Chronic Coronary Syndrome Patients Research Articles

J-shaped association between apolipoprotein B and CV outcomes in statin-treated patients with chronic coronary syndrome

The association between apolipoprotein B (apoB) and residual cardiovascular (CV) risk in patients with chronic coronary syndrome (CCS) remains unclear. We aimed to investigate the association between apoB levels and CV outcomes in statin-treated CCS patients. We enrolled 8641 statin-treated CCS patients at Fuwai Hospital. The patients were divided into 5 groups based on to apoB quintiles (Q1 to Q5). The primary endpoint was 3-year CV events, including CV death, nonfatal myocardial infarction, and nonfatal stroke. During a median follow-up of 3.17 years, there were 232 (2.7%) CV events. After multivariable adjustment, a restricted cubic spline illustrated a J-shaped relationship between apoB levels and 3-year CV events, with the risk remaining flat until apoB levels exceeded 0.73 g/L, after which the risk increased (nonlinear P < .05). Kaplan-Meier curves showed the lowest CV event rate in the Q3 group (0.68-0.78 g/L). Compared with the Q3 group, multivariable Cox regression models revealed that both low (Q1, ≤ 0.57 g/L) and high (Q5, > 0.93 g/L) apoB levels were associated with an increased risk of major adverse cardiac events (all P < .05). Notably, patients with low apoB levels (Q1) had the highest risk of CV death (HR, 2.44; 95%CI, 1.17-5.08). Our analysis indicates that both low and high levels of apoB are associated with elevated CV risk, with the risk being particularly pronounced at higher levels (> 0.73 g/L).

Comparison of high-risk characteristics of non-culprit plaques in relation to plaque severity in acute coronary syndrome

IntroductionPatients with acute coronary syndrome (ACS) have high event rates related to non-culprit (NC) lesions, therefore plaque composition of these lesions is of great interest. Although marginal atherosclerotic lesions were studied extensively, more significant lesions might have more high-risk characteristics. AimTo compare differences in high-risk lesion characteristics between significant versus non-stenotic NC plaques in ACS and the discrepancies with chronic coronary syndrome (CCS) patients. MethodsNon-culprit vessels of 26 ACS patients with 26 angiographically significant lesions and 37 patients (17 ACS and 20 CCS) with 48 non-stenotic lesions were investigated with intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS). Overall, 74 segments of 30 mm length were analyzed in 1 mm intervals. External elastic lamina (EEM), plaque burden (PB), minimal luminal area (MLA), percent atheroma volume (PAV) and lipid core burden index maximum 4 mm (maxLCBI4mm) were determined for each segment. ResultsCardiovascular risk factors were similar in all groups. PB was higher and MLA smaller in significant non-culprit ACS lesions vs non-stenotic lesions: PB 73.5 % (IQR 68.7–78.5) vs 59.2 (IQR 49.6–71.5), p = 0.003, MLA 3.0 mm2 (IQR 2.3–3.9) vs 4.0 mm2 (IQR 2.8–4.7). MaxLCBI4mm was similar 308.1 (±155.4) vs 287.8 (±165.7), p = 0.67.Among non-stenotic plaques, MaxLCBI4mm was comparable between ACS and CCS patients, 275.7 (±151.5) in CCS patients vs 287.8 (±165.7) in ACS patients, p = 0.79. ConclusionAlthough visually significant non-culprit lesions had a higher plaque burden compared to non-stenotic lesions, a significant relation between MaxLCBI4mm and hemodynamic significance of the plaques couldn't be established.

Joint Association of Lipoprotein(a) and a Family History of Coronary Artery Disease with the Cardiovascular Outcomes in Patients with Chronic Coronary Syndrome.

No data are currently available regarding the association between Lp(a) and the cardiovascular outcomes in patients with coronary artery disease (CAD) according to their family history (FHx) of CAD. This study aimed to evaluate the significance of Lp(a) in predicting major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome (CCS) with or without FHx. A total of 6056 patients with CCS were enrolled. Information on FHx was collected, and the plasma Lp(a) levels were measured. All patients were followed up regularly. The independent and joint associations of Lp(a) and FHx with the risk of MACEs, including cardiovascular death, nonfatal myocardial infarction, and stroke, were analyzed. With over an average of 50.35±18.58 months follow-up, 378 MACEs were recorded. A Cox regression analysis showed an elevated Lp(a) level to be an independent predictor for MACEs in patients with [hazard ratio (HR): 2.77, 95% confidence interval (CI): 1.38-5.54] or without FHx (HR: 1.35, 95% CI: 1.02-1.77). In comparison to subjects with non-elevated Lp(a) and negative FHx, patients with elevated Lp(a) alone were at a nominally higher risk of MACEs (HR: 1.26, 95% CI: 0.96-1.67), while those with both had the highest risk (HR: 1.93, 95% CI: 1.14-3.28). Moreover, adding Lp(a) to the original model increased the C-statistic by 0.048 in subjects with FHx (p=0.004) and by 0.004 in those without FHx (p=0.391). The present study is the first to suggest that Lp(a) could be used to predict MACEs in CCS patients with or without FHx; however, its prognostic significance was more noteworthy in patients with FHx.

Comparison of Short-Term Outcomes between Fractional Flow Reserve Guided and Intra-Vascular Ultrasound Guided Percutaneous Coronary Intervention in Chronic Coronary Syndrome

Background: Fractional flow reserve (FFR) can provide information about physiologically significant coronary lesions that can be intervened. Intravascular ultrasound (IVUS) is also useful in providing thorough assessment of the intermediate lesions. This study was conducted to compare the short-term outcomes of FFR and IVUS guided percutaneous coronary intervention of intermediate coronary artery lesions in chronic coronary syndrome (CCS) patients. Methods: This Quasi-experimental study was conducted in the department of Cardiology, NICVD, Dhaka, for 12-months following ethical approval. A total of 100 CCS patients were enrolled in this study and divided into Group-I (FFR guided PCI, n=50) and Group-II (IVUS guided PCI, n=50) after taking written informed consent. Patients were followed up to three months after PCI. Detailed history, thorough clinical examination and necessary investigations were carried out in each patient and recorded in predesigned structured questionnaire. Data were analyzed by SPSS 26.0. Results: Both groups were statistically similar in terms of demographic profile, clinical findings, risk factors, angiographic findings (p&gt;0.05) and angiographic success. Also, 96% in group-I and 92% in group-II respondents had procedural success. According to in hospital outcome, 1(2%) in group-I and 1(2%) in group-II respondents had myocardial infarction. 1(2%) respondent both in group -I and group-II also had LVF, while only 1(2%) respondent in group-II had death and cardiogenic shock respectively. Considering MACE after 03 months of follow up, 1(2%) death occurred in Group-II. However, no death in Group-I. 1(2%) respondent had NSTEMI in both groups. 1(2%) respondent had target vessel revascularization in Group-I and no respondents had in Group-II. While considering 1(2%) study population had faced cardiogenic shock, 1(2%) respondent had arrhythmia in both groups respectively and 1(2%) respondent had LVF in Group-I and 2(4%) had LVF in Group-II. ............

Cardioprotective potential of oleuropein, hydroxytyrosol, oleocanthal and their combination: Unravelling complementary effects on acute myocardial infarction and metabolic syndrome

Clinical studies have previously established the role of olive products in cardiovascular disease (CVD) prevention, whilst the identification of the responsible constituents for the beneficial effects is still pending. We sought to assess and compare the cardioprotective potential of oleuropein (OL), hydroxytyrosol (HT), oleocanthal (OC) and oleanolic Acid (OA), regarding Ischemia/Reperfusion Injury (IRI) and CVD risk factors alleviation. The scope of the study was to design a potent and safe combinatorial therapy for high-cardiovascular-risk patients on a bench-to-bedside approach. We evaluated the IRI-limiting potential of 6-weeks treatment with OL, HT, OC or OA at nutritional doses, in healthy and metabolic syndrome (MS)-burdened mice. Three combinatorial regimens were designed and the mixture with preponderant benefits (OL-HT-OC, Combo 2), including infarct sparing and antiglycemic potency, compared to the isolated compounds, was further investigated for its anti-atherosclerotic effects. In vivo experiments revealed that the combination regimen of Combo 2 presented the most favorable effects in limiting infarct size and hyperglycemia, which was selected to be further investigated in the clinical setting in Chronic Coronary Artery Syndrome (CCAS) patients. Cardiac function, inflammation markers and oxidative stress were assessed at baseline and after 4 weeks of treatment with the OL-HT-OC supplement in the clinical study. We found that OL, OC and OA significantly reduced infarct size in vivo compared to Controls. OL exhibited antihyperglycemic properties and OA attenuated hypercholesterolemia. OL-HT-OA, OL-HT-OC and OL-HT-OC-OA combination regimens were cardioprotective, whereas only OL-HT-OC mitigated hyperglycemia. Combo 2 cardioprotection was attributed to apoptosis suppression, enhanced antioxidant effects and upregulation of antioxidant enzymes. Additionally, it reduced atherosclerotic plaque extent in vivo. OL-HT-OC supplement ameliorated cardiac, vascular and endothelial function in the small-scale clinical study. Conclusively, OL-HT-OC combination therapy exerts potent cardioprotective, antihyperglycemic and anti-atherosclerotic properties in vivo, with remarkable and clinically translatable cardiovascular benefits in high-risk patients.

The combined effect of triglyceride-glucose index and high-sensitivity C-reactive protein on cardiovascular outcomes in patients with chronic coronary syndrome: A multicenter cohort study.

The triglyceride-glucose (TyG) index and high-sensitivity C-reactive protein (hsCRP) are the commonly used biomarkers for insulin resistance and systemic inflammation, respectively. We aimed to investigate the combined association of TyG and hsCRP with the major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS). A total of 9421 patients with CCS were included in this study. The primary endpoint was defined as a composite of MACE covering all-cause death, nonfatal myocardial infarction, and revascularization. During the 2-year follow-up period, 660 (7.0%) cases of MACE were recorded. Participants were divided equally into three groups according to TyG levels. Compared with the TyG T1 group, the risk of MACE was significantly higher in the TyG T3 group. It is noteworthy that among patients in the highest tertile of TyG, hsCRP >3 mg/L was significantly associated with an increased risk of MACE, whereas the results were not significant in the medium to low TyG groups. When patients were divided into six groups according to hsCRP and TyG, the Cox regression analysis showed that patients in the TyG T3 and hsCRP >3 mg/L group had a significantly higher risk of MACE than those in the TyG T1 and hsCRP ≤3 mg/L group. However, no significant interaction was found between TyG and hsCRP on the risk of MACE. Our study suggests that the concurrent assessment of TyG and hsCRP may be valuable in identifying high-risk populations and guiding management strategies among CCS patients.

Coronary bypass surgery for multivessel disease after percutaneous coronary intervention in acute coronary syndromes: why, for whom, how early?

Multivessel coronary artery disease is present in ∼50% of patients with acute coronary syndrome and, compared with single-vessel disease, entails a higher risk of new ischaemic events and a worse prognosis. Randomized controlled trials have shown the superiority of 'complete revascularization' over culprit lesion-only treatment. Trials, however, only included patients treated with percutaneous coronary intervention (PCI), and evidence regarding complete revascularization with coronary artery bypass graft (CABG) surgery after culprit lesion-only PCI ('hybrid revascularization') is lacking. The CABG after PCI is an open, non-negligible therapeutic option, for patients with non-culprit left main and/or left anterior descending coronary artery disease where evidence in chronic coronary syndrome patients points in several cases to a preference of CABG over PCI. This valuable but poorly studied 'PCI first-CABG later' option presents, however, relevant challenges, mostly in the need of interrupting post-stenting dual antiplatelet therapy (DAPT) for surgery to prevent excess bleeding. Depending on patients' clinical characteristics and coronary anatomical features, either deferring surgery after a safe interruption of DAPT or bridging DAPT interruption with intravenous short-acting antithrombotic agents appears to be a suitable option. Off-pump minimally invasive surgical revascularization, associated with less operative bleeding than open-chest surgery, may be an adjunctive strategy when revascularization cannot be safely deferred and DAPT is not interrupted. Here, the rationale, patient selection, optimal timing, and adjunctive strategies are reviewed for an ideal approach to hybrid revascularization in post-acute coronary syndrome patients to support physicians' choices in a case-by-case patient-tailored approach.

Long-term clinical outcomes following percutaneous coronary intervention in patients aged 90 years and older

BackgroundIn an aging society, percutaneous coronary intervention (PCI) for super-elderly patients is commonly performed in clinical practice. However, data are scarce regarding the clinical features and outcomes of this population. MethodsThis multicenter observational study enrolled patients aged over 90 years who underwent PCI across 10 hospitals between 2011 and 2020. The study included patients presenting with acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). The occurrence of all-cause and cardiac deaths during hospitalization and after discharge was investigated. ResultsIn total, 402 patients (91.9 ± 2.0 years, 48.3 % male) participated in the study, of whom 77.9 % presented with ACS. The rate of in-hospital death was significantly higher in patients with ACS compared to patients with CCS (15.3 % vs. 2.2 %, p < 0.001). The estimated cumulative incidence rates of all-cause death were 24.3 %, 39.5 %, and 60.4 % at 1, 3, and 5 years, respectively. No significant difference was observed in the occurrence of all-cause death between patients with ACS and CCS. Regarding causes of death after discharge, non-cardiac deaths accounted for just over half of the cases. ConclusionThis study highlights the clinical features and long-term clinical course of patients aged over 90 years who underwent PCI in a real-world setting. Patients presenting with ACS exhibited a higher rate of in-hospital mortality compared to those with CCS. Following discharge, both ACS and CCS patients experienced comparable and substantial increases in the incidence rates of both cardiac and non-cardiac mortality over time, and a more holistic management approach is warranted.

Comparison of the Gut Microbiome between Single-Vessel Disease and Multivessel Disease in Chronic Coronary Syndrome Patients

Background: Chronic coronary syndrome (CCS) has a high mortality rate worldwide, especially in developing countries. The degree of vessel stenosis and the number of stenotic vessels impact the mortality rate in coronary artery disease (CAD) patients. Additionally, multivessel disease (MVD) significantly influences clinical outcomes more than single-vessel disease (SVD). Objective: To examine if gut microbial communities could be used as biomarkers to discriminate patients with varying numbers of coronary stenotic vessels. Materials and Methods: Patients between 35 and 70 years old hospitalized at Chulabhorn Hospital were recruited between February 25 and July 15, 2023. Participants were divided into three groups, CCS patients with SVD, CCS patients with MVD, and healthy participants. On the day of the assessment, blood was drawn from each patient. The day before an appointment, the feces of every patient were collected. The present study was cross-sectional. Results: Forty-nine patients were included, and were divided into 11 SVD patients, 19 MVD patients, and 19 healthy participants. The patients were 38.78% female, with a mean age of 59.38±7.66 years, and 48.98% had hypertension. Based on sequencing of the V3-V4 regions of the 16S rRNA gene, it was revealed that the relative abundance of the Prevotella and Veillonella genera was significantly higher in MVD than in SVD patients. In the present study, MVD patients had differences in the diversity and composition of the gut microbiome compared to SVD patients and healthy participants. Conclusion: The development of SVD and MVD is correlated with changes in the gut microbiome, which may create a diagnostic marker of CAD to distinguish MVD patients from SVD patients and may be useful for further therapy and prevention.

Evaluación invasiva de la disfunción microvascular coronaria y resultados cardiovasculares en todo el espectro de la EC: un metanálisis

Introduction and objectivesCoronary microvascular dysfunction (CMD) is highly prevalent and is recognized as an important clinical entity in patients with coronary heart disease (CHD). Nevertheless, the association of CMD with adverse cardiovascular events in the spectrum of CHD has not been systemically quantified. MethodsWe searched electronic databases for studies on patients with CHD in whom coronary microvascular function was measured invasively, and clinical events were recorded. The primary endpoint was major adverse cardiac events (MACE), and the secondary endpoint was all-cause death. Estimates of effect were calculated using a random-effects model from published risk ratios. ResultsWe included 27 studies with 11 404 patients. Patients with CMD assessed by invasive methods had a higher risk of MACE (RR, 2.18; 95%CI, 1.80-2.64; P<.01) and all-cause death (RR, 1.88; 95%CI, 1.55-2.27; P<.01) than those without CMD. There was no significant difference in the impact of CMD on MACE (interaction P value=.95) among different invasive measurement modalities. The magnitude of risk of CMD assessed by invasive measurements for MACE was greater in acute coronary syndrome patients (RR, 2.84, 95%CI, 2.26-3.57; P<.01) than in chronic coronary syndrome patients (RR, 1.77, 95%CI, 1.44-2.18; P<.01) (interaction P value<.01). ConclusionsCMD based on invasive measurements was associated with a high incidence of MACE and all-cause death in patients with CHD. The magnitude of risk for cardiovascular events in CMD as assessed by invasive measurements was similar among different methods but varied among CHD populations.

Gut barrier dysfunction, endotoxemia and inflammatory response in STEMI patients and effect of primary PCI

BackgroundGut-derived bacterial and endotoxin translocation induce systemic inflammation, which exerts a pivotal pathogenetic role in all phases of atherosclerosis. ObjectivesTo investigate prospectively the gut barrier function, endotoxin translocation and inflammatory response in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary artery intervention (PPCI). MethodsTwenty-seven patients with STEMI that underwent successful PPCI were subjected to peripheral blood sampling at 3-time points; before PPCI (day0), 24 h (day1) and 96 h (day4) after PPCI and were compared with 20 chronic coronary syndrome (CCS) patients and 11 healthy controls. Serum ZO-1, I-FABP and endotoxin concentrations were determined by ELISA. Concentrations of cytokines IL-1β, -6, -8, -10 and TNF-α were determined by flow cytometry. ResultsPatients with STEMI before PPCI (day0) had increased serum ZO-1 and endotoxin, both at significantly higher levels compared to CCS patients. STEMI induced also significant increases of the cytokines IL-6, -8 and -10. After PPCI, a significant improvement of gut barrier integrity (ZO-1) and endotoxemia was observed from the first day. At day4 post PPCI, systemic endotoxin and cytokines IL-6, -8 and -10 levels were reduced to control levels. Serum ZO-1 levels were positively correlated with systemic IL-10 concentrations (r = 0.471). ConclusionSTEMI is associated with gut barrier dysfunction, systemic endotoxemia and inflammatory response, which improve rapidly following successful PPCI.

The Role of Multimodality Imaging (CT & MR) as a Guide to the Management of Chronic Coronary Syndromes.

Chronic coronary syndrome (CCS) is one of the leading cardiovascular causes of morbidity, mortality, and use of medical resources. After the introduction by international guidelines of the same level of recommendation to non-invasive imaging techniques in CCS evaluation, a large debate arose about the dilemma of choosing anatomical (with coronary computed tomography angiography (CCTA)) or functional imaging (with stress echocardiography (SE), cardiovascular magnetic resonance (CMR), or nuclear imaging techniques) as a first diagnostic evaluation. The determinant role of the atherosclerotic burden in defining cardiovascular risk and prognosis more than myocardial inducible ischemia has progressively increased the use of a first anatomical evaluation with CCTA in a wide range of pre-test probability in CCS patients. Functional testing holds importance, both because the role of revascularization in symptomatic patients with proven ischemia is well defined and because functional imaging, particularly with stress cardiac magnetic resonance (s-CMR), gives further prognostic information regarding LV function, detection of myocardial viability, and tissue characterization. Emerging techniques such as stress computed tomography perfusion (s-CTP) and fractional flow reserve derived from CT (FFRCT), combining anatomical and functional evaluation, appear capable of addressing the need for a single non-invasive examination, especially in patients with high risk or previous revascularization. Furthermore, CCTA in peri-procedural planning is promising to acquire greater importance in the non-invasive planning and guiding of complex coronary revascularization procedures, both by defining the correct strategy of interventional procedure and by improving patient selection. This review explores the different roles of non-invasive imaging techniques in managing CCS patients, also providing insights into preoperative planning for percutaneous or surgical myocardial revascularization.

Long-term outcomes following paclitaxel-coated balloons versus thin-strut drug-eluting stents for treatment of in-stent restenosis in chronic coronary syndrome (CCS Dragon-Registry).

The long-term outcomes for patients with in-stent restenosis (ISR) presenting with chronic coronary syndrome (CCS) are not well studied. We aimed to investigate the outcomes for patients with drug-eluting stents (DES)-ISR and CCS undergoing percutaneous coronary intervention (PCI) with drug-coated balloons (DCB) or thin strut-DES. A total of 846 consecutive patients from the Dragon-Registry with CCS and DES-ISR who underwent PCI with thin (strut thickness <100 μm) strut-DES (381 [45%]) or paclitaxel-DCB (465 [55%]) for DES-ISR were enrolled between February 2008 and October 2021. The median follow-up was 1006 (IQR 426-1770) days. The primary outcome was target lesion revascularization (TLR). Secondary outcomes were target vessel revascularization (TVR) and device-oriented composite endpoint (DOCE: cardiac death, TLR, or target vessel myocardial infarction [TV-MI]). Patients who received DES, compared with those who received DCB, had lower crude rates of TLR (hazard ratio [HR], 0.50 [95% CI, 0.34-0.74]; P <0.001), TVR (HR, 0.56 [95% CI, 0.39-0.86]; P <0.001), and DOCE (HR, 0.63 [95% CI, 0.45-0.88]; P = 0.007). The incidence of cardiac death and TV-MI were similar in both groups. After matching, the observed differences persisted in terms of TLR (HR, 0.54 [95% CI, 0.33-0.88]; P = 0.013), TVR (HR, 0.57 [95% CI, 0.41-0.80]; P = 0.009) and DOCE (HR, 0.65 [95% CI, 0.42-0.99]; P = 0.046) between the DES and DCB groups, respectively. In long-term follow-up of CCS patients undergoing PCI of ISR, the use of DES was associated with reduced rates of TLR, TVR, and DOCE compared with patients treated with DCB.

Invasive assessment of coronary microvascular dysfunction and cardiovascular outcomes across the full spectrum of CHD: a meta-analysis

Introduction and objectivesCoronary microvascular dysfunction (CMD) is highly prevalent and is recognized as an important clinical entity in patients with coronary heart disease (CHD). Nevertheless, the association of CMD with adverse cardiovascular events in the spectrum of CHD has not been systemically quantified. MethodsWe searched electronic databases for studies on patients with CHD in whom coronary microvascular function was measured invasively, and clinical events were recorded. The primary endpoint was major adverse cardiac events (MACE), and the secondary endpoint was all-cause death. Estimates of effect were calculated using a random-effects model from published risk ratios. ResultsWe included 27 studies with 11 404 patients. Patients with CMD assessed by invasive methods had a higher risk of MACE (RR, 2.18; 95%CI, 1.80-2.64; P<.01) and all-cause death (RR, 1.88; 95%CI, 1.55-2.27; P<.01) than those without CMD. There was no significant difference in the impact of CMD on MACE (interaction P value=.95) among different invasive measurement modalities. The magnitude of risk of CMD assessed by invasive measurements for MACE was greater in acute coronary syndrome patients (RR, 2.84, 95%CI, 2.26-3.57; P<.01) than in chronic coronary syndrome patients (RR, 1.77, 95%CI, 1.44-2.18; P<.01) (interaction P value<.01). ConclusionsCMD based on invasive measurements was associated with a high incidence of MACE and all-cause death in patients with CHD. The magnitude of risk for cardiovascular events in CMD as assessed by invasive measurements was similar among different methods but varied among CHD populations.

Unraveling the transcriptomic landscape of platelets: RPs vs. MPs in CCS patients

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Else Kröner Fresenius Stiftung Background Reticulated platelets (RPs), characterized by youth, hyper-reactivity, and RNA abundance, signify pro-thrombotic potential and serve as predictors for inadequate antiplatelet therapy response post-myocardial infarction. Their pivotal role in chronic coronary syndrome (CCS) and high on-treatment platelet reactivity highlights their significance as promising biomarkers for adverse cardiovascular events in diverse pathological settings. Purpose We aimed to compare for the first time the transcriptomic profiles of RPs and MPs in CCS patients. Methods Using fluorescent activated cell sorting (FACS), RPs and MPs were isolated based on RNA content from peripheral blood of 19 CCS patients. RNA assessment involved the Tapestation 4200 platform (Agilent), and totalRNA libraries were sequenced on a NextSeq 500 Illumina platform. RNA sequencing analysis, with a cut-off of p &amp;lt;0.005 and a log2fc &amp;gt;1, and alternative splicing event detection using MAJIQ, were performed. Circular RNA (circRNA) analysis employed CIRCexplorer. Results Total RNA-sequencing identified 1589 differentially expressed genes, with 1100 transcripts upregulated in RPs and 489 enriched in MPs (Figure 1 A, B and D). Notably, collagen receptor GP6 (log2FC 1.12, p=6.89x10-41), thrombin receptor PAR4 (F2RL3, log2FC 1.1, p=3.54*10-21) and Von Willebrand Factor (log2FC 1.2, p=1.26*10-38) transcripts were significantly enriched in RPs. Gene Ontology identified a higher enrichment of relevant biological categories in RPs compared to MPs, such as "platelet activation", "platelet degranulation" and "blood coagulation" (Figure 1C). These findings are consistent with our previously established discovery and support the hypothesis that RPs in cardiovascular disease are hyper-reactive and pro-thrombotic due to their different RNA content compared to other platelets. Several splicing events were detected as differentially regulated: there is an upregulation of an alternative splicing on the collagen receptor transcript GP6 in RPs (Figure 1E); by the transcript of the G-protein GNAQ, one alternative splicing event was found upregulated in RPs, whilst two others were upregulated in MPs. Moreover, we found an enrichment of the total level of circular RNAs in MPs as compared to RPs (Figure 1F). Several previously undescribed circular RNAs were discovered to be enriched in RPs, as shown in Figure 1F. Conclusion This groundbreaking transcriptomic profiling of RPs and MPs in CCS patients elucidates the biological basis for RPs' hyperreactivity, emphasizing the differential enrichment of platelet activation transcripts. The pronounced upregulation of prothrombotic signaling in RPs provides insight into their hyperactivity and correlation with cardiovascular events. These findings illuminate a novel therapeutic niche in CCS patients, although further investigations are essential to comprehend the detrimental role of RPs in coronary artery disease.

Deep proteome profiling of reticulated platelets in patients with chronic coronary syndrome using mass cytometry

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Else Körner Fresenius Stiftung (EKFS) Background Immature or reticulated platelets (RPs), a subgroup of larger and RNA-rich platelets, which are newly released by megakaryocytes from the bone marrow into blood, have gained rising interest because of the further decryption of RPs’ prothrombotic biology and the potential as biomarkers for predicting adverse events in cardiovascular disease. Purpose The biological features of RPs in patients with chronic coronary syndrome (CCS) are largely unknown. With this project, we aimed to perform the first high resolution proteomic characterisation of reticulated platelets using mass cytometry(CyTOF). Method Two samples of thrombocytes from peripheral blood (non-stimulated, TRAP-stimulated) were prepared from each patient with a custom-made CyTOF-antibody panel of 20 antibodies targeting essential transmembrane proteins(anti-CD9, anti-CD29, anti-CD31, anti-CD36-, anti-CD40, anti-CD41, anti-CD42a, anti-CD42b-, anti-CD47, anti-CD61, anti-CD62P-, anti-CD63, anti-CD69, anti-CD107a, anti-CD154, anti-GPVI, anti-GPIIbIIa complex, anti-Par1, anti-PEAR-1 and the negative control anti-CD3 coupled with different metal isotopes). RPs and mature platelets (MPs) were detected based on their RNA content. Earth mover’s distance (EMD) was assessed as a measure of differential expression. Results CyTOF detected an upregulation of important transmembrane receptors in RPs compared to MPs in quiescent platelets (Fig.1A and B). The collagen receptor GPVI (EMD 33.95), the collagen integrin receptor unit ITGB1 (EMD 32.37), the adhesion protein CD9 (EMD 31.78) and the von Willebrand receptor unit CD42b (EMD 30.08) were upregulated in RPs which all serve as crucial regulators of platelet activation and aggregation. RPs show higher median signal intensities of typical activation markers compared to MPs upon TRAP stimulation (Fig.1C). Conclusion We provide the first proteomic characterization of RPs’ pro-thrombotic profile offering the first biomolecular explanation of their hyperactivity and detrimental role in CCS patients.

Long-Term Outcomes of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention of Moderate Lesions in Patients with Chronic Coronary Syndrome

Background: Fractional flow reserve (FFR) is crucial to evaluating coronary artery stenosis in patients diagnosed with chronic coronary syndrome (CCS). By assessing the severity of stenosis, FFR assists in determining whether percutaneous coronary intervention (PCI) is necessary. Methods: Conducted at Tehran Heart Center from 2013 through 2017, this cohort study involved 52,248 CCS patients who underwent coronary angiography. Among them, 598 symptomatic individuals, despite receiving comprehensive medical treatment, underwent FFR assessment. Subsequently, 225 patients with positive FFR (≤0.80) underwent PCI, while 373 patients received solely medical treatment. The patients were monitored for 3 years to evaluate primary and secondary endpoints. Results: After 3 years, the PCI group demonstrated a lower incidence of the primary composite endpoint, consisting of all-cause mortality, nonfatal myocardial infarction, repeat target vessel/lesion revascularization (TVR/TLR), and coronary artery bypass graft surgery, than the medical treatment group (HR, 0.85; 95% CI, 0.74 to 0.98; P=0.012). Additionally, urgent TVR/TLR significantly decreased in the PCI group (HR, 0.56; 95% CI, 0.42 to 0.74; P&lt;0.001). Conclusion: FFR-guided PCI demonstrated effectiveness in reducing long-term major adverse cardiac events, primarily by lowering the incidence of TVR/TLR. The results emphasize the significance of FFR-guided PCI in addressing stenosis rather than alleviating ischemia.

A Narrative Review of Revascularization in Chronic Coronary Syndrome/Disease: Concepts and Misconceptions.

Ischemic heart disease represents a significant global burden of morbidity and mortality. While revascularization strategies are well defined in acute settings, there are uncertainties regarding chronic coronary artery disease treatment. Recent trials have raised doubts about the necessity of revascularization for "stable", chronic coronary syndromes or disease, leading to a shift towards a more conservative approach. However, the issue remains far from settled. In this narrative review, we offer a summary of the most pertinent evidence regarding revascularization for chronic coronary disease, while reflecting on less-often-discussed details of major clinical trials. The cumulative evidence available indicates that there can be a prognostic benefit from revascularization in chronic coronary syndrome patients, provided there is significant ischemia, as demonstrated by either imaging or coronary physiology. Trials that have effectively met this criterion consistently demonstrate a reduction in rates of spontaneous myocardial infarction, which holds both prognostic and clinical significance. The prognostic benefit of revascularization in patients with heart failure with reduced ejection fraction remains especially problematic, with a single contemporary trial favouring surgical revascularization. The very recent publication of a trial focused on revascularizing non-flow-limiting "vulnerable" plaques adds further complexity to the field. The ongoing debates surrounding revascularization in chronic coronary syndromes emphasize the importance of personalized strategies. Revascularization, added to the foundational pillar of medical therapy, should be considered, taking into account symptoms, patient preferences, coronary anatomy and physiology, ischemia tests and intra-coronary imaging.

HYPERTRIGLYCERIDEMIA IN PATIENTS WITH ACUTE AND CHRONIC CORONARY SYNDROME: PREVALENCE AND THEIR ASSOCIATION WITH EXTREME CARDIOVASCULAR RISK AND LEFT VENTRICULAR FUNCTION

Objective: Hypertriglyceridemia prevalence in Acute and Chronic Coronary Syndrome (ACS and CCS respectively) patients in the era of very low LDL target is still unknow. The objective of our study is to evaluate the prevalence of triglyceride levels above 150 or 200 mg/dL despite statin therapy and LDL cholesterol at targets in ACS and CCS subjects enrolled in a Cardiac Rehabiliatitation (CR) program Design and method: This cross-sectional observational study was conducted at the Niguarda Hospital (Milan, Italy). Patients undergoing CR after ACS/CCS from January 1, 2012, to March 28, 2023, were included. Data on demographic, clinical, laboratory, and instrumental variables were collected. Results: The study population consisted of 740 patients with a mean age of 64.3±10.7 years, predominantly male (81.7%). Triglyceride levels significantly decrease during the CR period (131.1±63.8 vs 116.9±75.9 mg/dL; p &lt; 0.001) similarly to LDL cholesterol (107.9 ± 38.8 mg/dL vs 69.9 ± 25.9mg/dL, p&lt;0.001). 50.8% of the subjects reach the LDL cholesterol target. The percentage of patients with triglycerides &gt;150 mg/dL at CR ends was 17.8% (15.6% when considering only patients that reach the LDL target of 55 mg/dL) while it is only 6.8% for triglycerides &gt;200 mg/dL (5.9% when considering only patients that reach LDL target). Patients with triglycerides &gt;150 mg/dL had higher baseline BMI, LDL cholesterol and uric acid with lower ejection fraction at CR ends. Hypertriglyceridemia significantly correlates with extreme CV risk (R= 0.08, p= 0.025). At multivariate analysis, FE (dependent variable) was significantly associated with triglycerides (beta= - 0,145, p= 0,026) and systolic BP (beta= 0,137, p= 0,032). Conclusions: Despite high intensity statin therapy and lower LDL cholesterol targets, a substantial proportion of patients in cardiac rehabilitation still had elevated triglyceride levels. This study highlights the potential role of Icosapent Ethyl in managing hypertriglyceridemia in these patients.

Exploring of gut microbiota features in dyslipidemia and chronic coronary syndrome patients undergoing coronary angiography.

Chronic coronary syndrome (CCS) has a high mortality rate, and dyslipidemia is a major risk factor. Atherosclerosis, a cause of CCS, is influenced by gut microbiota dysbiosis and its metabolites. The objective of this study was to study the diversity and composition of gut microbiota and related clinical parameters among CCS patients undergoing coronary angiography and dyslipidemia patients in comparison to healthy volunteers in Thailand. CCS patients had more risk factors and higher inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) than others. The alpha diversity was lower in dyslipidemia and CCS patients than in the healthy group. A significant difference in the composition of gut microbiota was observed among the three groups. The relative abundance of Proteobacteria, Fusobacteria, Enterobacteriaceae, Prevotella, and Streptococcus was significantly increased while Roseburia, Ruminococcus, and Faecalibacterium were lower in CCS patients. In CCS patients, Lachnospiraceae, Peptostreptococcaceae, and Pediococcus were positively correlated with hs-CRP. In dyslipidemia patients, Megasphaera was strongly positively correlated with triglyceride (TG) level and negatively correlated with high-density lipoprotein cholesterol (HDL-C). The modification of gut microbiota was associated with changes in clinical parameters involved in the development of coronary artery disease (CAD) in CCS patients.