Development Of Cardiovascular Disease Research Articles

Important aspects of carbohydrate metabolism disorders development in hematology/oncology patients during therapy with glucocorticosteroids: a review of the literature

Glucocorticosteroids are highly effective anti-inflammatory and immunosuppressive agents. The drugs were introduced into therapeutic practice from the mid-20th century and are still widely used in the treatment of various diseases. They are an integral part of the treatment of patients with hematological malignancies. One of the clinically significant complications of glucocorticosteroid therapy is steroid-induced carbohydrate metabolism disorders. Diabetes mellitus is one of the main risk factors for the development of cardiovascular diseases, which are the main non-oncological cause of death in the population and a significant treatment complication in patients with malignant neoplasms. Early detection of the disease and improved treatment efficiency increase the survival rate of patients with various types of neoplasms. It is also important to pay attention to quality of life improving in cancer patients after treatment.The aim of this review is to analyze the pathogenesis features, as well as predictors of early detection and prevention of possible complications of persistent hyperglycemia in patients with hematological malignancies.

Updated guidelines for cardiac patients with diabetes - Pragmatic diagnostic and therapeutic algorithm

AbstractIndividuals with type 2 diabetes are subjected to a disproportionately increased risk for development and progression of cardiovascular disease. Positive outcomes of recent clinical trials have led to the introduction of seminal novel therapeutic options for patients with type 2 diabetes and accompanying cardiovascular risk factors and disease. Consequently, the European Society of Cardiology published an update of the existing guideline for the management of these patients. The aim of this article is to provide a simplified and pragmatic algorithm for diagnostics and treatment for the vast majority of patients with type 2 diabetes, based on current guideline recommendations.

Cardiovascular disease risk in Australians following plant-based dietary patterns compared to regular meat eaters

The adoption of dietary patterns emphasising higher intakes of plant foods and lower intakes of animal foods (plant-based diets, PBDs), continue to rise worldwide. PBDs have been associated with a lower risk of cardiovascular morbidity and mortality as well as major risk factors such as overweight/obesity and type 2 diabetes. Evidence regarding the dietary profile and disease risk associated with various PBDs in comparison to traditional meat-eating diets are scarce within the Australian population. The aim of this study is to investigate the 5-year and 10-year risk of developing cardiovascular disease (CVD) among Australians habitually following various PBDs compared to a regular meat diet (RMD). The Plant-based Diet (PBD) Study is a cross-sectional study consisting of healthy adults between aged 30-75 years from the Hunter Region (NSW) between 2021-2023. A validated FFQ was used to assess eligibility and categorise individuals who were habitually consuming one of five dietary patterns for at least 6 months into the following groups: vegan (nil animal products), lacto-vegetarian (LOV, including eggs and dairy), pesco-vegetarian (PV, including seafood with/without dairy and eggs), semi-vegetarian (SV, minimal consumption of animal products) or RMDs (including animal meat daily or multiple times/day)(1). 5-year and 10-year CVD risk was quantified using the Framingham Risk Equation(2) and the Australian Absolute CVD risk calculator, respectively. CVD risk and other quantitative measures was compared using One-way ANOVA or Kruskal Wallis, and Chi-square or Fisher’s Exact for qualitative data. Directed acyclic graphs displayed confounding variables and mediators and a regression model was used to adjust for these. A total of 240 participants (median age 55(16), 77.5% female) with 48 participants in each group showed a significant difference in predicted 5-year risk of CVD (P<0.05), however 10-year risk did not significantly differ across groups. 5-year CVD risk was significantly lower in the vegan group (1%) compared to the RMD, SV, PV, and LOV diet groups (all 2%). In comparison to a vegan diet, crude association showed those consuming a RMD had a 2.4% (95% CI 0.7, 4.1) higher 5-year risk of developing CVD, followed by 1.7% in LOV (95% CI 0.6, 2.9), 1.8% in PV (95% CI 0.5, 3), and 1.1% in SV (95% CI 0.2, 2.1). Significance was lost after adjusting for confounders such as age, gender, smoking status, alcohol intake, physical activity levels and BMI. This is the first study to purposefully sample Australians habitually following PBD, presenting novel population-based evidence for CVD risk. These findings suggest more restrictive PBDs such as vegan diets when compared to RMD may lead to lower CVD risk, however population-based longitudinal studies primary investigating the development of CVDs in the context of PBDs are warranted.

The 10-year cardiovascular risk of physicians estimated by the Thai CV risk score and its association with current coronary artery disease: A retrospective study.

To assess the 10-year cardiovascular disease (CVD) risk among Thai physicians. The risk compared to the general population and their relationship with the current coronary artery disease (CAD) were also examined. This retrospective study collected data of Thai physicians who underwent cardiovascular assessments between February 14, 2022, and October 31, 2022. The CVD risk was calculated using the Thai CVD risk (TCVR) score, which incorporated variables of age, gender, smoking, diabetes mellitus, blood pressure, and total cholesterol. Additional collected data included family history of CAD, weekly work hours, fiber diet, exercise, body mass index, coronary artery calcium (CAC) score, and presence of CAD. The association between the risk levels with presence of CAD and clinical features including CAC score were analyzed. Of 1225 physicians, the risk for CVD development was categorized as low in 80.0%, moderate in 11.2%, high in 4.9%, and very high in 3.9%. Among these, 33.6% were found to have higher relative risk compared to the general population of the same age and gender. The overall prevalence of CAD was 11.2%. This prevalence was escalated by risk or relative risk groups: 4.9% in low-, 33.8% in moderate-, 35.1% in high-, and 46.8% in very high-risk groups or 7.2% in lower risk, 8.0% the same risk, and 18.4% higher relative risk groups. Approximately, 20% of Thai physicians in the study exhibited a moderate to very high 10-year risk of CVD. Furthermore, 33.6% of the physicians had higher risk than individuals of the same age and gender in the general population. The prevalence of CAD increased with higher CVD risk and higher relative risk.

Contemporary hypolipemic therapy: possibilities of novel hypolipemic drugs in correction of lipid metabolism disorders. Review

Dyslipidemia plays a role of significant risk factor for development and progression of cardiovascular diseases. Today several classes of hypolipemic drugs with evidenced effectiveness are used. But some patients don’t tolerate medicines with high efficacy or can’t achieve the targeted blood lipid profile levels even in case of the use of maximal doses or combined therapy. This necessitates the creation of new hypolipidemic agents.
 The review is devoted to discussion of new directions of influence on impaired lipid metabolism through creation of new classes of hypolipemic drugs with some perspectives of effective correction of lipid factors of cardiovascular risk (CVR) in cases of impossibility to achieve the targeted levels of low‑density lipoprotein cholesterol (LDL‑C) or there is a residual CVR caused by elevated serum triglyceride (TG) levels and/or low levels of high‑density lipoprotein cholesterol (HDL‑C).
 Among the novel drugs for hypercholesterolemia (HCE) correction, considerations are given for some mechanisms of action and efficacy of application of proprotein convertase subtilisin‑kexine type 9 (PCSK9) inhibitors as well as bempedoic acid (adenosine triphosphate citrate lyase inhibitor) and inclisiran, a small synthesized interfering ribonucleic acid (RNA) with its ability to blockade genes‑regulators of hepatic PCSK9 activity. The novel agents for hypertriglyceridemia correction, discussed in the review, include icosapent ethyl (a high purified and firm ester of ethyl‑eicosapentoenic acid), pemafibrate (the first selective modulator of α‑receptors activated by peroxisome proliferator), apolipoprotein C‑III (ApoC‑III) inhibitors (volasenorsen, olesarsen), mipomersen (antisense nucleotide for matrix RNA of apolipoprotein B‑100), lomitapide (inhibitor of microsomal TG transfer protein) and inhibitors of angiopoietin‑like protein 3 (ANGPTL3) (evinacumab, vupanorsen). Among the new approaches to HDL‑C elevation an attention is paid to the experimental and clinical investigations of recombinant HDL, agents with recombinant lecithin‑cholesterol‑acyl‑transferase (LCAT), and apolipoprotein A‑I (ApoA‑I) mimetic peptides. For the lowering of blood lipoprotein(a) (LP(a)) level the possibilities of pelacarsen, an antisense oligonucleotide for matrix RNA of apolipoprotein(a) (apo(a)) contained in LP(a) molecule and olpasiran, a small interfering RNA for LP(a) molecule inhibited apo(a) synthesis are uncovered. A high probability of clinical application in the nearest future will have novel drugs approved by US Food and Drug Administration (FDA) and European Medicines Agency (EMA) such as bempedoic acid and inclisiran for HCE correction as well as lomitapide for the treatment of familial HCE.

Prevalence of risk factors for development of cardiovascular diseases in urban and rural areas of Eastern Croatia: a cross-sectional study.

Cardiovascular diseases are the leading global cause of death. Due to the disparities in cardiovascular risk factors between rural and urban populations, this study aims to assess the differences in the prevalence of risk factors in urban and rural areas of eastern Croatia. The cross-sectional study included 280 participants (140 from urban and 140 from rural areas) registered at studied general practice offices. Methods included e-health records, questionnaire, physical examination methods, and blood sampling for laboratory tests. The most common risk factors among participants were elevated total cholesterol (83.6%), elevated LDL cholesterol (81.8%), increased body mass index (75.0%), increased waist-hip ratio (82.9%), increased waist circumference (63.2%), and arterial hypertension (70.1%). The rural participants had a significantly higher prevalence of arterial hypertension (p = 0.023), increased body mass index (p = 0.004), increased waist circumference (p = 0.004), increased waist-hip ratio (p < 0.001), and increased LDL cholesterol (p = 0.029), while the urban participants had a significantly higher prevalence of insufficient physical activity (p < 0.001). In the examined sample, the prevalence of cardiovascular risk factors is generally high. Participants from rural areas are significantly more susceptible to cardiovascular risk factors than participants from urban areas.

Prevalence of polymorphism of &lt;i&gt;АDRВ1, AGT, SOD2, CAT&lt;/i&gt; genes and their combinations to assess the risk of developing cardiovascular disease

BACKGROUND: Cardiovascular disease remains a major public health problem associated with high mortality. The development of these diseases is associated with many genetic and cardiovascular risk factors, so the study of a person’s genetic predisposition to the development of cardiovascular disease based on gene polymorphism remains actual. The aim of research was to study the combination of polymorphisms of the ADRB1 rs1801253, AGT rs4762, SOD2 rs4880 and CAT rs1001179 genes in healthy young people to assess individual genetic predisposition to the development of cardiovascular disease.&#x0D; MATERIALS AND METHODS: The study involved 33 people aged 19 to 21 years who currently had no pathology of the cardiovascular system. DNA was isolated from oral epithelial cells. Genotyping of DNA samples was determined using real-time polymerase chain reaction.&#x0D; RESULTS: Among those examined, 39.4% had one or two unfavorable alleles for the ADRB1, AGT genes, suggesting a genetic predisposition to the development of cardiovascular disease. Unfavorable alleles of the ADRB1 gene were more common compared to the AGT gene. Each of those examined at risk of developing cardiovascular disease had one or two alleles associated with a decrease in the functioning of enzymes of the antioxidant system. Of the 33 people, only four (12.1%) do not have an unfavorable allele for the SOD2 and CAT genes.&#x0D; CONCLUSIONS: We believe that the determination of polymorphisms in genes for enzymes of the antioxidant system will be an important additional criterion for earlier and more active prevention of cardiovascular disease.

Effects of obstructive sleep apnea syndrome on clinical and instrumental indicators in obese patients

Due to the high prevalence of obstructive sleep apnea syndrome (OSAS), its diagnosis and treatment remains one of the urgent problems of medicine. Hypodiagnosis of OSAS is observed in everyday clinical practice. The early OSAS diagnosis and treatment, including the use of non‑invasive assisted ventilation of the lungs with constant positive pressure during sleep, could prevent the development and progression of cardiovascular diseases, and significantly improve the quality of life of a person.&#x0D; Objective — to assess OSAS impact on the clinical and instrumental indicators in obese patients, to establish correlation between the characteristics of cardiorespiratory sleep monitoring and indicators of carbohydrate and lipid metabolism in obese patients.&#x0D; Materials and methods. Observations involved 78 patients with I ‑ II degree obesity. According to the results of cardiorespiratory monitoring (CRM) of sleep, three groups of obese patients were formed. The first group included 26 patients with an apnea‑hypopnea index &lt;30 episodes per hour (mild OSAS degree). The second group was consisted of 26 patients with apnea/hypopnea index (AHI) over 30 episodes per hour (severe OSAS degree). The groups matched by percentage of men and women, the mean age and body mass index.&#x0D; Results. An increase in body weight and body mass index (BMI) in obese patients was associated with an increase in the number and total duration of episodes of apnea/hypopnea, AHI, as well as a decrease in blood oxygen saturation (SpO2). Parameters of waist circumference (WC), hip circumference (HC), WC/HC positively correlated with the number and duration of episodes of apnea/hypopnea, AHI, and negatively correlated with SpO2. Positive values of the Spearman r coefficient ranged from 0.23 to 0.57, negative values — from –0.26 to –0.48 (р &lt;0.05).&#x0D; Conclusions. In obese patients with OSAS, the parameters of cardiorespiratory sleep monitoring — apnea‑hypopnea index, total duration of apnea episodes, directly correlated with body mass index, waist circumference, blood pressure level, total cholesterol, blood triglycerides. An inverse correlation was found between oxygen saturation and fasting glycemia and the level of glycated hemoglobin.

The role of intestinal microbiota in the development of dyslipidemia and cardiovascular disease risk

The aim of the study: to summarize the study results on the interaction between intestinal microbiota and the human body in terms of the risk for dyslipidemia and cardiovascular system diseases. Material and methods. A descriptive and comparative study was conducted based on the analysis of scientific literature focused on the role of intestinal microbiota in the occurrence of dyslipidemia and the development of cardiovascular diseases. The following research methods were used: search, comparative, analysis of scientific literature, generalization, synthesis. Results. Gut microbiota plays an important role in maintaining health, and its pathology contributes to the risk for cardiovascular diseases. In some cases, monitoring the intestinal microbiota and the preventive use of pre- and probiotics can reduce the risk for developing cardiovascular system diseases. Conclusions. It has been found that trimethylamine-N-oxide, a microbiota-dependent metabolite, is the first of many existing bacterial products with the proven role in the development of cardiovascular system diseases.

FEATURES OF THE COURSE OF STABLE CORONARY ARTERY DISEASE WITH BORDERLINE CORONARY ARTERY STENOSES DEPENDING ON THE EPICARDIAL FAT THICKNESS

HighlightsPatients with stable coronary artery disease, borderline coronary artery stenoses (BCAS) and increased thickness of epicardial adipose tissue (EAT) are characterized by development of cardiovascular diseases (CVD) at a younger age and higher levels of proinflammatory markers compared to patients without increased thickness of EAT (in case of comparable obesity class, diabetes type, angina grade and apolipoprotein B levels). Aim. To study the features of the course of stable coronary artery disease with borderline coronary artery stenoses (BCAS) depending on the epicardial fat thickness.Methods. 201 patients with stable angina of 1–3 grade with BCAS (50–70%) were included in the study. The 1st group consisted of 57 (28,4%) patients with high EAT levels, the 2nd group consisted of 144 (71,6%) patients without normal EAT levels. The results of biochemical blood tests and systemic inflammation markers (high-sensitivity C-reactive protein, IL 1, 6, 8, 10, TNF-a, cystatin С, MMP-9, NTproBNP) concentration were evaluated. The epicardial fat thickness was determined by echocardiography. All patients underwent coronary angiography.Results. The general EAT thickness was at 6.00 [5.00; 6.50] mm in the 1st group and at 3.00 [2.30; 4.00] mm in the 2nd group (p&lt;0.001). Hypertension (p&lt;0.001), CAD (p&lt;0.001), and myocardial infarction in particular (p = 0.003) were detected at a younger age in the 1st group. There were no significant differences in terms of prevalence of obesity, diabetes mellitus, angina grade and type of prescribed medication. Patients in the 1st group showed higher levels of NTproBNP (p = 0.002) and hsCRP (p = 0.027). Moreover, patients in the 1st group had a higher Apo-A1 levels (p = 0.023) and a lower Apo B/Apo-A1 ratio (p = 0.019). Proinflammatory cytokine levels were comparable, however anti-inflammatory cytokine IL-10 levels (р =0.005) and the frequency of elevated IL-10 levels (p&lt;0.001) were lower in the 1st group. Higher cystatin C levels and the frequency of elevated cystatin C levels (p&lt;0.001) were observed more often in patients with high EAT levels.Conclusion. Patients with stable CAD, borderline coronary artery stenoses and high EAT levels can be characterized by cardiovascular diseases detected at a younger age and higher levels of proinflammatory markers compared with patients with normal EAT levels in case of comparable obesity class, diabetes mellitus, angina grade, and Apo B levels.

SUMO-specific proteases: SENPs in oxidative stress-related signaling and diseases.

Oxidative stress is employed to depict a series of responses detrimental to normal cellular functions resulting from an imbalance between intracellular oxidants, mainly reactive oxygen species and antioxidant defenses. Oxidative stress often contributes to the development of various diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases. In this process, the relationship between small ubiquitin-like modifier (SUMO) and oxidative stress has garnered significant attention, with its posttranslational modification (PTM) frequently serving as a marker of oxidative stress status. Sentrin/SUMO-specific proteases (SENPs), affected by alternative splicing, PTMs such as phosphorylation and ubiquitination, and various protein interactions, are crucial molecules in the SUMO process. The human SENP family has six members (SENP1-3, SENP5-7), which are classified into two categories based on sequence similarity, substrate specificity, and subcellular location. They have two core functions in the human body: first, by cleaving the precursor SUMO and exposing the C-terminal glycine, they initiate the SUMO process; second, they can specifically recognize and dissociate SUMO proteins bound to substrates, a process known as deSUMOylation. However, the connection between deSUMOylation and oxidative stress remains a relatively unexplored area despite their strong association with oxidative diseases such as cancer and cardiovascular disease. This article aims to illustrate the significant contribution of SENPs to the oxidative stress pathway through deSUMOylation by reviewing their structure and classification, their roles in oxidative stress, and the changes in their expression and activity in several typical oxidative stress-related diseases.

MODERN BIOMARKERS - PREDICTORS OF EARLYCARDIOVASCULAR AGEING (LITERATURE REVIEW)

An analysis of the current state of the problem of studying biomarkers of human cardiovascular ageing was carried out based on an analysis of international experience. Ageing is an inevitable, constantly progressive systemic process, which is a significant risk factor for the development of most common chronic human diseases, including cardiovascular diseases. Therefore, studying markers of early cardiovascular ageing is a logical goal for developing measures to prevent the development of cardiovascular disease and toimprove the quality of life and prolong active longevity. the intensive care unit. The application of a multidisciplinary approach to diagnose and treat a life-threatening complication as tracheal rupture in a short time allowed us to stabilize the patient’s condition and avoid the development of further complications.

Sudden cardiac death in young athletes: exome sequencing results

BACKGROUND: Ranking risks and prevention of sudden cardiac death in professional young athletes is a crucial unresolved problem in sports medicine. Intense physical exertion can lead to adaptive changes in the cardiovascular system, which can mask inherited diseases with predominant myocardial involvement, such as hypertrophic cardiomyopathy. Undiagnosed cases of such diseases can be a risk factor for fatal outcomes associated with training and competitive activities, making this problem extremely relevant.&#x0D; AIM: To conduct a diagnostic search for possible molecular causes of cardiovascular diseases associated with a high risk of sudden death in young athletes.&#x0D; MATERIALS AND METHODS: Whole-exome sequencing of DNA extracted from two groups of biomaterials was performed: nine autopsy samples of heart tissues from young athletes who died during intense physical exertion and three venous blood samples from active athletes of the Russian national team. Obtained data were subjected to bioinformatic analysis and clinical interpretation.&#x0D; RESULTS: In total, 12 DNA samples were analyzed using a panel of 277 genes associated with the development of cardiovascular diseases with a high risk of sudden death. In 4 of 12 samples (33.3%), variants possibly related to the phenotype were found upon clinical interpretation of the sequencing results. A pathogenic variant was found in the MYBPC3 gene, leading to the development of hypertrophic cardiomyopathy (OMIM: 115197), and a potential pathogenic variant was found in the TRPM4 gene, associated with progressive familial heart block type IB (OMIM: 618531). Moreover, two variants with uncertain clinical significance were found in CAV3 and SCN1B.&#x0D; CONCLUSION: Currently, data from high-throughput sequencing are collected to identify the molecular basis of cardiovascular diseases with a high risk of sudden cardiac death. Identifying young athletes who are carriers of pathogenic and possibly pathogenic gene variants is beneficial for preventing fatal outcomes and personalizing medical support for professional athletes.

Comorbid pathology in patients with hyperuricemia in the Khabarovsk region

BACKGROUND: Uric acid can affect many metabolic processes in the human body. In recent decades, great importance has been given to increased levels of uric acid — hyperuricemia. Hyperuricemia has been proven to be an independent risk factor for the development of cardiovascular, renal and metabolic diseases, and not just their marker, as had previously ben considered. AIM: To determine the incidence of hyperuricemia at the primary outpatient stage, as well as to assess the prevalence of comorbid pathology among patients with hyperuricemia in the Khabarovsk Territory. MATERIALS AND METHODS: We analyzed 5261 medical records of the patients who applied for an initial outpatient appointment at the Clinical Diagnostic Center and the Viveya Consultative and Diagnostic Center in Khabarovsk from November 2022 to November 2023. From the total number of medical records 2428 patients had elevated level of uric acid in the blood. RESULTS: Arterial hypertension (60.5%) was the most common pathology; obesity – the second (27.35%); diabetes mellitus type 2 was less common in the patients with hyperuricemia (17.75%), and nephrolithiasis was the least common pathology (7.91%). CONCLUSIONS: A high prevalence of hyperuricemia among the population of the Khabarovsk Territory was revealed. Elevated levels of uric acid affect the development of comorbid pathology in the patients, in particular cardiovascular pathology. The results obtained during the study indicate a high prevalence of comorbid diseases in hyperuricemia with arterial hypertension being the most frequent.

Circ_0104652 Promotes the Proliferation and Migration of ox-LDL-Stimulated Vascular Smooth Muscle Cells via Stabilizing ADAMTS7 and HMGB1.

Atherosclerosis (AS) stands as the primary contributor to cardiovascular disease, a pervasive global health concern. Extensive research has underscored the pivotal role of circular RNAs (circRNAs) in cardiovascular disease development. However, the specific functions of numerous circRNAs in AS remain poorly understood. Quantitative real-time PCR analysis revealed a significant upregulation of circ_0104652 in oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs). Loss-of-function experiments were subsequently employed to assess the impact of circ_0104652 on ox-LDL-induced VSMCs. Silencing circ_0104652 was found to impede the proliferation and migration while promoting the apoptosis of ox-LDL-stimulated VSMCs. Mechanistic assays unveiled that circ_0104652 stabilized ADAM metallopeptidase with thrombospondin type 1 motif 7 (ADAMTS7) and high mobility group box 1 (HMGB1) by recruiting eukaryotic translation initiation factor 4A3 (EIF4A3) protein. Rescue assays further confirmed that circ_0104652 exerted its influence on ox-LDL-induced VSMC proliferation through modulation of ADAMTS7 and HMGB1. This study elucidates the role of the circ_0104652/EIF4A3/ADAMTS7/HMGB1 axis in ox-LDL-stimulated VSMCs, providing valuable insights into the intricate mechanisms involved.

Effects of moderate ethanol exposure on risk factors for cardiovascular disease and colorectal cancer in adult Wistar rats

While past studies have provided evidence linking excessive alcohol consumption to increased risk for cardiovascular diseases (CVDs) and colorectal cancer (CRC), existing data on the effects of moderate alcohol use on these conditions have produced mixed results. The purpose of this study was to investigate the effects of moderate alcohol consumption on risk factors associated with the development of CVDs and CRC in adult rats. Twenty-four, 14-month-old, non-deprived male Wistar rats were randomly assigned to either an ethanol group, which consisted of voluntary access to a 20% (v/v) ethanol solution on alternate days, or a water control group (n = 12/group) for 13 weeks. Blood samples were collected to analyze levels of albumin, glucose, adiponectin, lipids, oxidized low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (apoA1), C-reactive protein (CRP), high-mobility group box 1 protein (HMGB-1), tumor necrosis factor-alpha (TNF-α), thyroxine, thyroid-stimulating hormone, 8-oxo-2′-deoxyguanosine (8-oxo-dG), liver function enzymes, and antioxidant capacity. Colonic gene expression related to colon carcinogenesis was also assessed. Ethanol-treated rats were found to have significantly higher HDL-C and apoA1 levels compared to controls. Moderate alcohol consumption led to significantly lower CRP levels and a trend for decrease in HMGB-1, TNF-α, and 8-oxo-dG levels. In the ethanol-exposed group, colonic gene expression of superoxide dismutase was upregulated while aldehyde dehydrogenase 2 showed a trend for increase compared to the control group. These results indicate that adopting a moderate approach to alcohol consumption could potentially improve health biomarkers related to CVD and CRC by increasing HDL-C levels and antioxidant activity and reducing DNA damage and inflammatory activity.

Immunopathogenesis and detection methods of type 2 diabetes

Diabetes is a disease that is increasingly prevalent on a global scale. Type 2 diabetes (T2D) accounts for 90% of all diabetes cases and is a chronic condition primarily influenced by factors such as obesity and genetics. This condition often leads to the development of various cardiovascular diseases. A diverse of different detection methods for the T2D have been developed and achieved good detection and analysis results. In addition, numerous studies have indicated a close connection between T2D and immune inflammation. This research primarily introduces the current status of diabetes, provides a detailed summary of the connection betweenT2D and the immune system, and presents novel immune biomarkers related to T2D. Some new immunological testing methods will be analyzed in this research. In the future, there is hope that these new biomarkers can be used to design more advantageous therapeutic drugs for diabetes patients and more convenient, sensitive, and low-cost detection methods.

Abstract 2227: Physical activity at breast cancer diagnosis and incident cardiovascular disease in the Pathways Study

Abstract Background: Breast cancer survivors are at increased risk of cardiovascular disease (CVD) compared to women without a history of breast cancer. Although cardiotoxic cancer treatments influence these risks, lifestyles that are associated with both breast cancer and CVD also contribute. With the number of breast cancer survivors expected to increase, a growing need exists to identify modifiable risk factors that protect against the development of CVD after diagnosis. Physical activity at breast cancer diagnosis is associated with lower cancer recurrence and mortality risk. However, associations between physical activity at diagnosis and incident CVD have yet to be investigated in detail. Methods: The Pathways Study is a prospective cohort study of 4,504 women who were members of Kaiser Permanente Northern California (KPNC) when diagnosed with first primary invasive breast cancer between 2005 and 2013. At enrollment, women self-reported their frequency, duration, and intensity of physical activities during the previous six months using the Arizona Activity Frequency Questionnaire. This information was used to dichotomize the women’s physical activity levels by the CDC’s Physical Activity Guidelines for Americans (≥ 150 minutes of moderate-to-vigorous physical activity per week vs less). CVD events were obtained from electronic health records as part of the Pathways Heart Study and were defined as post-diagnostic incidence of ischemic heart disease, heart failure, cardiomyopathy, and stroke. Deaths were documented through several sources, including the National Death Index. Women were followed until the first of disenrollment from the KPNC health plan, death, or December 31, 2021. Competing risk Cox regression models were used to estimate associations between meeting CDC physical activity guidelines and CVD. Results: In this cohort of breast cancer survivors, women who self-reported meeting physical activity guidelines at diagnosis experienced lower rates of post-diagnostic CVD events (8.6% vs 13.1%). After adjustment for socio-demographic factors, meeting physical activity guidelines remained associated with lower risk of CVD (HR: 0.78, 95% CI: 0.61, 0.98); this association appeared to be driven by reduced risk of heart failure (HR: 0.68, 95% CI: 0.50, 0.93) and cardiomyopathy (HR: 0.51, 95% CI: 0.28, 0.92). Approximately 15% of the CVD risk reduction in Pathways Study participants can be attributed to meeting physical activity guidelines (population attributable risk percent: 14.5%, 95% CI: 8%, 21%). Conclusions: Compared to women who did not meet CDC physical activity guidelines, women who reported meeting guidelines near the time of their breast cancer diagnosis had decreased risk of future CVD, including heart failure and cardiomyopathy. Future studies investigating changes in post-diagnostic physical activity patterns and CVD risk are warranted. Citation Format: Jacob K. Kresovich, Alicia R. Richards, Isaac J. Ergas, Cecile A. Laurent, Rikki Cannioto, Jamal S. Rana, Janise M. Roh, Catherine Thomsen, Salma Shariff-Marco, Eileen Rillamas-Sun, Richard K. Cheng, Song Yao, Christine B. Ambrosone, Lawrence H. Kushi, Heather Greenlee, Marilyn L. Kwan. Physical activity at breast cancer diagnosis and incident cardiovascular disease in the Pathways Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2227.

Human recombinant relaxin-2 (serelaxin) regulates the proteome, lipidome, lipid metabolism and inflammatory profile of rat visceral adipose tissue

Recombinant human relaxin-2 (serelaxin) has been widely proven as a novel drug with myriad effects at different cardiovascular levels, which support its potential therapeutic efficacy in several cardiovascular diseases (CVD). Considering these effects, together with the influence of relaxin-2 on adipocyte physiology and adipokine secretion, and the connection between visceral adipose tissue (VAT) dysfunction and the development of CVD, we could hypothesize that relaxin-2 may regulate VAT metabolism. Our objective was to evaluate the impact of a 2-week serelaxin treatment on the proteome and lipidome of VAT from Sprague-Dawley rats. We found that serelaxin increased 1 polyunsaturated fatty acid and 6 lysophosphatidylcholines and decreased 4 triglycerides in VAT employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) based platforms, and that regulates 47 phosphoproteins using SWATH/MS analysis. Through RT-PCR, we found that serelaxin treatment also caused an effect on VAT lipolysis through an increase in the mRNA expression of hormone-sensitive lipase (HSL) and a decrease in the expression of adipose triglyceride lipase (ATGL), together with a reduction in the VAT expression of the fatty acid transporter cluster of differentiation 36 (Cd36). Serelaxin also caused an anti-inflammatory effect in VAT by the decrease in the mRNA expression of tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), chemerin, and its receptor. In conclusion, our results highlight the regulatory role of serelaxin in the VAT proteome and lipidome, lipolytic function, and inflammatory profile, suggesting the implication of several mechanisms supporting the potential benefit of serelaxin for the prevention of obesity and metabolic disorders.

Bridging Metabolic-Associated Steatotic Liver Disease and Cardiovascular Risk: A Potential Role for Ketogenesis.

The prevalence of cardiovascular diseases (CVDs) is a growing global health concern. Recent advances have demonstrated significant reductions in acute cardiovascular events through the management of modifiable cardiovascular risk factors. However, these factors are responsible for about 50% of the global cardiovascular disease burden. Considering that CVDs are one of the top mortality causes worldwide, the concept of residual cardiovascular risk is an important emerging area of study. Different factors have been proposed as sources of residual risk markers, including non-HDL particles characterization, as well as inflammation measured by serum and imaging technics. Among these, metabolic-associated steatotic liver disease (MASLD) remains controversial. Two opposing viewpoints contend: one positing that fatty liver disease merely reflects classical risk factors and thus adds no additional risk and another asserting that fatty liver disease independently impacts cardiovascular disease incidence. To address this dilemma, one hypothetical approach is to identify specific hepatic energy-yielding mechanisms and assess their impact on the cardiovascular system. Ketogenesis, a metabolic intermediate process particularly linked to energy homeostasis during fasting, might help to link these concepts. Ketogenic metabolism has been shown to vary through MASLD progression. Additionally, newer evidence supports the significance of circulating ketone bodies in cardiovascular risk prediction. Furthermore, ketogenic metabolism modification seems to have a therapeutic impact on cardiovascular and endothelial damage. Describing the relationship, if any, between steatotic liver disease and cardiovascular disease development through ketogenesis impairment might help to clarify MASLD's role in cardiovascular risk. Furthermore, this evidence might help to solve the controversy surrounding liver steatosis impact in CVD and might lead to a more accurate risk assessment and therapeutic targets in the pursuit of precision medicine.