects of low-molecular-weight heparin treatment on fibrinolytic markers in unstable coronary artery disease

Objectives: Low-molecular-weight heparins (LMWHs) efficiently reduce the coagulant activity, but their influence on the fibrinolytic system and fibrin turnover is not fully elucidated. We therefore determined markers offibrinolytic activity, fibrin turnover and inflammation in LMWH treated patients with acute coronary artery disease.Design: Double-blind placebo controlled clinical trial.Setting: Consecutive patients admitted at two centers.Subjects: Individuals with unstable angina or non-Q-wave MI (n= 87).Interventions: Randomized to placebo-controlled subcutaneous dalteparin treatment, 120 IU/kg bw twice daily for 5–8 days and 7500IU once daily over the next 35–45 days.Main outcome measures: Markers of fibrinolytic activity, i.e. tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor 1 (PAI-1) activity, plasminogen anti-plasmin (PAP) complex, and D-dimer determined at inclusion, after 2, 5 and 40–50 days. C-reactive protein (CRP), fibrinogen and prothrombin fragment 1+2 (F1+2) were determined at inclusion.Results: At inclusion there were positive correlations between fibrinogen, CRP and D-dimer levels. During LMWH treatment there was a marked increase in t-PA antigen concentration, a rise in PAI-1 activity and a slight decrease in PAP-complex levels. The LMWH administration was also associated with a long-lasting decrease in the D-dimer concentrations. In the placebo group there was a slight and transient increase in all the evaluated markers of fibrinolytic activity and fibrin turnover.Conclusion: In unstable CAD increased inflammatory activity is associated with increased thrombin generation and fibrin turnover. During LMWH treatment there is a sustained reduction in fibrin turnover and no rise in plasmin generation despite an increase in t-PA level.

Invasive strategy preferable for unstable CAD?

Invasive strategy preferable for unstable CAD?