Development Of Cardiovascular Disease Research Articles

Senescence of endothelial cells promotes phenotypic changes in adventitial fibroblasts: possible implications for vascular aging.

Aging is the most important risk factor for the development of cardiovascular diseases. Senescent cells release plethora of factors commonly known as the senescence-associated secretory phenotype, which can modulate the normal function of the vascular wall. It is currently not well understood if and how endothelial cell senescence can affect adventitial niche. The aim of this study was to characterize oxidative stress-induced endothelial cells senescence and identify their paracrine effects on the primary cell type of the adventitia, the fibroblasts. Human aortic endothelial cells (HAEC) were treated with hydrogen peroxide to induce premature senescence. Mass spectrometry analysis identified several proteomic changes in senescent HAEC with top upregulated secretory protein growth differentiation factor 15 (GDF-15). Treatment of the human adventitial fibroblast cell line (hAdv cells) with conditioned medium (CM) from senescent HAEC resulted in alterations in the proteome of hAdv cells identified in mass spectrometry analysis. Majority of differentially expressed proteins in hAdv cells treated with CM from senescent HAEC were involved in the uptake and metabolism of lipoproteins, mitophagy and ferroptosis. We next analyzed if some of these changes and pathways might be regulated by GDF-15. We found that recombinant GDF-15 affected some ferroptosis-related factors (e.g. ferritin) and decreased oxidative stress in the analyzed adventitial fibroblast cell line, but it had no effect on erastin-induced cell death. Contrary, silencing of GDF-15 in hAdv cells was protective against this ferroptotic stimuli. Our findings can be of importance for potential therapeutic strategies targeting cell senescence or ferroptosis to alleviate vascular diseases.

Unveiling the oral-gut connection: chronic apical periodontitis accelerates atherosclerosis via gut microbiota dysbiosis and altered metabolites in apoE−/− Mice on a high-fat diet

The aim of this study was to explore the impact of chronic apical periodontitis (CAP) on atherosclerosis in apoE−/− mice fed high-fat diet (HFD). This investigation focused on the gut microbiota, metabolites, and intestinal barrier function to uncover potential links between oral health and cardiovascular disease (CVD). In this study, CAP was shown to exacerbate atherosclerosis in HFD-fed apoE−/− mice, as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining. 16S rRNA sequencing revealed significant alterations in the gut microbiota, with harmful bacterial species thriving while beneficial species declining. Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis, leading to elevated levels of taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), and tauroursodeoxycholic acid (TDCA). These metabolic shifts may contribute to atherosclerosis development. Furthermore, impaired intestinal barrier function, characterized by reduced mucin expression and disrupted tight junction proteins, was observed. The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions, highlighting the importance of the intestinal barrier in cardiovascular health. In conclusion, this research underscores the intricate interplay among oral health, gut microbiota composition, metabolite profiles, and CVD incidence. These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues, as well as the need for further investigations into the intricate mechanisms linking oral health, gut microbiota, and metabolic pathways in CVD development.

Standard and New Echocardio Techniques, Such as Global Longitudinal Strain, to Monitor the Impact of Diets on Cardiovascular Diseases and Heart Function

“The Seven Countries Study”, published in 1984, was the first study to find a correlation between diet and mortality related to cardiovascular diseases (CVDs). Since then, many investigations have addressed the relationship between type of diet, or specific nutrients, and CVDs. Based on these findings, some traditional dietary models, such as the Mediterranean or Nordic diet, are recommended to prevent CVDs. Meanwhile, new diets have been proposed for optimal nutrition therapy, for example, the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean–DASH Intervention Diet for Neurodegenerative Delay (MIND). The main outcomes evaluated after implementing these dietary models are as follows: CVD-related death; the development of specific CVDs, such as myocardial infarction and hypertension; or biochemical parameters related to CVDs, i.e., non-HDL cholesterol, C-reactive protein (CPR) and homocysteine. However, the early impact of diet on heart functionality is less evaluated. Recently, the echographic measurement of left ventricle (LV) deformation by global longitudinal strain (GLS) has been introduced as a novel marker of clinical and subclinical cardiac dysfunction. This technology allows a subclinical evaluation of heart functionality since, differently from the traditional evaluation of left ventricle ejection fraction (LVEF), it is capable of detecting early myocardial dysfunction. In this review, we analyzed the available studies that correlate dietetic regimens to cardiovascular diseases, focusing on the relevance of LV strain to detect subclinical myocardial alteration related to diet. Evidence is presented that DASH and MIND can have a positive impact on heart functionality and that myocardial strain is useful for early detection of diet-related changes in cardiac function.

Association between non-registration of chronic kidney disease and mortality and cardiovascular outcome: a time-to-event analysis of retrospective primary care data

ObjectivePatients with impaired kidney function and increased albuminuria are at risk of developing cardiovascular disease (CVD). Previous research has revealed that a substantial proportion of patients with chronic kidney disease...

The association between energy‐adjusted dietary inflammatory index and 10‐year cardiovascular risk: Fasa adult cohort study

AbstractA healthy diet is dominant in cardiovascular disease (CVD) prevention. Inflammation is pivotal for CVD development. This study aimed to evaluate the association between the pro‐inflammatory diet and the CVD risk. This cross‐sectional study involved 10,138 Fasa adult cohort study participants. After excluding participants with missing data, the Energy‐Adjusted Dietary Inflammatory Index (E‐DII) was calculated to assess the inflammatory potential of diet using the recorded Food Frequency Questionnaire. Framingham risk score (FRS) was used to predict the 10‐year risk of CVD. The association between E‐DII and high risk for CVD was investigated using multinominal regression. After exclusion, the mean age of studied individuals (n = 10,030) was 48.6 ± 9.6 years, including 4522 men. Most participants were low risk (FRS <10%) for CVD (87.6%), while 2.7% of them were high risk (FRS ≥20%). The median FRS was 2.80 (1.70, 6.30). The E‐DII ranged from −4.22 to 4.49 (mean E‐DII = 0.880 ± 1.127). E‐DII was significantly associated with FRS. This result persisted after adjusting for confounding factors and in both genders. This study revealed that the pro‐inflammatory diet significantly increases the CVD risk. Consequently, reducing the inflammatory potential of diet should be considered an effective dietary intervention in CVD prevention.

Protocol for the nationwide registry of patients with polycystic kidney disease: japanese national registry of PKD (JRP).

Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are major genetic polycystic kidney diseases that can progress to end-stage kidney disease (ESKD). Longitudinal data on the clinical characteristics associated with clinical outcomes in polycystic kidney disease (PKD), including the development of ESKD and cardiovascular disease (CVD) are lacking in Japan. To address this unmet need the authors are establishing a novel, web-based, Nationwide Cohort Registry Study-the Japanese Registry of PKD (JRP). The JRP is a prospective cohort study for ADPKD (aim to recruit n = 1000 patients), and both a retrospective and prospective study for ARPKD (aim to recruit n = 100). In the prospective registry, patients will be followed-up for 10years every 6months and 12months for patients with ADPKD and ARPKD, respectively. Data collection will be recorded on Research Electronic Data Capture (REDCap) starting on April 1, 2024, with recruitment ending on March 31, 2029. (jRCT 1030230618). Data to be collected include: baseline data, demographics, diagnostic and genetic information, radiological and laboratory findings, and therapeutic interventions. During follow-up, clinical events such as development of ESKD, hospitalization, occurrence of extra kidney complications including CVD events, and death will be recorded, as well as patient-reported health-related quality of life for patients with ADPKD. The JRP is the first nationwide registry study for patients with ADPKD and ARPKD in Japan, providing researchers with opportunities to advance knowledge and treatments for ADPKD and ARPKD, and to inform disease management and future clinical practice.

Analysis of the Associations of Measurements of Body Composition and Inflammatory Factors with Cardiovascular Disease and Its Comorbidities in a Community-Based Study

The associations of cardiovascular disease (CVD) with comorbidities and biochemical and body composition measurements are repeatedly described but have not been studied simultaneously. In the present cross-sectional study, information on CVD and comorbidities [type 2 diabetes mellitus (T2DM), hypertension (HTN), and hyperlipidemia (HDL)], body composition, levels of soluble markers, and other measures were collected from 1079 individuals. When we examined the association of each comorbidity and CVD, controlling for other comorbidities, we observed a clear pattern of the comorbidity-related specific associations with tested covariates. For example, T2DM was significantly associated with GDF-15 levels and the leptin/adiponectin (L/A) ratio independently of two other comorbidities; HTN, similarly, was independently associated with extracellular water (ECW) levels, L/A ratio, and age; and HDL was independently related to age only. CVD showed very strong independent associations with each of the comorbidities, being associated most strongly with HTN (OR = 10.89, 6.46–18.38) but also with HDL (2.49, 1.43–4.33) and T2DM (1.93, 1.12–3.33). An additive Bayesian network analysis suggests that all three comorbidities, particularly HTN, GDF-15 levels, and ECW content, likely have a main role in the risk of CVD development. Other factors, L/A ratio, lymphocyte count, and the systemic inflammation response index, are likely indirectly related to CVD, acting through the comorbidities and ECW.

The Role of Angiopoietins in Cardiovascular Outcomes of Kidney Transplant Recipients- An Ancillary Study From the FAVORIT.

Kidney transplant recipients (KTRs) have increased risk of cardiovascular disease (CVD) mortality. We investigated vascular biomarkers, angiopoietin-1 and angiopoietin-2 (angpt-1, -2), in CVD development in KTRs. This ancillary study from the FAVORIT, evaluates the associations of baseline plasma angpt-1,-2 levels in CVD development (primary outcome) and graft failure (GF) and death (secondary outcomes) in 2000 deceased donor KTRs. We used Cox regression to analyze the association of biomarker quartiles with outcomes. We adjusted for demographic, CVD and transplant-related variables; medications; urine albumin-to-creatinine ratio and randomization status. We calculated areas under the curves (AUC) to predict CVD or death, and GF or death by incorporating biomarkers alongside clinical variables. Participants' median age was 52 IQR [45, 59] years: with 37% women and 73% identifying as white. Median time from transplantation was 3.99 IQR [1.58, 7.93] years and to CVD development was 2.54 IQR [1.11-3.80] years. Quartiles of angpt-1 were not associated with outcomes. Whereas higher levels of angpt-2 (quartile 4) were associated with about 2 times the risk of CVD, GF and death [aHR 1.85 (1.25 - 2.73), P<.01; 2.24 (1.36 - 3.70), P<.01; 2.30 (1.48 - 3.58), P<.01, respectively] as compared to quartile 1. Adding angiopoietins to pre-existing clinical variables improved prediction of CVD or death (AUC improved from 0.70 to 0.72, P=0.005) and GF or death (AUC improved from 0.68 to 0.70, P =0.005). Angpt-2 may partially explain the increased risk of future CVD in KTRs. Further research is needed to assess the utility of using angiopoietins in the clinical care of KTRs. Angpt-2 may be a useful prognostic tool for future CVD in KTRs. Combining angiopoietins with clinical markers may tailor follow-up to mitigate CVD risk.

Pacemaker Channels and the Chronotropic Response in Health and Disease

Loss or dysregulation of the normally precise control of heart rate via the autonomic nervous system plays a critical role during the development and progression of cardiovascular disease—including ischemic heart disease, heart failure, and arrhythmias. While the clinical significance of regulating changes in heart rate, known as the chronotropic effect, is undeniable, the mechanisms controlling these changes remain not fully understood. Heart rate acceleration and deceleration are mediated by increasing or decreasing the spontaneous firing rate of pacemaker cells in the sinoatrial node. During the transition from rest to activity, sympathetic neurons stimulate these cells by activating β-adrenergic receptors and increasing intracellular cyclic adenosine monophosphate. The same signal transduction pathway is targeted by positive chronotropic drugs such as norepinephrine and dobutamine, which are used in the treatment of cardiogenic shock and severe heart failure. The cyclic adenosine monophosphate–sensitive hyperpolarization–activated current (I f ) in pacemaker cells is passed by hyperpolarization-activated cyclic nucleotide-gated cation channels and is critical for generating the autonomous heartbeat. In addition, this current has been suggested to play a central role in the chronotropic effect. Recent studies demonstrate that cyclic adenosine monophosphate–dependent regulation of HCN4 (hyperpolarization-activated cyclic nucleotide-gated cation channel isoform 4) acts to stabilize the heart rate, particularly during rapid rate transitions induced by the autonomic nervous system. The mechanism is based on creating a balance between firing and recently discovered nonfiring pacemaker cells in the sinoatrial node. In this way, hyperpolarization-activated cyclic nucleotide-gated cation channels may protect the heart from sinoatrial node dysfunction, secondary arrhythmia of the atria, and potentially fatal tachyarrhythmia of the ventricles. Here, we review the latest findings on sinoatrial node automaticity and discuss the physiological and pathophysiological role of HCN pacemaker channels in the chronotropic response and beyond.

Diagnosis and treatment of dyslipidemia in children and adolescents

Background: Atherosclerotic cardiovascular disease is a major cause of morbidity and mortality worldwide, including in South Korea. Dyslipidemia is an independent risk factor for the development of atherosclerotic cardiovascular diseases. There is strong evidence that atherosclerosis begins early in life and that elevated lipid levels in childhood predict elevated lipid levels into adulthood.Current Concepts: A universal approach for cholesterol screening in all children is recommended. Lipid profiles should be studied for all children aged 9 to 11 years and then for those aged 17 to 21 years, as cholesterol levels may vary after puberty. The non-fasting lipid profile can be as useful in detecting severe genetic dyslipidemias as the fasting lipid profile and thus can be used as a first-line screening in children. The initial treatment for dyslipidemia in a child always begins with a 6-month trial of lifestyle modifications, such as improvements in dietary and physical activity patterns. Statins are as effective in children as in adults and can lower low-density lipoprotein cholesterol levels by up to 50%. Therefore, they are considered first-line therapy for children who meet the criteria for pharmacological therapy.Discussion and Conclusion: Statins and non-statin lipid-lowering agents can lower cholesterol levels with minimal adverse effects in children and adolescents with hypercholesterolemia. However, limited data is currently available on the long-term safety and efficacy of lipid-lowering agents in the pediatric population. Furthermore, non-statin lipid-lowering agents are used far less frequently in children. Therefore, further long-term safety and efficacy studies on lipid-lowering agents in pediatric populations and clinical trials with non-statin lipid-lowering agents are required.

Management of Cardiovascular Risk in the Non‑alcoholic Fatty Liver Disease Setting

Non-alcoholic fatty liver disease (NAFLD) is an overlooked and undetected pathology, which affects more than 32% of adults worldwide. NAFLD is becoming more common in Western industrialised countries, particularly in patients with central obesity, type 2 diabetes, dyslipidaemia and metabolic syndrome. Although NAFLD has traditionally been interpreted as a liver disease with a high risk of liver-related complications, NAFLD is an underappreciated and independent risk factor for atherosclerotic cardiovascular disease, which is the principal cause of death in patients with NAFLD. Treatment options to counteract both the progression and development of cardiovascular disease and NAFLD include lifestyle interventions, such as weight loss, increased physical activity and dietary modification, and optimal medical therapy of comorbid conditions; nevertheless, further studies are needed to define optimal treatment strategies for the prevention of both hepatic and cardiovascular complications of NAFLD.

Navigating the Link Between Non-alcoholic Fatty Liver Disease/Non-alcoholic Steatohepatitis and Cardiometabolic Syndrome

The global prevalence of non-alcoholic fatty liver disease (NAFLD) is nearly 25% and is increasing rapidly. The spectrum of liver damage in NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis, characterised by the presence of lobular inflammation and hepatocyte ballooning degeneration, with or without fibrosis, which can further develop into cirrhosis and hepatocellular carcinoma. Not only is NAFLD a progressive liver disease, but numerous pieces of evidence also point to extrahepatic consequences. Accumulating evidence suggests that patients with NAFLD are also at increased risk of cardiovascular disease (CVD); in fact, CVDs are the most common cause of mortality in patients with NAFLD. Obesity, type 2 diabetes and higher levels of LDL are common risk factors in both NAFLD and CVD; however, how NAFLD affects the development and progression of CVD remains elusive. In this review, we comprehensively summarise current data on the key extrahepatic manifestations of NAFLD, emphasising the possible link between NAFLD and CVD, including the role of proprotein convertase substilisin/kenin type 9, extracellular vesicles, microbiota, and genetic factors.

Identification of Clonal Hematopoiesis Driver Mutations through In Silico Saturation Mutagenesis

Abstract Clonal hematopoiesis (CH) is a phenomenon of clonal expansion of hematopoietic stem cells driven by somatic mutations affecting certain genes. Recently, CH has been linked to the development of hematologic malignancies, cardiovascular diseases, and other conditions. Although the most frequently mutated CH driver genes have been identified, a systematic landscape of the mutations capable of initiating this phenomenon is still lacking. Here, we trained machine-learning models for 12 of the most recurrent CH genes to identify their driver mutations. These models outperform expert-curated rules based on prior knowledge of the function of these genes. Moreover, their application to identify CH driver mutations across almost half a million donors of the UK Biobank reproduces known associations between CH driver mutations and age, and the prevalence of several diseases and conditions. We thus propose that these models support the accurate identification of CH across healthy individuals.

Herbal Interactions with Cardiac Medications: A Comprehensive Review of Potential Interactions between Herbal Drugs and Commonly Prescribed Cardiac Medications.

The concomitant use of herbal remedies in conjunction with conventional cardiac medications has increased significantly in recent years, primarily due to improvements in the quality standards of herbal medicines and the pervasive belief that natural products pose no harm to the human body. Contrary to this belief, multiple phytoconstituents found in herbal products have the potential to interact with conventional cardiac drugs, potentially resulting in severe adverse effects. <p> Objective: This review aimed to elucidate the intricacies of these interactions highlighting herbal medications that interact with established pharmaceuticals used for the treatment of cardiovascular disorders. Moreover, the review draws attention to safety concerns and preventative steps that should be taken by patients and medical professionals.. This endeavor is vital to avert adverse events stemming from such interactions. <p> Methods: Our approach entailed a comprehensive literature review employing keywords such as "mechanisms of herb-drug interactions," "herbal medications," and "cardiovascular disorders." The drugs presented in this review were selected based on their popularity among the general population, frequency of their employability, and potential to manifest drug interactions. We sourced pertinent information from reputable databases, including PubMed, Scopus, and Elsevier. <p> Results: Heart or blood vessel disorders are referred to as cardiovascular diseases (CVDs), which include conditions such as heart failure, stroke, hypertensive heart disease, and peripheral arterial disease. The primary underlying factor for the development of CVDs is dyslipidemia, which can be treated with classical antihyperlipidemic drugs such as statins, ezetimibe, and PCSK9-inhibitors. The use of herbal remedies is often unregulated, and there is a lack of scientific evidence supporting their use, particularly in the management of heart failure. Patients may not disclose their use of herbal remedies to health care practitioners, which can result in potential harm. <p> Conclusion: Uncontrolled dyslipidemia leads to hypercholesterolemia, which can result in atherosclerotic plaques and blocked arteries and veins. Herbal remedies and botanical products are also used to prevent or treat illnesses, and many prescription pharmaceuticals are made from plant compounds. Herbal remedies are often preferred because of the belief that they are safe and have no potential to cause harm. However, there is insufficient scientific data to support the use of herbal remedies, especially when treating heart disease. Using herbal remedies in conjunction with medicinal pharmaceuticals may result in unfavorable effects.

A Bayesian Joint Model of Longitudinal Kidney Disease Progression, Recurrent Cardiovascular Events, and Terminal Event in Patients with Chronic Kidney Disease

AbstractNearly 15% (37 million) of adults in the United States (US) have chronic kidney disease (CKD). The longitudinal decline of kidney function is intricately related to the development of cardiovascular disease (CVD) and eventual “terminal” event (kidney failure and mortality) in patients with CKD. Understanding the mechanism and risk factors underlying the three key outcome processes, (1) CKD progression, (2) CVD, and (3) subsequent terminal event in the CKD patient population remains incomplete. Thus, in this work, we develop a novel trivariate joint model to study the risk factors associated with the interdependent outcomes of kidney function (as measured by longitudinal estimated glomerular filtration rate), recurrent cardiovascular events, and the terminal event. Efficient estimation and inference is proposed within a Bayesian framework using Markov Chain Monte Carlo and Bayesian P-splines for hazard functions. The proposed Bayesian framework is directly generalizable beyond trivariate outcome processes to accommodate other potential modeling of complex multi-disease processes. The method is applied to study the aforementioned trivariate processes using data from the Chronic Renal Insufficiency Cohort Study, an ongoing prospective cohort study, established by the National Institute of Diabetes and Digestive and Kidney Diseases to address the rising epidemic of CKD in the US.

Gut microbiota response to consumption of milks fermented with specific strains of Lactococcus lactis with hypocholesterolemic effect

The alteration of structure and function of gut microbiota (dysbiosis) appears to be a major factor associated with metabolic disorders such as dyslipidemia and subsequent development of cardiovascular diseases. However, the consumption of fermented milks is a promising strategy to enhance health and restore the function of gut microbiota; specifically, in individuals with intestinal dysbiosis and hypercholesterolemia. Therefore, the aim of the present study was to evaluate the potential association between gut microbiota and the hypocholesterolemic effect of fermented milks with Lactococcus lactis NRRL B-571 (FM-571), NRRL B-572 (FM-572) and NRRL B-600 (FM-600) in Sprague–Dawley rats. Fermented milks were administered to hypercholesterolemic Sprague–Dawley rats during seven weeks. At the end of the experimental period, fecal and colonic microbiota were characterized using 16S RNA gene sequencing. Also, the short chain fatty acids (SCFAs) content was quantified in feces. Results showed that a high-cholesterol diet (HCD) altered the bacterial community in both fecal and mucosal samples. The consumption of fermented milks, specifically FM-572 promoted changes in the structure (beta diversity) in fecal, but not in mucosal microbiota. The levels of SCFAs in feces were improved after fermented milks consumption. From all SCFAs, butyrate was negatively correlated with total cholesterol, LDL-C (p < 0.05) and positively correlated with HDL-C (p < 0.05). Furthermore, Ruminococcaceae, Lactobacillaceae, Lachnospiraceae and Oscillospiraceae families, were negatively associated with total cholesterol, LDL-C (p < 0.05) and positively associated with HDL-C (p < 0.05). The abundance of these families was increased in groups treated with fermented milks, particularly with FM-572 (p < 0.05). Thus, the in vivo hypocholesterolemic effect after the consumption of milks fermented with Lactococcus lactis strains may be related with the modulation of fecal microbiota associated with the increase of butyrate-producing bacteria. Furthermore, these associations may suggest that butyrate may influence the cholesterol metabolism, resulting in the decreasing cholesterol levels.Graphical

Association Between Hemoglobin A1c and Development of Cardiovascular Disease in Canadian Men and WomenWithout Diabetes at Baseline: A Population-Based Study of 608 474 Adults.

We examined the association between hemoglobin A1c (HbA1c) and the development of cardiovascular disease (CVD) in men and women, without diabetes or CVD at baseline. This retrospective cohort study included adults aged 40 to <80 years in Alberta, Canada. Men and women were divided into categories based on a random HbA1c during a 3-year enrollment period. The primary outcome of CVD hospitalization and secondary outcome of combined CVD hospitalization/mortality were examined during a 5-year follow-up period until March 31, 2021. A total of 608 474 individuals (55.2% women) were included. Compared with HbA1c 5.0% to 5.4%, men with HbA1c of 5.5% to 5.9% had an increased risk of CVD hospitalization (adjusted hazard ratio [aHR], 1.12 [95% CI, 1.07-1.19]) whereas women did not (aHR, 1.01 [95% CI, 0.95-1.08]). Men and women with HbA1c of 6.0% to 6.4% had a 38% and 17% higher risk and men and women with HbA1c ≥6.5% had a 79% and 51% higher risk of CVD hospitalization, respectively. In addition, HbA1c of 6.0% to 6.4% and HbA1c ≥6.5% were associated with a higher risk (14% and 41%, respectively) of CVD hospitalization/death in men, but HbA1c ≥6.5% was associated with a 24% higher risk only among women. In both men and women, HbA1c ≥6.0% was associated with an increased risk of CVD and mortality outcomes. The association between CVD and HbA1c levels of 5.5% to 5.9%, considered to be in the "normal" range, highlights the importance of optimizing cardiovascular risk profiles at all levels of glycemia, especially in men.

Contributing factors to endothelial dysfunction in individuals with spinal cord injuries

Background: Patients with spinal cord injuries (SCIs) are at a greater risk for the development of cardiovascular diseases (CVDs) than able-bodied individuals due to high risks of endothelial dysfunction. Summary: For instance, patients with SCIs lose autonomic control of the heart and vasculature, which results in severe fluctuations in blood pressure. These oscillations between hypotension and hypertension have been shown to damage blood vessel endothelial cells and may contribute to the development of atherosclerosis. Furthermore, the loss of skeletal muscle control results in skeletal muscle atrophy and inward remodeling of the conduit arteries. It has been shown that blood vessels in the legs are chronically exposed to high shear, while the aorta experiences chronically low shear. These alterations to shear forces may adversely impact endothelial vasodilatory capacity and promote inflammatory signaling and leukocyte adherence. Additionally, microvascular endothelial vasodilatory capacity is impaired in patients with an SCI, and this may precede changes in conduit artery endothelial function. Finally, due to immobility and a loss of skeletal muscle mass, patients with SCIs have a higher risk of metabolic disorders, inflammation, and oxidative stress. Key Messages: Collectively, these factors may impair endothelium-dependent vasodilatory capacity, promote leukocyte adhesion and infiltration, promote the peroxidation of lipids, and ultimately support the development of atherosclerosis. Therefore, future interventions to prevent CVDs in patients with SCIs should focus on the management of endothelial health to prevent endothelial dysfunction and atherosclerosis.

The development of cardiovascular disease or cancer is correlated with higher FIB-4 in patients with T2DM

The development of cardiovascular disease or cancer is correlated with higher FIB-4 in patients with T2DM

Analysis of the contribution of obstructive sleep apnea/hypopnea syndrome and glycemic level variability to the development and progression of cardiac arrhythmias in patients with type 2 diabetes mellitus

In this review, information is presented within the triad: obstructive sleep apnea/hypopnea syndrome (OSA), glycemic variability, and cardiac arrhythmias in patients with type 2 diabetes mellitus (DM2). Epidemiological aspects, pathogenetic relationships, possible instrumental and laboratory diagnostic methods, as well as approaches to personalized therapy are analyzed. Research is being actively conducted in certain areas of the designated triad, however, no studies have been found that include simultaneous monitoring of indicators reflecting these disorders in patients with DM2. Many issues are still controversial. Sleep disturbances in patients with DM2 are actively studied, but more often questionnaires are used for diagnosis, rather than instrumental methods. There is insufficient data examining the effect of hypoxia on the progression of complications in patients with DM2. Rhythm disturbances are being actively studied in patients with DM2 in combination with various cardiological problems. Of greatest interest is the study of rhythm disturbances in patients with DM2 without concomitant comorbid conditions of the cardiovascular system, in order to identify early signs of diabetic cardiovascular autonomic neuropathy and cardiomyopathy, as well as additional early risk factors for the development and progression of cardiovascular diseases. Most of the studies are devoted to the study of the association of OSA and various arrhythmias in cardiac patients. However, there is no data on the combined effect of glycemic variability and OSA on the development of cardiac arrhythmias in patients with DM2. Additional studies are needed to identify the features of the effect of OSA on cardiac arrhythmias in patients with DM2.