Manifestations Of Cardiovascular Disease Research Articles

Obesity and cardiovascular disease: an ESC clinical consensus statement.

The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention.

Obesity and cardiovascular disease: an ESC clinical consensus statement.

The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention.

Complications of new-onset atrial fibrillation in critically ill COVID-19 patients admitted to the intensive care unit (ICU): a meta-analysis

BackgroundCOVID-19 infections can result in severe acute respiratory distress syndrome (ARDS) requiring admission to the intensive care unit (ICU). Cardiovascular manifestation or exacerbation of cardiovascular diseases could be another complication. Cardiac arrhythmias including New-Onset Atrial Fibrillation (NOAF), have been observed in hospitalized patients with COVID-19 infections. In this analysis, we aimed to systematically compare the complications associated with NOAF in critically ill COVID-19 patients admitted to the ICU.MethodsMEDLINE, EMBASE, Web of Science, the Cochrane database, http://www.ClinicalTrials.gov, Google Scholar and Mendeley were searched for relevant publications based on COVID-19 patients with NOAF admitted to the ICU. Complications including in-hospital mortality, ICU mortality, patients requiring mechanical ventilation, acute myocardial infarction, acute kidney injury, renal replacement therapy and pulmonary embolism were assessed. This is a meta-analysis and the analytical tool which was used was the RevMan software version 5.4. Risk ratios (RR) and 95% confidence intervals (CIs) were used to represent the data post analysis.ResultsIn critically ill COVID-19 patients with NOAF admitted to the ICU, the risks of ICU mortality (RR: 1.39, 95% CI: 1.07 – 1.80; P = 0.01), in-hospital mortality (RR: 1.56, 95% CI: 1.20 – 2.04; P = 0.001), patients requiring mechanical ventilation (RR: 1.32, 95% CI: 1.04 – 1.66; P = 0.02) were significantly higher when compared to the control group without AF. Acute myocardial infarction (RR: 1.54, 95% CI: 1.31 – 1.81; P = 0.00001), the risk for acute kidney injury (RR: 1.31, 95% CI: 1.11 – 1.55; P = 0.002) and patients requiring renal replacement therapy (RR: 1.83, 95% CI: 1.60 – 2.09; P = 0.00001) were also significantly higher in patients with NOAF.ConclusionsCritically ill COVID-19 patients with NOAF admitted to the ICU were at significantly higher risks of developing complications and death compared to similar patients without AF.

Connections Between Hypertension, Atherosclerosis, Acute Myocardial Infarction, and Risk of Dementia

As the percentage of geriatric patients continues to increase in both the United States and globally, the prevalence of both cardiovascular disease and dementia continues to climb. Both dementia and cardiovascular disease are devastating diseases that impose a significant burden economically, socially, and medically on both a local and systemic level. The most common fatal manifestation of cardiovascular disease is acute myocardial infarction, responsible for death in more than 80% of patients with cardiovascular disease. Prominent risk factors for acute myocardial infarction including hypertension and atherosclerosis have been independently associated with an increased risk for cognitive decline and all-cause dementia and Alzheimer disease, separate from vascular dementia. Acute myocardial infarction itself has also been independently associated with an increased incidence of all-cause dementia and Alzheimer disease. It is based on the connection between acute myocardial infarction, its major risk factors, and the incidence of dementia that it is of importance to define and explore the potential role that therapies for these conditions, as well as acute myocardial infarction itself, may play in mitigating the risk of dementia onset and severity. In this review, we assess current therapeutics that exist for atherosclerosis, hypertension and acute myocardial infarction that have been demonstrated to reduce later risk of dementia, and explore the mechanism that underlies the association between the incidence of acute myocardial infarction and the risk of dementia.

Lipoprotein Metabolism, Dyslipidemia, and Lipid-Lowering Therapy in Women: A Comprehensive Review.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a), and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses the diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

Sudden cardiac death as first manifestation of cardiovascular disease - a Danish nationwide study

Abstract Background and objective Sudden cardiac death (SCD) is a leading cause of death and previous studies have shown that approximately half of all cases have no known history of cardiovascular disease (CVD). Epidemiological studies of SCD cases of all ages are sparse. The aim of this study was to examine differences in incidence rates, clinical characteristics, comorbidities, and socioeconomic status between SCD cases with and without a known history of cardiovascular disease. Methods All 54,028 deaths in Denmark in 2010 were reviewed. Autopsy reports, death certificates, discharge summaries, and nationwide health and social registries were reviewed to identify cases of SCD. Information on previous history of CVD was extracted from the comprehensive Danish nationwide health and social registries. Results A total of 6,867 SCD cases were identified, of which 3,056 (44.5%) had no history of cardiovascular disease and 3,811 (55.5 %) had a history of CVD. Incidence rates of SCD increased with age and were higher in cases of SCD with a history of CVD across all age groups. The difference in incidence of SCD between persons with and without history of cardiovascular disease decreased with increasing age with incidence rate ratios ranging from 11.7 (95 % CI: 5.51 – 25.00) to 3.19 (95 % CI: 2.79-3.64) in those age 0-29 years and >90 years, respectively. Persons living in a low-income household (OR: 0.76, 95 % CI: 0.58-0.98, p=0.037), persons living in rural municipalities (OR: 0.87, 95 % CI: 0.78-0.98, p=0.021), and persons living in single-person households (OR: 0.73, 95 % CI: 0.66-0.82, p=0.037) had a lower likelihood of having a CVD prior to SCD. Conclusion This is the first nationwide study of SCD cases with and without history of CVD across all ages. SCD cases with no known CVD were significantly younger, more female and had less comorbidities. Although a substantial amount of SCD cases occur in persons with no known CVD, SCD is more common in the populations of persons with a history of CVD. Socioeconomic factors such as low income, living alone and living in rural communities were associated with a lower risk of having a cardiovascular diagnosis prior to SCD.Crude numbers and incidence rates of SCDIncidence rate ratios

Sex and age significantly modulate cardiovascular disease presentation in type 2 diabetes: a large population-based cohort study.

We aimed to describe and compare the incidence of the first cardiovascular event and its major subtypes, coronary heart disease (CHD), cerebrovascular disease, heart failure (HF), or peripheral artery disease (PAD), according to age and sex in a population-based cohort of individuals with type 2 diabetes (T2D) from a Mediterranean region. We used linked primary care electronic medical reports, pharmacy-invoicing data, and hospital admission disease registry records from the SIDIAP database, which contains linked data for 74% of the Catalonian population. We selected individuals with T2D aged 30 to 89 years free of cardiovascular disease (CVD). The primary outcome was the first presentation of CVD. The study cohort included 247,751 individuals (48.6% women, 66.8 ± 11.9 years). During a 6.99-year follow-up, the cumulative incidence of the first cardiovascular event was 23.4%. Men were at higher risk for CVD (hazard ratio [HR]: 1.47 95%CI: 1.45-1.50), CHD (HR: 1.52 95%CI: 1.47-1.57), cerebrovascular disease (HR:1.07 95%CI: 1.03-1.10) and PAD (HR: 2.30 95%CI: 2.21-2.39) than women but at a lower risk for HF (HR:0.70 95%CI: 0.68-0.73). CHD and PAD were the most frequent CVD presentations among men (28.1% and 27.5%) and HF (40.1%) in women. CHD predominated among young participants of both sexes, while HF predominated among women older than 65 and men older than 75. In individuals with T2D, the overall risk and the type of first CVD manifestation largely varied by sex and age. This epidemiological evidence should be considered in clinical practice.

Endothelial dysfunction and complement activation are independently associated with disease duration in patients with systemic vasculitis

ObjectivesSystemic vasculitis is a heterogenous group of autoimmune diseases characterized by enhanced cardiovascular mortality. Endothelial dysfunction is associated with accelerated vascular damage, representing a core pathophysiologic mechanism contributing to excess CV risk. Recent studies have also shown that complement activation holds significant role in the pathogenesis of Anti-Neutrophilic Cytoplasmic Autoantibody (ANCA) -associated vasculitis (AAV). Given the potential crosstalk between the endothelium and complement, we aimed to assess, for the first time simultaneously, easily accessible biomarkers of endothelial dysfunction and complement activation in SV. MethodsWe measured circulating endothelial microvesicles (EMVs) and soluble complement components representative of alternative, classical and terminal activation (C5b-9, C1q, Bb fragments, respectively) in a meticulously selected group of patients with systemic vasculitis, but without cardiovascular disease. Individuals free from systemic diseases, who were matched with patients for cardiovascular risk factors(hypertension, diabetes, smoking, dyslipidemia), comprised the control group. ResultsWe studied 60 individuals (30 in each group). Patients with systemic vasculitis had elevated EMVs, higher levels of C5b-9 [536.4(463.4) vs 1200.94457.3), p = 0.003] and C1q [136.2(146.5 vs 204.2(232.9), p = 0.0129], compared to controls [232.0 (243.5) vs 139.3(52.1), p < 0.001]. In multivariate analysis both EMVs and C5b-9 were independently associated with disease duration (p = 0.005 and p = 0.004 respectively), yet not with disease activity. ConclusionPatients with systemic vasculitis exhibit impaired endothelial function and complement activation, both assessed by easily accessible biomarkers, even in the absence of cardiovascular disease manifestations. EMVs and soluble complement components such as C5b-9 and C1q could be used as early biomarkers of endothelial dysfunction and complement activation, respectively, in clinical practice during the course of SV, yet their predictive value in terms of future cardiovascular disease warrants further verification in appropriately designed studies.

Elucidating the role of chemokines in inflammaging associated atherosclerotic cardiovascular diseases

Age-related inflammation or inflammaging is a critical deciding factor of physiological homeostasis during aging. Cardiovascular diseases (CVDs) are exquisitely associated with aging and inflammation and are one of the leading causes of high mortality in the elderly population. Inflammaging comprises dysregulation of crosstalk between the vascular and cardiac tissues that deteriorates the vasculature network leading to development of atherosclerosis and atherosclerotic-associated CVDs in elderly populations. Leukocyte differentiation, migration and recruitment holds a crucial position in both inflammaging and atherosclerotic CVDs through relaying the activity of an intricate network of inflammation-associated protein-protein interactions. Among these interactions, small immunoproteins such as chemokines play a major role in the progression of inflammaging and atherosclerosis. Chemokines are actively involved in lymphocyte migration and severe inflammatory response at the site of injury. They relay their functions via chemokine-G protein-coupled receptors-glycosaminoglycan signaling axis and is a principal part for the detection of age-related atherosclerosis and related CVDs. This review focuses on highlighting the detailed intricacies of the effects of chemokine-receptor interaction and chemokine oligomerization on lymphocyte recruitment and its evident role in clinical manifestations of atherosclerosis and related CVDs. Further, the role of chemokine mediated signaling for formulating next-generation therapeutics against atherosclerosis has also been discussed.

Objectively Measured Hot Flashes and Moderate-Vigorous Activity Predict Arterial Stiffness in Healthy Perimenopausal Women

Perimenopause is the period of transition when midlife women experience increases in cardiovascular disease (CVD) risk. Arterial stiffness (AS) is a preclinical CVD risk factor that precedes the manifestation of clinical CVD. Hot flashes (HF) are bothersome symptoms of menopause which are correlated with some subclinical CVD risk factors, but the exact relationship between HF and CVD risk factors remain equivocal. Habitual physical activity (PA) is effective in the prevention and treatment of CVD in many populations. However, the relationship between PA and CVD risk remains unclear for perimenopausal women. Therefore, the objective of our study was to determine the effects of HF and PA on AS in healthy perimenopausal women. We hypothesized that HFs would be associated with AS and PA would influence the association between HFs and AS. There were 61 participants (age 43-54) free from CVD risk factors included in this analysis. Arterial stiffness was measured via augmentation index (AIx), backwards wave (PB, mmHg), and reflection magnitude (RM, %). Hot flashes were measured objectively for 24 hours using ambulatory sternal skin conductance monitoring. Objective HF rate was calculated by normalizing HF count to wear time. Habitual PA activity was quantified objectively as average daily minutes of waking moderate-vigorous PA (MVPA) over 7-day using actigraphy and the R package GGIR. All statistical analyses were performed using R (version 4.2.3) and RStudio (2023.06.2+561). Pearson’s correlation and multiple regression were used to evaluate the associations between dependent and outcome variables. Age and body mass index (BMI) were controlled, and assumption testing was completed for all models. Objective HF rate was significantly positively correlated with PB, r(53) = 0.38, p &lt; 0.01, and RM, r(53) = 0.35, p &lt;0.01. Objective MVPA was significantly negatively associated with AIx, r(61) = -0.45, p &lt;0.001, PB, r(61) = -0.29, p &lt;0.05, and RM, r(61) = -0.34, p &lt; 0.01. Objective HF rate significantly predicted arterial stiffness variables, AIx (β = 14.58, p =0.05; adjR2 = 0.38), PB (β = 6.48, p&lt;0.01; adjR2 = 0.24), and RM (β = 17.79, p &lt;0.01; adjR2 = 0.39). Objective MVPA significantly predicted AIX (β = -0.12, p &lt;0.01; adjR2 = 0.41), and RM (β = -0.06, p = 0.05; adjR2 = 0.29). When HF and MVPA were added in the same model, HF and MVPA were both significant predictors of RM (βHF = 16.25, p &lt;0.01, βMVPA = -0.06, p &lt;0.05; adjR2 = 0.42), MVPA only was significant with AIx (βHF = 11.38, p = 0.10, βMVPA = -0.13, p &lt;0.01; adjR2 = 0.49), and HF only was significant with PB (βHF = 6.11, p &lt;0.01, βMVPA = -0.02, p = 0.212; adjR2 = 0.25). Adding the interaction between HF and MVPA did not help explain variation in any AS variable. In conclusion, our data showed that more objectively-measured HF were associated with negative AS outcomes and that greater MVPA may be worth considering in decreasing arterial stiffness in perimenopausal women. Contrary to our hypothesis, MVPA did not help to explain the effects of HF on AS. Future studies should focus on understanding the mechanisms behind the negative relationship between hot flashes and arterial stiffness in midlife women. NIH NHLBI R15 Grant 1R15HL145650-01A1 (Witkowski); Smith College McKinley Honors Fellowship (Tha Ra Wun). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Clinical and psychological associations and coping strategies for personality type D and depression in patients with coronary artery disease

The comorbidity of manifestations of psychological distress and cardiovascular diseases is complex. The degree of impact of psychological stress on the patient depends on the possibilities of the adaptive potential of the individual in the environment.Aim: To study the cognitive assessment of stress, coping strategies and clinical and psychological associations in personality type D and depression in patients with coronary artery disease (CAD).Material and Methods. The study included 112 CAD patients. The DS-14 questionnaire was used to determine personality type D.To determine the level of depression the hospital scale HADS (Hospital Anxiety and Depression Scale). To assess coping strategies, the questionnaires “Methods of Coping Behavior” and “Indicator of Stress Coping Strategies” were used. Difficult life situation (DLS) assessment was determined using the “Cognitive Assessment of DLS” methodology. The questionnaire “Types of Orientations in Difficult Situations” was used to study orientations in DLS.Results. Patients were divided into groups based on manifestations of psychological distress: with type D (n = 40), without type D (n = 72); with depression (n = 48) without depression (n = 82). In type D, there was a more frequent assessment of the situation as out of control (12.0 ± 4.6 points versus 11.0 ± 4.6 points, p = 0.049) and orientation towards losses in difficult situations (17.0 ± 4.1 points 15.5 ± 5.1, points, p = 0.016). In depression, less pronounced desire for difficulties (19.0 ± 5.0 points versus 23.0 ± 5.9 points, p = 0.006), orientation towards opportunities (15.5 ± 3.2 points versus 18.0 ± 3.5 points, p &lt; 0.001). In type D, the strategies “Escape-avoidance” (p = 0.05) and “Self-control” (p = 0.04) were used more often. In depression, the strategies “Problem resolution” (p = 0.02), “Search for social support” (p &lt; 0.001) and “Avoidance” (p = 0.02) were more often used, less often – “Confrontational coping” (p = 0.001).Conclusion. Differences in cognitive assessment and coping strategies were revealed in patients with coronary artery disease in personality type D and the development of depression symptoms. This study emphasizes the need for individualized behavioral interventions for patients with coronary artery disease with manifestations of psychological distress.

Abstract P111: Pre-Diagnostic Free Testosterone and Estradiol Influence Heart Failure Risk in Both Women and Men: A Prospective Cohort Study in the UK Biobank

Introduction: Heart failure (HF) is a highly fatal manifestation of many cardiovascular diseases (CVDs). Free testosterone and 17β-estradiol have been linked to future risk of CVD. However, their roles in the pathogenesis of HF in both men and women are unclear. Hypothesis: We investigated the associations between free testosterone and 17β-estradiol (unbound to sex hormone binding globulin), and future risk of HF in the UK Biobank. Methods: Multivariable Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of incident HF (first hospitalization) in relation to quartiles (Q) of free testosterone and 17β-estradiol, and potential confounders, while stratifying by sex and in women by menopausal status. Non-linear relationships were tested using cubic splines. Results: There were 180,712 men (5585 cases with free testosterone and 571 cases with 17β-estradiol), and 177,324 women (2858 cases with free testosterone and 314 with 17β-estradiol). Increased free testosterone was associated with decreased HF risk in both men (HR Q4 vs. Q1 =0.86, 95%CI: 0.79-0.94, p-trend continuous &lt;0.0001) and post-menopausal women (HR Q4 vs. Q1 =0.83, 95%CI: 0.73-0.95), with non-linear relationships. Additionally, 17β-estradiol was significantly associated with decreased HF risk among men (HR Q4 vs. Q1 =0.76, 95%CI: 0.59-0.98), but positively associated among pre-menopausal women (HR Q4 vs. Q1 =2.16, 95%CI: 1.11-4.18). Conclusions: In this large cohort free of CVD at baseline, we detected a significant protective association between free testosterone and new HF diagnosis among men. In women however, the association differed by menopausal status as increased free testosterone was associated with elevated risk of HF before menopause but not after menopause. Further, 17β-estradiol was associated to elevated HF risk among pre-menopausal women but not post-menopausal women and men. Our findings suggest that sex hormones influence the pathogenesis HF and may offer potential pathways for interventions.

Morroniside improves AngII-induced cardiac fibroblast proliferation, migration, and extracellular matrix deposition by blocking p38/JNK signaling pathway through the downregulation of KLF5.

Myocardial fibrosis (MF), which is an inevitable pathological manifestation of many cardiovascular diseases in the terminal stage, often contributes to severe cardiac dysfunction and sudden death. Morroniside (MOR) is the main active component of Cornus officinalis with a variety of biological activities. This study was designed to explore the efficacy of MOR in MF and to investigate its pharmacological mechanism. The viability of MOR-treated human cardiac fibroblast (HCF) cells with or without Angiotensin II (AngII) induction was assessed with Cell Counting Kit-8 (CCK-8). The migration of AngII-induced HCF cells was appraised with a transwell assay. Gelatin zymography analysis was adopted to evaluate the activities of MMP2 and MMP9, while immunofluorescence assay was applied for the estimation of Collagen I and Collagen III. By means of western blot, the expressions of migration-, fibrosis-, and p38/c-Jun N-terminal kinase (JNK) signal pathway-related proteins were resolved. The transfection efficacy of oe-Kruppel-like factor 5 (KLF5) was examined with reverse transcription-quantitative PCR (RT-qPCR) and western blot. In this study, it was found that MOR treatment inhibited AngII-induced hyperproliferation, migration, and fibrosis of HCF cells, accompanied with decreased activities of matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), connective tissue growth factor (CTGF), Fibronectin, and α-SMA, which were all reversed by KLF5 overexpression. Collectively, MOR exerted protective effects on MF by blocking p38/JNK signal pathway through the downregulation of KLF5.

Epigenetic regulation of sex dimorphism in cardiovascular health.

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality, affecting people of all races, ages, and sexes. Substantial sex dimorphism exists in the prevalence, manifestation, and outcomes of CVDs. Understanding the role of sex hormones as well as sex-hormone-independent epigenetic mechanisms could play a crucial role in developing effective and sex-specific cardiovascular therapeutics. Existing research highlights significant disparities in sex hormones, epigenetic regulators, and gene expression related to cardiac health, emphasizing the need for a nuanced understanding of these variations between men and women. Despite these differences, current treatment approaches for CVDs often lack sex-specific considerations. A pivotal shift toward personalized medicine, informed by comprehensive insights into sex-specific DNA methylation, histone modifications, and non-coding RNA dynamics, holds the potential to revolutionize CVD management. By understanding sex-specific epigenetic complexities, independent of sex hormone influence, future cardiovascular research can be tailored to achieve effective diagnostic and therapeutic interventions for both men and women. This review summarizes the current knowledge and gaps in epigenetic mechanisms and sex dimorphism implicated in CVDs.

Associations between birth weight and adult apolipoproteins: The LifeGene cohort.

Early life factors may predict cardiovascular disease (CVD), but the pathways are still unclear. There is emerging evidence of an association of early life factors with apolipoproteins, which are linked to CVD. The study objective was to assess the associations between birth variables and adult apolipoproteins (apoA1 and apoB, and their ratio) in a population-based cohort. The LifeGene Study is a prospective cohort comprising index participants randomly sampled from the general population. Blood samples were collected between 2009 and 2016. In this sub-study, we used birth variables, obtained from a national registry for all participants born 1973 or later, including birth weight and gestational age, while adult CVD risk factors included age, sex, body mass index (BMI), lipids, and smoking history. We employed univariate and multivariate general linear regression to explore associations between birth variables, lipid levels and other adult CVD risk factors. The outcomes included non-fasting apoA1 and apoB and their ratio, as well as total cholesterol and triglycerides. A total of 10,093 participants with both birth information and lipoprotein levels at screening were included. Of these, nearly 42.5% were men (n = 4292) and 57.5% were women (n = 5801). The mean (standard deviation) age of men was 30.2 (5.7) years, and for women 28.9 (5.8) years. There was an increase of 0.022 g/L in apoA1 levels per 1 kg increase in birth weight (p = 0.005) after adjusting for age, sex, BMI, gestational age, and smoking history. Similarly, there was a decrease of 0.023 g/L in apoB levels per 1 kg increase in birth weight (p<0.001) after adjusting for the same variables. There were inverse associations of birth weight with the apoB/apoA1 ratio. No independent association was found with total cholesterol, but with triglyceride levels (ẞ-coefficient (95% Confidence Interval); -0.067 (-0.114, -0.021); p-value 0.005). Lower birth weight was associated with an adverse adult apolipoprotein pattern, i.e., a higher apoB/apoA1 ratio, indicating increased risk of future CVD manifestations. The study highlights the need of preconception care and pregnancy interventions that aim at improving maternal and child outcomes with long-term impacts for prevention of cardiovascular disease by influencing lipid levels.

Biomarkers and subclinical left ventricular dysfunction in patients with type 2 diabetes without clinical manifestations of cardiovascular diseases

Aim. To study the relationship between the structural and functional left ventricular (LV) parameters and N-terminal pro-brain natriuretic peptide (NT-proBNP) and inflammatory markers in patients with type 2 diabetes (T2D) without clinical manifestations of cardiovascular diseases, as well as to evaluate the possibility of their use for early diagnosis of subclinical LV dysfunction.Material and methods. Data from 120 patients of both sexes aged 45-75 years (57,11±7,9 years) were analyzed. They were divided into three following groups: 1st — with T2D (n=47), 2nd — with prediabetes (n=20), 3rd — control (n=53). All participants underwent transthoracic echocardiography with assessment of the linear and volumetric heart dimensions, systolic and diastolic LV function. Speckle tracking echocardiography was analyzed with calculation of LV global longitudinal strain (GLS). The blood levels of NT-proBNP and inflammatory markers were determined (high-sensitivity C-reactive protein (hsCRP), fibrinogen, interleukin-6).Results. According to echocardiography, patients with carbohydrate metabolism disorders revealed significantly higher LV mass values, LV posterior wall thickness, and relative wall thickness in comparison with the control group. Transmitral flow parameters, as well as tissue Doppler sonography, in the T2D and prediabetes groups were significantly different from those in the control group. GLS in the groups of patients with carbohydrate metabolism disorders was lower than in the control group (p=0,001). The level of NT-proBNP was significantly higher in the T2D and prediabetes groups compared to the control group, while in all three groups it did not exceed normal values (p&lt;0,001). A higher level of NT-proBNP was associated with hypertension — odds ratio (OR) 3,64 [1,02-13,04] (p=0,005), a decrease in LV ejection fraction — OR 1,25 [1,06-1 ,47] (p=0,007), concentric hypertrophy — OR 4,84 [1,43-16,41] (p=0,011) and decreased GLS — OR 1,85 [1,62-2,06] (p=0,005), an increase in the ratio of early and late diastolic transmitral flow (E/A) — OR 0,01 [0,008-0,416] (p=0,024) and isovolumic relaxation time (IVRT) — OR 1,08 [1,03-1,14] (p=0,03). The sensitivity and specificity of NT-proBNP as a test for predicting GLS reduction &lt;-18% were 86 and 27%, respectively. The hsCRP level, within the reference values, was significantly higher in the T2D and prediabetes groups compared to the control group (p&lt;0,001) and demonstrated a direct linear relationship with E/A, IVRT, early diastolic deceleration time (p&lt;0,05). A higher level of hsCRP was significantly associated with diastolic dysfunction — OR 1,16 [1,02-1,32] (p=0,023), as well as with a GLS decrease &lt;-18% — OR 1,58 [1,12-4,65] (p=0,03).Conclusion. In patients with T2D without clinical manifestations of cardiovascular disease, the presence of concentric LV myocardial hypertrophy, LV diastolic dysfunction and decreased GLS (&lt;-18%) is associated with higher blood levels of NT-proBNP and hsCRP. However, in all cases, the levels of biomarkers do not exceed the reference values, which does not allow their use in the early diagnosis of subclinical LV dysfunction in T2D.

Correlation between uric acid/HDL ratio and total calcium score in coronary CT angiography

Aim: Coronary artery disease (CAD) is a common manifestation of cardiovascular disease (CVD). The identification of reliable biomarkers for early CAD detection and risk assessment is crucial for effective prevention and management. This article examines the correlation between the uric acid to HDL cholesterol ratio (UHR) and the total calcium score (TCS) obtained from coronary CT angiography (CCTA) in the assessment of CAD. Methods: The study included 60 patients (34 males and 26 females) without endocrine diseases or relevant medications to ensure a homogeneous population. Blood samples collected after an eight hour overnight fasting were analyzed for laboratory parameters. CCTA was performed using a standardized protocol. The total calcium score was calculated using established methods. Results: The analysis showed a significant positive correlation between UHR and TCS (r=0.479, P=0.0001). Patients with coronary artery plaque had significantly higher UHR values compared to those without it (p = 0.001). Conclusion: These findings suggest that UHR could serve as a promising biomarker for predicting CAD presence and severity, although further research is necessary to validate its clinical utility in CAD diagnosis and management.

Smoking Behavior Change and the Risk of Heart Failure in Patients With Type 2 Diabetes: Nationwide Retrospective Cohort Study.

Heart failure (HF) is one of the most common initial manifestations of cardiovascular disease in patients with type 2 diabetes. Although smoking is an independent risk factor for HF, there is a lack of data for the incidence of HF according to changes in smoking behaviors in patients with type 2 diabetes. We aimed to examine the association between interval changes in smoking behavior and the risk of HF among patients with type 2 diabetes. We conducted a retrospective cohort study using the National Health Insurance Service database. We identified 365,352 current smokers with type 2 diabetes who had 2 consecutive health screenings (2009-2012) and followed them until December 31, 2018, for the incident HF. Based on smoking behavior changes between 2 consecutive health screenings, participants were categorized into quitter, reducer I (≥50% reduction) and II (<50% reduction), sustainer (reference group), and increaser groups. During a median follow-up of 5.1 (IQR 4.0-6.1) years, there were 13,879 HF cases (7.8 per 1000 person-years). Compared to sustainers, smoking cessation was associated with lower risks of HF (adjusted hazard ratio [aHR] 0.90, 95% CI0.86-0.95), whereas increasers showed higher risks of HF than sustainers; heavy smokers who increased their level of smoking had a higher risk of HF (aHR 1.13, 95% CI 1.04-1.24). In the case of reducers, the risk of HF was not reduced but rather increased slightly (reducer I: aHR 1.14, 95% CI 1.08-1.21; reducer II: aHR 1.03, 95% CI 0.98-1.09). Consistent results were noted for subgroup analyses including type 2 diabetes severity, age, and sex. Smoking cessation was associated with a lower risk of HF among patients with type 2 diabetes, while increasing smoking amount was associated with a higher risk for HF than in those sustaining their smoking amount. There was no benefit from reduction in smoking amount.

Molecular mechanism of triptolide in myocardial fibrosis through the Wnt/β-catenin signaling pathway

Objective. Myocardial fibrosis (MF) is a common manifestation of end-stage cardiovascular diseases. Triptolide (TP) provides protection against cardiovascular diseases. This study was to explore the functional mechanism of TP in MF rats via the Wnt/β-catenin pathway. Methods. The MF rat model was established via subcutaneous injection of isoproterenol (ISO) and treated with low/medium/high doses of TP (L-TP/M-TP/H-TP) or Wnt agonist BML-284. Cardiac function was examined by echocardiography. Pathological changes of myocardial tissues were observed by HE and Masson staining. Col-I/Col-III/Vimentin/α-SMA levels were detected by immunohistochemistry, RT-qPCR, and Western blot. Collagen volume fraction content was measured. Expression levels of the Wnt/β-catenin pathway-related proteins (β-catenin/c-myc/Cyclin D1) were detected by Western blot. Rat cardiac fibroblasts were utilized for in vitro validation experiments. Results. MF rats had enlarged left ventricle, decreased systolic and diastolic function and cardiac dysfunction, elevated collagen fiber distribution, collagen volume fraction and hydroxyproline content. Levels of Col-I/Col-III/Vimentin/α-SMA, and protein levels of β-catenin/c-myc/Cyclin D1 were increased in MF rats. The Wnt/β-catenin pathway was activated in the myocardial tissues of MF rats. TP treatment alleviated impairments of cardiac function and myocardial tissuepathological injury, decreased collagen fibers, collagen volume fraction, Col-I, Col-III, α-SMA and Vimentin levels, HYP content, inhibited Wnt/β-catenin pathway, with H-TP showing the most significant effects. Wnt agonist BML-284 antagonized the inhibitive effect of TP on MF. TP inhibited the Wnt/β-catenin pathway to repress the proliferation and differentiation of mouse cardiac fibroblasts in vitro. Conclusions. TP was found to ameliorate ISO-induced MF in rats by inhibiting the Wnt/β-catenin pathway.

Pediatric hypertension as an early manifestation of cardiovascular disease in children

RESUMO Em adultos, eventos cardiovasculares associados à hipertensão arterial (HA) apresentam grande repercussão na morbimortalidade. À luz dos novos conhecimentos, a HA na criança tem sido interpretada como doença cardiovascular (DCV) precoce, enquanto a exposição da criança aos fatores de risco CV revela-se preditora de DCV subclínica em adultos. As classificações da medida de pressão arterial (PA) no adulto e na faixa pediátrica foram recentemente atualizadas pelo American College of Cardiology/American Heart Association. A HA primária na criança é em geral assintomática, e se associa com história familiar de HA, sobrepeso/obesidade e normalidade morfofuncional do sistema urinário. Quanto mais jovem a criança e mais elevada a PA, maior a chance de se tratar de HA secundário. A investigação da etiologia da HA inicia-se com anamnese detalhada, que deve incluir informações clínicas e de utilização de medicamentos, fumo e álcool, desde o período perinatal até o momento da consulta. A modificação de fatores de risco, com redução do peso, redução do consumo de álcool e aumento do consumo de vegetais, entre a infância e a idade adulta, mostrou associação com a resolução da HA na transição infância-idade adulta e com a reversão dos efeitos adversos cardiometabólicos nos indivíduos adultos não obesos. A terapêutica farmacológica deve ser iniciada para casos de HA sintomática, HA secundária a doença renal crônica ou a diabetes mellitus, presença de lesões de órgão alvo, HA estágio 2 sem causa modificável e HA persistente não responsiva à mudança de estilo de vida.