Angina Research Articles

Composition of non-HDL cholesterol and residual cardiovascular risk in secondary prevention

Abstract Background Non-high-density lipoprotein cholesterol (non-HDL-C) is associated with atherosclerotic cardiovascular disease (ASCVD) and is a recommended secondary prevention treatment target. However, the composition of non-HDL-C, that is, the relative contribution of remnant cholesterol (remnant-C) and low-density-lipoprotein cholesterol (LDL-C), is not considered for cardiovascular risk prediction. Purpose To examine ASCVD risk by composition of non-HDL-C. Methods Based on the Western Denmark Heart Registry, we established a cohort of patients with ischemic heart disease, including patients with acute coronary syndrome or stable angina pectoris, undergoing coronary angiography for evaluation of coronary artery disease between 2011 and 2020. A complete lipid panel within 1 year after coronary angiography on statin treatment was required. Patients with triglycerides >4.5 mmol/L were excluded. Exposures were remnant-C, LDL-C, non-HDL-C, and composition of non-HDL-C. The latter was defined as remnant-C of non-HDL-C, and LDL-C of non-HDL-C, in percentages. Cox regression analyses obtained adjusted hazard ratios (aHR) for myocardial infarction, ASCVD (myocardial infarction, ischemic stroke, and cardiovascular death), and all-cause death occurring from 1 year after coronary angiography to end of follow-up November 1, 2022. Results The secondary prevention cohort included 42,341 statin-treated patients (67.7% were men; median [IQR] age 66 [58-73] years). During median 4.1 years of follow-up, 3,846 patients developed ASCVD. Per 1 mmol/L increase in remnant-C, LDL-C, and non-HDL-C, the aHR for ASCVD was 1.41 (95% CI 1.28-1.55), 1.12 (95% CI 1.08-1.17), and 1.17 (95% CI 1.13-1.21), respectively (Figure 1). The relative contribution of remnant-C and LDL-C was median (IQR) 24.6% (18.5-33.1) and 75.4% (66.9-81.5) of non-HDL-C, respectively. When remnant-C constituted a larger percentage of non-HDL-C (and LDL-C a lower percentage), the aHR for ASCVD showed a linear increase in risk whereas the opposite trend was observed for LDL-C (Figure 2). Thus, per 10% increase in remnant-C of non-HDL-C, the aHR of ASCVD was 1.06 (95% CI 1.03-1.09) compared to 0.94 (95% CI 0.91-0.97) per 10% increase in LDL-C of non-HDL-C. Results were comparable for myocardial infarction and all-cause death, and by age, sex, and other clinically relevant subgroups. Conclusions The composition of non-HDL-C is strongly associated with ASCVD risk, with the risk escalating as remnant-C constitutes a larger percentage, and LDL-C a smaller percentage, of non-HDL-C. These findings challenge current guidelines and demonstrate the value of considering composition of non-HDL-C in clinical practice for more accurate risk assessment.Figure 1Figure 2

Prognostic significance of plasma molecular lipid species in coronary artery disease patients: A prospective cohort study

Abstract Background Circulating plasma lipids are vital indicators for quantifying coronary artery disease (CAD) risk, yet traditional biomarkers like LDL, HDL, and triglycerides often exhibit limited predictive capacity. Advancements in lipidomics have identified novel molecular constituents with the potential to improve prognostication in CAD patients. However, the prognostic value of lipidomics for long-term mortality has not yet been investigated. Objective In our study, which was part of the European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis (ATHEROREMO), we aimed to investigate the predictive value of specific molecular lipid species for long-term mortality. Methods We utilized data from the 581 CAD patients enrolled in the ATHEROREMO clinical imaging study, who were admitted for either diagnostic coronary angiography or percutaneous coronary intervention. We measured a series of serum lipid species, comprising ceramides (Cer) and cholesteryl esters (CE), by mass spectrometry-based shotgun lipidomics. Long-term all-cause mortality follow-up was conducted in 2022 via the Civil Registry. We used the Kaplan-Meier method and multivariable Cox-proportional hazards regression (correction for age, sex, cardiac risk factors, statin use, hypercholesterolemia, and angiography indication) to assess survival distributions and associations with all-cause mortality. Results Mean age was 61.5 years (IQR: 53.5-61.5), 75% were male. A total of 55% patients were diagnosed with acute coronary syndrome (ACS) and 45% with stable angina pectoris (SAP). During a median follow-up of 11 years (IQR: 10.1-13.4) 179 patients died. Five molecular lipid species (two cholesteryl esters, one ceramide and two ceramide ratios) correlated with mortality (see Table). As an example, Figure 1 demonstrates a clear survival difference between patients with Cer(d18:1/16:0)/Cer(d18:1/24:0) ratio below versus above the median. Findings were consistent for ACS and SAP. Conclusion Our study demonstrates the prognostic value of specific cholesteryl esters, ceramides and ceramide ratios for 11-year mortality in patients with CAD. To the best of our knowledge, this is the longest follow-up study so far within this domain.Table.Lipid molecule and Mortality 11-yFig.1 Kaplan Meier Ceramide ratio

Angina pectoris prevalence and sick leave burden one year after MINOCA

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents approximately 5-10% of all myocardial infarctions (MI), with heterogenous etiologies and insufficient knowledge on symptom burden after the acute phase. Purpose To evaluate the prevalence of angina and sick leave in MINOCA, using individuals with MI due to coronary artery disease (MI-CAD) as control. Methods This observational study used prospectively collected data from the Swedish national quality register SWEDEHEART. All individuals with invasively assessed, first time MI between 2005 – 2022, available at one year follow-up were included and categorized as MINOCA (normal coronary arteries or <50% lumen obstruction) or MI-CAD (>50% lumen obstruction). We excluded subjects with previous coronary intervention, previous heart failure, tachy- or bradyarrhythmia at admission and not fully revascularized MI-CAD. Chest pain was assessed by a clinical nurse and angina graded according to the Canadian Cardiovascular Society, excluding non-ischemic chest pain. Occupational status was self-reported. Results We included N=46 428 individuals (mean age 62, 71% male; MINOCA n= 5281/MI-CAD n=41 157). Subjects with MINOCA were predominantly females, more commonly divorced or widowed, non-smoking and had a higher degree of hypertension, hyperlipidemia, and chronic obstructive pulmonary disease, compared to fully revascularized MI-CAD. Angina prevalence was 11.6 % and 8.8% in MINOCA and MI-CAD respectively (p <0.001). After adjustment for background variables clinically relevantly associated to both MI type and anginal status OR was 1.21 [95% CI 1.10 – 1.34] (Figure 1). Sick leave was more common in MINOCA both at index care, and at one year (8.0 vs 5.6 % and 13.4 vs 10.9%, both p <0.001) (Figure 2). Conclusion MINOCA patients suffer significant distress, with higher levels of angina and sick leave compared to fully revascularized MI-CAD counterparts. Further research on causes of ischemic symptoms in this heterogenous condition is warranted.

The relationship between daily blood glucose fluctuation and readmission in patients with acute coronary syndrome

Abstract Background Although the comprehensive diagnos and treatment of patients with acute coronary syndrome(ACS) has been greatly improved,the morbidity and mortality are still high. Previous literature has reported that about 70-75% of patients diagnosed with acute coronary syndrome have abnormal blood glucose metabolism1,and there existed gender differences. At present, most research results showed that elevated blood glucose is related to the prognosis of ACS. However, further intervention studies indicated that simply strengthen the reducement of blood glucose did not improve prognosis of these patients2. Glucose fluctuations, another dimension of blood glucose, reflect acute changes in blood glucose. However, there are few studies on the effect of blood glucose fluctuation on the prognosis of patients with ACS. Purpose This study aimed to explore the relationship between seven daily fluctuations of blood glucose and readmission in ACS patients. Methods In this study, a total of 664 patients admitted to our University from January 1, 2019 to December 31, 2019 were included and their blood glucose was monitored seven times a day during their hospitalization. The coefficient of variation of blood glucose (CV) was calculated from the results of seven daily blood glucose monitoring to represent the daily fluctuation of blood glucose. Univariate and multivariate regression analyses were performed to determine whether CV was an independent risk factor for re-hospitalization. In addition, the area under the curve (AUC) was used to evaluate the predictive efficacy of CV for outcome events. Finally, we performed a subgroup analysis based on gender and diabetes status to assess the association between CV and readmission in each subgroup. Results After a median follow-up of 21 months, the rate of readmission was 38.4%. Unstable angina pectoris (71.4%) and heart failure (16.4%) were the most common reasons for readmission. Patients with greater CV levels typically exhibited lower fasting blood glucose, higher post breakfast blood glucose, and higher admission blood glucose.The readmission rate increased with the increasing blood glucose variability after the cox regression analysis. Moreover, independent of glycated hemoglobin,CV could predict the risk of readmission in patients with ACS.When using 26.66% as the cutoff point of CV, the study population was divided into two groups and showed a significant differentiation for rehospitalization.In subgroup analysis, there was no significant association between seven daily blood glucose fluctuations and readmission in female and non-diabetes mellitus patients with acute coronary syndrome. Conclusions Besides some normal blood glucose index,seven daily fluctuations of blood glucose was associated with readmission in ACS patients. ACS patients who were male and combined with diabetes were more likely to be readmitted if their CV levels were greater.

Efficacy and safety of Shexiang Baoxin pill in patients with ischemia with non-obstructive coronary arteries (LESS): a phase 4, multicenter, randomized, double-blind, placebo-controlled clinical trial

Abstract Background Patients with ischemia with non-obstructive coronary arteries (INOCA) present with ischemic signs and symptoms but no obstructive coronary artery disease (CAD) at coronary angiography. Shexiang Baoxin pill (MUSKARDIA) is effective in reducing angina frequency in patients with stable CAD. Purpose This phase 4 trial was conducted to evaluate the efficacy and safety of MUSKARDIA in INOCA patients. Methods This was a multicenter, randomized, double-blind, placebo-controlled clinical trial (NCT04897126). The enrolled patients with INOCA confirmed as eligible by leading PI were randomly assigned in a 1:1 ratio to receive MUSKARDIA or placebo (oral 4 pills 3 times a day) on the basis of conventional treatment until the end of follow-up. The primary endpoint was the angina-related outcomes based on the Seattle Angina Questionnaire (SAQ) score that assessed by same doctor at week 12. Results 236 INOCA patients were randomized (MUSKARDIA group, n = 117; placebo group, n=119). At week 12, patients in MUSKARDIA group showed higher SAQ scores compared with placebo group (all P<0.0001, Figure 1) indicating MUSKARDIA could significantly relieve symptoms of angina. According to the Canadian Cardiovascular Society (CCS) grading of angina pectoris, the severity of angina pectoris was significantly reduced in MUSKARDIA group compared with placebo group at week 12 (grade Ⅰ [91.09% vs 48.15%]; grade Ⅱ [8.91% vs 25.93%]; grade Ⅲ [0% vs 19.44%]; grade Ⅳ [0% vs 6.48%]; P<0.001). After 12 weeks of treatment with MUSKARDIA, numbers of weekly angina attacks were significantly reduced compared with placebo group (-2.60 vs -0.42; LSM difference: -2.18; P<0.0001). The percentage of patients who did not used nitroglycerin was noticeably higher in MUSKARDIA group than that in placebo group (84.16% vs 58.33%, P<0.001). The incidence of adverse events did not differ meaningfully between two groups. Conclusion MUSKARDIA was confirmed to be an effective, safe and well-tolerated treatment for INOCA patients in clinical settings.

Interplay between family History and polygenic risk for coronary heart disease: a cohort study among over 60 thousand individuals

Abstract Background The degree to which background genetic risk adds to self-report of family history of coronary heart disease (CHD) remains an important question. Methods We utilized data from the multiethnic Genetic Epidemiology Resource in Adult Health and Aging (GERA) cohort of 60,070 Kaiser Permanente of Northern California (KPNC) members (mean ± SD age=59 ± 9 years; 67% female; 18% non-white). We characterized the cohort at baseline in 2003-2007. Excluding those with missing self-report of family history of CHD (n=1,718) resulted in a final sample of 61,352. We stratified the cohort into not having (n=42,866; 70%) and having (n=18,486; 30%) self-reported family history of CHD and then (within stratum of family history of CHD) by three groups of CHD polygenic risk (low: quintile 1; intermediate: quintiles 2, 3 and 4 combined; and high: quintile 5) using a validated 12-SNP polygenic risk score (PRS) for CHD (CARDIO inCode-Score®). Incident CHD was based on ICD-9/10 codes for angina pectoris, myocardial infarction, revascularization procedures or CHD death (n=3,040) through 12/31/2022; mean follow-up was 14.5 years. Results Age-adjusted CHD incidence rates per 10,000 person years were estimated using Poisson regression (accounting for death and health plan disenrollment) by absence/presence of family history of CHD and polygenic risk groups. As shown in the Figure, polygenic risk provided additional risk stratification within categories of family history. The hazard ratio of high PRS (vs low PRS) adjusted for age, sex, 10 principal components of ancestry, smoking, body mass index, diabetes, hypertension, total cholesterol/HDL ratio and cholesterol lowering therapy was 1.62 (95% CI, 1.39-1.87; p<0.001) in those with no family history of CHD, and 1.66 (95% CI, 1.37-2.00; p<0.001) in those with family history of CHD (p-interaction PRS continuous*family history of CHD=0.93). Conclusions Our results show that polygenic risk predicts future CHD regardless of the presence of family history of CHD. Thus, it is not enough to rely of family history to fully characterize potential genetic burden. These data are therefore important for the future of precision medicine.

Medication adherence and antithrombotic therapy outcomes: insights from a post-hoc analysis of the AFIRE trial

Abstract Background The AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial established noninferiority in efficacy and superiority in safety endpoints of rivaroxaban monotherapy over rivaroxaban plus antiplatelet therapy (combination therapy) in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD). However, the impact of medication adherence to rivaroxaban on AFIRE study outcomes remains unclear. Purpose This post-hoc analysis aimed to explore the influence of medication adherence on AFIRE trial results. Methods Among 2,120 patients, participants were classified into adherent and non-adherent groups based on self-reported measures, which were further verified through on-site visits to the facilities. Adherent patients were defined as those who reported consistently taking their medication as prescribed. The primary efficacy endpoint comprised stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or all-cause death, including cerebral events. Analysis also examined differences in the primary efficacy endpoint between adherent and non-adherent patients. Results Of the 2,120 patients, 2,012 (94.9%) were adherent to rivaroxaban, while 108 (5.1%) were non-adherent. Among adherent patients, rivaroxaban monotherapy showed significantly better efficacy outcomes compared to combination therapy (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.54–0.98; p=0.04, Figure 1A). However, primary efficacy outcomes did not significantly differ among non-adherent patients (HR 0.64, 95% CI 0.23–1.81, p=0.40, Figure 1B). Adherent patients exhibited improved outcomes relative to non-adherent patients, though this difference was not statistically significant (HR 1.68; 95% CI 0.99–2.85; p=0.05, Figure 2A). In clinically high-risk patients with a history of angina pectoris, those who demonstrated adherence to medication (n=1281) exhibited significantly better efficacy outcomes compared to non-adherent patients (n=68) (HR 1.97; 95% CI 1.09–3.56; p=0.03, Figure 2B). Conclusions Rivaroxaban monotherapy versus combination therapy showed favorable efficacy outcomes in patients with good adherence, consistent with the overall AFIRE trial. However, these benefits were not observed in non-adherent patients. Adherence to rivaroxaban is crucial for achieving its maximum therapeutic effect as monotherapy.Figure1Figure2

The evolution of endothelial dysfunction according to the length of the implanted stent on the background of nebivolol therapy

Abstract Introduction The development of atherosclerosis is the driving cause for arterial interventions using coronary stents. Long-stent implantation can increase the vascular injury thereby contributing to the progression of endothelial dysfunction (ED) by the degradation and reduction bioavailability of the nitric oxide (NO) - thus increasing the risk of major cardiovascular events. Purpose Evaluation the evolution of endothelial dysfunction biomarker depending on the length of the stent implanted on the background of nebivolol therapy. Methods The study included 100 patients with stable angina pectoris II–III functional class (age 59.72±0.59 years) undergoing PCI with stent implantation who started the treatment with nebivolol 5mg per day tangent to the conventional treatment and were exposed to PCI with stent implantation, depending on the stent’s length they were divided in three groups: I group - 14 patients with implanted stent’s length ≤15 mm, II group - 57 subjects with implanted stent’s length =15-30 mm and the III group -29 cases where the implanted stent’s length was ≥30 mm. In all the groups was appreciated in blood the endothelial dysfunction’s marker - NO. This marker was assessed preprocedural, postprocedural (after 24 hours) and at intervals of one month, 3,6,12 months after coronary angioplasty, the NO level being compared between these groups and the reference pattern consisting of 20 healthy people. Results The circulating level of nitric oxide determined in I group -61,28±6,92 μM/L and in the II group -56.6±3.03 μM/L and the III group52.39±3.35 was compromised at the preprocedural stage versus the reference pattern - 78.67±2.72 μM/L. During the post- PCI period (first 24 hours), the biomarker level’s was reduced in I group -52.35±1.66 μM/ L, II group -53.74±2.77 μM/L and III group - 52.98±2.91 μM/L. After one month after the intervention on the backroung of the treatment with nebivolol, was recorded a gaing of the NO value in I group - 64.97±5.35 μM/L, II group -63.15±3.99 μM /L and the III group-59.38±4.46 μM/L. The NO serum concentration during the period 3 and 6 months continued to increase in all groups vs the reference pattern. At the 12-month period, the NO level remained high in all the studied groups versus the baseline: I group 99.2±1.1 μM / L (p>0.05), II group-97.96±2.2 μM/L (p<0.001) and the III group -97.65±1.9 μM/L (p<0.001). Conclusion The stent’s length = 15-30 mm and ≥30 mm reveals the presence of an expanded atherosclerotic process, the substrate of which is constituted by the endothelial dysfunction, this being confirmed by the low preprocedural level of NO. The stent implantation procedure induced the accentuation of endothelial dysfunction, and the 12-month nebivolol treatment favored the increase of NO serum concentraon in all groups by 24.9% vs the reference pattern and by 73.3% vs baseline.

Association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and angina pectoris in US adults: a cross-sectional retrospective study based on NHANES 2009–2018

BackgroundThe non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) plays a potential role in cardiovascular diseases. However, its association with angina pectoris remains unclear. Herein, we aimed to explore their relationship.MethodsThis cross-sectional retrospective study included the 2009–2018 data from 22,562 adults diagnosed with angina pectoris, retrieved from the National Health and Nutrition Examination Survey (NHANES) database. NHHR was estimated from laboratory data, and angina pectoris diagnosis was ascertained from the NHANES questionnaire.ResultsAngina pectoris risk was greater in the highest than in the lowest NHHR tertile (odds ratio [OR] = 1.61; 95% confidence interval (CI), 1.15–2.54; P = 0.006). Weighted logistic regression showed a positive association between NHHR and angina pectoris in the fully adjusted model (OR = 1.17; 95% CI, 1.07–1.28; P = 0.001). Restricted cubic spline analysis showed a linear association (P = 0.6572). Subgroup analyses indicated no significant differences across different stratifications (P > 0.05, all). Random forest analyses and Boruta algorithm corroborated that NHHR is a strong predictor of angina pectoris. Among the eight machine-learning models evaluated for predictive capabilities, the logistic regression model demonstrated the strongest predictive capability, with an area under the curve of 0.831.ConclusionsOur study suggests that NHHR is a risk factor for angina pectoris and may be used for risk prediction and to inform future intervention programs to reduce its incidence.

Characteristics and predictors of persistent somatic symptoms in patients with cardiac disease

Persistent somatic symptoms (PSS) are a diagnostic core criterion of the somatic symptom disorder. This longitudinal study aims to determine the frequency of PSS in patients with cardiac disease, identify potential predictive factors, and investigate its impact on healthcare utilization. Somatic symptoms were assessed with the Somatic Symptom Scale-8 four times over the course of three months in consecutively approached cardiac outpatients. Patients were grouped having PSS vs. not having PSS following a psychometric-driven approach based on the SSS-8 cut-off score and a data-driven approach applying cluster analysis. T-tests were performed to compare the characteristics between patients having vs. not having PSS. To identify predictors of group affiliation, we conducted multivariable logistic regressions. Additionally, analyses of covariance were used to further examine associations between healthcare utilization and group affiliation. The study included 95 patients (30.5% female) with a mean age of 60.5 years (SD = 8.7). All patients had at least one of the following cardiac diseases recorded in their medical history: coronary heart disease (n = 51), myocardial infarction (n = 21), valve disease (n = 22), cardiomyopathy (n = 15), cardiac dysrhythmia (n = 43), and heart failure (n = 12). 30 (32%) were grouped having PSS according to the psychometric-driven approach and 27 (28%) according to the data-driven approach. For both approaches, patients with PSS were more likely to be female, unemployed, reporting angina pectoris, having higher depression, and higher anxiety severity (for all: p ≤ 0.05). Predictors of PSS group affiliation were female gender, higher age, depression severity, and angina pectoris (for all: p ≤ 0.015). Patients with PSS more frequently visited general practitioners and cardiologists compared to patients without PSS (p ≤ 0.013). Enhancing our knowledge of PSS in patients with cardiac disease could help to improve identification of patients’ specific needs and the factors to consider in diagnosis and individualized treatment.

Ambulatory care sensitive diseases/conditions in adult patients. A systematic review

Aim. To summarize the published data on the nomenclature of ambu­latory care sensitive diseases/conditions (ACSCs) in adult patients as one of the tools for a comprehensive assessment of the effectiveness of primary health care (PHC) measures implemented.Material and methods. The study was implemented in 4 following stages: 1 — search for articles by keywords in electronic bibliographic databases; 2 — duplicate elimination; 3 — review of abstracts with an as­sessment for compliance with the inclusion/exclusion criteria, fol­lowed by a search for full-text versions and final selection of pub­lications; 4 — systematization and analysis of data on the ACSCs. Articles published in the period from January 1, 2012 to December 31, 2022 and containing information on ACSC nomenclature were searched in 4 domestic and foreign electronic bibliographic databases (Elibrary, NLM (PubMed), MEDLINE, PreMEDLINE). The PRISMA (Preferred Re­porting Items for Systematic reviews and Meta-Analyses) system was used in the preparation of the systematic review. Systematization of information on the obtained results was carried out in Microsoft Office Excel 2016 spreadsheets.Results. In total, out of 10898 initially found publications, 11 full-text pa­pers describing studies that fully met the inclusion/exclusion criteria we­re admitted to stage 4 and were included in the final analysis. In none of the 11 publications was ACSC nomenclature identical to any other pub­lication included in stage 4 of the analysis. Variability in the total num­ber of ACSCs was noted in each of the assessed papers. In 100% of the analyzed publications, the NCAs included chronic obstructive pul­monary disease/chronic bronchitis, heart failure, diabetes, and hypertension. In 91% (10 publications), the ACSCs included angina pectoris, asthma, iron deficiency anemia, dental and oral diseases, urinary tract infections, acute skin infections, and gastroenteritis.Conclusion. The nomenclature of the ACSCs in different countries is characterized by variability due to demographic, epidemiological, organizational, and other features. The conducted systematic review showed that the nomenclature of the ACSCs has not been defined in the Russian Federation. The data obtained in this work can serve as a basis for initiating a project aimed at developing a domestic nomenclature of ACSCs as one of the tools for a comprehensive assessment of the effectiveness of PHC measures implemented.

PD-1/PD-L1 and coronary heart disease: a mendelian randomization study.

It has been found that programmed cell death protein-1 (PD-1) or its ligand PD-L1 may play an important role in the onset and progression of coronary heart disease (CHD). Thus, we conducted this mendelian randomization analysis (MR) to estimate the causal relationship between PD-1/PD-L1 and 5 specific CHDs (chronic ischemic heart disease, acute myocardial infarction, angina pectoris, coronary atherosclerosis, and unstable angina pectoris), complemented by gene set enrichment analysis (GSEA) for further validation. Publicly available summary-level data were attained from the UK Biobank with genetic instruments obtained from the largest available, nonoverlapping genome-wide association studies (GWAS). Our analysis involved various approaches including inverse variance-weighted meta-analysis, alternative techniques like weighted median, MR-Egger, MR-multipotency residuals and outliers detection (PRESSO), along with multiple sensitivity assessments such as MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis to evaluate and exclude any anomalies. Gene expression profile (GSE71226) was obtained from Gene Expression Omnibus (GEO) database for GSEA. IVW analysis showed a causal association between PD-1 and chronic ischemic heart disease (OR, 0.997; 95%CI, 0.995-0.999; P, 0.009), chronic ischemic heart disease and PD-1 (beta, -3.1; 95%CI, -6.017 to -0.183; P, 0.037), chronic ischemic heart disease and PD-L1 (beta, -3.269; 95%CI, -6.197 to -0.341; P, 0.029). No significant causal relationship was found between PD-1/PD-L1 and other 4 CHDs. The accuracy and robustness of these findings were confirmed by sensitivity tests. GSEA found that the KEGG pathway and related core genes of "PD-L1 expression and PD-1 checkpoint pathway in cancer" pathway were downregulated in CHD. This study provided evidence of a bidirectional causal relationship between PD-1 and chronic ischemic heart disease and a protective association between chronic ischemic heart disease and PD-L1.

Clinical development and proof of principle testing of new regenerative vascular endothelial growth factor-D therapy for refractory angina: rationale and design of the phase 2 ReGenHeart trial

BackgroundDespite tremendous therapeutic advancements, a significant proportion of coronary artery disease patients suffer from refractory angina pectoris, that is, quality-of-life-compromising angina that is non-manageable with established pharmacological and interventional treatment...

Coronary artery calcium measurement on attenuation correction computed tomography using artificial intelligence: correlation with coronary flow capacity and prognosis.

This study aimed to test whether the coronary artery calcium (CAC) burden on attenuation correction computed tomography (CTac), measured using artificial intelligence (AI-CACac), correlates with coronary flow capacity (CFC) and prognosis. We retrospectively enrolled patients who underwent [13N]ammonia positron emission tomography (PET) between September 2021 and May 2023. CTac data were obtained from all the patients. Patients with (history of) acute coronary syndrome, previous coronary stent insertion or bypass surgery, or left ventricular ejection fraction < 40% were excluded. The total Agatston score measured using a dedicated AI-CAC quantification software on CTac was defined as AI-CACac. The correlations between AI-CACac and PET-measured myocardial blood flow (MBF) and CFC and significant ischaemia (summed difference score ≥ 7) were analysed. Their prognostic values for major cardiovascular events (MACE), including death, nonfatal myocardial infarction, hospitalisation due to angina pectoris or heart failure, and late (> 90 days) revascularisation, were also evaluated. In total, 289 patients were included in this study. Significant negative correlations were found between AI-CACac and stress MBF (ρ = -0.363, p < 0.001) and MFR (ρ = -0.305, p < 0.001). AI-CACac > 10 was associated with a significantly higher prevalence of impaired CFC (31% vs. 7%, p < 0.001) and significant ischaemia (20% vs. 7%), which remained significant after adjusting for other risk factors. MACE occurred in 49 (17%) patients (median follow-up, 284 days), and those who experienced MACE had significantly higher AI-CACac (median, 166 vs. 56; p = 0.039). However, multivariable analysis revealed an independent prognostic association among impaired CFC, diabetes, smoking, but not for AI-CACac. AI-measured CACac correlates well with PET-measured MBF and CFC, but its prognostic significance requires further validation.

Do adult children increase the chances of receiving the recommended hospital treatment among older adults with heart disease?

BackgroundWe investigated whether having children and their socioeconomic resources are associated with receiving coronary angiogram (CAG) and coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI) among older...

Effect of glycemic gap on prognosis and complications in vulnerable period of acute heart failure

Background: To investigate the effect of glycemic gap on the prognosis and complications of heart failure in patients with acute heart failure. Methods: 100 patients with acute heart failure treated in our hospital from January 2022 to August 2023 were divided into two groups according to the prognosis: good prognosis group (n = 58) and poor prognosis group (n = 42). Univariate analysis of the prognostic factors of acute heart failure patients in vulnerable period, multivariate Logistics regression analysis of the prognostic factors of acute heart failure patients. ROC analysis of the value of glycemic gap in predicting the prognosis of patients with acute heart failure in the vulnerable period of heart failure, and compare the occurrence of complications between the two groups. Including: arrhythmia, angina pectoris, cardiogenic shock, thrombosis. Results: There was no significant difference in age, sex, history of hypertension, BMI, TG, history of diabetes and serum potassium between the two groups. The glycemic gap, BNP, Ang II, cTnI and SCR in the good prognosis group were lower than those in the poor prognosis group, while LVEF and hemoglobin were higher than those in the poor prognosis group. Binary Logistics regression analysis showed that. Glycemic gap, BNP, Ang II, cTnI, SCR, LVEF and hemoglobin were independent prognostic factors in patients with acute heart failure. The area under the glycemic gap value curve was determined to be 0.8071. The sensitivity of the assessment was 72.8, while the specificity was 70.5, . The incidence of complications in the good prognosis group (1.72%) was significantly lower than that in the poor prognosis group (16.67%). Conclusions: Glycemic gap is related to the prognosis and complications of heart failure in patients with acute heart failure. Hyperglycemia gap will affect the prognosis of heart failure in patients with acute heart failure, resulting in poor prognosis and increasing the incidence of complications.

Major Adverse Cardiovascular Events Following Coronary Artery Stenting by History of Hypertensive Disorder of Pregnancy.

A history of hypertensive disorders of pregnancy is associated with at least twice the risk of incident ischemic heart disease. Whether the long-term outcome following treatment with coronary artery stenting is associated to the history of hypertensive disorders of pregnancy is unknown. We included 8364 women (age ≤65 years) undergoing first coronary artery stenting 2006 to 2022 following their first delivery in 1973 or later, linking nationwide data on percutaneous coronary intervention and delivery history. In total, 1122 women (13.4%) had a history of hypertensive disorders of pregnancy. The main outcome, a major adverse cardiovascular event, was defined as any incident myocardial infarction, ischemic heart disease, cardiac arrest, arrhythmias, angina pectoris, heart failure, cerebral infarction, or sudden death. During a median follow-up time of 5 years, 258 women with a history of hypertensive disorders of pregnancy had a major adverse cardiovascular event, compared with 1465 women without a history of hypertensive disorders of pregnancy (23% versus 20.2%, P=0.028 for log-rank test). Estimates adjusted for patient- and procedural characteristics in proportional hazards regression models suggested that the hazard rate increased only after 4-8 years of follow-up (hazard ratio [HR], 1.36 [95% CI, 1.05-1.78]) and was primarily driven by women with history of gestational hypertension (HR, 2.15 [95% CI, 1.49-3.11]). Women with a history of hypertensive disorders of pregnancy have an increased risk of a major adverse cardiovascular event following coronary artery stenting compared with other parous women. A history of hypertensive disorders of pregnancy warrants further attention in the secondary prevention setting of coronary artery disease.

Treatment of microvascular angina pectoris by activating blood circulation to remove blood stasis: A systematic review and meta-analysis.

To systematically evaluate the clinical efficacy of using the method of activating blood circulation and removing blood stasis in the treatment of microvascular angina (MVA) based on the meta-analysis method. A comprehensive search of randomized controlled trials on the treatment of MVA using the method of activating blood circulation and removing blood stasis in Chinese and English databases such as China National Knowledge Infrastructure Database, Wanfang Data Knowledge Service Platform, Vipshop Journal Resource Integration Service Platform, PubMed, Cochrane Library, Embase, Web of Science, and CBM was conducted, and the search time limit was from the establishment of each database to February 2023. All retrieved literature was screened, and data extracted according to the specified inclusion and exclusion criteria, and data analysis was completed using Revman 5.4 software. Fifteen studies with a total of 1031 patients were finally included, and the results of the meta-analysis showed that the treatment with the method of activating blood circulation and removing blood stasis was more advantageous compared with the group of Western medicine alone. Among them, clinical effect of activating blood circulation and removing blood stasis (relative risk = 1.20, 95% confidence intervals [CI] [1.11, 1.31], P < .0001) and electrocardiographic efficacy (relative risk = 1.32, 95% CI [1.15, 1.51], P < .0001) were more effective, concentration levels of endothelin-1 (standardized mean difference = -2.14, 95% CI [-2.97, -1.31], P < .00001) and high sensitivity C-reactive protein (mean difference = -0.84, 95% CI [-0.93, -0.75], P < .00001) were lower, concentration levels of nitric oxide (standardized mean difference = 0.61, 95% CI [0.33, 0.89], P < .0001) was higher, and ST-segment depression range (mean difference = -0.07, 95% CI [-0.09, -0. 04], P < .00001) was smaller. Compared with the treatment with Western medicine alone, the treatment of MVA is more effective by choosing the method of activating blood circulation and removing blood stasis.

Targeted metabolomic profiling of acute ST-segment elevation myocardial infarction

Myocardial infarction is a major cause of morbidity and mortality worldwide. Metabolomic investigations may be useful for understanding the pathogenesis of ST-segment elevation myocardial infarction (STEMI). STEMI patients were comprehensively examined via targeted metabolomic profiling, machine learning and weighted correlation network analysis. A total of 195 subjects, including 68 STEMI patients, 84 patients with stable angina pectoris (SAP) and 43 non-CVD patients, were enrolled in the study. Metabolomic profiling involving the quantitative analysis of 87 endogenous metabolites in plasma was conducted. This study is the first to perform targeted metabolomic profiling in patients with STEMI. We identified 36 significantly altered metabolites in STEMI patients. Increased levels of four amino acids, eight acylcarnitines, six metabolites of the NO–urea cycle and neurotransmitters, and three intermediates of tryptophan metabolism were detected. The following metabolites exhibited decreased levels: six amino acids, three acylcarnitines, three components of the NO–urea cycle and neurotransmitters, and three intermediates of tryptophan metabolism. We found that the significant changes in tryptophan metabolism observed in STEMI patients—the increase in anthranilic acid and tryptophol and decrease in xanthurenic acid and 3-OH-kynurenine—may play important roles in STEMI pathogenesis. On the basis of the differences in the constructed weighted correlation networks, new significant metabolite ratios were identified. Among the 22 significantly altered metabolite ratios identified, 13 were between STEMI patients and non-CVD patients, and 17 were between STEMI patients and SAP patients. Seven of these ratios were common to both comparisons (STEMI patients vs. non-CVD patients and STEMI patients vs. SAP patients). Additionally, two ratios were consistently observed among the STEMI, SAP and non-CVD groups (anthranilic acid: aspartic acid and GSG (glutamine: serine + glycine)). These findings provide new insight into the diagnosis and pathogenesis of STEMI.

Increased CD14+HLA-DR-/low myeloid-derived suppressor cells can be regarded as a biomarker on disease severity and response to therapy in acute coronary syndrome.

This study aimed to investigate the dynamic changes in monocytic myeloid-derived suppressor cells (M-MDSCs) and their implications in the pathogenesis of acute coronary syndrome (ACS), shedding light on potential therapeutic targets. Peripheral blood samples were collected from 68 ACS patients, 35 stable angina pectoris (SAP) patients, and 30 healthy controls (HC). Multi-parameter flow cytometry was employed for analysis of M-MDSCs, explored with disease characteristics and progression. ACS patients exhibited an increased frequency of circulating M-MDSCs compared to SAP patients and HC. M-MDSCs levels demonstrated associations with ACS type, coronary artery lesions, multi-vessel disease, and cardiac dysfunction severity. Higher M-MDSCs levels were found in obese patients. Notably, therapy led to a significant decrease in M-MDSCs frequency. Furthermore, ACS patients exhibited elevated levels of interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α) in the cytokine profile associated with M-MDSCs. Increased expression of arginase-1(Arg-1) was observed in ACS patients, with positive correlations between M-MDSCs levels and IL-6, GM-CSF, and Arg-1 expression. The diagnostic performance of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and M-MDSCs levels varied in predicting the severity of coronary artery stenosis, with TG showing higher specificity, HDL-C displaying higher sensitivity, and M-MDSCs levels demonstrating balanced sensitivity and specificity. Assessment of M-MDSCs frequency holds promise as a predictive marker for disease progression and therapy response of coronary artery stenosis. The elevated presence of M-MDSCs suggests their potential role in modulating ACS-related inflammation.