BACKGROUND Cardiovascular disease(CVD)is a leading cause of morbidity and mortality worldwide,the global burden of which is rising.It is still unclear the extent to which prediabetes contributes to the risk of CVD in ...BACKGROUND Cardiovascular disease(CVD)is a leading cause of morbidity and mortality worldwide,the global burden of which is rising.It is still unclear the extent to which prediabetes contributes to the risk of CVD in various age brackets among adults.To develop a focused screening plan and treatment for Chinese adults with prediabetes,it is crucial to identify variations in the connection between prediabetes and the risk of CVD based on age.AIM To examine the clinical features of prediabetes and identify risk factors for CVD in different age groups in China.METHODS The cross-sectional study involved a total of 46239 participants from June 2007 through May 2008.A thorough evaluation was conducted.Individuals with prediabetes were categorized into two groups based on age.Chinese atherosclerotic CVD risk prediction model was employed to evaluate the risk of developing CVD over 10 years.Random forest was established in both age groups.SHapley Additive exPlanation method prioritized the importance of features from the perspective of assessment contribution.RESULTS In total,6948 people were diagnosed with prediabetes in this study.In prediabetes,prevalences of CVD were 5(0.29%)in the younger group and 148(2.85%)in the older group.Overall,11.11%of the younger group and 29.59% of the older group were intermediate/high-risk of CVD for prediabetes without CVD based on the Prediction for ASCVD Risk in China equation in ten years.In the younger age group,the 10-year risk of CVD was found to be more closely linked to family history of CVD rather than lifestyle,whereas in the older age group,resident status was more closely linked.CONCLUSION The susceptibility to CVD is age-specific in newly diagnosed prediabetes.It is necessary to develop targeted approaches for the prevention and management of CVD in adults across various age brackets.展开更多
The Mediterranean diet has long been recognized as one of the most effective ways to prevent and improve cardiovascular disease.Extra virgin olive oil(EVOO)is the typical sources of fat in the Mediterranean diet which...The Mediterranean diet has long been recognized as one of the most effective ways to prevent and improve cardiovascular disease.Extra virgin olive oil(EVOO)is the typical sources of fat in the Mediterranean diet which have been shown to have noteworthy nutritional value and positive impact on human health.It is worth noting that EVOO owes its superior nutritional value to its bioactive composition.The main component of EVOO is monounsaturated fatty acids(MUFAs)in the form of oleic acid.Oleic acid accounts for up to 70%-80%of EVOO.Secondly,EVOO contains approximately more than 30 phenolic compounds,of which HT is essential for the protection against cardiovascular diseases.In this review,we focused on the potential mechanisms of oleic acid and polyphenols combat cardiovascular diseases risk in terms of oxidative stress,inflammation,blood pressure,endothelial function and cholesterol.This review might provide a reference for the studies on cardiovascular protective effects of EVOO.展开更多
Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is incre...Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is increasing yearly.Hypertension is a major risk factor for cardiovascular disease.Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes.Wnt signaling pathways include the canonical Wnt pathway(or Wnt/β-catenin pathway),the non canonical planar cell-polarity pathway,and the non-canonical calcium-dependent pathways.Abnormal Wnt signaling promotes cell proliferation and differentiation,cardiac malformations,various malignancies,so drugs targeting Wnt signaling play a great therapeutic potential.Wnt/β-catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation,migration,apoptosis,blood-brain barrier permeability,inflammation,oxidative stress,and immune response.Based on the latest research progress,this review summarizes the role of Wnt/β-catenin signaling in cardiovascular diseases,in order to provide new ideas for the prevention and treatment of cardiovascular diseases.展开更多
This editorial is intended to be a reflection on cardiovascular disease(CVD)burden in European ethnic minorities.In some European countries,ethnic minority realities,due to their recent appearance,are still to be stud...This editorial is intended to be a reflection on cardiovascular disease(CVD)burden in European ethnic minorities.In some European countries,ethnic minority realities,due to their recent appearance,are still to be studied in depth.The experience of several European countries,where the migration processes started earlier,even more than a century ago,can help by being an example.Many studies have shown that major differences in CVD burden exist not only between countries,but also within the same country when considering different social strata and ethnic groups.The CV risk factors underlying heart disease have been well established.Important epidemiological studies have helped us understand that the underlying causes of heart disease as well as the behaviors that can help prevent them are the same.We are now well aware that CVD should be treated by considering a holistic approach.This is why the social determinants(SDs)of health that may worsen the disease burden or that,vice versa,may improve the treatment,and even more significantly,the prognosis of a patient’s illness should be taken into consideration.For ethnic minority patients,this holistic,hermeneutic approach is of importance.Several SDs of health that influence CVDs have been identified but their relevance for the health of ethnic minorities has not yet been clearly defined.In some European countries,most ethnic minorities are largely also religious minorities.Only a few studies have evaluated the role of religion,which is an important SD that affects the probability of having CV risk factors and diseases.Adolescents,particularly those belonging to the second generation,seem to be the weak link.If we believe that these young people are really citizens of their country of birth,then a way of recognizing their belonging to the community starts from a will to better understand their condition,in order to assist them while they grow physically and mentally.Thinking about safeguarding the health of this population should be more than a health task,rather a goal of social justice.展开更多
Clonal hematopoiesis(CH)is a clonally expanded population of hematopoietic stem cells carrying somatic mutations that differentiate through multilineage hematopoiesis to form terminally differentiated mature hematopoi...Clonal hematopoiesis(CH)is a clonally expanded population of hematopoietic stem cells carrying somatic mutations that differentiate through multilineage hematopoiesis to form terminally differentiated mature hematopoietic cells carrying markers of the clonal mutation.Genes integral to critical cellular processes such as epigenetic regulation,DNA damage response,and inflammation frequently carry these mutations.Clonal hematopoiesis becomes increasingly prevalent with age and is associated with an increased risk of hematological tumors and some nonhematological conditions.Recent insights have revealed that the mutations driving CH are not only implicated in hematologic neoplasms but also possess the potential to influence cardiovascular pathogenesis.Here,we reviewed up-to-date findings about the roles of CH in cardiovascular diseases and tumors and explored the clinical significance of CH,as well as look forward to future related studies,so as to provide valuable references for future research and clinical practice.展开更多
Background: Guidelines are issued by most major organizations that focus on a specific disease entity. Guidelines should be a significant help to the practicing physician who may not be up-to-date with the recent medi...Background: Guidelines are issued by most major organizations that focus on a specific disease entity. Guidelines should be a significant help to the practicing physician who may not be up-to-date with the recent medical literature. Unfortunately, when conflicting guidelines for a specific disease are published, confusion results. Purpose: This article provides a suggested guideline outcome measure that would benefit the physician and patient. Methods: A review of 19 different guidelines for cardiovascular disease treatment is one example of the lack of specific outcomes that currently exist. The basic problem with most guidelines is that they do not state the expected end result (i.e., the benefit to the patient) if that guideline is followed. When guidelines use cardiovascular disease risk factors to dictate therapy, the end benefit is never stated so that the patient can make an appropriate choice of which (if any) guideline to follow. Results: A good example is guidelines published by the American Heart Association for reducing cardiovascular disease. These guidelines are risk factor based and only indicate that cardiovascular disease would be reduced if followed. No specific percentage in the reduction of the incidence of disease is given. In contrast, when elimination of the disease is the stated goal of the guideline, the end result is clear. To date, this goal has been stated by only one organization devoted to eliminating cardiovascular disease. Conclusion: Guidelines need to be written to provide the physician and the patient with a specific end point that is expected when the guideline is followed. Patient acceptance and compliance will be much improved if the patient knows the risk/benefit of following the guideline’s recommendations.展开更多
Gastrodia elata,a traditional Chinese medicine belonging to the Orchidaceae family,contains several major components such as gastrodin,polysaccharides of Gastrodia elata,and parishin.The pharmacological studies conduc...Gastrodia elata,a traditional Chinese medicine belonging to the Orchidaceae family,contains several major components such as gastrodin,polysaccharides of Gastrodia elata,and parishin.The pharmacological studies conducted on Gastrodia elata have revealed a variety of therapeutic properties,including antihypertensive,hypolipidemic,analgesic,and sedative-hypnotic properties.Thus,in this paper,we summarized the pharmacological effects of Gastrodia elata’s major components,namely gastrodin,polysaccharides of Gastrodia elata,parishin,and different types of Gastrodia elata extracts,on cardiovascular diseases such as atherosclerosis,hypertension,hyperglycemia,myocardial ischemia,myocardial hypoxia,myocarditis,and heart failure.Additionally,we conclude the mechanisms through which these active ingredients exert their therapeutic effects,including antioxidants,anti-inflammatory,and nitric oxide regulation.We provide insights into the therapeutic potential of Gastrodia elata with a detailed review of its pharmacological effects and molecular targets in cardiovascular disease protection and therapy,and can better understand the effect of traditional medicines in cardiovascular disease.展开更多
Prolactin(PRL)is a polypeptide hormone that is mainly synthesized and secreted by the lactotroph cells of the pituitary.There are two main isoforms of PRL:23-kDa PRL(named full-l ength PRL)and vasoinhibins(including ...Prolactin(PRL)is a polypeptide hormone that is mainly synthesized and secreted by the lactotroph cells of the pituitary.There are two main isoforms of PRL:23-kDa PRL(named full-l ength PRL)and vasoinhibins(including 5.6–18 kDa fragments).Both act as circulating hormones and cytokines to stimulate or inhibit vascular formation at different stages and neovascularization,including endothelial cell proliferation and migration,protease production,and apoptosis.However,their effects on vascular function and cardiovascular diseases are different or even contrary.In addition to the structure,secretion regulation,and signal transduction of PRL/vasoinhibins,this review focuses on the pathological mechanism and clinical significance of PRL/vasoinhibins in cardiovascular diseases.展开更多
Cold stimulation has been linked to acute myocardial infarction and other cardiovascular diseases.Residents in the frigid zones,such Heilongjiang Province,experience a higher incidence of adverse cardiovascular events...Cold stimulation has been linked to acute myocardial infarction and other cardiovascular diseases.Residents in the frigid zones,such Heilongjiang Province,experience a higher incidence of adverse cardiovascular events during winter,posing a significant health threat and increasing the overall medical burden.Cold stimulation serves as an detrimental stressor,inducing inflammation in the body.Therefore,understanding the role of inflammatory responses induced by cold stimulation in the occurrence and development of cardiovascular diseases is of paramount importance.Given the impact of cold on inflammation in cardiovascular diseases and the expanding array of anti-inflammatory methods for the treatment of cardiovascular diseases,delving into the inflammatory responses mediated by can significantly complement cardiovascular disease management.This review explorest the synergistic relationship between cold stimulation and inflammation induction,elucidating how this interplay influences the occurrence and progression of cardiovascular diseases.展开更多
Background: Cardiovascular Disease (CVD) is one of the leading chronic diseases in Saudi Arabia (SA) that cause disability and death. CVD predisposition risk varies according to age, gender, education, socioecono...Background: Cardiovascular Disease (CVD) is one of the leading chronic diseases in Saudi Arabia (SA) that cause disability and death. CVD predisposition risk varies according to age, gender, education, socioeconomic factors, and place of residency. In addition, CVD risk factors include physical inactivity, sedentary lifestyle, saturated fatty acid high diet, smoking, and stress. Aim: This is a systematic review study that aims to determine the effect of mindful mediation, physical activity, and diet on CVD in SA. Materials and Methods: This is a systematic electronic search method in Google scholar, PubMed, and Medline. Papers collected are papers that have been published since 2015. The search uses the following keywords: (Cardiovascular disease OR physical activity OR Physical inactivity OR meditation OR diet) AND Saudi Arabia. Data were extracted from each study through a narrative summary of each study. Results: Forty papers collected from 2015 to 2022 were included in the narrative study. Physical activity, diet, and mindful meditation are among the factors that can reduce the risk of development of CVD or severity of disease in patients with a CVD. Conclusion: This systematic review emphasized risk factors like physical inactivity, poor diet, and low level of awareness among Saudis and CVD Saudi patients. The findings show the role of physical activity, mindful meditation, and diet in reducing the onset or severity of cardiovascular disease.展开更多
Introduction: Cardiovascular diseases (CVD) are the most important cause of morbidity and mortality in type 2 diabetes (T2D). The objective of this study was to describe the profile of cardiovascular diseases of diabe...Introduction: Cardiovascular diseases (CVD) are the most important cause of morbidity and mortality in type 2 diabetes (T2D). The objective of this study was to describe the profile of cardiovascular diseases of diabetics admitted at the cardiology departments of Aristide Le Dantec and Fann hospitals. Patients and Methods: This was a retrospective, descriptive and analytical study conducted on January 1st and December 31st, 2020 at the Dantec and Fann cardiology departments in Dakar. We studied epidemiological, diagnostic, therapeutic and evolutionary data. The data 7 was analyzed with STATA 14 software. Results: Of the 1483 patients hospitalized in both cardiology departments, one hundred and thirty-three (133) were diabetic, the hospital frequency was 9.01%. The average age was 62.3 ± 11.2 years. The sex ratio (M/F) was 0.8. Almost half (47.4%) of patients had a duration of diabetes greater than 10 years. Cardiovascular risk factors were dominated by physical inactivity (84.2%), menopause (81.9%) and hypertension (64.7%). Heart failure was the most common clinical manifestation with 45.1%. The prevalence of acute coronary artery disease in our study was 37.59%, followed by lower limbs peripheral arterial disease (9.7%) and stroke (3%). Concerning the treatment, 119 patients were on anti-diabetic treatment. Most patients were on aspirin (79%), cholesterol-lowering drugs (78.95%) and ACE inhibitor (77.44%). Percutaneous coronary intervention was performed in 19 patients. 12.03% of patients diabetics died during hospitalization. Conclusion: Cardiovascular events are common during type 2 diabetes. Their management is important to avoid complications that can be fatal.展开更多
Atherosclerotic cardiovascular disease(ASCVD)frequently results in sudden death and poses a serious threat to public health worldwide.The drugs approved for the prevention and treatment of ASCVD are usually used in co...Atherosclerotic cardiovascular disease(ASCVD)frequently results in sudden death and poses a serious threat to public health worldwide.The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets.Therefore,the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention.Andrographolide(AG)is a diterpenoid lactone compound extracted from Andrographis paniculata.In addition to its use in conditions such as sore throat,AG can be used to prevent and treat ASCVD.It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity,diabetes,hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis(AS)including lipid accumulation,inflammation,oxidative stress and cellular abnormalities by regulating various targets and pathways.However,the pharmacological mechanisms of AG underlying the prevention and treatment of ASCVD have not been corroborated,which may hinder its clinical development and application.Therefore,this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD.The findings support the use of the old pharmacological compound(‘old bottle’)as a novel drug(‘novel wine’)for the prevention and treatment of ASCVD.Additionally,this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG,aiming to provide more information regarding the clinical application and further research and development of AG.展开更多
1 Introduction Major and profound changes have taken place in China over the past 30 years. An epidemic of cardiovascular diseases （CVD） in China is emerging as a result of lifestyle changes, urbanization, and the ...1 Introduction Major and profound changes have taken place in China over the past 30 years. An epidemic of cardiovascular diseases （CVD） in China is emerging as a result of lifestyle changes, urbanization, and the accelerated process of aging. The incidence of CVD is continuously increasing and will remain an upward trend in the next decade. Since 2005,展开更多
1 Introduction Rapid socioeconomic progress has greatly affected the lifestyle in China.Consequently,owing to lifestyle changes,urbanization,and accelerated population aging,the risk of cardiovascular diseases(CVD)has...1 Introduction Rapid socioeconomic progress has greatly affected the lifestyle in China.Consequently,owing to lifestyle changes,urbanization,and accelerated population aging,the risk of cardiovascular diseases(CVD)has increased.The incidence of CVD has been increasing continuously and this upward trend is projected to continue in the next decade.The growing burden of CVD has become a major public health issue.展开更多
The prevalence of cardiovascular diseases （CVDs） is associated with the socioeconomic prosperity, lifestyle changes, accelerated process of ageing and urbanization. The prevalence of CVDs is continuously increasing ...The prevalence of cardiovascular diseases （CVDs） is associated with the socioeconomic prosperity, lifestyle changes, accelerated process of ageing and urbanization. The prevalence of CVDs is continuously increasing in China and will remain an upward trend in the next 10 years. CVDs are the leading cause of death for Chinese in both urban area and rural area. Nowadays, 41.09% of deaths in rural area and 42.52% of deaths in urban area are caused by CVDs in China. The burden of CVDs remains heavy and has become an important public health problem. Effective strategies should be enforced urgently for the prevention of CVDs under the supervision of the government. In 2012, the Ministry of Health of China and 14 governmental departments jointly issued the Work Plan for Chronic Disease Prevention and Control in China （2012-2015）, a guideline for the prevention of chronic diseases, especially CVDs in China.展开更多
Cardiovascular diseases are the most common causes of mortality worldwide.They are frequently the reasons for patient hospitalization,their incapability for work,and disability.These diseases represent a significant s...Cardiovascular diseases are the most common causes of mortality worldwide.They are frequently the reasons for patient hospitalization,their incapability for work,and disability.These diseases represent a significant socio-economic burden affecting the medical system as well as patients and their families.It has been demonstrated that the etiopathogenesis of cardiovascular diseases is significantly affected by lifestyle,and so modification of the latter is an essential component of both primary and secondary prevention.Cardiac rehabilitation(CR)represents an efficient secondary prevention model that is especially based on the positive effect of regular physical activity.This review presents an overview of basic information on CR with a focus on current trends,such as the issue of the various training modalities,utilization,and barriers to it or the use of telemedicine technologies.Appropriate attention should be devoted to these domains,as CR continues evolving as an effective and readily available intervention in the future.展开更多
Classical risk factors only partially account for variations in cardiovascular disease incidence;therefore,also other so far unknown features,among which meteorological factors,may influence heart diseases(mainly coro...Classical risk factors only partially account for variations in cardiovascular disease incidence;therefore,also other so far unknown features,among which meteorological factors,may influence heart diseases(mainly coronary heart diseases,but also heart failure,arrhythmias,aortic dissection and stroke)rates.The most studied phenomenon is ambient temperature.The relation between mortality,as well as cardiovascular diseases incidence,and temperature appears graphically as a"U"shape.Exposure to cold,heat and heat waves is associated with an increased risk of acute coronary syndromes.Other climatic variables,such as humidity,atmospheric pressure,sunlight hours,wind strength and direction and rain/snow precipitations have been hypothesized as related to fatal and nonfatal cardiovascular diseases incidence.Main limitation of these studies is the unavailability of data on individual exposure to weather parameters.Effects of weather may vary depending on other factors,such as population disease profile and age structure.Climatic stress may increase direct and indirect risks to human health via different,complex pathophysiological pathways and exogenous and endogenous mechanisms.These data have attracted growing interest because of the recent earth’s climate change,with consequent increasing ambient temperatures and climatic fluctuations.This review evaluates the evidence base for cardiac health consequences of climate conditions,and it also explores potential further implications.展开更多
The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on eluc...The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on elucidating the role of genes in human diseases. One powerful method to reveal insight into gene functions is the systematic analysis of gene expression. Two popular high-throughput gene expression technologies, microarray and Serial Analysis of Gene Expression (SAGE) are capable of producing large amounts of gene expression data with the potential of providing novel insights into fundamental disease processes, especially complex syndromes such as cardiovascular disease, whose etiologies are due to multiple genetic factors and their interplay with the environment. Microarray and SAGE have already been used to examine gene expression patterns of cell-culture, animal and human tissues models of cardiovascular diseases. In this review, we will first give a brief introduction of microarray and SAGE technologies and point out their limitations. We will then discuss the major discoveries and the new biological insightsthat have emerged from their applications to cardiovascular diseases. Finally we will touch upon potential challenges and future developments in this area.展开更多
Background Endogenous aldehyde damages DNA and potentiates an ageing phenotype. The aldehyde dehydrogenase 2(ALDH2) rs671 polymorphism has a prevalence of 30%–50% in Asian populations. In this study, we aimed to anal...Background Endogenous aldehyde damages DNA and potentiates an ageing phenotype. The aldehyde dehydrogenase 2(ALDH2) rs671 polymorphism has a prevalence of 30%–50% in Asian populations. In this study, we aimed to analyze risk factors contributing to the development of heart failure with preserved ejection fraction(HFpEF) along with the genetic exposure in Chinese patients hospitalized with cardiovascular diseases(CVD). Methods From July 2017 to October 2018, a total of 770 consecutive Chinese patients with normal left ventricular ejection fractions(LVEF) and established CVD(hypertension, coronary heart diseases, or diabetes) were enrolled in this prospective cross-sectional study. HFpEF was defined by the presence of at least one of symptom(dyspnoea and fatigue) or sign(rales and ankle swelling) related to heart failure;N-terminal pro-B-Type natriuretic peptide(NT pro-BNP ≥ 280 pg/mL);LVEF ≥ 50%;and at least one criterion related to elevated ventricular filling pressure or diastolic dysfunction(left atrial diameter > 40 mm, E/E’ ≥ 13, E’/A’ < 1 or concurrent atrial fibrillation). Logistic regression was performed to yield adjusted odds ratios(ORs) for HFp EF incidence associated with traditional and/or genetic exposures. Results Finally, among 770 patients with CVD, 92(11.9%) patients were classified into the HFpEF group according to the diagnostic criteria. The mean age of the participants was 67 ± 12 years, and 278(36.1%) patients were females. A total of 303(39.4%) patients were ALDH2*2 variant carriers. In the univariate analysis, eight exposures were found to be associated with HFpEF: atrial fibrillation, ALDH2*2 variants, hypertension, age, anaemia, smoking, alcohol consumption and sex. Multivariable logistic regression showed that 4 ‘A’ variables(atrial fibrillation, ALDH2*2 variants, age and anaemia) were significantly associated with an increased risk of HFpEF. Atrial fibrillation was associated with a 3.8-fold increased HFpEF risk(95% CI: 2.21–6.61, P < 0.001), and the other three exposures associated with increased HFpEF risk were the ALDH2*2 variant(OR = 2.41, 95% CI: 1.49–3.87, P < 0.001), age(OR = 2.14, 95% CI: 1.27–3.60, P = 0.004), and anaemia(OR = 1.79, 95% CI: 1.05–3.03, P = 0.032). These four variables predicted HFpEF incidence in Chinese CVD patients(C-statistic = 0.745, 95% CI: 0.691–0.800, P < 0.001). Conclusions 4 A traits(atrial fibrillation, ALDH2*2 variants, age and anaemia) were associated with an increased risk of HFpEF in Chinese CVD patients. Our results provide potential clues to the aetiology, pathophysiology and therapeutic targets of HFpEF.展开更多
The roles of androgens on cardiovascular physiology and pathophysiology are controversial as both beneficial and detrimental effects have been reported. Although the reasons for this discrepancy are unclear, multiple ...The roles of androgens on cardiovascular physiology and pathophysiology are controversial as both beneficial and detrimental effects have been reported. Although the reasons for this discrepancy are unclear, multiple factors such as genetic and epigenetic variation, sex-specificity, hormone interactions, drug preparation and route of administration may contribute. Recently, growing evidence suggests that androgens exhibit beneficial effects on cardiovascular function though the mechanism remains to be elucidated. Endothelial cells （ECs） which line the interior surface of blood vessels are distributed throughout the circulatory system, and play a crucial role in cardiovascular function. Endothelial progenitor cells （EPCs） are considered an indispensable element for the reconstitution and maintenance of an intact endothelial layer. Endothelial dysfunction is regarded as an initiating step in development of atherosclerosis and cardiovascular diseases. The modulation of endothelial functions by androgens through either genornic or nongenomic signal pathways is one possible mechanism by which androgens act on the cardiovascular system. Obtaining insight into the mechanisms by which androgens affect EC and EPC functions will allow us to determine whether androgens possess beneficial effects on the cardiovascular system. This in turn may be critical in the prevention and therapy of cardiovascular diseases. This article seeks to review recent progress in androgen regulation of endothelial function, the sex-specificity of androgen actions, and its clinical applications in the cardiovascular system.展开更多
文摘BACKGROUND Cardiovascular disease(CVD)is a leading cause of morbidity and mortality worldwide,the global burden of which is rising.It is still unclear the extent to which prediabetes contributes to the risk of CVD in various age brackets among adults.To develop a focused screening plan and treatment for Chinese adults with prediabetes,it is crucial to identify variations in the connection between prediabetes and the risk of CVD based on age.AIM To examine the clinical features of prediabetes and identify risk factors for CVD in different age groups in China.METHODS The cross-sectional study involved a total of 46239 participants from June 2007 through May 2008.A thorough evaluation was conducted.Individuals with prediabetes were categorized into two groups based on age.Chinese atherosclerotic CVD risk prediction model was employed to evaluate the risk of developing CVD over 10 years.Random forest was established in both age groups.SHapley Additive exPlanation method prioritized the importance of features from the perspective of assessment contribution.RESULTS In total,6948 people were diagnosed with prediabetes in this study.In prediabetes,prevalences of CVD were 5(0.29%)in the younger group and 148(2.85%)in the older group.Overall,11.11%of the younger group and 29.59% of the older group were intermediate/high-risk of CVD for prediabetes without CVD based on the Prediction for ASCVD Risk in China equation in ten years.In the younger age group,the 10-year risk of CVD was found to be more closely linked to family history of CVD rather than lifestyle,whereas in the older age group,resident status was more closely linked.CONCLUSION The susceptibility to CVD is age-specific in newly diagnosed prediabetes.It is necessary to develop targeted approaches for the prevention and management of CVD in adults across various age brackets.
基金supported by the CACMS Innovation Fund(CI2021A00914)the Beijing Novaprogram(Z211100002121062)+1 种基金the Opening Project of the Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province(2C32001)the National Natural Science Foundation of China(82004193)。
文摘The Mediterranean diet has long been recognized as one of the most effective ways to prevent and improve cardiovascular disease.Extra virgin olive oil(EVOO)is the typical sources of fat in the Mediterranean diet which have been shown to have noteworthy nutritional value and positive impact on human health.It is worth noting that EVOO owes its superior nutritional value to its bioactive composition.The main component of EVOO is monounsaturated fatty acids(MUFAs)in the form of oleic acid.Oleic acid accounts for up to 70%-80%of EVOO.Secondly,EVOO contains approximately more than 30 phenolic compounds,of which HT is essential for the protection against cardiovascular diseases.In this review,we focused on the potential mechanisms of oleic acid and polyphenols combat cardiovascular diseases risk in terms of oxidative stress,inflammation,blood pressure,endothelial function and cholesterol.This review might provide a reference for the studies on cardiovascular protective effects of EVOO.
文摘Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is increasing yearly.Hypertension is a major risk factor for cardiovascular disease.Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes.Wnt signaling pathways include the canonical Wnt pathway(or Wnt/β-catenin pathway),the non canonical planar cell-polarity pathway,and the non-canonical calcium-dependent pathways.Abnormal Wnt signaling promotes cell proliferation and differentiation,cardiac malformations,various malignancies,so drugs targeting Wnt signaling play a great therapeutic potential.Wnt/β-catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation,migration,apoptosis,blood-brain barrier permeability,inflammation,oxidative stress,and immune response.Based on the latest research progress,this review summarizes the role of Wnt/β-catenin signaling in cardiovascular diseases,in order to provide new ideas for the prevention and treatment of cardiovascular diseases.
文摘This editorial is intended to be a reflection on cardiovascular disease(CVD)burden in European ethnic minorities.In some European countries,ethnic minority realities,due to their recent appearance,are still to be studied in depth.The experience of several European countries,where the migration processes started earlier,even more than a century ago,can help by being an example.Many studies have shown that major differences in CVD burden exist not only between countries,but also within the same country when considering different social strata and ethnic groups.The CV risk factors underlying heart disease have been well established.Important epidemiological studies have helped us understand that the underlying causes of heart disease as well as the behaviors that can help prevent them are the same.We are now well aware that CVD should be treated by considering a holistic approach.This is why the social determinants(SDs)of health that may worsen the disease burden or that,vice versa,may improve the treatment,and even more significantly,the prognosis of a patient’s illness should be taken into consideration.For ethnic minority patients,this holistic,hermeneutic approach is of importance.Several SDs of health that influence CVDs have been identified but their relevance for the health of ethnic minorities has not yet been clearly defined.In some European countries,most ethnic minorities are largely also religious minorities.Only a few studies have evaluated the role of religion,which is an important SD that affects the probability of having CV risk factors and diseases.Adolescents,particularly those belonging to the second generation,seem to be the weak link.If we believe that these young people are really citizens of their country of birth,then a way of recognizing their belonging to the community starts from a will to better understand their condition,in order to assist them while they grow physically and mentally.Thinking about safeguarding the health of this population should be more than a health task,rather a goal of social justice.
基金Supported by a grant from the National Natural Science Founda-tion of China(no.82200319).
文摘Clonal hematopoiesis(CH)is a clonally expanded population of hematopoietic stem cells carrying somatic mutations that differentiate through multilineage hematopoiesis to form terminally differentiated mature hematopoietic cells carrying markers of the clonal mutation.Genes integral to critical cellular processes such as epigenetic regulation,DNA damage response,and inflammation frequently carry these mutations.Clonal hematopoiesis becomes increasingly prevalent with age and is associated with an increased risk of hematological tumors and some nonhematological conditions.Recent insights have revealed that the mutations driving CH are not only implicated in hematologic neoplasms but also possess the potential to influence cardiovascular pathogenesis.Here,we reviewed up-to-date findings about the roles of CH in cardiovascular diseases and tumors and explored the clinical significance of CH,as well as look forward to future related studies,so as to provide valuable references for future research and clinical practice.
文摘Background: Guidelines are issued by most major organizations that focus on a specific disease entity. Guidelines should be a significant help to the practicing physician who may not be up-to-date with the recent medical literature. Unfortunately, when conflicting guidelines for a specific disease are published, confusion results. Purpose: This article provides a suggested guideline outcome measure that would benefit the physician and patient. Methods: A review of 19 different guidelines for cardiovascular disease treatment is one example of the lack of specific outcomes that currently exist. The basic problem with most guidelines is that they do not state the expected end result (i.e., the benefit to the patient) if that guideline is followed. When guidelines use cardiovascular disease risk factors to dictate therapy, the end benefit is never stated so that the patient can make an appropriate choice of which (if any) guideline to follow. Results: A good example is guidelines published by the American Heart Association for reducing cardiovascular disease. These guidelines are risk factor based and only indicate that cardiovascular disease would be reduced if followed. No specific percentage in the reduction of the incidence of disease is given. In contrast, when elimination of the disease is the stated goal of the guideline, the end result is clear. To date, this goal has been stated by only one organization devoted to eliminating cardiovascular disease. Conclusion: Guidelines need to be written to provide the physician and the patient with a specific end point that is expected when the guideline is followed. Patient acceptance and compliance will be much improved if the patient knows the risk/benefit of following the guideline’s recommendations.
基金This study was funded by the National Natural Science Foundation of China(82260096)the Science and Technology Foundation of Basic Research Program of Guizhou Province([2023]General 371,[2020]1Y381)the Science and Technology Foundation of Health Commission of Guizhou Province(2022XMSB00037954).
文摘Gastrodia elata,a traditional Chinese medicine belonging to the Orchidaceae family,contains several major components such as gastrodin,polysaccharides of Gastrodia elata,and parishin.The pharmacological studies conducted on Gastrodia elata have revealed a variety of therapeutic properties,including antihypertensive,hypolipidemic,analgesic,and sedative-hypnotic properties.Thus,in this paper,we summarized the pharmacological effects of Gastrodia elata’s major components,namely gastrodin,polysaccharides of Gastrodia elata,parishin,and different types of Gastrodia elata extracts,on cardiovascular diseases such as atherosclerosis,hypertension,hyperglycemia,myocardial ischemia,myocardial hypoxia,myocarditis,and heart failure.Additionally,we conclude the mechanisms through which these active ingredients exert their therapeutic effects,including antioxidants,anti-inflammatory,and nitric oxide regulation.We provide insights into the therapeutic potential of Gastrodia elata with a detailed review of its pharmacological effects and molecular targets in cardiovascular disease protection and therapy,and can better understand the effect of traditional medicines in cardiovascular disease.
基金National Natural Science Foundation of China,Grant/Award Number:81700045,81870042 and 81900050Natural Science Foundation of Shanghai,Grant/Award Number:22ZR1452400+1 种基金Shanghai Municipal Commission of Health,Grant/Award Number:20204Y0384Shanghai Pulmonary Hospital,Grant/Award Number:fk18003 and fkyq1605。
文摘Prolactin(PRL)is a polypeptide hormone that is mainly synthesized and secreted by the lactotroph cells of the pituitary.There are two main isoforms of PRL:23-kDa PRL(named full-l ength PRL)and vasoinhibins(including 5.6–18 kDa fragments).Both act as circulating hormones and cytokines to stimulate or inhibit vascular formation at different stages and neovascularization,including endothelial cell proliferation and migration,protease production,and apoptosis.However,their effects on vascular function and cardiovascular diseases are different or even contrary.In addition to the structure,secretion regulation,and signal transduction of PRL/vasoinhibins,this review focuses on the pathological mechanism and clinical significance of PRL/vasoinhibins in cardiovascular diseases.
基金This work was supported by National Natural Science Foundation of China(No.82170262,No.82200546)。
文摘Cold stimulation has been linked to acute myocardial infarction and other cardiovascular diseases.Residents in the frigid zones,such Heilongjiang Province,experience a higher incidence of adverse cardiovascular events during winter,posing a significant health threat and increasing the overall medical burden.Cold stimulation serves as an detrimental stressor,inducing inflammation in the body.Therefore,understanding the role of inflammatory responses induced by cold stimulation in the occurrence and development of cardiovascular diseases is of paramount importance.Given the impact of cold on inflammation in cardiovascular diseases and the expanding array of anti-inflammatory methods for the treatment of cardiovascular diseases,delving into the inflammatory responses mediated by can significantly complement cardiovascular disease management.This review explorest the synergistic relationship between cold stimulation and inflammation induction,elucidating how this interplay influences the occurrence and progression of cardiovascular diseases.
文摘Background: Cardiovascular Disease (CVD) is one of the leading chronic diseases in Saudi Arabia (SA) that cause disability and death. CVD predisposition risk varies according to age, gender, education, socioeconomic factors, and place of residency. In addition, CVD risk factors include physical inactivity, sedentary lifestyle, saturated fatty acid high diet, smoking, and stress. Aim: This is a systematic review study that aims to determine the effect of mindful mediation, physical activity, and diet on CVD in SA. Materials and Methods: This is a systematic electronic search method in Google scholar, PubMed, and Medline. Papers collected are papers that have been published since 2015. The search uses the following keywords: (Cardiovascular disease OR physical activity OR Physical inactivity OR meditation OR diet) AND Saudi Arabia. Data were extracted from each study through a narrative summary of each study. Results: Forty papers collected from 2015 to 2022 were included in the narrative study. Physical activity, diet, and mindful meditation are among the factors that can reduce the risk of development of CVD or severity of disease in patients with a CVD. Conclusion: This systematic review emphasized risk factors like physical inactivity, poor diet, and low level of awareness among Saudis and CVD Saudi patients. The findings show the role of physical activity, mindful meditation, and diet in reducing the onset or severity of cardiovascular disease.
文摘Introduction: Cardiovascular diseases (CVD) are the most important cause of morbidity and mortality in type 2 diabetes (T2D). The objective of this study was to describe the profile of cardiovascular diseases of diabetics admitted at the cardiology departments of Aristide Le Dantec and Fann hospitals. Patients and Methods: This was a retrospective, descriptive and analytical study conducted on January 1st and December 31st, 2020 at the Dantec and Fann cardiology departments in Dakar. We studied epidemiological, diagnostic, therapeutic and evolutionary data. The data 7 was analyzed with STATA 14 software. Results: Of the 1483 patients hospitalized in both cardiology departments, one hundred and thirty-three (133) were diabetic, the hospital frequency was 9.01%. The average age was 62.3 ± 11.2 years. The sex ratio (M/F) was 0.8. Almost half (47.4%) of patients had a duration of diabetes greater than 10 years. Cardiovascular risk factors were dominated by physical inactivity (84.2%), menopause (81.9%) and hypertension (64.7%). Heart failure was the most common clinical manifestation with 45.1%. The prevalence of acute coronary artery disease in our study was 37.59%, followed by lower limbs peripheral arterial disease (9.7%) and stroke (3%). Concerning the treatment, 119 patients were on anti-diabetic treatment. Most patients were on aspirin (79%), cholesterol-lowering drugs (78.95%) and ACE inhibitor (77.44%). Percutaneous coronary intervention was performed in 19 patients. 12.03% of patients diabetics died during hospitalization. Conclusion: Cardiovascular events are common during type 2 diabetes. Their management is important to avoid complications that can be fatal.
基金This research was funded by the National Natural Science Foundation of China(Grant Nos.:81891012 and U19A2010)the National Interdisciplinary Innovation TeamProgram of Traditional Chinese Medicine(Grant No.:ZYYCXTD-D-202209)+1 种基金Chinese Medicine Science and Technology Industry Innovation Team Program of Sichuan Province(Grant No.:2022C001)Chengdu University of Traditional Chinese Medicine“Xinglin Scholars”Discipline Talent Research Promotion Program(Grant No.:XCZX2022010).
文摘Atherosclerotic cardiovascular disease(ASCVD)frequently results in sudden death and poses a serious threat to public health worldwide.The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets.Therefore,the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention.Andrographolide(AG)is a diterpenoid lactone compound extracted from Andrographis paniculata.In addition to its use in conditions such as sore throat,AG can be used to prevent and treat ASCVD.It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity,diabetes,hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis(AS)including lipid accumulation,inflammation,oxidative stress and cellular abnormalities by regulating various targets and pathways.However,the pharmacological mechanisms of AG underlying the prevention and treatment of ASCVD have not been corroborated,which may hinder its clinical development and application.Therefore,this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD.The findings support the use of the old pharmacological compound(‘old bottle’)as a novel drug(‘novel wine’)for the prevention and treatment of ASCVD.Additionally,this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG,aiming to provide more information regarding the clinical application and further research and development of AG.
文摘1 Introduction Major and profound changes have taken place in China over the past 30 years. An epidemic of cardiovascular diseases （CVD） in China is emerging as a result of lifestyle changes, urbanization, and the accelerated process of aging. The incidence of CVD is continuously increasing and will remain an upward trend in the next decade. Since 2005,
文摘1 Introduction Rapid socioeconomic progress has greatly affected the lifestyle in China.Consequently,owing to lifestyle changes,urbanization,and accelerated population aging,the risk of cardiovascular diseases(CVD)has increased.The incidence of CVD has been increasing continuously and this upward trend is projected to continue in the next decade.The growing burden of CVD has become a major public health issue.
文摘The prevalence of cardiovascular diseases （CVDs） is associated with the socioeconomic prosperity, lifestyle changes, accelerated process of ageing and urbanization. The prevalence of CVDs is continuously increasing in China and will remain an upward trend in the next 10 years. CVDs are the leading cause of death for Chinese in both urban area and rural area. Nowadays, 41.09% of deaths in rural area and 42.52% of deaths in urban area are caused by CVDs in China. The burden of CVDs remains heavy and has become an important public health problem. Effective strategies should be enforced urgently for the prevention of CVDs under the supervision of the government. In 2012, the Ministry of Health of China and 14 governmental departments jointly issued the Work Plan for Chronic Disease Prevention and Control in China （2012-2015）, a guideline for the prevention of chronic diseases, especially CVDs in China.
基金Masaryk University,No.MUNI/A/1294/2019Ministry of Health,Czech Republic–Conceptual Development of Research Organization,No.65269705.
文摘Cardiovascular diseases are the most common causes of mortality worldwide.They are frequently the reasons for patient hospitalization,their incapability for work,and disability.These diseases represent a significant socio-economic burden affecting the medical system as well as patients and their families.It has been demonstrated that the etiopathogenesis of cardiovascular diseases is significantly affected by lifestyle,and so modification of the latter is an essential component of both primary and secondary prevention.Cardiac rehabilitation(CR)represents an efficient secondary prevention model that is especially based on the positive effect of regular physical activity.This review presents an overview of basic information on CR with a focus on current trends,such as the issue of the various training modalities,utilization,and barriers to it or the use of telemedicine technologies.Appropriate attention should be devoted to these domains,as CR continues evolving as an effective and readily available intervention in the future.
文摘Classical risk factors only partially account for variations in cardiovascular disease incidence;therefore,also other so far unknown features,among which meteorological factors,may influence heart diseases(mainly coronary heart diseases,but also heart failure,arrhythmias,aortic dissection and stroke)rates.The most studied phenomenon is ambient temperature.The relation between mortality,as well as cardiovascular diseases incidence,and temperature appears graphically as a"U"shape.Exposure to cold,heat and heat waves is associated with an increased risk of acute coronary syndromes.Other climatic variables,such as humidity,atmospheric pressure,sunlight hours,wind strength and direction and rain/snow precipitations have been hypothesized as related to fatal and nonfatal cardiovascular diseases incidence.Main limitation of these studies is the unavailability of data on individual exposure to weather parameters.Effects of weather may vary depending on other factors,such as population disease profile and age structure.Climatic stress may increase direct and indirect risks to human health via different,complex pathophysiological pathways and exogenous and endogenous mechanisms.These data have attracted growing interest because of the recent earth’s climate change,with consequent increasing ambient temperatures and climatic fluctuations.This review evaluates the evidence base for cardiac health consequences of climate conditions,and it also explores potential further implications.
基金Part of studies cited in this review was in partsupported by Johns Hopkins Institutional ResearchGrant(Ye,SQ),a pilot project(Ye,SQ)in The Hop-kins DK Center for the Analysis of Gene Expres-sion(R24DK58757-01,NIDDK)and Dorothy WallisWagner Charitable Tru
文摘The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on elucidating the role of genes in human diseases. One powerful method to reveal insight into gene functions is the systematic analysis of gene expression. Two popular high-throughput gene expression technologies, microarray and Serial Analysis of Gene Expression (SAGE) are capable of producing large amounts of gene expression data with the potential of providing novel insights into fundamental disease processes, especially complex syndromes such as cardiovascular disease, whose etiologies are due to multiple genetic factors and their interplay with the environment. Microarray and SAGE have already been used to examine gene expression patterns of cell-culture, animal and human tissues models of cardiovascular diseases. In this review, we will first give a brief introduction of microarray and SAGE technologies and point out their limitations. We will then discuss the major discoveries and the new biological insightsthat have emerged from their applications to cardiovascular diseases. Finally we will touch upon potential challenges and future developments in this area.
基金supported by the he National Natural Science Foundation of China (No. 81770441, No. 81700398, No. 81970309)Nanjing Municipal Healthcare Grant YKK16127
文摘Background Endogenous aldehyde damages DNA and potentiates an ageing phenotype. The aldehyde dehydrogenase 2(ALDH2) rs671 polymorphism has a prevalence of 30%–50% in Asian populations. In this study, we aimed to analyze risk factors contributing to the development of heart failure with preserved ejection fraction(HFpEF) along with the genetic exposure in Chinese patients hospitalized with cardiovascular diseases(CVD). Methods From July 2017 to October 2018, a total of 770 consecutive Chinese patients with normal left ventricular ejection fractions(LVEF) and established CVD(hypertension, coronary heart diseases, or diabetes) were enrolled in this prospective cross-sectional study. HFpEF was defined by the presence of at least one of symptom(dyspnoea and fatigue) or sign(rales and ankle swelling) related to heart failure;N-terminal pro-B-Type natriuretic peptide(NT pro-BNP ≥ 280 pg/mL);LVEF ≥ 50%;and at least one criterion related to elevated ventricular filling pressure or diastolic dysfunction(left atrial diameter > 40 mm, E/E’ ≥ 13, E’/A’ < 1 or concurrent atrial fibrillation). Logistic regression was performed to yield adjusted odds ratios(ORs) for HFp EF incidence associated with traditional and/or genetic exposures. Results Finally, among 770 patients with CVD, 92(11.9%) patients were classified into the HFpEF group according to the diagnostic criteria. The mean age of the participants was 67 ± 12 years, and 278(36.1%) patients were females. A total of 303(39.4%) patients were ALDH2*2 variant carriers. In the univariate analysis, eight exposures were found to be associated with HFpEF: atrial fibrillation, ALDH2*2 variants, hypertension, age, anaemia, smoking, alcohol consumption and sex. Multivariable logistic regression showed that 4 ‘A’ variables(atrial fibrillation, ALDH2*2 variants, age and anaemia) were significantly associated with an increased risk of HFpEF. Atrial fibrillation was associated with a 3.8-fold increased HFpEF risk(95% CI: 2.21–6.61, P < 0.001), and the other three exposures associated with increased HFpEF risk were the ALDH2*2 variant(OR = 2.41, 95% CI: 1.49–3.87, P < 0.001), age(OR = 2.14, 95% CI: 1.27–3.60, P = 0.004), and anaemia(OR = 1.79, 95% CI: 1.05–3.03, P = 0.032). These four variables predicted HFpEF incidence in Chinese CVD patients(C-statistic = 0.745, 95% CI: 0.691–0.800, P < 0.001). Conclusions 4 A traits(atrial fibrillation, ALDH2*2 variants, age and anaemia) were associated with an increased risk of HFpEF in Chinese CVD patients. Our results provide potential clues to the aetiology, pathophysiology and therapeutic targets of HFpEF.
基金The researches described in this article were partially supported by grants from the National Natural Science Foundation of China （No. 81570271 and 81400357） and NIH （UL1 RR024996）. We are very grateful to John R Lee （Assistant Professor of Medicine, Weill Comell Medical College, New York）, and Jeff J Zhu （Research Manager, Weill Comell Medical College, New York） for critical review of the article. The authors have nothing to disclosure.
文摘The roles of androgens on cardiovascular physiology and pathophysiology are controversial as both beneficial and detrimental effects have been reported. Although the reasons for this discrepancy are unclear, multiple factors such as genetic and epigenetic variation, sex-specificity, hormone interactions, drug preparation and route of administration may contribute. Recently, growing evidence suggests that androgens exhibit beneficial effects on cardiovascular function though the mechanism remains to be elucidated. Endothelial cells （ECs） which line the interior surface of blood vessels are distributed throughout the circulatory system, and play a crucial role in cardiovascular function. Endothelial progenitor cells （EPCs） are considered an indispensable element for the reconstitution and maintenance of an intact endothelial layer. Endothelial dysfunction is regarded as an initiating step in development of atherosclerosis and cardiovascular diseases. The modulation of endothelial functions by androgens through either genornic or nongenomic signal pathways is one possible mechanism by which androgens act on the cardiovascular system. Obtaining insight into the mechanisms by which androgens affect EC and EPC functions will allow us to determine whether androgens possess beneficial effects on the cardiovascular system. This in turn may be critical in the prevention and therapy of cardiovascular diseases. This article seeks to review recent progress in androgen regulation of endothelial function, the sex-specificity of androgen actions, and its clinical applications in the cardiovascular system.
