Occupational burnout is associated with an elevated risk of cardiovascular events, but the mechanisms underlying this connection have rarely been studied. Low grade inflammation with interleukin (IL)-6 as a key player has been postulated as a possible link between low-grade inflammation and cardiovascular events. Another possibility could be attenuated inflammatory responses to stress reflecting a dysregulated innate immune response. The aim of this study was to examine the relationship between burnout and IL-6 reactivity to acute stress in physicians with burnout. Sixty male physicians were recruited, 30 with burnout, assessed with the Maslach Burnout Inventory, and 30 without burnout. Participants underwent the Trier Social Stress Test, inflicting uncontrollability, and social evaluative threat. Blood samples for IL-6 measurements were taken five times at predefined intervals during stress. Repeated measures analysis of covariance was conducted across the five time points, adjusting for age. IL-6 reactivity over time was significantly lower in physicians with burnout compared to their matched healthy counterparts (F(1.90, 108.10) = 4.88, p = 0.010) during stress. Confirming these results, there was also a significantly lower area under the curve with respect to increase in physicians with burnout compared to those without burnout (F(1, 57) = 4.99, p = 0.029). This study suggests that burnout is associated with lowered IL-6 reactivity in male physicians with burnout. An attenuated innate immune response in burnout complies with increased allostatic load such that dysfunctional stress responses might increase the risk of cardiovascular events in the long term.

The inflammatory phenotype of vascular smooth muscle cells (VSMCs) is an important factor in triggering vascular disease, and interleukin-6 (IL-6) is one of the earliest inflammatory cytokines upregulated in many inflammatory contexts. Angiotensin II-1 receptor autoantibody (AT1-AA) can promote the phenotypic transformation of VSMCs into macrophage-like cells, then synthesize abundant IL-6 to induce vascular inflammation. Previous studies suggested that abnormal BK channel function on the surface of VSMCs played an important role in the synthesis of IL-6, but the mechanism of abnormal BK channel involvement in AT1-AA-induced IL-6 synthesis in VSMCs was unclear. In this study, the agonist NS1619 of the BK channel and the inhibitor Paxilline were used to reverse or exacerbate IL-6 synthesis in AT1-AA-induced VSMCs. It is known that NF-κB can enter the nucleus due to increased calcium ion concentration caused by BK channel dysfunction, thereby increasing IL-6 transcription. This study observed that Paxilline pretreatment significantly increased the residence time of AT1-AA-induced NF-κB in the nucleus, while NS1619 pretreatment showed the opposite trend. JSH-23 inhibiting NF-κB nuclear entry reversed the increase in IL-6 expression in VSMCs induced by AT1-AA. This study found that AT1-AA enhanced NF-κB nuclear translocation by inhibiting BK channel function, which in turn promoted IL-6 transcription in VSMCs, increased IL-6 synthesis, and induced vascular inflammation. This study revealed the importance of BK channel dysfunction in the process of AT1-AA increasing IL-6 synthesis and promoting vascular inflammation, and provided a new idea for alleviating vascular inflammatory diseases from the perspective of improving potassium channel function.

Immune system plays a crucial role in the physiological and pathological regulation of the cardiovascular system. The exploration history and milestones of immune system in cardiovascular diseases (CVDs) have evolved from the initial discovery of chronic inflammation in atherosclerosis to large-scale clinical studies confirming the importance of anti-inflammatory therapy in treating CVDs. This progress has been facilitated by advancements in various technological approaches, including multi-omics analysis (single-cell sequencing, spatial transcriptome et al.) and significant improvements in immunotherapy techniques such as chimeric antigen receptor (CAR)-T cell therapy. Both innate and adaptive immunity holds a pivotal role in CVDs, involving Toll-like receptor (TLR) signaling pathway, nucleotide-binding oligomerization domain-containing proteins 1 and 2 (NOD1/2) signaling pathway, inflammasome signaling pathway, RNA and DNA sensing signaling pathway, as well as antibody-mediated and complement-dependent systems. Meanwhile, immune responses are simultaneously regulated by multi-level regulations in CVDs, including epigenetics (DNA, RNA, protein) and other key signaling pathways in CVDs, interactions among immune cells, and interactions between immune and cardiac or vascular cells. Remarkably, based on the progress in basic research on immune responses in the cardiovascular system, significant advancements have also been made in pre-clinical and clinical studies of immunotherapy. This review provides an overview of the role of immune system in the cardiovascular system, providing in-depth insights into the physiological and pathological regulation of immune responses in various CVDs, highlighting the impact of multi-level regulation of immune responses in CVDs. Finally, we also discuss pre-clinical and clinical strategies targeting the immune system and translational implications in CVDs.

The integration of 2D-materials and optoelectronic devices has attracted great attention for advanced applications. We propose the first perovskite/graphene heterostructure-based FET biosensor with uniquely biotunable ternary logic gating functionality. The biosensor integrates a lateral perovskite-on-graphene heterostructure phototransistor with a vertical bio-nano-photonic filter, with a decoupled construction inset. In the phototransistor, photoactive perovskite quantum dots (PQDs) serve as sensitizers to absorb light while a high mobility single-layer graphene (SLG) acts as an expressway for carrier transport. In the bio-nano-photonic filter, a localized surface plasmon resonance (LSPR) is induced by gold nanoparticles (AuNPs) in conjunction with antigen-antibody binding, tuning the delivery of light passing through the filter and facilitating biotunable functionality with ternary modes. The biosensor is set up to detect human interleukin-6 (IL6) in order to determine and achieve ultrahigh sensitivity with a limit of detection (LOD) of 0.9 fg mL-1 (43 aM), which is 4 orders of magnitude greater than graphene-FET biosensors. This ultrahigh sensitivity is achieved due to the synergistic effect of PQDs/SLG heterostructure, exhibiting superior electrical, optical, and physicochemical properties, consequently providing significantly high performance of the biosensor in terms of label-free, ultrahigh sensitivity (attomolar level), rapid responsivity (5 min), excellent stability, and selectivity. This heterostructure-based biotunable configuration could open a new avenue for 2D materials in the realm of next-generation bio-nano-photonic platforms for applications in healthcare, early diagnosis, and rapid detection.

Background: Firefighters are at risk for developing metabolic diseases such as type 2 diabetes due to occupational-related stress and poor health behaviors. Firefighters often experience chronic inflammatory responses that may contribute to the development of insulin resistance. This study examined the relationship between systemic inflammation markers and glycemic control markers in firefighters. Methods: Blood samples were collected from twenty full-time male firefighters to assess HbA1c, fasting glucose, and insulin to estimate the Homeostatic Model of Assessment of Insulin Resistance (HOMA-IR), C-reactive protein (CRP), and homocysteine. Body composition and cardiovascular metrics were also recorded. Pearson partial correlation analyses were performed to evaluate relationships between homocysteine and CRP and the variables HOMA-IR and HbA1c while controlling for age and body fat percentage (BF%). SPSS version 29 was used for all analyses (α = 0.05). Data transformation was used where appropriate to ensure the normal distribution of each variable. Results: A significant positive correlation was found between homocysteine and HbA1c before (p = 0.006, r = 0.605) and after controlling for age and BF% (ppartial = 0.013, rpartial = 0.588), indicating that homocysteine levels are associated with impaired glycemic control in firefighters. No other relationships were found to be significant. Conclusions: The findings support a potential link between systemic inflammation and poor glycemic control in firefighters. Due to the occupational hazards that contribute to chronic inflammation, targeted interventions such as dietary modifications may help decrease the risk of diabetes and cardiovascular disease in this high-risk population.

This study aims to evaluate the association between the dietary inflammatory index (DII) and stroke risk in hypertensive patients. Data were sourced from the National Health and Nutrition Examination Survey (NHANES) spanning 1999-2020, including 23,712 hypertensive patients. DII scores were calculated based on dietary intake data, and stroke diagnoses were determined through self-reported physician diagnoses. The relationship between DII and stroke risk was assessed using multivariable logistic regression models. Dose-response relationships and subgroup differences were explored through stratified analysis and restricted cubic spline (RCS) methods. Key dietary factors associated with stroke were identified using least absolute shrinkage and selection operator (LASSO) regression and incorporated into a risk prediction nomogram model. The model's discriminatory ability for stroke was evaluated using receiver operating characteristic (ROC) curves. After adjusting for confounding factors, the highest DII quartile was associated with an adjusted odds ratio (OR) of 1.44 (95% CI 1.19, 1.74) for stroke compared to the lowest quartile, and each unit increase in DII was associated with an OR of 1.08 (95% CI 1.04-1.13) for stroke prevalence. The RCS curve demonstrated a nonlinear relationship between DII and stroke, with a turning point at 0.29. The nomogram model based on key dietary factors identified by LASSO regression had an area under the curve (AUC) of 70.93% (95% CI 69.81%-72.06%). There is a nonlinear relationship between DII and stroke risk in hypertensive patients. Given the inherent limitations of a cross-sectional study design, further research is needed to establish causality.

Zinc (Zn)- and copper (Cu)-containing welding fumes elevate inflammatory markers (CRP, TNF-α, IL-6, IL-8) in healthy individuals and welders. Zn- and Cu-containing nanoparticles are toxic to human macrophages. Therefore, ZnO exposure limits are under discussion. In this study, the effects of Zn/Cu-containing welding fume suspensions on A549 alveolar epithelial cells (exposure concentrations: 0.01/0.1/1/10/100 µg/mL) and THP-1 macrophages (additionally 0.001 µg/mL) were investigated over a period of 48 h. Effects on apoptosis, cytotoxicity, genotoxicity, superoxide dismutase (SOD) activity, and cytokine levels (IL-6, IL-8, MIP-1β/CCL4, TNF-α) were evaluated. Welding fume exposure increased SOD activity, and it increased Annexin-V binding and cytotoxicity effects starting at 10 µg/mL in A549 cells and particularly in THP-1 macrophages. A549 cells showed increased IL-6 at 10 and 100 µg/mL, and significant IL-8 release occurred at 10 µg/mL for A549 and 0.1 µg/mL for macrophages. Exposed macrophages released TNF-α at 1 µg/mL after 24 and 48 h and MIP-1β/CCL4 at 0.01 µg/mL after 6 h and at 0.001 µg/mL after 48 h. No genotoxic effects were detected. MIP-1β/CCL4 is a sensitive new biomarker for human macrophages exposed to Zn/Cu-containing welding fumes. The findings suggest that Zn/Cu particles affect lung cells already at doses below current occupational thresholds.

Coronary artery disease (CAD) is one of the primary causes of morbidity and death worldwide. Premature CAD (pCAD) is the term used to describe the 3-10% of CAD occurrences that occur in people under 45 worldwide. Diagnostic difficulties arise from the different risk factor profiles of pCAD and late-onset CAD. Better cardiovascular risk prediction in younger populations has been made possible by the development of biomarker detection tools. This can be applied to a diagnostic tool, including electrochemical biosensors, which have been predicted to be instrumental because of their adaptability for point-of-care applications for quicker diagnoses. These biosensors provide efficient, scalable, and reasonably priced solutions for the quick identification and tracking of CAD. Multiplex biomarker detection has been adopted as a viable approach for early diagnosis and risk assessment due to the constraints of using a single biomarker for pCAD diagnosis. Thus, this study looks at current developments in biosensing technology and discusses established and new cardiac biomarker panels for pCAD identification.

Omega-3 (n-3) (e.g., EPA/DHA) and omega-6 (n-6) (e.g., linoleic acid [LA]) FAs are suggested to have opposite effects on inflammation, but results are inconsistent and direct comparisons of n-3 and n-6 are lacking. In a double-blind, randomized, and crossover study, females (n = 16) and males (n = 23) aged 30-70 years with abdominal obesity were supplemented with 3-4 g/d EPA/DHA (fish oil) or 15-20 g/d LA (safflower oil) for 7 weeks, with a 9-week washout phase. Cytokines and chemokines (multiplex assay), acute-phase proteins (MALDI-TOF mass spectrometry), endothelial function (vascular reaction index), blood pressure, FA composition (red blood cell membranes/serum/adipose tissue, GC-MS/MS), and adipose gene expression (microarrays, quantitative PCR) were measured. While significant differences between treatments in relative change scores were found for systolic blood pressure (n-3 vs. n-6: -1.81% vs. 2.61%, P = 0.003), no differences between n-3 and n-6 were found for any circulatory inflammatory markers. However, compared with baseline, n-3 was followed by reductions in circulating TNF (-24.9%, P < 0.001), regulated upon activation, normal T cell expressed and secreted (-12.1%, P < 0.001), and macrophage inflammatory protein 1-beta (-12.5%, P = 0.014), and n-6 by lowered TNF (-18.8%, P < 0.001), regulated upon activation, normal T cell expressed and secreted (-7.37%, P = 0.027), monocyte chemoattractant protein-1 (-7.81%, P = 0.020), and macrophage inflammatory protein 1-beta (-14.2%, P = 0.010). Adipose tissue showed significant treatment differences in weight percent of EPA (n-3 vs. n-6: 50.2%∗ vs. -1.38%, P < 0.001, ∗: significant within-treatment change score), DHA (16.0%∗ vs. -3.67%, P < 0.001), and LA (-0.033 vs. 4.91%∗, P < 0.001). Adipose transcriptomics revealed overall downregulation of genes related to inflammatory processes after n-3 and upregulation after n-6, partly correlating with changes in circulatory markers. These data point to tissue-specific proinflammatory effects of high n-6 intake, but a net systemic anti-inflammatory effect as for n-3.

The rise in mental health conditions and stress has attracted global attention. Non-pharmacological and traditional approaches like meditative practices are showing promising results. Therefore, the aim of the study was to evaluate the effect of Heartfulness meditation on stress biomarkers, burnout, and well-being. A double-arm prospective randomized controlled study was carried out on 100 participants aged between 18 and 24 years, experiencing moderate to high perceived stress as assessed by the Perceived Stress Scale (PSS-10). These participants were randomized into a study group (meditation) and control group (sham meditation). An intervention of Heartfulness meditation was carried out daily for 12 weeks. Psychometric analysis was carried out to study burnout (exhaustion, cynicism and professional efficacy) and well-being using the standard validated questionnaires- Maslach Burnout Inventory (MBI) and WHO-Well-being Index (WHO-WBI). Biochemical analysis was also carried out to study psychological stress (serum cortisol), and oxidative stress (serum nitrate/nitrite and serum malondialdehyde (MDA) at baseline and post-intervention. Statistical analysis was carried out using the IBM SPSS software version 26.0. p values < 0.05 were considered statistically significant. A significant increase in serum nitrate/nitrite levels, professional efficacy, and well-being, and a significant decrease in measures such as exhaustion, cynicism, and cortisol levels were observed in the study group than the control group post-intervention. A significant negative correlation was also observed between serum MDA and well-being, whereas a positive correlation was observed between MDA and cortisol. The findings from this research suggest the role of Heartfulness meditation in reducing stress and burnout along with improving the well-being of an individual. Therefore, Heartfulness meditation can be used as a potential tool to improve mental health and well-being. However, future studies with a larger number of samples are needed to strengthen our findings. Trial Registration: Clinical Trial Registry of India: CTRI/2023/10/058,423 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=ODIyOTA=&Enc=&userName=CTRI/2023/10/058423).

Background/Objectives: Inhaled corticosteroids (ICS) affect oxidative stress and systemic inflammation, which might modify the risk of thrombosis in asthmatic patients exposed to particulate matter with an aerodynamic diameter smaller than 2.5 microns (PM2.5). Therefore, we aim to know the systemic biomarkers of oxidative stress, inflammation, and coagulation in ICS-treated, well-controlled adult asthmatic patients after exposure to PM2.5. Methods: This study was conducted to compare urinary biomarkers of oxidative stress, i.e., 8-hydroxydeoxyguanosine (8-OHdG), and blood biomarkers of inflammation and hypercoagulation, i.e., complete blood count (CBC), high-sensitivity C-reactive protein (hsCRP), fibrinogen, D-dimer, tumor necrosis factor-alpha (TNF-α), and interleukins (IL-6 and IL-8), between well-controlled adult asthmatic patients and healthy controls in low and high-pollution periods. Results: Forty-one ICS-controlled asthmatic patients and twenty controls were included. Urinary 8-OHdG, white blood cells and differential counts, platelets count, hsCRP, IL-6, and IL-8 in the asthma group were not significantly higher than controls during the same period. The D-dimer level of the asthma patients was significantly higher than the controls (p < 0.05). The median level of TNF-α levels during the pollution period in asthma patients was significantly higher than the non-pollution period with levels of 14.3 (9.3, 27.4) and 11.3 (7.8, 21.1) pg/mL, p = 0.041, respectively. Conclusions: During exposure to PM2.5, serum TNF-α was increased while the other markers of oxidative stress and inflammation were not high in ICS-treated asthma. ICS might mitigate PM2.5-induced systemic oxidative stress, inflammation, and hypercoagulation in asthma.

Inflammation is an important driver of disease in the context of atherosclerosis, and several landmark trials have shown that targeting inflammatory pathways can reduce cardiovascular event rates. However, the high cost and potentially serious adverse effects of anti-inflammatory therapies necessitate more precise patient selection. Traditional biomarkers of inflammation, such as high-sensitivity C-reactive protein, show an association with cardiovascular risk on a population level but do not have specificity for local plaque inflammation. Nowadays, advancements in non-invasive imaging of the vasculature enable direct assessment of vascular inflammation. Positron emission tomography (PET) tracers such as 18F-fluorodeoxyglucose enable detection of metabolic activity of inflammatory cells but are limited by low specificity and myocardial spillover effects. 18F-sodium fluoride is a tracer that identifies active micro-calcification in plaques, indicating vulnerable plaques. Gallium-68 DOTATATE targets pro-inflammatory macrophages by binding to somatostatin receptors, which enhances specificity for plaque inflammation. Coronary computed tomography angiography (CCTA) provides high-resolution images of coronary arteries, identifying high-risk plaque features. Measuring pericoronary adipose tissue attenuation on CCTA represents a novel marker of vascular inflammation. This review examines both established and emerging methods for assessing atherosclerosis-related inflammation, emphasizing the role of advanced imaging in refining risk stratification and guiding personalized therapies. Integrating these imaging modalities with measurements of systemic and molecular biomarkers could shift atherosclerotic cardiovascular disease management towards a more personalized approach.

The coagulation and immune system, both essential physiological systems in the human body, are intricately interconnected and play a critical role in determining the overall health of patients. These systems collaborate via various shared regulatory pathways, such as the Tissue Factor (TF) Pathway. Immunological cells that express TF and generate pro-inflammatory cytokines have the ability to affect coagulation. Conversely, coagulation factors and processes have a reciprocal effect on immunological responses by stimulating immune cells and regulating their functions. These interconnected pathways play a role in both preserving well-being and contributing to a range of pathological disorders. The close relationship between blood clotting and inflammation in the development of vascular disease has become a central focus of clinical study. This research specifically examines the crucial elements of this interaction within the contexts of cardiovascular disease and acute coronary syndrome. Tissue factor, the primary trigger of the extrinsic coagulation pathway, has a crucial function by inducing a proinflammatory reaction through the activation of coagulation factors. This, in turn, initiates coagulation and subsequent cellular signalling pathways. Protease-activated receptors establish the molecular connection between coagulation and inflammation by interacting with activated clotting factors II, X, and VII. Thrombosis, a condition characterised by the formation of blood clots, is the most dreaded consequence of cardiovascular disorders and a leading cause of death globally. Consequently, it poses a significant challenge to healthcare systems. Antithrombotic treatments efficiently target platelets and the coagulation cascade, but they come with the inherent danger of causing bleeding. Furthermore, antithrombotics are unable to fully eliminate thrombotic events, highlighting a treatment deficiency caused by a third mechanism that has not yet been sufficiently addressed, namely inflammation. Understanding these connections may aid in the development of novel approaches to mitigate the harmful mutual exacerbation of inflammation and coagulation. Gaining a comprehensive understanding of the intricate interaction among these systems is crucial for the management of diseases and the creation of efficacious remedies. Through the examination of these prevalent regulatory systems, we can discover novel therapeutic approaches that specifically target these complex illnesses. This paper provides a thorough examination of the reciprocal relationship between the coagulation and immune systems, emphasising its importance in maintaining health and understanding disease processes. This review examines the interplay between inflammation and thrombosis and its role in the development of thrombotic disorders.

The purpose of this study was to examine the secretion of inflammatory cytokines by cultured monocytes/macrophages in patients with premature coronary artery disease (CAD). The study included 38 patients with premature CAD and 35 patients without CAD. A primary culture of CD14+ monocytes was obtained by immunomagnetic separation. The inflammatory response was induced by incubation of a cell culture with lipopolysaccharide (LPS) for 24 hours on Days 1 and 6. Basal and LPS-stimulated secretion of the cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) was assessed by enzyme immunoassay on Days 2 and 7 of cultivation. The level of basal secretion of TNF-α, IL-1β, IL-6, MCP-1 was higher in patients with CAD compared to patients in the control group. The levels of re-stimulated TNF-α secretion and the levels of LPS-stimulated and re-stimulated IL-1β secretion on the second and sixth days were also higher in patients with CAD. LPS-stimulated MCP-1 secretion on the second day did not differ in patients of both groups, but re-stimulated MCP-1 secretion was higher in patients with CAD. The results of logistic regression analysis showed that the basal secretion levels of IL-1β and IL-6 were independently associated with premature CAD, along with smoking, body mass index and serum HDL-cholesterol levels.

Chronic coronary artery disease (CAD) remains a significant global healthcare burden. Current risk assessment methods have notable limitations in early detection and risk stratification. Hence, there is an urgent need for innovative biomarkers that facilitate the premature CAD diagnosis, ultimately leading to reduction in associated morbidity and mortality rates. This review comprehensively examines recent advances in emerging biomarkers for CAD detection. Our analysis delves into various aspects of these biomarkers such as their mechanisms of action, roles in the pathophysiology of the disease, and different measurement techniques employed in clinical practice. Comparative assessment of biomarker performance between CAD patients and control groups was also presented relying on their sensitivity, specificity, and area under the curve at specific cutoff points. In this regard, prominent biomarkers including Tenascin-C, IL-37, PTX3, transthyretin, soluble interleukin-6 receptor α, and miR-15a are identified as having high diagnostic potential for chronic CAD that indeed showcase promising performance metrics. These findings underscore the role of novel biomarkers in enhancing CAD risk stratification and improving patient outcomes through early intervention. However, the pursuit of an ideal and inclusive biomarker continues due to the multifaceted nature of CAD. Future randomized controlled trials are essential to bridge the gap between research findings and clinical practice in order to augment the practical application of these biomarkers in routine healthcare settings.

Continuous Positive Airway Pressure (CPAP) treatment brings more benefits than risks to most coronary heart disease (CHD) patients with obstructive sleep apnea (OSA). However, the pathophysiological mechanism by which CPAP treatment improves the prognosis of patients with CHD and OSA remains unclear. The purpose of this study was to clarify whether CPAP can improve arterial stiffness and inflammatory factor levels in CHD patients with OSA, and to further improve prognosis.

59 patients with coronary heart disease complicated by moderate to severe sleep apnea were divided into a CPAP treatment group (CPAP + coronary heart disease standard treatment) and a control group (only coronary heart disease standard treatment). Peripheral blood test reports were collected and pulse wave velocity (PWV) measurements were performed for each patient at the beginning, 3 months, and 6 months of treatment.

After 6 months of treatment, the CPAP group showed more significant improvement in the levels of inflammatory factors such as white blood cell (WBC), neutrophil (N), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and PWV than the control group.

After active treatment with CPAP, arterial stiffness and inflammatory cytokine levels in patients with coronary heart disease and OSA improved. This association should be given more attention in clinical practice, and sleep apnea should be actively treated.

Objectives Patients with rheumatoid arthritis (RA) have a high incidence of arteriosclerotic disease. These are partly attributed to high levels of C-reactive protein (CRP) and inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. Tocilizumab (TCZ) is an IL-6 receptor antagonist that lowers CRP levels by directly blocking IL-6 signaling. Tocilizumab has been reported to increase serum lipid levels. However, its effect on arteriosclerosis remains unclear. Therefore, we investigated the effect of TCZ on arteriosclerosis in patients with RA. Methods Eighteen Japanese patients with RA who were administered TCZ were included and assessed at baseline and six and 12 months. The Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR), CRP, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and carotid intima-media thickness (IMT) were measured and analyzed using high-resolution B-mode ultrasonography. Additionally, the effects of concurrent statin administration on any changes in IMT were evaluated. Results From baseline to six or 12 months, TCZ decreased CRP (P < 0.0005) and DAS28-ESR (P < 0.0005) significantly, whereas TC, LDL-C, and HDL-C levels increased significantly (P < 0.005). However, there was no change in the LDL-C/HDL-C ratio (P = 0.821 at six months and P = 0.168 at 12 months), and carotid IMT (P = 0.6874 at six months and P = 0.6951 at 12 months). Comparison of percentage changes in mean IMT revealed no statistical differences between the patient groups with or without statin administration (P = 0.7208 at six months, P = 0.5928 at 12 months). Conclusions According to the 12-month observation data, no significant association was detected between TCZ use and IMT changes in patients with RA, despite its effects on serum lipids. Further long-term studies are needed to confirm that IL-6 receptor blockers have cardiovascular effects.

Over the last 30 years, the widespread use of cardiac biomarkers has transformed the diagnostic evaluation of patients with coronary heart disease. Cardiac troponin is integral to the definition of acute myocardial infarction. High-sensitivity cardiac troponin (hs-cTn) assays can improve risk stratification to facilitate both the rapid rule out of myocardial infarction and prediction of future cardiovascular events. Numerous circulating biomarkers representing different pathological pathways improve prediction of atherosclerotic cardiovascular disease (ACVD) and coronary artery disease (CAD). In parallel, coronary computed tomography angiography (CCTA) has become the most widely used imaging modality for the evaluation of patients with possible angina. CCTA now allows for the quantification of coronary calcification, atherosclerotic plaque volume and different plaque characteristics, enabling the identification high-risk features and inflammation. In the future, the use of CCTA is likely to extend to risk stratification for the prevention of ACVD. As such, how to integrate these diagnostic and prognostic circulating and imaging biomarkers is a topic of considerable interest. This review aims to describe current status and future possibilities for the integration of CCTA and cardiac biomarker testing to improve the identification and treatment of individuals with coronary heart disease and heightened cardiovascular risk.

Cardiovascular (CV) disease remains the leading cause of morbidity and mortality worldwide, highlighting the necessity of understanding its underlying molecular and pathophysiological pathways. Conversely, physical activity (PA) and exercise are key strategies in reducing CV event risks. Detecting latent CV conditions in apparently healthy individuals, such as athletes, presents a unique challenge. The early identification and treatment of CV disorders are vital for long-term health and patient survival. Cardiac troponin is currently the most commonly used biomarker for assessing CV changes in both athletes and the general population. However, there remains considerable debate surrounding the mechanisms underlying exercise-induced troponin elevations and its release in non-ischemic contexts. Thus, there is a pressing need to identify and implement more sensitive and specific biomarkers for CV disorders in clinical practice. Indeed, research continues to explore reliable biomarkers for evaluating the health of athletes and the effectiveness of physical exercise. It is essential to analyze current evidence on troponin release in non-ischemic conditions, post-strenuous exercise, and the complex biological pathways that influence its detection. Furthermore, this study summarizes current research on cytokines and exosomes, including their physiological roles and their relevance in various CV conditions, especially in athletes. In addition, this paper gives special attention to underlying mechanisms, potential biomarkers, and future perspectives.

Hypertriglyceridaemia and systemic inflammation are prevalent in patients with schizophrenia and contribute to an increased risk of cardiovascular disease. Although elevated triglycerides (TGs) and remnant cholesterol are linked to inflammation in the general population and individuals with metabolic syndrome, whether they are associated in patients with schizophrenia remains unclear.

Fasting levels of TG, cholesterol (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and remnant cholesterol)), and markers of systemic inflammation including high-sensitivity C-reactive protein (hsCRP), leukocyte counts and their differentials (neutrophils, monocytes and lymphocytes) were determined in 147 patients diagnosed with schizophrenia on long-term antipsychotic regimens and compared with 56 age- and sex-matched healthy controls. Apolipoprotein B and glycosylation of acute phase reactant (GlycA) signatures were assessed by NMR. Circulating cytokine levels were measured by a cytokine/chemokine multiplex assay.

Patients with schizophrenia had markedly elevated TG and remnant cholesterol relative to controls and had evidence of systemic inflammation with increased circulating hsCRP, GlycA, leukocyte, neutrophil counts and neutrophil-to-lymphocyte ratio (NLR). Unexpectedly TG and remnant cholesterol did not correlate with systemic inflammatory markers in patients with schizophrenia, and differences in inflammatory markers between controls and patients persisted after adjusting for the lipid profile. Interleukin (IL)-10 levels were increased in patients with schizophrenia, suggesting an anti-inflammatory signature.

The discordance between TG, remnant cholesterol and systemic inflammation in patients with schizophrenia suggests these are likely independent contributors to cardiovascular risk in this population.

Cardiovascular disease (CVD) is the leading cause of death in the United States, and sepsis significantly contributes to hospitalization and mortality. This study aims to assess the trends of sepsis-associated CVD mortality rates and variations in mortality based on demographics and regions in the US.

The Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database was used to identify CVD and sepsis-related deaths from 1999 to 2022. Data on gender, race and ethnicity, age groups, region, and state classification were statistically analyzed to obtain crude and age-adjusted mortality rates (AAMR). The Joinpoint Regression Program was used to determine trends in mortality within the study period.

During the study period, there were a total of 1,842,641 deaths with both CVD and sepsis listed as a cause of death. Sepsis-associated CVD mortality decreased between 1999 and 2013, from AAMR of 65.7 in 1999 to 58.8 in 2013 (APC -1.06*%, 95% CI: -2.12% to -0.26%), then rose to 74.3 in 2022 (APC 3.23*%, 95% CI: 2.18%-5.40%). Throughout the study period, mortality rates were highest in men, NH Black adults, and elderly adults (65+ years old). The Northeast region, which had the highest mortality rate in the initial part of the study period, was the only region to see a decline in mortality, while the Northwest, Midwest, and Southern regions experienced significant increases in mortality rates.

Sepsis-associated CVD mortality has increased in the US over the past decade, and both this general trend and the demographic disparities have worsened since the onset of the COVID-19 pandemic.

Aging is a dynamic process that requires a continuous response and adaptation to internal and external stimuli over the life course. This eventually results in people aging differently and women aging differently than men. The "gender paradox" describes how women experience greater longevity than men, although linked with higher rates of disability and poor health status. Recently, the concept of frailty has been incorporated into this paradox giving rise to the "sex-frailty paradox" which describes how women are frailer because they manifest worse health status but, at the same time, appear less susceptible to death than men of the same age. However, very little is known about the biological roots of this sex-related difference in frailty. Inflamm-aging, the chronic low-grade inflammatory state associated with age, plays a key pathophysiological role in several age-related diseases/conditions, including Alzheimer's disease (AD), for which women have a higher lifetime risk than men. Interestingly, inflamm-aging develops at a different rate in women compared to men, with features that could play a critical role in the development of AD in women. According to this view, a continuum between aging and age-related diseases that probably lacks clear boundaries can be envisioned in which several shared biological mechanisms that progress at different pace may lead to different aging trajectories in women than in men. It, therefore, becomes urgent to consider a holistic approach in the study of aging, and decline it from a gender medicine perspective also considering the biological roots of the sex-frailty paradox.

Cinnamon has positive effects on markers of cardiometabolic health, including blood pressure (BP), oxidative stress, and inflammation. Despite the evidence accumulated from meta-analysis studies on the effects of cinnamon on these markers, the reported findings are still controversial. This umbrella review was conducted to evaluate the evidence and provide a definitive clarification.

We conducted a systematic search in four scientific databases, including PubMed, Scopus, Web of Science, and Embase electronic databases, up to March 2024 to identify systematic reviews and meta-analyses of randomized clinical trials investigating the impact of cinnamon on blood pressure, oxidative stress, and inflammation. The findings revealed that cinnamon might exert favorable effects on systolic blood pressure (SBP) (ES = -2.36 mmHg; 95% CI: 3.86, -1.40), diastolic blood pressure (DBP) (ES = -1.65 mmHg; 95% CI: 2.41, -0.90), total antioxidant capacity (TAC) (WMD = 0.34; 95% CI: 0.04, 0.64), and interleukin-6 (IL-6) (WMD = -1.48; 95% CI: 2.96, -0.01). However, the results did not show any significant effect of cinnamon on malondialdehyde (MDA) (WMD = -0.47; 95% CI: 0.99, 0.05), C-reactive protein (CRP) (WMD = -1.33; 95% CI: 2.66, 0.00), and intercellular adhesion molecule 1 (ICAM-1) (WMD= 1.53, 95% CI: 12.03, 15.10).

The results of the studies included in this umbrella review support the usefulness of cinnamon consumption in modulating BP as well as improving TAC and IL-6 in metabolic disorders. Due to the limited number of studies, clinical diversity, and other limitations, more high-quality studies must be conducted to provide more precise and comprehensive recommendations.

PROSPERO, CRD42023487350.

On the cardiovascular system, obesity accelerates atherosclerosis progression, inducing pathophysiological changes that are detectable already from young adults. Endothelial dysfunction is one of the earliest vascular alterations observed in obesity. In this study, we aimed to determine endothelial functions and carotid intima-media thickness in patients with obesity without overt cardiovascular disease.

The study was conducted with 112 individuals with obesity without overt cardiovascular disease and any chronical diseases (BMI>30 kg/m2) (84 female, 28 male, mean age: 46.3±11.2 years) and 49 healthy individuals with no diseases (33 female, 16 male, mean age: 44.6±10.2 years). All patients were examined for endothelial functions by the flow-mediated dilatation (FMD) method and carotid intima-media thicknesses (CIMT). All measurements were performed by the same imaging specialist, averaging 3 different measurements. In addition to the body mass index and waist circumference visceral adiposity index (VAI) and triponderal mass index (TPI) also calculated.

The percentage of FMD obtained by brachial artery ultrasound was significantly lower, visceral adipose tissue, perirenal adipose tissue thicknesses measured by abdominal ultrasound and CIMT were significantly thicker in Group 1 compared to Group 2. FMD had a negative significant correlation with body mass index, visceral adipose tissue thickness, perirenal adipose tissue thickness, and waist and hip circumferences, and carotid intima-media thickness and CIMT had a significant correlation with visceral adipose tissue thickness, perirenal adipose tissue thickness, VAI, TPI and waist, hip circumferences.

Individuals with obesity have impaired endothelial functions and greater carotid intima-media thicknesses compared to healthy individuals. This impairment in endothelial functions is proportional to the amount of visceral and perirenal fat accumulation. Parameterss reflecting visceral fat distribution such as VAI and TPI are also related with these impairment.

The aim of this study was to evaluate the systemic effect of non-surgical peri-implantitis treatment (NSPIT) with or without the administration of systemic metronidazole.

In this secondary analysis from a previously published clinical trial (NCT03564301), peri-implantitis patients were randomized into two groups: test, receiving NSPIT plus 500 mg of oral systemic metronidazole three times a day for 7 days (n = 10); and control group, receiving NSPIT plus placebo (n = 11). Serum samples were obtained at baseline, 3 and 6 months after therapy to determine levels of inflammatory biomarkers, lipid fractions and complete blood counts.

Both treatment modalities produced improvements in clinical and radiographic parameters. After 6 months from NSPIT, a substantial reduction in C-reactive protein (6.9 mg/dL; 95% CI: 3.7 to 9.9, p < .001) and low-density lipoprotein cholesterol (21.8 mg/dL; 95% CI: -6.9 to 50.5, p = .013) as well as a modest increase in neutrophils counts (0.4 × 103/μL; 95% CI: -0.4 to 1.1, p = .010) was observed in the control group while the test group showed a significant reduction of TNF-α (110.1; 95% CI: 38.9 to 181.4, p = .004).

NSPIT showed a short-term beneficial systemic effect regardless of adjunctive use of systemic metronidazole.

This article deals with the role of c-reactive protein (CRP) in the development of atherosclerosis and its treatment. CRP has a predictive value in ischemic heart disease, restenosis, coronary artery disease, aortic atherosclerosis, and cerebrovascular disease. This article deals with the synthesis and mechanism of CRP-induced atherosclerosis and its treatment. CRP increases the formation of numerous atherogenic biomolecules such as reactive oxygen species (ROS), cytokines (interleukin [IL]-1β and IL-6), cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, activated complement C 5 , monocyte colony-stimulating factor, and numerous growth factors [insulin-like growth factor, platelet-derived growth factor, and transforming growth factor-β]). ROS mildly oxidizes low-density lipoprotein (LDL)-cholesterol to form minimally modified LDL which is further oxidized to form oxidized LDL. The above atherogenic biomolecules are involved in the development of atherosclerosis and has been described in detail in the text. This paper also deals with the treatment modalities for CRP-induced atherosclerosis which includes lipid-lowering drugs, antihypertensive drugs, antioxidants, aspirin, antidiabetic drugs, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, regular physical activity, weight reduction, and stoppage of cigarette smoking. In conclusion, CRP induces atherosclerosis through increases in atherogenic biomolecules and the treatment modalities would prevent, regress, and slow the progression of CRP-induced atherosclerosis.

The objective of this narrative review is to summarize data from recently published prospective observational studies that analyze the association between circulating interleukin-6 (IL-6) levels and cardiovascular clinical or imaging endpoints.

Higher levels of IL-6 are associated with a higher risk of cardiovascular death, major adverse cardiovascular events, myocardial infarction, stroke, peripheral artery disease, and heart failure. Imaging studies have also shown an association between IL-6 and carotid intima-media thickness progression, carotid plaque progression, severity, and vulnerability. These observations have been consistent across a wide range of study populations and after adjusting for traditional and emerging risk factors including high-sensitivity C-reactive protein. Robust epidemiologic evidence supports IL-6 as a central mediator of cardiovascular risk along with human genetic studies and mechanistic experiments. Ongoing clinical studies are testing the therapeutic hypothesis of IL-6 inhibition in patients with atherosclerotic cardiovascular disease or heart failure.

Cardiovascular diseases are among the most common chronic diseases, generating high social and economic costs. Secondary immunodeficiencies occur more often than primary ones and may result from the co-occurrence of specific diseases, treatment, nutrient deficiencies and non-nutritive bio-active compounds that result from the industrial nutrient practices.

The aim of this article is to present selected secondary immunodeficiencies and their impact on the cardiovascular system.

The treatment of a patient with cardiovascular disease should include an assess-ment for immunodeficiencies, because the immune and cardiovascular systems are closely linked.

Immune system dysfunctions can significantly affect the course of cardiovascular diseases and their treatment. For this reason, comprehensive care for a patient with cardiovascular disease requires taking into account potential immunodeficiencies, which can have a significant impact on the patient's health.

Atherosclerosis is a cardiovascular disease caused by cholesterol-laden arterial plaques. This study evaluated the correlation between interleukin-6 (IL-6), its receptors (IL6R/CD126), and glycoprotein 130 (gp130) alongside atherosclerosis biomarkers in a cohort of 142 subjects, equally divided between lean and obese individuals. Subsequent analyses used THP-1-derived macrophages to assess the biochemical impact of inhibiting IL-6 receptors. IL-6 secretion increased with atherosclerosis in obese subjects, while IL6R/CD126 and gp130 on monocytes decreased. Pharmacological gp130 inhibition altered lipid metabolism, increasing LDLR gene expression and cholesterol synthesis via SREBF2 and mevalonate kinase, along with HMG-CoA reductase at protein levels. gp130-deficient cells produced more cholesterol and had lower ABCA1 levels, suggesting hindered cholesterol efflux. Filipin III staining confirmed cholesterol retention in gp130-inhibited cells. Ex-vivo investigation on lean PBMCs further defined the impact of gp130 inhibition on the reduction of cholesterol efflux. Our results indicates gp130 is crucial for macrophage reverse cholesterol transport and may be a target for atherosclerosis treatments.

Studies on predictive value of circulating inflammatory biomarkers after myocardial infarction (MI) have often been limited by blood sampling only in an acute setting and short follow-up time. We aimed to compare the long-term predictive value of nine inflammatory biomarkers, known to be involved in atherosclerosis, in young patients investigated three months after a first-time MI.

Nine biomarkers (high-sensitivity C-reactive protein, interleukin (IL)-6, IL-18, monocyte chemoattractant protein-1, matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, serum amyloid A and tumor necrosis factor-alfa) were sampled in 382 young (<60 years) patients and in age and sex-matched controls, three months after a first-time MI between 1996 and 2000. Swedish national patient registers were used to determine cardiovascular (CV) outcomes during 20 years of follow-up.

In cases, random forest models identified IL-6 as the most important predictor of the primary composite endpoint of death, heart failure (HF) or MI hospitalization, and the separate endpoints death and HF hospitalization. IL-18 was the most important predictor of MI hospitalization. In a Cox regression, the highest tertile of IL-6 was associated with the composite endpoint (HR (95% CI) 1.91 (1.31-2.79)), death (2.38 (1.42-3.98)) and HF hospitalization (2.70 (1.32-5.50)), when adjusting for age, sex and CV risk factors. The highest tertile of IL-18 was associated with MI hospitalization (2.31 (1.08-4.91)) when severity of coronary atherosclerosis was added to the same type of model.

When nine inflammatory markers involved in atherosclerosis were analyzed three months after the acute event in young MI patients, IL-6 and IL-18 were the most important biomarkers to predict long-term CV outcomes during 20 years of follow-up.

The formation of secondary organic aerosols (SOA) by atmospheric oxidation reactions substantially contributes to the burden of fine particulate matter (PM2.5), which has been associated with adverse health effects (e.g., cardiovascular diseases). However, the molecular and cellular effects of atmospheric aging on aerosol toxicity have not been fully elucidated, especially in model systems that enable cell-to-cell signaling.

In this study, we aimed to elucidate the complexity of atmospheric aerosol toxicology by exposing a coculture model system consisting of an alveolar (A549) and an endothelial (EA.hy926) cell line seeded in a 3D orientation at the air‒liquid interface for 4 h to model aerosols. Simulation of atmospheric aging was performed on volatile biogenic (β-pinene) or anthropogenic (naphthalene) precursors of SOA condensing on soot particles. The similar physical properties for both SOA, but distinct differences in chemical composition (e.g., aromatic compounds, oxidation state, unsaturated carbonyls) enabled to determine specifically induced toxic effects of SOA.

In A549 cells, exposure to naphthalene-derived SOA induced stress-related airway remodeling and an early type I immune response to a greater extent. Transcriptomic analysis of EA.hy926 cells not directly exposed to aerosol and integration with metabolome data indicated generalized systemic effects resulting from the activation of early response genes and the involvement of cardiovascular disease (CVD) -related pathways, such as the intracellular signal transduction pathway (PI3K/AKT) and pathways associated with endothelial dysfunction (iNOS; PDGF). Greater induction following anthropogenic SOA exposure might be causative for the observed secondary genotoxicity.

Our findings revealed that the specific effects of SOA on directly exposed epithelial cells are highly dependent on the chemical identity, whereas non directly exposed endothelial cells exhibit more generalized systemic effects with the activation of early stress response genes and the involvement of CVD-related pathways. However, a greater correlation was made between the exposure to the anthropogenic SOA compared to the biogenic SOA. In summary, our study highlights the importance of chemical aerosol composition and the use of cell systems with cell-to-cell interplay on toxicological outcomes.

The objective of our study was to examine the association between composite dietary antioxidant index (CDAI) and atherosclerotic cardiovascular disease (ASCVD) in adults.

Data was gathered from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2018. To examine the connection between CDAI and ASCVD, multiple logistic regression analyses were performed. Restricted cubic splines were utilized to examine non-linear correlations, and the inflection point was identified using a two-piecewise linear regression approach. Subgroup analyses were performed to demonstrate stability of results. A total of 44,494 individuals were included in the study. The multivariate logistic regression model was fully adjusted and revealed an odds ratio of 0.968 (95% CI: 0.959-0.978; P < 0.001) for the correlation between CDAI and ASCVD. Furthermore, individuals in the highest quartile of CDAI exhibited a decreased risk of ASCVD compared to those in the lowest quartile [0.716 (0.652-0.787); P < 0.001]. Moreover, restricted cubic spline (RCS) analysis revealed non-linear relationship between CDAI and ASCVD, with inflection point at -0.387. The analysis of subgroups showed that the importance of CDAI remained consistent among various age, sex, race, body mass index (BMI), and physical activity.

Our research revealed an inverse and non-linear relationship between CDAI and ASCVD in adults. The implications of these findings are significant for future studies and the formulation of dietary guidelines.

This review aimed to highlight the pivotal role of Mendelian randomization (MR) in advancing atherosclerotic cardiovascular disease (ASCVD) research-a field often hindered by the complexities and limitations of traditional studies. MR, which uses genetic variants as instrumental variables, provides a robust mechanism for inferring causality, offering insights untainted by the confounding factors and biases often prevalent in observational and randomized controlled trials. We explored the significant contributions of MR for elucidating the causal relationship between low-density lipoprotein cholesterol and ASCVD, and analyzed its assumptions and methodological nuances. We discussed issues surrounding instrumental variable selection, pleiotropy, and ethical considerations, in an effort to offer a balanced and insightful analysis. We highlighted the promising integration of MR with emerging technologies and global data sharing, as well as its potential to drive personalized medicine. This review provided a concise yet comprehensive journey into MR's transformative impact on ASCVD research, offering a blend of current insights and challenges, in addition to future prospects. We aimed to serve a valuable resource for those seeking to navigate the intricate pathways of causality and intervention in ASCVD, to aid the development of enhanced understanding and targeted treatment strategies in the future.

Skeletal muscle atrophy and dysfunction commonly accompany cardiovascular diseases such as peripheral arterial disease and may be partially attributable to systemic inflammation. We sought to determine whether acute systemic inflammation in a model of hindlimb ischaemia (HLI) could affect skeletal muscle macrophage infiltration, fibre size, or capillarization, independent of the ischaemia. Eight-week-old C57BL/6 male mice underwent either Sham or HLI surgery, and were killed 1, 3, or 7 days post-surgery. Circulating inflammatory cytokine concentrations were measured, as well as immune cell infiltration and morphology of skeletal muscle from both limbs of HLI and Sham mice. In HLI compared with Sham mice at day 1, plasma interleukin-1β levels were 216% higher (0.48 ± 0.10 vs. 0.15 ± 0.01 pg/μL, P = 0.005) and decreased by day 3. This was followed by increased macrophage presence in muscle from both ischaemic and non-ischaemic limbs of HLI mice by day 7 (7.3- and 2.3-fold greater than Sham, respectively, P < 0.0001). In HLI mice, muscle from the ischaemic limb had 21% lower fibre cross-sectional area than the non-ischaemic limb (724 ± 28 vs. 916 ± 46 μm2, P = 0.01), but the non-ischaemic limb of HLI mice was no different from Sham. This shows that HLI induces acute systemic inflammation accompanied by immune infiltration in both ischaemic and remote skeletal muscle; however, this did not induce skeletal muscle atrophy in remote muscle within the 7-day time course of this study. This effect of local skeletal muscle ischaemia on the inflammatory status of remote skeletal muscle may signal a priming of muscle for subsequent atrophy over a longer time course. HIGHLIGHTS: What is the central question of this study? Does hindlimb ischaemia-induced inflammation cause acute immune, inflammatory and morphological alterations in remote non-ischaemic skeletal muscle? What is the main finding and its importance? Hindlimb ischaemia induced systemic inflammation with subsequent neutrophil and macrophage infiltration in both ischaemic and non-ischaemic skeletal muscle; however, morphological changes did not occur in non-ischaemic muscle within 7 days. These immune alterations may have functional implications that take longer than 7 days to manifest, and subsequent or prolonged systemic inflammation and immune infiltration of muscle could lead to morphological changes and functional decline.

To investigate the relationship between chronic low-grade inflammation, as measured by high-sensitivity C-reactive protein (hsCRP) levels, and incident heart failure (HF) or cancer.

We assessed the relationship between baseline hsCRP concentrations and subsequent HF or cancer in two community-based cohorts, the Trøndelag Health Study (HUNT3) and the Health, Aging and Body Composition (ABC) study. In the latter, the analysis was replicated with interleukin (IL)-1, IL-6, or tumour necrosis factor (TNF)-α instead of hsCRP. In HUNT3, hsCRP was measured in 47 163 subjects (mean age 52.3 ± 15.8 years). During a median follow-up of 12.1 years, 2034 (4.3%) individuals developed HF and 5024 (10.7%) cancer, with 442 (0.9%) being diagnosed with both. After adjusting for age, male sex, diabetes, obesity, previous or current smoking, and comorbidities, elevated baseline hsCRP was associated with a higher risk of HF or cancer [hazard ratio (HR) 1.09; 95% confidence interval (CI), 1.07-1.10]. In the Health ABC study, hsCRP levels were assessed in 2803 participants, who had a mean age of 72.6 ± 2.9 years and a higher burden of comorbidities than in HUNT3. During a median follow-up of 8.2 years, HF and cancer were diagnosed in 346 (12.3%) and 776 (27.7%) subjects, respectively, with 77 (2.7%) having both conditions. After adjusting for the same variables used for the HUNT3 cohort, hsCRP remained significantly associated with incident HF or cancer (HR 1.11; 95% CI, 1.05-1.18), as were IL-1 (HR 1.15; 1.07-1.24), IL-6 (HR 1.09; 1.02-1.17), and TNF-α (HR 1.15; 1.07-1.24).

A state of chronic, low-grade inflammation captured by an increase in hsCRP levels is associated with an increased risk of developing HF or cancer, with potential implications for clinical trials with anti-inflammatory therapies.

Despite the high phenolic content of Annona muricata, little is known about its anti-hypertensive and antihyperlipidemic properties. This study evaluated the anti-hypertensive and antihyperlipidemic potential of A. muricata leaf extracts.

Forty-two male Wistar rats were divided into seven groups of six animals each. N-nitro-L-arginine methyl ester (L-NAME) was used to induce hypertension and hyperlipidemia.

Phytochemical screening of Annona muricata leaf extracts (AMLE) revealed the presence of saponins, alkaloids, flavonoids, tannins, coumarins, steroids, terpenoids, and phenols. Comparing the methanol extract with the ethyl acetate fraction, quantification revealed that the methanol extract contained more phenolics, flavonoids, and alkaloids. The AMLE rats significantly reduced triglycerides, total cholesterol, LDL, VLDL, atherogenic index, coronary risk index, and blood pressure. The significant decrease in GSH, catalase, SOD, GST, and oxidative stress markers (MDA, nitrites, and MPO) was reversed by AMLE in a dose-dependent manner. Also, the elevated serum levels of TNF-α and IL-1β in the hypertensive rats were attenuated in the treatment groups.

This study suggests the potential ameliorative effects of Annona muricata leaf extracts against L-NAME-induced hypertension in rats. Notably, the study showed the antioxidant and anti-inflammatory properties of A. muricata leaf extracts, which is seen in its ability to attenuate oxidative stress and inflammatory cytokines in L-NAME-induced hypertensive rats. A. muricata extracts also decreased atherogenic risk and improved lipid profiles.

Elevated interleukin (IL)-6 levels have been linked to adverse outcomes in patients with and without baseline cardiovascular disease (CVD).

The purpose of this study was to examine the association between circulating IL-6 levels and CVD events without baseline CVD across racial and ethnic groups.

We conducted an observational analysis utilizing the MESA (Multi-Ethnic Study of Atherosclerosis), a multicenter, prospective community-based study of CVD at baseline from four racial and ethnic groups. IL-6 levels were measured at the time of enrollment (visit 1) and were divided into 3 terciles. Patient baseline characteristics and outcomes, including all-cause mortality, CV mortality, heart failure, and non-CV mortality, were included. Cox proportional hazard regression models were used to assess associations between IL-6 levels and study outcomes with IL-6 tercile 1 as reference.

Of 6,622 individuals, over half were women (53%) with a median age of 62 (IQR: 53-70) years. Racial and ethnic composition was non-Hispanic White (39%) followed by African American (27%), Hispanic (22%), and Chinese American (12%). Compared to tercile 1, participants with IL-6 tercile 3 had a higher adjusted risk of and all-cause mortality (HR: 1.98 [95% CI: 1.67-2.36]), CV mortality (HR: 1.55 [95% CI: 1.05-2.30]), non-CV mortality (HR: 2.05 [95% CI: 1.65-2.56]), and heart failure (HR: 1.48 [95% CI: 0.99-2.19]). When tested as a continuous variable, higher levels of IL-6 were associated with an increased risk of all individual outcomes. Compared to non-Hispanic White participants, the unadjusted and adjusted risk of all outcomes across all races and ethnicities was similar across all IL-6 terciles.

High levels of circulating IL-6 are associated with worse CV outcomes and increased all-cause mortality consistently across all racial and ethnic groups.