Estudio de prevalencia, conocimiento y control de la hipertensión arterial en barrios vulnerables de Argentina / Prevalence, knowledge and control of arterial hypertension in vulnerable neighborhoods of Argentina: A Cross-sectional Study

Introducción: La hipertensión arterial (HTA) representa el principal factor de riesgo individual, con mayor carga a nivel mundial de enfermedades cardiovasculares (ECV). En nuestro país, algunos trabajos epidemiológicos han mostrado marcadas diferencias en las prevalencias de estos factores de riesgo de acuerdo con la población evaluada. Sin embargo, no hay estudios epidemiológicos de evaluación de factores de riesgo cardiovascular exclusivos referentes a barrios vulnerables con muy bajos recursos económicos, socioculturales y poca accesibilidad a los sistemas de salud. Materiales y métodos: Estudio observacional de corte transversal multicéntrico en habitantes de comunas vulnerables de muy bajos recursos, como asentamientos populares y barrios carenciados con muestreo aleatorizado simple de casas. Se realizaron tomas de presión arterial (PA), medidas antropométricas, así como cuestionarios epidemiológicos, económicos y socioculturales. Se describen los hallazgos: prevalencia, conocimiento y control de la PA en las distintas regiones. Se efectuó una regresión logística para determinar las variables independientes a los resultados principales. Resultados: Se analizaron 989 participantes. La prevalencia de HTA global fue de 48,2%. Un total de 82% tenía un índice de masa corporal (IMC) >25 kg/m2. De estos pacientes, 45,3% tenían menos de seis años de educación. Este último aspecto se asoció a mayor prevalencia de HTA de forma independiente. De los hipertensos, 44% desconocían su padecimiento y solo en 17,2% estaba controlado, asociándose esto a tener obra social (OS) y mayor nivel educativo. Únicamente 24% estaban bajo tratamiento combinado. Conclusión: La prevalencia de HTA en barrios vulnerables es elevada, superando a la de otros estratos sociales con niveles de conocimiento, tratamiento y control de la HTA bajos, similar a otras poblaciones. Se detectó un uso insuficiente de la terapia combinada.

Introduction: Hypertension (HTN) represents the primary individual risk factor, contributing significantly to the global burden of cardiovascular diseases (CVD). In our country, epidemiological research has highlighted substantial variations in the prevalence of these risk factors across different populations. However, there is a lack of epidemiological studies assessing exclusive cardiovascular risk factors within vulnerable neighborhoods characterized by extremely limited economic resources, sociocultural challenges, and inadequate healthcare access. Methods: A multicenter cross-sectional observational study was conducted among individuals residing in economically deprived and marginalized communities, including informal settlements and underprivileged neighborhoods. Simple random sampling of households was employed. Blood pressure measurements, anthropometric assessments, and epidemiological, economic, and sociocultural questionnaires were administered. Results encompass prevalence rates, awareness levels, and blood pressure control across diverse regions. Logistic regression was utilized to identify independent variables influencing primary outcomes. Results: A total of 989 participants were analyzed. The overall prevalence of hypertension was 48.2%. About 82% had a body mass index (BMI) >25. Approximately 45.3% had less than 6 years of formal education. Independent association was established between education levels below 6 years and higher hypertension prevalence Among hypertensive individuals, 44% were unaware of their condition, with only 17.2% achieving control, correlated with having health insurance and a higher educational background. Merely 24% were receiving combined therapy. Conclusion: The prevalence of hypertension within vulnerable neighborhoods is alarmingly high, surpassing rates in other social strata. Knowledge, treatment, and control levels of hypertension are suboptimal, comparable to other populations... (AU)

Type 2 diabetes patients requiring empagliflozin in Southeast of Iran: Frequency and guideline adherence (2022–2023) / Pacientes con diabetes tipo 2 que requieren empagliflozina en el sureste de Irán: frecuencia y cumplimiento de las directrices (2022-2023)

Introduction: Empagliflozin plays a beneficial role in individuals with type 2 diabetes at high risk of cardiovascular complications. This study aimed to assess the prevalence of individuals with type 2 diabetes who required empagliflozin based on clinical guidelines between the years 2022 and 2023. Material and methods: This study was a descriptive-analytical cross-sectional study conducted on a target population of patients with type 2 diabetes. Patient data, including demographic characteristics, smoking status, hypertension, hyperlipidemia, renal insufficiency, retinopathy, and proteinuria, were collected. The indication for prescribing empagliflozin was determined based on the risk of cardiovascular complications. Results: A total of 398 individuals with type 2 diabetes with a mean age of 58.4 years were examined. Overall, 87.4% of the patients had an indication for empagliflozin prescription. The indication for empagliflozin prescription was significantly higher in men, individuals with hyperlipidemia, those over 55 years of age, obese individuals, and smokers. The mean age, body mass index, and triglyceride levels were higher in candidates for empagliflozin prescription. Male candidates for empagliflozin had significantly higher rates of smoking and systolic blood pressure compared to females. Conclusions: The findings of this study demonstrated that a significant percentage of individuals with type 2 diabetes had an indication for empagliflozin prescription based on clinical and laboratory criteria. (AU)

Introducción: La empagliflozina tiene un papel beneficioso en las personas con diabetes tipo 2 con alto riesgo de complicaciones cardiovasculares. Este estudio tuvo como objetivo evaluar la prevalencia de pacientes con este padecimiento que requerían empagliflozina según las guías clínicas entre los años 2022 y 2023. Material y métodos: Se trata de un estudio transversal descriptivo-analítico realizado en una población objetivo de personas con diabetes tipo 2. Se recogieron los datos de los pacientes, incluyendo las características demográficas, el hábito tabáquico, la hipertensión, la hiperlipidemia, la insuficiencia renal, la retinopatía y la proteinuria. La indicación para prescribir empagliflozina se determinó en función del riesgo de complicaciones cardiovasculares. Resultados: Se examinaron un total de 398 individuos con diabetes tipo 2 con una edad media de 58,4 años. En general, 87,4% de estos tenía una indicación para la prescripción de empagliflozina, la cual fue significativamente mayor en los hombres, aquellos con hiperlipidemia, obesidad, los mayores de 55 años y los fumadores. La edad media, el índice de masa corporal y los niveles de triglicéridos fueron mayores en los candidatos a la prescripción de este medicamento. Los candidatos masculinos a este fármaco tenían tasas significativamente más altas de tabaquismo y presión arterial sistólica, en comparación con las mujeres. Conclusiones: Los resultados de este estudio demostraron que un porcentaje significativo de personas con diabetes tipo 2 tenía una indicación para la prescripción de empagliflozina según los criterios clínicos y de laboratorio. (AU)

Renin–angiotensin–aldosterone system blockers effect in chronic kidney disease progression in hypertensive elderly patients without proteinuria: PROERCAN trial / Efecto de los bloqueantes del sistema renina-angiotensina-aldosterona en la progresión de enfermedad renal crónica en pacientes hipertensos añosos sin proteinuria: ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos

Introduction: Evidence about nefroprotective effect with RAAS blockers in elderly patients with chronic kidney disease (CKD) without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria. Materials and methods: Multicenter open-label, randomized controlled clinical trial including patients over 65 year-old with hypertension and CKD stages 3–4 without proteinuria. Patients were randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs and were followed up for three years. Primary outcome is estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcome measures include BP control, renal and cardiovascular events and mortality. Results: 88 patients were included with a mean age of 77.9±6.1 years and a follow up period of 3 years: 40 were randomized to RAAS group and 48 to standard treatment. Ethiology of CKD was: 53 vascular, 16 interstitial and 19 of unknown ethiology. In the RAAS group eGFR slope during follow up was −4.3±1.1ml/min, whereas in the standard treatment group an increase on eGFR was observed after 3 years (+4.6±0.4ml/min), p=0.024. We found no differences in blood pressure control, number of antihypertensive drugs, albuminuria, potassium serum levels, incidence of cardiovascular events nor mortality during the follow up period. Conclusions: In elderly patients without diabetes nor cardiopathy and with non proteinuric CKD the use of RAAS blockers does not show a reduction in CKD progression. The PROERCAN (PROgresión de Enfermedad Renal Crónica en ANcianos) trial (trial registration: NCT03195023). (AU)

Introducción: Actualmente no existe suficiente evidencia sobre el efecto nefroprotector de los bloqueantes del sistema renina-angiotensina-aldosterona (BSRAA) en pacientes añosos con enfermedad renal crónica (ERC) sin proteinuria y sin cardiopatía. El objetivo es evaluar el efecto de los BSRAA en la progresión de la ERC en este grupo poblacional. Métodos: Se trata de un estudio prospectivo, aleatorizado, que compara la eficacia de los BSRAA vs. otros tratamientos antihipertensivos en la progresión renal en personas mayores de 65 años con ERC estadios 3 y 4 e índice albúmina/creatinina<30mg/g. Aleatorización 1:1 BSRAA o tratamiento antihipertensivo estándar. Se recogieron cifras tensionales y parámetros analíticos de un año previo a la aleatorización y durante el seguimiento. Resultados: Se incluyeron 88 pacientes seguidos durante tres años con edad media de 77,9±6,1 años. De estos, se aleatorizaron 40 al grupo BSRAA y 48 al estándar. La etiología de ERC fue: 53 vascular, 16 intersticial y 19 no filiada. En el primer grupo se observó una progresión de la ERC con una caída del filtrado glomerular estimado (FGe) de -4,3±1,1mL/min, mientras que en el grupo estándar un aumento del FGe durante el seguimiento de 4,6±0,4mL/min, p=0,024. No se apreciaron diferencias entre ambos en el control tensional, el número de antihipertensivos, la albuminuria, los niveles de potasio, la incidencia de eventos cardiovasculares ni la mortalidad durante el seguimiento. Conclusiones: En pacientes añosos no diabéticos con ERC no proteinúrica y sin cardiopatía el uso de BSRAA no añade beneficio en la progresión de la ERC. Ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos (PROERCAN) (NCT03195023). (AU)

Asociación entre los marcadores lipídicos en la infancia/ adolescencia y los eventos cardiovasculares en la adultez: una revisión sistemática / Association between lipid markers in childhood/ adolescence and cardiovascular events in adulthood: A systematic review

Introducción. La asociación entre los marcadores lipídicos en la infancia/adolescencia y la incidencia de eventos clínicos cardiovasculares en la adultez está poco explorada en la literatura. El objetivo de esta revisión sistemática fue analizar la evidencia disponible sobre este tema. Población y métodos. Esta revisión sistemática se realizó de acuerdo con las guías PRISMA. Se realizó una búsqueda bibliográfica para detectar los estudios que evaluaron la asociación entre los niveles lipídicos en la edad pediátrica y la incidencia de eventos cardiovasculares en la edad adulta. No hubo restricciones idiomáticas ni geográficas en la búsqueda. Resultados. En total, cinco estudios observacionales (todas cohortes prospectivas) que incluyeron 43 540 pacientes fueron identificados y considerados elegibles para este estudio. Cuatro estudios evaluaron el nivel de triglicéridos; todos reportaron una asociación significativa entre este marcador en la edad pediátrica y los eventos cardiovasculares en la adultez. Un estudio reportó la misma asociación con el nivel de colesterol total, mientras que otro evidenció el valor predictivo de la lipoproteína (a) para el mismo desenlace clínico. Un solo estudio evaluó el colesterol asociado a lipoproteínas de alta densidad (C-HDL), sin encontrar una relación con el punto final de interés. El análisis del colesterol asociado a lipoproteínas de baja densidad (C-LDL) arrojó resultados contradictorios, aunque la asociación fue significativa en los estudios con un tamaño muestral más grande y con un mayor número de eventos durante el seguimiento. Conclusión. Los datos de esta revisión sugieren que las alteraciones de los marcadores lipídicos en la infancia y la adolescencia se asocian con un mayor riesgo cardiovascular en la adultez temprana y media.

Introduction. The association between lipid markers in childhood/adolescence and the incidence of clinical cardiovascular events in adulthood has been little explored in the bibliography. The objective of this systematic review was to analyze available evidence on this topic. Population and methods. This systematic review was conducted in accordance with the PRISMA guidelines. A comprehensive bibliographic search was done to find studies assessing the association between lipid levels in childhood and the incidence of cardiovascular events in adulthood. There were no language or geographic restrictions. Results. A total of 5 observational studies (all prospective cohorts) including 43 540 patients were identified and considered eligible for this study. Four studies assessed triglyceride levels; all reported a significant association between this lipid marker in childhood and cardiovascular events in adulthood. A study reported the same association with total cholesterol level, while another showed the predictive value of lipoprotein (a) for the same clinical outcome. Only one study assessed high-density lipoprotein cholesterol (HDL-C), but it did not find an association with the endpoint of interest. The analysis of lowdensity lipoprotein cholesterol (LDL-C) showed contradictory results, although the association was significant in the studies with a larger sample size and a higher number of events during follow-up. Conclusion. According to this review, alterations in lipid markers in childhood and adolescence are associated with a higher cardiovascular risk in early and middle adulthood.

Higher ratio of plasma omega-6/omega-3 fatty acids is associated with greater risk of all-cause, cancer, and cardiovascular mortality: A population-based cohort study in UK Biobank.

Background: Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality. Methods: We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors. Results: Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15-38%) higher total mortality, 14% (95% CI, 0-31%) higher cancer mortality, and 31% (95% CI, 10-55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects. Conclusions: Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality. Funding: Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Fatty acids play an essential role in health. Studies have shown that diets high in omega-3 fatty acids found in foods like fish, fish oil, flaxseed and walnuts may be beneficial. Yet some studies have raised concern that too many omega-6 fatty acids in Western diets rich in vegetable oils may be harmful. Some scientists have proposed that the balance of omega-3 and omega-6 in diets is vital to health. They hypothesize that a higher omega-6 to omega-3 fatty acids ratio is detrimental. But, proving that a higher ratio of omega-6 to omega-3 fatty acids is harmful has been difficult. Many studies have found conflicting results. Scientists have struggled to accurately measure fatty acid intake as tracking an individual's dietary intake is challenging and self-reported dietary intake may be incorrect. Additionally, scientists must follow individuals for many years to determine if a high ratio of omega-6 to omega-3 is linked with cancer, heart disease, or death. But, measuring circulating fatty acids in an individual's blood may offer an easier and more reliable approach to studying the health impacts of these vital nutrients. Zhang et al. show that people with higher ratios of omega-6 to omega-3 fatty acids in their blood are at greater risk of dying from cancer, heart disease, or any cause than those with lower ratios. The experiments measured omega-6 and omega-3 fatty acid levels in more than 85,000 participants in the UK Biobank who scientists followed for an average of about 13 years. Participants with the highest ratios of omega-6 to omega-3 fatty acids were 26% more likely to die of any cause, 14% more likely to die of cancer, and 31% more likely to die of heart disease than individuals with the lowest ratios. Individually, high levels of omega-6 fatty acids and high levels of omega-3 fatty acids were both associated with a lower risk of dying. But the protective effects of omega-3 were greater. For example, individuals with the highest levels of omega-6 fatty acids were 23% less likely to die of any cause. By comparison, those with the highest levels of omega-3s were 31% less likely to die. The stronger protection offered by high levels of omega-3s likely explains why having a high ratio of omega-6s to omega-3s was linked to harm. Both are protective. But the protection provided by omega-3s is more robust. The experiments support dietary interventions to raise omega-3 fatty acid levels and maintain a low omega-6 to omega-3 fatty acid ratio to prevent early deaths from cancer, heart disease or other causes. More research is needed to understand the impact of dietary fatty acid intake on other diseases and how genetics may influence the health impact of fatty acids.

Cardiovascular disease risk assessment through sensing the circulating microbiome with perovskite quantum dots leveraging deep learning models for bacterial species selection.

Perovskite quantum dots (PQDs) are novel nanomaterials wherein perovskites are used to formulate quantum dots (QDs). The present study utilizes the excellent fluorescence quantum yields of these nanomaterials to detect 16S rRNA of circulating microbiome for risk assessment of cardiovascular diseases (CVDs). A long short-term memory (LSTM) deep learning model was used to find the association of the circulating bacterial species with CVD risk, which showed the abundance of three different bacterial species (Bauldia litoralis (BL), Hymenobacter properus (HYM), and Virgisporangium myanmarense (VIG)). The observations suggested that the developed nano-sensor provides high sensitivity, selectivity, and applicability. The observed sensitivities for Bauldia litoralis, Hymenobacter properus, and Virgisporangium myanmarense were 0.606, 0.300, and 0.281 fg, respectively. The developed sensor eliminates the need for labelling, amplification, quantification, and biochemical assessments, which are more labour-intensive, time-consuming, and less reliable. Due to the rapid detection time, user-friendly nature, and stability, the proposed method has a significant advantage in facilitating point-of-care testing of CVDs in the future. This may also facilitate easy integration of the approach into various healthcare settings, making it accessible and valuable for resource-constrained environments.

Association between atherosclerosis and height loss among older individuals.

Atherosclerosis and height loss are each reportedly associated with cardiovascular disease. However, no studies have found an association between atherosclerosis and height loss. A retrospective study of 2435 individuals aged 60-89 years who underwent annual health check-ups was conducted. Atherosclerosis was defined as carotid intima-media thickness (CIMT) ≥ 1.1 mm. Height loss was defined as being in the highest quintile of height decrease per year, as in our previous studies. Among study participants, 555 were diagnosed as having atherosclerosis. Independent of known cardiovascular risk factors, atherosclerosis was positively associated with height loss. The adjusted odds ratio (OR) was 1.46 (95% confidence interval, 1.15, 1.83). Essentially the same associations were observed for men and women. The adjusted OR (95% CI) was 1.43 (1.01, 2.04) for men and 1.46 (1.07, 1.99) for women. Among older individuals, atherosclerosis is associated with height loss. This result can help clarify the mechanism underlying the association between height loss and cardiovascular disease.

Associations between sleep duration, sleep disturbance and cardiovascular disease biomarkers among adults in the United States.

BACKGROUND: Sleep problems are associated with abnormal cardiovascular biomarkers and an increased risk of cardiovascular diseases (CVDs). However, studies investigating associations between sleep problems and CVD biomarkers have reported conflicting findings. This study examined the associations between sleep problems and CVD biomarkers in the United States. METHODS: Data were from the National Health and Nutrition Examination Survey (NHANES) (2007-2018) and analyses were restricted to adults ≥ 20 years (n = 23,749). CVD biomarkers [C-reactive Protein (CRP), low-density lipoproteins, high-density lipoproteins (HDL), triglycerides, insulin, glycosylated hemoglobin (HbA1c), and fasting blood glucose] were categorized as abnormal or normal using standardized cut-off points. Sleep problems were assessed by sleep duration (short [≤ 6 h], long [≥ 9 h], and recommended [> 6 to < 9 h) and self-reported sleep disturbance (yes, no). Multivariable logistic regression models explored the associations between sleep duration, sleep disturbance, and CVD biomarkers adjusting for sociodemographic characteristics and lifestyle behaviors. RESULTS: The mean sleep duration was 7.1 ± 1.5 h and 25.1% of participants reported sleep disturbances. Compared to participants with the recommended sleep duration, those with short sleep duration had higher odds of abnormal levels of HDL (adjusted odds ratio [aOR] = 1.20, 95% confidence interval [CI] = 1.05-1.39), CRP (aOR = 3.08, 95% CI = 1.18-8.05), HbA1c (aOR = 1.25, 95% CI = 1.05-1.49), and insulin (aOR = 1.24, 95% CI = 1.03-1.51). Long sleep duration was associated with increased odds of abnormal CRP (aOR = 6.12, 95% CI = 2.19-17.15), HbA1c (aOR = 1.54, 95% CI = 1.09-2.17), and blood glucose levels (aOR = 1.45, 95% CI = 1.07-1.95). Sleep disturbance predicted abnormal triglyceride (aOR = 1.18, 95% CI = 1.01-1.37) and blood glucose levels (aOR = 1.24, 95% CI = 1.04-1.49). CONCLUSION: Short and long sleep durations were positively associated with abnormal CRP, HDL, HbA1c, blood glucose, and insulin levels, while sleep disturbance was associated with abnormal triglyceride and blood glucose levels. Since sleep is a modifiable factor, adopting healthy sleeping habits may create a balanced metabolism and reduce the risk of developing a CVD. Our study may provide insights into the relationship between sleep duration, sleep disturbance, and CVD risk.

Triglyceride-glucose-waist circumference index predicts the incidence of cardiovascular disease in Korean populations: competing risk analysis of an 18-year prospective study.

BACKGROUND: The triglyceride and glucose-waist circumference (TyG-WC) index demonstrated a strong association with insulin resistance, especially in Asian population. However, evidence on the association between TyG-WC index and the occurrence of cardiovascular disease (CVD) is limited. This study aimed to verify association between the TyG-WC index and the occurrence of CVD by considering all-cause mortality as a competing risk. METHODS: The study included 7482 participants divided into four groups based on the TyG-WC index quartiles. Kaplan-Meier curves illustrated cumulative incidence rates of CVD and all-cause mortality during the follow-up period. Log-rank tests determined group differences. The Cox proportional hazard spline curve demonstrates the dose-dependent relationship between the TyG-WC index and incident CVD. Modified Cox regression (Fine and Gray) estimated hazard ratios (HRs) with 95% CIs for incident CVD, treating death as a competing risk. Death event after incident CVD was excluded from the death count. RESULTS: During the median 15.94 year of follow-up period, a total of 691 (9.24%) new-onset CVD cases and 562 (7.51%) all-cause mortality cases were confirmed. Cox proportional hazard spline curves suggested that TyG-WC index exhibited a dose-dependent positive correlation with incident CVD. The cumulative incidence rate of CVD was significantly higher in the groups with higher TyG-WC index quartiles in Kaplan-Meier curves. The adjusted HR (95% CI) for incident CVD in Q2-Q4, compared with Q1, was 1.47 (1.12-1.93), 1.91 (1.44-2.54) and 2.24 (1.63-3.07), respectively. There was no significant association between TyG-WC index and all-cause mortality. Specifically, angina and stroke were significantly associated with the TyG-WC index, in contrast to myocardial infarction and peripheral artery disease. CONCLUSIONS: The TyG-WC index was positively associated with incident CVD even considering all-cause mortality as a competing risk. Therefore, TyG-WC index may be a valuable marker for predicting the occurrence of CVD.

RhoA/rho kinase pathway activation in age-associated endothelial cell dysfunction and thrombosis.

The small GTPase RhoA and the downstream Rho kinase (ROCK) regulate several cell functions and pathological processes in the vascular system that contribute to the age-dependent risk of cardiovascular disease, including endothelial dysfunction, excessive permeability, inflammation, impaired angiogenesis, abnormal vasoconstriction, decreased nitric oxide production and apoptosis. Frailty is a loss of physiological reserve and adaptive capacity with advanced age and is accompanied by a pro-inflammatory and pro-oxidative state that promotes vascular dysfunction and thrombosis. This review summarises the role of the RhoA/Rho kinase signalling pathway in endothelial dysfunction, the acquisition of the pro-thrombotic state and vascular ageing. We also discuss the possible role of RhoA/Rho kinase signalling as a promising therapeutic target for the prevention and treatment of age-related cardiovascular disease.

Role of Treg cell subsets in cardiovascular disease pathogenesis and potential therapeutic targets.

In the genesis and progression of cardiovascular diseases involving both innate and adaptive immune responses, inflammation plays a pivotal and dual role. Studies in experimental animals indicate that certain immune responses are protective, while others exacerbate the disease. T-helper (Th) 1 cell immune responses are recognized as key drivers of inflammatory progression in cardiovascular diseases. Consequently, the CD4+CD25+FOXP3+ regulatory T cells (Tregs) are gaining increasing attention for their roles in inflammation and immune regulation. Given the critical role of Tregs in maintaining immune-inflammatory balance and homeostasis, abnormalities in their generation or function might lead to aberrant immune responses, thereby initiating pathological changes. Numerous preclinical studies and clinical trials have unveiled the central role of Tregs in cardiovascular diseases, such as atherosclerosis. Here, we review the roles and mechanisms of Treg subsets in cardiovascular conditions like atherosclerosis, hypertension, myocardial infarction and remodeling, myocarditis, dilated cardiomyopathy, and heart failure. While the precise molecular mechanisms of Tregs in cardiac protection remain elusive, therapeutic strategies targeting Tregs present a promising new direction for the prevention and treatment of cardiovascular diseases.

The advent of RNA-based therapeutics for metabolic syndrome and associated conditions: a comprehensive review of the literature.

Metabolic syndrome (MetS) is a prevalent and intricate health condition affecting a significant global population, characterized by a cluster of metabolic and hormonal disorders disrupting lipid and glucose metabolism pathways. Clinical manifestations encompass obesity, dyslipidemia, insulin resistance, and hypertension, contributing to heightened risks of diabetes and cardiovascular diseases. Existing medications often fall short in addressing the syndrome's multifaceted nature, leading to suboptimal treatment outcomes and potential long-term health risks. This scenario underscores the pressing need for innovative therapeutic approaches in MetS management. RNA-based treatments, employing small interfering RNAs (siRNAs), microRNAs (miRNAs), and antisense oligonucleotides (ASOs), emerge as promising strategies to target underlying biological abnormalities. However, a summary of research available on the role of RNA-based therapeutics in MetS and related co-morbidities is limited. Murine models and human studies have been separately interrogated to determine whether there have been recent advancements in RNA-based therapeutics to offer a comprehensive understanding of treatment available for MetS. In a narrative fashion, we searched for relevant articles pertaining to MetS co-morbidities such as cardiovascular disease, fatty liver disease, dementia, colorectal cancer, and endocrine abnormalities. We emphasize the urgency of exploring novel therapeutic avenues to address the intricate pathophysiology of MetS and underscore the potential of RNA-based treatments, coupled with advanced delivery systems, as a transformative approach for achieving more comprehensive and efficacious outcomes in MetS patients.

Serum albumin and cardiovascular disease: a Mendelian randomization study.

BACKGROUND: An increasing body of evidence suggests that serum albumin levels play a role in cardiovascular diseases. However, the specific causal relationship between serum albumin levels and cardiovascular disease remains partially unknown. METHODS: Mendelian randomization (MR) was employed in this study to examine potential causal relationships between instrumental variables and cardiovascular diseases. Specifically, we utilized genetic variants of serum albumin levels within the reference range as our instrumental variables. To acquire data on genetic associations with cardiovascular diseases, we sourced information from renowned genome-wide association studies such as UK BioBank, EMBL-EBI, and FinnGen. Notably, our study leveraged summary statistics from large cohorts that have been previously described. RESULTS: We explored the association between serum albumin levels and various conditions, including heart failure (HF), venous thromboembolism (VTE), stroke, atrial fibrillation (AF), coronary artery disease (CAD), type 2 diabetes (T2DM), and pulmonary heart disease (PHD). Genetically predicted serum albumin levels were associated with PHD (odds ratio = 0.737, 95% CI = 0.622 - 0.874, P < 0.001), AF (odds ratio = 0.922, 95% CI = 0.870 - 0.977, P = 0.006), VTE (odds ratio = 0.993, 95% CI = 0.991 - 0.995, P < 0.001), and Stroke (odds ratio = 0.997, 95% CI = 0.995 - 0.999, P = 0.002). However, genetically predicted serum albumin level traits were not associated with HF, CAD and T2DM. CONCLUSION: Our study demonstrates a significant association between serum albumin levels and cardiovascular disease, underscoring the crucial role of low serum albumin as a predictive factor in patients with cardiovascular disease.

Reproductive factors and risk of cardiovascular diseases and all-cause and cardiovascular mortality in American women: NHANES 2003-2018.

BACKGROUND: The evidence regarding the association of reproductive factors with cardiovascular diseases (CVDs) is limited. AIMS: To investigate the relationship of reproductive factors with the risk of CVDs, as well as all-cause and cardiovascular mortality. METHODS: This study included 16,404 adults with reproductive factors from the National Health and Nutrition Examination Survey (NHANES) and followed up until 31 December 2019. Logistic models and restricted cubic spline models were used to assess the association of reproductive factors with CVDs. COX proportional hazards models and restricted cubic spline models, with adjustment for potential confounding, were employed to analyze the relation between reproductive factors and cardiovascular and all-cause death. RESULTS: There is a nonlinear relationship between age at menarche and CVDs. Age at menopause ≤ 11(OR 1.36, 95% CI 1.10-1.69) was associated with an increased risk of CVDs compared to ages 12-13 years. Age at Menopause ≤ 44 (OR 1.69, 95% CI 1.40-2.03) was associated with increased CVDs compared to age 35-49 years. Number of pregnancies ≥ 5(OR 1.26, 95% CI 1.02-1.55) was associated with an increased risk of CVDs compared to one pregnancy. In continuous variable COX regression models, a later age at menopause (HR 0.98, 95% CI 0.97-0.99) and a longer reproductive lifespan (HR 0.98, 95% CI 0.97-0.99) were associated with a decreased risk of all-cause death. A later age at menopause (HR 0.98, 95% CI 0.97-0.99) and a longer reproductive lifespan (HR 0.98, 95% CI 0.97-0.99) were associated with a decreased risk of cardiac death. CONCLUSIONS: Female reproductive factors are significant risk factors for CVDs American women.

Bidirectional relation between dipeptidyl peptidase 4 and angiotensin II type I receptor signaling.

Cardiometabolic diseases are often associated with heightened levels of angiotensin II (Ang II), which accounts for the observed oxidative stress, inflammation, and fibrosis. Accumulating evidence indicates a parallel upregulation of dipeptidyl dipeptidase 4 (DPP4) activity in cardiometabolic diseases, with its inhibition shown to mitigate oxidative stress, inflammation, and fibrosis. These findings highlight an overlap between the pathophysiological mechanisms used by Ang II and DPP4. Recent evidence demonstrates that targeted inhibition of DPP4 prevents the rise in Ang II and its associated molecules in experimental models of cardiometabolic diseases. Similarly, inhibitors of the angiotensin I-converting enzyme (ACE) or Ang II type 1 receptor (AT1R) blockers downregulate DPP4 activity, establishing a bidirectional relationship between DPP4 and Ang II. Here, we discuss the current evidence supporting the cross talk between Ang II and DPP4, along with the potential mechanisms promoting this cross regulation. A comprehensive analysis of this bidirectional relationship across tissues will advance our understanding of how DPP4 and Ang II collectively promote the development and progression of cardiometabolic diseases.

Missed postoperative metabolic acidosis associated with sodium-glucose transporter 2 inhibitors in cardiac surgery patients: a retrospective analysis.

The increasing use of sodium glucose transporter 2 inhibitors (SGLT2i) for treating cardiovascular (CV) diseases and type 2 diabetes (T2D) is accompanied by a rise in euglycemic diabetic ketoacidosis occurrences in cardiac surgery patients. Patients undergoing cardiac surgery, due to their pre-existing CV disease which often requires SGLT2i prescriptions, face an increased risk of postoperative metabolic acidosis (MA) or ketoacidosis (KA) associated with SGLT2i, compounded by fasting and surgical stress. The primary aim of this study is to quantify the incidence of SGLT2i-related postoperative MA or KA and to identify related risk factors. We analyzed data retrospectively of 823 cardiac surgery patients, including 46 treated with SGLT2i from November 2019 to October 2022. Among 46 final cohorts treated preoperatively with SGLT2i, 29 (63%) developed postoperative metabolic complications. Of these 46 patients, stratified into two categories based on postoperative laboratory findings, risk factor analysis were conducted and compared. Analysis indicated a prescription duration over one week significantly elevated the risk of complications (Unadjusted OR, 11.7; p = 0.032*; Adjusted OR, 31.58; p = 0.014*). A subgroup analysis showed that a cardiopulmonary bypass duration of 60 min or less significantly raises the risk of SGLT2i-related postoperative MA in patients with a sufficient prescription duration. We omitted the term "diabetes" in describing complications related to SGLT2i, as these issues are not exclusive to T2D patients. Awareness of SGLT2i-related postoperative MA or KA can help clinicians distinguish between non-life-threatening conditions and severe causes, thereby preventing unnecessary tests and ensuring best practice.

The Senescent Heart-"Age Doth Wither Its Infinite Variety".

Cardiovascular diseases are a leading cause of morbidity and mortality world-wide. While many factors like smoking, hypertension, diabetes, dyslipidaemia, a sedentary lifestyle, and genetic factors can predispose to cardiovascular diseases, the natural process of aging is by itself a major determinant of the risk. Cardiac aging is marked by a conglomerate of cellular and molecular changes, exacerbated by age-driven decline in cardiac regeneration capacity. Although the phenotypes of cardiac aging are well characterised, the underlying molecular mechanisms are far less explored. Recent advances unequivocally link cardiovascular aging to the dysregulation of critical signalling pathways in cardiac fibroblasts, which compromises the critical role of these cells in maintaining the structural and functional integrity of the myocardium. Clearly, the identification of cardiac fibroblast-specific factors and mechanisms that regulate cardiac fibroblast function in the senescent myocardium is of immense importance. In this regard, recent studies show that Discoidin domain receptor 2 (DDR2), a collagen-activated receptor tyrosine kinase predominantly located in cardiac fibroblasts, has an obligate role in cardiac fibroblast function and cardiovascular fibrosis. Incisive studies on the molecular basis of cardiovascular aging and dysregulated fibroblast function in the senescent heart would pave the way for effective strategies to mitigate cardiovascular diseases in a rapidly growing elderly population.

Serum Induces the Subunit-Specific Activation of NF-κB in Proliferating Human Cardiac Stem Cells.

Cardiovascular diseases (CVDs) are often linked to ageing and are the major cause of death worldwide. The declined proliferation of adult stem cells in the heart often impedes its regenerative potential. Thus, an investigation of the proliferative potential of adult human cardiac stem cells (hCSCs) might be of great interest for improving cell-based treatments of cardiovascular diseases. The application of human blood serum was already shown to enhance hCSC proliferation and reduce senescence. Here, the underlying signalling pathways of serum-mediated hCSC proliferation were studied. We are the first to demonstrate the involvement of the transcription factor NF-κB in the serum-mediated proliferative response of hCSCs by utilizing the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). RNA-Sequencing (RNA-Seq) revealed ATF6B, COX5B, and TNFRSF14 as potential targets of NF-κB that are involved in serum-induced hCSC proliferation.

Non-Coding RNA-Targeted Therapy: A State-of-the-Art Review.

The use of non-coding RNAs (ncRNAs) as drug targets is being researched due to their discovery and their role in disease. Targeting ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), is an attractive approach for treating various diseases, such as cardiovascular disease and cancer. This seminar discusses the current status of ncRNAs as therapeutic targets in different pathological conditions. Regarding miRNA-based drugs, this approach has made significant progress in preclinical and clinical testing for cardiovascular diseases, where the limitations of conventional pharmacotherapy are evident. The challenges of miRNA-based drugs, including specificity, delivery, and tolerability, will be discussed. New approaches to improve their success will be explored. Furthermore, it extensively discusses the potential development of targeted therapies for cardiovascular disease. Finally, this document reports on the recent advances in identifying and characterizing microRNAs, manipulating them, and translating them into clinical applications. It also addresses the challenges and perspectives towards clinical application.

Online application for the diagnosis of atherosclerosis by six genes.

BACKGROUND: Atherosclerosis (AS) is a primary contributor to cardiovascular disease, leading to significant global mortality rates. Developing effective diagnostic indicators and models for AS holds the potential to substantially reduce the fatalities and disabilities associated with cardiovascular disease. Blood sample analysis has emerged as a promising avenue for facilitating diagnosis and assessing disease prognosis. Nonetheless, it lacks an accurate model or tool for AS diagnosis. Hence, the principal objective of this study is to develop a convenient, simple, and accurate model for the early detection of AS. METHODS: We downloaded the expression data of blood samples from GEO databases. By dividing the mean values of housekeeping genes (meanHGs) and applying the comBat function, we aimed to reduce the batch effect. After separating the datasets into training, evaluation, and testing sets, we applied differential expression analyses (DEA) between AS and control samples from the training dataset. Then, a gradient-boosting model was used to evaluate the importance of genes and identify the hub genes. Using different machine learning algorithms, we constructed a prediction model with the highest accuracy in the testing dataset. Finally, we make the machine learning models publicly accessible by shiny app construction. RESULTS: Seven datasets (GSE9874, GSE12288, GSE20129, GSE23746, GSE27034, GSE90074, and GSE202625), including 403 samples with AS and 325 healthy subjects, were obtained by comprehensive searching and filtering by specific requirements. The batch effect was successfully removed by dividing the meanHGs and applying the comBat function. 331 genes were found to be related to atherosclerosis by the DEA analysis between AS and health samples. The top 6 genes with the highest importance values from the gradient boosting model were identified. Out of the seven machine learning algorithms tested, the random forest model exhibited the most impressive performance in the testing datasets, achieving an accuracy exceeding 0.8. While the batch effect reduction analysis in our study could have contributed to the increased accuracy values, our comparison results further highlight the superiority of our model over the genes provided in published studies. This underscores the effectiveness of our approach in delivering superior predictive performance. The machine-learning models were then uploaded to the Shiny app's server, making it easy for users to distinguish AS samples from normal samples. CONCLUSIONS: A prognostic Shiny application, built upon six potential atherosclerosis-associated genes, has been developed, offering an accurate diagnosis of atherosclerosis.