Coronary Disease Research Articles

A Comprehensive Review of Clinical Studies Applying Flow-Mediated Dilation

Flow-mediated dilation (FMD) is a noninvasive method to evaluate vascular endothelial function, which manifests the vascular inflammatory response, cell proliferation, and autoregulation. Since FMD is noninvasive and assesses commonly in the brachial artery by ultrasound, compared to other invasive methods such as optical coherence tomography (OCT) and intravascular ultrasound (IVUS), it is widely used to evaluate endothelial function and allows serial assessment. In this review, we present the currently accepted mechanisms and methods of FMD measurement with the studies applied in the current clinical practice using FMD. After all, the association with cardiovascular diseases is of substance, and so we introduce clinical studies of FMD related to cardiovascular disease such as diabetes, hyperlipidemia, chronic kidney disease, coronary artery disease, and peripheral vascular disease. In addition, studies related to pregnancy and COVID-19 were also inspected. Yet, endothelial examination is not endorsed as a cardiovascular prevention measure, for the lack of a clear standardized value methodology. Still, many studies recommend practicable FMD and would be a better prognostic value in the cardiovascular prognosis in future clinical research.

Right mini-thoracotomy for concomitant aortic valve replacement and right coronary artery bypass graft

Background Full sternotomy is the standard approach for combined surgery. Evidence of the minimally invasive approach’s advantages for aortic and mitral valve surgery has been reported. Our aim was to report our experience with minithoracotomy for elective patients presenting with aortic valve stenosis associated with right coronary artery disease. Material and methods Between January 2016 and August 2021, 17 patients underwent concomitant aortic valve replacement and right coronary artery bypass grafting by right anterior thoracotomy. Results The mean age was 73.3 years and the mean EuroSCORE 2 was 2.07 ± 1.24. Mean cardiopulmonary bypass and aortic cross-clamp times were 148 ± 29 min and 111 ± 20 min. Thirteen patients (76.0%) had femoral cannulation. Nine saphenous veins (53%), seven right internal thoracic arteries (41%), and one radial artery (6%) were used as a graft. Twelve patients benefited from ultrasonic flow measurements to control the graft. The mean flow rate was 47 ± 39 ml/min, and the mean pulsatility index was 2.4 ± 1.2. The mean postoperative transvalvular gradient was 10.9 ± 4 mmHg. Two patients presented with Grade 1 aortic insufficiency (12%). There was no 30-day mortality. Conclusions Combined aortic valve replacement and right coronary artery bypass grafting through right anterior thoracotomy is reliable and reproducible in selected patients.

Palmitoleic and oleic fatty acids as biomarkers for coronary heart disease: A predictive model.

saturated and unsaturated fatty acid showed a significant link with coronary artery health and disease. This study aimed to compare plasma levels of unsaturated fatty acids (UFAs) between individuals with coronary heart disease (CHD) and those without. It also investigated the association between specific UFA ratios and the presence or severity of acute coronary syndrome (ACS). Additionally, the study explored the potential of UFAs as biomarkers for assessing CHD risk or disease severity. Patients suspected of coronary heart disease (CHD) at Northern Jiangsu People's Hospital were categorized by coronary angiography into non-CHD (53 cases) and CHD (182 cases). The CHD group was divided into non-acute coronary syndrome (non-ACS) (40 cases) and ACS (142 cases) subgroups. The ACS group was further classified into unstable angina (61 cases), non-ST-elevation myocardial infarction (NSTEMI) (40 cases), and ST-elevation myocardial infarction (STEMI) (41 cases). Lipid profiles, myocardial injury markers, and fourteen unsaturated fatty acids were analyzed using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The CHD group had significantly higher triglycerides (TG), palmitoleic acid (PA), oleic acid (OA), docosahexaenoic acid (DHA), ω-6 fatty acids, and a higher ω-6/ω-3 ratio, but lower ω-3 fatty acids compared to non-CHD. In ACS, PA, LA, OA, and the ω-6/ω-3 ratio were elevated, while EPA and HDL were reduced. Logistic regression identified TG, ω-6/ω-3 ratio, PA, OA, and ω-6 fatty acids as risk factors, with ω-3 fatty acids being protective. PA was protective, while OA posed risk. A combined PA and OA model had a diagnostic efficacy (AUC 0.746). Altered fatty acid metabolism in CHD patients, particularly PA and OA, offers potential as biomarkers. The ω-6/ω-3 ratio is crucial for cardiovascular health.

The Unusual Presentation of Non-ST Elevation Myocardial Infarction Following Acute Carbon Monoxide Poisoning in an Elderly Female: A Case Report

Carbon monoxide (CO) poisoning is a leading cause of poisoning-related deaths, particularly affecting organs with high oxygen demands such as the heart and brain. Cardiac complications, including non-ST elevation myocardial infarction (NSTEMI), can occur due to CO poisoning but are not frequently reported in the elderly. We present the case of an 82-year-old female with a medical history of diabetes, hypertension, dyslipidemia, and previous ischemic heart disease. She was brought to the emergency department after being found drowsy in a closed room with a burning charcoal heater. The initial assessment revealed a carboxyhemoglobin level of 33.5%, which decreased to 9.3% after high-flow oxygen therapy and hyperbaric oxygen therapy (HBOT). Laboratory tests indicated elevated troponin levels, and an ECG showed asymmetrical T-wave inversion and ST depression. Despite the improvement in carboxyhemoglobin, the patient experienced persistent chest pain and rising troponin levels. She was treated with dual antiplatelet therapy and low molecular weight heparin as per acute coronary syndrome protocol, leading to a gradual improvement and a subsequent discharge in a stable condition. This case highlights the potential for CO poisoning to induce NSTEMI in elderly patients. A prompt diagnosis and appropriate management, including the use of HBOT, were crucial for the patient’s recovery.

Psmb8 inhibits mitochondrial fission and alleviates myocardial ischaemia/reperfusion injury by targeting Drp1 degradation

The mitochondrial dynamic imbalance is an important cause of myocardial ischaemia/reperfusion (I/R) injury and dysfunction. Psmb8, as one of the immunoproteasome catalytic subunits, is a key regulator of protein homoeostasis, inflammation and some cardiac diseases. Here, we found that the expression level and activity of Psmb8 were significantly reduced in the heart of I/R mice and in subjects with myocardial infarction (MI). Cardiomyocyte-specific Psmb8 overexpression in mice markedly ameliorated I/R-mediated cardiac injury and dysfunction, which was accompanied by reduced mitochondrial division via the downregulation of dynamin-related protein-1 (Drp1). However, Psmb8 knockout (KO) mice exhibited the opposite changes. The effects of Psmb8 on mitochondrial fission and apoptosis was confirmed in primary cardiomyocytes with overexpression or knockdown of Psmb8 in vitro. Mechanistically, Psmb8 was directly associated with Drp1 and enhanced its degradation, which subsequently suppressed I/R-mediated mitochondrial fission and cardiac injury. Conversely, knockdown of Drp1 in Psmb8-KO mice restored I/R-induced cardiac dysfunction and mitochondrial dynamic imbalance. Our study identified a new cardioprotective role of Psmb8 in cardiac I/R damage through targeting Drp1, and highlight that increasing Psmb8 activity may constitute a promising therapy for ischaemic heart disease.

A higher mortality in men compared to women with heart failure in primary care and ejection fraction equal to or more than 40%

ABSTRACT The aim of this study was to describe gender-related differences in characteristics and mortality in heart failure (HF) patients managed in primary care (PC). We included 1802 hF patients aged 77.5 ± 8.8 years (47% women) with ejection fraction (EF) ≥ 40% from the Swedish Heart Failure (SwedeHF) registry. The patients were divided by gender, and by heart failure with mildly reduced ejection fraction (HFmrEF; EF 40–49%) or heart failure with preserved ejection fraction (HFpEF; EF ≥ 50%). Men included in the study were younger (mean-age 76.4 vs 78.7 years, p < 0.0001) and showed a higher age-adjusted mortality (p < 0.0001). Men more often showed ischemic heart disease, 49% vs. 38% (p < 0.0001), atrial fibrillation, 56% vs. 50%, and diabetes, 25% vs. 17% (both p < 0.01). Women had higher blood pressure compared to men (p < 0.01), more commonly had kidney dysfunction (p < 0.01), and a worse functional capacity (p < 0.01). Cardiovascular diseases were the dominating causes of death in men and women (60% and 56%) but were less dominating in individuals with EF ≥ 50%, especially among women (56% in men vs. 46% in women). Among women with EF ≥ 50%, the mortality was dominated of mixed and unspecified diseases. Other important causes of death were cancer (15%) and chronic obstructive pulmonary disease (13%). Men managed in PC with HF and EF ≥ 40% have a higher age-adjusted mortality than women. Cardiovascular disease is the dominating cause of death in both genders. Other frequent causes of death were malignant tumors and respiratory diseases, illustrating the need to carefully diagnose and treat all associated comorbidities.

Clinical Impact of Sarcopenia Screening on Long-Term Mortality in Patients Undergoing Coronary Bypass Grafting.

Sarcopenia is an aging-related condition characterized by loss of skeletal muscle mass and is an indicator of subclinical atherosclerosis. The relationship between reduced muscle mass and long-term clinical outcomes in patients with advanced coronary artery disease who have undergone coronary artery bypass grafting (CABG) is not fully understood. This study is sought to evaluate the prognostic implications of sarcopenia screening in patients undergoing CABG. A total of 2810 patients who underwent CABG were analysed and classified according to presence of reduced muscle mass. The skeletal muscle index (SMI) was calculated as L3 muscle area (cm2)/height (m)2 on computed tomography. Reduced SMI was defined as SMI ≤ 45 cm2/m2 in male and ≤ 38 cm2/m2 in female. The primary outcome was all-cause mortality, and survival analysis was performed using the Kaplan-Meier method and compared with the log-rank test. The median follow-up was 8.7 years, and 924 patients (32.9%) had reduced SMI. Patients with reduced SMI were older (67.7 ± 8.8 vs. 62.2 ± 9.8 years; p < 0.001) and less frequently male (69.8% vs. 81.1%; p < 0.001). SMI was significantly associated with risk of death on a restricted cubic spline curve (HR = 1.04 per-1 decrease; 95% CI 1.03-1.05; p < 0.001). Patients with reduced SMI had a higher incidence of long-term mortality than those with preserved SMI (survival rate 41.4% vs. 62.8%; HRadj = 1.18, 95% CI 1.03-1.36, p = 0.020). Subgroup analysis showed that the prognostic implication of reduced SMI on long-term survival was more evident in male (HRadj = 2.01, 95% CI 1.72-2.35) than female (HRadj = 1.28, 95% CI 0.98-1.68) (interaction p = 0.006). Reduced muscle mass, defined by SMI on computed tomography, was associated with long-term mortality after CABG. These results provide contemporary data to allow the evaluation of physical frailty in patients with advanced coronary artery disease before surgery. Long-Term Outcomes and Prognostic Factors in Patients Undergoing CABG or PCI: NCT03870815.

Comparison of the effectiveness of drug therapy and non-drug technology of post-COVID rehabilitation of workers with intensive computer load

Currently, there is sufficient evidence of the importance and clinical effectiveness of non-drug therapy. The scientific discussion on the priority of the clinical application of pharmacological and non-pharmacological methods of rehabilitation of patients with mononeuropathies has acquired particular importance against the background of neurological post-COVID complications in patients with COVID-19. The study aims to compare the effectiveness of drug therapy and non–drug technology of post-covid rehabilitation of workers with intensive computer workload based on the study of clinical and laboratory parameters. Scientists have conducted a survey of two groups of workers with intensive computer workload who underwent rehabilitation after COVID-19 with the use of drug therapy and non-drug technologies, including balneotherapy, drinking narcotherapy, aerosol inhalations, low-frequency magnetic therapy. The authors have evaluated the effectiveness of therapy based on the results of studies of asthenization, degree of fatigue, latent coronary insufficiency, the state of the blood microcirculation system, immune status, the state of the POL-AOSIS system and endogenous intoxication of patients. Asthenization, the degree of fatigue, and latent coronary insufficiency decreased in the majority of the examined patients after post-COVID non-drug measures. Whereas in patients of the drug group, a decrease in these indicators was noted in a small number of examined patients. The indicators of the immune status of patients after non-drug therapy returned to normal, after drug therapy they only approached the limits of the norm, but did not reach it. After the treatment, the indicators of lipid peroxidation in the group of patients undergoing post-COVID rehabilitation using non-drug technologies decreased more significantly than in the group receiving drug treatment. The content of the antioxidant enzymes catalase and ceruloplasmin and the fat-soluble antioxidant α-tocopherol after treatment increases in both groups, but in the group of drug treatment they do not reach the lower limit of the reference intervals. The decrease in the content of medium-molecular peptides is more pronounced when using non-drug technologies. The application of the proposed non-drug technology for the rehabilitation of patients with post-COVID syndrome who are subjected to intense computer loads during work showed a significantly more pronounced normalization of asthenization, fatigue, latent coronary insufficiency and the state of the blood microcirculation system, immune status, the state of the POL-AOSIS system and endogenous intoxication of patients. The data obtained indicate a high therapeutic effect of the use of non-drug technology. Limitations. The surveyed groups included only persons permanently registered in Kislovodsk. Ethics. The research was conducted in accordance with the principles of biomedical ethics and approved by the local Ethics Committee of the Izmerov Research Institute of Occupation Health, Moscow (Protocol No. 4 dated 04/14/2021). Each participant of the study submitted a voluntary written informed consent signed by him after explaining to him the potential risks and benefits.

Clinical and angiographic characteristics of patients with familial hypercholesterolemia presenting with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention

Familial hypercholesterolemia (FH) is a world public health problem that enhances the risk of premature coronary artery disease (CAD) with a high incidence of acute coronary syndrome. This study aimed to evaluate the clinical and angiographic characteristics of the patients with and without FH who had ST-elevation myocardial infarction (STEMI). It included 690 patients who presented with the first attack of STEMI and underwent primary percutaneous coronary interventions (PPCI). The patients were analyzed to diagnose FH according to the Dutch Lipid Clinic Network (DLCN) criteria. All angiograms were analyzed for the number of diseased vessels, Syntax score, thrombus burden grade, and final Thrombolysis in Myocardial Infarction (TIMI) flow grade. The majority of patients were male (72.6%) with a mean age of 54 ± 12 years. Based on DLCN criteria, they were classified into unlikely/possible FH (86.1%) and probable/definite FH (13.9%) groups. Probable/definite FH patients were significantly younger, and higher incidence of males < 55 years compared with unlikely/possible FH patients (p < 0.001 for each). Moreover, probable/definite FH patients had a higher frequency of three-vessel disease (p = 0.007) and Syntax score (p < 0.001) with a moderate positive correlation with the DLCN score (r = 0.592, p < 0.001). Furthermore, probable/definite FH patients showed a higher thrombus burden and final TIMI slow/no-reflow when compared to the unlikely/possible FH patients (p = 0.006 and p = 0.027, respectively). Patients with probable/definite FH and LDL-C level were independent predictors of high thrombus burden besides males < 55 years, and the number of diseased vessels. In conclusion, STEMI patients with FH were younger males and associated with severe CAD with frequent multivessel CAD, high anatomical complexity of CAD, and frequent high thrombus burden. Furthermore, FH was one of the predictors of high thrombus burden.

Recurrent Hospitalizations for Fluid Overload in Diabetes with Kidney Failure Treated with Dialysis.

Background &amp; Aims Diabetes Mellitus is the most common cause of end-stage kidney disease (ESKD) in Singapore. ESKD patients have high disease burden and are at increased risk of recurrent hospitalizations, including fluid overload. This study aimed to characterize the risk factors associated with readmissions for fluid overload that will identify high-risk hospitalizations for interventions to reduce readmissions. Methods Retrospective cohort study of all hospitalizations for fluid overload in adults with diabetes and ESKD on dialysis in SingHealth hospitals between 2018 and 2021. Fluid overload was defined by discharge codes for fluid overload, heart failure, pulmonary edema, and generalized edema until 30th December 2022. Multivariable Cox regression analysis using the Prentice, Williams and Peterson Total Time (PWP-TT) model was performed for the outcomes of readmissions for fluid overload within 30 days and 90 days of discharge. Results Among 3234 hospitalizations for fluid overload, readmission for fluid overload within 30-day and 90-day occurred in 585 (18.1%) and 967 (29.9%) hospitalizations, respectively. Ischemic heart disease, peripheral vascular disease and lower hemoglobin level were independently associated with readmissions for fluid overload within 30 and 90 days. Additionally, heart failure, hemodialysis (compared to peritoneal dialysis) and lack of statin at discharge were associated with increased 90-day readmission risk. Conclusion Modifiable (hemoglobin level, statin use) and non-modifiable factors (ischemic heart disease, peripheral vascular disease and heart failure) influenced the risk of readmission for fluid overload. These results may guide risk stratification and inform targeted interventions to reduce avoidable, unplanned readmissions for recurrent fluid overload among individuals with diabetes and ESKD.

Causal association between remnant cholesterol level and risk of cardiovascular diseases: a bidirectional two sample mendelian randomization study

Serum lipids have been associated with an increased risk of various cardiovascular diseases (CVDs) in several observational studies, but the causal inference between the remnant cholesterol (RC) levels and several CVDs risk has not been established. The purpose of this study was to investigate whether there is a causal relationship between RC levels and risk of developing CVDs by a bidirectional two-sample Mendelian randomization (TSMR) analysis. One TSMR analysis was performed using the publicly released large-scale genome-wide association study (GWAS) data. Inverse variance weighted (IVW) method was chosen as the main analysis method, and MR-Egger, weighted median, simple mode, and weighted mode were used as supplementary methods. We conducted a series of sensitivity analyses to assess the robustness of the main results, including the Cochran’s Q test, MR-Egger intercept test, leave-one-out sensitivity analysis, and funnel plot. The main IVW method revealed that genetically predicted serum level of RC is significantly associated with an increased risk of developing ischemic heart disease (OR = 1.409, 95%CI = 1.284–1.546, P value = 4.753E-13), unstable angina pectoris (OR = 1.621, 95%CI = 1.398–1.880, P value = 1.672E-10), myocardial infarction (OR = 1.526, 95%CI = 1.337–1.741, P value = 3.771E-10), cardiac arrest (OR = 1.595, 95%CI = 1.322–1.924, P value = 1.076E-06), heart failure (OR = 1.086, 95%CI = 1.009–1.169, P value = 0.028), hypertension (OR = 1.089, 95%CI = 1.043–1.136, P value = 9.458E-05), major coronary heart disease (CHD) events (OR = 1.515, 95%CI = 1.376–1.669, P value = 3.217E-17), coronary atherosclerosis (OR = 1.388, 95%CI = 1.231–1.564, P value = 7.739E-08), cardiac arrhythmias (OR = 1.067, 95%CI = 1.008–1.130, P value = 0.025), and atrial fibrillation and flutter (OR = 1.122, 95%CI = 1.039–1.211, P value = 0.003). Additionally, the causal associations between the RC levels and these CVDs remained significant after correcting for the false discovery rate (all P value < 0.05). However, this study did not find any significant association of RC with cardiomyopathy and pericarditis (both P value > 0.05). Heterogeneity existed in the IVs of RC and ischemic heart disease, unstable angina pectoris, myocardial infarction, heart failure, hypertension, major CHD events, cardiomyopathy, coronary atherosclerosis, cardiac arrhythmias and atrial fibrillation and flutter using the Cochran’s Q test (all P value < 0.05). Moreover, there was no horizontal pleiotropy in this study (all P value > 0.05). The leave-one-out sensitivity analyses showed that the causal effects between RC level and CVDs (except for heart failure, cardiomyopathy, pericarditis and cardiac arrhythmias) are not driven by a single SNP. The funnel plots showed that there is no obvious potential bias in our study. In the replication analysis, the genetically predicted RC levels were positively associated with a 43.12% higher risk of coronary artery disease. This present study supported the causal link between RC and heightened the risk of CVDs, indicating that RC-lowering treatment might be effective in preventing CVDs.

Comparative analysis of canine and human HtrA2 to delineate its role in apoptosis and cancer.

Therapeutically, targeting the pro- and anti-apoptotic proteins has been one of the major approaches behind devising strategies to combat associated diseases. Human high-temperature requirement serine protease A2 (hHtrA2), which induces apoptosis through both caspase-dependent and independent pathways is implicated in several diseases including cancer, ischemic heart diseases, and neurodegeneration, thus making it a promising target molecule. In the recent past, the canine model has gained prominence in the understanding of human pathophysiology that was otherwise limited to the rodent system. Moreover, canine models in cancer research provide an opportunity to study spontaneous tumors as their size, lifespan, and environmental exposure are significantly closer to that of humans compared with laboratory rodents. Therefore, using HtrA2 as a model protein, comparative analysis has been done to revisit the hypothesis that canines might be excellent models for cancer research. We have performed evolutionary phylogenetic analyses that confirm a close relationship between canine and human HtrA2s. Molecular modeling demonstrates structural similarities including orientation of the catalytic triad residues, followed by in silico docking and molecular dynamics simulation studies that identify the potential interacting partners for canine HtrA2 (cHtrA2). In vitro biophysical and protease studies depict similarities in interaction with their respective substrates as well as transient transfection of cHtrA2 in mammalian cell culture shows induction of apoptosis. This work, therefore, promises to open a new avenue in cancer research through the study of spontaneous cancer model systems in canines.

Associations Between Mosaic Loss of Sex Chromosomes and Incident Hospitalization for Atrial Fibrillation in the United Kingdom.

Mosaic loss of chromosome Y (mLOY) in leukocytes of men reflects genomic instability from aging, smoking, and environmental exposures. A similar mosaic loss of chromosome X (mLOX) occurs among women. However, the associations between mLOY, mLOX, and risk of incident heart diseases are unclear. We estimated associations between mLOY, mLOX, and risk of incident heart diseases requiring hospitalization, including atrial fibrillation, myocardial infarction, ischemic heart disease, cardiomyopathy, and heart failure. We analyzed 190 613 men and 224 853 women with genotyping data from the UK Biobank. Among these participants, there were 37 037 men with mLOY and 13 978 women with mLOX detected using the Mosaic Chromosomal Alterations caller. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs of each incident heart disease in relation to mLOY in men and mLOX in women. Additionally, Mendelian randomization was conducted to estimate causal associations. Among men, detectable mLOY was associated with elevated risk of atrial fibrillation (HR, 1.06 [95% CI, 1.03-1.11]). The associations were apparent in both never smokers (HR, 1.07 [95% CI, 1.01-1.14]) and ever smokers (HR, 1.05 [95% CI, 1.01-1.11]) as well as men aged >60 and ≤60 years. Mendelian randomization analyses supported causal associations between mLOY and atrial fibrillation (HRMR-PRESSO, 1.15 [95% CI, 1.13-1.18]). Among postmenopausal women, we found a suggestive inverse association between detectable mLOX and atrial fibrillation risk (HR, 0.90 [95% CI, 0.83-0.98]). However, associations with mLOY and mLOX were not found for other heart diseases. Our findings suggest that mLOY and mLOX reflect sex-specific biological processes or exposure profiles related to incident atrial fibrillation requiring hospitalization.

Association of Ozone and Temperature with Ischemic Heart Disease Mortality Risk: Mediation and Interaction Analyses.

Global warming and elevated ozone (O3) levels are gradually gaining widespread attention, and exposure to which may cause many physiological changes associated with cardiovascular events such as hypertension, cardiomyocyte apoptosis, etc. In addition, ischemic heart disease (IHD) is the leading cause of death worldwide. However, the contributions of temperature and O3, independently or in combination, to IHD mortality are not well understood. This study employs a two-stage analytical protocol (generalized additive model followed by meta-analysis) to explore the respective associations of temperature and O3 with IHD mortality, and determine their possible mediation and interaction effects. Our results suggest that increases of 10 μg/m3 in O3 and 1 °C in temperature at lag01 day are associated with increased IHD mortality risks of 0.789% and 0.686%, respectively. O3 can mediate the relationship between temperature and IHD mortality, with a pooled estimate of 0.140%, while temperature can mediate the association between O3 and IHD mortality, with a pooled estimate of 0.162%. The additive and multiplicative interaction effects of O3 and temperature were significantly associated with IHD mortality. The study findings demonstrate that higher temperature and O3 concentrations can increase human IHD mortality risk through interaction and mediation effects, providing a scientific basis for the synergistic management of temperature and O3 or associated interventions.

Prognostic Value of Coronary Flow Capacity by 82Rb PET in Patients With Suspected Coronary Artery Disease and Normal Myocardial Perfusion at Semiquantitative Imaging Analysis.

Coronary flow capacity (CFC) is a measure that integrates hyperemic myocardial blood flow and myocardial flow reserve to quantify the pathophysiological impact of coronary artery disease on vasodilator capacity. We assessed the prognostic value of CFC derived from 82Rb positron emission tomography/computed tomography in patients with suspected coronary artery disease and normal myocardial perfusion imaging. We studied 1967 patients with suspected coronary artery disease and normal myocardial perfusion at the semiquantitative analysis of stress/rest cardiac 82Rb positron emission tomography/computed tomography imaging. Coronary artery calcium scores were calculated and categorized into 3 groups: 0, 0.1 to 99.9, and ≥100. Patients were classified as having myocardial steal, severely reduced CFC, moderately reduced CFC, mildly reduced CFC, minimally reduced CFC, or normal flow using previously defined thresholds. The outcome end points were myocardial infarction and cardiac death, whichever occurred first. During a mean time of 41±27 months, 49 events occurred (2.5% cumulative event rate, with an annualized event rate of 0.5% person-years). At multivariable Cox analysis, coronary artery calcium score categories and impaired CFC resulted as independent predictors of events (both P<0.001). The annualized event rate was higher in patients with impaired CFC compared with those with normal CFC (P<0.05). Kaplan-Meier analysis showed that patients with impaired CFC were at the highest risk of events. In patients with suspected coronary artery disease and normal myocardial perfusion, impaired CFC is associated with a higher risk of cardiac events. Evaluating CFC can help identify patients' candidates for additional therapies to prevent future events.

The role of COX2 deficiency attenuates cardiac damage in acute myocardial infarction

Cardiac cell damage frequently occurs as a consequence of acute myocardial infarction (AMI), a critical complication of coronary atherosclerotic heart disease. There is an escalating recognition of the association between COX2 and myocardial damage induced by ischemia. The objective of this study is to investigate the inhibitory effect of the COX2 on cardiomyocyte damage in the context of AMI. To create an AMI model, mice with the genetic background of wild-type C57BL6/J (WT) and COX2-/- mice were utilized. The left anterior descending (LAD) coronary artery in their hearts was obstructed, and subsequent assessment of hemodynamic parameters and heart function was conducted. Notably, increased levels of COX2 were observed in AMI mice. Through correlational analysis between COX2 expression and cardiac function following AMI, it was revealed that COX2 knockout mice had smaller infarct sizes, better cardiac performance, and suppressed levels of reactive oxygen species (ROS) compared to WT mice. Additionally, we discovered that COX2 knockout mice exhibited significantly higher mRNA levels of smooth muscle actin, collagen I, and collagen III than normal mice with AMI. Conversely, the levels of superoxide dismutase (SOD), malondialdehyde (MDA) were higher but iron content was decreased in COX2 knockout mice compared to normal mice with AMI.In summary, our research demonstrates that the downregulation of COX2 enhances cardiac tissue recovery in the context of AMI.

Distinct Genetic Risk Profile in Aortic Stenosis Compared With Coronary Artery Disease.

Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist. However, it is unknown which genetic and cardiovascular risk factors might be AS-specific and which could be shared between AS and CAD. To identify genetic risk loci and cardiovascular risk factors with AS-specific associations. This was a genomewide association study (GWAS) of AS adjusted for CAD with participants from the European Consortium for the Genetics of Aortic Stenosis (EGAS) (recruited 2000-2020), UK Biobank (recruited 2006-2010), Estonian Biobank (recruited 1997-2019), and FinnGen (recruited 1964-2019). EGAS participants were collected from 7 sites across Europe. All participants were of European ancestry, and information on comorbid CAD was available for all participants. Follow-up analyses with GWAS data on cardiovascular traits and tissue transcriptome data were also performed. Data were analyzed from October 2022 to July 2023. Genetic variants. Cardiovascular traits associated with AS adjusted for CAD. Replication was performed in 2 independent AS GWAS cohorts. A total of 18 792 participants with AS and 434 249 control participants were included in this GWAS adjusted for CAD. The analysis found 17 AS risk loci, including 5 loci with novel and independently replicated associations (RNF114A, AFAP1, PDGFRA, ADAMTS7, HAO1). Of all 17 associated loci, 11 were associated with risk specifically for AS and were not associated with CAD (ALPL, PALMD, PRRX1, RNF144A, MECOM, AFAP1, PDGFRA, IL6, TPCN2, NLRP6, HAO1). Concordantly, this study revealed only a moderate genetic correlation of 0.15 (SE, 0.05) between AS and CAD (P = 1.60 × 10-3). Mendelian randomization revealed that serum phosphate was an AS-specific risk factor that was absent in CAD (AS: odds ratio [OR], 1.20; 95% CI, 1.11-1.31; P = 1.27 × 10-5; CAD: OR, 0.97; 95% CI 0.94-1.00; P = .04). Mendelian randomization also found that blood pressure, body mass index, and cholesterol metabolism had substantially lesser associations with AS compared with CAD. Pathway and transcriptome enrichment analyses revealed biological processes and tissues relevant for AS development. This GWAS adjusted for CAD found a distinct genetic risk profile for AS at the single-marker and polygenic level. These findings provide new targets for future AS research.

Causal Links Between Renal Function and Cardiac Structure, Function, and Disease Risk.

Chronic kidney disease (CKD) increases the risk of adverse cardiovascular outcomes. However, the causal relationships between renal function and cardiovascular diseases (CVD) remain incompletely understood. This study aimed to determine the causal relationships between genetic susceptibility to impaired renal function and the risk of CVD endpoints, as well as cardiac structure and function detectable by cardiac magnetic resonance imaging (CMR). Bidirectional Mendelian randomization (MR) analyses were conducted using summary-level data from genome-wide association studies. The exposures were blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and CKD. The outcomes included atrial fibrillation, coronary artery disease (CAD), myocardial infarction, heart failure, stroke, and various CMR parameters. Sensitivity analyses, multivariable MR adjusting for cardiometabolic traits, and replication in the FinnGen cohort were performed. Elevated BUN levels (OR 1.505; 95% CI 1.077 to 2.103; P = 0.017) were causally associated with increased CAD risk, but this relationship was attenuated after adjusting for cardiometabolic traits. Increased UACR was causally linked to higher risks of CAD (OR 1.260; 95% CI 1.042 to 1.523; P = 0.017), myocardial infarction (OR 1.424; 95% CI 1.137 to 1.783; P = 0.002), and stroke (OR 1.182; 95% CI 1.012 to 1.379; P = 0.035), with the association for stroke remaining significant after multivariable adjustment. Reduced eGFR was causally related to decreases in ascending aorta diameter, proximal pulmonary artery diameter, right atrial size, left ventricular stroke volume, and right ventricular volumes, even after accounting for potential confounders. CKD was causally associated with a reduced pulmonary artery-to-aorta ratio and proximal pulmonary artery diameter. This comprehensive MR study establishes causal roles of genetic susceptibility to impaired renal function influencing cardiovascular outcomes and cardiac structure.

Early onset colorectal cancer, not just the age: Data from a large health organization.

Early onset colorectal cancer (EO-CRC) is increasing. We investigated the risk factors for ER-CRC compared to late onset colorectal cancer (LO-CRC). CRC patients between the years 1999 and 2021 were retrospectively evaluated. Data regarding demographics, comorbidities, malignancies, and mortality were collected. Data were retrieved using the MdClone platform from a large Health Maintenance Organization. The cohort was subdivided into EO-CRC (age ≤ 50 years) and LO-CRC (age ≥ 51 years) groups. 61,679 patients diagnosed with CRC were included in our analysis, 30,456 (49.4%) males, and 4891 (7.9%) Arabs, with an average age at diagnosis of 70.1 ± 13.1 years. 5561 (9%) patients were included in the EO-CRC group. Over the last decades, higher rates of EO-CRC were diagnosed compared to the previous decade, 9.8% vs 8.3%, p < 0.001. A higher percentage of EO-CRC patients were females (52.8% vs 50.4%), had a family history of CRC (9.9% vs 5.5%), were Arabs (18.7% vs 6.9%), and were smokers (32.7% vs 30.2%) compared to LO-CRC patients. Significantly lower rates of comorbidities such as ischemic heart disease, diabetes mellitus, hypertension, obesity, and iron deficiency anemia were found among EO-CRC patients, with a lower all-cause mortality (27.7% vs 63.1%, p < 0.001). 348 (6.3%) of the EO-CRC patients had another Lynch-related cancer until age 50 years compared to 45 (0.1%) at the LO-CRC. Young individuals with increased risk for CRC need special consideration and should be referred early for screening and endoscopic investigation, particularly those with a family history of CRC, smokers, and those of Arab ethnicity.

A forensic overview of deaths in mountainous terrain.

Deaths at high altitudes may arise from a range of quite disparate entities including trauma (e.g. falls), environmental factors (e.g. hypothermia and hypoxia), and pre-existing medical conditions (e.g. coronary artery disease). Unique conditions include high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE) which may contribute to lethal mechanisms or precipitate a traumatic event. Forensic issues that may arise in these cases are logistical problems due to remote locations, sometimes with failure to find a body, delay in discovery and/or repatriation, prior local autopsies being performed with embalming, and the non-specificity of pathology markers. Traumatic deaths involve blunt force impacts, falls, suffocation, crush asphyxia and hypothermia. The assessment of cases requires careful integration of the autopsy findings with the medical history of the decedent and an accurate description of their behaviour in the hours leading up to death.