Imaging of the brain-heart axis: prognostic value in a European setting.

BACKGROUND AND AIMS: Increasing data suggest that stress-related neural activity (SNA) is associated with subsequent major adverse cardiovascular events (MACE) and may represent a therapeutic target. Current evidence is exclusively based on populations from the U.S. and Asia where limited information about cardiovascular disease risk was available. This study sought to investigate whether SNA imaging has clinical value in a well-characterized cohort of cardiovascular patients in Europe. METHODS: In this single-centre study, a total of 963 patients (mean age 58.4 ± 16.1 years, 40.7% female) with known cardiovascular status, ranging from 'at-risk' to manifest disease, and without active cancer underwent 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography between 1 January 2005 and 31 August 2019. Stress-related neural activity was assessed with validated methods and relations between SNA and MACE (non-fatal stroke, non-fatal myocardial infarction, coronary revascularization, and cardiovascular death) or all-cause mortality by time-to-event analysis. RESULTS: Over a maximum follow-up of 17 years, 118 individuals (12.3%) experienced MACE, and 270 (28.0%) died. In univariate analyses, SNA significantly correlated with an increased risk of MACE (sub-distribution hazard ratio 1.52, 95% CI 1.05-2.19; P = .026) or death (hazard ratio 2.49, 95% CI 1.96-3.17; P < .001). In multivariable analyses, the association between SNA imaging and MACE was lost when details of the cardiovascular status were added to the models. Conversely, the relationship between SNA imaging and all-cause mortality persisted after multivariable adjustments. CONCLUSIONS: In a European patient cohort where cardiovascular status is known, SNA imaging is a robust and independent predictor of all-cause mortality, but its prognostic value for MACE is less evident. Further studies should define specific patient populations that might profit from SNA imaging.

Differential regulation of miRNAs involved in the susceptible and resistance responses of wheat cultivars to wheat streak mosaic virus and Triticum mosaic virus.

BACKGROUND: Wheat streak mosaic virus (WSMV) and Triticum mosaic virus (TriMV) are components of the wheat streak mosaic virus disease complex in the Great Plains region of the U.S.A. and elsewhere. Co-infection of wheat with WSMV and TriMV causes synergistic interaction with more severe disease symptoms compared to single infections. Plants are equipped with multiple antiviral mechanisms, of which regulation of microRNAs (miRNAs) is a potentially effective constituent. In this investigation, we have analyzed the total and relative expression of miRNA transcriptome in two wheat cultivars, Arapahoe (susceptible) and Mace (temperature-sensitive-resistant), that were mock-inoculated or inoculated with WSMV, TriMV, or both at 18 °C and 27 °C. RESULTS: Our results showed that the most abundant miRNA family among all the treatments was miRNA166, followed by 159a and 168a, although the order of the latter two changed depending on the infections. When comparing infected and control groups, twenty miRNAs showed significant upregulation, while eight miRNAs were significantly downregulated. Among them, miRNAs 9670-3p, 397-5p, and 5384-3p exhibited the most significant upregulation, whereas miRNAs 319, 9773, and 9774 were the most downregulated. The comparison of infection versus the control group for the cultivar Mace showed temperature-dependent regulation of these miRNAs. The principal component analysis confirmed that less abundant miRNAs among differentially expressed miRNAs were strongly correlated with the inoculated symptomatic wheat cultivars. Notably, miRNAs 397-5p, 398, and 9670-3p were upregulated in response to WSMV and TriMV infections, an observation not yet reported in this context. The significant upregulation of these three miRNAs was further confirmed with RT-qPCR analysis; in general, the RT-qPCR results were in agreement with our computational analysis. Target prediction analysis showed that the miRNAs standing out in our analysis targeted genes involved in defense response and regulation of transcription. CONCLUSION: Investigation into the roles of these miRNAs and their corresponding targets holds promise for advancing our understanding of the mechanisms of virus infection and possible manipulation of these factors for developing durable virus resistance in crop plants.

Cardiovascular Risk in Prostate Cancer Patients Using Luteinizing Hormone-Releasing Hormone Agonists or a Gonadotropin-Releasing Hormone Antagonist.

PURPOSE: Luteinizing hormone-releasing hormone (LHRH) agonists are believed to have higher cardiovascular risk relative to gonadotropin-releasing hormone (GnRH) antagonists. However, previous studies have not consistently demonstrated this. We used real-world clinical practice data to evaluate differences in major adverse cardiovascular events (MACE) risk between LHRH agonists compared to a GnRH antagonist following androgen deprivation therapy (ADT) initiation. MATERIALS AND METHODS: We performed a retrospective analysis of data in the Decision Resources Group (now Clarivate) Real World Evidence repository, which represents >300 million US patients from 1991 to 2020 across all US regions. Patients with prostate cancer who received at least 1 injection of ADT were included. The risks of MACE and all-cause mortality as independent endpoints were evaluated, Kaplan-Meier curves were constructed, and associations between MACE and all available confounding risk factors were evaluated by Cox regression analysis using Statistical Package for the Social Sciences. RESULTS: A total of 45,059 men with prostate cancer treated with ADT were analyzed. Overall, the risks of MACE and all-cause mortality were slightly lower in the first year after ADT initiation compared to subsequent years. MACE risk was higher for the GnRH antagonist compared to LHRH agonists (HR=1.62; 95% CI 1.21-2.18, P = .001). The risk of all-cause mortality was also higher for the GnRH antagonist vs LHRH agonists (HR=1.87; 95% CI 1.39-2.51, P < .001). CONCLUSIONS: The adjusted incidence of MACE was higher for men treated with the GnRH antagonist compared to the LHRH agonists. The demographic and risk factors with the greatest impact on MACE risk were higher age, baseline metastasis, oncology (vs urology) setting, personal MACE history, antagonist (vs agonist), tobacco history, White (vs Black) race, and lower BMI.

Major cardiovascular events in patients with cardiovascular monosodium urate deposits in atherosclerotic plaques.

OBJECTIVE: To determine the association of cardiovascular atherosclerotic plaque monosodium urate deposits with the occurrence of major cardiovascular events in gout and hyperuricemia patients. METHODS: This retrospective cohort study included patients with clinically suspicion of gout, who performed a dual energy computed tomography of the affected limb and thorax between June 1st, 2012 and December 5th, 2019. Clinical and laboratory parameters were retrieved from patients charts. Established cardiovascular risk factors were evaluated. Medical history review identified the presence of major adverse cardiac events with a median follow up time of 33 months (range 0-108 months) after the performed computed tomography scan. RESULTS: Full data sets were available for 189 patients: 131 (69.3%) gout patients, 40 (21.2%) hyperuricemia patients, and 18 (9.5%) controls. Patients with cardiovascular monosodium urate deposits (n = 85/189, 45%) revealed increased serum acute phase reactants, uric acid levels and calcium scores in computed tomography compared with patients without cardiovascular monosodium urate deposits. Major adverse cardiac events were observed in 35 patients (18.5%) with a higher prevalence in those patients revealing cardiovascular monosodium urate deposits (n = 22/85, 25.9%) compared with those without cardiovascular monosodium urate deposits (n = 13/104, 12.5%, OR 2.4, p= 0.018). CONCLUSION: This is the first study demonstrating the higher hazard of major adverse cardiac events in patients with dual energy computed tomography-verified cardiovascular monosodium urate deposits. The higher prevalence of cardiac events in patients with cardiovascular monosodium urate deposits may facilitate risk stratification of gout patients, as classical cardiovascular risk scores or laboratory markers fail in their proper identification.

Protein glycation products associate with progression of kidney disease and incident cardiovascular events in individuals with type 1 diabetes.

BACKGROUND: Despite improved glycemic treatment, the impact of glycation on pathological consequences may persist and contribute to adverse clinical outcomes in diabetes. In the present study we investigated the association between serum protein glycation products and progression of kidney disease as well as incident major adverse cardiovascular events (MACE) in type 1 diabetes. METHODS: Fructosamine, advanced glycation end products (AGEs), and methylglyoxal-modified hydro-imidazolone (MG-H1) were measured from baseline serum samples in the FinnDiane study (n = 575). Kidney disease progression was defined as steep eGFR decline (> 3 mL/min/1.73 m2/year) or progression of albuminuria (from lower to higher stage of albuminuria). MACE was defined as acute myocardial infarction, coronary revascularization, cerebrovascular event (stroke), and cardiovascular death. RESULTS: Fructosamine was independently associated with steep eGFR decline (OR 2.15 [95% CI 1.16-4.01], p = 0.016) in the fully adjusted model (age, sex, baseline eGFR). AGEs were associated with steep eGFR decline (OR 1.58 per 1 unit of SD [95% CI 1.07-2.32], p = 0.02), progression to end-stage kidney disease (ESKD) (HR 2.09 per 1 unit of SD [95% CI 1.43-3.05], p < 0.001), and pooled progression (to any stage of albuminuria) (HR 2.72 per 1 unit of SD [95% CI 2.04-3.62], p < 0.001). AGEs (HR 1.57 per 1 unit of SD [95% CI 1.23-2.00], p < 0.001) and MG-H1 (HR 4.99 [95% CI 0.98-25.55], p = 0.054) were associated with incident MACE. MG-H1 was also associated with pooled progression (HR 4.19 [95% CI 1.11-15.89], p = 0.035). Most AGEs and MG-H1 associations were no more significant after adjusting for baseline eGFR. CONCLUSIONS: Overall, these findings suggest that protein glycation products are an important risk factor for target organ damage in type 1 diabetes. The data provide further support to investigate a potential causal role of serum protein glycation in the progression of diabetes complications.

GLP-1 receptor agonists-SGLT-2 inhibitors combination therapy and cardiovascular events after acute myocardial infarction: an observational study in patients with type 2 diabetes.

BACKGROUND: Few studies explored the effect of the combination of glucose sodium-cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on the incidence of cardiovascular events in patients with type 2 diabetes (T2D) and acute myocardial infarction (AMI). METHODS: We recruited patients with T2D and AMI undergoing percutaneous coronary intervention, treated with either SGLT-2i or GLP-1RA for at least 3 months before hospitalization. Subjects with HbA1c < 7% at admission were considered in good glycemic control and maintained the same glucose-lowering regimen, while those with poor glycemic control (HbA1c ≥ 7%), at admission or during follow-up, were prescribed either a SGLT-2i or a GLP-1RA to obtain a SGLT-2i/GLP-1RA combination therapy. The primary outcome was the incidence of major adverse cardiovascular events (MACE) defined as cardiovascular death, re-acute coronary syndrome, and heart failure related to AMI during a 2-year follow-up. After 3 months, the myocardial salvage index (MSI) was assessed by single-photon emission computed tomography. FINDINGS: Of the 537 subjects screened, 443 completed the follow-up. Of these, 99 were treated with SGLT-2i, 130 with GLP-1RA, and 214 with their combination. The incidence of MACE was lower in the combination therapy group compared with both SGLT-2i and GLP-1RA treated patients, as assessed by multivariable Cox regression analysis adjusted for cardiovascular risk factors (HR = 0.154, 95% CI 0.038-0.622, P = 0.009 vs GLP-1RA and HR = 0.170, 95% CI 0.046-0.633, P = 0.008 vs SGLT-2i). The MSI and the proportion of patients with MSI > 50% was higher in the SGLT-2i/GLP-1RA group compared with both SGLT-2i and GLP-1RA groups. INTERPRETATION: The combination of SGLT-2i and GLP-1RA is associated with a reduced incidence of cardiovascular events in patients with T2D and AMI compared with either drug used alone, with a significant effect also on peri-infarcted myocardial rescue in patients without a second event. Trial registraition ClinicalTrials.gov ID: NCT06017544.

BMI variability and cardiovascular outcomes within clinical trial and real-world environments in type 2 diabetes: an IMI2 SOPHIA study.

BACKGROUND: BMI variability has been associated with increased cardiovascular disease risk in individuals with type 2 diabetes, however comparison between clinical studies and real-world observational evidence has been lacking. Furthermore, it is not known whether BMI variability has an effect independent of HbA1c variability. METHODS: We investigated the association between BMI variability and 3P-MACE risk in the Harmony Outcomes trial (n = 9198), and further analysed placebo arms of REWIND (n = 4440) and EMPA-REG OUTCOME (n = 2333) trials, followed by real-world data from the Tayside Bioresource (n = 6980) using Cox regression modelling. BMI variability was determined using average successive variability (ASV), with first major adverse cardiovascular event of non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death (3P-MACE) as the primary outcome. RESULTS: After adjusting for cardiovascular risk factors, a + 1 SD increase in BMI variability was associated with increased 3P-MACE risk in Harmony Outcomes (HR 1.12, 95% CI 1.08-1.17, P < 0.001). The most variable quartile of participants experienced an 87% higher risk of 3P-MACE (P < 0.001) relative to the least variable. Similar associations were found in REWIND and Tayside Bioresource. Further analyses in the EMPA-REG OUTCOME trial did not replicate this association. BMI variability's impact on 3P-MACE risk was independent of HbA1c variability. CONCLUSIONS: In individuals with type 2 diabetes, increased BMI variability was found to be an independent risk factor for 3P-MACE across cardiovascular outcome trials and real-world datasets. Future research should attempt to establish a causal relationship between BMI variability and cardiovascular outcomes.

Cardiac risk after elective endovascular repair for infrarenal abdominal aortic aneurysm: Results from the Italian Collaborators for EVAR multicenter registry.

OBJECTIVE: Major adverse cardiac events (MACEs) were common complications after endovascular aortic repair (EVAR) causing significant postoperative morbidity and mortality. The aim of the study was to evaluate the cardiac risk after elective EVAR for uncomplicated noninfected infrarenal abdominal aortic aneurysm in a large multicenter cohort. METHODS: This is a multicenter, retrospective, financially unsupported physician-initiated observational cohort study conducted by four academic tertiary referral hospitals from January 2018 to March 2021. Baseline, perioperative, and postoperative information of elective EVARs was evaluated. The primary outcome was the incidence of MACEs after EVAR, which was defined as acute coronary syndrome, non-ST-elevation myocardial infarction, unstable angina pectoris, de novo atrial fibrillation, hospitalization for heart failure, and revascularization as well as cardiovascular death. Secondary outcomes were 1-year overall survival (all-cause mortality) and freedom from aorta-related mortality. Comparative analysis was conducted between MACE and overall population, and univariate and multivariate logistic regression analyses were used to analyze factors associated with the risk of the MACE occurrence and early 1-year mortality. RESULTS: The study has enrolled 497 patients (35 females, 7%) with a mean age of 75.3 ± 7.8 years. The MACE rate was 6.4% (32/497, events/patients), and the majority of the events were recorded in the postoperative period (24/32, 75%; overall 24/497, 4.8%). One-year survival from all-cause mortality was 94% (95% confidence interval [CI]: 91-96), and the MACE population showed a significantly lower survival estimation rate (Overall - MACEs, 95.8% [95% CI: 93-97] - 67.9% [95% CI: 47-82], log-rank 41.950, P = .0001). Freedom from aorta-related mortality was 99.3% (95% CI: 98-100). The perioperative need for red blood cell transfusions was strongly related to the MACE occurrence (odds ratio: 2.67, 95% CI: 1.52-4.68, P = .001) and 1-year mortality (hazard ratio: 2.14, 95% CI: 1.48-3.09, P = .0001). CONCLUSIONS: MACEs represent a common complication in the postoperative and early period after elective EVAR. Blood loss requiring red blood cell transfusions is associated with increased postoperative MACEs and early mortality, suggesting that all the efforts should be carried out to reduce the bleeding during and after elective interventions.

Proficiently partitioning of bioactive peptide-ssDNA conjugates by microbead-assisted capillary electrophoresis (MACE).

Low-molecular drug discovery using DNA-encoded chemical library (DEL) is a powerful technology, although improving the partitioning efficiency of affinity ligands from DEL remains a challenge. Here, we assessed the usefulness of microbead-assisted capillary electrophoresis (MACE) for partitioning peptide-oligonucleotide conjugates (POCs), in which high selection pressure is applied because of different mobility of target-modified beads and POCs during CE. Despite their different charge characteristics, all POCs were well separated from the beads. When bead extraction was performed, the tagged DNA amplification was observed only in the couple of a ligand/target, suggesting proficiently specific partitioning of peptide ligands was accomplished using MACE.

Proximal optimization technique and percutaneous coronary intervention for left main disease: POTENTIAL-LM.

BACKGROUND: Optimal stent deployment in left main (LM) bifurcation is paramount, and incomplete stent apposition may cause major adverse cardiac events (MACE). Bench studies show that the proximal optimization technique (POT) provides the best stent apposition. AIMS: We aimed to investigate the impact of POT on clinical outcomes in patients treated for unprotected LM (ULM) disease at our institution. METHODS: We identified 162 patients who underwent percutaneous coronary intervention (PCI) for ULM coronary disease in the Cardio-FR database. Out of these, 99 (61%) had undergone POT, while 63 patients were treated without POT. The primary outcome was the bifurcation-oriented composite endpoint (BOCE) of cardiac death, target-bifurcation myocardial infarction and target-bifurcation revascularization at maximal follow-up. RESULTS: Mean age was 76 years, and 69% presented with acute coronary syndrome. Mean follow-up was 2.25 years (822 days). The BOCE occurred in 43 (27%) of which 20 (20%) in the POT group and 23 (37%) in the no-POT group (p = 0.009). Cardiac death occurred in 15 (15%) patients in the POT- and 17 (27%) in no-POT group (p = 0.26). Target bifurcation revascularization occurred in 4 (4%) patients in the POT- and 6 (10%) patients in the no-POT group (p = 0.19). POT In the multivariate analysis, POT was the strongest parameter and was associated with BOCE, cardiac death, occurrence of any revascularization and all-cause mortality. CONCLUSION: The POT improves clinical outcomes. These findings strongly support the systematic use of POT in patients undergoing ULM-PCI.

Population-wide eGFR percentiles in younger adults and clinical outcomes.

BACKGROUND AND HYPOTHESIS: Identifying meaningful estimated glomerular filtration rate (eGFR) reductions in younger adults (<65 years) could guide prevention efforts. To aid in interpretation and identification of young adults at risk, we examined the association of population-level eGFR percentiles relative to the median by age and clinical outcomes. METHODS: We conducted a retrospective cohort study of 8.7 million adults from Ontario, Canada from age 18 to 65 from 2008 to 2021 with an eGFR measure (both single outpatient value and repeat measures). We calculated median eGFR values by age and examined the association of reduced eGFR percentiles (≤10th, 5th, 2.5th and 1st) with outcomes using time to event models. Outcomes were a composite of all-cause mortality, major adverse cardiac outcomes (MACE) with/without heart failure (MACE+) and kidney failure as well as each component individually. RESULTS: From age 18 to 65, the median eGFR declined with age (range 128 to 90) and across percentiles [eGFR ranges 102 to 68 for ≤10th, 96 to 63 for ≤5th, 90 to 58 for ≤2.5th and 83 to 54 for 1st]. The adjusted rate for any adverse outcome was elevated at ≤ 10th percentile (HR 1.14 95%CI 1.10-1.18) and was consistent for all-cause mortality, MACE, MACE+ and predominant for kidney failure (HR 5.57 95%CI 3.79-8.19) compared to the median eGFR for age. Young adults with an eGFR in the lower percentiles were less likely to be referred to a specialist, have a repeat eGFR or albumin to creatinine ratio measure. CONCLUSIONS: eGFR values at the 10th percentile or lower based on a population-level distribution are associated with adverse clinical outcomes and in younger adults (18 to 39) this corresponds to a higher level of eGFR that may be underrecognized. Application of population-based eGFR percentiles may aid interpretation and improve identification of younger adults at risk.

Effects of hypoglycaemic agents on reducing surrogate metabolic parameters for the prevention of cardiovascular events and death in patients with type 2 diabetes: A systematic review and meta-analysis.

AIMS: To investigate the impact of glucose-lowering therapy-induced glycated haemoglobin (HbA1c) reduction on the risk of major clinical events according to body weight change and, as a secondary objective, to evaluate the impact of concomitant reductions in HbA1c and body weight on major clinical events. MATERIALS AND METHODS: We searched the MEDLINE and EMBASE databases up to June 30, 2022, for large-scale studies on glucose-lowering therapies in which more than 1000 patient-years of follow-up in each randomized group were completed. The primary outcome was all-cause mortality. The study was registered in PROSPERO (CRD42022355479). RESULTS: Thirty-four trials involving 227 220 patients with type 2 diabetes were meta-analysed using a random-effects model. Each 1% reduction in HbA1c was associated with a different risk of mortality depending on the ability of glucose-lowering therapies to induce body weight loss or gain. When glucose-lowering therapies were associated with weight gain, the risk of mortality increased by 8% (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.00-1.16) for each 1% reduction in HbA1c. When glucose-lowering therapies were associated with weight loss, the risk of mortality was reduced by 22% (HR 0.78, 95% CI 0.72-0.85) for each 1% reduction in HbA1c. In addition, concomitant reductions in HbA1c and body weight were associated with a significantly lower risk of mortality and vascular events. CONCLUSIONS: In patients with type 2 diabetes, concomitant reductions in HbA1c and body weight might be more effective in preventing the risk of vascular events and mortality.

Integration of silicon nanostructures for health and energy applications using MACE: a cost-effective process.

Silicon in its nanoscale range offers versatile scope in biomedical, photovoltaic and solar cell applications. Due to its compatibility in integration with complex molecules owing to changes in charge density of as-fabricated SiNSs to realize label-free and real-time detection of certain biological and chemical species with certain biomolecules, it can be exploited as an indicator for ultra-sensitive and cost-effective biosensing applications in disease diagnosis. The morphological changes of SiNSs modified receptors (PNA, DNA etc) finds huge future scope in optimized sensitivity (due to conductance variations of SiNSs) of target biomolecules in health care applications. Further, due to unique optical and electrical properties of SiNSs realized using chemical etching technique, they can be used as an indicator for photovoltaic and solar cell applications. In this review, emphasis is done on different critical parameters that control the fabrication morphologies of SiNSs using metal assisted chemical etching technique (MACE) and its corresponding fabrication mechanisms focussing on numerous applications in energy storage and health care domains. The evolution of MACE as a low cost, easy process control, reproducibility and convenient fabrication mechanism makes it a highly reliable-process friendly technique employed in photovoltaic, energy storage and biomedical fields. Analysis of the experimental fabrication to obtain high aspect ratio SiNSs was carried out using iMAGE J software for understanding the role of surface to volume ratio in effective bacterial interfacing. Also, the role of Silicon nanomaterials has been discussed as effective anti-bacterial surfaces due to the presence of Silver investigated in the post fabrication Energy Dispersive X-Ray Spectroscopy (EDS) analysis using MACE.

Perspectives on the Cardiovascular and Metabolic Effects of Androgen Deprivation Therapy in Prostate Cancer.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is the leading cause of non-cancer mortality in men with prostate cancer. This review summarizes the existing and emerging literature examining the cardiometabolic effects of androgen deprivation therapy (ADT) in prostate cancer. RECENT FINDINGS: The evidence behind the metabolic effects of ADT is derived from older studies and has not been validated in modern cohorts. Most of the newer studies focus on the risk of cardiovascular disease (CVD) with ADT. Recently published studies like the HERO and PRONOUNCE trials have once again sparked debate about the effects of different types and durations of ADT on cardiovascular outcomes. The link between ADT and CVD is inherently complex with a majority of the evidence collected from population-based or non-randomized trials without enriching for high-risk populations. Ongoing clinical trials may provide more informative data to guide the cardiovascular care of prostate cancer survivors.

Bempedoic Acid: How Will It Shape the Future Lipid-Lowering Landscape? Mode of Action, Evidence, and Clinical Use.

BACKGROUND: Low-density lipoproteins are now proven to be causal for atherosclerosis. Pharmacological treatment focuses on an increase of low-density lipoprotein (LDL) receptors, particularly in the hepatocyte, which leads to uptake of LDL from blood, thereby reducing the burden to the arterial wall. This mechanism has first been proven by statins to be effective to reduce cardiovascular morbidity and mortality. The concept of "the lower, the better" was shown by high-intensity statins and new compounds like ezetimibe, PCSK9 antibodies, inclisiran, and ultimately bempedoic acid. SUMMARY: Although first considered only a relatively weak LDL-C lowering drug, bempedoic acid proved to be very effective, for example, in statin-intolerant patients to reduce cardiovascular events in the CLEAR-Outcomes study. In the era of personalized medicine, it should not be forgotten that the individual response to a LDL-C lowering drug can vary considerably. Bempedoic acid has a favorable safety profile, particularly it does not induce muscle problems because its precursor is not metabolized to the active drug in the muscle, and it does not induce hyperglycemia. Bempedoic acid probably is best used in combination with ezetimibe, which leads to LDL-C reductions in the range of moderately intensive statins; in an oral triple combination with a high-intensity statin, LDL-C reductions in the range of two-thirds can be achieved. KEY MESSAGES: Bempedoic acid is a further weapon against the atherogenic effect of LDL cholesterol - in both primary and secondary prevention.

Glycemic control target for liver and cardiovascular events risk in metabolic dysfunction-associated steatotic liver disease.

AIMS: Optimizing glycemic control may prevent liver-related events and major adverse cardiovascular events (MACE) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, the optimal hemoglobin A1c (HbA1c) threshold associated with a lower risk of complications, particularly liver-related events as well as MACE is unknown. METHODS: We investigated a nationwide population-based cohort and identified 633 279 patients with MASLD, with a mean follow-up of 4.2 years. Hemoglobin A1c levels were measured annually. The primary endpoint was the risk of liver-related events and MACE and to determine the optimal HbA1c level associated with the risk of complications. RESULTS: Mean HbA1c (per 1%) was associated with liver-related events (subdistribution hazard ratio [sHR] 1.26; 95% confidence interval [CI], 1.12-1.42) as well as MACE (sHR 1.36; 95% CI, 1.32-1.41) after adjustment for confounders. Multivariable sHR (95% CI) for HbA1c of <5.0%, 6.0%-6.9%, 7.0%-7.9%, 8.0%-8.9%, and ≥9.0% (reference, 5.0%-5.9%) were 14 (9.1-22), 1.70 (1.2-2.3), 3.32 (2.3-4.8), 3.81 (2.1-6.8), and 4.83 (2.4-9.6) for liver-related events, and 1.24 (0.8-1.8), 1.27 (1.2-1.4), 1.70 (1.5-2.0), 2.36 (1.9-2.9), and 4.17 (3.5-5.0) for MACE. An HbA1c level of 7% was selected as the optimal threshold for predicting complications (sHR 2.40 [1.8-3.2] for liver-related events and 1.98 [1.8-2.2] for MACE). CONCLUSION: The risk of liver-related events as well as MACE increased in a dose-dependent fashion with an increase in HbA1c levels, except for patients with HbA1c <5.0% for liver-related events. An HbA1c level of 7% was the optimal threshold associated with a lower risk of complications and may be utilized as a target for glycemic control in patients with MASLD.

Coronary artery disease severity and risk stratification of patients with non ST-elevation acute coronary syndrome using CHA2DS2-VASc-HSF score.

BACKGROUND: Risk stratification assessment of patients with non-ST elevation acute coronary syndrome (NSTE ACS) plays an important role in optimal management and defines the patient's prognosis. This study aimed to evaluate the ability of CHA2DS2-VASc-HSF score (comprising of the components of the CHA2DS2-VASc score with a male instead of female sex category, hyperlipidemia, smoking, and family history of coronary artery disease respectively) to predict the severity and complexity of CAD and its efficacy in stratification for major adverse cardiovascular events (MACE) in patients with NSTE ACS without known atrial fibrillation. METHODS: This study included 200 patients (males 72.5%, mean age 55.8 ± 10.1 years) who were admitted with NSTE ACS. CHA2DS2-VASC-HSF score was calculated on admission. Patients were classified into three groups according to their CHA2DS2-VASC-HSF score: low score group (< 2; 29 patients), intermediate score group (2-4; 83 patients), and high score group (≥ 5; 88 patients). Coronary angiography was conducted and the Syntax score (SS) was calculated. Clinical follow-up at 6 months of admission for the development of MACE was recorded. RESULTS: SS was significantly high in the high CHA2DS2-VASc-HSF score group compared with low and intermediate score groups. CHA2DS2-VASc-HSF score had a significant positive strong correlation with syntax score (r = 0.64, P < 0.001). Smoking, vascular disease, hyperlipidemia, and CHA2DS2-VASc-HSF score were independent predictors of high SS. For the prediction of severe and complex CAD, CHA2DS2-VASc-HSF score had a good predictive power at a cut-off value ≥ 5 with a sensitivity of 86% and specificity of 65%. Hypertension, vascular disease, high SS, and CHA2DS2-VASc-HSF score were independent predictors of MACE. CHA2DS2-VASC-HSF score ≥ 4 was identified as an effective cut-off point for the development of MACE with 94% sensitivity and 70% specificity. CONCLUSIONS: CHA2DS2-VASC-HSF score is proposed to be a simple bedside score that could be used for the prediction of the severity and complexity of CAD as well as a risk stratification tool for the development of MACE in NSTE ACS patients.

Potential impact of blood cholesterol guidelines on statin treatment in the U.S. population using interrupted time series analysis.

BACKGROUND: The 2013 ACC/AHA Guideline was a paradigm shift in lipid management and identified the four statin-benefit groups. Many have studied the guideline's potential impact, but few have investigated its potential long-term impact on MACE. Furthermore, most studies also ignored the confounding effect from the earlier release of generic atorvastatin in Dec 2011. METHODS: To evaluate the potential (long-term) impact of the 2013 ACC/AHA Guideline release in Nov 2013 in the U.S., we investigated the association of the 2013 ACC/AHA Guideline with the trend changes in 5-Year MACE survival and three other statin-related outcomes (statin use, optimal statin use, and statin adherence) while controlling for generic atorvastatin availability using interrupted time series analysis, called the Chow's test. Specifically, we conducted a retrospective study using U.S. nationwide de-identified claims and electronic health records from Optum Labs Database Warehouse (OLDW) to follow the trends of 5-Year MACE survival and statin-related outcomes among four statin-benefit groups that were identified in the 2013 ACC/AHA Guideline. Then, Chow's test was used to discern trend changes between generic atorvastatin availability and guideline potential impact. RESULTS: 197,021 patients were included (ASCVD: 19,060; High-LDL: 33,907; Diabetes: 138,159; High-ASCVD-Risk: 5,895). After the guideline release, the long-term trend (slope) of 5-Year MACE Survival for the Diabetes group improved significantly (P = 0.002). Optimal statin use for the ASCVD group also showed immediate improvement (intercept) and long-term positive changes (slope) after the release (P < 0.001). Statin uses did not have significant trend changes and statin adherence remained unchanged in all statin-benefit groups. Although no other statistically significant trend changes were found, overall positive trend change or no changes were observed after the 2013 ACC/AHA Guideline release. CONCLUSIONS: The 2013 ACA/AHA Guideline release is associated with trend improvements in the long-term MACE Survival for Diabetes group and optimal statin use for ASCVD group. These significant associations might indicate a potential positive long-term impact of the 2013 ACA/AHA Guideline on better health outcomes for primary prevention groups and an immediate potential impact on statin prescribing behaviors in higher-at-risk groups. However, further investigation is required to confirm the causal effect of the 2013 ACA/AHA Guideline.

Machine learning prediction of major adverse cardiac events after elective bariatric surgery.

BACKGROUND: Machine learning (ML) is an emerging technology with the potential to predict and improve clinical outcomes including adverse events, based on complex pattern recognition. Major adverse cardiac events (MACE) after bariatric surgery have an incidence of 0.1% but carry significant morbidity and mortality. Prior studies have investigated these events using traditional statistical methods, however, studies reporting ML for MACE prediction in bariatric surgery remain limited. As such, the objective of this study was to evaluate and compare MACE prediction models in bariatric surgery using traditional statistical methods and ML. METHODS: Cross-sectional study of the MBSAQIP database, from 2015 to 2019. A binary-outcome MACE prediction model was generated using three different modeling methods: (1) main-effects-only logistic regression, (2) neural network with a single hidden layer, and (3) XGBoost model with a max depth of 3. The same set of predictor variables and random split of the total data (50/50) were used to train and validate each model. Overall performance was compared based on the area under the receiver operating curve (AUC). RESULTS: A total of 755,506 patients were included, of which 0.1% experienced MACE. Of the total sample, 79.6% were female, 47.8% had hypertension, 26.2% had diabetes, 23.7% had hyperlipidemia, 8.4% used tobacco within 1 year, 1.9% had previous percutaneous cardiac intervention, 1.2% had a history of myocardial infarction, 1.1% had previous cardiac surgery, and 0.6% had renal insufficiency. The AUC for the three different MACE prediction models was: 0.790 for logistic regression, 0.798 for neural network and 0.787 for XGBoost. While the AUC implies similar discriminant function, the risk prediction histogram for the neural network shifted in a smoother fashion. CONCLUSION: The ML models developed achieved good discriminant function in predicting MACE. ML can help clinicians with patient selection and identify individuals who may be at elevated risk for MACE after bariatric surgery.

Early coronary angiography in NSTEMI: a regional Victorian perspective.

BACKGROUND: Current guidelines highlight a paucity of evidence guiding optimal timing for non-ST-elevation myocardial infarction (NSTEMI) in high-risk and non-high-risk cases. AIM: We assessed long-term major adverse cardiovascular events (MACEs) in NSTEMI patients undergoing early (<24 h) versus delayed (>24 h) coronary angiography at 6 years. Secondary end-points included all-cause mortality and cumulative MACE outcomes. METHODS: Baseline characteristics and clinical outcomes were assessed among 355 patients presenting to a tertiary regional hospital between 2017 and 2018. Cox proportional hazard models were generated for MACE and all-cause mortality outcomes, adjusting for the Global Registry of Acute Coronary Events (GRACE) score, patient demographics, biomarkers and comorbidities. RESULTS: Two hundred and seventy patients were included; 147 (54.4%) and 123 (45.6%) underwent early and delayed coronary angiography respectively. Median time to coronary angiography was 13.3 and 45.4 h respectively. At 6 years, 103 patients (38.1%) experienced MACE; 41 in the early group and 62 in the delayed group (hazard ratio (HR) = 2.23; 95% confidence interval (CI) = 1.50-3.31). After multivariable adjustment, the delayed group had higher rates of MACE (HR = 1.79; 95% CI = 1.19-2.70), all-cause mortality (HR = 2.76; 95% CI = 1.36-5.63) and cumulative MACE (incidence rate ratio = 1.54; 95% CI = 1.12-2.11). Subgroup analysis of MACE outcomes in rural and weekend NSTEMI presentations was not significant between early and delayed coronary angiography (HR = 1.49; 95% CI = 0.83-2.62). CONCLUSION: Higher MACE rates in the delayed intervention group suggest further investigation is needed. Randomised control trials would be well suited to assess the role of early invasive intervention across all NSTEMI risk groups.