Acute Phase Of Acute Coronary Syndrome Research Articles

Initial decrease in the lipoprotein(a) level is a novel prognostic biomarker in patients with acute coronary syndrome.

Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular diseases; however, its role in acute coronary syndrome (ACS) remains unclear. To investigate the hypothesis that the Lp(a) levels are altered by various conditions during the acute phase of ACS, resulting in subsequent cardiovascular events. From September 2009 to May 2016, 377 patients with ACS who underwent emergent coronary angiography, and 249 who completed ≥ 1000 d of follow-up were enrolled. Lp(a) levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention (PCI) to 48 h after PCI. The primary endpoint was the occurrence of major adverse cardiac events (MACE; cardiac death, other vascular death, ACS, and non-cardiac vascular events). The mean circulating Lp(a) level decreased significantly from pre-PCI (0 h) to 12 h after (19.0 mg/dL to 17.8 mg/dL, P < 0.001), and then increased significantly up to 48 h after (19.3 mg/dL, P < 0.001). The changes from 0 to 12 h [Lp(a)Δ0-12] significantly correlated with the basal levels of creatinine [Spearman's rank correlation coefficient (SRCC): -0.181, P < 0.01] and Lp(a) (SRCC: -0.306, P < 0.05). Among the tertiles classified according to Lp(a)Δ0-12, MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups (66.2% vs 53.6%, P = 0.034). A multivariate analysis revealed that Lp(a)Δ0-12 [hazard ratio (HR): 0.96, 95% confidence interval (95%CI): 0.92-0.99] and basal creatinine (HR: 1.13, 95%CI: 1.05-1.22) were independent determinants of subsequent MACE. Circulating Lp(a) levels in patients with ACS decreased significantly after emergent PCI, and a greater decrease was independently associated with a worse prognosis.

Inflammasome activation dynamics within the first 24 hours in patients treated with PCI for myocardial infarction is influenced by the age of patients, preliminary report

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Presented study was financially supported by the Mini-student Grant for medical students of Medical University of Warsaw, No 24/M/MG/N/21 and Grant for Young Researchers of The Medical University of Warsaw, No 2W6/1/M/MBS/N/21. Background Until today, majority of data on the possible role of inflammasome activation in acute coronary syndrome (ACS) patients comes from preclinical studies. Purpose We aimed to determine the dynamics of the expression profile of selected inflammasome genes and inflammasome related factors by quantitative real-time polymerase chain reaction (qRT-PCR) in peripheral blood mononuclear cells (PBMCs) of patients in the acute phase of ACS. Methods In the study group the blood samples for RT-PCR were collected 3 times: at the beginning of the percutaneous coronary intervention (PCI) for ACS, 3h, and 24h after PCI. The study group samples were compared with blood collected from 10 patients with no significant coronary lesions identified during coronary angiography. The relative expression of evaluated genes was analyzed in relation to the β-actin gene in relation to the expression in 0-hour sample using the ΔΔCT method. Based on the literature, we defined a significant change in gene expression at a fold change of 1.5. Results For this preliminary study the population of 19 patients aged 64±13and 84% presented with ST-elevation myocardial infarction (STEMI). Expression of evaluated genes at 3h and 24h relative to 0h sample is presented in picture 1. Gene expression did not differ significantly between the study and control group except for NLR Family Pyrin Domain Containing 6 (NLRP6) (at 3h post-PCI: ΔΔCT=2.5425 vs 0.0005; p=0.002, 24h post-PCI: ΔΔCT=2.1794 vs 0.0005; p=0.009). However, we observed significant upregulation in samples taken at 3h post-PCI relative to 0h level for AIM2 [fold change relative to 0h 1.52 (0.63; 4.67)], IL-1β [2.81 (1.59; 5.93)], IL-18 [2.07 (0.59; 10.14)] and at 24 h for AIM2 [1.90 (0.78; 2.52)], IL-1β [5.16 (2.23; 13.32)] and IL-18 [2.20 (0.59; 5.96)] in the younger subgroup of patients (≤the median age of the study population which was equal 66 years old). We performed a comparison of younger (≤66) vs. older (&amp;gt;66) patients at 3h and 24h post-PCI and observed significantly higher relative gene expression in the younger subgroup compared to the older subgroup of patients at 3h in case of IL-1β (p=0.03), and at 24h in case of NLR Family Pyrin Domain Containing 1(NLRP1)(p=0.016), AIM2 (p=0.04), NLR Family Pyrin Domain Containing 12(NRLP12)(p=0.06), IL-1 (p=0.04), and IL-18 (p=0.03) – the exact fold change values are presented in Table 1. Conclusion NLRP6 is significantly upregulated in ACS patients compared to control subjects in the first 24h post-PCI. We also observed significant dynamics in NLRP3 inflammasome related factors, including IL-1β, IL-18, in the first 24h post-PCI for MI. Also, the activation of the inflammasome genes (NLRP1, NLRP12) and inflammasome effectors may present different dynamics dependent on the age of the patients, and it might be helpful in careful selection of the timepoint for the future administration of inflammasome dedicated inhibitors.Relative genes expressionFold change in gene expression

Identification of depression in patients with acute coronary syndrome using multiple serum biomarkers

BackgroundBiomarkers for depression in patients with acute coronary syndrome (ACS) have not been identified. MethodsThis study evaluated multiple serum biomarkers for depressive disorders after ACS. Thirteen serum biomarkers associated with seven functional systems, along with sociodemographic/clinical characteristics, were evaluated in 969 patients within 2 weeks after ACS onset (acute phase). In total, 711 patients were evaluated for depressive disorder using DSM-IV criteria 1 year later (chronic phase). Logistic regression was used for the analysis. ResultsDepressive disorders were observed in 378 patients (39.0%) in the acute phase of ACS and 183 patients (25.7%) in the chronic phase. The weighted scores of five serum biomarkers (high-sensitivity C-reactive protein, interleukin-6, homocysteine, troponin I, and creatine kinase-MB) were significantly associated with depressive disorder diagnosis in the acute phase, and the weighted scores of three other biomarkers (tumor necrosis factor-alpha, interleukin-1 beta, and homocysteine) were significantly associated with depressive disorders in the chronic phase, in a dose-dependent manner after adjusting for relevant covariates (all P-values <0.001). ConclusionsThe combination of several serum biomarkers exhibited robust associations with depressive disorders in both the acute and chronic phases of ACS.

Effect of evolocumab on platelet function in patients with acute coronary syndromes. An analysis of the randomized, double-blind, placebo-controlled EVOPACS Trial

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors substantially lower levels of low-density lipoprotein cholesterol (LDL-C) and favourably impact clinical outcomes in patients with acute coronary syndromes (ACS). Although PCSK9 inhibitors have been suggested in ex vivo studies to suppress platelet activation, the impact of evolocumab on platelet function in ACS patients receiving potent antiplatelet therapy remains largely unknown. Methods The EVOPACS trial was a randomized, double-blind, placebo-controlled trial assessing the use of evolocumab initiated in the acute phase of ACS. Patients presenting with ST-elevation myocardial infarction (STEMI) or Non-ST-elevation ACS (NSTE-ACS) were randomly allocated in a 1:1 ratio to either evolocumab 420mg SC or matching placebo at baseline (during hospitalization for index ACS event) and after 4 weeks. All patients received atorvastatin 40mg daily. Dual antiplatelet therapy consisting of aspirin and a potent P2Y12 inhibitor was initiated according to STEMI / NSTE-ACS guidelines, unless a less potent treatment was indicated (e.g. due to concomitant use of oral anticoagulation). Platelet function was measured at baseline (during index hospitalization) and after 8 weeks, using the Multiplate analyser. The main outcome for this analysis was the change from baseline to 8 weeks in adenosine diphosphate (ADP)-induced platelet aggregation. Results Serial platelet function measurements were available in 260 of all 308 enrolled patients, 124 in the evolocumab and 136 in the placebo group. Mean age was 60.2±11.0 years and 83% were men. Baseline clinical characteristics were well balanced between the two treatment groups. At discharge, the proportion of patients treated with ticagrelor, prasugrel, and clopidogrel was 73%, 11%, and 9% respectively, without differences between groups. Evolocumab significantly reduced LDL-C compared to placebo at 8 weeks (difference in mean percentage change -40.75%, 95% CI -45.39 to -36.11; p&amp;lt;0.001). Change in ADP-induced platelet aggregation between baseline and 8-week follow-up was -5.6±23.5 U (from 24.1±19.8 to 29.7±25.6 U) in the evolocumab group vs. -1.7±198.7 U (from 23.0±14.7 U to 24.7±19.1 U) in the placebo group (p=0.13). Similar results were found in a subgroup of 189 patients (86 in the evolocumab and 103 in the placebo group) treated with ticagrelor at discharge, showing a change in ADP-induced platelet aggregation of -2.7±19.5 U with evolocumab vs. -2.4±19.9 U with placebo (p=0.80). Conclusions In this randomized trial of ACS patients largely treated with a potent P2Y12 inhibitor, evolocumab initiated during index hospitalization on top of high-intensity statin therapy had no measurable effect on ADP-induced platelet aggregation. These findings suggest that the early therapeutic benefit of PCSK9 inhibitors in ACS patients is likely related to plaque regression/stabilization rather than changes in platelet activity.

Outcomes of a Cardiac Rehabilitation (CRH) Program after phase II: what about our patients almost 4 years later?

Abstract Funding Acknowledgements Type of funding sources: None. INTRODUCTION CRH in patients with ischemic heart disease is recommended by the different clinical practice guidelines with an IA level of evidence, with an important role in reducing cardiovascular mortality and hospital readmissions during follow-up. OBJECTIVE The goal of this study is to show the 4-year clinical results of a population of patients who participated in an CRH program after an Acute Coronary Syndrome (ACS). METHODS Between May/2014 and September/2017, 221 patients who had recently presented an ACS completed the 12 weeks of phase II of the CRH program at our center. In May/2020 we collected epidemiological, clinical and echocardiographic information at the time of the acute cardiovascular event; and we evaluate the current vital status of the patients and the incidence of readmissions for: angina, HF, new ACS, or arrhythmic events. RESULTS Of the 221 patients, 182 were men (82%). The mean age of our population was 58.3 ± 7.8 years. 58% (129 patients) suffered from ST-elevation ACS. The mean time of hospital stay was 6.20 ± 2.9 days. An echocardiogram was performed at discharge, which showed an average LVEF of 56 ± 6%. Eight patients (4%) developed early Ventricular Fibrilation (VF) during the acute phase of ACS. Among the classic CVRF, smoking (79%) was the most prevalent, followed by dyslipidemia (53%) and hypertension (47%). The mean time from hospital discharge to the start of phase II RHC was 42 ± 16 days. The overall incidence of events was 9%: 10 patients suffered reinfarction during follow-up, and 7 were readmitted for unstable angina, all of whom underwent PCI; no patient was admitted for HF; and none of the 8 patients with early VF had a new tachyarrhythmia, registering a single admission for VT during follow-up. None of the patients had sustained ventricular tachyarrhythmias during exercise-training. At the mean 4.5-year follow-up, 218 patients were still alive (98%). CONCLUSION The incidence of CV events in the follow-up of our cohort was low, which can be explained by the fact that it is a young population, with an LVEF at low limits of normality at discharge, which is one of the most important predictors in the prognosis after an ischemic event. As an improvement, we must shorten the time until the start of phase II of the program. CRH shows once again its clinical benefit after an ACS, in consonance with the existing evidence. Abstract Figure. Outcomes of a CRH program.

Is HBA1C reliable in diagnosing diabetes in the acute phase of acute coronary syndromes?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Hospitalization due to acute coronary syndromes (ACS) usually is the occasion that leads to diagnosis of type 2 diabetes mellitus (T2DM). Current literature suggests that the severity of the ACS could be associated with the presence and the severity of DM. Purpose To study the reliability of HbA1c in the diagnosis of T2DM in the acute phase of ACS, as well as the presence of possible correlation between the HbA1c and the severity of ACS. Methods We evaluated 160 consecutive patients admitted due to ACS. HbA1c was measured on day 1 and day 90. HbA1c &amp;gt;6.5% was used to diagnose T2DM and HbA1c 5.7-6.4% was used to diagnose pre-diabetes. The severity of ACS was assessed via Gensini score. Results are interpreted as mean ± SD. Comparisons were made by one way ANOVA(p &amp;lt; 0.05 was regarded statistically significant).Spearman’s rank correlation was used to study the correlation between Gensini score and the other parameters. Results Mean age was 59.73 ± 12.21 years. 103/160(64.37%) were male and 57/160(35.63%) were female. 19/160(11.87%) were diagnosed as STEMI and 141/160(88.13%) as NSTEMI. Mean BMI was 29.55 ± 8.41 kg/m2 and mean Hb 12.62 ± 2.08 g/dl. On day 1, 43/160 (26.87%) had HbA1c &amp;gt; 6.5% and 41/160(25.62%) HbA1c 5.7-6.4%. On day 90, 28/160 (17.5%) had HbA1c &amp;gt; 6.5% and 52/160(32.5%) HbA1c 5.7-6.4%. Gensini score varied between 0-144 with mean value 40.26 ±35.9. A strong correlation was found between Gensini score and HbA1c on admission as well as on day 90 (rho-0.36, p &amp;lt; 0.05 and rho = 0.32, p &amp;lt; 0.05 respectively). Conclusion HbA1c seems to be reliable in the identification of pre-diabetes but not T2DM in the acute phase of ACS. The correlation of the severity between ACS and HbA1c seems to relate with the worst prognosis of T2DM patients.

Obstructive sleep apnea during acute coronary syndrome is related to myocardial necrosis and wall stress

BackgroundThe relative contribution of pathophysiological mechanisms in acute coronary syndrome (ACS) towards obstructive sleep apnea (OSA) is not well-studied. We examined the correlation between severity of OSA and inflammation, myocardial necrosis, wall stress, and fibrosis. MethodsA total of 89 patients admitted with ACS underwent a sleep study during index admission. Plasma levels of high-sensitivity C-reactive protein (hs-CRP), troponin I, N-terminal pro-brain natriuretic peptide (NT-proBNP), and suppression of tumorigenicity 2 (ST2) were prospectively analyzed. Two patients diagnosed with central sleep apnea were excluded. ResultsThe recruited patients were divided into no (AHI <5 events/hour, 9.2%), mild (5-<15, 27.6%), moderate (15-<30, 21.8%), and severe (≥30, 41.4%) OSA. Compared to the no, mild and moderate OSA groups, the severe OSA group had a higher body mass index (p = 0.005). They were also more likely to present with ST-segment elevation ACS (versus non-ST-segment elevation ACS) (p = 0.041), have undergone previous coronary artery bypass grafting (p = 0.013), demonstrate complete coronary occlusion during baseline coronary angiography (p = 0.049), and have a larger left atrial diameter measured on echocardiography (p = 0.029). Likewise, the severe OSA group had higher plasma levels of hs-CRP (p = 0.004), troponin I (p = 0.017), and NT-proBNP (p = 0.004), but not ST2 (p = 0.10). After adjustment for the effects of confounding variables, OSA was independently associated with troponin I (ie, myocardial necrosis; p = 0.001) and NT-proBNP (ie, myocardial wall stress; p = 0.008). ConclusionSevere OSA during the acute phase of ACS was associated with extensive myocardial necrosis and high myocardial wall stress, but not with inflammation and myocardial fibrosis.

Close Association of Matrix Metalloproteinase-9 Levels With the Presence of Thin-Cap Fibroatheroma in Acute Coronary Syndrome Patients: Assessment by Optical Coherence Tomography and Intravascular Ultrasonography

BackgroundThin-cap fibroatheroma (TCFA) has been suggested as a precursor lesion of coronary plaque rupture. As elevated plasma matrix metalloproteinase-9 (MMP-9) levels have been documented in patients with acute coronary syndrome (ACS), we sought to determine whether the presence of TCFA is linked to MMP-9 levels in these patients. MethodsWe evaluated 51 ACS patients with de novo culprit lesions who were examined via optical coherence tomography and intravascular ultrasound. Blood samples were obtained from the peripheral vein (PV) and the ostium and culprit lesion of the infarct-related coronary artery (CA) in the acute phase of ACS and from the PV in the chronic phase (8 months after ACS). ResultsThe plasma MMP-9 level in the acute phase was significantly higher than that in the chronic phase. Plasma MMP-9 levels at the culprit lesion of the infarct-related CA were significantly higher than, but positively correlated with those in the PV (10.9 (5.9–16.1) ng/mL and 8.9 (5.6–13.0) ng/mL, p < 0.0001, respectively; Spearman ρ = 0.84, p < 0.0001). Significantly higher PV plasma MMP-9 levels were observed in patients with TCFA than in patients without TCFA (12.1 (7.0–13.5) and 5.7 (4.0–8.2) ng/ml, p<0.0001, respectively). Further, plasma MMP-9 levels in the PV were positively correlated with the remodeling index (Spearman ρ = 0.29, p = 0.039) and negatively correlated with fibrous cap thickness (Spearman ρ = −0.42, p = 0.0021). Receiver operating characteristic curve analysis showed that the plasma MMP-9 levels in the PV could predict the presence of TCFA at a cut-off value of 9.9 ng/mL. ConclusionsPlasma MMP-9 levels were closely associated with MMP-9 levels in the CA and were further linked with TCFA in patients with ACS.

Acute coronary syndromes with high thrombotic burden: therapeutic innovations.

Antiplatelet agents represent one of the cornerstones of drug therapy for acute coronary syndromes (ACS). In the last decade, the arrival of prasugrel and ticagrelor, faster and more powerful oral platelet receptor P2Y12 inhibitors compared to clopidogrel, significantly improved platelet inhibition in patients with ACS. However, the reduction of thrombotic risk came at the cost of increased bleeding risk. Despite having similar indications, prasugrel and ticagrelor have different characteristics and methods of use, essentially due to a different design of the trials in which they have been studied. The optimal use of these antiplatelets in clinical practice should therefore be tailored in individual patients. In the acute phase of ACS with high thrombotic burden, all oral P2Y12 inhibitors have limitations, mainly due to the delay of onset of action related to oral administration. In this scenario, parenteral antiplatelet agents (glycoprotein inhibitors IIb/IIIa and cangrelor) may play a key role in case of percutaneous coronary interventions of high thrombotic coronary lesions and in the prevention of early thrombotic complications. Cangrelor, an intravenous inhibitor of the P2Y2 receptor, has peculiar pharmacokinetic and pharmacodynamic characteristics that make it particularly suitable to be used as an antiplatelet during coronary angioplasty as it achieves a rapid and powerful antiplatelet effect in patients not pretreated with oral medications, and has a favourable safety profile in relation to the bleeding risk.

Inflammatory state does not affect the antiplatelet efficacy of potent P2Y12 inhibitors in ACS

Inflammation leads to atherosclerosis and acute coronary syndromes (ACS). We performed a prospective, observational study to assess association between the concentrations of inflammatory markers (high sensitivity C-reactive protein, hsCRP; high sensitivity interleukin6, hsIL-6; soluble CD40 ligand, sCD40 L) and platelet reactivity in 338 patients with ACS treated with ticagrelor and prasugrel. We also assessed whether hsCRP, hsIL-6, and sCD40 L are associated with standard inflammatory markers (white blood cell [WBC] and fibrinogen), and whether they differ according to patient diabetic status and pre-treatment with statins. Concentrations of hsCRP and concentrations of hsIL-6 and sCD40 L were assessed using turbidimetric assay and enzyme-linked immunosorbent assay, respectively. Platelet reactivity was measured using multiple electrode aggregometry. There was only a weak inverse correlation between hsIL-6 and platelet reactivity (r≤-0.125). In contrast, concentration of hsIL6 and hsCRP positively correlated with WBC and fibrinogen (r ≥ 0.199). Insulin-dependent diabetes mellitus (IDDM) was associated with higher concentration of hsIL-6 (p = .014), whereas pre-treatment with statins – with lower concentration of hsIL-6 (p = .035). In conclusion, inflammatory state does not affect the antiplatelet efficacy of potent P2Y12 inhibitors in the acute phase of ACS, confirming the safety and efficacy of potent P2Y12 inhibitors in patients with a high inflammatory burden.

1013 Cardiovascular Biomarkers and Pathophysiological Insights into Obstructive Sleep Apnea During Acute Coronary Syndrome

Abstract Introduction Obstructive sleep apnea (OSA) is prevalent and carries prognostic implication in patients with acute coronary syndrome (ACS). The relative contribution of pathophysiological mechanisms in ACS towards OSA is not well-studied. We examined the correlation between severity of OSA and myocardial necrosis, inflammation, wall stress, and fibrosis. Methods A total of 89 patients admitted with ACS underwent an overnight sleep study during index admission. Plasma levels of peak troponin I, high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and suppression of tumorigenicity 2 (ST2) were prospectively analyzed. Two patients diagnosed with central sleep apnea were excluded. Results The recruited patients were divided into no (AHI &amp;lt;5 events/hour, 9.2%), mild (5-&amp;lt;15, 27.6%), moderate (15-&amp;lt;30, 21.8%), and severe (≥30, 41.4%) OSA. The respective Epworth Sleepiness Scale scores were 3.8±3.7, 5.3±4.9, 4.0±2.8, and 5.5±4.5 (p=0.734). Compared to the no, mild and moderate OSA groups, the severe OSA group had a higher body mass index (p=0.005). They were also more likely to present with ST-segment elevation ACS (vs non-ST-segment elevation ACS) (p=0.041), have undergone previous coronary artery bypass grafting (p=0.013), demonstrate complete coronary occlusion during baseline coronary angiography (p=0.049), and have a larger left atrium diameter measured on echocardiography (p=0.029). Likewise, the severe OSA group had higher plasma levels of troponin I (10584±13078, 11699±20130, 19280±30670, 37571±31269 µg/L; p=0.017), hs-CRP (8.1±9.2, 23.1±52.3, 9.3±17.1, 39.4±44.7 mg/L; p=0.004), and NT-proBNP (667±604, 765±856, 636±728, 1395±1220 pg/mL; p=0.004), but not ST2 (p=0.10). After adjusting for the effects of the confounding variables, severe OSA was independently associated with troponin I (i.e., myocardial necrosis; OR 1.00003, 95% CI 1.000013-1.000048; p=0.001) and NT-proBNP (i.e., myocardial wall stress; OR 1.00081, 95% CI 1.00021-1.00141; p=0.008). Conclusion Severe OSA during the acute phase of ACS was associated with extensive myocardial necrosis and myocardial wall stress, but not with inflammation and myocardial fibrosis. Support Nil

Evolocumab for Early Reduction of LDL Cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS)

BackgroundAlthough guidelines recommend in-hospital initiation of high-intensity statin therapy in patients with acute coronary syndromes (ACS), low-density lipoprotein cholesterol (LDL-C) target levels are frequently not attained. Evolocumab, a rapidly acting, potent LDL-C–lowering drug, has not been studied in the acute phase of ACS. ObjectivesThe purpose of this study was to assess the feasibility, safety, and LDL-C–lowering efficacy of evolocumab initiated during the in-hospital phase of ACS. MethodsThe authors conducted an investigator-initiated, randomized, double-blind, placebo-controlled trial involving 308 patients hospitalized for ACS with elevated LDL-C levels (≥1.8 mmol/l on high-intensity statin for at least 4 weeks; ≥2.3 mmol/l on low- or moderate-intensity statin; or ≥3.2 mmol/l on no stable dose of statin). Patients were randomly assigned 1:1 to receive subcutaneous evolocumab 420 mg or matching placebo, administered in-hospital and after 4 weeks, on top of atorvastatin 40 mg. The primary endpoint was percentage change in calculated LDL-C from baseline to 8 weeks. ResultsMost patients (78.2%) had not been on previous statin treatment. Mean LDL-C levels decreased from 3.61 to 0.79 mmol/l at week 8 in the evolocumab group, and from 3.42 to 2.06 mmol/l in the placebo group; the difference in mean percentage change from baseline was −40.7% (95% confidence interval: −45.2 to −36.2; p < 0.001). LDL-C levels <1.8 mmol/l were achieved at week 8 by 95.7% of patients in the evolocumab group versus 37.6% in the placebo group. Adverse events and centrally adjudicated cardiovascular events were similar in both groups. ConclusionsIn this first randomized trial assessing a PCSK9 antibody in the very high-risk setting of ACS, evolocumab added to high-intensity statin therapy was well tolerated and resulted in substantial reduction in LDL-C levels, rendering >95% of patients within currently recommended target levels. (EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes [EVOPACS]; NCT03287609)

Metabolism of ticagrelor in patients with acute coronary syndromes

Ticagrelor is a state-of-the-art antiplatelet agent used for the treatment of patients with acute coronary syndromes (ACS). Unlike remaining oral P2Y12 receptor inhibitors ticagrelor does not require metabolic activation to exert its antiplatelet action. Still, ticagrelor is extensively metabolized by hepatic CYP3A enzymes, and AR-C124910XX is its only active metabolite. A post hoc analysis of patient-level (n = 117) pharmacokinetic data pooled from two prospective studies was performed to identify clinical characteristics affecting the degree of AR-C124910XX formation during the first six hours after 180 mg ticagrelor loading dose in the setting of ACS. Both linear and multiple regression analyses indicated that ACS patients presenting with ST-elevation myocardial infarction or suffering from diabetes mellitus are more likely to have decreased rate of ticagrelor metabolism during the acute phase of ACS. Administration of morphine during ACS was found to negatively influence transformation of ticagrelor into AR-C124910XX when assessed with linear regression analysis, but not with multiple regression analysis. On the other hand, smoking appears to increase the degree of ticagrelor transformation in ACS patients. Mechanisms underlying our findings and their clinical significance warrant further research.

Genetic predisposition toward suicidal ideation in patients with acute coronary syndrome.

The genetic predisposition toward suicidal ideation has been explored to identify subgroups at high risk and to prevent suicide. Acute coronary syndrome (ACS) is associated with an increased risk of suicide, but few studies have explored the genetic predisposition toward suicide in ACS populations. Therefore, this longitudinal study explored the genetic predisposition toward suicidal ideation in ACS patients. In total, of 969 patients within 2 weeks after ACS, 711 were followed at 1 year after ACS. Suicidal ideation was evaluated with the relevant items on the Montgomery–Åsberg Depression Rating Scale. Ten genetic polymorphisms associated with serotonergic systems, neurotrophic factors, carbon metabolism, and inflammatory cytokines were examined. Associations between genetic polymorphisms and suicidal ideation within 2 weeks and 1 year of ACS were investigated using logistic regression models. The 5-HTTLPR s allele was significantly associated with suicidal ideation within 2 weeks of ACS after adjusting for covariates and after the Bonferroni correction. TNF-α –308G/A, IL-1β –511C/T, and IL-1β + 3953C/T were significantly associated with suicidal ideation within 2 weeks after ACS, but these associations did not reach significance after the Bonferroni correction in unadjusted analyses and after adjusting for covariance. However, no significant association between genetic polymorphisms and suicidal ideation was found at 1 year. Genetic predisposition, 5-HTTLPR s allele in particular, may confer susceptibility to suicidal ideation in ACS patients during the acute phase of ACS.

Effects of statins on plaque rupture assessed by optical coherence tomography in patients presenting with acute coronary syndromes: insights from the optical coherence tomography (OCT)-FORMIDABLE registry.

Chronic pre-treatment with statins may reduce mortality and morbidity in patients experiencing acute coronary syndromes (ACS), but mechanisms accounting for these findings are not completely understood. The optical coherence tomography (OCT)-Formidable registry retrospectively enrolled 285 consecutive patients with ACS undergoing OCT in 9 European centres. Mean age was 60.4 ± 12.8 years, 148 (51.9%) patients had hyperlipemia, 45 (15.8%) diabetes mellitus and 142 (49.8%) presented with ST Segment Elevation Myocardial Infarction (STEMI). Patients were stratified according to statin prescription: 150 (52.6%) were on chronic pre-treatment with statins before ACS and were more likely to present with non-ST segment elevation acute coronary syndromes (NSTE-ACS) at admission (111, 74%) rather than STEMI, while the opposite was observed for patients not on statins. The primary end-point of ruptured plaque at OCT occurred significantly less frequently in the patients on chronic pre-treatment with statins [odds ratio (OR) 0.375, 95% confidence interval (CI) 0.185-0.759, P = 0.006]. The secondary end-point of thin-cap fibro-atheroma (TCFA) at any site was significantly less frequent in the statin group (OR 0.423, 95%CI 0.213-0.840, P = 0.014). No differences were observed for the secondary end-point of not-ruptured TCFA as the culprit lesion. Pre-specified sensitivity analysis was conducted according to the pattern of ACS: the reported differences were confirmed for NSTE-ACS patients, with a trend towards less plaque rupture and a significant reduction of TCFA at any site with statins, but not for STEMI. Chronic pre-treatment with statins is associated with a reduced prevalence of ruptured plaques in patients presenting with ACS, particularly in those with NSTE-ACS. Statins bear hence the potential to reduce morbidity during the acute phase of ACS.

A consensus statement on lipid management after acute coronary syndrome.

In patients admitted for acute coronary syndrome (ACS), the guidelines of the European Society of Cardiology give a Class I, Level A recommendation for the prescription of high-intensity statins to be initiated as early as possible, regardless of the low-density lipoprotein cholesterol (LDL-C) level. Although statins are widely prescribed after ACS, the intensity of therapy and the proportion of patients achieving target LDL-C values are often not in line with recommendations due to a lack of compliance with guidelines by the physicians, a lack of compliance with treatment or poor tolerance by patients, and poor dose adaptation. In this context, a group of French physicians came together to define strategies to facilitate and improve the management of lipid-lowering therapy after ACS. This paper outlines the scientific rationale for the use of statins at the acute phase of ACS, the utility of ezetimibe, the measurement of LDL-C during the course of ACS, the opportunities for detecting familial hypercholesterolaemia and the results of the consensus for the management of lipid-lowering therapy, illustrated in two decision-making algorithms.

Determinants and escitalopram treatment effects on suicidal ideation in patients with acute coronary syndrome: Findings from the K-DEPACS and EsDEPACS studies

BackgroundThis study is aimed to investigate the determinants of suicidal ideation as well as to assess escitalopram treatment effects on suicidal ideation in patients with acute coronary syndrome (ACS). MethodsA total of 1152 patients were consecutively recruited at baseline, 2 to 14weeks after a confirmed ACS episode. Of 446 baseline participants with comorbid depressive disorders, 300 were randomized to a 24-week double-blind trial of escitalopram or placebo treatment. Suicidal ideation was determined using the “suicidal thoughts” item of the Montgomery and Asberg Depression Rating Scale. Socio-demographic and clinical characteristics, including depressive and anxiety symptoms, cardiovascular risk factors, and current cardiac status, were assessed. ResultsSuicidal ideation was independently associated with past history of depression, depressive and anxiety disorders, and higher troponin I levels. Escitalopram treatment was significantly more efficacious in reducing and treating suicidal ideation than placebo treatment over a 24-week period. These effects were largely explained by remission status of depressive and anxiety disorders. ConclusionsSuicidal ideation is associated with unfavorable psychiatric and ACS status during the acute phase of ACS. Successful treatment of depression and anxiety with escitalopram had significant beneficial effects on suicidal ideation in these patients.

DYNAMICS OF CYTOKINE LEVELS IN THE HOSPITALIZED PATIENTS WITH DIFFERENT CLINICAL TYPES OF ACUTE CORONARY SYNDROME

The study included 120 patients with acute coronary syndrome (ACS), which were divided: in two groups, respectively, with ACS-ST segment elevation (group 1, n = 80), and without this clinical sign (group 2, n = 40). The levels of interleukins (IL)-6, -8, -10, and tumor necrosis factor-α (TNFα) were determined by quantitative ELISA test on the 1st and 10th days of the study. In both groups, the IL-8 and TNFα values on day 1 were similar to the reference level, whereas IL-10 levels were significantly reduced as compared to the standard values. IL-6 level was increased in patients with ACS-ST elevation only in acute phase of ACS, while the patients from group 2 showed normal IL-6 values. On the day 10, TNFα levels in the both groups of patients were significantly increased as compared to the 1st day, whereas IL-6 and IL-10 levels were significantly decreased by the day 10 in both groups of patients. Differential dynamics of IL-8 was observed for these groups of the patients from the day 1 to day 10, i.e., the IL-8 concentration showed a tendency to increase (by 40%) for the group 1 and decrease by 54% in the group 2. In conclusion, the patient grouped by different clinical ACS variants exhibit a similar dynamics of cytokine concentrations, but an increase of IL-8 by the day 10 of the disease was seen only in patients with ACS segment elevation. It may be indicative of different intensity of the inflammatory response.

Detrimental Effects of Hyperglycemia in Acute Coronary Syndromes: from Pathophysiological Mechanisms to Therapeutic Strategies.

Hyperglycemia recognized during hospitalization for acute coronary syndromes (ACS) is common. It is a powerful predictor of worse prognosis in patients both with and without previously known diabetes mellitus. Hyperglycemia during ACS is caused by an inflammatory and adrenergic response to ischemic stress, when catecholamines are released and glycogenolysis induced. The link between hyperglycemia and prognosis in ACS patients is multi-factorial. Hyperglycemia exerts detrimental effects on left ventricular and platelet function and it also activates other systemic pathological processes that contribute to cellular and tissue injury such as increasing oxidative stress and worsening endothelial function. Glucose management strategies in ACS may improve outcome in patients with hyperglycemia, by reducing inflammatory and clotting mediators, by improving endothelial function and fibrinolysis and by reducing infarct size. Most of available oral anti-diabetic drugs are contraindicated for the increased risk of hypoglycemia. Thus, insulin is the preferred agent for glycemic control in ACS and conversion from intravenous to subcutaneous therapy commonly occurs when the critical acute phase of ACS resolves. Pharmacodynamics of insulin allows it to be adaptable to the changing physiology of the ACS patient, is easily titrated and has no dosage threshold. Nevertheless, findings concerning the effect on ACS-related mortality of the control of glucose levels by intravenous infusion of insulin have been conflicting and intervention trials are needed to optimize the definition of hyperglycemia and to establish appropriate modalities and goals of glucose lowering treatment. In particular, the clinical benefit of an aggressive treatment with insulin is yet unproved.

Impact of atrial fibrillation type during acute coronary syndromes: Clinical features and prognosis

IntroductionAtrial fibrillation (AF) is widely recognized as an adverse prognostic factor during acute myocardial infarction, although the impact of AF type – new-onset (nAF) or pre-existing (pAF) – is still controversial. ObjectivesTo identify the clinical differences and prognosis of nAF and pAF during acute coronary syndromes (ACS). MethodsWe performed a retrospective observational cohort study including 1373 consecutive patients (mean age 64 years, 77.3% male) admitted to a single center over a three-year period, with a six-month follow-up. ResultsAF rhythm was identified in 14.5% patients, of whom 71.4% presented nAF and 28.6% pAF. When AF types were compared, patients with nAF more frequently presented with ST-elevation ACS (p=0.003). Patients with pAF, in turn, were older (p=0.032), had greater left atrial diameter (p=0.001) and were less likely to have significant coronary lesions (p=0.034). Regarding therapeutic strategy, nAF patients were more often treated by rhythm control during hospital stay (p<0.001) and were less often anticoagulated at discharge (p=0.001). Compared with the population without AF, nAF was a predictor of death during hospital stay in univariate (p<0.001) and multivariate analysis (OR 2.67, p=0.047), but pAF was not. During follow-up, pAF was associated with higher mortality (p=0.014), while nAF patients presented only a trend towards worse prognosis. ConclusionsAF during the acute phase of ACS appears to have a negative prognostic impact only in patients with nAF and not in those with pAF.