Risk Of Myocardial Infarction Research Articles

Increased perivascular fibrosis and pro-fibrotic cellular transition in intramyocardial blood vessels in patients with myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): China Scholarship Council Background Myocardial infarction (MI) is pathologically characterized by irreversible myocardial necrosis caused by ischemia. Intramyocardial vascular dysfunction is believed to increase the risk of MI. In this study, we investigated intramyocardial blood vessels in deceased patients during the early and chronic phases of MI to explore the involvement of perivascular fibrosis and pro-fibrotic cellular transitions in the pathological process of MI. Methods Left ventricular tissue (LV) was obtained from the infarction area of autopsied patients with early-phase MI (3-6 hours old; n=23), chronic-phase MI (5-14 days old; n=12), and from non-infarcted controls (n=14). We quantified perivascular fibrosis using EVG staining and fibroblast activation protein (FAP) expression using immunohistochemistry. Co-localization of smooth muscle actin (SMA) or CD31 with fibroblast marker S100A4 indicative of transition of smooth muscle cells (SMC) and endothelial cells (EC) toward fibroblast-like cells in intramyocardial vessels was quantified using immunofluorescent microscopy. Results Compared to controls (61.03%), perivascular fibrosis was significantly elevated in MI patients (early-phase 77.20%; chronic-phase 82.58%)(p<0.0001), with the highest level observed in the infarct cores of chronic-phase patients (95.18%). Compared to controls, FAP expression was 3.5-fold higher in early-phase- and 15.3-fold higher in chronic-phase MI patients (p<0.05), wherein FAP expression again was highest in the infarct cores. Furthermore, in both early- and chronic-phase MI, SMC- and EC fibroblast-like cellular transition was increased. The fraction of SMA+S100A4+ vessels was significantly higher in early-phase MI (31.96%) and chronic-phase MI (21.9%: border zone; 37.25%: infarct core) compared to controls (8.95%)(p<0.05). Similarly, the fraction of CD31+S100A4+ area was significantly increased in early-phase MI (10.14%) and chronic-phase MI (8.31%: border zone 10.15%: infarct core) compared to controls (2.67%)(p<0.05). Conclusion We observed increased perivascular fibrosis, fibroblast activation and fibroblast-like cellular transition toward a pro-fibrotic phenotype of vascular cells in intramyocardial blood vessels in MI patients, that may contribute to the development of MI. The further increase of FAP expression and perivascular fibrosis, particularly in the infarct core, in the chronic-phase suggest that MI itself can exacerbate fibroblast activation and perivascular fibrosis, theoretically increasing the risk of reinfarction.FAP expression and perivascular fibrosispro-fibrotic vascular cellular transitio

Murine matrix metalloproteinase 13 and human matrix metalloproteinase 1 are involved in remodelling processes after myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): German Centre for Cardiovascular Research (DZHK) Background Cardiovascular diseases such as myocardial infarction (MI) remain a leading cause of death in the world. Matrix metalloproteinases (MMPs) are not only essential for the cleavage of collagen, but are also modifying inflammatory cytokines. Thus, MMPs are playing a substantial role in the context of fibrotic as well as inflammatory processes in tissue remodelling after MI. Purpose Mmp13 is the highest expressed collagenase in the murine left ventricle (LV). After ligation of the left anterior descending artery (LAD) in mice, Mmp13 is highly upregulated in the LV. Therefore, the aim of this study was to characterize the role of MMP13 in MI. In the human LV, the highest expressed collagenase is MMP1. Single nucleotide polymorphisms (SNPs) in the promotor region of MMP1 can lead to alterations in gene expression level. Therefore, we analysed the genotype of 3 SNPs in about 2000 patients admitted to the emergency department with suspected MI to reveal associations with the development of MI and outcome after MI. Methods A MMP13-knockout (KO) mouse model was examined after induction of MI and gene expression analysis, histological staining, in-situ hybridisation and hemodynamic measurements were conducted. Mmp13 expression in different cardiac cell types was investigated at quiescent stage and under ischaemic conditions, to determine the cellular origin of Mmp13 expression. Out of the human cohort, 2 patient groups (non-MI and MI) were restricted. Hazard ratios adjusted to age and male sex were assessed, to evaluate risk for MI and risk for death after MI in dependency of the SNPs. Results After activation with ischaemic secretome of cardiomyocytes, the Mmp13 expression of macrophages (6.6-fold; p=0.0286) and fibroblasts (4.9-fold; p=0.0079) was significantly increased. Under stimulation with ischaemic secretome of fibroblasts, Mmp13 expression of macrophages (4.3-fold; p=0.0286) and leukocytes (2.3-fold; p=0.0260) was significantly elevated. Additionally, in situ hybridisation revealed Mmp13 expression in immune cells in the border zone of the infarct region. While the survival of WT mice was about 50%, only very few KO mice died after MI (p=0.0107). Moreover, KO mice showed benefits in cardiac function compared to WT littermates 28 days post-MI. In the human cohort, risk for death was significantly altered between the examined genotypes in 2 of 3 investigated SNPs, indicating a role of MMP1 in the remodelling process after MI. Conclusion High levels of Mmp13 after MI originate mainly from activated macrophages and from activated fibroblasts in the infarct border zone. MMP13-deficiency is beneficial for mice after MI, leading to an improved cardiac function 28 days post-MI compared to WT controls. Analysis of SNPs of the human functional homologue of Mmp13 – MMP1 – revealed an association of MMP1 with remodelling processes after MI.

Ensemble machine learning for predicting in-hospital mortality in Asian women with ST-elevation myocardial infarction (STEMI)

The accurate prediction of in-hospital mortality in Asian women after ST-Elevation Myocardial Infarction (STEMI) remains a crucial issue in medical research. Existing models frequently neglect this demographic's particular attributes, resulting in poor treatment outcomes. This study aims to improve the prediction of in-hospital mortality in multi-ethnic Asian women with STEMI by employing both base and ensemble machine learning (ML) models. We centred on the development of demographic-specific models using data from the Malaysian National Cardiovascular Disease Database spanning 2006 to 2016. Through a careful iterative feature selection approach that included feature importance and sequential backward elimination, significant variables such as systolic blood pressure, Killip class, fasting blood glucose, beta-blockers, angiotensin-converting enzyme inhibitors (ACE), and oral hypoglycemic medications were identified. The findings of our study revealed that ML models with selected features outperformed the conventional Thrombolysis in Myocardial Infarction (TIMI) Risk score, with area under the curve (AUC) ranging from 0.60 to 0.93 versus TIMI's AUC of 0.81. Remarkably, our best-performing ensemble ML model was surpassed by the base ML model, support vector machine (SVM) Linear with SVM selected features (AUC: 0.93, CI: 0.89–0.98 versus AUC: 0.91, CI: 0.87–0.96). Furthermore, the women-specific model outperformed a non-gender-specific STEMI model (AUC: 0.92, CI: 0.87–0.97). Our findings demonstrate the value of women-specific ML models over standard approaches, emphasizing the importance of continued testing and validation to improve clinical care for women with STEMI.

Frequency of CYP2C19, P2RY12, ITGB3, ITGA2, and eNOS3 gene polymorphism in patients with myocardial infarction

The aim of the study was to assess the distribution of polymorphic variants G681A (*2) of the CYP2C19 gene, H1/H2 of the P2RY12 gene, T1565C of the ITGB3 gene, C807T of the ITGA2 gene, and T786C of the eNOS3 gene in the population of the Grodno region, and to study their associations with myocardial infarction (MI). The study of the population consists of 493 people, including 400 patients with MI aged 31 to 74 years and 93 people of the control group aged 32 to 60 years. Research data (clinical and genotyping performed by polymerase chain reaction) were analyzed using STATISTICA 10.0 software. The prevalence of carriage of genotypes associated with high residual platelet reactivity and variability in response to dual antiplatelet therapy among patients with MI was 25.2 % for the G681A polymorphic locus of the CYP2C19 gene (GA + AA), and for the H1/H2 polymorphic locus of the P2RY12 gene (H1/H2 + H2/H2) – 40.0 %, for the C807T polymorphic locus of the ITGA2 gene (CT + TT) – 65.8, for the T1565C polymorphic locus of the ITGB3 gene (TC + CC) – 25.5, for the polymorphic locus T786C of the eNOS gene (TC + CC) – 69.2 %. Among the individuals of the control group, the frequency of occurrence of these genotypes was 18.3, 46.2, 60.2, 37.6, 48.4 %, respectively. In patients with MI, compared to the control group, the TT genotype of the eNOS gene was less common (χ2 = 13.6, p = 0.0002), the CC genotype of the eNOS gene (χ2 = 5.4, p = 0.02) and the allele 786C of the eNOS gene (χ2 = 15.1, p = 0.0001) were more often detected. The carriage of the 786C allele of the eNOS gene increased the risk of MI in the studied population (OR = 2.0, 95 % CI: 1.41‒2.82, p = 0.0001). Gender differences were not found in the distribution of genotypes and alleles within the studied groups. There were no differences in carriage by the number of combinations of minor alleles between the control group and patients with MI. The most common combinations of minor alleles in both groups were comparable.

Impact of Elevated Lipoprotein A on Clinical Outcomes in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis.

Lipoprotein(a) (Lp(a)) is an inherited lipoprotein particle associated with increased risk of atherosclerotic cardiovascular (CV) diseases. However, its impact on outcomes after percutaneous coronary intervention (PCI) remains unclear. The objective of this study was to assess the relationship between elevated Lp(a) levels and major adverse cardiovascular events (MACEs)and other outcomes in patients undergoing PCI. We systematically searched Embase, MEDLINE/PubMed, and Web of Science for studies published from 2015 to 2024 comparing CV outcomes between patients with elevated versus non-elevated Lp(a) levels after PCI. Primary outcome was MACE. Secondary outcomes included all-cause mortality, CV mortality, stroke, myocardial infarction, and revascularization. Risk ratios (RRs) were pooled using a random-effectmodel. Fifteen studies with 45,059 patients were included. Patients with elevated Lp(a) had a significantly higher risk of MACE (RR 1.38, 95% confidence interval (CI) 1.23-1.56). Elevated Lp(a) was also associated with increased risks of all-cause death (RR 1.26), CV death (RR 1.58), myocardial infarction (RR 1.44), revascularization (RR 1.38), and stroke (RR 1.18). Heterogeneity was considerable for some outcomes. This meta-analysis demonstrates that elevated Lp(a) levels are associated with worse CV outcomes, including higher rates of MACE, mortality, and recurrent ischemic events in patients undergoing PCI. Novel therapeutic approaches specifically targeting Lp(a) reduction may help mitigate residual CV risk in this high-risk population.

Blood lipid levels mediating the effects of sex hormone-binding globulin on coronary heart disease: Mendelian randomization and mediation analysis

Observational studies indicate that serum sex hormone-binding globulin (SHBG) levels are inversely correlated with blood lipid levels and coronary heart disease (CHD) risk. Given that dyslipidemia is an established risk factor for CHD, we aim to employ Mendelian randomization (MR) in conjunction with mediation analysis to confirm the mediating role of blood lipid levels in the association between SHBG and CHD. First, we assessed the causality between serum SHBG levels and five cardiovascular diseases using univariable MR. The results revealed causality between SHBG levels and reduced risk of CHD, myocardial infarction, as well as hypertension. Specifically, the most significant reduction was observed in CHD risk, with an odds ratio of 0.73 (95% CI 0.63–0.86) for each one-standard-deviation increase in SHBG. The summary-level data of serum SHBG levels and CHD are derived from a sex-specific genome-wide association study (GWAS) conducted by UK Biobank (sample size = 368,929) and a large-scale GWAS meta-analysis (60,801 cases and 123,504 controls), respectively. Subsequently, we further investigated the mediating role of blood lipid level in the association between SHBG and CHD. Mediation analysis clarified the mediation proportions for four mediators: high cholesterol (48%), very low-density lipoprotein cholesterol (25.1%), low-density lipoprotein cholesterol (18.5%), and triglycerides (44.3%). Summary-level data for each mediator were sourced from the UK Biobank and publicly available GWAS. The above results confirm negative causality between serum SHBG levels and the risk of CHD, myocardial infarction, and hypertension, with the causal effect on reducing CHD risk largely mediated by the improvement of blood lipid profiles.

Three-Year Outcomes With Fractional Flow Reserve-Guided or Angiography-Guided Multivessel Percutaneous Coronary Intervention for Myocardial Infarction.

In patients with multivessel disease with successful primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction, the FLOWER-MI trial (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) showed that a fractional flow reserve (FFR)-guided strategy was not superior to an angiography-guided strategy for treatment of noninfarct-related artery lesions regarding the 1-year risk of death from any cause, myocardial infarction, or unplanned hospitalization leading to urgent revascularization. The extension phase of the trial was planned using the same primary outcome to determine whether a difference in outcomes would be observed with a longer follow-up. In this multicenter trial, we randomly assigned patients with ST-segment-elevation myocardial infarction and multivessel disease with successful percutaneous coronary intervention of the infarct-related artery to receive complete revascularization guided by either FFR (n=586) or angiography (n=577). After 3 years, a primary outcome event occurred in 52 of 498 patients (9.40%) in the FFR-guided group and in 44 of 502 patients (8.17%) in the angiography-guided group (hazard ratio, 1.19 [95% CI, 0.79-1.77]; P=0.4). Death occurred in 22 patients (4.00%) in the FFR-guided group and in 23 (4.32%) in the angiography-guided group (hazard ratio, 0.96 [95% CI, 0.53-1.71]); nonfatal myocardial infarction in 23 (4.13%) and 14 (2.56%), respectively (hazard ratio, 1.63 [95% CI, 0.84-3.16]); and unplanned hospitalization leading to urgent revascularization in 21 (3.83%) and 18 (3.36%; hazard ratio, 1.15 [95% CI, 0.61-2.16]), respectively. Although event rates in the trial were lower than expected, in patients with ST-segment-elevation myocardial infarction undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization up to 3 years. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02943954.

Bone fracture is associated with incident myocardial infarction in long-term follow-up

BackgroundThe association between bone fracture and cardiovascular diseases is examined in this study. While basic research has established a connection between fractures and heart attacks through the linkage between bones and arteries, population studies have not provided clear evidence. The aim of the present study is to investigate the association between bone fracture and the occurrence of myocardial infarction in a natural population during long-term follow-up.MethodsA total of 13,196 adult participants with bone fracture history at baseline from the China Health and Nutrition Survey (CHNS) prospective cohort were included in this study. Baseline investigation was performed in 1997–2009 and the outcome was followed up till 2015. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using Cox proportional hazards models.ResultsFrom 1997 to 2015, a total of 329 incident myocardial infarction cases were identified. In univariate and multivariate Cox regression analysis, a history of bone fracture was associated with an increased risk of myocardial infarction incidence in the total population (for the crude model: HR = 2.56, 95% CI 1.83–3.53, P < 0.001; for the multivariate model: HR = 1.43, 95% CI 1.02–1.99, P = 0.036). In the stratified analysis, bone fracture was not associated with an increased risk of incident myocardial infarction in subjects with age < 50 years (HR = 0.71, 95% CI 0.34–1.47, P = 0.356), but significantly associated with an increased risk of incident myocardial infarction in subjects with age ≥ 50 years (HR = 1.80, 95% CI 1.23–2.63, P = 0.003).ConclusionsIt is suggested by the present study that bone fracture may be associated with an increased risk of incident myocardial infarction in the elderly population during long-term follow-up.

#1081 Associations of MRI-derived kidney volume, kidney function, body composition, and physical performance in &amp;gt;38 000 UK Biobank participants

Abstract Background and Aims Kidney volume is used as predictive and therapeutic marker for several clinical conditions. However, there is a lack of large-scale studies examining the relationship between kidney volume and various clinicodemographic factors, including kidney function, body composition, and physical performance. Method In this observational study, MRI-derived kidney volume measurements from 38,526 UK Biobank participants were analyzed. Major kidney volume-related measures included body surface area (BSA)-adjusted total kidney volume (TKV) and the difference of bilateral kidneys. Multivariable-adjusted linear regression and cubic spline analyses were used to explore the association between kidney volume-related measures and clinicodemographic factors. Cox regression was used to identify the risks of death, non-kidney cancer, myocardial infarction (MI), and ischemic stroke. Results The median of BSA-adjusted TKV and difference in kidney volume were 141.9 (128.1–156.9) mL/m2 and 1.08 (1.04–1.15) fold, respectively. Higher BSA-adjusted TKV was significantly associated with higher eGFR (beta [95% CIs], 0.43 [0.42–0.44]; P &amp;lt; 0.001), higher composition of muscle volume (beta [95% CIs], 0.50 [0.48–0.51]; P &amp;lt; 0.001), and higher mean handgrip strength (beta [95% CIs], 0.15 [0.13–0.16]; P &amp;lt; 0.001), while associated with lower visceral adipose tissue volume (VAT, beta [95% CIs], −0.09 [−0.11 – −0.07]; P &amp;lt; 0.001) in adjusted models. Higher difference in bilateral kidney volumes was associated with lower eGFR, muscle volume, and physical performance, while associated with higher proteinuria and VAT. Conclusion Higher BSA-adjusted TKV and lower discrepancies in bilateral kidney volumes are associated with higher renal function, muscle volume, and physical performance.

Patient knowledge about risk factors, achievement of target values, and guideline-adherent secondary prevention therapies 12 months after acute myocardial infarction.

The prospective GULLIVE-R study aimed to evaluate adherence to guideline-recommended secondary prevention, physicians' and patients' estimation of cardiac risk, and patients' knowledge about target values of risk factors after acute myocardial infarction (AMI). We performed a prospective study enrolling patients 9-12 months after AMI. Guideline-recommended secondary prevention therapies and physicians as well as patients' estimation about their risk and patients' knowledge about target values were prospectively collected. Between July 2019 and June 2021, a total of 2509 outpatients were enrolled in 150 German centres 10 months after AMI. The mean age was 66 years, 26.4% were women, 45.3% had ST elevation myocardial infarction, 54.7% had non-ST elevation myocardial infarction, and 93.6% had revascularization (84.0% percutaneous coronary intervention, 7.4% coronary artery bypass graft, 1.8% both). Guideline-recommended secondary drug therapies were prescribed in over 80% of patients, while only about 50% received all five recommended drugs (aspirin, P2Y12 inhibitors, statins, beta-blockers, renin-angiotensin-aldosterone system inhibitors), and regular exercise was performed by only one-third. About 90% of patients felt well informed about secondary prevention, but the correct target value for blood pressure was known in only 37.9% and for LDL-cholesterol in only 8.2%. Both physicians and patients underestimated the objective risk of future AMIs as determined by the thormbolysis in myocardial infarction (TIMI) risk score for secondary prevention. There is still room for improvement in patient education and implementation of guideline-recommended non-pharmacological and pharmacological secondary prevention therapies in patients in the chronic phase after AMI.

High Risk Non-ST Elevation Myocardial Infarction - A Case Report

Coronary artery disease (CAD) is the leading cause of cardiovascular mortality worldwide. Electrocardiogram (ECG) remains an important tool in the diagnosis of acute myocardial infarction (MI) and further risk stratification. ST segment elevation myocardial infarction (STEMI) is a medical emergency requiring early diagnosis and prompt reperfusion of occluded coronary artery to prevent morbidity and mortality. Recent studies have shown that a subset of patients with acute MI in the absence of ST segment elevation (non-ST elevation myocardial infarction [NSTEMI]) have an acute occlusion of the culprit artery on coronary angiography. The Aslanger’s pattern is a specific ECG finding in acute inferior myocardial infarction with multivessel disease. It allows identification of inferior wall myocardial infarction that does not show ST elevation in contiguous leads but needs rapid evaluation by coronary angiogram and revascularization. We presented a case of acute coronary syndrome whose ECG showed Aslanger’s pattern and was confirmed to have significant stenosis of the left main coronary artery and right coronary artery (RCA) by coronary angiogram. STEMI criteria of ST elevation involving two contiguous leads may not be sufficient in diagnosing critical coronary artery occlusions in clinical practice. Keywords: Acute Myocardial Infarction; Aslanger’s Pattern; ST-Elevation; NSTEMI

A 20-Year Autopsy Study of Myocardial Bridging Among Sudden Deaths

Myocardial bridging (MB) is a condition, where the cardiac muscle overlies the intramyocardial segment of the major epicardial coronary artery. This study aims to analyse the demographics and anatomical characteristics of MB within a pool of 2093 sudden cardiac-related death cases examined at the Forensic Unit of Universiti Kebangsaan Malaysia Medical Centre between 2000 and 2019. In this cross-sectional study, postmortem data collected were gender, racial affiliations, MB anatomical properties, and association with cardiac pathologies entered into the statistical software SPSS version 25 for analysis. The prevalence of MB was 12.9%. It was commoner in males (91.5%). MB was predominant between age 21-40 years old (50.2%). Chinese race showed the highest number of recorded MB cases (24.3%) among local races. MB was mostly found in left anterior descending (LAD) artery (98.2%), with the commonest length of 11-20mm (44.6%), depth of 1-5mm (49.8%), and distance from the ostium of 21-40mm (54.0%). The prevalence of isolated MB (43.2%) was nearly comparable to that of MB with cardiac pathologies (56.8%). MB was mostly associated with atherosclerosis (50.1%) and atheroma formation was mostly proximal to MB (78.3%). MB is a common occurrence and commonly found in the LAD as a single entity. It has a higher preponderance in the male gender among the adult population. In conclusion, the findings not only contribute to a deeper understanding of MB but also hold potential implications for identifying and managing risks related to sudden cardiac-related deaths. It is a pathological condition at a certain length and depth whether it exists as an isolated entity or associated with cardiac pathologies. Atherosclerosis tends to form proximal to MB and might pose a risk for myocardial infarction.

Immune Checkpoint Inhibitors and Cardiotoxicity: A Comparative Meta-Analysis of Observational Studies and Randomized Controlled Trials.

Immune checkpoint inhibitors (ICIs) have uncommon associations with cardiotoxicity, yet these cardiotoxic effects are associated with high mortality. An accurate assessment of risk for cardiotoxicity is essential for clinical decision-making, but data from randomized controlled trials often differ from real-world observational studies. A systematic search of PubMed, Embase, Cochrane Library, and Scopus was performed, including phase II and III randomized controlled trials (RCTs) and observational studies (OSs) reporting myocarditis or pericardial disease, myocardial infarction, or stroke with an immunotherapy. Odds ratios (ORs) were used to pool results between ICIs and other cancer therapy in RCTs and OSs. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed. In total, 54 RCTs (N=38 264) and 24 OSs (N=12 561 455) were included. In RCTs, ICI use resulted in higher risk of myocarditis (OR, 3.55 [95% CI, 2.10-5.98]), pericardial disease (OR, 2.73 [95% CI, 1.57-4.77]), and myocardial infarction (OR, 1.83 [95% CI, 1.03-3.25]), compared with non-ICI (placebo or chemotherapy). In OSs, ICI use was not associated with myocarditis, pericardial disease, or myocardial infarction compared with controls; however, combination ICIs demonstrated higher risk of myocarditis compared with single ICI use (OR, 3.07 [95% CI, 1.28-7.39]). Stroke risk was not increased with use of ICIs in RCTs. We demonstrated increased risk of ICI myocarditis, pericardial disease, and myocardial infarction in RCTs but not OSs. Results of this study suggest there are differences between ICI cardiotoxicity risk, possibly suggesting differences in diagnoses and management, in clinical trials versus the OSs.

Exploring the Link between Head and Neck Cancer and the Elevated Risk of Acute Myocardial Infarction: A National Population-Based Cohort Study.

Enhanced screening protocols for cancer detection have increased survival in patients with head and neck cancer (HNC), which highlights the need to address the sequelae of therapy-induced cardiovascular complications. This study was conducted to assess the incidence and risk of acute myocardial infarction (AMI) in patients with HNC who have not undergone radiation or chemotherapy using a comprehensive, population-based cohort dataset. A total of 2976 individuals without cancer and 744 individuals with HNC were matched using the propensity score method. The findings indicated that the occurrence rates of AMI were comparable between the HNC (2.19) and non-cancer groups (2.39). Cox regression analysis did not demonstrate a significant increase in the risk of AMI in patients with HNC (hazard ratio: 0.93, 95% confidence interval: 0.50-1.73). No increased risk of AMI was observed in the HNC group compared to the non-cancer group, regardless of the time since the HNC diagnosis. Subgroup analyses showed no notable differences in the AMI risk between the groups when considering sex, age, comorbidities, and cancer type. This study showed that patients with HNC who have not been treated with radiation or chemotherapy did not exhibit an increased incidence or risk of AMI compared to individuals without cancer.

Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91)

The 20-year UK Prospective Diabetes Study showed major clinical benefits for people with newly diagnosed type 2 diabetes randomly allocated to intensive glycaemic control with sulfonylurea or insulin therapy or metformin therapy, compared with conventional glycaemic control. 10-year post-trial follow-up identified enduring and emerging glycaemic and metformin legacy treatment effects. We aimed to determine whether these effects would wane by extending follow-up for another 14 years. 5102 patients enrolled between 1977 and 1991, of whom 4209 (82·5%) participants were originally randomly allocated to receive either intensive glycaemic control (sulfonylurea or insulin, or if overweight, metformin) or conventional glycaemic control (primarily diet). At the end of the 20-year interventional trial, 3277 surviving participants entered a 10-year post-trial monitoring period, which ran until Sept 30, 2007. Eligible participants for this study were all surviving participants at the end of the 10-year post-trial monitoring period. An extended follow-up of these participants was done by linking them to their routinely collected National Health Service (NHS) data for another 14 years. Clinical outcomes were derived from records of deaths, hospital admissions, outpatient visits, and accident and emergency unit attendances. We examined seven prespecified aggregate clinical outcomes (ie, any diabetes-related endpoint, diabetes-related death, death from any cause, myocardial infarction, stroke, peripheral vascular disease, and microvascular disease) by the randomised glycaemic control strategy on an intention-to-treat basis using Kaplan-Meier time-to-event and log-rank analyses. This study is registered with the ISRCTN registry, number ISRCTN75451837. Between Oct 1, 2007, and Sept 30, 2021, 1489 (97·6%) of 1525 participants could be linked to routinely collected NHS administrative data. Their mean age at baseline was 50·2 years (SD 8·0), and 41·3% were female. The mean age of those still alive as of Sept 30, 2021, was 79·9 years (SD 8·0). Individual follow-up from baseline ranged from 0 to 42 years, median 17·5 years (IQR 12·3-26·8). Overall follow-up increased by 21%, from 66 972 to 80 724 person-years. For up to 24 years after trial end, the glycaemic and metformin legacy effects showed no sign of waning. Early intensive glycaemic control with sulfonylurea or insulin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 10% (95% CI 2-17; p=0·015) for death from any cause, 17% (6-26; p=0·002) for myocardial infarction, and 26% (14-36; p<0·0001) for microvascular disease. Corresponding absolute risk reductions were 2·7%, 3·3%, and 3·5%, respectively. Early intensive glycaemic control with metformin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 20% (95% CI 5-32; p=0·010) for death from any cause and 31% (12-46; p=0·003) for myocardial infarction. Corresponding absolute risk reductions were 4·9% and 6·2%, respectively. No significant risk reductions during or after the trial for stroke or peripheral vascular disease were observed for both intensive glycaemic control groups, and no significant risk reduction for microvascular disease was observed for metformin therapy. Early intensive glycaemic control with sulfonylurea or insulin, or with metformin, compared with conventional glycaemic control, appears to confer a near-lifelong reduced risk of death and myocardial infarction. Achieving near normoglycaemia immediately following diagnosis might be essential to minimise the lifetime risk of diabetes-related complications to the greatest extent possible. University of Oxford Nuffield Department of Population Health Pump Priming.

Prognostic Impact of Iron Metabolism Changes in Patients with Acute Coronary Syndrome and its Correlation with TIMI Risk Score and 6-month Left Ventricular Performance

Objectives: Iron is vital for human metabolism and function. One major cause of anemia is a shortage of iron. On the other hand, a low blood iron level does not always indica te an abnormal hemoglobin concentration. Left ventricular function, ferritin, and blood iron levels were investigated 6 months following the acute coronary syndrome (ACS) index event. In addition, we searched for correlations between thrombolysis in myocardial infarction (TIMI) risk score, cytokines such as C-reactive protein (CRP), and serum iron content. Materials and Methods: From August 2021 to July 2022, 100 consecutive patients with ACS who were requesting admission to the critical care unit of the Cardiology Department at SCB Medical College in Cuttack, Odisha, were the subject of this study. Participants in our research with ST-elevation or non-ST-elevation myocardial infarction (ST elevation myocardial infarction [STEMI] or Non ST elevation myocardial infarction [NSTEMI]) ranged in age from 18 to 70 years. We measured CRP, transferrin saturation, total iron binding capacity, ferritin, and blood iron at baseline. The left ventricular ejection fraction (LVEF %) difference was assessed 6 months after baseline echocardiography and follow-up. Various factors were considered while calculating the short- and long-term prognoses, including the patient’s heart failure at admission and any deaths that took place in hospitals within 6 months after the index event. Results: There was no improvement in LVEF for 56.25% of patients (36 out of 66) 6 months after the index event; however, for 43.75% (28 patients) of the 66 STEMI patients, LVEF improved. Out of 34 NSTEMI patients, 14 (42.42%) improved their LVEF 6 months after ACS, whereas 19 (57.58%) did not. Serum iron levels and LVEF at 6 months were shown to be significantly correlated in all patients (overall P &lt; 0.001, STEMI P &lt; 0.001, and NSTEMI P = 0.001). Serum iron levels are positively correlated with improvements in LVEF after 6 months in both patients with STEMI; P &lt; 0.001, and NSTEMI P = 0.006. Serum iron levels and hospitalized STEMI patients’ TIMI risk scores showed a significant connection (P &lt; 0.001). Conclusion: Regardless of hemoglobin content, patients with &lt;10% improvement in LVEF from baseline had considerably lower blood iron levels. Six months after their initial ACS incident, patients with ACS who had lower blood iron concentrations at baseline recovered less well in terms of left ventricular systolic function. In our study, 48% of men and 68% of women were found to be iron deficient. In addition to being an indicator of inflammation, hypoferremia may be the target of a novel biomarker with potential applications in medicine in the near future. It could be useful in predicting left ventricular function following ACS.

Cholesteryl Ester Transfer Protein Inhibitors and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

Atherosclerosis is a multi-factorial disease, and low-density lipoprotein cholesterol (LDL-C) is a critical risk factor in developing atherosclerotic cardiovascular disease (ASCVD). Cholesteryl-ester transfer-protein (CETP), synthesized by the liver, regulates LDL-C and high-density lipoprotein cholesterol (HDL-C) through the bidirectional transfer of lipids. The novelty of CETP inhibitors (CETPis) has granted new focus towards increasing HDL-C, besides lowering LDL-C strategies. To date, five CETPis that are projected to improve lipid profiles, torcetrapib, dalcetrapib, evacetrapib, anacetrapib, and obicetrapib, have reached late-stage clinical development for ASCVD risk reduction. Early trials failed to reduce atherosclerotic cardiovascular occurrences. Given the advent of some recent large-scale clinical trials (ACCELERATE, HPS3/TIMI55-REVEAL Collaborative Group), conducting a meta-analysis is essential to investigate CETPis' efficacy. We conducted a thorough search of randomized controlled trials (RCTs) that commenced between 2003 and 2023; CETPi versus placebo studies with a ≥6-month follow-up and defined outcomes were eligible. major adverse cardiovascular events (MACEs), cardiovascular disease (CVD)-related mortality, all-cause mortality. stroke, revascularization, hospitalization due to acute coronary syndrome, myocardial infarction (MI). Nine RCTs revealed that the use of a CETPi significantly reduced CVD-related mortality (RR = 0.89; 95% CI: 0.81-0.98; p = 0.02; I2 = 0%); the same studies also reduced the risk of MI (RR = 0.92; 95% CI: 0.86-0.98; p = 0.01; I2 = 0%), which was primarily attributed to anacetrapib. The use of a CETPi did not reduce the likelihood any other outcomes. Our meta-analysis shows, for the first time, that CETPis are associated with reduced CVD-related mortality and MI.

INITIAL EXPERIENCE IN TOTAL ENDOSCOPIC MITRAL VALVE SURGERY WITH THREE–DIMENSIONAL VIDEO–ASSISTED TECHNOLOGY

Abstract Background Minimally invasive approach is nowadays the gold standard for mitral valve disease treatment. New technological tools are the key to improve surgical results and to reduce the biological invasiveness. We report our initial experience in total endoscopic mitral valve surgery using three–dimensional video–assisted technology (EinsteinVision® 3.0, B. Braun, Aesculap AG, Tuttlingen, Germany). Methods From July 2023 to December 2023, 29 patients underwent total endoscopic mitral valve surgery with three–dimensional video–assisted technology and discharged. Results Median (Q1–Q3) age of our population was 60 years (47–67) and 65.5% were males. Median (Q1–Q3) logistic Euroscore was 2.09 (1.5–4.4) and median (Q1–Q3) EuroSCORE II was 0.84 (0.6–1.2). The majority of patients were in NYHA class II and the 48.3% presented with pulmonary hypertension (PAPs &amp;gt; 30 mmHg). Median PAPs resulted 34.5 mmHg. One patient (3.4%) suffered from mitral valve endocarditis. No conversion to full sternotomy was necessary. In six patients with left coronary dominance (20.6%) we used indocyanine green fluorescence to conduct a real–time analysis of the course of the circumflex artery during surgery. No perioperative acute myocardial infarction was observed. No 30–day mortality was reported. One patient (3.4%) suffered from renal failure requiring dialysis, respiratory failure with tracheostomy and pneumonia. Post–operative atrial fibrillation was observed in 7 patients (24.1%) and 1 patient (3.4%) required Pace–maker implantation due to third degree AV block. No re–thoracotomy for bleeding was observed and 24.1% of patients required transfusions with packed blood cells. Non stroke were detected. Median (Q1–Q3) ventilation time was 5 hours (4–7). Median (Q1–Q3) intensive care unit postoperative length of stay were 2 (2–2) days and 7 (7–8) days respectively. Conclusions In our experience, total endoscopic mitral valve surgery with three–dimensional video–assisted technology is safe and feasible with good postoperative outcomes. Moreover, the possibility to use indocyanine green fluorescence to detect the course of the circumflex artery significantly assist surgeons in localizing and avoiding it, thus reducing the risk of perioperative myocardial infarction.

The clonal hematopoiesis mutation Jak2V617F aggravates endothelial injury and thrombosis in arteries with erosion-like intimas

BackgroundSuperficial plaque erosion causes many acute coronary syndromes. However, mechanisms of plaque erosion remain poorly understood, and we lack directed therapeutics for thrombotic complication. Human eroded plaques can harbor neutrophil extracellular traps (NETs) that propagate endothelial damage at experimental arterial lesions that recapitulate superficial erosion. Clonal Hematopoiesis of Indeterminate Potential (CHIP) denotes age-related clonal expansion of bone marrow-derived cells harboring somatic mutations in the absence of overt hematological disease. CHIP heightens the risk of cardiovascular disease, with the greatest increase seen in individuals with JAK2V617F. Neutrophils from mice and humans with JAK2V617F undergo NETosis more readily than Jak2WT (wild-type) cells. We hypothesized that JAK2V617F, by increasing propensity to NETosis, exacerbates aspects of superficial erosion. Methods and resultsWe generated Jak2V617F and Jak2WT mice with heterozygous Jak2V617F in myeloid cells. We induced areas of denuded endothelium that recapitulate features of superficial erosion and assessed endothelial integrity, cellular composition of the erosion, thrombosis rates, and response to ruxolitinib, a clinically available JAK1/2 inhibitor, in relation to genotype. Following experimental erosion, Jak2V617F mice have greater impairment of endothelial barrier function and increased rates of arterial thrombosis. Neointimas in Jak2V617F mice exhibit increased apoptosis, NETosis, and platelet recruitment. Jak2V617F mice treated with ruxolitinib show increased endothelial continuity and reduced apoptosis in the neointima comparable to levels in Jak2WT. ConclusionsThese observations provide new mechanistic insight into the pathophysiology of superficial erosion, the heightened risk for myocardial infarction in JAK2V617F CHIP, and point the way to personalized therapeutics based on CHIP status.

Coronary Artery Plaque Phenotype and 5-Year Clinical Outcomes in Older Patients with Non-ST Elevation Acute Coronary Syndrome.

Lesions with thin-cap fibroatheroma (TCFA), small luminal area and large plaque burden (PB) have been considered at high risk of cardiovascular events. Older patients were not represented in studies which demonstrated correlation between clinical outcome and plaque characteristics. This study aims to investigate the prognostic role of high-risk plaque characteristics and long-term outcome in older patients presenting with non-ST elevation acute coronary syndrome (NSTEACS). This study recruited older patients aged 75 years with NSTEACS undergoing virtual-histology intravascular ultrasound (VH-IVUS) imaging from the Improve Clinical Outcomes in high-risk patieNts with acute coronary syndrome (ICON-1). Primary endpoint was the composite of major adverse cardiovascular events (MACE) consisting of all-cause mortality, myocardial infarction (MI), and any revascularisation. Every component of MACE and target vessel failure (TVF) including MI and any revascularisation were considered as secondary endpoints. Eighty-six patients with 225 vessels undergoing VH-IVUS at baseline completed 5-year clinical follow-up. Patients with minimal lumen area (MLA) 4 demonstrated increased risk of MACE (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.00-5.59, p = 0.048) with a worse event-free survival (Log Rank 4.17, p = 0.041) than patients with MLA 4 . Patients with combination of TCFA, MLA 4 and PB 70% showed high risk of MI (HR 5.23, 95% CI 1.05-25.9, p = 0.043). Lesions with MLA 4 had 6-fold risk of TVF (HR 6.16, 95% CI 1.24-30.5, p = 0.026). Small luminal area appears as the major prognostic factor in older patients with NSTEACS at long-term follow-up. Combination of TCFA, MLA 4 and PB 70% was associated with high risk of MI. NCT01933581.