Cardiovascular Medicine
The Association between Serum Follistatin-like Proteins and Cardiovascular Diseases: A Systematic Review and Meta-analysis
Follistatin-like proteins (FSTLs) are adipomyokines secreted by adipocytes and myocytes. Previous studies have reported an increase in circulating FSTL1 levels in response to cardiovascular injuries. In this study we conducted a systematic review and meta-analysis to assess the association between circulating FSTLs and Cardiovascular Diseases (CVDs).
We performed a comprehensive literature search using PubMed Web of Science Scopus and Embase databases. After screening the articles we selected eligible studies extracted relevant data and calculated the pooled Standardized Mean Difference (SMD). We also conducted a sensitivity analysis to identify sources of heterogeneity and assessed publication bias.
Among the 577 articles initially retrieved we included 5 studies comprising a total of 941 cases with CVDs and 446 controls. All included studies measured FSTL1 levels. The pooled SMD analysis revealed a significant difference in circulating FSTL1 levels between subjects with CVDs and control groups (SMD = 0.853 95% CI = 0.158-1.548 P = 0.016). Heterogeneity was primarily attributed to a single study that measured FSTL1 levels in heart failure patients with preserved ejection fraction. No publication bias was observed.
Our findings demonstrate significantly higher levels of FSTL1 in patients with CVD compared to control subjects. This suggests that FSTL1 may have potential as a diagnostic and prognostic biomarker in CVDs. However further well-designed studies are needed to validate its clinical utility.
Invasive Treatment of Left Main Coronary Artery Disease: From Anatomical Features to Mechanistic Differences
There is debate on the best treatment for significant stenoses of the left main (LM) coronary artery. The available evidence is based on four randomized trials which were either performed specifically to assess patients with LM disease (EXCEL NOBLE PRECOMBAT) or had a significant fraction of patients with this disease pattern (SYNTAX). A meta-analysis revealed no difference in periprocedural and 5-year mortality but demonstrated a significant reduction of spontaneous myocardial infarction (MI) with CABG. Furthermore the recently published SWEDEHEART registry data have shown survival advantage and fewer MACCE with CABG for LM disease after adjustment. In general patients with more severe coronary artery disease (CAD) appear to have a survival advantage with CABG both over PCI and medical therapy (independent of the presence or absence of LM stenosis) which is always associated with a reduction of spontaneous MI in the CABG arm. Since the nomenclature of LM disease does not automatically reflect the complexity of CAD we review the nature of LM disease in this article. We mechanistically assess the treatment effects of PCI and CABG for patients with LM disease which is rarely isolated often distal and mostly associated with varying degrees of single and multi-vessel disease. We conclude that in patients with isolated LM shaft lesions and associated diseases of low complexity the risk of spontaneous MI is lower and PCI may achieve similar long-term outcomes compared to CABG. Thus heart teams are essential for selecting the best treatment option and should focus on assessing infarction risk in chronic CAD.
Heart Disease in Mothers of Children with Duchenne Muscular Dystrophy
Female carriers of Duchenne Muscular Dystrophy (DMD) carry a heterozygous pathogenic variant in the dystrophin gene and can transmit pathogenic variants to their offspring. DMD is an X-linked recessive disease that affects up to 19.8 in every 100000 male births. Those carriers with symptoms can be referred to as women with dystrophinopathy. Even among asymptomatic carriers cardiac involvement can be verified in between 2.5% and 75% through echocardiography. The most commonly affected wall of the left ventricle is the inferolateral with myocardial fibrosis detected by cardiac nuclear resonance. Therefore screening is recommended for these women carriers due to the risk of cardiomyopathy. There is a lack of longitudinal studies on the evolution of these carriers. In this article data on clinical presentation cardiac assessment for female patients with dystrophinopathy and DMD carriers and approaches for these patients are discussed.
Cardiac Amyloidosis in Venezuela: A Pending Issue
Cardiac amyloidosis (CA) is an infiltrative disease characterized by the deposition of misfolded proteins in cardiac interstitial tissue. Interest towards studying this pathology has been growing in the last decade as new epidemiological insights have revealed that it is not as uncommon as previously believed. Likewise advances in non-invasive diagnostic approaches and the identification of molecules that modify its long-term progression even in terms of mortality have also bolstered interest in CA. Despite this global panorama in Venezuela limitations remain regarding the diagnosis of CA partly associated with a lack of knowledge of the disease. Therefore additional efforts are necessary for clinical cardiologists to hone their diagnostic skills regarding this disease as opportune identification is an essential step for its effective management.
A Systematic Review of Economic Evidence of Cardiovascular Interventions in India
Cardiovascular diseases (CVDs) continue to be the primary cause of mortality globally and invariably in India as well. The rapid upsurge in the prevalence of CVDs in India has created a pressing need to promote contemporary sustainable and cost-effective interventions to tackle the CVD burden. This systematic review integrates the research-based evidence of the cost-effectiveness of various interventions that can be adapted to control CVDs in India.
Databases namely PubMed Cochrane Library Embase and Google Scholar were searched for data on the economic evaluation of interventions targeting CVD based on the Indian population for a period of 30 years (1991-2021). Two reviewers assessed the articles for eligibility and data were extracted from the shortlisted articles as per a predefined template including the quantification of methodological aspects.
In total 1249 studies were examined out of which 23 completely met the inclusion criteria for full-text review. A total of 16 studies were based solely on the Indian population while the rest (7) included South Asia/Asia for the intervention of which India was a participant nation. Most of the economic evaluations targeted treatment-based or pharmacological interventions (14) for CVDs. The evaluations were based on Decision-based models (10) Randomized controlled Trials (RCTs) (9) and Observational studies (4). The cost-effectiveness ratio for the included studies exhibited a diverse range due to variations in methodological approaches such as differences in study settings populations and inconsistencies in study design. The mean ICER (Incremental Cost-effectiveness ratio) for primordial and primary preventions was found to be 3073.8 (US $2022) and 17489.9 (US $2022) respectively. Moreover the combined mean value for secondary and tertiary prevention was 2029.6 (US$2022).
The economic evidence of public health interventions are expanding but their focus is restricted towards pharmacological interventions. There is an urgency to emphasize primordial and primary prevention for better outcomes in health economics decision-making. Technology-based avenues for intervention need more exploration in order to cater to a large population like India.
CT-derived Fractional Flow Reserve: How, When, and Where to use this Novel Cardiac Imaging Tool
Fractional flow reserve computed tomography (FFRCT) is a novel imaging modality. It utilizes computational fluid dynamics analysis of coronary blood flow obtained from CCTA images to estimate the decrease in pressure across coronary stenosis during the maximum hyperemia.
The FFRCT can serve as a valuable tool in the assessment of coronary artery disease (CAD). This non-invasive option can be used as an alternative to the invasive fractional Flow Reserve (FFR) evaluation which is presently considered the gold standard for evaluating the physiological significance of coronary stenoses. It can help in several clinical situations including Assessment of Acute and stable chest pain virtual planning for coronary stenting and treatment decision-making.
Although FFRCT has demonstrated potential clinical applications as a non-invasive imaging technique it is also crucial to acknowledge its limitations in clinical practice. As a result it is imperative to meticulously evaluate the advantages and drawbacks of FFRCT individually and contemplate its application in combination with other diagnostic examinations and clinical data.
Assessment of Lifetime Risk for Cardiovascular Disease: Time to Move Forward
Over the past decades there has been a notable increase in the risk of Cardiovascular Disease (CVD) even among younger individuals. Policymakers and the health community have revised CVD prevention programs to include younger people in order to take these new circumstances into account. A variety of CVD risk assessment tools have been developed in the past years with the aim of identifying potential CVD candidates at the population level; however they can hardly discriminate against younger individuals at high risk of CVD.Therefore in addition to the traditional 10-year CVD risk assessment lifetime CVD risk assessment has recently been recommended by the American Heart Association/American College of Cardiology and the European Society of Cardiology prevention guidelines particularly for young individuals. Methodologically the benefits of these lifetime prediction models are the incorporation of left truncation observed in survival curves and the risk of competing events which are not considered equivalent in the common survival analysis. Thus lifetime risk data are easily understandable and can be utilized as a risk communication tool for Public Health surveillance. However given the peculiarities behind these estimates structural harmonization should be conducted in order to create a sex- race-specific tool that is sensitive to accurately identifying individuals who are at high risk of CVD. In this review manuscript we present the most commonly used lifetime CVD risk tools elucidate several methodological and critical points their limitations and the rationale behind their integration into everyday clinical practice.
Volatilome is Inflammasome- and Lipidome-dependent in Ischemic Heart Disease
Ischemic heart disease (IHD) is a pathology of global interest because it is widespread and has high morbidity and mortality. IHD pathophysiology involves local and systemic changes including lipidomic proteomic and inflammasome changes in serum plasma. The modulation in these metabolites is viable in the pre-IHD during the IHD period and after management of IHD in all forms including lifestyle changes and pharmacological and surgical interventions. Therefore these biochemical markers (metabolite changes; lipidome inflammasome proteome) can be used for early prevention treatment strategy assessment of the patient's response to the treatment diagnosis and determination of prognosis. Lipidomic changes are associated with the severity of inflammation and disorder in the lipidome component and correlation is related to disturbance of inflammasome components. Main inflammasome biomarkers that are associated with coronary artery disease progression include IL‐1β Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) and caspase‐1. Meanwhile the main lipidome biomarkers related to coronary artery disease development involve plasmalogen lipids lysophosphatidylethanolamine (LPE) and phosphatidylethanolamine (PE). The hypothesis of this paper is that the changes in the volatile organic compounds associated with inflammasome and lipidome changes in patients with coronary artery disease are various and depend on the severity and risk factor for death from cardiovascular disease in the time span of 10 years. In this paper we explore the potential origin and pathway in which the lipidome and or inflammasome molecules could be excreted in the exhaled air in the form of volatile organic compounds (VOCs).
A Rare Case of Brucellosis with Multivalvular Endocarditis and Complete Heart Block
Brucellosis is a public health concern that affects multiple organs. However cardiovascular problems arise infrequently affecting fewer than 2% of cases typically presenting as endocarditis.
A 50-year male was admitted with low-grade fever night sweats weight loss (13 kg) malaise and generalized weakness for the past 6 months. On clinical examination he was febrile with 39.0°C an average heart rate of 54 bpm and 100/40 mmHg blood pressure. On cardiovascular examination S1 and S2 were soft with pan systolic murmur present in the mitral area and the early diastolic murmur was present in the left third intercostal space. Electrocardiography was suggestive of third-degree heart block with AV dissociation. Transthoracic echocardiography showed mobile vegetations attached to multiple valves- an aortic valve (18.2x11.9 mm) and a mitral valve (2.9x7.5 mm) with perivalvular abscess. He was given oral doxycycline (100 mg B.D.) and rifampicin (600 mg/day); the patient responded but the AV block did not resolve.
This report has drawn attention to multivalvular involvement and cardiac rhythm abnormalities in Brucellosis (in this case A.V. dissociation was present) because early diagnosis and treatment can cause a significant decrease in morbidity as well as mortality by appropriate treatment.
Volatilome: A Novel Tool for Risk Scoring in Ischemic Heart Disease
Developing a novel risk score for accurate assessment of cardiovascular disease (CVD) morbidity and mortality is an urgent need in terms of early prevention and diagnosis and thereafter management particularly of ischemic heart disease. The currently used scores for the evaluation of cardiovascular disease based on the classical risk factors suffer from severe limitations including inaccurate predictive values. Therefore we suggest adding a novel non-classical risk factor including the level of specific exhaled volatile organic compounds that are associated with ischemic heart disease to the SCORE2 and SCORE2-OP algorithms. Adding these non-classical risk factors can be used together with the classical risk factors (gender smoking total cholesterol low-density lipoprotein cholesterol high-density lipoprotein cholesterol diabetes mellitus arterial hypertension ethnicity etc.) to develop a new algorithm and further program to be used widely.
Association between Dietary Vitamin E Intake and the Risk of Hypertension in US Adults
Many studies have shown that Vitamin E (VitE) intake has beneficial effects on human health but the relationship between VitE intake and Blood Pressure (BP) is not well understood. Thus our present study aimed to assess the relationship between VitE intake and hypertension systolic and diastolic BP in US (United States) adults.
We used data from the 2003-2018 National Health and Nutrition Examination Survey (NHANES). Weighted multivariate regression analysis subgroup analysis and Restricted Cubic Splines (RCS) were used to explore the independent associations between VitE intake and hypertension systolic and diastolic BP. A total of 32371 participants were included in this study. The mean VitE intake of participants was 8.50 ± 0.08 mg/d. The prevalence of hypertension in subjects was 37.76% and it decreased with increasing VitE intake quartiles (quartile 1: 40.97% quartile 2: 37.60% quartile 3: 37.47% quartile 4: 35.66%). A significant negative correlation was found between VitE intake and hypertension.
We also observed a significant negative association between VitE intake and systolic BP (model 1: β = -0.11 95% CI: -0.15 ~ -0.07; model 2: β = -0.09 95% CI: -0.12 ~ -0.05; and model 3: β = -0.05 95% CI: -0.10 ~ -0.01). Quartile 2 of dietary VitE intake significantly correlated to a lower diastolic BP compared to the lowest quartile of VitE intake (model 3: β = -0.72 95%CI: -1.26~-0.18).
In US adults VitE intake has not been significantly found to be associated with hypertension but it has been found to exhibit a negative association with both systolic and diastolic BP in US adults.
Identification of Vascular Genes Differentially Expressed in the Brain of Patients with Alzheimer's Disease
Alzheimer's disease (AD) plays a prominent role as the most common form of dementia. Moreover the traditional mechanism of AD does not explain the microvascular damage observed in about 25-30 years between the onset of AD which results in late application treatment that inhibits or delays neurodegeneration.
Our objective was to identify differentially expressed genes in human brain samples associated with vascular disruption in AD.
We analyzed 1633 post-mortem brain samples in the GEO database and after applying clinical and bioinformatic exclusion criteria worked with 581 prefrontal and frontal samples. All datasets were analyzed using GEO2R from NCBI. We identified common genes using the Venny tool and their metabolic relevance associated with AD and the vascular system was analyzed using MetaboAnalyst tools.
Our bioinformatic analysis identified PRKCB MAP2K2 ADCY1 GNA11 GNAQ PRKACB KCNMB4 CALD1 and GNAS as potentially involved in AD pathogenesis. These genes are associated with signal transductions cell death signaling and cytoskeleton suggesting potential modulation of cellular physiology including endoplasmic reticulum and mitochondrial activity.
This study generates hypotheses regarding the roles of novel genes over critical pathways relevant to AD and its relation with vascular dysfunction. These findings suggest potential new targets for further investigation into the pathogenesis of dementia and AD.
Assessment of Early Vascular Aging Ambulatory Score (EVAAs): A Large Population-based External Validation Study
Pulse Wave Velocity (PWV) remains the gold-standard method to assess Early Vascular Aging (EVA) defined by arterial stiffness. However its high cost time-consuming process and need for qualified medical staff shows the importance of identifying alternative methods for the EVA evaluation.
In order to simplify the process of assessing patient's EVA we recently developed the Early Vascular Aging Ambulatory score (EVAAs) a simple tool to predict the risk of EVA. The aim of the present study was the external validation of EVAAs in an independent population.
Eight hundred seventy-nine (46.3% men) patients who were referred to our Hypertension ESH Excellence Center were included in this study. The mean age was 46.43 ± 22.87 years. EVA was evaluated in two different ways. The first assessment included c-f PWV values whereas the second one included EVAAs without the direct measurement of carotid-femoral PWV.
The null hypothesis was that the prediction of EVA based on EVAAs does not present any statistically significant difference compared to the prediction based on the calculation from c-f PWV. Mean squared error (MSE) was used for the assessment of the null hypothesis which was found to be 0.40. The results revealed that the EVAAs shows the probability of EVA with 0.98 sensitivity and 0.75 specificity. The EVAAs present 95% positive predictive value and 92% negative predictive value.
Our study revealed that EVAAs could be as reliable as the carotid-femoral PWV to identify patients with EVA. Hence we hope that EVAAs will be a useful tool in clinical practice.
Neovascularization as a Leading Mechanism of Intraplaque Hemorrhage and Carotid Plaque Destabilization: A Narrative Review
Intraplaque neovascularization (IPN) is considered a leading mechanism causing carotid plaque destabilization. We provide an objective and comprehensive summary of the biology imaging techniques and treatment options related to carotid IPN. Plaque neovascularization has been reported to originate mainly from the adventitial vasa vasorum as a response to hypoxia. The leakage and rupture of neovessels lead to the formation of extravasations and foci of inflammation that destabilize the plaque. Vascular endothelial growth factor and its receptors are key regulators of neoangiogenesis. Neovascularization can be analyzed by advanced computed tomography and magnetic resonance imaging. The basic tools for the ultrasound assessment of IPN are contrast-enhanced ultrasound superb microvascular imaging and ultrasound molecular imaging. A promising direction of research seems to be the identification of patients with advanced plaque neovascularization. A simple test assessing low-velocity flow in the IPN can detect patients at risk of stroke before they experience rupture of defective neovessels and intracerebral embolism. In addition to surgical treatment the stabilization of carotid atherosclerotic plaque can be supported pharmacologically. Statins have the best-documented role in this respect. The ideal moment of intensified therapeutic intervention in patients with previously stable carotid plaque is its increased neovascularization. However the time frame in which intracerebral embolization may occur is unknown and therapeutic intervention may be too late. The formation of deficient neovessels can currently be non-invasively evaluated with ultrasound. Superb microvascular imaging may change the clinical approach for asymptomatic patients at risk of cerebral ischemia.
Burden of Ischemic Heart Diseases among US States from 1990-2019
Ischemic Heart Disease (IHD) is a leading cause of global mortality including in the United States. Understanding the burden of IHD in the United States is crucial for informed decision-making and targeted interventions aimed at reducing morbidity and mortality associated with this leading cause of death. This study aimed to understand the burden of IHD identify gender disparities and risk factors explore the relationship between socioeconomic growth and IHD and analyze risk factor distribution across the states of the United States.
This study utilized data from the Global Burden of Diseases Study 2019 which provided comprehensive information on IHD from 1990 to 2019. Data related to IHD from these years were extracted using a query tool from the Institute for Health Metrics and Evaluation (IHME) website. The study assessed the relationship between IHD and socioeconomic development using the Socio-demographic Index (SDI) and measured the overall impact of IHD using Disability-adjusted Life Years (DALYs) considering premature death and disability. Additionally the study analyzed the burden of IHD attributed to six main risk factors. Data analysis involved comparing prevalence mortality SDI DALYs attributable burden and risk estimation among the states.
Between 1990 and 2019 there was an improvement in socioeconomic development in all states. Age-standardized rates of disease burden for IHD decreased by 50% [ASDR 3278.3 to 1629.4 (95% UI: 1539.9-1712.3) per 100000] with the most significant decline observed in Minnesota. Males had higher burden rates than females in all states and the southeast region had the highest mortality rates. The prevalence of IHD showed a declining trend with approximately 8.9 million cases (95% UI: 8.0 million to 9.8 million) in 2019 representing a 37.1% decrease in the Age-standardized Prevalence Rate (ASPR) from 1990. Metabolic risks were the leading contributors to the disease burden accounting for 50% of cases with Mississippi having the highest attributable risk. Arkansas had the highest attributable risk for high cholesterol and smoking. Conversely Minnesota had the lowest burden of IHD among all the states.
This study highlights variations in the burden of IHD across US states and emphasizes the need for tailored prevention programs to address specific risk factors and gender differences. Understanding the trend in IHD may inform policymakers and healthcare professionals in effectively allocating resources to reduce the burden of IHD and improve national health outcomes.
Bosentan and Pulmonary Hypertension Caused by COVID-19: A Pilot Randomized Double-blind Clinical Study
Coronavirus disease 2019 (COVID-19) has been the biggest pandemic in history with severe complications such as acute respiratory distress syndrome and pulmonary hypertension (PH). An endothelin-1 (ET-1) receptor antagonist such as bosentan may be beneficial in treating elevated ET-1 levels. Hence our study aimed to evaluate the therapeutic effects of bosentan in patients with COVID-19-induced PH.
A single-centre randomized double-blind study involving 72 participants was carried out; 36 received bosentan and the other 36 received a placebo. Pulmonary arterial pressure tricuspid valve pressure gradient and right atrial pressure were measured using echocardiography. The Cox proportional hazards regression model was used to investigate the impact of bosentan and patients' age on mortality during a 6-month follow-up period.
In-hospital mortality was significantly lower in the case group (13%) compared with the control group (33.3%) (P=0.003). Additionally bosentan improved echocardiographic parameters such as systolic pulmonary artery pressure and tricuspid regurgitation gradient (P=0.011 and P=0.003 respectively). Bosentan use was a significant predictor of long-term mortality rates for 600 days [age-adjusted hazard ratio of 5.24 (95% CI 1.34 to 20.46)].
This study provided a mixed perspective on the use of bosentan therapy in patients with COVID-19-related PH. Bosentan effectively reduced in-hospital mortality and improved echocardiographic measures. However the treatment group showed an increased requirement for supplemental oxygen therapy and long-term mortality. Further studies with larger sample sizes are necessary to elucidate the effects of bosentan in PH following COVID-19.