Onset Of Cardiovascular Disease Research Articles

Air pollution, dementia, and lifespan in the socio-economic gradient of aging: perspective on human aging for planning future experimental studies.

Air pollution (AirPoll) accelerates human aging, as assessed by increased adult mortality and earlier onset of cardiovascular diseases, and dementia. Socio-economic strata (SES) of wealth and education have parallel differences of mortality and these diseases. Children from impoverished homes differ in brain development at birth and in risk of early fat excess and hypertension. To further enhance the healthspan, biogerontologists may consider a wider range of environmental exposures from gestation through later life morbidity that comprise the Gero-Exposome. Experimental studies with rodents and nematodes document shared transcriptional responses to AirPoll. In rodents, AirPoll exposure activates gene systems for body-wide detoxification through Nrf2 and NFkB transcription factors that mediate multiple aging processes. Gestational environmental factors include maternal diet and exposure to AirPoll and cigarette smoke. Correspondingly, gestational exposure of mice to AirPoll increased adult body fat, impaired glucose clearance, and decreased adult neurogenesis in the hippocampus, a brain region damaged in dementia. Nematode larvae also respond to AirPoll with Alzheimer relevant responses. These experimental approaches could identify to interventions for expanded human health and longevity across SES gradients.

Gender differences in lifestyle and psycho-social aspects of medical students. A cross sectional study

Abstract Background Incidence of premature cardiovascular deaths in medical practitioners is on the increase. Lifestyle habits, psychosocial and emotional status of medical students has the potential to initiate the premature onset of cardiovascular disease. Gender differences in diagnosis and management of cardiovascular diseases is well known. However, data on gender differences in heart healthy status of medical students are sparce. Purpose To investigate the gender differences heart healthy lifestyle habits among undergraduate medical students of a medical college from low-and-middle income country in south Asia. Methods All students pursing MBBS between 2017 and 2018 were included in the cross-sectional study. The study had Institutional ethics committee approval and the participation was voluntary. Anthropometric measurements (weight using digital weighting scale, height, waist and hip circumference using measuring tape), vital signs (pulse and blood pressure using digital manometer) and self-reported lifestyle/psychosocial cum behavioural pattern (using a specially designed proforma) were collected for all the participants. (525) Results 824 medical students were enrolled in the study of whom 377 (45.8%) were women. Overall 37.1% had abnormal body mass index (BMI) and 27.8% had abnormal waist hip ratio (WHR). Overall 14% and 10.3% students had abnormal systolic (≤ 85 mm of Hg) or diastolic blood pressure(BP) (≤ 135 mm of Hg) readings respectively. 19.4% of students had either systolic or diastolic abnormal BP values. Gender differences: Abnormal BMI and abnormal WHR (Figure 1A) were found in similar proportion among women and men. However less women has abnormal BP readings compared to men. More men has abnormal diastolic BP and abnormal systolic BP compared to women. Either systolic or diastolic BP values were abnormal in lower proportion of women (7.8% vs 29.4%; P<0.001). Women had less physically active minutes per day compared to men (71.15 ± 68.2 vs 109. 38± 81.7; P < 0.001). A feeling of lack of self-worth (73.5%) was common among medical students, however no significant gender differences were observed (Figure 1B). Significantly more women students have harbored suicidal thoughts than men. Women students were more likely to feel life style counseling is necessary for medical students and were more likely to implement lifestyle changes if advised. Conclusion High blood pressure and feeling of lack of self-worth is commonly observed in medical students. Women were more likely to harbor suicidal thoughts, bitterness and anger more likely to implement lifestyle modifications if advised. Interventions warranted at improving heart healthy lifestyle patterns is warranted, and must be optimized by observed gender differences.Figure 1Gender and life style habits

Abstract 16476: Association Between Atrial Fibrillation and Deep Learning Derived Retinal Features Trained on Electrocardiogram versus Coronary Artery Calcium

Introduction: This study aimed to assess the ability of a deep learning algorithm, Reti-AF, developed from retinal photos, to predict atrial fibrillation (AF) incidence. Its predictive performance was evaluated using the UK Biobank and compared to Reti-CAC, a similar algorithm trained on coronary artery calcium (CAC) scores. Hypothesis: We hypothesised that Reti-AF and Reti-CAC could potentially predict the incidence of AF. Methods: Due to the lack of atrial fibrillation (AF) patients in the UK Biobank, a Masked AutoEncoder method was used with a Vision Transformer (ViT) model. The model was first trained on 636,992 fundus images from a health screening dataset, then fine-tuned with an additional 6,068 retinal images from the UK Biobank. The survival analysis of the UK Biobank's longitudinal data was performed to assess the model's predictive performance for AF, with hazard ratios calculated. Results: In longitudinal validation among participants without baseline AF, Reti-AF was significantly associated with AF incidence (HR=5.50, 95% CI, 1.98-2.57, highest tertile of Reti-AF versus the first tertile) in a univariable model. However, this significance was not maintained in a multivariable model (HR=1.23, 95% CI, 0.93-1.30). When Reti-CAC was applied to predict AF, it showed a significant association with AF incidence in both univariable (HR=9.30, 95% CI, 6.68-12.96, highest tertile of Reti-CAC versus the first tertile) and multivariable (HR=1.84, 95% CI, 1.26-2.70) models after adjustment for age, gender, smoking, diabetes, hyperlipidemia, hypertension, and baseline chronic kidney disease. Conclusions: The study found that combining deep learning with retinal photos and coronary artery calcium (CAC) as a reference, led to more accurate prediction of atrial fibrillation (AF) incidence compared to using AF. Furthermore, Reti-CAC was shown to be capable of predicting both cardiovascular disease onset and AF incidence.

Abstract 13282: Parental Allostatic Load Predicts Time to the Onset of Cardiovascular Disease in Offspring

Background: Allostatic load, a measure of cumulative stress-related physiologic dysregulation, is associated with major cardiovascular disease (CVD) events. However, despite evidence of familial aggregation of CVD risk factors, the impact of parental allostatic load on the onset and timing of CVD in offspring remains unknown. Hypothesis: We hypothesize that offspring of parents with lower allostatic load will have longer CVD-free survival time. Aim: To examine whether CVD-free survival in offspring is associated with parental allostatic load and potential sex-specific differences. Methods: A secondary data analysis of 6,145 offspring-mother-father trios derived from the Framingham Heart Study Original (exam 10) and Offspring Cohorts (exam 1). Allostatic load was defined as an index (0-16) of 8 variables (systolic and diastolic blood pressure, total cholesterol, HDL, LDL, total cholesterol/ HDL ratio, fasting blood glucose and body mass index). Kaplan-Meier plots, and Irwin’s restricted mean and multivariable-adjusted Cox proportional hazards regression models were used to examine sex-specific differences and the association between parental allostatic load and offspring’s CVD-free survival. Results: Parents mean age (SD) was 60.8 (8.1) and offspring’s 34.8 (10.5). 22.8% of parents (n=458) and 12.1% (n=412) of offspring had high allostatic load (>8). In a total of 118,132 person-years of follow-up among the offspring, 1060 incident CVD events occurred. The overall CVD incidence rate was 8.9 per 1000 person-years (95% confidence interval [CI] 8.4-9.5) and sons had a higher CVD incident rate than daughters (11.0 vs 7.2, p<0.001). Offspring of mothers with low allostatic load lived 4 more years free of CVD compared to offspring of mothers with high allostatic load. Similarly, offspring of fathers with low allostatic load lived 3 more years free of CVD. The hazard rate of having incident CVD among offspring of mothers and fathers with high (compared to low) allostatic load was 1.58 (1.28-1.95) and 1.39 (95% CI: 1.11-1.75), respectively. Conclusion: Parents' allostatic load has a significant impact on the cardiovascular health of their offspring, with those of mothers with high allostatic load being at a higher risk of developing CVD at a younger age.

Utilizing a Two-Stage Taguchi Method and Artificial Neural Network for the Precise Forecasting of Cardiovascular Disease Risk.

The complexity of cardiovascular disease onset emphasizes the vital role of early detection in prevention. This study aims to enhance disease prediction accuracy using personal devices, aligning with point-of-care testing (POCT) objectives. This study introduces a two-stage Taguchi optimization (TSTO) method to boost predictive accuracy in an artificial neural network (ANN) model while minimizing computational costs. In the first stage, optimal hyperparameter levels and trends were identified. The second stage determined the best settings for the ANN model's hyperparameters. In this study, we applied the proposed TSTO method with a personal computer to the Kaggle Cardiovascular Disease dataset. Subsequently, we identified the best setting for the hyperparameters of the ANN model, setting the hidden layer to 4, activation function to tanh, optimizer to SGD, learning rate to 0.25, momentum rate to 0.85, and hidden nodes to 10. This setting led to a state-of-the-art accuracy of 74.14% in predicting the risk of cardiovascular disease. Moreover, the proposed TSTO method significantly reduced the number of experiments by a factor of 40.5 compared to the traditional grid search method. The TSTO method accurately predicts cardiovascular risk and conserves computational resources. It is adaptable for low-power devices, aiding the goal of POCT.

156 Increased risk of onset of cardiovascular diseases in vitiligo patients: a retrospective large-scale real-world based population study based on the US Collaboratie Network

156 Increased risk of onset of cardiovascular diseases in vitiligo patients: a retrospective large-scale real-world based population study based on the US Collaboratie Network

Increased risk of dementia differs across cardiovascular diseases and types of dementia - Data from a nationwide study.

Dementia is a major health problem. Cardiovascular diseases (CVD) and risk factors are associated with incident dementia. However, whether there is an association among CVD, Alzheimer's disease (AD) and vascular dementia (VD) at the population level remains unclear. We analysed the association between CVD (heart failure [HF], atrial fibrillation [AF], myocardial infarction [MI], peripheral arterial disease, stroke and transient ischemic attack) and the incidence of dementia using nationwide FinnGen data of 218,192 individuals. The last follow-up information on dementia was available from October 2021. The age at the end of the follow-up was 61.7±17.1 years, and 53% were women. Overall, we observed 9701 (4.4%) dementia, 6323 (2.9%) AD and 1918 (0.7%) VD cases. Individuals with CVD had a higher risk of developing dementia than unexposed individuals. In the multivariable-adjusted Cox models, stroke was most strongly associated with dementia (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.6-1.8). CVD was more strongly associated with VD than with AD. Individuals with HF and MI had an increased risk of AD (HF: HR 1.11, 95% CI 1.04-1.19; MI: HR 1.10, 95% CI 1.02-1.18). AF was associated with VD (HR 1.58, 95% CI 1.42-1.77), but not with AD (HR 1.03, 95% CI 0.97-1.09). Clinical characteristics, such as diabetes, smoking and alcohol abuse, were associated with both types of dementia. All major CVDs were associated with an increased risk of developing dementia, particularly VD. Therefore, CVD onset should prompt an assessment of cognitive decline and possible preventive measures.

Physical Fitness Variables, General Health, Dementia and Quality of Life in Individuals with Intellectual and Developmental Disabilities: A Cross-Sectional Study.

The average life expectancy of individuals with intellectual and developmental disabilities (IDDs) is increasing. However, living more years does not mean living better, leading to the need for research on comorbidities associated with the aging process. Associated with this process are the physical characteristics most prevalent in an individual with IDD: low levels of all physical capacities, the accumulation of central fat, hyperglycemia, dyslipidemia, and hypertension, variables considered to be some of the main risk factors of the onset of metabolic and cardiovascular diseases, and variables that can negatively impact quality of life (QoL). Therefore, the aim of this study is to evaluate a sample of 21 institutionalized adults with IDD (42.81 ± 10.99 years old) in terms of their anthropometric characteristics, body composition, general health status, functional capacity, neuromuscular capacity, and dementia/cognitive function, and the possible associations with QoL. All assessments were performed in the laboratory of the Faculty of Sport Sciences and Physical Education-University of Coimbra. Participants, in the present study, have low levels of physical fitness and high metabolic and cardiovascular markets, which need to be improved. On the other hand, functional and neuromuscular ability seems to be associated with QoL (p ≤ 0.05). This study highlights the role of primary and secondary care providers in diagnosis, prevention, and supporting individuals with IDDs to promote QoL.

FRI033 Metabolically Healthy Obesity In A Young Population Assisted By The Family Health Strategy

Abstract Disclosure: R.B. Boghossian: None. G.F. Maselli: None. C.C. Lopes: None. C.A. Vasconcellos: None. C.A. Parente: None. D.D. Ferreira: None. J.C. Garcia: None. L.M. Guimarães: None. E.S. Muxfeldt: None. C.P. Damião: None. Background: Obesity is increasing in younger populations, and is associated with a high cardiovascular (CV) risk, however, it is not clear whether metabolically healthy obesity (MHO) may have a lower CV risk or if it is just an earlier stage of the disease. Objective: To evaluate the prevalence and cardiovascular (CV) risk factors associated with metabolically healthy obesity (MHO) in a young population assisted by a Family Health Care unit in a large urban center. Design and Methods: A cross-sectional population study for CV risk assessment in adults aged 20-50 years old from a Family Health Care unit. Demographic, anthropometric data and CV risk factors were recorded. All underwent office blood pressure (BP) measurements, laboratory evaluation (lipid and glycidic profile), Home Blood Pressure Monitoring (HBPM), and bioimpedance. Obesity was defined as a body mass index (BMI) > 30 kg/m2 and MHO are those who have less than 3 of the following criteria for metabolic syndrome: office BP higher or equal to 130 x 85 mmHg, hypertension, fasting blood sugar higher or equal to 100 mg/dL, HDL < 40 mg/dL (men) and 50 mg/dL (women), triglycerides >150 mg/dL and waist circumference > 102 cm (men) and > 88 cm (women). Results: A total of 726 individuals were evaluated (60% female; mean age 37 ± 9 years). The prevalence of obesity was 24.9%, of which 73.4% were classified as MHO. Obeses are older, with a higher prevalence of physical inactivity (51% vs 42%, p=0.03), hypertension (44% vs 19%, p<0.001), and diabetes (10% vs 2%, p=0.001) with higher office and home blood pressure. MHO compared to unhealthy ones are significantly younger and smoke less. Despite being obese, they have lower waist circumference (102 vs 110 cm, p=0.03), with lower office and home BP. There is no significant difference in relation to corporal composition. Conclusion: MHO was more prevalent in this young population and seems to have a lower CV risk, however it is not clear whether these younger and less obese individuals are only at an earlier stage of the disease. Perhaps the CV diseases onset is postponed for a few years. Even so, these individuals should not be excluded from public health policies as a form of primary prevention Presentation: Friday, June 16, 2023

Lovastatin regulates hypercholesterolemia and type II diabetes via BIRC2, LDLR, APOB, CASP3, CASP6, CASP9, XIAP and APAF1 genes: A System Pharmacology approach

Cardiovascular diseases are considered a major causative factor for the increasing rate of global mortality rate. Rendering to an approximation of the World Health Organization (WHO), 17.9 million people worldwide were affected by cardiovascular diseases. The behavioral risk factors such as tobacco use, unhealthy diet, obesity, physical inactivity, and harmful use of alcohol were found to play a significant role in the onset of cardiovascular diseases. Hypertension, diabetes, and hyperlipidemia are considered clinical factors associated with the prevalence of cardiovascular diseases. Among these clinical factors hyperlipidemia, which is characterized by increased levels of serum cholesterol, is highly related to the pathophysiological mechanism associated with cardiovascular diseases. Several medications are available for lowering abnormal serum cholesterol levels. Lovastatin, which belongs to the class of statins aids in lowering cholesterol levels by inhibiting hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a significant enzyme required for cholesterol biosynthesis. Lovastatin is also involved in regulating the pathogenesis of type 2 diabetes. In this study, we explored the association between Lovastatin interacting genes in Hypercholesterolemia pathways with genes associated with Type 2 Diabetes mellitus by employing systems biology approach. Our studies identified the significance of key genes such as BIRC2, LDLR, APOB, CASP3, CASP6, CASP9, XIAP, and APAF1 in the regulation of hypercholesterolemia and type 2 diabetes.

C2C12 Muscle Myotubes, but not Kidney Proximal Tubule HK-2 Cells, Elevate Erythritol Synthesis in Response to Oxidative Stress

BackgroundAs a biomarker, elevated serum erythritol concentrations predict type 2 diabetes and cardiovascular disease onset. Erythritol was recently shown to be a product of human glucose metabolism through the pentose phosphate pathway. The regulation of erythritol synthesis from glucose has been explored in cancer cells but not in nontransformed cells. ObjectiveThe kidneys and skeletal muscle have increased erythritol content in response to dietary sucrose, which suggests that they may significantly contribute to circulating erythritol concentrations. In the present study, we evaluated if conditions that promote erythritol synthesis in cancer cells are consistent in skeletal muscle and kidney cells. MethodsC2C12 myotubules were used as a model for skeletal muscle, and human kidney (HK)-2 human proximal tubule cells were used to model kidney. C2C12 cells were exposed to high- or low-glucose conditions. Both C2C12 and HK-2 cells were exposed to the free radical generator menadione, then intracellular reactive oxygen species (ROS) and erythritol concentrations were measured. Intracellular sorbitol concentrations were also measured because increased polyol flux was also observed after exposure to excess glucose and oxidative stress. ResultsIntracellular erythritol concentrations were significantly elevated in C2C12 cells following both high-glucose and menadione treatment. In contrast, HK-2 cells did not increase erythritol synthesis in response to oxidative stress. Generation of ROS through hydrogen peroxide exposure elevated sorbitol concentrations in both C2C12 and HK-2 cells, whereas generation of radicals with menadione treatment did not affect sorbitol production in either cell type. ConclusionsThese findings highlight that the factors contributing to elevated erythritol synthesis vary between cell types. More specifically, these studies demonstrate that muscle cells increase erythritol synthesis in response to both high glucose in culture medium and oxidative stress, whereas kidney cells increase erythritol synthesis only in response to high glucose.

A Review on Thrombolysis Enhancing Indian Edible Plants

Impaired thrombolysis is one of the causes of the development of cardiovascular diseases (CVD). The synthetic thrombolytic agents such as streptokinase, urokinase and antistreplase have their own side effects. Plants are always considered as safe and cost-effective therapeutic agents. Dietary therapeutics is an emerging branch for the prevention and treatment of several ailments. The present article compiles 43 edible plants which have shown in vitro thrombolytic potential and are also employed in the diets of several ethnic communities in India. Among these, Bauhinia purpurea and Baccaurea ramiflora are two plants having more than 70% in vitro clot lysis potential; Coccinia grandis, Curcuma longa, Cyperus rotundus, and Typha domingensis have 50-70% thrombolytic activity; and the rest of the plants have 11-49% thrombolytic activity. These 43 plants also include spices and condiments such as Turmeric, Black pepper, Indian Bayleaf, Coriander and Ginger, which affirms the traditional saying of using food as medicine. Besides, these edible plants also possess various phyto-constituents and health-beneficial pharmacological activities. If these plants could be incorporated into a routine diet, it might be possible to prevent or delay the onset of CVD. However, detailed studies are required to evaluate the pattern of CVD in ethnic communities consuming such plants, as well as systematic clinical trials are warranted to investigate the thrombolytic efficacy of these plants.

Antihyperlipidemic and Hepatoprotective Effect of Zingiber Cassumunar Rhizome Extract in High-Fat Diet-Induced Hyperlipidemic Rats: The Role of Antioxidant Activity

Hyperlipidemia and oxidative stress are major risk factors for the onset of cardiovascular diseases, and the oxidative stress caused by high level of lipids can cause liver damage. Zingiber cassumunar has been reported to contain a high antioxidant content that may provide therapeutic advantages. The present study was to evaluate the antihyperlipidemic and hepatoprotective effects of Z. cassumunar rhizome extract (ZCRE) in high-fat diet (HFD)-induced hyperlipidemicrats model and investigate the mechanism through its effect on the endogenous antioxidant enzymes. In this study, the rhizomes of Z. cassumunar was extracted using ethanol 96% (v/v) and evaporated to get the concentrated Z. cassumunar rhizome extract (ZCRE). Thin layer chromatography (TLC)-densitometry was performed to determine the curcumin content in the extract. High fat diet-induced hyperlipidemia model was used to evaluate the anti-hyperlipidemic and hepatoprotectiveactivities of ZCRE in rats. Male Wistar rats were randomly divided into five groups: normal control; High fat diet-induced hyperlipidemic rats (HFD); High Fat Diet and 100 mg/kgBW of ZCRE (HFD + 100 mg/kgBW); High Fat Diet and 200 mg/kgBW of ZCRE (HFD + 200 mg/kgBW); and High Fat Diet and 400 mg/kgBW of ZCRE (HFD + 400 mg/kgBW). The antihyperlipidemic and hepatoprotective potential of ZCRE were assessed through a series of analyses of body weight, blood biochemical parameters, which include total cholesterol (TC), triglycerides (TG), the serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT). The antioxidant activity of catalase (CAT) and glutation peroxidase (GSH-Px) were assessed on the liver homogenate. Data of the study were presented as mean ± SD and analyzed by using one way analysis of variance (ANOVA) followed by Least Significant Difference (LSD) test for multiple comparisons. The TLC analysis showed that ZCRE contained a significant amount of Curcumin. In addition, the study has also shown that ZRCE was able to significantly lower the levels of total cholesterol, triglyceride, SGPT, and SGOT as compared to hyperlipidemic rats (p <0.05). Concomitantly, the activity of CAT and GSH-Px was found significantly increased (p <0.05) when compared to hyperlipidemic control, with the dose of 400 mg/kg BW being the most effective. This study showed the significant antihyperlipidemic and hepatoprotective effects of ZCRE in HFD-induced hyperlipidemic rats, which mechanism might possibly connect to the increased antioxidant enzyme activities.

Elevated high-sensitivity C-reactive protein levels increase the risk of new-onset cardiac conduction disorders

BackgroundPrevious studies have reported that inflammatory responses can promote the onset of cardiovascular diseases; however, its association with cardiac conduction disorders remains unclear. The present community-based cohort study aimed to elucidate the effects of inflammatory responses on the risk of developing cardiac conduction disorders.MethodsAfter the exclusion of participants failing to meet the inclusion criteria, 86,234 eligible participants (mean age: 50.57 ± 11.88 years) were included. The participants were divided into high-sensitivity C-reactive protein (hsCRP) ≤ 3 mg/L, and hsCRP > 3 mg/L groups based on hsCRP values. Multivariate Cox proportional hazard model was used to analyze the relationship between inflammatory responses and various cardiac conduction disorders.ResultsAfter adjusting for confounding factors, we observed that compared with the hsCRP ≤ 3 mg/L group, the hsCRP > 3 mg/L group exhibited increased risks of atrioventricular block (hazard ratio [HR]:1.64, 95%confidence interval [CI] 1.44–1.87) and left (HR:1.25, 95% CI 1.07–1.45) and right bundle branch block (HR:1.31, 95% CI 1.17–1.47). Moreover, the risk of various cardiac conduction disorders increased for every 1 standard deviation increase in log (hsCRP). The restricted cubic spline function confirmed a linear relationship between log (hsCRP) and the risk of developing cardiac conduction disorders (All nonlinearity P > 0.05).ConclusionsHigh hsCRP levels are an independent risk factor for cardiac conduction disorders, and hsCRP levels are dose-dependently associated with the risk of conduction disorders. Our study results may provide new strategies for preventing cardiac conduction disorders.

Atherosclerosis preventive effects of marrubiin against (TNF-α)-induced oxidative stress and apoptosis.

Atherosclerosis is a complicated cascade of inflammatory processes, oxidative stress, and apoptosis, making it the most prevalent cardiovascular disease. The onset and progression of cardiovascular diseases are greatly influenced by oxidative stress. Targeting oxidative stress is an effective strategy for treating such diseases. Marrubiin is a bioactive furan labdane diterpenoid acts as a strong antioxidant to protect against oxidative damage. This study aimed to investigate the protective effects of marrubiin against oxidative stress and apoptosis in a cellular model of the vascular system. Human umbilical vein endothelial cells were treated with varying concentration of marrubiin and its IC50 value was determined. The antioxidant potential of marrubiin was assessed by measuring the intracellular level of glutathione (GSH) using a colorimetric technique. Since apoptosis plays a significant role in the plaque rupture, the study also evaluated the protective effects of marrubiin on the expression of key genes involved in apoptotic pathways. Cells treated with marrubiin showed increased GSH levels compared to cell therapy control cells, indicating marrubiin's ability to counteract the effects of TNF-α's on GSH levels. Furthermore real-time PCR analysis demonstrated that marrubiin upregulated Bcl-xl while downregulating caspase3 and Nox4 in treated cells. These findings suggest that marrubiin protects against apoptosis and oxidative stress. Based on our findings, marrubiin is recommended as a preventive/therapeutic treatment for diseases caused by elevated intracellular reactive oxygen species levels in cardiovascular diseases.

Anthocyanin Effects on Vascular and Endothelial Health: Evidence from Clinical Trials and Role of Gut Microbiota Metabolites.

Hypertension and derived cardiovascular disease (CVD) are among the leading causes of death worldwide. Increased oxidative stress and inflammatory state are involved in different alterations in endothelial functions that contribute to the onset of CVD. Polyphenols, and in particular anthocyanins, have aroused great interest for their antioxidant effects and their cardioprotective role. However, anthocyanins are rarely detected in blood serum because they are primarily metabolized by the gut microbiota. This review presents studies published to date that report the main results from clinical studies on the cardioprotective effects of anthocyanins and the role of the gut microbiota in the metabolism and bioavailability of anthocyanins and their influence on the composition of the microbiota. Even if it seems that anthocyanins have a significant effect on vascular health, more studies are required to better clarify which molecules and doses show vascular benefits without forgetting the crucial role of the microbiota.

Menstrual Cycle Irregularity in Adolescence Is Associated With Cardiometabolic Health in Early Adulthood.

Background Menstrual cycle irregularities are associated with cardiovascular and cardiometabolic disease. We tested associations between age at menarche and cycle irregularity in adolescence and cardiometabolic health in early adulthood in a subsample from the Pittsburgh Girls Study. Methods and Results Data from annual interviews were used to assess age at menarche and cycle irregularity (ie, greater or less than every 27-29 days) at age 15 years. At ages 22 to 25 years, cardiometabolic health was measured in a subsample of the Pittsburgh Girls Study (n=352; 68.2% Black), including blood pressure, waist circumference, and fasting serum insulin, glucose, and lipids. T tests were used for continuous data and odds ratios for dichotomous data to compare differences in cardiometabolic health as a function of onset and regularity of menses. Early menarche (ie, before age 11 years; n=52) was associated with waist circumference (P=0.043). Participants reporting irregular cycles (n=50) in adolescence had significantly higher levels of insulin, glucose, and triglycerides, and higher systolic and diastolic blood pressure (P values range from 0.035 to 0.005) and were more likely to have clinical indicators of cardiometabolic predisease in early adulthood compared with women who reported regular cycles (odds ratios ranged from 1.89 to 2.56). Conclusions Increasing rates and earlier onset of cardiovascular and metabolic disease among women, especially among Black women, highlights the need for identifying early and reliable risk indices. Menstrual cycle irregularity may serve this purpose and help elucidate the role of women's reproductive health in protecting and conferring risk for later cardiovascular and cardiometabolic diseases.

Abstract 006: Age And Sex Differentially Regulate Epigenetic Mechanisms In The Heart

Understanding epigenetic mechanisms associated with aging might reveal potential biomarkers for aging as well as therapeutic targets for reversing or ameliorating aging pathologies, including cardiovascular disease. There is a sex difference in the age of onset of cardiovascular disease, where females are protected against age related changes, including hypertension and fibrosis, until menopause. We hypothesized that epigenetic mechanisms would be differentially regulated in a sex and age dependent manner, with changes in the older females reflecting the loss of estrogen with aging. To test this hypothesis, we examined heart tissue from 4-month (4M), 12-month (12M), and 24-month (24M)-old male and female C57BL/6JN mice (National Institute of Aging). Surprisingly histone deacetylase (HDAC) activity (ELISA) was significantly higher in all female mice than in age-matched males (4M, female 5.2 ± 0.6 vs male 2.8 vs 0.5; 12M, female 4.2 ± 0.4 vs male 1.3 ± 0.2; 24M, female 8.1 ± 0.6 vs male 2.3 ± 0.4; ng/min/mg protein; p < 0.05). In females age increased HDAC activity (35% increase 24M v 4M; p < 0.05). Western blot analysis revealed that expression levels of profibrotic class I HDACs were significantly higher in 12M and 24M old female mice (HDAC1, 52% and 48%, p < 0.05 and HDAC2, 52% and 79%, p < 0.05), respectively, as compared with age-matched males. However, histone acetyltransferase activity was comparable in all male and female groups as was histone 3 (H3) acetylation at lysine 9 and 27. Levels of circulating histones were determined in the serum. Histones are released in the extracellular space during disease state, act as damage-associated molecular pattern molecules and activate inflammatory pathways. Circulating H3 levels in serum increased significantly with age in both sexes (male 12M, 17.1 ± 1.4; and 24M, 21.4 ± 0.8 vs. 4M, 4.0 ± 0.6; ng/ml, p < 0.05; female 12M, 13.8 ± 2.1 and 24M, 17.4 ± 1.4 vs. 4M, 7.2 ± 1.0 p < 0.05). The data demonstrate the effect of age and sex in heart tissues with aged female mice exhibiting higher levels of profibrotic epigenetic enzymes compared to males. These findings will have important implications in age-related cardiac injury as aging is a primary risk factor for hypertension and related heart disease in men and women.

Role of Epigenetics and Metabolomics in Predicting Endothelial Dysfunction in Type 2 Diabetes.

Type 2 diabetes (T2D) is a worldwide health problem and cardiovascular disease (CVD) is a leading cause of morbidity and mortality in T2D patients, making the prevention of CVD onset a major priority. It is therefore crucial to optimize diagnosis and treatment to reduce this burden. Endothelial dysfunction is one of the most important prognostic factors for CVD progression, thus novel approaches to identify the early phase of endothelial dysfunction may lead to specific preventive measures to reduce the occurrence of CVD. Nowadays, multiomics approaches have provided unprecedented opportunities to stratify T2D patients into endotypes, improve therapeutic treatment and outcome and amend the survival prediction. Among omics strategies, epigenetics and metabolomics are gaining increasing interest. Recently, a dynamic correlation between metabolic pathways and gene expression through chromatin remodeling, such as DNA methylation, has emerged, indicating new perspectives on the regulatory networks impacting cellular processes. Thus, a better understanding of epigenetic-metabolite relationships can provide insight into the physiological processes altered early in the endothelium that ultimately head to disease development. Here, recent studies on epigenetics and metabolomics related to CVD prevention potentially useful to identify disease biomarkers, as well as new therapies hopefully targeting the early phase of endothelial dysfunction are highlighted.

Challenges of a Patient with Thromboembolism

Challenges of a Patient with Thromboembolism