Assessment of platelet functional activity in healthy individuals and patients receiving antiplatelet therapy. Possible inconsistencies between aggregation and flow cytometry tests.

Platelet functional activity was assessed in healthy volunteers (HV, n=92), patients with stable angina pectoris (SA, n=42) and acute coronary syndrome (ACS, n=73), treated with acetylsalicylic acid (ASA) + clopidogrel and ASA + ticagrelor, respectively. In all HV and patients we have compared parameters of platelet aggregation (maximum light transmission and velocity, Tmax and Vmax) and parameters, characterizing exposure of platelet activation markers, evaluated by flow cytometry. HV platelets were activated by 10 µM, 1 µM TRAP, and 20 µM, 5 µM, 2.5 µM ADP; patient platelets were activated by 10 µM TRAP and by 20 µM and 5 µM ADP. Strong and significant correlations between the aggregation and flow cytometry parameters (the r correlation coefficient from 0.4 up to >0.6) most frequently were registered in HV platelet during activation by 1 µM TRAP and in SA patients during platelet activation by 20 µM and 5 µM ADP. However, in many other cases these correlations were rather weak (r < 0.3) and sometimes statistically insignificant. In HV the differences in PAC-1 binding parameters between platelets activated by 10 µM TRAP (the strongest agonist) and all ADP concentrations were negligible (≤ 10%), while CD62P binding (at all ADP concentrations) and LTA parameters for (5 µM and 2.5 µM ADP) were significantly lower (by 40-60%). Antiplatelet therapy in patients decreased all parameters as compared to HV, but to varying extents. For 10 µM TRAP the MFI index for PAC-1 binding (40-50% decrease) and for both ADP concentrations the Tmax values (60-85% decrease) appeared to be the most sensitive in comparison with the other parameters that decreased to a lesser extent. The data obtained indicate a possibility of inconsistency between different LTA and flow cytometry parameters in assessing platelet activity and efficacy of antiplatelet drugs.

Coronary sinus reducer for the treatment of refractory angina (ORBITA-COSMIC): a randomised, placebo-controlled trial.

BACKGROUND: The coronary sinus reducer (CSR) is proposed to reduce angina in patients with stable coronary artery disease by improving myocardial perfusion. We aimed to measure its efficacy, compared with placebo, on myocardial ischaemia reduction and symptom improvement. METHODS: ORBITA-COSMIC was a double-blind, randomised, placebo-controlled trial conducted at six UK hospitals. Patients aged 18 years or older with angina, stable coronary artery disease, ischaemia, and no further options for treatment were eligible. All patients completed a quantitative adenosine-stress perfusion cardiac magnetic resonance scan, symptom and quality-of-life questionnaires, and a treadmill exercise test before entering a 2-week symptom assessment phase, in which patients reported their angina symptoms using a smartphone application (ORBITA-app). Patients were randomly assigned (1:1) to receive either CSR or placebo. Both participants and investigators were masked to study assignment. After the CSR implantation or placebo procedure, patients entered a 6-month blinded follow-up phase in which they reported their daily symptoms in the ORBITA-app. At 6 months, all assessments were repeated. The primary outcome was myocardial blood flow in segments designated ischaemic at enrolment during the adenosine-stress perfusion cardiac magnetic resonance scan. The primary symptom outcome was the number of daily angina episodes. Analysis was done by intention-to-treat and followed Bayesian methodology. The study is registered with ClinicalTrials.gov, NCT04892537, and completed. FINDINGS: Between May 26, 2021, and June 28, 2023, 61 patients were enrolled, of whom 51 (44 [86%] male; seven [14%] female) were randomly assigned to either the CSR group (n=25) or the placebo group (n=26). Of these, 50 patients were included in the intention-to-treat analysis (24 in the CSR group and 26 in the placebo group). 454 (57%) of 800 imaged cardiac segments were ischaemic at enrolment, with a median stress myocardial blood flow of 1·08 mL/min per g (IQR 0·77-1·41). Myocardial blood flow in ischaemic segments did not improve with CSR compared with placebo (difference 0·06 mL/min per g [95% CrI -0·09 to 0·20]; Pr(Benefit)=78·8%). The number of daily angina episodes was reduced with CSR compared with placebo (OR 1·40 [95% CrI 1·08 to 1·83]; Pr(Benefit)=99·4%). There were two CSR embolisation events in the CSR group, and no acute coronary syndrome events or deaths in either group. INTERPRETATION: ORBITA-COSMIC found no evidence that the CSR improved transmural myocardial perfusion, but the CSR did improve angina compared with placebo. These findings provide evidence for the use of CSR as a further antianginal option for patients with stable coronary artery disease. FUNDING: Medical Research Council, Imperial College Healthcare Charity, National Institute for Health and Care Research Imperial Biomedical Research Centre, St Mary's Coronary Flow Trust, British Heart Foundation.

[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.

Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial.

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Effect of DLT-SML on Chronic Stable Angina Through Ameliorating Inflammation, Correcting Dyslipidemia, and Regulating Gut Microbiota.

ABSTRACT: Chronic stable angina (CSA) is caused by coronary atherosclerosis. The gut microbiota (GM) and their metabolite trimethylamine-N-oxide (TMAO) levels are associated with atherosclerosis. Danlou tablet (DLT) combined with Salvia miltiorrhiza ligustrazine (SML) injection has been used to treat CSA. This study aims to investigate how DLT combined with SML (DLT-SML) regulates serum lipids, inflammatory cytokines, GM community, and microbial metabolite in patients with CSA. In this study, 30 patients with CSA were enrolled in the DLT-SML group, and 10 healthy volunteers were included in the healthy control group. The patients in the DLT-SML group were subdivided as the normal total cholesterol (TC) group and high-TC group according to their serum TC level before treatment. Blood samples were collected to investigate the (1) lipid content, including triglyceride (TG), TC, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, (2) fasting blood glucose (Glu), (3) inflammatory cytokines, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α), and (4) gut-derived metabolite, including lipopolysaccharides and TMAO level. GM composition was analyzed by sequencing 16S rRNA of fecal samples. Results showed that DLT-SML significantly decreased serum TG, TC, low-density lipoprotein cholesterol, IL-1ß, TNF-α, and TMAO levels of patients with CSA. DLT-SML increased the abundance of Firmicutes and decreased Proteobacteria, which were significantly lower or higher in patients with CSA, respectively, compared with the healthy control group. In particular, DLT-SML increased the microbial diversity and decreased Firmicutes/Bacteroidetes ratio of patients with high-TC. The abundance of Sarcina, Anaerostipes, Streptococcus, Weissella, and Erysipelatoclostridium was decreased, whereas Romboutsia, Faecalibacterium, and Subdoligranulum were increased by DLT-SML treatment in patients with CSA. These findings indicated that DLT-SML improved patients with CSA by ameliorating dyslipidemia profile, decreasing the circulating inflammatory cytokines, and regulating the GM composition and their metabolites.

The Role of Nicorandil in the Management of Chronic Coronary Syndromes in the Gulf Region.

Chronic coronary syndromes (CCS) and stable angina are a growing clinical burden worldwide. This is of particular concern in the Gulf region given its high prevalence of cardiovascular risk factors, especially diabetes mellitus and smoking. Despite recommendations on the use of first- and second-line anti-anginal medication, management challenges remain. Current guidelines for pharmacologic treatment are not determined by the range of pathophysiological mechanisms of ischaemia and consequent angina, which may occur either in isolation or co-exist. In this article, we highlight the need to improve knowledge of the epidemiology of chronic coronary syndromes in the Middle East and Gulf region, and the need for studies of stratified pharmacologic approaches to improve symptomatic angina and quality of life in the large and growing number of patients with coronary artery disease from this region. We discuss the role of nicorandil, currently recommended as a second-line anti-anginal drug in CCS patients, and suggest that this may be a particularly useful add-on therapy for patients in the Gulf region.

Treatment selection and medication adherence for stable angina: The role of area-based health literacy.

RATIONALE, AIMS, AND OBJECTIVES: Clinical studies show equivalent health outcomes from interventional procedures and treatment with medication only for stable angina patients. However, patients may be subject to overuse or access barriers for interventional procedures and may exhibit suboptimal adherence to medications. Our objective is to evaluate whether community-level health literacy is associated with treatment selection and medication adherence patterns. METHOD: The sample included Medicare fee-for-service beneficiaries (20% random sample) with stable angina in 2007-2013. We used an area-level health literacy variable because of the lack of an individual measure in claims. We measured the association between (a) area-based health literacy with treatment selection (medication only, percutaneous coronary intervention [PCI], or coronary artery bypass grafting (CABG) surgery) and (b) area-based health literacy with medication adherence. We controlled for other factors including demographics, co-morbidity burden, dual eligibility, and area deprivation index. RESULTS: We identified 8300 patients of whom 8.7% lived in a low health literacy area. Overall, 56% of patients received medication only, 28% received PCI, and 15% received CABG. Patients in low health literacy areas were less likely to receive CABG (-3.5 percentage points; 95% CI, -6.8 to -0.3) than were patients in high health literacy areas, but the significance was sensitive to specification. Overall, 81.5% and 71.5% of patients were adherent to antianginals and statins, respectively. Living in low health literacy areas was associated with lower adherence to antianginals (-3.3 percentage points; 95% CI, -6.1 to -0.6) but not statins. CONCLUSIONS: Low area-based health literacy was associated with being less likely to receive CABG and lower adherence, but the differences between low and high health literacy areas were small and sensitive to model specification. Individual factors such as dual eligibility status and race/ethnicity had stronger associations with outcomes than had area-based health literacy, suggesting that this area-based measure was inadequate to account for social determinants in this study.

Low Response to Clopidogrel in Coronary Artery Disease.

BACKGROUND: In patients with coronary artery disease, cardiovascular mortality and other acute events showed a clear correlation with risk factors and biomarkers including platelet activation. STUDY QUESTION OF THIS RESEARCH: Which was the incidence of low response to clopidogrel and its correlation with risk factors and biomarkers in coronary artery disease? STUDY DESIGN: Four hundred patients (pts) with coronary artery disease-stable angina (SA) and acute coronary syndrome-were divided into 8 groups of study, consistent with low response to clopidogrel and the type of coronary artery disease. Low response to clopidogrel-defined as adenosine diphosphate test-ADP-test of >46 U by multiple electrode platelet aggregometry was evaluated in correlation with cardiovascular risk factors and biomarkers of oxidative stress, endothelial dysfunction, hypercoagulability, high platelet reactivity. RESULTS: In coronary artery disease, low response to clopidogrel significantly correlated with older than 65 years, smoking, hypertension, diabetes mellitus, body mass index of >25, previous aspirin treatment (P < 0.05), high value of total and low-density lipoprotein cholesterol, low value of high-density lipoprotein cholesterol, low response to aspirin, high mean platelets volume and von Willebrand factor activity, low flow-mediated vasodilatation, total antioxidant status (P < 0.01) and only in patients with SA of male gender (P < 0.01). The incidence of other hypercoagulability biomarkers, such as reduced values of S protein, C protein, antithrombin III, and V Factor Leiden resistance to activated protein C, was very low and not correlated with low response to clopidogrel. CONCLUSIONS: In coronary artery disease, low response to clopidogrel significantly correlated with the most of old cardiovascular risk factors, with previous aspirin treatment, low response to aspirin, higher mean platelets volume, higher von Willebrand factor activity, lower flow-mediated vasodilatation, and lower total antioxidant status values and only in patients with SA of male gender.

Nicorandil: A drug with ongoing benefits and different mechanisms in various diseased conditions.

Nicorandil is a well-known antianginal agent, which has been recommended as one of the second-line treatments for chronic stable angina as justified by the European guidelines. It shows an efficacy equivalent to that of classic antianginal agents. Nicorandil has also been applied clinically in various cardiovascular diseases such as variant or unstable angina and reperfusion-induced damage following coronary angioplasty or thrombolysis. Different mechanisms have been involved in the protective effects of nicorandil in various diseases through either opening of adenosine triphosphate-sensitive potassium (KATP) channel or donation of nitric oxide (NO). The predominance or participation of any of these proposed mechanisms depends on the dose of nicorandil used, the location of diseased conditions, and if this mechanism is still functioning or not. The protection afforded by nicorandil has been shown to be mainly attributed to KATP channel opening in experimental models of myocardial and pulmonary fibrosis as well as renal injury or glomerulonephritis, whereas NO donation predominates as a mechanism of protection in hepatic fibrosis and inflammatory bowel diseases. Therefore, in different diseased conditions, it is important to know which mechanism plays the major role in nicorandil-induced curative or protective effects. This can bring new insights into the proper use of selected medication and its recommended dose for targeting certain disease.

Effects of Puerarin on Clinical Parameters, Vascular Endothelial Function, and Inflammatory Factors in Patients with Coronary Artery Disease.

BACKGROUND The aim of this study was to investigate the effects of puerarin on vascular endothelial function and inflammatory factors in coronary artery disease (CAD) patients with stable angina pectoris (SAP). MATERIAL AND METHODS To evaluate the effects of angina pectoris, the differences of scores of the Seattle angina questionnaire (SAQ), vascular endothelial function [endothelial progenitor cells (EPCs), nitric oxide (NO) and endothelin 1 (ET-1)], and inflammatory factors [tumor necrosis factor a (TNF-α), hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6)] in 2 groups were assessed before and after treatment. RESULTS Regarding the curative effect of angina pectoris, the total effective rate of the treatment group was significantly superior to that of the control group (89% vs. 65%, P<0.05). The duration of angina pectoris, the number of abnormal leads, the improvement of the ST segment depression of electrocardiogram, and the scores of SAQ life quality indexes in the treatment group were better than those of the control group (P<0.05). In the 2 groups, EPCs and NO were both elevated, while ET-1 was decreased, and the improvements of the treatment group were superior to those of the control group (P<0.05). After treatment, the average levels of serum TNF-α, hs-CRP and IL-6 in the 2 groups were all decreased, which the treatment group showed a much sharper decrease than in the control group (P<0.05). CONCLUSIONS Puerarin effectively improves clinical symptoms and vascular endothelial function and reduces the levels of inflammatory factors in patients with CAD.

Comparison of serum levels of IL-6, IL-8, TGF-ß and TNF-α in coronary artery diseases, stable angina and participants with normal coronary artery.

Cytokines, which typically regulate the immune responses, play a role in cardiovascular diseases such as coronary artery diseases (CAD) and ischemic heart diseases (IHD). The aims of this study were to evaluate serum levels of IL-6, IL-8, TGF-ß and TNF-α in patients with or without CAD, as well as stable angina, and to assess the effects of drug administration on the serum levels of these cytokines. Serum levels of the cytokines were analyzed in the three groups: patients with acute coronary syndrome, stable angina and participants with normal coronary arteries as controls. Cohort study of the patients showed that Nitrocontin was the only drug used in a significantly different pattern between the groups where it was used less frequently in patients with stable angina compared to the acute coronary syndrome or control groups. Serum levels of the evaluated cytokines were not different neither between the studied groups nor between the groups with variable Gensini scores. However, IL-8 in controls that were not engaged in regular exercise was higher than the controls performing regular exercise. In the stable angina group, TNF-α in non-smokers was higher than the smokers. It was revealed that serum levels of pro-inflammatory cytokines are not associated with atherosclerosis and stable angina in patients from the South-East of Iran. However, suppressed expression of TGF-ß, may increase the risk of CAD. Exercise can reduce the risk of CAD through downregulation of pro-inflammatory cytokines.

Benefits and risks of P2Y12 inhibitor preloading in patients with acute coronary syndrome and stable angina.

Treatment with P2Y12 inhibitors is an integral part of the standard of care for patients undergoing percutaneous coronary intervention. However, the most appropriate timing for P2Y12 inhibitor administration remains unclear, and the value of "preloading" with P2Y12 inhibitors prior to cardiac catheterization is controversial. While pre-catheterization treatment with P2Y12 inhibitors is performed with the goal of decreasing adverse cardiovascular events, this potential benefit must be weighed against the increased risk of bleeding complications and operative delay if coronary artery bypass graft surgery is indicated. A number of studies have been conducted to evaluate the utility of preloading with P2Y12 inhibitors prior to cardiac catheterization for varying indications including stable angina and acute coronary syndrome (ACS). In this article, we review the literature and discuss the advantages and disadvantages of the preloading strategy. Several individual studies offer inconclusive and even conflicting findings. However, when taken in sum, these studies allow for several conclusions about the utility of P2Y12 inhibitor pretreatment. The existing literature demonstrate that preloading is associated with some degree of reduction in adverse ischemic events, although this benefit comes with an increased risk of bleeding complications. The appropriateness of preloading therefore varies based on the indication for catheterization, likely justified in patients with ACS but unlikely to benefit patients with stable angina.

Lutein exerts anti-inflammatory effects in patients with coronary artery disease.

BACKGROUND AND AIMS: Many coronary artery disease (CAD) patients exhibit chronic low-grade inflammation. Carotenoids are anti-oxidants with potential anti-inflammatory properties. Here, we first assessed relationships between interleukin (IL)-6 and individual carotenoids in plasma from CAD patients. Based on the results, we proceeded to assess anti-inflammatory effects of one carotenoid, lutein, in peripheral blood mononuclear cells (PBMCs) from CAD patients. METHODS: Lutein + zeaxanthin (isomers with lutein being dominant), ß-cryptoxanthin, lycopene, α- and ß-carotene and IL-6 were measured in plasma from 134 patients with stable angina (SA) and 59 patients with acute coronary syndrome. In 42 patients, plasma measurements were also performed 3 months after coronary intervention. PBMCs from SA patients were pre-treated with lutein (1, 5 and 25 µM) for 24 h followed by 24 h incubation ± lipopolysaccharide (LPS). Cell pellets were collected for IL-6, IL-1ß and TNF mRNA and intracellular lutein. Cytokine secretion was measured in cell media. RESULTS: Only lutein + zeaxanthin were inversely correlated with IL-6 in SA patients at baseline (r = -0.366, p < 0.001) and follow-up (r = -0.546, p < 0.001). Ex vivo, lutein was taken up by PBMCs from SA patients in a dose- and time-dependent manner. Pre-treatment with lutein dose-dependently lowered LPS-induced secretion of IL-6, IL-1ß (p < 0.01) and TNF (p < 0.05), and also reduced IL-6, IL-1ß and TNF mRNA expression (p < 0.05). CONCLUSIONS: Clinical findings highlighted the inverse association between lutein and IL-6 in CAD patients. Anti-inflammatory effects of lutein in PBMCs from CAD patients were consolidated in ex vivo experiments. Taken together, these results show that lutein has the potential to play a role in resolution of chronic inflammation in CAD patients.

Drug Therapy for Stable Angina Pectoris.

Chronic stable angina pectoris refers to the predictable, reproducible occurrence of pressure or a choking sensation in the chest or adjacent areas caused by myocardial ischemia in association with physical or emotional stress, and cessation of exertion and or sublingual nitroglycerin invariably relieves the discomfort. It is a common presenting symptom of severe narrowing of one or more coronary arteries, non-obstructive coronary arteries, or even when the coronary arteries are angiographically normal. Patients often avoid activities which precipitate symptoms and have impaired quality of life. Most patients with angina pectoris can be managed with lifestyle changes, especially abstinence from smoking and regular exercise, and anti-anginal drugs. However, the choice of initial or combination antianginals as recommended in the guidelines is not evidence based. In addition, patients with stable angina due to coronary artery disease should also receive aspirin and a statin. Treatment of patients with angina and normal coronary arteries remains to be established. The aim of this article is to provide the readers not only with a guideline-based approach, which varies from one country to another, but also an individual-based approach, which takes into consideration circulatory status and the presence or absence of comorbidities in the treatment decision-making process. This manuscript primarily deals with drug therapy of stable angina pectoris and not coronary artery revascularization, which also provides angina relief but is usually reserved for patients who fail to respond to adequate drug therapy.

Effect of atorvastatin on serum omentin-1 in patients with coronary artery disease.

OBJECTIVE: An association between coronary artery disease (CAD) and serum omentin-1 was recently identified. The aim of the present study was to investigate the effect of atorvastatin on serum levels of omentin-1 in patients with CAD. METHODS: One-hundred and ninety-eight patients with CAD were divided into two groups: those with acute coronary syndrome (ACS) and those with stable angina pectoris (SAP). All patients were randomized to receive atorvastatin therapy at a dose of either 20 or 40 mg/day for 12 weeks. Serum omentin-1 levels and other parameters were determined at baseline and at the end of the study. RESULTS: Atorvastatin at 20 and 40 mg/day increased serum omentin-1 levels in patients with ACS (20 mg, P=0.007; 40 mg, P<0.001) and in those with SAP (20 mg, P=0.017; 40 mg, P<0.001). Atorvastatin at 40 mg induced greater changes in serum omentin-1 levels compared with 20 mg atorvastatin in both the ACS group (P=0.003) and the SAP group (P=0.012). The increments of serum omentin-1 levels with atorvastatin administration inversely correlated with changes in LDL cholesterol (r=-0.145, P=0.041), interleukin-6 (r=-0.162, P=0.023), and high-sensitivity C-reactive protein (r=-0.185, P=0.009) in patients with CAD. Furthermore, changes in LDL cholesterol (ß=-0.158, P=0.027) and interleukin-6 (ß=-0.154, P=0.044) remained independent determinants of omentin-1 alterations in standard multiple regression analysis (R=0.122, P=0.006) after adjusting for age, sex, smoking, family history of CAD, and BMI in patients with CAD. CONCLUSION: Atorvastatin increased serum omentin-1 concentrations in patients with CAD in a dose-dependent manner.

A Destabilized Case of Stable Effort Angina Pectoris Induced by Low-dose Adenosine Triphosphate.

A 79-year-old man was diagnosed with sudden deafness. He had previously experienced a suspected episode of angina pectoris. At a local hospital, after 500 mg of hydrocortisone and 80 mg adenosine triphosphate (ATP) were administered, he became aware of chest discomfort. An electrocardiogram revealed serious ST-segment depressions. He was diagnosed with a non-ST elevated myocardial infarction (NSTEMI). Emergency coronary angiography revealed triple vessel disease, and the lesion was successfully stented. The mechanisms whereby the stable effort angina pectoris destabilized in this case were thought to include a reduction of the local blood flow because of an ATP product and probable thrombus formation in response to the administered steroids.

Comparison of the Effect of Rosuvastatin 2.5 mg vs 20 mg on Coronary Plaque Determined by Angioscopy and Intravascular Ultrasound in Japanese With Stable Angina Pectoris (from the Aggressive Lipid-Lowering Treatment Approach Using Intensive Rosuvastatin for Vulnerable Coronary Artery Plaque [ALTAIR] Randomized Trial).

Diminishing yellow color, evaluated by coronary angioscopy, is associated with plaque stabilization and regression. Our aim was to assess the effect of aggressive lipid-lowering therapy with rosuvastatin on plaque regression and instability. Thirty-seven patients with stable angina or silent myocardial ischemia who planned to undergo elective percutaneous coronary intervention and had angioscopic yellow plaques of grade 2 or more were randomized to high-dose (group H, 20 mg/day, n = 18) or low-dose (group L, 2.5 mg/day, n = 19) rosuvastatin therapy for 48 weeks. Yellow plaque was graded on a 4-point scale of 0 (white) to 3 (bright yellow) by angioscopy, and plaque volume was determined by intravascular ultrasound for plaques with a length of 5 to 15 mm. Color and volume were assessed at baseline and after 48 weeks by the investigators blinded to the rosuvastatin dosage, and were compared between the 2 dosing groups. The level of low-density lipoprotein-cholesterol decreased from 130.3 ± 25.5 mg/dl to 61.7 ± 16.5 mg/dl (-50 ± 19%: high intensity) in group H (p <0.001) and from 130.9 ± 28.5 mg/dl to 89.7 ± 29.0 mg/dl (-30 ± 22%: moderate intensity) in group L (mean ± SD, p <0.001). The average color grade of yellow plaques decreased from 2.0 to 1.5 in group H (p <0.001) and from 2.0 to 1.6 in group L (p <0.001) after 48 weeks. Plaque volume decreased significantly in group H but not in group L. The percent change in plaque volume was significantly larger in group H than in group L (p = 0.005). In conclusion, both high-dose and low-dose rosuvastatin increased plaque stability. However, high-dose rosuvastatin was more effective than low-dose rosuvastatin in inducing plaque volume regression. Clinical Trial Registration No: UMIN-CTR, UMIN000003276.

Obesity and antiplatelet effects of acetylsalicylic acid and clopidogrel in patients with stable angina pectoris after percutaneous coronary intervention.

INTRODUCTION: Obesity is a cluster of medical conditions affecting several pathophysiological processes, including platelet (PLT) function. OBJECTIVES: We evaluated the association between obesity and PLT response to dual antiplatelet therapy over 1 month in patients with stable angina pectoris after percutaneous coronary intervention (PCI).  PATIENTS AND METHODS: Patients with stable angina pectoris (n = 130) and prior therapy with acetylsalicylic acid (ASA, 75 mg/d) after PCI were enrolled into the study and divided based on a body mass index (BMI): BMI <25 kg/m² (group A); BMI = 25-29.9 kg/m² (group B); and BMI ≥30 kg/m² (group C). PLT function was assessed by impedance aggregometry 24 hours after PCI and a loading dose (LD) of clopidogrel (CLO, 600 mg) and after 30 days of a maintenance dose (MD) of CLO and ASA of 75 mg/d. The delta values were calculated as the difference between the tests performed 30 days and 24 hours after PCI. RESULTS: The PLT function changed significantly over a 30-day follow-up. The initial PLT reactivity to adenosine diphosphate (ADP1) was lower in group A and was the highest in group C (P <0.05). The PLT reactivity to collagen (COL1) and arachidonic acid was lower in group A (P <0.05) with no differences between groups B and C. There were no differences among the subgroups in PLT reactivity assessed after 30 days. A multivariate regression analysis showed that BMI (P = 0.03), creatinine serum concentration (P <0.01), male sex (P <0.01), and active smoking (P <0.001) are the independent predictors of ΔADP. CONCLUSIONS Obesity is associated with a lower response to CLO LD but PLT function after 30 days of CLO MD is similar in patients with obesity and normal-weight.

Management of Patients With Stable Angina and Type 2 Diabetes.

Type 2 diabetes (T2D) is a well-established risk factor for patients with coronary artery disease (CAD). Patients with CAD and comorbid T2D also have a higher risk of cardiovascular complications, such as silent ischemia and stable angina. In treating the symptoms of stable angina in patients with CAD and comorbid T2D, it is vital to utilize therapies that reduce symptoms and improve outcomes. At the same time, there is significant concern about the preservation of glycometabolic parameters, such as glycosylated hemoglobin (HbA1c), particularly because some antianginal therapies, such as ß-blockers and calcium channel blockers-although effective at improving the symptoms of stable angina and reducing ischemia-may also worsen glycemic control by increasing HbA1c levels. Available trial data on the efficacy of antianginal agents in patients with stable angina and comorbid T2D are limited. Therefore, in patients with stable angina and T2D, a tailored approach to treatment of stable angina by selecting therapies with a neutral or positive glycometabolic profile may improve outcomes and increase treatment compliance. Additionally, patients with a dual diagnosis may benefit from therapies that have beneficial effects on both stable angina and T2D, thereby reducing polypharmacy. Prospective studies in patients with stable angina and T2D are needed to guide therapy decisions.