Search

Background: The effect of milk on the risk of ischemic heart disease (IHD) and acute myocardial infarction (MI) is unclear. We aimed to examine the association between non-fermented and fermented milk consumption on these endpoints and investigate the relationship between milk intake and cardiometabolic-related proteins in plasma., Methods: Our study is based on two Swedish prospective cohort studies that included 59,998 women and 40,777 men without IHD or cancer at baseline who provided repeated measures of diet and lifestyle factors and plasma proteomics data in two subcohorts. Through registry linkage, 17,896 cases with IHD were documented during up to 33 years of follow-up, including 10,714 with MI. We used time-updated multivariable Cox regression analysis to examine non-fermented or fermented milk intake with time to IHD or MI. Using high-throughput multiplex immunoassays, 276 cardiometabolic plasma proteins were measured in two subcohorts. We applied multivariable-adjusted regression models using a discovery-replication design to examine protein associations with increasing consumption of non-fermented or fermented milk., Results: The results for non-fermented milk differed by sex (p-value for interaction = 0.01). In women, we found a pattern of successively greater risk of IHD and MI at non-fermented milk intake levels higher than 1.5 glasses/day. Compared with an intake of 0.5 glass/day (100 mL/day), non-fermented milk intake of 2 glasses/day in women conferred a multivariable-adjusted hazard ratio (HR) of 1.05 (95% CI 1.01-1.08) for IHD, an intake of 3 glasses/day an HR of 1.12 (95% CI 1.06-1.19), and an intake of 4 glasses/day an HR of 1.21 (95% CI 1.10-1.32). Findings were similar for whole, medium-fat, and low-fat milk. We did not detect higher risks of IHD with increasing milk intakes in men. Fermented milk intake was unrelated to the risk of IHD or MI in either sex. Increasing non-fermented milk intake in women was robustly associated with a higher concentration of plasma ACE2 and a lower concentration of FGF21., Conclusions: We show a positive association between high amounts of non-fermented milk intake and IHD in women but not men. We suggest metabolic pathways related to ACE2 and FGF21 potentially underlie the association., (© 2024. The Author(s).)

The implication of Torquetenovirus (TTV) in ischemic heart disease (IHD) has not been thoroughly explored. This study investigated the association between TTV viremia, pro-inflammatory cytokines, and IHD risk in an aging population. This cross-sectional study included 900 non-IHD subjects and 86 individuals with IHD (aged 55-75 years) selected from the MARK-AGE project. Results were verified in another independent Report-Age cohort, including 94 inpatients with chronic IHD and 111 inpatients with non-IHD (aged 65-96 years). Multivariable logistic regression in the MARK-AGE cohort revealed that male sex, TTV viremia ≥4log, Cu/Zn ratio, diabetes, hypertension, and smoking were significant IHD predictors. Notably, TTV viremia ≥4log independently increased the IHD risk (odds ratio [OR]: 2.51, 95% confidence interval [CI]: 1.42-4.43), confirmed in the Report-Age cohort (OR: 4.90, 95% CI: 2.32-10.39). In a RASIG subgroup, individuals with TTV viremia ≥4 log, both with and without IHD, exhibited increased plasma pro-inflammatory cytokine levels (IFN-γ, IL-1β, IL-6, IL-10, IL-12p70, TNF-α) compared to those with TTV viremia <4 log. No significant difference in cytokine production was observed between IHD patients and non-IHD with TTV viremia ≥4 log. A positive correlation between TTV viremia and DNA methylation estimator of leukocyte telomere length was observed in Report-Age patients. Additionally, IHD Report-Age patients with TTV viremia ≥4 log displayed higher NLR and SIRI index than those with TTV viremia <4 log. In conclusion, a high TTV viremia is associated with an elevated IHD risk in the older population, potentially arising from an augmented pro-inflammatory response and immunosenescence., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

The triglyceride glucose (TyG) index has been suggested as a reliable substitute to indicate insulin resistance. Several studies have identified the association between the TyG index and cardiovascular disease. However, the association between the TyG index and the incidence of myocardial ischemia in patients with minimal to moderate coronary artery disease (CAD) has not been clearly assessed. We aimed to investigate the association between the TyG index and the incidence of myocardial ischemia in patients with minimal to moderate CAD. A total of 1,697 patients who underwent coronary computed tomography angiography (CTA) examinations and had minimal to moderate CAD were retrospectively included in the study. The TyG index and computed tomography-derived fractional flow reserve (CT-FFR) were used to assess insulin resistance (IR) and myocardial ischemia, respectively. Myocardial ischemia was defined as a CT-FFR value ≤ 0.80. Logistic regression models were used to explore the associations between the TyG index and myocardial ischemia. The incidence of myocardial ischemia was higher in the highest TyG index tertile (T3) group than in the lowest TyG index tertile (T1) group. After adjusting for other variables, the T3 group remained associated with a higher risk of myocardial ischemia than the T1 group did (OR, 1.43; 95% CI, 1.01-2.04; p = 0.047). A 1- standard deviation (SD) increase in the TyG index was correlated with a 19-24% elevated risk of myocardial ischemia when regarding the TyG index was considered as a continuous variable. Subgroup analysis revealed similar effects. A TyG index is associated with a higher risk of myocardial ischemia detected by CT-FFR in patients with minimal to moderate CAD., (© 2024. The Author(s).)

Polygonatum cyrtonema Hua and its processed products have demonstrated cardio-protective effects, though the underlying mechanisms remain unclear. In this study, plasma metabolic profiling and pattern recognition were employed to explore the cardio-protective mechanisms of both crude and processed P. cyrtonema in a myocardial ischemia model induced by ligation, using gas chromatography-mass spectrometry. Post-modeling, plasma levels of creatine kinase-MB, lactate dehydrogenase, troponin T, and malondialdehyde were significantly elevated but were notably reduced after treatment. Conversely, plasma levels of glutathione peroxidase and superoxide dismutase, which were significantly decreased post-modeling, were restored following treatment. Hematoxylin-eosin (HE) and Masson staining revealed that both crude and processed P. cyrtonema effectively reduced inflammatory infiltration and fibrosis in cardiac tissue. Metabolic profiling identified 34 differential endogenous metabolites in the treatment groups, with 19 confirmed using standard compounds. The linear correlation coefficients (R2) for these standards ranged from 0.9960 to 0.9996, indicating high accuracy. The method exhibited excellent precision and repeatability, with relative standard deviation (RSD) values below 8.57%. Recovery rates were between 95.02% and 105.15%, and the stability of the standard compounds was confirmed after three freeze-thaw cycles, with RSD values under 4.42%. Both crude and processed P. cyrtonema were found to alleviate myocardial ischemia symptoms by regulating branched-chain amino acid metabolism and energy metabolism. These findings provide a solid foundation for the potential clinical use of this herb and its processed products in treating heart disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Myocardial ischemia (MI) in children living with sickle cell anemia (SCA) is rarely reported. MI among children living with this disease could portend untoward outcomes on their quality of life and survival. This study evaluated the prevalence and associated risk factors of MI in children living with SCA during a vaso-occlusive crisis (VOC) compared with those with SCA who had no symptoms nor an MI in the past (those in "steady state") in Lagos, Nigeria. This comparative cross-sectional study was conducted over 10 months (between March and December 2019) among 250 children living with SCA aged 6 months-18 years (125 in VOC and 125 age and sex-matched controls in steady state). The assessment of MI was determined by measuring cardiac troponin T (cTnT) and electrocardiography (ECG). The prevalence of MI measuring cTnT alone in children with SCA during VOC and steady state was 42.4% and 23.2%, respectively. Comparatively, measuring ECG alone, the prevalence of MI in VOC and steady state was 40.8% and 20.8%, respectively. The prevalence of MI measuring cTnT and ECG in children with SCA in VOC and steady state was 38.4% and 20%, respectively. Older age, severity of pain, longer duration of illness, frequent crises per year, elevated white blood cells, and platelet count were significantly associated with MI in participants with SCA. However, with multivariate analysis, age, severity of pain, and elevated platelet counts remained significantly associated with the occurrence of MI. This study affirms the high prevalence of MI in children with SCA irrespective of the diagnostic criteria. Routine evaluation should be done in this cohort to avert MI-associated sequelae., (© The Author(s) [2024]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: It is known that the risk of ischemic heart disease increases in patients with type 2 diabetes mellitus (T2DM). For female patients, the incidence of heart disease can be even greater after menopause, accompanied by dramatic changes in sex hormones. We investigated the correlations between sex hormones and markers of ischemic heart diseases in postmenopausal females with T2DM patients., Methods: This cross-sectional study collected data from 324 hospitalized postmenopausal females with T2DM. Multiple linear regression analyses were conducted to determine the correlations between sex hormones and cardiac markers including high-sensitive cardiac troponin T (hs-cTnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels., Results: Multiple linear regression analyses revealed that luteinizing hormone (LH) was positively and independently associated with hs-cTnT concentrations in postmenopausal females with T2DM (β = 0.189, p = 0.002). Postmenopausal females with T2DM and subclinical myocardial injury had higher LH levels than those without subclinical myocardial injury (29.67 vs. 25.08 mIU/mL, p < 0.001). A multivariate logistic regression analysis confirmed an independent and significant association between elevated LH and subclinical myocardial injury in postmenopausal females with T2DM (adjusted odds ratio [OR] = 1.077, 95% confidence interval [CI], 1.033-1.124; p < 0.001). As another gonadotropin, the follicle-stimulating hormone did not show independent correlations with hs-cTnT or NT-proBNP (p > 0.05). Neither estrogen nor testosterone was correlated with cardiac markers., Conclusions: Elevated LH levels were positively and independently associated with increased hs-cTnT levels in postmenopausal women with T2DM. Our findings suggest that LH could serve as a potential marker for assessing the risk of subclinical myocardial injury in postmenopausal females with T2DM., (© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background and Aims: We tested the association of polygenic risk scores (PRS) for low-density lipoprotein cholesterol (LDL-C) and coronary artery disease (CAD) with LDL-C and risk of ischemic heart disease (IHD) in the Danish general population., Methods: We included a total of 21,485 individuals from the Copenhagen General Population Study and Copenhagen City Heart Study. For everyone, LDL-PRS and CAD-PRS were calculated, each based on >400,000 variants. We also genotyped four rare variants in LDLR or APOB known to cause familial hypercholesterolemia (FH)., Results: Heterozygous carriers of FH-causing variants in APOB or LDLR had a mean LDL-C of 5.40 and 6.09 mmol/L, respectively, and an odds ratio for IHD of 2.27 (95 % CI 1.43-3.51) when compared to non-carriers. The LDL-PRS explained 13.8 % of the total variation in LDL-C in the cohort. Individuals in the lowest and highest 1 % of LDL-PRS had a mean LDL-C of 2.49 and 4.75 mmol/L, respectively. Compared to those in the middle 20-80 %, those in the lowest and highest 1 % of LDL-PRS had odds ratios for IHD of 0.58 (95 % CI, 0.38-0.88) and 1.83 (95 % CI, 1.33-2.53). The corresponding odds ratios for CAD-PRS were 0.61 (95 % CI, 0.41-0.92) and 2.06 (95 % CI, 1.49-2.85)., Conclusions: The top 1 % of LDL-PRS and CAD-PRS conferred effects on LDL-C and risk of IHD comparable to those seen for carriers of rare FH-causing variants in APOB or LDLR. These results highlight the potential value of implementing such PRS clinically., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ischemia-modified albumin (IMA) has emerged as a pivotal biomarker for the early detection of ischemic conditions, particularly myocardial ischemia, where timely diagnosis is crucial for effective intervention. This review provides an overview of the analytical methods for assessment of IMA, including Albumin Cobalt Binding (ACB), Albumin Copper Binding (ACuB), Enzyme-Linked Immunosorbent Assay (ELISA), new techniques such as liquid crystal biosensors (LCB), quantum dot coupled X-ray fluorescence spectroscopy (Q-XRF), mass spectrometry (MS), and electron paramagnetic resonance (EPR) spectroscopy. Each method was thoroughly examined for its analytical performance in terms of sensitivity, specificity, and feasibility. The ACB assay is the most readily implementable method in clinical laboratories for its cost-effectiveness and operational simplicity. On the other hand, the ACuB assay exhibits enhanced sensitivity and specificity, driven by the superior binding affinity of copper to IMA. Furthermore, nanoparticle-enhanced immunoassays and liquid crystal biosensors, while more resource-intensive, significantly improve the analytical sensitivity and specificity of IMA detection, enabling earlier and more accurate identification of ischemic events. Additionally, different biological matrices, such as serum, saliva, and urine, were reviewed to identify the most suitable for accurate measurements in clinical application. Although serum was considered the gold standard, non-invasive matrices such as saliva and urine are becoming increasingly feasible due to advances in technology. This review underscores the role of IMA in clinical diagnostics and suggests how advanced analytical techniques have the potential to significantly enhance patient outcomes in ischemic disease management.

Objective: To explore the association between the triglyceride-glucose index (TyG) and TyG-obesity composite indices, including TyG-waist circumference (TyG-WC), TyG-body mass index (TyG-BMI), and TyG-waist-to-height ratio (TyG-WHtR), and the risk of ischemic heart disease (IHD), and to provide reference for the prevention of IHD., Methods: The sample of this study was derived from the West China Elderly Preventive and Treatment Merging Cohort, from which 9628 elderly individuals from the retrospective cohort were selected. Cox regression models were used to analyze the association between TyG-related indices and the risk of IHD. Receiver operating characteristic (ROC) curves were plotted to assess and compare the performance of TyG-related indices in predicting the occurrence of IHD., Results: The participants were followed up for a median of 2.82 years, with 7.2% (694/9628) of the participants experiencing IHD events. Multivariate Cox regression showed that after controlling for the covariates, including sex, age, educational attainment, smoking, drinking, exercise, dietary habits, medication history, and whether the participant had hypertension, every time TyG, TyG-WC, TyG-BMI and TyG-WHtR increased by one standard deviation (SD), the risk of IHD increased by 12% (hazard ratio [HR]=1.12, 95% confidence interval [CI]: 1.04-1.20), 21% (HR=1.21, 95% CI: 1.12-1.31), 20% (HR=1.20, 95% CI: 1.12-1.29), and 19% (HR=1.19, 95% CI: 1.10-1.28), respectively. Both the TyG index and TyG-obesity composite indices were positively correlated with IHD risk, showing a linear relationship ( P <0.05). TyG-WC (area under the curve[AUC]=0.680, 95% CI: 0.660-0.700, P <0.001), TyG-BMI (AUC=0.674, 95% CI: 0.654-0.695, P <0.001), and TyG-WHtR (AUC=0.678, 95% CI: 0.658-0.698, P <0.001) demonstrated better predictive performance than TyG did (AUC=0.669, 95% CI: 0.648-0.689, P <0.001)., Conclusion: Elevated levels of TyG and TyG-obesity composite indices were associated with a higher risk for IHD, and combining TyG with BMI, WC, and WHtR may lead to better performance in risk assessment for IHD than using TyG alone., Competing Interests: 利益冲突　本文作者李佳圆是本刊编委会编委，姜侠是本刊编委会青年编委。该文在编辑评审过程中所有流程严格按照期刊政策进行，且未经其本人经手处理。除此之外，所有作者声明不存在利益冲突。, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

Aims: The purpose of this study was to analyze the dynamic trends of ischemic heart disease (IHD) mortality attributable to high low-density lipoprotein cholesterol (LDL-C)., Methods: Data on IHD mortality attributable to high LDL-C from 1990 to 2021 were extracted from the global disease burden database. Joinpoint software was used to estimate the average annual percentage change (AAPC) in the age-standardized mortality rate (ASMR). An age‒period‒cohort model was used to analyze the impacts of age, period, and cohort on these changes. The Bayesian framework was used to predict IHD mortality attributable to high LDL-C from 2022 to 2040., Results: The overall ASMR of IHD attributable to high LDL-C decreased from 50. 479 per 100,000 people in 1990 to 32.286 per 100,000 people in 2021, and ASMR of IHD attributable to high LDL-C was higher in males than in females. The longitudinal age curves of the overall IHD mortality attributable to high LDL-C showed a monotonic upward trend, especially after 65 years of age. The period and cohort effect relative risk (RR) values of overall IHD mortality attributable to high LDL-C showed a downward trend. The overall ASMR of IHD attributable to high LDL-C is predicted to show a downward trend, and male IHD mortality attributable to high LDL-C is expected to be higher than that of females., Conclusion: This study revealed a sustained decrease in IHD mortality attributable to high LDL-C over three decades, with a continued decline expected. Despite this, gender disparities persist, with males experiencing higher mortality rates and elderly individuals remaining a vulnerable group., (© 2024. The Author(s).)

Subjects who have ischemia with non-obstructive coronary arteries (INOCA) experience angina pectoris with evidence of myocardial ischemia but without coronary stenosis. Few studies have investigated factors associated with its survival, especially insulin resistance. In this study, subjects with angina pectoris, without known diabetes mellites (DM), and with non-invasive tests showing myocardial ischemia were admitted for coronary angiography (CAG). Those whose CAG did not reveal stenosis and agreed to receive an oral glucose tolerance test (OGTT) 2 weeks after hospital discharge were enrolled for analysis. All-cause mortality was recorded, which served as the outcome of the study. A total of 587 subjects with INOCA, without known DM, and with OGTT data were analyzed. After OGTT and HbA1c tests, 86 subjects (14.7%) were newly diagnosed with DM and 59.8% had pre-DM. The median duration of follow-up was 7.03 years. Thirty-nine subjects died during the follow-up period. The incidence rate of mortality was 9.9 /1000 person-year. Those who died had a higher fasting glucose (101 ± 17 vs. 94 ± 13 mg/dl, p = 0.003) but a lower estimated glomerular filtration rate (eGFR) (54 ± 22 vs. 87 ± 30 ml/min, p < 0.001). In the Cox survival analysis, a higher fasting glucose (hazard ratio 1.053, p = 0.007) was associated with worse mortality for INOCA without DM (N = 501). On the contrary, a higher eGFR (hazard ratio 0.967, p = 0.012) was protective of better survival for non-diabetic INOCA (N = 501). In conclusion, for non-diabetic INOCA, higher fasting glucose was associated with worse mortality and higher eGFR was protective for better survival., (© 2024. The Author(s).)

Background and Aims: Emerging evidence suggests an arrhythmogenic effect of Anti-Ro/SSA (anti-Ro) and anti-La/SSB (anti-La) antibodies in adults, potentially involving a subclinical intracardiac inflammatory process. Despite the established association between inflammation and ischemic heart disease (IHD), it is noteworthy that as of now no study has delved into the potential link between these antibodies and IHD. This population-based study aimed to examine the association between anti-Ro/La seropositivity and IHD in the general adult population., Methods: We conducted a retrospective study using electronic medical records from the largest health maintenance organization in Israel. Patients with positive serology for either or both anti-Ro and anti-La antibodies were included, along with matched controls. Multivariate logistic regression models were utilized to assess the odds of IHD in seropositive patients compared to controls., Results: Among 17,231 seropositive patients and 84,368 controls, the rate of IHD was significantly higher in the seropositive group (9.7 % vs. 8.1 %,OR = 1.23; 95%CI 1.14-1.31; p<0.001). The association was more pronounced in younger patients [<40 years old (OR = 3.36; 95%CI 1.66-6.82; p<0.001), 40-49 years old (OR = 1.85; 95%CI 1.26-2.73; p<0.01), 50-59 years old (OR = 1.87; 95%CI 1.55-2.26; p<0.001), 60-69 years old (OR = 1.26; 95%CI 1.11-1.42; p<0.001), ≥70 years old (OR = 1.11; 95%CI 1.03-1.20; p<0.01)], as well as in patients with fewer traditional cardiovascular risk-factors (none:OR = 1.29; 95 % CI 1.09 to 1.77; p<0.01, 1-2:OR = 1.30; 95 % CI 1.19 to 1.41; p<0.001, ≥3:OR = 1.09; 95 % CI 0.99 to 1.21; p=0.076)., Conclusions: Our study demonstrates for the first time a positive association between anti-Ro/La seropositivity and IHD in the general adult population, especially among younger individuals with fewer traditional cardiovascular risk factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Ischemic heart disease (IHD) is a leading cause of morbidity and mortality worldwide, requiring innovative management strategies. Traditional disease management programs often struggle to maintain patient engagement and ensure long-term adherence to lifestyle modifications and treatment plans. Mobile health (mHealth) technologies have emerged as a promising approach to address these challenges by providing continuous, personalized support and monitoring. However, the reported use and effectiveness of mHealth in the management of chronic diseases, such as IHD, have not been fully explored., Objective: The primary aim of this study was to evaluate the feasibility and initial impact of an mHealth-based disease management program on coronary risk factors, specifically focusing on low-density lipoprotein cholesterol (LDL-C) levels, in individuals with chronic IHD. This formative study assessed changes in LDL-C and other metabolic health indicators over a 6-month period to determine the initial impact of the program on promoting cardiovascular health and lifestyle modification., Methods: This study was conducted using data from 266 individuals enrolled in an mHealth-based disease management program between December 2018 and October 2022. Eligibility was based on a documented history of IHD, with participants undergoing a comprehensive cardiac risk assessment before enrollment. The program included biweekly telephone sessions, health tracking via a smartphone app, and regular progress reports to physicians. The study measured change in LDL-C levels as the primary outcome, with secondary outcomes including body weight, triglyceride levels, and other metabolic health indicators. Statistical analysis used paired 2-tailed t tests and stratified analyses to assess the impact of the program., Results: Participants experienced a significant reduction in LDL-C, with LDL-C levels decreasing from a mean of 98.82 (SD 40.92) mg/dL to 86.62 (SD 39.86) mg/dL (P<.001). The intervention was particularly effective in individuals with high baseline LDL-C levels. Additional improvements were seen in body weight and triglyceride levels, suggesting a broader impact on metabolic health. Program adherence and engagement metrics suggested high participant satisfaction and compliance., Conclusions: The results of this study suggest that the mHealth-based disease management program is feasible and has an initial positive impact on reducing LDL-C levels and improving metabolic health in individuals with chronic IHD. However, the study design does not allow for a definitive conclusion regarding whether mHealth-based disease management programs are more effective than traditional face-to-face care. Future studies are needed to further validate these findings and to examine the comparative effectiveness of these interventions in more detail., (©Takahiro Miki, Junya Yamada, Shinpei Ishida, Daisuke Sakui, Masashi Kanai, Yuta Hagiwara. Originally published in JMIR Formative Research (https://formative.jmir.org), 22.08.2024.)

Background: High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction., Methods and Results: Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 μg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped., Conclusions: Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

Objective: The primary objective of this study was to assess the diagnostic potential of galectin-3 (Gal-3), fractalkine (FKN), interleukin (IL)-6, microRNA(miR)-21, and cardiac troponin I (cTnI) in patients with ischemic cardiomyopathy (ICM)., Method: A total of 78 ICM patients (Case group) and 80 healthy volunteers (Control group) admitted to our hospital for treatment or physical examination from Aug. 2018 to Feb. 2020 were included in the current study. The serum concentration of Gal-3, FKN, IL-6, miR-21, and plasma expression of cTnI of both groups were determined. The severity of ICM was classified using New York Heart Association (NYHA) scale., Results: When compared with the control group, the case group had a significantly high blood concentration of Gal-3, FKN, IL-6, miR-21, and cTnI ( P < 0.001). NYHA class II patients had lower blood levels of Gal-3, FKN, IL-6, miR-21, and cTnI than that in patients of NYHA class III and IV without statistical significance ( P > 0.05). However, statistical significance could be achieved when comparing the above-analyzed markers in patients classified between class III and IV. Correlation analysis also revealed that serum levels of Gal-3, FKN, IL-6, miR-21, and cTnI were positively correlated with NYHA classification (R = 0.564, 0.621, 0.792, 0.981, P < 0.05)., Conclusion: Our study revealed that up-regulated serum Gal-3, FKN, IL-6, miR-21, and cTnI levels were closely related to the progression of ICM. This association implies that these biomarkers have diagnostic potential, offering a promising avenue for early detection and monitoring of ICM progression.

Aims: To explore the associations between visit-to-visit lipid variability and risk of ischemic heart disease (IHD) in a population-based cohort in China., Methods: We evaluated lipid variability in 30,217 individuals from the Yinzhou Health Information System who had ≥3 recorded lipid measurements during 2010-2014. We used various indicators including standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV) to quantify the variability in triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Overall, a total of 1305 participants with IHD were identified during the follow-up of 194,421 person-years. Subjects in Q4 had a 21% elevated risk of IHD (HR = 1.21, 95% CI: 1.03-1.41) for LDL-C variability (CV) compared with the reference (Q1). The HRs for Q4 vs Q1 were 1.21 (95% CI: 1.04-1.42) for HDL-C variability, and 1.28 (95% CI: 1.10-1.50) for TC variability. However, no association was observed between triglycerides variability and risk of IHD., Conclusions: Higher variability in LDL-C, HDL-C, and TC levels was associated with an elevated risk of IHD, suggesting that lipid variability could be considered as an independent risk factor of IHD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The present study aimed to explore the predictive value and prognosis of SYNTAX score, nerve growth factor (NGF), trimethylamino oxide (TMAO), silent information regulator 1 (SIRT1), and apolipoprotein A1 (apoA1) for ischemic heart failure (IHF) patients., Methods: From January 2020 to January 2021, 87 patients diagnosed with IHF in the Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, and 42 healthy people were included and analyzed retrospectively. The 87 patients were divided into 3 subgroups according to New York Heart Association (NYHA) heart function classification, as group 1 (n=9, classes I-II heart function), group 2 (n = 7, class III heart function), and group 3 (n = 31, class IV heart function). The levels of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left atrium diameter (LAD), NGF, TMAO, SIRT1, SYNTAX score, and apoA1 were compared among these groups., Results: The SIRT1 and apoA1 of patients with classes I-II, III, and IV heart function were significantly lower than that of healthy people in the control group, while TMAO and NGF were significantly higher than those of healthy people (all P < .05). The SYNTAX score of grade I-II, grade III, and grade IV groups was significantly lower than that of the healthy group (P < .05). The two groups had no significant difference in the number of coronary artery lesions (P > .05). The SIRT1 and apoA1 of patients with classes III and IV heart function were significantly lower than that of patients with classes I -II heart function, while TMAO and NGF were significantly higher than those of class I-II people (all P < .05). The SIRT1 and apoA1 of patients with class IV heart function were significantly lower than those of patients with class III heart function, while TMAO and NGF were significantly higher than those of patients with class III heart function (all P < .05). After 1 year follow-up of these IHF patients, 22 patients were readmission because of cardiac events, and 6 patients died in hospital or during follow-up. These 28 patients were allocated to the event group, while the rest 59 patients were allocated to the events-free group. The SIRT1 and apoA1 level in event group was significantly lower than those of event-free group, while the TMAO, SYNTAX score, and NGF level were significantly higher than those of the event-free group (all P < .001). Baseline characters and heart function with significant differences (LVEF, LAD and LVEDD) among these groups, and NGF, TMAO, SIRT1, SYNTAX score and apoA1 were enrolled into Logistic regression. SYNTAX score, NGF, TMAO, SIRT1 and apoA1 were independent risk factors for the prognosis of IHF patients (all P < .05)., Conclusion: SIRT1, apoA1, TMAO and NGF serum levels in patients with IHF are abnormally expressed and closely related to cardiac function. The levels of SYNTAX score, NGF, TMAO, SIRT1, and apoA can effectively predict adverse events in patients with IHF.

Background: Ischemia and no obstructive coronary artery disease (INOCA) is increasingly recognized and associated with poor outcomes. The triglyceride-glucose (TyG) index is a reliable alternative measure of insulin resistance significantly linked to cardiovascular disease and adverse prognosis. We investigated the association between the TyG index and myocardial ischemia and the prognosis in INOCA patients., Methods: INOCA patients who underwent both coronary angiography and myocardial perfusion imaging (MPI) were included consecutively. All participants were divided into three groups according to TyG tertiles (T1, T2, and T3). Abnormal MPI for myocardial ischemia in individual coronary territories was defined as summed stress score (SSS) ≥ 4 and summed difference score (SDS) ≥ 2. SSS refers to the sum of all defects in the stress images, and SDS is the difference of the sum of all defects between the rest images and stress images. All patients were followed up for major adverse cardiac events (MACE)., Results: Among 332 INOCA patients, 113 (34.0%) had abnormal MPI. Patients with higher TyG index had a higher rate of abnormal MPI (25.5% vs. 32.4% vs. 44.1%; p = 0.012). Multivariate logistic analysis showed that a high TyG index was significantly correlated with abnormal MPI in INOCA patients (OR, 1.901; 95% CI, 1.045-3.458; P = 0.035). During the median 35 months of follow-up, 83 (25%) MACE were recorded, and a higher incidence of MACE was observed in the T3 group (T3 vs. T2 vs. T1: 36.9% vs. 21.6% vs. 16.4%, respectively; p = 0.001). In multivariate Cox regression analysis, the T3 group was significantly associated with the risk of MACE compared to the T1 group (HR, 2.338; 95% CI 1.253-4.364, P = 0.008)., Conclusion: This study indicates for the first time that the TyG index is significantly associated with myocardial ischemia and poor prognosis among INOCA patients., (© 2024. The Author(s).)

Background: Interleukin-17 (IL-17) has been hypothesized to be involved in ischemic cardiovascular disease (ICVD). However, the association of IL-17 with ICVD remained unclear. The aim of this study was to systematically analyze the available evidence regarding the association between IL-17 and ICVD., Methods: We searched the PubMed, Web of Science, Cochrane Library, and Embase databases up to October 2023 to identify publications on the association between IL-17 and ICVD. The merged results were analyzed using a random effects model for meta-analysis and subgroup analysis., Results: A total of 955 publications were initially identified in our search and screened; six studies were eventually included in the analysis. The average age of study participants was 60.3 ± 12.6 years and 65.5% were men. There was a high degree of heterogeneity among studies. The results showed that IL-17 level were higher in the case group than those in the control group (standardized mean difference, SMD = 1.60, 95% confidence interval (95% CI): 0.53-2.66, P = 0.003). In sensitivity analysis, the merged results showed good robustness. Additionally, subgroup analysis showed that race and ethnicity, sample size, and detection methods were significant factors influencing heterogeneity in the published studies., Conclusion: Our finding revealed that increased IL-17 level contributed to the development of ICVD, suggesting IL-17 as a potential risk marker. Further research is needed to establish IL-17 as a therapeutic biomarker of ICVD., (© 2024. The Author(s).)

Objective: To investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related., Research Design and Methods: Observational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC., Results: Observationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (β-coefficient: 0.02 (0.02, 0.03), p = 3 × 10 - 20 ); however, one- and two-sample MR did not support a causal effect of CRP on glucose (-0.04 (-0.12, 0.32) and - 0.03 (-0.13, 0.06)), nor of glucose on CRP (-0.01 (-0.08, 0.07) and - 0.00 (-0.14, 0.13))., Conclusions: Elevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation., (© 2024. The Author(s).)

Background: Previous studies showed that exercise may increase cardiac troponin serum levels; whether the occurrence of myocardial ischemia influences the changes of exercise-induced troponin raise, however, remains debatable., Methods: We prospectively enrolled consecutive patients undergoing for the first time an elective stress myocardial perfusion scintigraphy (MPS) because of clinical suspicion of obstructive coronary artery disease (CAD). Patients were divided into 3 groups based on the evidence and degree of stress-induced myocardial ischemia at MPS: 1) group 1, no myocardial ischemia (≤4 %); 2) group 2, mild myocardial ischemia (5-10 %); 3) group 3, moderate-to-severe myocardial ischemia (≥10 %). High-sensitivity cardiac troponin I (cTnI) was measured immediately before (T 0 ) and 1 hour (T 1 ) and 4 h (T 2 ) after the stress test., Results: One hundred-seven patients (71 males; age 65.6 ± 9.4 years) were enrolled in the study. Serum hs-cTnI concentrations (logarithmic values) significantly increased after MPS, compared to baseline, in the whole population, from 1.47±1.26 ng/L at T 0 , to 1.68±1.12 ng/L at T 1 (p<0.001) and 2.15±1.02 ng/L at T 2 (p<0.001 vs. both T 0 and T 1 ). The increase in hs-cTnI did not significantly differ between the 3 groups (p = 0.44). The heart rate achieved during the test was the strongest determinant of cTnI increase (p < 0.001) after the stress test., Conclusions: In patients with suspected CAD, stress MPS induces an increase of cTnI that is independent of the induction and extension/severity of myocardial ischemia and is mainly related to myocardial work, as indicated by the heart rate achieved during the test., (Copyright © 2023. Published by Elsevier B.V.)

In patients with sickle cell disease (SCD), SCD-related cardiomyopathy may be partly due to repeated ischaemic events related to sickling during vaso-occlusive crises, but few clinical studies support this hypothesis. We evaluated the incidence of acute myocardial ischaemia during vaso-occlusive crises as assessed by the left ventricular global longitudinal strain (LVGLS) and high-sensitive cardiac troponin T (hs-cTnT). We included adult patients with SCD admitted to the intensive care unit (ICU) for vaso-occlusive crisis. We collected hs-cTnT and measured LVGLS with echocardiography at admission (day 1), day 2, day 3 and ICU discharge. Among 55 patients included, considering only the first hospitalization of patients admitted several times, 3 (5%) had elevated hs-cTnT at ≥1 time point of the ICU stay. It was ≤2 times the upper limit of normal in two of these patients. LVGLS was altered at ≥1 time point of the ICU stay in 13 (24%) patients. Both hs-cTnT and LVGLS were abnormal at ≥1 time point of the hospital stay in 2 (4%) patients. Acute myocardial injury as assessed by troponin elevation and LVGLS impairment was a rare event during vaso-occlusive crises., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Objectives: Ischemia-modified albumin (IMA) is a new biochemical marker of ischemia. We aimed to search blood IMA levels in neonates with congenital heart defects., Study Design: During the study period, patients diagnosed with congenital heart disease and newborns with a diagnosis of hyperbilirubinemia as a control group were included in the study. IMA level was analyzed using the IMA absorbance unit (ABSU) method., Results: In total, 57 newborns with congenital heart disease requiring cardiac operation for the study group and 38 newborns for the control group were included. There was no difference between the two groups in terms of gender, mode of delivery, and weeks of gestation. The average IMA values in the control group were 0.19 ± 0.09 ABSU. The prepostoperative mean IMA values of the patient group were 0.22 ± 0.07 and 0.23 ± 0.07 ABSU, respectively. Comparison of the postoperative IMA with the mean of the control group was statistically significant. Preoperative and postoperative IMA values of patients who have died due to primary heart disease and surgical complications were 0.21 ± 0.07 (0.08-0.32) ABSU and 0.25 ± 0.06 (0.12-0.36) ABSU, respectively. IMA levels were not statistically different between the two groups., Conclusion: Hypoxia and ischemia in congenital heart disease in the newborn period both preoperatively and postoperatively were important in prognosis. IMA was higher in the postoperative group. Many comprehensive studies are important in terms of preventing complications and decreasing mortality and morbidity by commenting on prognosis., Key Points: · IMA is a new biochemical marker of ischemia.. · In the literature, there are no reports about the relation between congenital heart defects and IM.. · The exposure of CHD patients to hypoxia/asphyxia in the preintra and postoperative periods cause neurologic deficits., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular disease including stroke, heart failure, and ischemic heart disease (IHD). To prevent the occurrence and progression of CVD, a reliable prognostic cardiac biomarker is essential. We investigated the prognostic value of NT-proBNP for each incident type of CVD., Methods: Male patients from the Ibaraki Dialysis Initiation Cohort (iDIC) study with preserved serum samples from dialysis initiation day (n = 212) were analyzed. Patients were classified into four groups according to quartiles of baseline NT-pro BNP levels. The relationship between NT-proBNP levels at the initiation of dialysis and the subsequent incidence of hospitalization events due to IHD, heart failure, and stroke was analyzed., Results: The incidence rate for hospitalization due to IHD was significantly higher in the highest NT-proBNP category (Log rank p = 0.008); those of stroke and heart failure showed no significant differences among quartiles. Cox proportional hazards regression analysis revealed that serum NT-proBNT was the only prognostic factor for hospitalization for IHD after adjustment by major known IHD risk factors. (HR, 1.008; 95% confidence interval, 1.002-1.014; p = 0.01) The ROC curve analysis for the incidence of hospitalization due to IHD showed that NT-proBNP had an area under the curve (AUC) of 0.759 (95% CI 0.622-0.897; p = 0.004) at a cut-off value of 956.6 pg/mL., Conclusion: NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD., Trial Registration: UMIN000010806., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Aims: The impact of newly detected diabetes mellitus (NDDM) on metabolic parameters and extent of myocardial necrosis in patients with acute coronary syndrome (ACS) is not fully explored. We examined the impact of NDDM on cardiometabolic characteristics and myocardial necrosis in ACS patients., Methods: CALLINICUS-Hellas Registry is an ongoing prospective multicenter observational study evaluating the adherence to lipid-lowering therapy (LLT) among ACS patients in Greece. Three groups were created: a) patients with NDDM (abnormal fasting glucose, HbA1c ≥ 6.5 % and no previous history of DM), b) patients without known DM and HbA1c < 6.5 % (non-DM) and c) patients with prior DM., Results: The prevalence of NDDM among 1084 patients was 6.9 %. NDDM patients had lower HDL-C [38 (32-45) vs 42 (36-50) mg/dL] and higher triglycerides levels [144 (104-231) vs 115 (87-152) mg/dL] compared to non-DM patients (p < 0.05). NDDM patients featured both higher body mass index [29.5 (26.4-34.3) vs 27.1 (24.9-29.9) kg/m 2 ] and waist circumference [107 (100-114) vs 98 (91-106) cm] compared to non-DM patients (p < 0.05). In addition, NDDM patients had more extensive myocardial necrosis than patients with prior DM., Conclusions: ACS patients with NDDM have an adverse cardiometabolic profile similar to patients with prior DM and have more extensive myocardial insult., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Extracellular potassium concentration might modify electrophysiological properties in the border zone of ischemic myocardium. We evaluated the depolarization and repolarization characteristics across the ischemic-normal border under [K + ] variation. Sixty-four-lead epicardial mapping was performed in 26 rats ([K + ] 2.3-6.4 mM) in a model of acute ischemia/reperfusion. The animals with [K + ] < 4.7 mM (low-normal potassium) had an ischemic zone with ST-segment elevation and activation delay, a border zone with ST-segment elevation and no activation delay, and a normal zone without electrophysiological abnormalities. The animals with [K + ] >4.7 mM (normal-high potassium) had only the ischemic and normal zones and no transitional area. Activation-repolarization intervals and local conduction velocities were inversely associated with [K + ] in linear regression analysis with adjustment for the zone of myocardium. The reperfusion extrasystolic burden (ESB) was greater in the low-normal as compared to normal-high potassium animals. Ventricular tachycardia/fibrillation incidence did not differ between the groups. In patch-clamp experiments, hypoxia shortened action potential duration at 5.4 mM but not at 1.3 mM of [K + ]. IK(ATP) current was lower at 1.3 mM than at 5.4 mM of [K + ]. We conclude that the border zone formation in low-normal [K + ] was associated with attenuation of IK(ATP) response to hypoxia and increased reperfusion ESB., Competing Interests: The authors report no conflicts of interest in this work.

Resolvins and maresins, members of the specialized proresolving mediator (SPM) family, are omega-3 fatty acid-derived lipid mediators that attenuate inflammation. We hypothesized that they play a role in the pathophysiology of coronary microvascular dysfunction (CMD) in women with ischemia and no obstructive coronary disease. In a pilot study, we measured the D-series resolvins (D1, D2, D3, and D5), resolvin E1, maresin 1, docosahexaenoic acid, eicosapentaenoic acid (precursor of resolvin E1), and 18-hydroxyeicosapentaenoic acid by mass spectrometry in the peripheral blood of 31 women enrolled in the Women's Ischemia Trial to Reduce Events in Nonobstructive CAD (WARRIOR) trial who had confirmed CMD assessed by coronary flow reserve. We compared SPM levels with 12 gender and age-matched reference subjects. Compared with the reference subject group, those with CMD had significantly lower plasma concentrations of resolvin D1 and maresin 1 and significantly higher levels of docosahexaenoic acid and 18-hydroxyeicosapentaenoic acid. In conclusion, insufficient or ineffective SPM production may play a role in the pathophysiology of CMD. If our results are validated in a larger cohort, omega-3 fatty acid supplementation could be tested as a novel treatment for these patients., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: The purpose of this study was to investigate the mechanism and effects of "Danggui-kushen" herb pair (DKHP) better than single drug in ischemic heart disease (IHD)., Methods: IHD model was established by left anterior descending branch of coronary artery in rats. Rats were randomized into six groups and oral administration for 7 days: control, model, Danshen dripping pills (DS) (5.103 g/kg), Danggui (DG) (2.7 g/kg), Kushen (KS) (2.7 g/kg) and DKHP (2.7 g/kg). Electrocardiogram (ECG), myocardial infarction and damage assessment, histological inspection analysis, and various biochemical indexes of myocardial tissue were measured to evaluate the myocardial damage and the protective effects of drugs. The inflammatory levels were identified by HE staining and serum cytokine, and the expression of hypoxia-inducible factor 1α (HIF-1α), inhibitor kappa B kinaseβ (IKKβ) and nuclear transcription factor kappa B (NF-κB) were measured by immunohistochemistry., Key Findings: The results suggested that: compared with the control group, model group showed significantly myocardial tissue abnormalities, and increased levels of inflammatory cytokine. Treatment with drugs inhibited the increase of α-hydroxybutyrate dehydrogenase (α-HBDH), creatine kinase (CK), creatinekinase isoenzyme (CK-MB), interleukin 1 (IL-1) and interleukin 6 (IL-6). The results of immunohistochemical showed that drugs-treatment inhibited the expression of IKKβ and the P-p65, increased the expression of HIF-1α, which demonstrated that the anti-inflammatory effects of DKHP was achieved by suppressing of NF-κB signaling., Conclusion: These observations indicated that DKHP can ameliorate myocardial injury better than single. And these are related to the inhibition of NF-κB and actives HIF-1α signaling., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: In women, preeclampsia has a known association with increased long-term cardiovascular morbidity and mortality. However, it is unknown whether it is associated with increased postoperative cardiovascular morbidity and mortality in women. We aimed to determine if preeclampsia is an independent risk factor for myocardial injury after noncardiac surgery (MINS) and postoperative 30-day mortality., Methods: This study was a large international multicentre cohort study of a representative sample of 40,004 patients recruited from August 2007 to November 2013. Participants were ≥ 45 years of age and underwent inpatient noncardiac surgery. Within this cohort, our study examined women with a history of pregnancy. Using multivariable models, we explored the association between a history of pregnancy affected by preeclampsia and our primary outcome of MINS and secondary outcome of postoperative mortality within 30 days. MINS was defined as prognostically relevant myocardial injury due to ischemia that occurred during or within 30 days after noncardiac surgery., Results: Analyses were restricted to the 13,902 participants with a history of pregnancy. Among these women, 976 (7.0%) had a history of preeclampsia. A history of preeclampsia was associated with an increased risk of MINS, with an adjusted hazard ratio of 1.26 (95% confidence interval 1.03-1.53; P = 0.02). Preeclampsia was not significantly associated with 30-day mortality., Conclusions: Preeclampsia is a risk factor for MINS and should be considered in the preoperative cardiovascular risk assessment of women., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

In a group of 208 patients with chronic ischaemic heart disease, the variation of A 2 -associated-LDL phosphatase (Lp-PLA 2 ) serum concentration values was analysed in dynamics at a two-week interval. The conclusion of the study is that the values of serum concentration of Lp-PLA 2 can be accepted as a biomarker with diagnostic specificity for chronic ischaemic heart disease, a parameter of real utility in medical practice, both in situations where the patient, although clinically reporting the existence of angina pectoris, does not show specific changes on an EKG, and for the assessment of the response to personalised therapy.

Aim: A prospective cohort study in a Japanese urban general population was performed to investigate whether triglyceride (TG) and its related indices were associated with the risk for the incidence of ischemic cardiovascular disease (CVD) after the adjustment for low-density lipoprotein cholesterol (LDL-C) in Asian community dwellers., Methods: A 15.1-year prospective cohort study was performed in 6,684 Japanese community dwellers aged 30-79 years without a history of CVD and whose fasting TG levels were ＜400 mg/dL. After adjusting for covariates, including LDL-C, the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of the deciles (D) of TG and those of 1-standard deviation (SD) increment of log-transformed TG (1-SD of TG) according to LDL-C level (≥ 140 and ＜140 mg/dL) for ischemic CVD incidence were estimated. The multivariable-adjusted HRs and 95%CIs of the quintiles (Q) of TG, TG/HDL-C, and the cardiometabolic index (CMI) for ischemic CVD were also estimated., Results: In 101,230 person-years, 464 ischemic CVD cases occurred. For D 10 of TG, the HR (95%CI) was 1.56 (1.05-2.32), and for 1-SD of TG, it was 1.30 (1.00-1.70) in participants with LDL-C ＜140 mg/dL and 1.07 (0.77-1.50) in those with LDL-C ≥ 140 mg/dL. For Q 5 of the CMI, the multivariable-adjusted HR was higher than those of TG and TG/HDL-C., Conclusions: Fasting TG was an independent predictor for ischemic CVD incidence after adjusting for LDL-C in Japanese community dwellers with TG ＜400 mg/dL. Among TG, TG/HDL-C, and the CMI, the CMI could be the most powerful predictor for ischemic CVD.

Background: With high-sensitivity troponin testing, approximately a third of patients presenting to emergency departments (EDs) with suspected acute coronary syndromes will have mildly abnormal values. However, data regarding rest-stress myocardial perfusion imaging (MPI) in these patients are limited. We hypothesize that stress testing is safe and that the yield for detecting myocardial ischemia is associated with risk stratification by the HEART score., Methods and Results: We conducted a retrospective cohort study of consecutive patients referred for rest-stress MPI with mildly abnormal high-sensitivity troponin T (hs-cTn) values. Outcomes were adverse events related to stress MPI, defined as myocardial infarction or ventricular tachyarrhythmia, and the presence of ischemia, defined as a reversible perfusion defect. Among 213 patients, the median age was 67, most were male (61.5%, n = 131), and prior CAD was common (53.5%, n = 114). Myocardial ischemia was present in 13.6% (n = 29), and there were no adverse events attributable to stress MPI. A higher HEART score was associated with myocardial ischemia (Odds Ratio [OR] 1.50, 95% Confidence Interval [CI] 1.08 to 2.08, P = .002)., Conclusion: Rest-stress MPI appears safe in patients with mildly abnormal hs-cTn values, and the yield for detecting ischemia is associated with the HEART score, though further validation studies are needed., (© 2020. American Society of Nuclear Cardiology.)

Background: No guideline-directed pharmacological therapy has been established for patients with myocardial injury without type 1 myocardial infarction. We investigated the impact of statin treatment in patients with myocardial injury., Methods: Patients with myocardial injury (nonischemic acute and chronic myocardial injury), type 2 myocardial infarction, and type 1 myocardial infarction with at least 1 emergency department visit for chest pain from 2011 to 2014 were included. Dispensed prescriptions of all types of statins with dosage within 180 days from the index visit were collected. In total, 2054 patients were divided into 3 groups: 1) acute myocardial injury (type 2 myocardial infarction, acute nonischemic myocardial injury), 2) chronic myocardial injury, and 3) type 1 myocardial infarction. We estimated the adjusted hazard ratio with 95% confidence interval for death with low- (reference), moderate-, and high-intensity statin therapy., Results: The mean follow-up was 4.2 ± 1.8 years. Only 13% of patients with acute and chronic myocardial injury and 30% with type 1 myocardial infarction were treated with high-intensity statins. Adjusted mortality rates were higher in patients with acute and chronic myocardial injury than in those with type 1 myocardial infarction across all statin intensity categories. In patients with type 1 myocardial infarction, the adjusted mortality risk was 20% (hazard ratio, 0.80; 95% confidence interval, 0.36-1.77) lower in patients with high-intensity therapy. Point estimates in the adjusted models indicated similar associations between statin intensity and mortality risk in patients with acute and chronic myocardial injury., Conclusion: Patients with myocardial injury may benefit from high-intensity statin treatment, but the associations were not statistically significant when adjusting for confounders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Sympathetic and parasympathetic nerve remodeling play an important role in cardiac function after myocardial ischemia (MI) injury. Increasing evidence indicates that electroacupuncture (EA) can regulate cardiac function by modulating the autonomic nervous system (ANS), but little is known about its effectiveness on neural remodeling post-MI., Objectives: To investigate the role of EA in ANS remodeling post-MI., Methods: Adult male C57/BL6 mice were equally divided into the Control (Ctrl), MI and EA groups after generating the MI model by ligating the left anterior descending (LAD) coronary artery. Echocardiography and 2,3,5-triphenyltetrazolium (TTC) staining were employed to evaluate cardiac function and infarct size after EA treatment for five consecutive days. Serum norepinephrine (NE) levels were measured by ELISA to quantify sympathetic activation. Then, ANS remodeling was detected by immunohistochemistry (IHC), RT-qPCR, and Western blotting., Results: Our preliminary findings showed that EA increased ejection fraction and fractional shortening and reduced infarct area after MI injury. Serum NE levels in the EA group were significantly decreased compared with those in the MI group. IHC staining results demonstrated that the density of growth associated protein (GAP)43 and tyrosine hydroxylase (TH) positive nerve fibers in the EA group were decreased with increased choline acetyltransferase (CHAT) and vesicular acetylcholine transporter (VACHT). Meanwhile, the results verified that mRNA and protein expression of GAP43 and TH were significantly inhibited by EA treatment in the MI mice, accompanied by elevated CHAT and VACHT., Conclusions: EA treatment could improve cardiac function and reduce infarct size by modulating sympathetic and parasympathetic nerve remodeling post-MI, thus helping the cardiac ANS reach a new balance to try to protect the heart from further possible injury.

Introduction: Non-ischaemic heart disease (NIHD) is the underlying pathology in∼20% of all sudden cardiac deaths (SCDs). Heavy drinking is known to be associated with SCD due to ischaemic heart disease, but studies on association of recent alcohol consumption and SCD in patients with NIHD are scarce. We evaluated the blood alcohol levels of autopsy verified non-ischaemic SCD victims., Methods: Study population was derived from the Finnish Genetic Study of Arrhythmic Events (Fingesture) ( n  = 5869, mean age 65 ± 12, 79% males). All deaths occurred in Northern Finland during 1998-2017. All victims underwent a medico-legal autopsy. Subjects of SCD due to ischaemic heart disease were excluded., Results: A total of 1301 (mean age 57 ± 12, 78% males) victims of SCD due to NIHD were included in the study. The blood ethanol level was elevated in 543 (42%) subjects, out of which the blood alcohol level was ≥0.10%in 339 (62%) subjects and ≥0.15%in 252 (46%) subjects. Male SCD victims had alcohol in blood more frequently compared to females (45% versus 31%, p  < .001)., Conclusion: Elevated blood alcohol level is common in SCD victims due to NIHD, especially in males. Recent alcohol consumption might contribute to the subsequent SCD in many non-ischaemic SCD victims.KEY MESSAGESElevated blood alcohol level is common in victims of sudden cardiac death due to non-ischaemic heart disease, especially in males.Recent alcohol consumption may contribute to the subsequent death in many nonischemic sudden cardiac death victims.

Background: The cardioprotective ability of n-3 polyunsaturated fatty acids (PUFAs) is controversial. Most studies suggest a specific role for PUFAs in cardioprotection from ischemic heart disease (IHD). However, few studies have used genetic biomarkers of n-3 PUFAs to examine their potential relationships with IHD. This study aimed to use Mendelian randomization to evaluate whether genetically-predicted n-3 PUFAs affect IHD and cardiometabolic risk factors (CRFs)., Methods: Genetic variants strongly (p < 5 × 10 -8 ) and independently (r 2  > 0.1) associated with n-3 PUFAs were derived from the CHARGE Consortium (including 8,866 subjects of European ancestry) and were used as instrumental variables (IVs) for evaluating the effect of n-3 PUFAs, including α-linolenic acid (ALA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Data on the associations between the IVs and IHD, myocardial infarction, and CRFs (including diabetes, lipids, blood pressure, body mass index, and waist-to-hip ratio (WHR)) were obtained from the UK Biobank SOFT CAD GWAS with the CARDIoGRAMplusC4D 1000 Genomes-based GWAS (113,937 IHD cases and 339,115 controls), the Myocardial Infarction Genetics and CARDIoGRAM Exome consortia (42,335 MI cases and 78,240 controls), the DIAbetes Genetics Replication And Meta-analysis consortium (26,676 diabetes mellitus cases and 132,532 controls), the Global Lipids Genetics Consortium (n = 196,475), the International Consortium for Blood Pressure (n = 69,395), and the meta-analysis of GWAS for body fat distribution in the UK Biobank and Genetic Investigation of Anthropometric Traits (n = 694,649)., Results: Genetically-predicted higher ALA was associated with lower risk of IHD, type 2 diabetes (T2D), and lower serum lipids. The effect size per 0.05-unit increase (about 1 standard deviation) in plasma ALA level) was - 1.173 (95% confidence interval - 2.214 to - 0.133) for IHD. DPA and EPA had no association with IHD but were associated with a higher risk of T2D, higher levels of lipids or WHR. DHA had no association with IHD or CRFs., Conclusions: Our study suggests a benefit of ALA for IHD and its main risk factors. DHA, DPA, and EPA had no association with IHD but were partly associated with increasing cardiometabolic risk factors., (© 2021. The Author(s).)

Background and Aims: Musculoskeletal manifestations (carpal tunnel syndrome, Dupuytren's contracture, etc.) may occur in poorly controlled and longstanding diabetes. In this study, we evaluated the relationship of musculoskeletal diseases with microvascular and macrovascular complicationsin patients with diabetes., Methods: A total of 600 patients with diabetes were enrolled in this cross-sectional study. Demographic data and historical records of the patients were retrieved. Musculoskeletal diseases were assessed by clinical examinations and then confirmed by a rheumatologist., Results: Out of the 600 patients with diabetes, 61.5% (369/600) were female and 38.5% (231/600) were male. Diabetic retinopathy, diabetic nephropathy, diabetic peripheral neuropathy, CVA, and diabetes related ischemic heart disease were rated as 43.1%, 33.2%, 7.8%, 7.5%, and 39.6%, respectively. Significant gender differences were observed in the rates of diabetic nephropathy [56.28% for women and 43.71% for men (p value < 0.000)], diabetic peripheral neuropathy [72.34% for women and 27.65% for men (p value < 0.002)], and ischemic heart disease [57.98% for women and 42.01% for men(p value < 0.001)]., Conclusion: Musculoskeletal diseases usually occur in patients with poorly controlled and long-term diabetes. Due to the clear association of microvascular complications with musculoskeletal disease, more attention should be paid to the early detection of these complications in patients with diabetes., Competing Interests: Declaration of competing interest No conflicts of interest exist for Mahdie Fatollahzade and other authors as well as there is no secondary interest, such as financial again., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: The prognostic value of human epididymis protein 4 (HE4) in patients with ischemic cardiomyopathy (ICM) is unknown., Methods: A total of 103 patients with ICM were prospectively enrolled in this study from Hunan Provincial People's Hospital between February 2019 and June 2019. All patients were tested for HE4 levels at baseline and follow-up. Endpoints of the study included cardiovascular death and heart failure-related hospitalization., Results: A total of 96 patients with ICM were included for analysis. After a mean follow-up period of 263 (153-313) days, cardiovascular events were observed in 45 patients. Serum HE4 levels in patients with events were significantly higher than those in patients without events [188.70 (113.35-326.82) pmol/L versus 92.90 (61.50-123.20) pmol/L, P < 0.001]. Multivariate Cox regression analysis revealed that HE4 [χ 2 : 9.602, hazard ratio (HR): 1.003, 95% confidence interval (CI): 1.001-1.005, P = 0.002] and age [χ 2 : 4.55, HR: 1.044, 95% CI: 1.003-1.085, P = 0.033] were independent predictors of events. After adjusting for age and sex, the risk of events in patients with HE4 > 100.2 pmol/L was higher than that in patients with HE4 ≤ 100.2 pmol/L [HR: 3.372, 95% CI: 1.409-8.065, P < 0.001]., Conclusion: HE4 is an independent predictor of cardiovascular death and heart failure-related rehospitalization in patients with ICM., (© 2021. The Author(s).)

This study aimed to detect the defects of the current methods used to monitor unfractionated heparin (UFH) anticoagulant effect and find possible assistive parameters for activated partial thromboplastin time (aPTT) test to improve treatment performance. The required information was gathered from patients' case records, treatment charts and laboratory reports. Kendall's tau correlation coefficient was calculated for analysing the relationship between variables. The partial least squares (PLS) and the stepwise multiple regression were operated, and the area under the receiver operating characteristic curve (AUC) and the r-squared (r2) were used to show the analytical ability of the models, respectively. Overall, 102 UFH-receiving ischemic heart disease patients participated in this study. The aPTT value varied from 30 to 95 s (mean ± SD = 44 ± 14). Therapeutic aPTT values were observed in 15% of hospitalization days. The aPTT value showed statistically significant correlations with mean UFH infusion (U/kg/h), age, prothrombin time (PT), smoking, international normalized ratio, haemoglobin (Hgb) and blood triglyceride level. Triglyceride level and PT were efficacious predictors of aPTT value (P < 0.001, r2 = 0.336). Moreover, blood urea nitrogen (BUN) and blood creatinine (Cr) levels were the best predictors for mortality. The mean BUN/Cr ratio was 18 ± 5 and 25 ± 12 in nonexpired and expired subjects, respectively. If calibrated institution-specific therapeutic aPTT ranges and updated weight-based UFH nomograms get employed, aPTT test, along with the BUN/Cr ratio and Hgb level, as assistive parameters for predicting haemorrhagic incidents, would be near ideal monitoring method in UFH-receiving patients., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The atherogenic index of plasma (AIP), composed of triglycerides and high-density lipoprotein cholesterol, is a novel critical marker for assessing the risk of atherogenicity and cardiometabolic health. We aimed to prospectively study the association between AIP and incident ischemic heart disease (IHD) risk in a large cohort of non-diabetic Korean adults. Data were assessed from 17,944 participants without diabetes from the Health Risk Assessment Study (HERAS) and Korea Health Insurance Review and Assessment (HIRA) data. The participants were divided into four groups according to AIP quartiles, calculated as log (triglyceride/high-density lipoprotein cholesterol). We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional-hazard regression models over a 50-month period that followed the baseline survey. During the follow-up period, 332 participants (1.9%) developed IHD. HRs of IHD for AIP quartiles 2-4 were 1.58 (95% CI, 1.03-2.43), 1.82 (95% CI, 1.20-2.78), and 2.11 (95% CI, 1.37-3.24) after adjusting for age, sex, body mass index, smoking status, alcohol intake, physical activity, mean arterial blood pressure, fasting plasma glucose, high-sensitivity C-reactive protein level, and hypertension medication. Higher AIP levels may precede and predict the development of IHD in non-diabetic Korean adults.

Galectin-3 is a lectin that binds beta-galactosides. It is involved in cardiac remodeling and fibrosis through the activation of macrophages and fibroblasts. ST2 is secreted by myocardial cells due to cardiac overload. These two biomarkers have been traditionally studied in the field of heart failure to guide medical therapy and detect the progression of the disease. Nevertheless, there are novel evidences that connect galectin-3 and ST2 with coronary heart disease and, specifically, with atrial fibrillation. The aim of this article is to concisely review the diagnostic and prognostic role of galectin-3 and ST2 in different cardiac diseases.

Soluble fibrinogen‑like protein 2 (sFGL2), as a novel effector of regulatory T cells (Tregs), exhibits immune regulatory activity in several inflammatory diseases. Immune activation and persistent inflammation participate in the progression of ischemic heart failure (IHF). The present study aimed to determine serum sFGL2 levels in patients with IHF and explore the relationship between sFGL2 levels and cardiac function. A total of 104 patients with IHF and 32 healthy controls were enrolled. patients with IHF were further split into subgroups according to the New York Heart Association functional classification or left ventricular ejection fraction (LVEF). Serum sFGL2 levels and peripheral Tregs frequencies were analyzed by ELISA and flow cytometry, respectively. The suppressive function of Tregs was measured by proliferation and functional suppression assays. Serum levels of sFGL2 and circulating Tregs frequencies were significantly decreased in patients with IHF compared with healthy controls. In patients with IHF, sFGL2 levels and Tregs frequencies were decreased with the deterioration of cardiac function. Tregs from patients with IHF exhibited compromised ability to suppress CD4 + CD25 ‑ T cells proliferation and inflammatory cytokines secretion. Specifically, sFGL2 levels and Tregs frequencies positively correlated with LVEF, whereas negatively correlated with left ventricular end‑diastolic dimension and N‑terminal pro‑brain natriuretic peptide. sFGL2 levels were positively correlated with Tregs frequencies. In conclusion, the reduction of serum sFGL2 levels are associated with the progression of IHF and sFGL2 could be used as a potential indicator for predicting disease severity.

This study aimed to evaluate the concentration of plasma elabela (ELA) in patients with coronary heart disease (CHD) and its correlation with the disease classification.We enrolled 238 patients diagnosed by coronary angiography as CHD and 86 controls. The CHD group was divided into three subgroups: stable angina (SA), unstable angina (UAP), and acute myocardial infarction (AMI). The plasma levels of ELA were measured in all participants and compared among different groups. The relationship between ELA and CHD classification was analyzed.ELA levels were markedly higher by 10.71% in patients with CHD than in controls (P < 0.05). The concentration of ELA in UAP and AMI subgroups were higher than in controls and SA subgroup. The former difference was significant (P < 0.05), but the latter was not. In addition, the ELA concentration was not correlated with SYNTAX score, left ventricular ejection fraction, and other biochemical variables.The newfound hormone, ELA, significantly increased in patients with UAP and AMI. There is a tendency that ELA levels might be correlated with CHD classification, but not with lesion severity. ELA may play a role in acute coronary syndrome.

Background Prior studies have shown an association between myocardial injury after noncardiac surgery (MINS) and all-cause mortality in patients following noncardiac surgery. However, the association between preoperative risk assessments, Revised Cardiac Risk Index and American College of Surgeons National Surgical Quality Improvement Program, and postoperative troponin elevations and long-term mortality is unknown. Methods and Results A retrospective chart review identified 548 patients who had a troponin I level drawn within 14 days of noncardiac surgery that required an overnight hospital stay. Patients aged 40 to 80 years with at least 2 cardiovascular risk factors were included, while those with trauma, pulmonary embolism, and neurosurgery were excluded. Kaplan-Meier survival and odds ratio (OR) with sensitivity/specificity analysis were performed to assess the association between preoperative risk and postoperative troponin elevation and all-cause mortality at 1 year. Overall, 69%/31% were classified as low-risk/high-risk per the Revised Cardiac Risk Index and 66%/34% per American College of Surgeons National Surgical Quality Improvement Program. Comparing the low-risk versus high-risk groups, preoperative risk assessment was not associated with either postoperative troponin elevation or 1-year mortality. MINS portended a 1-year mortality of OR, 3.9 (95% CI, 2.44-6.33) in the total population. Patients classified as low risk preoperatively with MINS had the highest risk of 1-year mortality (OR, 9.6; 95% CI, 4.27-24.38), with a low prevalence of statin use. Conclusions Current preoperative risk stratification tools do not prognosticate the risk of postoperative troponin elevation and all-cause mortality at 1 year. Interestingly, patients classified as low risk preoperatively with MINS had a markedly higher 1-year mortality risk compared with the general population, and most of them are not taking a statin. Our results suggest that evaluating preoperatively low-risk patients for MINS presents an opportunity for prognostication, risk reclassification, and initiating therapies such as statins to mitigate long-term risk.

Background: Patients with chest pain are often evaluated for acute myocardial infarction through troponin testing, which may prompt downstream services (cascades) of uncertain value., Objectives: This study sought to determine the association of high-sensitivity cardiac troponin (hs-cTn) assay implementation with cascade events., Methods: Using electronic health record and billing data, this study examined patient-visits to 5 emergency departments from April 1, 2017, to April 1, 2019. Difference-in-differences analysis compared patient-visits for chest pain (n = 7,564) to patient-visits for other symptoms (n = 100,415) (irrespective of troponin testing) before and after hs-cTn assay implementation. Outcomes included presence of any cascade event potentially associated with an initial hs-cTn test (primary), individual cascade events, length of stay, and spending on cardiac services., Results: Following hs-cTn implementation, patients with chest pain had a 2.8% (95% confidence interval [CI]: 0.72% to 4.9%) net increase in experiencing any cascade event. They were more likely to have multiple troponin tests (10.5%; 95% CI: 9.0% to 12.0%) and electrocardiograms (7.1 per 100 patient-visits; 95% CI: 1.8 to 12.4). However, they received net fewer computed tomography scans (-1.5 per 100 patient-visits; 95% CI: -1.8 to -1.1), stress tests (-5.9 per 100 patient-visits; 95% CI: -6.5 to -5.3), and percutaneous coronary intervention (PCI) (-0.65 per 100 patient-visits; 95% CI: -1.01 to -0.30) and were less likely to receive cardiac medications, undergo cardiology evaluation (-3.5%; 95% CI: -4.5% to 2.6%), or be hospitalized (-5.8%; 95% CI: -7.7% to -3.8%). Patients with chest pain had lower net mean length of stay (-0.24 days; 95% CI: -0.32 to -0.16) but no net change in spending., Conclusions: Hs-cTn assay implementation was associated with more net upfront tests yet fewer net stress tests, PCI, cardiology evaluations, and hospital admissions in patients with chest pain relative to patients with other symptoms., Competing Interests: Funding Support and Author Disclosures The work of Dr. Ganguli, Ms. Thakore, and Dr. Sequist was supported by the Agency for Healthcare Research and Quality (grant 1R01HS023812). The work of Dr. Wasfy was supported by the American Heart Association (grant 18 CDA 34110215). Dr. Ganguli has received consulting fees from Blue Cross Blue Shield Massachusetts; and has received grant funding from International Business Machines Corporation. Dr. Januzzi is supported by the Hutter Family Professorship; has served as a Trustee of the American College of Cardiology; has received grant support from Novartis Pharmaceuticals, Innolife, Applied Therapeutics, and Abbott Diagnostics; has received consulting income from Abbott, Janssen, Novartis, Pfizer, Merck, and Roche Diagnostics; and has participated in clinical endpoint committees and/or data safety monitoring boards for Abbott, AbbVie, Amgen, Bayer, CVRx, and Takeda. Dr. Baugh has received a paid speaking role and has served as an advisory board member for Roche Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The funders played no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, or approval of the manuscript., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Observationally plasma apolipoprotein E (apoE) is positively associated with ischemic heart disease (IHD). A Mendelian randomization (MR) study suggesting apoE is unrelated to cardiovascular mortality did not consider specific isoforms. We used MR to obtain estimates of plasma apoE2, apoE3 and apoE4 on IHD, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides and apolipoprotein B (apoB)., Methods: We obtained independent genetic instruments from proteome genome-wide association studies (GWAS) and applied them to large outcome GWAS. We used univariable MR to assess the role of each isoform and multivariable MR to assess direct effects., Results: In univariable MR, apoE4 was positively associated with IHD (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01 to 1.09), but apoE2 and apoE3 were less clearly associated. Using multivariable MR an association of apoE2 with IHD (OR 1.16, 95% CI 0.98 to 1.38) could not be excluded, and associations of apoE3 and apoE4 with IHD were not obvious. In univariable MR, apoE2 and apoE4 were positively associated with apoB, and a positive association of apoE2 with LDL cholesterol could not be excluded. Using multivariable MR apoE2 was positively associated with LDL cholesterol, and associations with apoB could not be excluded. After adjusting for apoB, no direct effects of apoE isoforms on IHD were evident., Conclusions: Plasma apoE2 and apoE4 may play a role in lipid modulation and IHD. Whether apoE could be a potential therapeutic target requires further clarification when larger genetic studies of apoE isoforms are available.

The association between type 2 diabetes (T2D) and ischemic heart disease (IHD) is well established but the potential causal association needs further studying. In an attempt to elucidate the causal effect of T2D on IHD, we used three different analytical approaches in two different datasets. A well-defined cohort of 6047 women aged 50-59 years were included at baseline (1995 to 2000) and followed until 2015 for IHD. The median follow-up was 16.3 years. We used a Marginal Structural Cox model (MSM Cox) to account for time-varying exposure (time at onset of T2D) and for ten confounders (using inverse probability weighting, IPW). We also compared the MSM-Cox models with traditional Cox regression modelling in the cohort. Finally, we analyzed information on individuals from Swedish population-based registers with national coverage in a comprehensive co-relative design and extrapolated the results to MZ twins. The Hazard Ratio (HR) for IHD in relation to T2D at baseline and T2D occurring during the follow-up in the MSM Cox model weighted by IPW (based on the ten included confounders) was 1.43 (95% confidence interval [CI] 1.07-1.92). The corresponding HR from the traditional Cox regression model was of similar effect size. The average extrapolated MZ twin estimate from our co-relative model was 1.61 (95% CI 1.48-1.86). Our findings, based on a triangular approach, support the existence of a causal association between T2D and IHD and that preventive long-term measures in order to avoid or postpone IHD should include monitoring and treatment of both the T2D itself as well as other cardiovascular risk factors.

Purpose: The syndromes of myocardial infarction/myocardial ischemia with No Obstructive Coronary Artery Disease (MINOCA/INOCA) are seen more and more often. Endothelial dysfunction (ED) leading to ischemic events has been reported in many of these patients. We aimed to compare patients with MINOCA and INOCA regarding brachial artery flow-mediated endothelium-dependent vasodilation (flow-mediated dilation [FMD]) and plasma concentration of cardiotrophin-1 (CT-1)., Methods: We included 42 patients with MINOCA and 38 patients with INOCA. Endothelial function was assessed by measuring FMD% and nitroglycerin-mediated dilatation (NMD%) in the brachial artery. The plasma level of CT-1 was determined by solid-phase enzyme-linked immunosorbent assay., Results: FMD% was significantly lower in MINOCA than in INOCA patients (6.45 ± 2.65 vs 8.94 ± 3.32, P < .001), without significant difference in NMD% (10.69 ± 3.19 vs 12.16 ± 3.69, P = .06). Plasma CT-1 levels were not significantly different: 40.1 pg/mL (22.5-102.1) vs 37.2 pg/mL (23.5-67.2), P = .53., Conclusion: Our results suggest worse ED in MINOCA than in INOCA patients, but demonstrated no difference in CT-1 levels between patients with stable and unstable ischemic heart disease and normal coronary arteries., (© 2020 Wiley Periodicals LLC.)