Giant unruptured sinus of Valsalva aneurysms causing angina pectoris.

BACKGROUND: Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly which can be congenital or acquired. Patients with SVA are commonly asymptomatic when the occupying effect of SVA is insignificant, while ruptured SVA usually causes severe symptoms including heart failure and myocardial ischemia. CASE PRESENTATION: We present an unusual case of a 64-year-old female manifesting with exertional dyspnea as well as angina pectoris for three months. Echocardiography and cardiac computed tomographic angiography confirmed unruptured left-coronary and non-coronary SVAs. The left anterior descending artery and left circumflex artery were stretched and compressed by the SVA which causing myocardial ischemia. The patient finally received aortic root replacement (Bentall procedure) and got symptom relieved. CONCLUSIONS: Giant unruptured SVA originating from left coronary sinus is extremely rare. Our case highlights that giant SVA should be considered in cases with angina pectoris. Echocardiography and coronary computed tomographic angiography are useful and important for diagnosis. Surgery is highly recommended in patients with SVA.

Association of relative hand grip strength with myocardial infarction and angina pectoris in the Korean population: a large-scale cross-sectional study.

BACKGROUND: Low hand grip strength (HGS) is associated with the risk of cardiovascular diseases, but the association between HGS and myocardial infarction/angina pectoris (MIAP) is unclear. Furthermore, there have been no studies examining the associations of MIAP with anthropometric indices, absolute HGS indices, and relative HGS indices calculated by dividing absolute HGS values by body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), or weight values. Therefore, the objective of this study was to examine the associations of MIAP with absolute and relative HGS combined with several anthropometric indices. METHODS: In this large-scale cross-sectional study, a total of 12,963 subjects from the National Health and Nutrition Examination Survey were included. Odds ratios and 95% confidence intervals for the associations of MIAP with anthropometric indices, absolute HGS indices, and relative HGS indices were computed from binary logistic regression models. We built 3 models: a crude model, a model that was adjusted for age (Model 1), and a model that was adjusted for other relevant covariates (Model 2). RESULTS: For men, the average age was 61.55 ± 0.16 years in the MIAP group and 66.49 ± 0.61 years in the non-MIAP group. For women, the average age was 61.99 ± 0.14 years in the MIAP group and 70.48 ± 0.61 years in the non-MIAP group. For both sexes, the MIAP group had lower diastolic blood pressure, shorter stature, greater WC, and a greater WHtR than did the non-MIAP group, and women tended to have greater systolic blood pressure, weight, and BMI than in men. HGS was strongly associated with the risk of MIAP in the Korean population. In men, relative HGS indices combined with WC and the WHtR had greater associations with MIAP than did the anthropometric indices and absolute HGS indices. However, in women, anthropometric indices, including weight, BMI, WC, and WHtR, were more strongly associated with MIAP than were absolute and relative HGS indices, unlike in men. When comparing absolute and relative HGS indices in women, relative HGS indices combined with BMI and weight was more strongly related to MIAP than was absolute HGS indices. CONCLUSIONS: MIAP might be better identified by relative HGS than absolute HGS in both sexes. The overall magnitudes of the associations of MIAP with absolute and relative HGS are greater in men than in women.

The clinical value of ß-blockers in patients with stable angina.

Stable angina, one manifestation of chronic coronary syndrome (CCS), is characterised by intermittent episodes of insufficient blood supply to the myocardium, provoking symptoms of myocardial ischaemia, particularly chest pain. These attacks usually occur during exercise or stress. Anti-ischaemic drugs are the mainstay of pharmacologic management of CCS with symptoms of angina. ß-blockers reduce heart rate and myocardial contractility, thus reducing myocardial oxygen consumption. These drugs have been shown to ameliorate the frequency of anginal attacks and to improve exercise capacity in these patients. Current management guidelines include ß-blockers as a first-line management option for most patients with CCS and symptoms of myocardial ischaemia, alongside dihydropyridine calcium channel blockers (CCB). The presence of comorbid angina and heart failure is a strong indication for starting with a ß-blocker. ß-blockers are also useful in the management of angina symptoms accompanied by a high heart rate, hypertension (with or without a renin-angiotensin-aldosterone-system [RAS] blocker or CCB), or microvascular angina (with a RAS blocker and a statin). A ß-blocker is not suitable for a patient with low heart rate (<50 bpm), although use of a ß-blocker may be supported by a pacemaker if the ß-blocker is strongly indicated) and should be used at a low dose only in patients with low blood pressure.

Ischemia with nonobstructive coronary arteries in a patient with a history of Kawasaki disease.

A 34-year-old man with a history of Kawasaki disease had been experiencing chest pain at rest since middle school. Multidetector-row computed tomography showed no aneurysm formation; however, the right coronary artery had an anomalous origin with moderate stenosis. Invasive coronary angiography revealed moderate right coronary artery stenosis with a fractional flow reserve of 0.97. Finally, with a positive acetylcholine provocation test and elevated index of microvascular resistance, the patient was diagnosed with microvascular and epicardial vasospastic angina in the endotypes of ischemia with nonobstructive coronary arteries. This is the first reported case of both microvascular and epicardial vasospastic angina after Kawasaki disease. In patients with a history of Kawasaki disease, even those without cardiac sequelae, coronary endothelial and microvascular dysfunctions should be taken into consideration. Learning objective: We report the first case of both microvascular and epicardial vasospastic angina in the endotypes of ischemia with nonobstructive coronary arteries after Kawasaki disease.Coronary endothelial and microvascular dysfunctions should be taken into consideration in patients with a history of Kawasaki disease, even those without cardiac sequelae.

Cardiovascular Risks of Simultaneous Use of Alcohol and Cocaine-A Systematic Review.

Background: The simultaneous use of cocaine and alcohol is highly prevalent and is associated with high numbers of emergency department admissions, primarily due to cardiovascular complications. Aims: To answer the question of whether the co-use of cocaine and alcohol increases the cardiovascular risk compared to the use of cocaine alone. Method: A systematic review of human studies comparing the cardiovascular risk of co-used cocaine and alcohol with the use of cocaine alone. Results: Despite a higher myocardial workload induced by the co-use of cocaine and alcohol and the potentiation of cocaine's cardiovascular effects by alcohol, the findings on the risk and severity of cardiovascular symptoms due to combined use are inconsistent. However, the co-use of cocaine and alcohol clearly leads to higher mortality. Interestingly, the presence of cocaethylene, a unique metabolite generated only via a pharmacokinetic interaction between alcohol and cocaine, carries an 18- to 25-fold increase over the absence of cocaethylene (cocaine-alone users) in the risk of sudden death and is associated with myocardial injury and cardiac arrest, probably due to the inhibition of cardiac ion channels by cocaethylene. Conclusion: Despite the inconsistency in some of the results, it is concluded that the co-use of cocaine and alcohol poses an additional risk of cardiovascular fatalities compared to the use of cocaine alone.

Elucidation of the Molecular Mechanism of Compound Danshen Dripping Pills Against Angina Pectoris based on Network Pharmacology and Molecular Docking.

BACKGROUND: Compound Danshen dripping pills (CDDP), a traditional Chinese medicine, has had an extensive application in the treatment of angina pectoris (AP) in China. However, research on the bioactive ingredients and underlying mechanisms of CDDP in AP remains unclear. OBJECTIVE: In the present study, we explored the major chemical components and potential molecular mechanisms linked to the anti-angina effects of CDDP through the application of network pharmacology and molecular docking. METHODS: The potential targets of active ingredients in CDDP were sourced from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and the Swiss Target Prediction Database (STPD). Additionally, targets related to angina pectoris (AP) were retrieved from various databases, including Gene Cards, DisGeNET, Dis Genet, the Drug Bank database (DBD), and the Therapeutic Target Database (TDD). Protein- protein interaction [1] networks were also established, and core targets were identified based on their topological significance. GO enrichment analysis and KEGG pathway analysis were conducted using the R software. Interactions between active ingredients and potential targets selected through the above process were investigated through molecular docking. RESULTS: Seventy-six active ingredients were selected with the following criteria: OB ≥ 30%, DL ≥ 0.18. 383 targets of CDDP and 1488 targets on AP were gathered, respectively. Afterwards, 194 common targets of CDDP and anti-AP targets were defined, of which 12 were core targets. GO enrichment analysis indicated that CDDP acted on AP by response to lipopolysaccharide, regulating the reactive oxygen species and metal ion metabolism, and epithelial cell proliferation. In addition, KEGG enrichment analysis indicated that the signaling pathways were notably enriched in lipid and atherosclerosis, fluid shear stress and atherosclerosis, IL-17 signaling pathway, EGFR tyrosine kinase inhibitor resistance, PI3K-Akt signaling pathway, and TNF signaling pathway. Moreover, the molecular docking manifested excellent binding capacity between the active ingredients and targets on AP. CONCLUSION: This study comprehensively illustrated the bioactive, potential targets, and molecular mechanisms of CDDP against AP, offering fresh perspectives into the molecular mechanisms of CDDP in preventing and treating AP.

Investigating the multitarget pharmacological mechanism of Rhodiola wallichiana var. cholaensis acting on angina pectoris using combined network pharmacology and molecular docking.

Background: Rhodiola wallichiana var. cholaensis (RW) is one of the traditional Chinese medicinal materials, which is used to treat angina pectoris (AP). However, the possible underlying mechanisms remains unclear. The aim of this study was to explore RW in the treatment of AP and to identify the potential mechanism of the core compounds. Methods: In this study, systematic and comprehensive network pharmacology and molecular docking were used for the first time to explore the potential pharmacological mechanisms of RW on AP. First, the relative compounds were obtained by mining the literature, and potential targets of these compounds using target prediction were collected. We then built the AP target database using the DigSee and GeneCards databases. Based on the data, overlapping targets and hub genes were identified with Maximal Clique Centrality (MCC) algorithm in Cytoscape, cytoHubba. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and protein-protein interaction (PPI) analysis were performed to screen the hub targets by topology. Molecular docking was utilized to investigate the receptor-ligand interactions on Autodock Vina and visualized in PyMOL. Results: A total of 218 known RW therapeutic targets were selected. Systematic analysis identified nine hub targets (VEGFA, GAPDH, TP53, AKT1, CASP3, STAT3, TNF, MAPK1 and JUN) mainly involved in the complex treatment effects associated with the protection of the vascular endothelium, as well as the regulation of glucose metabolism, cellular processes, inflammatory responses, and cellular signal transduction. Molecular docking indicated that the core compounds had good affinity with the core targets. Conclusions: The results of this study preliminarily identify the potential targets and signaling pathways of RW in AP therapy and lay a promising foundation for further experimental studies and clinical trials.

Effects of Remote Ischaemic Conditioning in Stable and Unstable Angina Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.

AIM: Type 4a myocardial infarction (T4aMI), defined as myocardial injury associated with percutaneous coronary intervention (PCI), is associated with a poor prognosis and there is conflicting evidence regarding the effectiveness of remote ischaemic conditioning (RIC) in its prevention. This review aimed to determine the effect of RIC on stable and unstable angina patients. METHOD: A systematic review was conducted in PubMed and Central database. Outcome measures were: changes in peak troponin, creatine kinase myocardial band (CKMB), C-reactive protein (CRP) level, incidence of T4aMI, and major adverse cardiovascular event (MACE). Data were meta-analysed and reported as standardised mean difference (SMD) and odds ratio (OR). Risk of bias was assessed with the Risk of Bias 2 (RoB2) tool. RESULTS: Fifteen studies with no significant risk of bias were included. Peak troponin level was reduced in the RIC group, particularly after excluding a study with low statin use, while CKMB and CRP levels resulted in a non-significant SMD between the groups. The incidence of T4aMI was significantly lower in the intervention group (OR 0.714; p=0.026); this finding was also seen in subgroups of elective PCI, pre-conditioning, and high statin use. Incidence of MACE also only reached statistically significant protective effects with OR <1 in similar subgroups. No substantial heterogeneity was found and the funnel plot did not show publication bias. CONCLUSION: Remote ischaemic conditioning in elective PCI patients has been proven to be potentially beneficial in reducing peak troponin levels and risk of T4aMI and MACE.

Real-World Data from the Use of Ranolazine in Patients with Stable Angina Pectoris: The RANGER Study.

Background: Although ranolazine has been available for years as a second-line treatment to reduce angina attacks in patients with stable angina pectoris, real-world data on the effectiveness, tolerability, and safety of ranolazine are limited. Methods: A non-interventional, prospective study was conducted to assess the effectiveness and safety of ranolazine. Patients eligible for enrolment had a baseline assessment between one and fourteen days after initiating ranolazine for the first time and a follow-up visit three months later. The primary endpoints comprised the weekly frequency of angina attacks, total adverse events, and ranolazine discontinuation rate. The secondary endpoints included the use of short-acting nitrates, changes on the Canadian Cardiovascular Society (CCS) angina classification score and quality of life scale score (QoL). Results: In total, 1101 patients were enrolled at 214 sites. Mean weekly angina attacks were reduced from 3.6 ± 2.9 to 0.4 ± 0.9 (p < 0.0001) and the mean weekly consumption of short-acting nitrates decreased by 1.7 ± 2.2 (p < 0.0001). CCS class and QoL were also improved (p < 0.0001). Adverse events were reported by 11 (1%) patients in total, while 2 of them (0.2%) were characterised as serious. Treatment was discontinued for various reasons in 23 patients (2.1%) after the follow-up period. Ranolazine treatment was equally effective in all subgroups tested, with larger benefits observed in patients with more frequent angina and CCS angina class III and IV. Up-titration of ranolazine during the study improved the outcomes. Conclusions: Ranolazine was well tolerated and effectively reduced angina attacks, with simultaneous improvement of the CCS class and QoL score in patients with stable angina.

Autoimmune blistering disorders and cardiovascular risks: A population-based cohort study.

BACKGROUND: Autoimmune blistering disorders (ABDs) might elevate cardiovascular risk, but studies are lacking. OBJECTIVE: The objective of this study was to examine if ABDs elevate the risk of atherosclerotic cardiovascular disease, heart failure, arrhythmia, venous thromboembolism, and cardiovascular death. METHODS: A population-based cohort of Danish patients with ABD (≥18 years of age) diagnosed during 1996-2021 (n = 3322) was compared with an age- and sex-matched comparison cohort from the general population (n = 33,195). RESULTS: Compared with the general population, patients with ABDs had higher 1-year risks of atherosclerotic cardiovascular disease (3.4% vs 1.6%), heart failure (1.9% vs 0.7%), arrhythmia (3.8% vs 1.3%), venous thromboembolism (1.9% vs 0.3%), and cardiovascular death (3.3% vs 0.9%). The elevated risk persisted after 10 years for all outcomes but arrhythmia. The hazard ratios associating ABDs with the outcomes during the entire follow-up were 1.24 (1.09-1.40) for atherosclerotic cardiovascular disease, 1.48 (1.24-1.77) for heart failure, 1.16 (1.02-1.32) for arrhythmia, 1.87 (1.50-2.34) for venous thromboembolism, and 2.01 (1.76-2.29) for cardiovascular death. The elevated cardiovascular risk was observed for both pemphigus and pemphigoid. LIMITATIONS: Our findings might only generalize to patients with ABDs without prevalent cardiovascular diseases. CONCLUSION: Patients with ABDs had an elevated cardiovascular risk compared with age- and sex-matched controls.

Efficacy and safety evaluation of Ginkgo biloba dropping pill (GBDP) on stable angina pectoris complicated with depression: A placebo-controlled, randomized, double-blind, multicenter study.

BACKGROUND: Stable angina pectoris (SAP) is a clinical condition characterized by reversible and temporary myocardial ischemia and hypoxia. A majority of SAP patients also experience depressive disorders, which adversely affect their disease prognosis and overall quality of life. However, the clinical utility of existing antidepressants is constrained by their side effects. Ginkgo biloba dropping pill (GBDP), a Chinese patented medication, has demonstrated efficacy in the treatment of both coronary heart disease and mental disorders. This prospective, randomized, double-blind, multicenter clinical trial aimed to assess the effectiveness and safety of GBDP as an adjuvant therapy for SAP complicated by depression. METHODS: Participants were randomly assigned in a 1:1 ratio to receive either GBDP or a placebo (5 pills, three times a day) in addition to standard therapy for a duration of 12 weeks. The Seattle Angina Questionnaire (SAQ) was administered every 4 weeks during the treatment, and angina event frequency was assessed weekly. The 36-item Short-Form (SF-36) and Hamilton Depression Scale (HAMD) scores were measured both before and after the treatment. RESULTS: Out of the 72 patients, 68 (n = 34 per group) completed the entire study. At the first visit (4 weeks ± 3 days), the SAQ-Angina Stability score in the GBDP group was significantly higher than that in the placebo group (p < 0.05). While the average weekly frequency of angina episodes in the placebo group notably increased after 12 weeks of treatment (p < 0.05), it displayed an improving trend in the GBDP group (p > 0.05). By the endpoint, each subcategory score of SF-36 in the GBDP group exhibited significant improvement compared to baseline (p < 0.05). The comparison of score improvement between the two groups revealed that the SF-PCS score of the GBDP group was higher than that of the placebo group (p < 0.05). HAMD scores in both groups significantly increased after treatment (p < 0.05). No discernible difference in the incidence of adverse reactions was observed between the two groups (p > 0.05). CONCLUSION: In patients with SAP complicated by depression, GBDP, when combined with standard treatment, rapidly and safely alleviates angina pectoris symptoms. It demonstrates therapeutic potential in enhancing the quality of life and alleviating depressive symptoms.

The efficacy of Chinese herbal drugs for adults with angina pectoris: Bayesian network meta-analysis of 331 RCTs involving 36,467 individuals.

ETHNOPHARMACOLOGICAL RELEVANCE: Hundreds of randomized controlled trials (RCT) on Chinese herbal drugs (CHDs) including Shexiang baoxin pill (BXP), compound Danshen dripping pill (DSP), compound Danshen tablet (DST), Suxiao jiuxin pill (JXP), Naoxintong capsule (NXT), Tongxinluo capsule (TXL), and Di'ao xinxuekang capsule (XXK) and conventional chemical drugs, such as isosorbide dinitrate (ISDN), for angina pectoris are available but have not been evaluated by a PRISMA-compliant network meta-analysis (NMA). AIM OF THE STUDY: This study aimed to compare the efficacy of nine anti-anginal drugs through NMA on RCTs. METHODS: RCTs of drug treatment for adult patients with angina pectoris for improvements in symptoms and electrocardiography were retrieved. Odds ratios and 95% credible intervals were computed to measure effect sizes. RCT quality was evaluated with the Cochrane risk of bias tool. Evidence synthesis was performed with Bayesian NMA. Essential analyses including subgroup analysis, sensitivity analysis, meta-regression analysis, publication bias analysis, and ranking analysis were conducted to assess the robustness of efficacies. Evidence strength was assessed with the GRADE approach. RESULTS: A total of 331 RCTs with 36,467 participants were eligible. The overall quality of all included RCTs was low. Overall efficacy estimates from different approaches of evidential synthesis found that BXP, TXL, and DSP were more efficacious than DST and ISDN. Essential analyses indicated consistent efficacy estimates, insignificant publication bias, and corroborative ranking results. The overall GRADE evidence strength was low. CONCLUSION: This comprehensive Bayesian NMA found BXP, TXL, and DSP to be the top three candidates among the seven tested CHDs for treating adults suffering from angina pectoris. However, the quality and the evidence strength of eligible RCTs were low. Further high-quality RCTs with more outcome measures and their NMAs are warranted. REGISTRATION: PROSPERO CRD42014007035.

Efficacy and safety of tongxinluo capsule for angina pectoris of coronary heart disease: an overview of systematic reviews and meta-analysis.

Background: Tongxinluo capsule (TXLC) is a common drug for treating angina pectoris of coronary heart disease (CHD). In recent years, many systematic reviews (SRs) and meta-analyses (MAs) have reported the efficacy and safety of TXLC for improving angina symptoms in patients with CHD. We aimed to comprehensively evaluate the existing SRs and MAs of TXLC in treating angina pectoris of CHD, summarize the evidence quality, and provide scientific evidence and recommendations. Methods: We searched seven databases for relevant SRs/MAs published up to 1 June 2023. Two reviewers independently completed the literature retrieval, screening, and data extraction. We used A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) to evaluate the methodological quality, the Risk of Bias in Systematic Reviews (ROBIS) to assess the risk of bias, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to determine the strength of the evidence. RevMan 5.3 was used to synthesize data. Results: We identified 15 SRs/MAs, including 329 RCTs and 33,417 patients. According to the evaluation results of AMSTAR-2, only one SR was of high methodological quality, the others were very low. ROBIS assessment showed that one SR (6.67%) had a low risk, 3 SRs (20%) had an unclear risk, and 11 SRs (73.33%) had a high risk. We assessed 42 outcomes by the GRADE, 10 (23.81%) for moderate-quality evidence, 17 (40.48%) for low-quality evidence, and 15 (35.71%) for very-low-quality evidence. Mate-analysis showed that TXLC combined with conventional western medications improved electrocardiogram efficacy (RR = 1.38, 95% CI: 1.23-1.43, P < 0.001) and angina efficacy (OR = 3.58, 95% CI: 3.02-4.24, P < 0.001), reduced angina attack frequency (SMD = -0.54, 95% CI: -0.64 to -0.44, P < 0.001) and angina duration (SMD = -0.42, 95% CI: -0.57 to -0.28, P < 0.001), with general heterogeneity. The pooled results showed that TXLC appears to have some efficacy in improving cardiac function and relieving angina symptoms, but there is limited evidence that it improves cardiovascular event rates, hemorheology, lipids, or hs-CRP. In the assessment of drug safety, TXLC was associated with different degrees of adverse drug reactions. Conclusion: Based on the evidence, TXLC may be effective as an adjuvant treatment for angina pectoris of CHD. However, the quality of the evidence is low, and the drug's safety must be carefully interpreted. In future studies, high-quality randomized controlled trials are needed to confirm the effectiveness and safety of TXLC. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022365372).

The Relationship Between Allergic Rhinitis, Asthma, and Cardiovascular Disease in the National Health Interview Surveys (NHIS), 1999-2018.

BACKGROUND: Atopic disease has been associated with immune dysregulation and chronic inflammation, but current practice guideline recommendations do not include the evaluation of inflammatory outcomes among patients with asthma and allergic rhinitis (AR). OBJECTIVE: This study investigates the relationship between asthma, AR, and cardiovascular disease (CVD) using data from the U.S. National Health Interview Survey (NHIS) between 1999 and 2018. METHODS: We used data from adults in the NHIS (n = 603,140, representing a population of 225,483,286). Exposures were physician-diagnosed asthma (lifetime/past-year) and AR (past-year). Outcomes were physician-diagnosed heart disease: coronary heart disease (CHD), angina, heart attack, and nonspecific "heart-condition" (all lifetime). We used survey-weighted descriptive analysis and logistic regression adjusting for demographic and socioeconomic factors. RESULTS: A total of 11.44% reported at least 1 heart condition, with CHD the most prevalent (4.27%) across 20 years of pooled data. Asthma and AR were associated with higher CVD in all bivariate analyses. Specifically, lifetime asthma was associated with increased odds of CHD, (odds ratio [OR] 1.36; 95% confidence interval [95% CI] 1.29-1.42), with stronger effects observed for a past-year asthma attack (OR 1.66; 95% CI 1.55-1.80). The strongest effect of all was observed in those with a past-year asthma attack having increased odds of angina (OR 2.42; 95% CI 2.24-2.63). Allergic rhinitis was independently associated with increased odds of CHD (OR 1.25; 95% CI 1.18-1.28). CONCLUSIONS: Asthma and AR are risk factors for all types of CVD in this nationally representative study covering a 2-decade period in the United States. Clinicians should consider screening patients with severe and/or uncontrolled asthma and AR early for CVD, particularly angina and CHD. Future studies are warranted to explore the immunological milieu in these patients and identify therapeutic targets.

The Correlation Between Serum Fibroblast Growth Factor 21 and the Severity and Occurrence of Coronary Artery Disease.

BACKGROUND: The burden of cardiovascular diseases (CVDs) is increasing worldwide with CVD being one of the leading causes of death, including atherosclerosis, myocardial infarction, cardiomyopathy, and heart failure (HF). Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates carbohydrate and lipid metabolism. It exerts direct effects on the cardiovascular system and can serve as an early indicator of CVDs. FGF21's therapeutic properties include reducing obesity, dyslipidaemia, and hyperglycemia, which can help treat metabolic disorders, autophagy, and apoptosis. Atherosclerosis is developed due to chronic inflammatory conditions, and the immune system's reaction to oxidized lipoproteins is mainly responsible for the development of atherosclerosis. FGF21's precise role in the pathogenesis of coronary artery disease (CAD) remains elusive.  Aim: This study aimed to assess the role of FGF21 in predicting the severity and magnitude of CAD in individuals diagnosed with stable angina pectoris (SAP). MATERIALS AND METHODS: A prospective cross-sectional study was conducted on 110 consecutive patients with SAP reported to the cardiology department of the Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, India. They were divided into two groups based on coronary angiography findings. Control groups included patients not showing any atherosclerotic lesions and case groups with atherosclerotic lesions. The SYNTAX score is a grading system that measures the location and complexity of coronary arteries using anatomical principles. The Gensini score assessment technique was employed to determine the severity of CAD. We compared serum FGF21 levels,left ventricular ejection fraction (LVEF), and inflammatory biomarker C-reactive protein (CRP) levels between the two groups. Moreover, we examined the correlation between the serum FGF21 level and the SYNTAX and Gensini scores. The statistical analysis was done using Version 23.0 of SPSS Statistics. P-values below 0.05 were considered statistically significant. RESULTS: The study found that the case group had a higher average age and a higher proportion of male patients. The case group had considerably higher levels of FGF21 (166.59 ± 94.49791 pg/mL) compared to the control group (54.13 ± 48.467 pg/mL) (p=0.034). The LVEF exhibited a significant difference between the case and control groups, with mean values of 50.3056 ± 7.8242% and 56.078 ± 5.3987%, respectively (p=0.031). CRP levels were comparable in both groups. The case group had mean values of SYNTAX and Gensini scores of 23.19±7.43 and 50.03±27.30, respectively. We found that there was no statistically significant association between the risk assessments for CAD severity and the levels of serum FGF21 (correlation coefficient r=0.14070, p>0.05, and r=0.206415, p>0.05, respectively) Conclusions: FGF21 is gaining recognition as a prospective addition to the FGF family, potentially playing a significant role in cardiovascular disease, particularly atherosclerosis. A statistically significant difference was seen in the serum FGF21 levels between the case and control groups, indicating that it can help in the diagnosis of CAD. However, there was no apparent correlation found between the serum FGF21 levels and the SYNTAX and Gensini scores. The role of FGF21 in the development of atherosclerosis and whether FGF21 could serve as a reliable marker need to be studied further.

Ranolazine as a First-Choice Anti-anginal Medication for Patients With Coronary Artery Ectasia: A Case Series.

Coronary artery ectasia (CAE) is characterized by the abnormal dilation of coronary arteries, resulting in disturbed or slow blood flow, which causes angina pectoris-the most prevalent symptom of CAE. To date, there is no consensus on the therapeutic management of CAE due to its rarity and the scarcity of research. We present a case series of five patients with different ethnicities, including both men and women, whose CAE was successfully managed by the administration of ranolazine. All five patients were found to have CAE by coronary angiography, which was also associated with slow blood flow. Clinically, the patients had accelerating angina. They were prescribed an initial dose of 500 mg of ranolazine twice daily, which led to the resolution of their anginal symptoms. They have been clinically and hemodynamically stable for the last several years. In light of these results, we propose that ranolazine be considered as a first-choice anti-anginal medication for patients with CAE.

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 Sinus Narrowing Improves Coronary Microcirculation Function in Patients With Refractory Angina: A Multicenter Prospective INROAD Study.

BACKGROUND: The underlying mechanisms responsible for the clinical benefits following coronary sinus narrowing and pressure elevation remain unclear. The present study aims to investigate whether coronary sinus narrowing improves the indexes of coronary microcirculatory function. METHODS: Patients with refractory angina who had a clinical indication for reducer implantation underwent invasive physiological assessments before and 4 months after the procedure. The primary outcome was the change in the values of the index of microcirculatory resistance. Secondary end points included changes in coronary flow reserve and the resistive resistance ratio values. Angina status was assessed with the Canadian Cardiology Society class and the Seattle Angina Questionnaire. RESULTS: Twenty-four patients with a history of obstructive coronary artery disease and prior coronary revascularization (surgical and percutaneous) treated with reducer implantation were enrolled, and 21 of them (87%) underwent repeated invasive coronary physiological assessment after 4 months. The index of microcirculatory resistance values decreased from 33.35±19.88 at baseline to 15.42±11.36 at 4-month follow-up (P<0.001; mean difference, -17.90 [95% CI, -26.16 to -9.64]). A significant (≥20% from baseline) reduction of the index of microcirculatory resistance was observed in 15 (71.4% [95% CI, 47.8%-88.7%]) patients. The number of patients with abnormal index of microcirculatory resistance (≥25) decreased from 12 (57%) to 4 (19%; P=0.016). Coronary flow reserve increased from 2.46±1.52 to 4.20±2.52 (mean difference, 1.73 [95% CI, 0.51-2.96]). Similar findings were observed for resistive resistance ratio values. Overall, 16 patients (76.1%) had an improvement of 1 Canadian Cardiology Society class. Seattle Angina Questionnaire summary score increase of around 3 points (3.01 [95% CI, 1.39-4.61]). CONCLUSIONS: Coronary sinus reduction implantation is associated with a significant improvement in the parameters of coronary microcirculatory function. These findings provide insights into the improvement of angina symptoms and may have implications for the treatment of coronary microvascular dysfunction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05174572.