Role of interleukin 6 signaling pathway in the anti-inflammatory effects of statins on coronary artery disease: Evidence from Mendelian randomization analysis.

BACKGROUND: Statins are currently widely used in the prevention of coronary artery disease (CAD) primarily for lipid-lowering with a potential anti-inflammatory effect. However, it is not clear if their potential anti-inflammatory effects are mediated through the interleukin 6 (IL-6) signaling pathway. METHODS: Using the Mendelian randomization (MR) approach followed by multivariable MR analyses, we examined the extent to which the effects of statins on CAD might be mediated through the IL-6 signaling pathway. RESULTS: Our observations showed that HMG-CoA reductase, using LDL levels as a proxy, had a significant effect on upstream IL-6 (ßMR = 0.47, P-IVW = 0.01) and nominally significant effects on IL-6RA (ßMR = 0.22, P-IVW = 0.047) and APOB (ßMR = 0.82, P-IVW = 1.8 × 10-33). While the IL-6 signaling cascade (IL-6RA ßMR = -0.06, P-IVW = 3.45 × 10-20 and IL-6 ßMR = -0.03, P-IVW = 0.09) and the anti-inflammatory effect of HMG-CoA reductase (ßMR = -0.31, P-IVW = 0.01) was found to influence the risk of CAD, the multivariable MR (MVMR) model indicated that the anti-inflammatory effect of HMG-CoA reductase is not likely to be mediated through the IL-6 signaling cascade, including APOB and IL-6RA (MVMRß = 0.23, P = 0.688). CONCLUSIONS: Our findings suggest that statins may use inflammatory mechanisms independent of the IL-6 signaling pathway to prevent CAD. This result could potentially affect the definition of the target population for statin use.

Update on the Role of Colchicine in Cardiovascular Disease.

PURPOSE OF REVIEW: This review focuses on the use of colchicine to target inflammation to prevent cardiovascular events among those at-risk for or with established coronary artery disease. RECENT FINDINGS: Colchicine is an anti-inflammatory drug that reduces cardiovascular events through its effect on the IL-1ß/IL-6/CRP pathway, which promotes the progression and rupture of atherosclerotic plaques. Clinical trials have demonstrated that colchicine reduces cardiovascular events by 31% among those with chronic coronary disease, and by 23% among those with recent myocardial infarction. Its ability to dampen inflammation during an acute injury may broaden its scope of use in patients at risk for cardiovascular events after major non-cardiac surgery. Colchicine is an effective anti-inflammatory therapy in the prevention of acute coronary syndrome. Ongoing studies aim to assess when, and in whom, colchicine is most effective to prevent cardiovascular events in patients at-risk for or with established coronary artery disease.

Cross-sectional analysis of cardiovascular disease and risk factors in patients with spondyloarthritis: a real-life evidence from biostar nationwide registry.

The association between spondyloarthritis and cardiovascular (CV) diseases is complex with variable outcomes. This study aimed to assess the prevalence rates of CV diseases and to analyze the impact of CV risk factors on CV disease in patients with spondyloarthritis. A multi-center cross-sectional study using the BioSTAR (Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drugs Registry) database was performed on patients with spondyloarthritis. Socio-demographic, laboratory, and clinical data were collected. Patients with and without major adverse cardiovascular events (MACE) were grouped as Group 1 and Group 2. The primary outcome was the overall group's prevalence rates of CV disease and CV risk factors. The secondary outcome was the difference in socio-demographic and clinical characteristics between the groups and predictive risk factors for CV disease. There were 1457 patients with a mean age of 45.7 ± 10.9 years. The prevalence rate for CV disease was 3% (n = 44). The distribution of these diseases was coronary artery disease (n = 42), congestive heart failure (n = 4), peripheral vascular disorders (n = 6), and cerebrovascular events (n = 4). Patients in Group 1 were significantly male (p = 0.014) and older than those in Group 2 (p < 0.001). There were significantly more patients with hypertension, diabetes mellitus, chronic renal failure, dyslipidemia, and malignancy in Group 1 than in Group 2 (p < 0.05). Smoking (36.7%), obesity (24.4%), and hypertension (13.8%) were the most prevalent traditional CV risk factors. Hypertension (HR = 3.147, 95% CI 1.461-6.778, p = 0.003), dyslipidemia (HR = 3.476, 95% CI 1.631-7.406, p = 0.001), and cancer history (HR = 5.852, 95% CI 1.189-28.810, p = 0.030) were the independent predictors for CV disease. A multi-center cross-sectional study using the BioSTAR (Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drugs Registry) database was performed on patients with spondyloarthritis. Socio-demographic, laboratory, and clinical data were collected. Patients with and without major adverse cardiovascular events (MACE) were grouped as Group 1 and Group 2. The primary outcome was the overall group's prevalence rates of CV disease and CV risk factors. The secondary outcome was the difference in socio-demographic and clinical characteristics between the groups and predictive risk factors for CV disease. There were 1457 patients with a mean age of 45.7 ± 10.9 years. The prevalence rate for CV disease was 3% (n = 44). The distribution of these diseases was coronary artery disease (n = 42), congestive heart failure (n = 4), peripheral vascular disorders (n = 6), and cerebrovascular events (n = 4). Patients in Group 1 were significantly male (p = 0.014) and older than those in Group 2 (p < 0.001). There were significantly more patients with hypertension, diabetes mellitus, chronic renal failure, dyslipidemia, and malignancy in Group 1 than in Group 2 (p < 0.05). Smoking (36.7%), obesity (24.4%), and hypertension (13.8%) were the most prevalent traditional CV risk factors. Hypertension (HR = 3.147, 95% CI 1.461-6.778, p = 0.003), dyslipidemia (HR = 3.476, 95% CI 1.631-7.406, p = 0.001), and cancer history (HR = 5.852, 95% CI 1.189-28.810, p = 0.030) were the independent predictors for CV disease. The prevalence rate of CV disease was 3.0% in patients with spondyloarthritis. Hypertension, dyslipidemia, and cancer history were the independent CV risk factors for CV disease in patients with spondyloarthritis.

Restoration of blood vessel regeneration in the era of combination SGLT2i and GLP-1RA therapy for diabetes and obesity.

Ischaemic cardiovascular diseases, including peripheral and coronary artery disease, myocardial infarction, and stroke, remain major comorbidities for individuals with type 2 diabetes (T2D) and obesity. During cardiometabolic chronic disease (CMCD), hyperglycaemia and excess adiposity elevate oxidative stress and promote endothelial damage, alongside an imbalance in circulating pro-vascular progenitor cells that mediate vascular repair. Individuals with CMCD demonstrate pro-vascular 'regenerative cell exhaustion' (RCE) characterized by excess pro-inflammatory granulocyte precursor mobilization into the circulation, monocyte polarization towards pro-inflammatory vs. anti-inflammatory phenotype, and decreased pro-vascular progenitor cell content, impairing the capacity for vessel repair. Remarkably, targeted treatment with the sodium-glucose cotransporter-2 inhibitor (SGLT2i) empagliflozin in subjects with T2D and coronary artery disease, and gastric bypass surgery in subjects with severe obesity, has been shown to partially reverse these RCE phenotypes. SGLT2is and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have reshaped the management of individuals with T2D and comorbid obesity. In addition to glucose-lowering action, both drug classes have been shown to induce weight loss and reduce mortality and adverse cardiovascular outcomes in landmark clinical trials. Furthermore, both drug families also act to reduce systemic oxidative stress through altered activity of overlapping oxidase and antioxidant pathways, providing a putative mechanism to augment circulating pro-vascular progenitor cell content. As SGLT2i and GLP-1RA combination therapies are emerging as a novel therapeutic opportunity for individuals with poorly controlled hyperglycaemia, potential additive effects in the reduction of oxidative stress may also enhance vascular repair and further reduce the ischaemic cardiovascular comorbidities associated with T2D and obesity.

Postoperative Insulin Dose for Cardiac Artery Bypass Graft and Other Cardiac Surgeries in Patients with Type 2 Diabetes: A Retrospective Study.

Purpose: Recommendations on perioperative glycemic control in cardiac surgery are based on coronary artery bypass graft surgery (CABG), though coronary artery disease and valvular disease are pathologically distinct. We aimed to compare the postoperative insulin requirement between CABG and other cardiac surgeries in type 2 diabetic patients and identify predictive factors for the maximum postoperative insulin dose. Patients and Methods: We retrospectively included 60 Japanese patients with diabetes/glucose intolerance (HbA1c > 37 mmol/mol [5.6%]) who were hospitalized for cardiovascular surgery between April 2017 and March 2019. We categorized the subjects into the CABG and non-CABG groups, and performed subgroup analysis on patients who received postoperative insulin therapy. Results: The CABG group required a significantly higher insulin dose on postoperative days 2, 5, 6, and 7, and a significantly higher maximum postoperative insulin dose (24.6 U vs 9.7 U, P < 0.001) than the non-CABG group. Multivariate linear regression analyses showed that the independent determinants of the maximum postoperative insulin dose were HbA1c and duration of diabetes in the non-CABG group, and HbA1c in the CABG group. Conclusion: CABG had a higher postoperative insulin requirement than other cardiovascular surgeries; early aggressive insulin therapy is indicated, especially for patients with higher HbA1c levels/longer duration of diabetes.

Hegemony of inflammation in atherosclerosis and coronary artery disease.

Inflammation drives coronary artery disease and atherosclerosis implications. Lipoprotein entry, retention, and oxidative modification cause endothelial damage, triggering innate and adaptive immune responses. Recruited immune cells orchestrate the early atherosclerotic lesions by releasing proinflammatory cytokines, expediting the foam cell formation, intraplaque haemorrhage, secretion of matrix-degrading enzymes, and lesion progression, eventually promoting coronary artery syndrome via various inflammatory cascades. In addition, soluble mediators disrupt the dynamic anti- and prothrombotic balance maintained by endothelial cells and pave the way for coronary artery disease such as angina pectoris. Recent studies have established a relationship between elevated levels of inflammatory markers, including C-reactive protein (CRP), interleukins (IL-6, IL-1ß), and tumour necrosis factor-alpha (TNF-α) with the severity of CAD and the possibility of future cardiovascular events. High-sensitivity C-reactive protein (hs-CRP) is a marker for assessing systemic inflammation and predicting the risk of developing CAD based on its peak plasma levels. Hence, understanding cross-talk interactions of inflammation, atherogenesis, and CAD is highly warranted to recalculate the risk factors that activate and propagate arterial lesions and devise therapeutic strategies accordingly. Cholesterol-inflammation lowering agents (statins), monoclonal antibodies targeting IL-1 and IL-6 (canakinumab and tocilizumab), disease-modifying antirheumatic drugs (methotrexate), sodium-glucose transport protein-2 (SGLT2) inhibitors, colchicine and xanthene oxidase inhibitor (allopurinol) have shown promising results in reducing inflammation, regressing atherogenic plaque and modifying the course of CAD. Here, we review the complex interplay between inflammatory, endothelial, smooth muscle and foam cells. Moreover, the putative role of inflammation in atherosclerotic CAD, underlying mechanisms and potential therapeutic implications are also discussed herein.

Coronary artery disease in older adults with congenital heart defects: risk factors and pharmacotherapy.

INTRODUCTION: With advancing age, adults with congenital heart disease (ACHD) are at a higher risk of developing atherosclerotic coronary artery disease (CAD). OBJECTIVES: We aimed to determine the prevalence of CAD, its risk factors, and use of guideline­directed pharmacotherapy among older patients with ACHD.  Patients and methods: We studied all ACHD patients aged 60 years or older hospitalized in our department between the years 2013 and 2020. CAD was defined as a history of acute coronary syndrome or coronary revascularization, or more than 50% diameter stenosis on coronary angiography. Data regarding the underlying heart defect, prevalence of cardiovascular risk factors, and drug prescriptions were collected. RESULTS: A total of 198 patients with known coronary artery status (mean [SD] age, 66.2 [5.3] years; 43.3% men) were included in the analysis. Of them, 54 (27.3%) had CAD. The individuals with CAD were more often men, and they were more likely to have a mild heart defect, dyslipidemia, and a history of hypertension and tobacco use. Multivariable analysis showed that male sex (P = 0.001), dyslipidemia (P = 0.003), and hypertension (P = 0.04) were positive independent predictors of CAD, whereas overweight / obesity was identified as a negative independent predictor (P = 0.04). The proportion of CAD patients on antiplatelet and / or anticoagulant drugs was 92.6%. ß­Blockers were prescribed to 87% of the patients, and a lipid­lowering agent to 96% of the study population. CONCLUSIONS: CAD is common in older patients with ACHD. Our results underline the importance of identification and treatment of modifiable CAD risk factors in individuals with ACHD. The obesity paradox might also play a role in this population. The rate of guideline­recommended pharmacotherapy implementation seems to be satisfactory.

Characteristics of Coronary Atherosclerosis Related to Plaque Burden Regression During Treatment With Alirocumab: The ARCHITECT Study.

BACKGROUND: Intensive lipid-lowering therapy may induce coronary atherosclerosis regression. Nevertheless, the factors underlying the effect of lipid-lowering therapy on disease regression remain poorly characterized. Our aim was to determine which characteristics of atherosclerotic plaque are associated with a greater reduction in coronary plaque burden (PB) after treatment with alirocumab in patients with familial hypercholesterolemia. METHODS: The ARCHITECT study (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) is a phase IV, open-label, multicenter, single-arm clinical trial to assess the effect of the treatment with alirocumab for 78 weeks on the coronary atherosclerotic PB and its characteristics in subjects with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent a coronary computed tomographic angiography at baseline and a final one at 78 weeks. Every patient received alirocumab 150 mg subcutaneously every 14 days in addition to high-intensity statin therapy. RESULTS: One hundred and four patients were enrolled. Median age was 53.3 (46.2-59.4) years and 54 were women (51.9%). The global coronary PB changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up, which is -4.6% (-7.7% to -1.9%; P<0.001) reduction. A decrease in the percentage of unstable core (fibro-fatty+necrotic plaque; from 14.1 [7.9-22.3] to 8.0 [6.4-10.6]; -6.6%; P<0.001) was found. A greater PB (ß, 0.36 [0.13-0.59]; P=0.002) and a higher proportion of unstable core (ß, 0.15 [0.08-0.22]; P<0.001) were significantly related to PB regression. CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy might produce a greater PB regression in patients with familial hypercholesterolemia with higher baseline PB and in those with larger unstable core. Further studies are needed to corroborate the hypothesis raised by these results. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05465278.

PCSK9 inhibitor use during pregnancy in a case of familial hypercholesterolemia complicated with coronary artery disease.

Limited data have been reported on the use of proprotein convertase subtilisin/kexin type 9 (PCSK 9) inhibitors during pregnancy in women with familial hypercholesterolemia (FH). Here, we present the first case of initiating evolocumab (PCSK9 inhibitor) in a compound heterozygous FH mother. The patient was a 34-year-old primipara with severe dyslipidemia and a history of coronary artery bypass surgery. An elevated low-density lipoprotein cholesterol (LDL-C) level of 420 mg/dL was detected in the first trimester and persistently increased throughout pregnancy. Evolocumab was administered at 31 and 35 weeks of gestation, showing a positive effect on stabilizing LDL-C levels. Planned delivery with labor analgesia was performed at 38 + 4 weeks. Both the mother and infant were discharged without any notable complications. Hence, evolocumab, an IgG2 monochromatic antibody with little placental permeability, may be an alternative medication with limited influence on infants. Further studies are needed to assess the safety of evolocumab administration during pregnancy.

Direct Oral Anticoagulants use in Patients with Stable Coronary Artery Disease, Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention.

The investigation for the optimal anticoagulation strategy for patients with stable coronary artery disease, acute coronary syndromes, and undergoing percutaneous coronary intervention constitutes a great challenge for physicians and is a field of extensive research. Although aspirin is commonly recommended as a protective measure for all patients with coronary artery disease and dual antiplatelet therapy for those undergoing procedures, such as percutaneous coronary intervention or coronary artery bypass graft surgery, the risk of recurrent cardiovascular events remains significant. In this context, the shortcomings associated with the use of vitamin K antagonists have led to the assessment of direct oral anticoagulants as promising alternatives. This review will explore and provide a comprehensive analysis of the existing data regarding the use of direct oral anticoagulants in patients with stable coronary artery disease or acute coronary syndrome, as well as their effectiveness in those undergoing percutaneous coronary intervention or coronary artery bypass graft surgery.

Transcriptome-wide map of N6-methyladenosine (m6A) profiling in coronary artery disease (CAD) with clopidogrel resistance.

BACKGROUND: Clopidogrel resistance profoundly increases the risk of major cardiovascular events in coronary artery disease (CAD) patients. Here, we comprehensively analyse global m6A modification alterations in clopidogrel-resistant (CR) and non-CR patients. METHODS: After RNA isolation, the RNA transcriptome expression (lncRNA, circRNA, and mRNA) was analysed via RNA-seq, and m6A peaks were identified by MeRIP-seq. The altered m6A methylation sites on mRNAs, lncRNAs, and circRNAs were identified, and then, GO and KEGG pathway analyses were performed. Through joint analysis with RNA-seq and MeRIP-seq data, differentially expressed mRNAs harbouring differentially methylated sites were identified. The changes in m6A regulator levels and the abundance of differentially methylated sites were measured by RT-PCR. The identification of m6A-modified RNAs was verified by m6A-IP-qPCR. RESULTS: The expression of 2919 hypermethylated and 2519 hypomethylated mRNAs, 192 hypermethylated and 391 hypomethylated lncRNAs, and 375 hypermethylated and 546 hypomethylated circRNAs was shown to be altered in CR patients. The m6A peaks related to CR indicated lower mark density at the CDS region. Functional enrichment analysis revealed that inflammatory pathways and insulin signalling pathways might be involved in the pathological processes underlying CR. The expression of mRNAs (ST5, KDM6B, GLB1L2, and LSM14B), lncRNAs (MSTRG.13776.1 and ENST00000627981.1), and circRNAs (hsa_circ_0070675_CBC1, hsa-circRNA13011-5_CBC1, and hsa-circRNA6406-3_CBC1) was upregulated in CR patients, while the expression of mRNAs (RPS16 and CREG1), lncRNAs (MSTRG.9215.1), and circRNAs (hsa_circ_0082972_CBC1) was downregulated in CR patients. Moreover, m6A regulators (FTO, YTHDF3, and WTAP) were also differentially expressed. An additional combined analysis of gene expression and m6A peaks revealed that the expression of mRNAs (such as ST5, LYPD2, and RPS16 mRNAs) was significantly altered in the CR patients. CONCLUSION: The expression of m6A regulators, the RNA transcriptome, and the m6A landscape was altered in CR patients. These findings reveal epitranscriptomic regulation in CR patients, which might be novel therapeutic targets in future.

Different effects of medications for hypertension on renal function between patients with and without diabetes mellitus undergoing percutaneous coronary intervention: a retrospective single-center cohort study.

BACKGROUND: Diabetes mellitus (DM) and hypertension are well-known atherosclerosis risk factors. Furthermore, renal dysfunction is a crucial risk factor for patients with coronary artery disease (CAD), and managing renal function in these patients is complicated because of comorbid conditions and potential side effects during treatment. Therefore, this study aimed to investigate the effect of medications for hypertension on renal function after percutaneous coronary intervention (PCI) between patients with and without DM with statins. METHODS: In 297 consecutive patients undergoing PCI for stable angina pectoris, cystatin C (CysC) was evaluated at baseline and 9 months after PCI, and the percent change in CysC (%CysC) was calculated. The association of worsening renal function (WRF: %CysC ≥ 0) and baseline characteristics, including medications, was assessed. RESULTS: Among 297 hypertensive patients with statins, 196 and 101 were with and without DM, respectively. Angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker, and ß-blocker were prescribed in 56 (29%), 82 (42%), and 91 (46%) patients in the DM group, and 20 (20%), 52 (51%), and 52 (51%) in the non-DM group, respectively. The patients with WRF after PCI were 100 (51%) and 59 (58%) in the DM and non-DM groups (p = 0.261). Additionally, the %CysC had no significant differences between groups [median: 0%, interquartile range (IQR): -7.9% to 8.5% vs. median: 1.1%, IQR: -6.6% to 9.6%, p = 0.521]. Multivariate logistic analysis for WRF using relevant factors from univariate analysis showed that only ß-blocker [odds ratio (OR): 2.76, 95% confidence interval (CI): 1.03-7.90, p = 0.048] was independently associated with WRF in the DM group whereas ACEI (OR: 0.07, 95% CI: 0.01-0.47, p = 0.012) was negatively correlated with WRF in the non-DM group. CONCLUSION: The ß-blocker was the independent risk factor for WRF in patients with DM in the late phase after PCI for stable angina pectoris, while the use of ACEI had a renoprotective effect in patients without DM.

Rosuvastatin versus atorvastatin treatment in adults with coronary artery disease: secondary analysis of the randomised LODESTAR trial.

OBJECTIVE: To compare the long term efficacy and safety of rosuvastatin with atorvastatin treatment in adults with coronary artery disease. DESIGN: Randomised, open label, multicentre trial. SETTING: 12 hospitals in South Korea, September 2016 to November 2019. PARTICIPANTS: 4400 adults (age ≥19 years) with coronary artery disease. INTERVENTIONS: Participants were assigned to receive either rosuvastatin (n=2204) or atorvastatin (n=2196) using 2×2 factorial randomisation. MAIN OUTCOME MEASURES: The primary outcome was a three year composite of all cause death, myocardial infarction, stroke, or any coronary revascularisation. Secondary outcomes were safety endpoints: new onset diabetes mellitus; hospital admissions due to heart failure; deep vein thrombosis or pulmonary thromboembolism; endovascular revascularisation for peripheral artery disease; aortic intervention or surgery; end stage kidney disease; discontinuation of study drugs owing to intolerance; cataract surgery; and a composite of laboratory detected abnormalities. RESULTS: 4341 of the 4400 participants (98.7%) completed the trial. Mean daily dose of study drugs was 17.1 mg (standard deviation (SD) 5.2 mg) in the rosuvastatin group and 36.0 (12.8) mg in the atorvastatin group at three years (P<0.001). The primary outcome occurred in 189 participants (8.7%) in the rosuvastatin group and 178 (8.2%) in the atorvastatin group (hazard ratio 1.06, 95% confidence interval 0.86 to 1.30; P=0.58). The mean low density lipoprotein (LDL) cholesterol level during treatment was 1.8 mmol/L (SD 0.5 mmol/L) in the rosuvastatin group and 1.9 (0.5) mmol/L in the atorvastatin group (P<0.001). The rosuvastatin group had a higher incidence of new onset diabetes mellitus requiring initiation of antidiabetics (7.2% v 5.3%; hazard ratio 1.39, 95% confidence interval 1.03 to 1.87; P=0.03) and cataract surgery (2.5% v 1.5%; 1.66, 1.07 to 2.58; P=0.02). Other safety endpoints did not differ between the two groups. CONCLUSIONS: In adults with coronary artery disease, rosuvastatin and atorvastatin showed comparable efficacy for the composite outcome of all cause death, myocardial infarction, stroke, or any coronary revascularisation at three years. Rosuvastatin was associated with lower LDL cholesterol levels but a higher risk of new onset diabetes mellitus requiring antidiabetics and cataract surgery compared with atorvastatin. TRIAL REGISTRATION: ClinicalTrials.gov NCT02579499.

The effect of magnesium sulfate on gene expression and serum level of inflammatory cytokines in coronary artery disease patients.

PURPOSE: To evaluate the effect of oral magnesium sulfate (MgSO4) on the gene expression and serum levels of inflammatory cytokines including TNF-α, IL-18, IL-1ß, IL-6, and IFN-γ in patients with moderate coronary artery disease (CAD). METHODS: 60 CAD patients were selected based on angiography findings and were randomly divided into two groups that received 300 mg/day MgSO4 (n = 30) or placebo (n = 30) for 3 months. Gene expression and serum levels of inflammatory cytokines were assessed. RESULTS: After 3 months of intervention, gene expression and serum levels of IL-18 and TNF-α in the MgSO4 group were significantly less than the placebo group (P < 0.05). However, no significant difference in gene expression and serum levels of IL-1ß, IL-6, and IFN-γ was observed between the two groups (P > 0.05). In addition, within group analysis demonstrate that Mg-treatment significantly decrease serum level of TNF-α and IL-18 as compared to pretreatment. CONCLUSION: The results of our study demonstrate that 3-month magnesium sulfate administration (300 mg/day) to CAD patients could significantly decrease serum concentration and gene expression levels of IL-18 and TNF-α. Our findings support the potential beneficial effect of magnesium supplementation on alleviating CAD complications through modulating inflammatory cytokines.

Effects of once-weekly glucagon-like peptide-1 receptor agonists on type 2 diabetes mellitus complicated with coronary artery disease: Potential role of the renin-angiotensin system.

AIM: To investigate the potential mechanism of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RA) in the treatment of type 2 diabetes mellitus (T2DM) complicated with coronary artery disease (CAD). METHODS: We searched both Chinese and English databases for randomized controlled trials related to once-weekly GLP-1 RA for T2DM complicated with CAD to verify the safety and efficacy of GLP-1 RA. The underlying mechanism was analysed by network pharmacology. RESULTS: In total, 13 studies with 35 563 participants were included in the analysis. The pooled analysis found that dulaglutide, exenatide and semaglutide outperformed placebo in cardiovascular outcomes in patients with T2DM, with a significant reduction in the incidence of non-fatal stroke (p < .00). Levels of cardiovascular risk factors were significantly reduced in the once-weekly GLP-1 RA group compared with the conventional treatment group (glycated haemoglobin: p < .00; fasting blood glucose: p < .00; weight: p < .00; systolic blood pressure: p < .00; total cholesterol: p < .00; low-density lipoprotein cholesterol: p < .00). Network pharmacology results were enriched to the renin-angiotensin system, and matrix metalloproteinase 2 and renin (REN) may be the key targets. In addition, four key targets of dulaglutide, five key targets of exenatide and two key targets of semaglutide were enriched. CONCLUSIONS: Our study suggests that once-weekly GLP-1 RA may have a potential protective effect on cardiovascular events in patients with T2DM combined with CAD, possibly through the renin-angiotensin system. However, further research is needed to confirm these findings and determine cause and effect.

Prognostic value of coronary atherosclerosis and CAC score for the risk of chemotherapy-related cardiac dysfunction (CTRCD): The protocol of ANTEC study.

BACKGROUND: Cardiological complications of oncological treatment, including the most serious one, heart failure, constitute a significant and still unsolved clinical problem. A history of dyslipidemia and complications of atherosclerosis, including coronary artery disease, are established risk factors for cardiotoxicity in cancer patients. In recent years, a protective effect of statin treatment on the development of heart failure in cancer patients has been observed. This protocol describes a study aiming to assess the prognostic value of coronary atherosclerosis burden and the CAC score on the onset of cardiac dysfunction associated with cancer therapy. METHODS: ANTEC (Atherosclerosis iN chemoTherapy-rElated Cardiotoxicity) is a single-site, prospective, observational study to evaluate the influence of the coronary atherosclerosis and CAC score assessed by computed tomography on the development of left ventricular systolic dysfunction in cancer patients with at least moderate cardiotoxicity risk. A group of 80 patients diagnosed with cancer prior to high-dose anthracycline chemotherapy (doxorubicin ≥ 240 mg / m2 body weight or epirubicin ≥ 600 mg / m2 body weight), without a history of heart failure and coronary artery disease, will be included in the study. Patient follow-up is planned for 12 months. In all patients, coronary computed tomographic angiography (CCTA) will be performed once at the beginning of the study. The primary endpoint is the onset of cancer therapy-related cardiovascular toxicity, defined as mild, moderate, severe and very severe according to ESC 2022 Cardio-oncology guidelines. During follow up, echocardiography with GLS assessment will be performed every three months. Additionally, new biomarkers of atherosclerosis (IL-6, MPO, TNF-alpha) will be measured every 6 months. The study registration identifier on clinicaltrials.gov is NCT05118178. CLINICAL TRIALS REGISTRY: This study is listed on cinicaltrials.gov with identifier NCT05118178.

Predictors of functional and morphological arterial wall properties in coronary artery disease patients with increased lipoprotein (a) levels before and after treatment with proprotein convertase subtilisin-kexin type 9 inhibitors.

BACKGROUND: In addition to proatherogenic properties, lipoprotein (a) (Lp(a)) has also pro-inflammatory, antifibrinolytic and prothrombogenic features. The aim of the current study was to identify the predictors of functional and morphological properties of the arterial wall in patients after myocardial infarction and increased Lp(a) levels at the beginning and after treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors. METHODS: Seventy-six post-myocardial infarction patients with high Lp(a) levels were included in the study. Ultrasound measurements of flow-mediated dilation of brachial artery (FMD), carotid intima-media thickness (c-IMT) and pulse wave velocity (PWV) were performed initially and after 6 months of treatment. At the same time points lipids, Lp(a), inflammatory and hemostasis markers were measured in blood samples. RESULTS: In linear regression model FMD significantly correlated with age at first myocardial infarction (ß = 0.689; p = 0.022), high-sensitivity C-reactive protein (ß = -1.200; p = 0.009), vascular cell adhesion protein 1 (VCAM-1) (ß = -0.992; p = 0.006), overall coagulation potential (ß = 1.428; p = 0.014) and overall hemostasis potential (ß = -1.473; p = 0.008). c-IMT significantly correlated with age at first myocardial infarction (ß = 0.574; p = 0.033) and Lp(a) (ß = 0.524; p = 0.040). PWV significantly correlated with systolic blood pressure (ß = 0.332; p = 0.002), tumor necrosis factor alpha (ß = 0.406; p = 0.002), interleukin-8 (ß = -0.315; p = 0.015) and plasminogen activator inhibitor 1 (ß = 0.229; p = 0.031). After treatment FMD reached statistical significance only in univariant analysis with systolic blood pressure (r = -0.286; p = 0.004) and VCAM-1 (r = -0.229; p = 0.024). PWV and c-IMT correlated with age (r = 0.334; p = 0.001 and r = 0.486; p < 0.0001, respectively) and systolic blood pressure (r = 0.556; p < 0.0001 and r = 0.233; p = 0.021, respectively). CONCLUSIONS: Our results suggest that age, systolic blood pressure, Lp(a) levels and other biochemical markers associated with Lp(a) are predictors of functional and morphological properties of the arterial vessel wall in post-myocardial patients with high Lp(a) levels initially. However, after 6 months of treatment with PCSK9 inhibitors only age and systolic blood pressure seem to be predictors of these properties. TRIAL REGISTRATION: The protocol for this study was registered with clinicaltrials.gov on November, 3 2020 under registration number NCT04613167.

P2Y12 Inhibitor or Aspirin Monotherapy for Secondary Prevention of Coronary Events.

BACKGROUND: Aspirin is the only antiplatelet agent with a Class I recommendation for long-term prevention of cardiovascular events in patients with coronary artery disease (CAD). There is inconsistent evidence on how it compares with alternative antiplatelet agents. OBJECTIVES: This study compared P2Y12 inhibitor monotherapy vs aspirin in patients with CAD. METHODS: We conducted a patient-level meta-analysis of randomized trials comparing P2Y12 inhibitor monotherapy vs aspirin monotherapy for the prevention of cardiovascular events in patients with established CAD. The primary outcome was the composite of cardiovascular death, myocardial infarction, and stroke. Prespecified key secondary outcomes were major bleeding and net adverse clinical events (the composite of the primary outcome and major bleeding). Data were pooled in a 1-step meta-analysis. RESULTS: Patient-level data were obtained from 7 trials. Overall, 24,325 participants were available for analysis, including 12,178 patients assigned to receive P2Y12 inhibitor monotherapy (clopidogrel in 7,545 [62.0%], ticagrelor in 4,633 [38.0%]) and 12,147 assigned to receive aspirin. Risk of the primary outcome was lower with P2Y12 inhibitor monotherapy compared with aspirin over 2 years (HR: 0.88; 95% CI: 0.79-0.97; P = 0.012), mainly owing to less myocardial infarction (HR: 0.77; 95% CI: 0.66-0.90; P < 0.001). Major bleeding was similar (HR: 0.87; 95% CI: 0.70-1.09; P = 0.23) and net adverse clinical events were lower (HR: 0.89; 95% CI: 0.81-0.98; P = 0.020) with P2Y12 inhibitors. The treatment effect was consistent across prespecified subgroups and types of P2Y12 inhibitors. CONCLUSIONS: Given its superior efficacy and similar overall safety, P2Y12 inhibitor monotherapy might be preferred over aspirin monotherapy for long-term secondary prevention in patients with established CAD. (P2Y12 Inhibitor or Aspirin Monotherapy as Secondary Prevention in Patients With Coronary Artery Disease: An Individual Patient Data Meta-Analysis of Randomized Trials [PANTHER collaborative initiative]; CRD42021290774).