Proteomics associated with coronary high-risk plaques by optical coherence tomography.

Biomarkers are widely used for the diagnosis and monitoring of cardiovascular disease. However, markers for coronary high-risk plaques have not been identified. The aim of this study was to identify proteins specific to coronary high-risk plaques. Fifty-one patients (71.2 ± 11.1 years, male: 66.7%) who underwent intracoronary optical coherence tomography imaging and provided blood specimens for proteomic analysis were prospectively enrolled. A total of 1470 plasma proteins were analyzed per patient using the Olink® Explore 1536 Reagent Kit. In patients with thin-cap fibroatheroma, the protein expression of Calretinin (CALB2), Corticoliberin (CRH) and Alkaline phosphatase, placental type (ALPP) were significantly increased, while the expression of Neuroplastin (NPTN), Folate receptor gamma (FOLR3) and Serpin A12 (SERPINA12) were significantly decreased. In patients with macrophage infiltration, the protein expressions of Fatty acid-binding protein, intestinal (FABP2), and Fibroblast growth factor 21 (FGF21) were significantly decreased. In patients with lipid-rich plaques, the protein expression of Interleukin-17 C (IL17C) was significantly increased, while the expression of Fc receptor-like protein 3 (FCRL3) was significantly decreased. These proteins might be useful markers in identifying patients with coronary high-risk plaques. Clinical Trial Registration: https://www.umin.ac.jp/ctr/ , UMIN000041692.

Coronary arterial repair in patients with stable angina pectoris or acute coronary syndrome after ultrathin biodegradable polymer sirolimus-eluting stent implantation at 1-year follow-up by coronary angioscopy.

BACKGROUND: Imaging modality-based evidence is limited that compares the extent of coronary arterial repair after percutaneous coronary intervention between patients with stable angina pectoris (SAP) and those with acute coronary syndrome (ACS). METHODS: Between December 2018 and November 2021, a single-center, nonrandomized, observational study was conducted in 92 patients with SAP (n = 42) or ACS (n = 50), who were implanted with Orsiro sirolimus-eluting stent (O-SES) providing a hybrid (active and passive) coating and underwent 1-year follow-up by coronary angioscopy (CAS) after implantation. CAS assessed neointimal coverage (NIC), maximum yellow plaque (YP), and mural thrombus (MT). RESULTS: Baseline clinical characteristics were comparable between the SAP and ACS groups. The follow-up periods were comparable between the two groups (390.1 ± 69.9 vs. 390.6 ± 65.7 days, p = 0.99). The incidences of MT at 1 year after implantation were comparable between the two groups (11.4% vs. 11.1%, p = 0.92). The proportions of "Grade 1" in dominant NIC grades were highest in both groups, and the proportions of maximum YP grades and MT were comparable between the two groups. CONCLUSION: O-SES-induced coronary arterial repair at the site of stent implantation, irrespective of the types of coronary artery disease.

Clinical Significance of Coronary Healed Plaques in Stable Angina Pectoris Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Coronary healed plaques (HPs) reportedly have high vulnerability or show advanced atherosclerosis and a risk of rapid plaque progression. However, the prognosis of stable angina pectoris (SAP) patients with HPs undergoing percutaneous coronary intervention (PCI) remains under-investigated.Methods and Results: We analyzed 417 consecutive lesions from SAP patients undergoing pre- and post-intervention optical coherence tomography (OCT) for which HPs were defined as having a layered appearance. We investigated the differences in clinical and lesion characteristics, and post-PCI outcomes between HPs and non-HPs. To account for differences in clinical characteristics, propensity score matching was performed between the groups. HPs were observed in 216 lesions (51.8%) in the total cohort. In the propensity-matched cohort (n=294), HPs had higher rates of angiographic-B2/C lesions (77.6% vs. 59.2%, P<0.001), OCT-lipid-rich plaques (40.8% vs. 25.9%, P=0.007), macrophages (78.2% vs. 44.2%, P<0.001), greater luminal area stenosis (73.5±11.0% vs. 71.5±10.3%, P=0.002), and a higher prevalence of post-stenting irregular tissue protrusion (45.1% vs. 14.7%, P<0.001) than non-HPs. In the total cohort, target lesion revascularization (TLR)-free survival was poorer for HPs (log-rank test 7.66; P=0.006), and Cox proportional hazards analysis showed HP as an independent predictor of TLR (hazard ratio, 5.98; 95% confidence interval, 1.72-20.82; P=0.005). CONCLUSIONS: In SAP patients, HPs had greater complexity of lesions and higher vulnerability, which may have contributed to the poorer post-PCI outcomes.

Impact of a comprehensive cardiac rehabilitation programme versus coronary revascularisation in patients with stable angina pectoris: study protocol for the PRO-FIT randomised controlled trial.

BACKGROUND: Currently, in the majority of patients with stable angina pectoris (SAP) treatment consists of optimal medical treatment, potentially followed by coronary angiography and subsequent coronary revascularisation if necessary". Recent work questioned the effectiveness of these invasive procedures in reducing re-events and improving prognosis. The potential of exercise-based cardiac rehabilitation on clinical outcomes in patients with coronary artery disease is well-known. However, in the modern era, no studies compared the effects of cardiac rehabilitation versus coronary revascularisation in patients with SAP. METHODS: In this multicentre randomised controlled trial, 216 patients with stable angina pectoris and residual anginal complaints under optimal medical treatment will be randomised to: 1) usual care (i.e., coronary revascularisation), or 2) a 12-month cardiac rehabilitation (CR) programme. CR consists of a multidisciplinary intervention, including education, exercise training, lifestyle coaching and a dietary intervention with a stepped decline in supervision. The primary outcome will be anginal complaints (Seattle Angina Questionnaire-7) following the 12-month intervention. Secondary outcomes include cost-effectiveness, ischemic threshold during exercise, cardiovascular events, exercise capacity, quality of life and psychosocial wellbeing. DISCUSSION: In this study, we will examine the hypothesis that multidisciplinary CR is at least equally effective in reducing anginal complaints as the contemporary invasive approach at 12-months follow-up for patients with SAP. If proven successful, this study will have significant impact on the treatment of patients with SAP as multidisciplinary CR is a less invasive and potentially less costly and better sustainable treatment than coronary revascularisations. TRIAL REGISTRATION: Netherlands Trial Register, NL9537. Registered 14 June 2021.

Combined assessment of frailty and nutritional status can be a prognostic indicator after percutaneous coronary intervention.

The cardiac prognosis of patients with frailty and malnutrition remains poorly investigated. This study aimed to investigate the impact of frailty and malnutrition on cardiac prognosis by combining the clinical frailty scale (CFS) and the geriatric nutritional risk index (GNRI) in patients who underwent percutaneous coronary intervention (PCI). In this study, 608 patients who underwent PCI for stable angina pectoris between January 2018 and December 2020 were included. CFS scores of ≥ 4 were defined as high CFS and patients with these scores were considered frail. GNRI scores of ≤ 98.0 were defined as low GNRI and patients with these scores were considered to have malnutrition. Patients were categorized into low-risk (n = 267, low CFS and high GNRI), intermediate-risk (n = 200, high CFS or low GNRI), and high-risk (n = 141, high CFS and low GNRI) groups. Major adverse clinical events (MACEs), including all-cause death, nonfatal myocardial infarction, revascularization, hospitalization for heart failure, and stroke, were assessed. The median follow-up period was 529 days. During the follow-up, MACEs were found in 135 patients. The high-risk group were older (77.0 ± 9.2 vs 71.4 ± 10.7 vs 65.0 ± 10.1 years, p < 0.001), had higher prevalence rates of chronic kidney disease [61.7% (87/141) vs 37.5% (75/200) vs 16.9% (45/267); p < 0.001] and heart failure [47.5% (67/141) vs 22.5% (45/200) vs 12.4% (33/267), p < 0.001], and had higher C-reactive protein levels (1.64 ± 2.66 vs 1.00 ± 2.02 vs 0.34 ± 0.90 mg/dL; p < 0.001) than the intermediate-risk and low-risk groups. The high-risk group [hazard ratio (HR), 4.39; 95% confidence interval (CI), 2.87-6.72; p < 0.001] was an independent predictor of MACEs. In conclusion, patients with both frailty and malnutrition had a higher risk of MACEs after PCI than patients with frailty or malnutrition. Post-PCI patients should be evaluated for combined frailty and malnutrition.

Coronary "Microvascular Dysfunction": Evolving Understanding of Pathophysiology, Clinical Implications, and Potential Therapeutics.

Until recently, it has been generally held that stable angina pectoris (SAP) primarily reflects the presence of epicardial coronary artery stenoses due to atheromatous plaque(s), while acute myocardial infarction (AMI) results from thrombus formation on ruptured plaques. This concept is now challenged, especially by results of the ORBITA and ISCHEMIA trials, which showed that angioplasty/stenting does not substantially relieve SAP symptoms or prevent AMI or death in such patients. These disappointing outcomes serve to redirect attention towards anomalies of small coronary physiology. Recent studies suggest that coronary microvasculature is often both structurally and physiologically abnormal irrespective of the presence or absence of large coronary artery stenoses. Structural remodelling of the coronary microvasculature appears to be induced primarily by inflammation initiated by mast cell, platelet, and neutrophil activation, leading to erosion of the endothelial glycocalyx. This leads to the disruption of laminar flow and the facilitation of endothelial platelet interaction. Glycocalyx shedding has been implicated in the pathophysiology of coronary artery spasm, cardiovascular ageing, AMI, and viral vasculitis. Physiological dysfunction is closely linked to structural remodelling and occurs in most patients with myocardial ischemia, irrespective of the presence or absence of large-vessel stenoses. Dysfunction includes the impairment of platelet and vascular responsiveness to autocidal coronary vasodilators, such as nitric oxide, prostacyclin, and hydrogen sulphide, and predisposes both to coronary vasoconstriction and to a propensity for microthrombus formation. These findings emphasise the need for new directions in medical therapeutics for patients with SAP, as well as a wide range of other cardiovascular disorders.

Predictors of Long-Term Mortality in Patients with Stable Angina Pectoris and Coronary Slow Flow.

Background and Objectives: Coronary slow flow (CSF) is an angiographic phenomenon characterized by the slow progression of an injected contrast agent during diagnostic coronary angiography in the absence of significant stenosis. Although CSF is a common angiographic finding, the long-term outcomes and mortality rates are still unknown. This study aimed to investigate the underlying causes of mortality over a 10-year period in patients diagnosed with stable angina pectoris (SAP) and CSF. Materials and Methods: This study included patients with SAP who underwent coronary angiography from 1 January 2012 to 31 December 2012. All patients displayed CSF despite having angiographically normal coronary arteries. Hypertension (HT), diabetes mellitus (DM), hyperlipidaemia, medication compliance, comorbidities, and laboratory data were recorded at the time of angiography. Thrombolysis in myocardial infarction (TIMI) frame count (TFC) was calculated for each patient. The cardiovascular (CV) and non-CV causes of long-term mortality were assessed. Results: A total of 137 patients with CSF (93 males; mean age: 52.2 ± 9.36 years) were included in this study. Twenty-one patients (15.3%) died within 10 years of follow-up. Nine (7.2%) and 12 (9.4%) patients died of non-CV and CV causes, respectively. Total mortality in patients with CSF was associated with age, HT, discontinuation of medications, and high-density lipoprotein cholesterol (HDL-C) levels. The mean TFC was associated with CV mortality. Conclusion: Patients with CSF exhibited a notable increase in cardiovascular-related and overall mortality rates after 10 years of follow-up. HT, discontinuation of medications, HDL-C levels, and mean TFC were associated with mortality in patients with CSF.

[Network Meta-analysis of Chinese medicine injection combined with conventional western medicine in treatment of stable angina pectoris].

This study aimed to systematically evaluate the efficacy and safety of different Chinese medicine injections combined with conventional western medicine for stable angina pectoris. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, and SinoMed were searched to collect randomized controlled trial(RCT) of Chinese medicine injection combined with conventio-nal western medicine in the treatment of stable angina pectoris from the inception of the databases to July 8, 2022. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias of the included studies. Stata 15.1 was used for network Meta-analysis. A total of 52 RCTs were included, involving 4 828 patients treated by 9 Chinese medicine injections(Danhong Injection, Salvia Miltiorrhiza Polyphenol Hydrochloride Injection, Tanshinone Sodium Ⅱ_A Sulfonate Injection, Salvia Miltiorrhiza Ligustrazine Injection, Dazhu Hongjingtian Injection, Puerarin Injection, Safflower Yellow Pigment Injection, Shenmai Injection and Xuesaitong Injection). The network Meta-analysis showed that:(1)in terms of improving the efficacy of angina pectoris, the surface under the cumulative ranking curve(SUCRA) followed the order of conventional western medicine combined with Salvia Miltiorrhiza Ligustrazine Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Danhong Injection>Salvia Miltiorrhiza Polyphenol Hydrochloride Injection>Xuesaitong Injection>Shenmai Injection>Puerarin Injection>Safflower Yellow Pigment Injection>Dazhu Hongjingtian Injection;(2)in terms of improving the efficacy of electrocardiogram(ECG), SUCRA followed the order of conventional western medicine combined with Salvia Miltiorrhiza Ligustrazine Injection>Puerarin Injection>Danhong Injection>Salvia Miltiorrhiza Polyphenol Hydrochloride Injection>Shenmai Injection>Xuesaitong Injection>Safflower Yellow Pigment Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection;(3)in terms of increasing high-density lipoprotein cholesterol(HDL-C), SUCRA followed the order of conventional western medicine combined with Danhong Injection>Shenmai Injection>Safflower Yellow Pigment Injection>Xuesaitong Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection;(4)in terms of lowering low-density lipoprotein cholesterol(LDL-C), SUCRA followed the order of conventional western medicine combined with Safflower Yellow Pigment Injection>Danhong Injection>Shenmai Injection>Tanshinone Sodium Ⅱ_A Sulfonate Injection>Dazhu Hongjingtian Injection>Xuesaitong Injection;(5)in terms of safety, the overall adverse reactions of Chinese medicine injection combined with conventional western medicine were less than those of the control group. Current evidence indicated that Chinese medicine injection combined with conventional western medicine could improve the curative effect of stable angina pectoris with higher safety. Limited by the number and quality of included studies, the above conclusion needed to be verified by more high-quality studies.

Platelet glycoprotein IIb/IIIa inhibitor tirofiban in clopidogrel-naïve patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The safety of administration of tirofiban, a platelet glycoprotein IIb/IIIa inhibitor, followed by a clopidogrel loading dose in clopidogrel-naïve patients undergoing ad-hoc percutaneous coronary intervention (PCI) is not yet clear. METHODS: In a retrospective observational cohort analysis, clopidogrel-naïve patients undergoing ad-hoc PCI who received a high-dose bolus of tirofiban (25 µg/kg) followed by a 600-mg clopidogrel loading dose (group 1) were compared with patients undergoing elective PCI who were pretreated with clopidogrel (group 2), between September 2014 and October 2021. The primary outcome was major adverse cardiovascular events (MACE) defined as the composite of death, myocardial infarction, stroke, target-lesion revascularisation and bleeding at 30 days. Secondary outcomes were MACE at 7 days and individual components of the primary outcome at 7 and 30 days. RESULTS: A total of 1404 patients were included: 432 (31%) in group 1 and 972 (69%) in group 2. Median age was 69 years, and 28% were female. At 7­day follow-up, MACE occurred in 1.4% in group 1 versus 3.0% in group 2 (p = 0.08). 30-day MACE were observed in 1.9% in group 1 and 4.2% in group 2 (p = 0.03). Secondary outcomes were comparable between the groups. Cox regression analysis, corrected for baseline differences, revealed no significant difference in the primary outcome (hazard ratio: 1.8; 95% confidence interval: 0.8-3.9). CONCLUSION: Ad-hoc PCI in clopidogrel-naïve patients who were treated with high-dose bolus of tirofiban followed by a clopidogrel loading dose immediately after the procedure appeared to be safe.

ASSESSMENT OF CARDIOVASCULAR DISEASE RISK FACTORS IN PATIENTS WITH CORONARY HEART DISEASE COMBINED WITH NONALCOHOLIC FATTY LIVER DISEASE.

OBJECTIVE: The aim: To study the risk factors of cardiovascular diseases in patients with coronary heart disease with stable angina pectoris II functional class in combi¬nation with NAFLD. PATIENTS AND METHODS: Materials and methods: The study included 245 patients with a diagnosis of CHD, stable angina pectoris II functional class (FC), who were being treated at the Communal Nonprofit Enterprise «Central City Clinical Hospital¼ of Uzhhorod City Council. We singled out 2 groups of patients: group 1 (n=145) - patients with CHD with stable angina pectoris II FC in combination with NAFLD and group 2 (n=100) - patients with CHD with stable angina pectoris II FC. RESULTS: Results: Analysis of the frequency of occurrence of CVD risk factors in patients with CHD showed that among patients of group 1 there are 50% more people with abdominal obesity, excess body and dyslipidemia. The reliability between the groups in the occurrence of hypertension and type 2 diabetes was not revealed. The obtained results confirm the data that the prevalence of NAFLD increases with increasing body weight and a high degree of obesity increases the risk of its development. CONCLUSION: Conclusions: The most frequent risk factors for CVD in patients with coronary artery disease in combination with NAFLD are hypertension, obesity, and dyslipidemia.

Glasgow prognostic score can be a prognostic indicator after percutaneous coronary intervention: a two-center study in Japan.

Glasgow prognostic score (GPS) has been used to evaluate inflammatory response and nutritional status. This study aimed to investigate the impact of nutritional status on cardiac prognosis by using GPS in patients after undergoing percutaneous coronary intervention (PCI). We included 862 patients who underwent PCI for stable angina pectoris between 2015 and 2018. We used the original cutoff values, which were an albumin (Alb) level of 3.5 g/dl and a C-reactive protein (CRP) level of 0.3 mg/dl. We categorized them into the three groups: originally defined GPS (od-GPS) 0 (high Alb and low CRP), 1 (low Alb or high CRP), and 2 (low Alb and high CRP). Major adverse clinical events (MACEs) included all-cause death, nonfatal myocardial infarction, revascularization, and hospitalization for heart failure. The median follow-up period was 398.5 days. During the follow-up, MACEs occurred in 136 patients. Od-GPS 2 had higher prevalence rates in terms of chronic kidney disease (CKD; 31.7% [229/722] vs. 44.9% [53/118] vs. 63.6% [14/22], p < 0.001), hemodialysis (6.4% [46/722] vs. 14.4% [17/118] vs. 31.8% [7/22], p < 0.001), and heart failure cases (HF; 9.1% [66/722] vs. 14.4% [17/118] vs. 27.3% [6/22], p = 0.007), with higher creatinine (1.17 ± 1.37 mg/dl vs. 1.89 ± 2.60 mg/dl vs. 3.49 ± 4.01 mg/dl, p < 0.001) and brain natriuretic peptide levels (104.1 ± 304.6 pg/ml vs. 242.4 ± 565.9 pg/ml vs. 668.1 ± 872.2 pg/ml, p < 0.001) and lower low-density lipoprotein cholesterol (101.5 ± 32.9 mg/dl vs. 98.2 ± 28.8 mg/dl vs. 77.1 ± 24.3 mg/dl, p = 0.002) than od-GPS 0 and 1.Od-GPS 2 (HR 2.42; 95% CI 1.16-5.02; p = 0.018), od-GPS 1 (HR 2.09; 95% CI 1.40-3.13; p < 0.001), diabetes (HR 1.41; 95% CI 1.00-1.99; p = 0.048), CKD (HR 2.10; 95% CI 1.49-2.96; p < 0.001), and HF (HR 1.64; 95% CI 1.05-2.56; p = 0.029) were independent predictors of MACEs. A scoring system using CRP and Alb levels with a milder definition than GPS suitably predicted the risk of MACEs in the patients who underwent PCI.

Coronary Microvascular Dysfunction: A Practical Approach to Diagnosis and Management.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of diagnostic and treatment considerations in patients with coronary microvascular dysfunction (CMD) in the absence of obstructive coronary artery disease (CAD). RECENT FINDINGS: The prevalence of obstructive CAD in unselected patient populations referred for evaluation of angina is less than 10%. A significant proportion of patients with angina and no obstructive CAD have CMD, a condition associated with impaired cardiovascular prognosis. Non-invasive and invasive evaluation of coronary microvascular function is feasible and widely available, yet CMD is underdiagnosed and undertreated. A patient-tailored treatment approach guided by coronary microvascular testing shows promising results for patient-reported outcomes of symptom burden and quality of life. Coronary microvascular testing should be considered in angina patients with no obstructive CAD, before other causes of chest pain are explored. A patient-tailored treatment approach guided by a complete evaluation of epicardial anatomy and macro-and microvascular function may help optimize treatment strategy and prevent unnecessary medical interventions. More research is needed to establish the long-term effect of patient-tailored therapies on risk reduction in CMD.

Healed Plaques in Patients With Stable Angina Pectoris.

OBJECTIVE: Healed plaques, signs of previous plaque destabilization, are frequently found in the coronary arteries. Healed plaques can now be diagnosed in living patients. We investigated the prevalence, angiographic, and optical coherence tomography features of healed plaques in patients with stable angina pectoris. Approach and Results: Patients with stable angina pectoris who had undergone optical coherence tomography imaging were included. Healed plaques were defined as plaques with one or more signal-rich layers of different optical density. Patients were divided into 2 groups based on layered or nonlayered phenotype at the culprit lesion. Among 163 patients, 87 (53.4%) had layered culprit plaque. Patients with layered culprit plaque had more multivessel disease (62.1% versus 44.7%, P=0.027) and more angiographically complex culprit lesions (64.4% versus 35.5%, P<0.001). Layered culprit plaques had higher prevalence of lipid plaque (83.9% versus 64.5%, P=0.004), macrophage infiltration (58.6% versus 35.5%, P=0.003), calcifications (78.2% versus 63.2%, P=0.035), and thrombus (28.7% versus 14.5%, P=0.029). Lipid index (P=0.001) and percent area stenosis (P=0.015) were greater in the layered group. The number of nonculprit plaques, evaluated using coronary angiograms, tended to be greater in patients with layered culprit plaque (4.2±2.5 versus 3.5±2.1, P=0.053). Nonculprit plaques in patients with layered culprit lesion had higher prevalence of layered pattern (P=0.002) and lipid phenotype (P=0.005). Lipid index (P=0.013) and percent area stenosis (P=0.002) were also greater in this group. CONCLUSIONS: In patients with stable angina pectoris, healed culprit plaques are common and have more features of vulnerability and advanced atherosclerosis both at culprit and nonculprit lesions.

Genetic dysregulation of endothelin-1 is implicated in coronary microvascular dysfunction.

AIMS: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide linked to vascular diseases through a common intronic gene enhancer [(rs9349379-G allele), chromosome 6 (PHACTR1/EDN1)]. We performed a multimodality investigation into the role of ET-1 and this gene variant in the pathogenesis of coronary microvascular dysfunction (CMD) in patients with symptoms and/or signs of ischaemia but no obstructive coronary artery disease (CAD). METHODS AND RESULTS: Three hundred and ninety-one patients with angina were enrolled. Of these, 206 (53%) with obstructive CAD were excluded leaving 185 (47%) eligible. One hundred and nine (72%) of 151 subjects who underwent invasive testing had objective evidence of CMD (COVADIS criteria). rs9349379-G allele frequency was greater than in contemporary reference genome bank control subjects [allele frequency 46% (129/280 alleles) vs. 39% (5551/14380); P = 0.013]. The G allele was associated with higher plasma serum ET-1 [least squares mean 1.59 pg/mL vs. 1.28 pg/mL; 95% confidence interval (CI) 0.10-0.53; P = 0.005]. Patients with rs9349379-G allele had over double the odds of CMD [odds ratio (OR) 2.33, 95% CI 1.10-4.96; P = 0.027]. Multimodality non-invasive testing confirmed the G allele was associated with linked impairments in myocardial perfusion on stress cardiac magnetic resonance imaging at 1.5 T (N = 107; GG 56%, AG 43%, AA 31%, P = 0.042) and exercise testing (N = 87; -3.0 units in Duke Exercise Treadmill Score; -5.8 to -0.1; P = 0.045). Endothelin-1 related vascular mechanisms were assessed ex vivo using wire myography with endothelin A receptor (ETA) antagonists including zibotentan. Subjects with rs9349379-G allele had preserved peripheral small vessel reactivity to ET-1 with high affinity of ETA antagonists. Zibotentan reversed ET-1-induced vasoconstriction independently of G allele status. CONCLUSION: We identify a novel genetic risk locus for CMD. These findings implicate ET-1 dysregulation and support the possibility of precision medicine using genetics to target oral ETA antagonist therapy in patients with microvascular angina. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03193294.

Correlation of Serum Adipolin with Epicardial Fat Thickness and Severity of Coronary Artery Diseases in Acute Myocardial Infarction and Stable Angina Pectoris Patients.

OBJECTIVE: Adipolin/C1q/TNF-related protein-12 is a family of CTRPs highly expressed in adipose tissue with glucose-lowering and anti-inflammatory effects. Various risk factors have been suggested in the incidence of cardiovascular diseases, such as a decrease in anti-inflammatory or an increase in inflammatory factors. The purpose of the present study was to investigate the correlation of adipolin with anthropometric, angiographic, echocardiographic, and biochemical parameters. SUBJECT AND METHODS: A total of 90 patients who were candidates for angiography were included in the study and divided into 3 groups: 30 patients with acute myocardial infarction (AMI), 30 patients with stable angina pectoris (SAP), and 30 subjects as a control group with a history of chest pain but normal angiography. Anthropometric, angiographic, echocardiographic, and biochemical parameters were measured in all subjects. RESULTS: Serum adipolin levels were significantly decreased in patients with AMI compared with the SAP and control groups (p < 0.001 for both). In addition, there was a negative association between serum levels of adipolin and epicardial fat thickness (EFT) and Gensini score in CAD patients. The results of multivariate linear regression analysis revealed that EFT values were independently associated with serum adipolin levels. CONCLUSION: The current study showed an independent association of adipolin with EFT for the first time in patients with AMI. Decreased adipolin levels in patients with AMI may be involved in the process of atherosclerosis, which requires further study.

Gender characteristics of lipid profile parameters and markers of vascular inflammation in patients with stable angina pectoris in groups with presence and absence of type 2 diabetes.

The study of the parameters of the lipid profile and markers of the inflammatory reaction of the vascular wall in patients with stable angina pectoris in the presence or absence of type 2 diabetes mellitus (T2DM) is of great importance for revealing the gender characteristics of the pathophysiological mechanisms of the development and course of diseases, developing secondary prevention of complications and determining the prognosis. 194 patients with stable angina pectoris (SA), single-vessel coronary artery disease, mean age 60.3 ± 7.8 years were examined. Patients were divided into two groups: group 1 - patients with SA without diabetes 2 (n = 152), group 2 - with SA and diabetes 2 (n = 42). In each group, subgroups of men and women are distinguished. The study of biomarkers was carried out upon admission to the hospital on the background of therapy, taken on an outpatient basis. The study included a complex of parameters of the lipid spectrum, markers of the inflammatory response, endothelial dysfunction, and carbohydrate metabolism parameters. A comparative analysis of biomarkers revealed an excess of reference values of atherogenic lipid fractions in both groups of patients, regardless of patient gender. Moreover, in the first group of patients, in the subgroup of women, a significant excess of the level of TC, PL (a), and ApoA-1 was registered compared with the subgroup of men. In the second group, there were no significant differences in parameters between the male and female subgroups. Evaluation of the parameters of the inflammatory reaction revealed in the subgroup of women with T2DM a steady tendency to exceed the level of hs-CRP, TNF-α, homocysteine compared with both men and women in the SA group without T2DM. The logistic regression revealed the main biochemical markers that affect the aggravation of the course of IHD in women with T2DM: this is a uric acid level of more than 380 mmol / l - OS 11.5 (95% CI 1.71-77.69), TNF-α more 8 pg / ml - OR 7.5 (95% CI 1.07-52.46) and an increase in TG - OR 3.33 (95% CI 1.073-10.335). Thus, women of the 2nd group with the presence of T2DM are characterized by the highest level of atherogenic fractions of lipids, markers of vascular inflammation, glucose and HbA1c, which may indicate the greatest potential for the development of atherothrombotic complications in this subgroup of patients.

Predictors for layered coronary plaques: an optical coherence tomography study.

Healed coronary plaques, morphologically characterized by a layered pattern, are signatures of previous plaque disruption and healing. Recent optical coherence tomography (OCT) studies showed that layered plaque is associated with vascular vulnerability. However, factors associated with layered plaques have not been studied. The aim of this study was to investigate predictors for layered plaque at the culprit plaques and at non-culprit plaques. Patients with coronary artery disease who underwent pre-intervention OCT imaging of the culprit lesion were included. Layered plaques were defined as plaques with one or more layers of different optical density and a clear demarcation from underlying components. Among 313 patients, layered plaque at the culprit lesion was observed in 18.8% of ST-segment elevation myocardial infarction patients, 36.3% of non-ST-segment elevation acute coronary syndrome patients, and 53.4% of stable angina pectoris (SAP) patients (p < 0.001). In the multivariable model, SAP, multivessel disease, type B2/C lesion, and diameter stenosis > 70% were independent predictors for layered plaque at the culprit lesion. In addition, 394 non-culprit plaques in 190 patients were assessed to explore predictors for layered plaques at non-culprit lesions. SAP, and thin-cap fibroatheroma and layered plaque at the culprit lesion were independent predictors for layered plaques at non-culprit lesions. In conclusion, clinical presentation of SAP was a strong predictor for layered plaque at both culprit plaques and non-culprit plaques. Development and biologic significance of layered plaques may be related to a balance between pan-vascular vulnerability and endogenous anti-thrombotic protective mechanism.

Prevalence and Clinical Significance of Layered Plaque in Patients With Stable Angina Pectoris　- Evaluation With Histopathology and Optical Coherence Tomography.

BACKGROUND: Healed plaques are identified as a layered pattern with optical coherence tomography (OCT) imaging, but the exact relationship between healed plaques and the development of significant coronary stenosis in stable angina pectoris (SAP) is not fully understood.Methods and Results:A retrospective clinincal study investigated the OCT characteristics of culprit lesions of SAP patients (n=205), and a prospective study examined the histopathological characteristics of layered plaque in directional coronary atherectomy (DCA) samples (42 samples from 18 SAP patients). In the retrospective study, layered plaque was observed in 36.6% of the SAP culprit lesions. Compared with patients with non-layered plaque, male sex and smoking were more frequent, and HbA1c level was significantly higher in the patients with layered plaque (81.3% vs. 65.9%, P<0.05; 62.7% vs. 41.8%, P<0.05; 6.6±1.3% vs. 6.2±1.0%, P<0.05, respectively). Furthermore, layered plaque was accompanied by higher plaque vulnerability and smaller minimal lumen area. In the histopathological study, the layered plaques had a significantly higher rate of intramural thrombus and macrophages infiltration than non-layered plaques (75.0% vs. 14.3%, P<0.05; 75.0% vs. 38.1%, P<0.05, respectively). CONCLUSIONS: Healed plaque containing intramural thrombus is identified as layered plaque by OCT, and was frequently observed, even in SAP patients. Intramural thrombus might play an important role in the development of coronary plaque with a high degree of stenosis in SAP patients.

Ivabradine drug utilization study in five European countries: A multinational, retrospective, observational study to assess effectiveness of risk-minimization measures.

PURPOSE: This drug utilization study of ivabradine evaluated prescriber compliance with the new risk minimization measures (RMMs), communicated starting 2014 following preliminary results from the SIGNIFY study. METHODS: This was a multinational (five European countries) chart review study with two study periods: pre-RMM and post-RMM. Patients initiating ivabradine for chronic stable angina pectoris in routine clinical practice were identified across general practitioners and specialists. The primary outcome analysis evaluated the compliance with the new RMMs, ie, use in patients with a heart rate greater than or equal to 70 bpm at initiation, no doses higher than those recommended in the summary of product characteristics (SmPC) at initiation and during 6 months of follow-up, and no concomitant use of verapamil or diltiazem. RESULTS: Overall, 711 and 506 eligible patients were included in the pre-RMM and post-RMM periods, respectively. The percentage of patients prescribed ivabradine according to the new RMMs increased significantly in the post-RMM period (70.6% and 78.4% in the pre- and post-RMM periods respectively; P value = .0035). The compliance to RMMs increased for all the criteria assessed independently: the proportions of patients with (a) heart rate ≥ 70 bpm at initiation (79.4% and 85.2%, respectively; P value = .0141), (b) no dose higher than the SmPC doses at initiation and during follow-up (92.8% and 94.1%, respectively; P value = .3957), and (c) no concomitance with verapamil or diltiazem (96.1% and 99.2%, respectively; P value = .0007). CONCLUSIONS: The RMMs for ivabradine were well implemented across the five participating European countries confirming a favorable benefit-risk balance of ivabradine in chronic stable angina pectoris.

3D-speckle tracking echocardiography for assessment of coronary artery disease severity in stable angina pectoris.

BACKGROUND AND AIM: Stable angina pectoris is a common disease that may cause disability. Some noninvasive new methods can be useful for the detection of early-stage coronary artery disease. The relationship between coronary artery disease (CAD) severity and resting 3-dimensional-speckle tracking echocardiography (3D-STE) in stable angina pectoris patients was evaluated in this study. METHODS: One hundred and twenty consecutive patients between 18-80 years of age and without a history of CAD to whom elective coronary angiography was planned after positive stress test or myocardial perfusion scintigraphy were enrolled in the study. 3D-STE was performed and global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and global area strain (GAS) were measured before coronary angiography. A Gensini score of ≥20 was accepted as critical CAD. Correlation between Gensini scores and 3D-STE results were evaluated. RESULTS: Mean age was 60.7 ± 10.01 years, and 55% of the patient population were male. There were not any significant differences between critical CAD and noncritical CAD groups for age, gender, history of hypertension, diabetes mellitus, hyperlipidemia, and Left Ventricular Ejection Fraction. Mean GLS was -12, GCS was -18.8, GRS was 33.4, GAS was -28.9, and mean Gensini score was 18.8. GLS and all other strain parameters were significantly worse in patients with critical CAD group compared with noncritical CAD group and also positive linear correlation was observed between Gensini score and all measured strain parameters (r = 0.568, P < 0.001 for Gensini score and GLS; r = 0.617, P < 0.001 for Gensini score and GAS). A GLS value of >-10 has 88.9% sensitivity and 92.9% specificity; A GAS value of >-21 has 97.2% sensitivity and 88.1% specificity to detect critical CAD. CONCLUSIONS: 3D-STE is a noninvasive and handy parameter to detect subclinical left ventricular dysfunction and global strain values were significantly correlated with CAD severity. GAS has the sensitivity of 97.2% and specificity of 88.1% to detect critical CAD. Adding 3D strain echocardiography to exercise test or myocardial perfusion scintigraphy might increase sensitivity to detect critical CAD in clinical practice.