Perfil lipídico e fatores de risco para doenças cardiovasculares em idosos acompanhados na atenção primária à saúde / Lipid profile and risk factors for cardiovascular diseases in older people seen in primary health care / Perfil lipídico y factores de riesgo de enfermedades cardiovasculares en ancianos seguidos en la atención primaria de salud

Introdução: As dislipidemias estão entre os fatores de riscos mais importantes para o desenvolvimento de doenças cardiovasculares (DCV), além de estarem relacionadas a outras patologias que predispõem às DCV. Em função da elevada prevalência e da incidência de complicações associadas à cronicidade da doença, as dislipidemias representam elevados custos ao setor da saúde e da previdência social. Diante disso, ressalta-se a importância do Sistema Único de Saúde, representado pela Atenção Primária à Saúde (APS), em prover práticas de prevenção, diagnóstico e acompanhamento dos pacientes dislipidêmicos, a fim de desonerar o sistema financeiro e promover o envelhecimento saudável. Objetivo: Descrever a prevalência de perfil lipídico alterado entre os idosos. Além disso, pretendeu-se caracterizar a amostra quanto aos aspectos sociodemográficos, de saúde e de comportamento, bem como analisar os fatores associados à distribuição do perfil lipídico alterado e às características da amostra. Métodos: Estudo transversal com dados secundários, obtidos de agosto de 2021 a julho de 2022, tendo como população pacientes idosos em acompanhamento na APS do município de Marau (RS). Todos os dados foram coletados dos prontuários eletrônicos da rede de APS e, após dupla digitação e validação dos dados, a amostra foi caracterizada por meio de estatística descritiva. Foi calculada a prevalência de perfil lipídico alterado com intervalo de confiança de 95% (IC95%) e foi verificada sua distribuição conforme as variáveis de exposição, empregando-se o teste do χ2 e admitindo-se erro tipo I de 5%. Resultados: A prevalência de dislipidemia proporcional entre os sexos foi maior no feminino (33%). A cor de pele predominante foi a branca (76,7%). Cerca de 20% dos pacientes apresentavam colesterol total, colesterol HDL-c e triglicerídeos alterados, enquanto cerca de 15% apresentavam o colesterol HDL-c anormal. Constatou-se que os pacientes dislipidêmicos apresentam mais diabetes e hipertensão em relação aos não dislipidêmicos, ocorrendo a sinergia de fatores de risco para as DCV. Conclusões: A caracterização exercida neste estudo serve de base científica para a compreensão da realidade local e, também, para o direcionamento de políticas públicas na atenção primária que atuem de forma efetiva na prevenção e no controle das dislipidemias e demais fatores de risco cardiovascular.

Introduction: Dyslipidemias are among the most important risk factors for the development of cardiovascular diseases (CVD), in addition to being related to other pathologies that predispose to CVD. Because of the high prevalence and incidence of complications associated with the chronicity of the disease, dyslipidemias represent high costs for the health and social security sector. This highlights the importance of the Unified Health System, represented by primary health care (PHC), in providing prevention, diagnosis and follow-up practices for dyslipidemic patients to relieve the financial system and promote healthy aging. Objective: The study aimed to describe the prevalence of altered lipid profile among older people. In addition, we sought to characterize the sample in terms of sociodemographic, health and behavioral aspects, as well as to analyze the factors associated with the distribution of the altered lipid profile and the characteristics of the sample. Methods: We conducted a cross-sectional study with secondary data, from August 2021 to July 2022, with older patients being followed up at the PHC in the city of Marau (RS) as the study population. All data were collected from the electronic medical records of the PHC network, and after double-typing and validation, the sample was characterized using descriptive statistics. The prevalence of altered lipid profile was determined with a 95% confidence interval (95%CI), and its distribution was verified according to the exposure variables, using the chi-square test and a type I error of 5%. Results: The prevalence of proportional dyslipidemia between sexes was higher in females (33%). The predominant skin color was white (76.7%). About 20% of the patients had altered total cholesterol, HDL-C and triglycerides, while about 15% had abnormal HDL-C. It was found that more dyslipidemic patients had diabetes and hypertension than non-dyslipidemic patients, with a synergy of risk factors for CVD. Conclusions: The characterization carried out in this study serves as a scientific basis for understanding the local reality and also for directing public policies in PHC that act effectively in the prevention and control of dyslipidemia and other cardiovascular risk factors.

Introducción: las dislipidemias se encuentran entre los factores de riesgo más importantes para el desarrollo de enfermedades cardiovasculares (ECV), además de estar relacionadas con otras patologías que predisponen a ECV. Debido a la alta prevalencia e incidencia de complicaciones asociadas a la cronicidad de la enfermedad, las dislipidemias representan altos costos para los sectores de salud y seguridad social. Frente a eso, se destaca la importancia del Sistema Único de Salud, representado por la Atención Primaria de Salud (APS), en la provisión de prácticas de prevención, diagnóstico y seguimiento de pacientes dislipidémicos, con el fin de descongestionar el sistema financiero y promover el envejecimiento saludable. Objetivo: El estudio tiene como objetivo describir la prevalencia del perfil lipídico alterado entre los ancianos. Además, se pretende caracterizar la muestra en cuanto a aspectos sociodemográficos, de salud y conductuales, así como analizar los factores asociados a la distribución del perfil lipídico alterado y las características de la muestra. Métodos: estudio transversal con datos secundarios, de agosto de 2021 a julio de 2022, con pacientes ancianos en seguimiento en la APS del municipio de Marau (RS) como población. Todos los datos fueron recolectados de la historia clínica electrónica de la red de la APS y, luego de doble digitación y validación, la muestra fue caracterizada mediante estadística descriptiva. Se calculó la prevalencia de perfil lipídico alterado con un intervalo de confianza del 95% (IC95%) y se verificó su distribución según las variables de exposición, utilizando la prueba de chi-cuadrado y admitiendo un error tipo I del 5%. Resultados: la prevalencia de dislipidemia proporcional entre sexos fue mayor en el sexo femenino (33%). El color de piel predominante fue el blanco (76,7%). Alrededor del 20% de los pacientes tenían colesterol total, colesterol HDL-C y triglicéridos alterados, mientras que alrededor del 15% tenían colesterol HDL-C anormal. Se encontró que los pacientes dislipidémicos tienen más diabetes e hipertensión que los pacientes no dislipidémicos, con una sinergia de factores de riesgo para ECV. Conclusiones: la caracterización realizada en este estudio sirve de base científica para comprender la realidad local y también para orientar políticas públicas en atención primaria que actúen de manera efectiva en la prevención y control de la dislipidemia y otros factores de riesgo cardiovascular.

Instrumentos de avaliação multidimensional de fragilidade para uso no cuidado de idosos com doença cardiovascular / Multidimensional frailty assessment tools for use in the care of older adults with cardiovascular disease / Instrumentos de evaluación multidimensional de la fragilidad en la atención de adultos mayores con enfermedad cardiovascular

Objetivo: identificar quais os instrumentos disponíveis para avaliação multidimensional da fragilidade em idosos com doença cardiovascular, potencialmente aplicáveis durante a realização do Processo de Enfermagem. Método: revisão sistemática conduzida em oito bases de dados/portais, para identificação de estudos que apresentassem instrumentos multidimensionais de avaliação de fragilidade em idosos com doença cardiovascular e que fossem aplicáveis ao processo de enfermagem. Resultados: foram incluídos 19 instrumentos multidimensionais. O Brief Frailty Index for Coronary Artery Disease foi desenvolvido para uso no cuidado cardiovascular de idosos. O Frailty Index for Adults e o Maastricht Frailty Screening Tool for Hospitalized Patients foram desenvolvidos para uso no Processo de Enfermagem. Conclusão: apesar de apenas um instrumento ter sido desenvolvido para o idosos com doença cardiovascular e apenas dois serem aplicáveis ao processo de enfermagem, a maioria deles tem potencial de adaptação e validação para uso nesta população durante a avaliação de enfermagem.

Objective: to identify which tools are available for multidimensional frailty assessment of older adult with cardiovascular disease and which are potentially applicable during the Nursing Process. Method: a systematic review conducted in eight databases/portals to identify studies that presented multidimensional frailty assessment tools for older adult with cardiovascular disease and that were applicable to the nursing process. Results: a total of 19 multidimensional tools were included. The Brief Frailty Index for Coronary Artery Disease was developed for use in the cardiovascular care of older adult. The Frailty Index for Adults and the Maastricht Frailty Screening Tool for Hospitalized Patients were developed for use in the Nursing Process. Conclusion: although only one tool was developed for older adults with cardiovascular disease and only two are applicable to the nursing process, most of them have the potential to be adapted and validated for use in this population during nursing assessment.

Objetivo: identificar qué instrumentos están disponibles para la evaluación multidimensional de la fragilidad en personas mayores con enfermedad cardiovascular, que se puedan aplicar en el Proceso de Enfermería. Método: revisión sistemática realizada en ocho bases de datos/portales, para identificar estudios que presentaran instrumentos multidimensionales para la evaluación de la fragilidad en adultos mayores con enfermedad cardiovascular y que fueran aplicables al proceso de enfermería. Resultados: se incluyeron 19 instrumentos multidimensionales. El Brief Frailty Index for Coronary Artery Disease se desarrolló para usarlo en el cuidado cardiovascular de las personas mayores. El Frailty Index for Adults y la Maastricht Frailty Screening Tool for Hospitalized Patients se elaboraron para ser usados en el Proceso de Enfermería. Conclusión: aunque sólo se elaboró un instrumento para adultos mayores con enfermedad cardiovascular y sólo dos son aplicables al proceso de enfermería, la mayoría de ellos tienen el potencial para ser adaptados y validados para ser usados en esa población en la evaluación de enfermería.

Role of Omega-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic (DHA) as modulatory and anti-inflammatory agents in noncommunicable diet-related diseases - Reports from the last 10 years.

BACKGROUND & AIMS: Fatty acids are a fundamental component of the human diet, particularly polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The importance of omega-3 fatty acids has been studied in the context of many diseases due to their pleiotropic effects, focusing on the anti-inflammatory effects of EPA and DHA. Currently, the results of these acids in noncommunicable diseases are being increasingly assessed in a broader context than just inflammation. However, the mechanisms underlying the modulatory and anti-inflammatory effects of omega-3 fatty acids remain the subject of intensive research. Therefore, we reviewed the literature covering articles from the last decade to assess not only the anti-inflammatory but, above all, the modulatory effect of EPA and DHA acids on noncommunicable diet-related diseases. METHODS: The PubMed, Web of Science and Scopus databases were searched for studies regarding the effects of omega-3 fatty acids on diet-related disorders from the last 10 years. RESULTS: The available research shows that EPA and DHA supplementation has a beneficial impact on regulating triglycerides, total cholesterol, insulin resistance, blood pressure, liver enzymes, inflammatory markers and oxidative stress. Additionally, there is evidence of their potential benefits in terms of mitochondrial function, regulation of plasma lipoproteins, and reduction of the risk of sudden cardiovascular events associated with atherosclerotic plaque rupture. CONCLUSIONS: Omega-3 polyunsaturated fatty acids (EPA, DHA) have many beneficial effects among patients with diet-related disorders. More well-designed randomised controlled trials are needed to fully determine the usefulness of EPA and DHA in treating and preventing noncommunicable diet-related diseases.

Growth differentiation factor 15 (GDF-15) as a biomarker of cardiovascular risk in chronic musculoskeletal pain.

BACKGROUND: It is unknown whether growth differentiation factor 15 (GDF-15) is associated with chronic musculoskeletal pain (CMP) and whether or not its association with incident cardiovascular disease (CVD) changes according to CMP status. METHODS: 1,957 randomly-selected adults aged ≥65 years without prior CVD were followed up between 2015-2023. CMP was classified according to its intensity, frequency, and interference with daily activities. The association between GDF-15 levels and CMP was assessed using linear models with progressive inclusion of potential confounders, whereas the association between GDF-15 and CVD risk was evaluated with Cox-proportional hazard models with similar adjustment and interaction terms between GDF-15 and CMP. The incremental predictive performance of GDF-15 over standard predictors was evaluated using discrimination and risk reclassification metrics. RESULTS: GDF-15 concentrations were 6.90% (95%CI:2.56;11.25) higher in individuals with CMP, and up to 8.89% (4.07;15.71) and 15.79% (8.43;23.16) higher in those with ≥3 CMP locations and interfering pain. These increased levels were influenced by a higher prevalence of cardiometabolic risk factors, functional impairments, depressive symptoms, and greater levels of inflammation in individuals with CMP. In fully-adjusted models, a two-fold increase in GDF-15 was associated with a with a 1.49 increased risk (95%CI: 1.08; 2.05) of a CVD event in individuals with CMP, but not among those without CMP [1.02 (0.77; 1.35)]; p-interaction 0.041. Adding GDF-15 to models including the Framingham Risk Score improved predictive performance among individuals with CMP. CONCLUSIONS: We provide evidence that GDF-15 could serve as a biomarker to assess CMP, as well as to predict CVD incidence in individuals with CMP.

Development of a novel 3D perfusable vascular graft model to elucidate the mechanisms for congenital heart disorders.

Pediatric heart transplantation is hampered by a chronic shortage of donor organs. This problem is further confounded by graft rejection. Identification of earlier indicators of pediatric graft rejection and development of subsequent strategies to counteract these effects will increase the longevity of transplanted pediatric hearts. Heart transplant reject is due to a complex series of events, resulting in CAV, which is thought to be mediated through a host immune response. However, the earlier events leading to CAV are not very well known. We hypothesize that early events related to ischemia reperfusion injury during pediatric heart transplantation are responsible for CAV and subsequent graft rejection. Identification of the molecular markers of ischemia reperfusion injury and development of subsequent therapies to block these pathways can potentially lead to a therapeutic strategy to reduce CAV and increase the longevity of the transplanted heart. To accomplish this goal, we have developed a perfusable vascular graft model populated with endothelial cells and demonstrated the feasibility of this model to understand the early events of ischemia reperfusion injury.

Association between high risk of obstructive sleep apnea and inflammatory markers in a population sample of young and middle-aged adults in the Miami Heart Study.

STUDY OBJECTIVES: There are limited data depicting the association between high risk of OSA and the levels of inflammatory markers in a population-based sample free from CVD. In a large U.S. cohort enriched with a Hispanic population and free of cardiovascular disease (CVD), we aimed to assess the association between high risk of obstructive sleep apnea (OSA) and inflammatory markers. METHODS: We analyzed data for 2359 clinical CVD-free participants from the Miami Heart Study, aged 40-65 (May 2015 - Sept 2018). High risk of OSA included those with a high risk using the Berlin questionnaire. Poisson regression analyses were utilized to examine the associations between high risk of OSA (reference: low risk of OSA) and hs-CRP, IL-6, and TNF-α levels (continuous) in univariate and multivariate models (adjusting for age, sex, race/ethnicity, and BMI, diabetes, hypertension, high cholesterol, and smoking). RESULTS: 552 (28%) participants were categorized as having a high risk of OSA. Patients with a high risk of OSA had higher median values of hs-CRP (2.3 vs. 1.0), IL-6 (1.9 vs. 1.4), and TNF-α (1.2 vs. 1.1) when compared to those with a low risk of OSA (all p < 0.001). When adjusting for age, sex, and race/ethnicity, the mean difference between patients with high and low risk of OSA in hs-CRP was 2.04 (95% CI 1.85, 2.23), and 0.73 (95% CI 0.57, 0.89) in IL-6. These differences were attenuated when further adjusting for CVD risk factors but remained statistically significant for hs-CRP: (0.38, 95% CI 0.21, 0.55). CONCLUSIONS: After accounting for CVD risk factors, individuals at high risk of OSA had significantly higher levels of hs-CRP, suggesting that OSA screening identified subclinical inflammation in this population sample of individuals free of CVD.

Trends in direct health care costs among US adults with atherosclerotic cardiovascular disease with and without diabetes.

OBJECTIVE: Population-based national data on the trends in expenditures related to coexisting atherosclerotic cardiovascular diseases (ASCVD) and diabetes is scarce. We assessed the trends in direct health care expenditures for ASCVD among individuals with and without diabetes, which can help to better define the burden of the co-occurrence of diabetes and ASCVD. METHODS: We used 12-year data (2008-2019) from the US national Medical Expenditure Panel Survey including 28,144 U.S individuals aged ≥ 18 years. Using a two-part model (adjusting for demographics, comorbidities and time), we estimated mean and adjusted incremental medical expenditures by diabetes status among individuals with ASCVD. The costs were direct total health care expenditures (out-of-pocket payments and payments by private insurance, Medicaid, Medicare, and other sources) from various sources (office-based visits, hospital outpatient, emergency room, inpatient hospital, pharmacy, home health care, and other medical expenditures). RESULTS: The total direct expenditures for individuals with ASCVD increased continuously by 30% from $14,713 (95% confidence interval (CI): $13,808-$15,619) in 2008-2009 to $19,145 (95% CI: $17,988-$20,301) in 2008-2019. Individuals with diabetes had a 1.5-fold higher mean expenditure that those without diabetes. A key driver of the observed increase in direct costs was prescription drug costs, which increased by 37% among all individuals with ASCVD. The increase in prescription drug costs was more pronounced among individuals with ASCVD and diabetes, in whom a 45% increase in costs was observed, from $5184 (95% CI: $4721-$5646) in 2008-2009 to $7501 (95% CI: $6678-$8325) in 2018-2019. Individuals with ASCVD and diabetes had $5563 (95% CI: $4643-$6483) higher direct incremental expenditures compared with those without diabetes, after adjusting for demographics and comorbidities. Among US adults with ASCVD, the estimated adjusted total direct excess medical expenditures were $42 billion per year among those with diabetes vs. those without diabetes. CONCLUSIONS: In the setting of ASCVD, diabetes is associated with significantly increased health care costs, an increase that was driven by marked increase in medication costs.

ProtecT-2-D trial protocol: cardiovascular protection in patients with type 2 diabetes and established heart and/or vascular disease at a cardio-metabolic clinic-a randomized controlled trial.

BACKGROUND: Cardiovascular disease remains the primary cause of morbidity and mortality despite advancements in the treatment of patients with type 2 diabetes. Effective diabetes management extends beyond blood glucose control and includes cardiovascular prevention and treatment. However, the conventional healthcare model often emphasizes single-disease-specific management, leading to fragmented care. We aim to establish an affordable Cardio-Metabolic Clinic (CMC) that can provide comprehensive assessment and specialized care with a focus on cardiovascular protection. METHODS: The ProtecT-2-D study is a prospective, randomized control trial at the Cardiovascular Research Unit, Odense University Hospital Svendborg, Denmark. In this study, 1500 participants with type 2 diabetes and cardiovascular disease will be randomly assigned in a 2:1 ratio to receive either the intervention: treatment in the CMC, or the control: standard of care. The Cardio-Metabolic Clinic applies a decision-making algorithm coded with the latest guidelines to evaluate lifestyle factors and manage medical treatment. Health examinations are conducted at baseline and after three years, and clinical events will be assessed through registry and journal audits after five and ten years. The primary outcome is the time to the first occurrence of a composite of cardiovascular deaths, non-fatal acute myocardial infarctions, non-fatal stroke, or hospitalization due to heart failure at a time frame of five years. DISCUSSION: The Cardio-Metabolic Clinic represents a pioneering approach to diabetes management that aims to improve patient outcomes by reducing the cardiovascular disease burden. This study could transform diabetes care and offer a multidisciplinary, cost-effective, and specialized treatment. We need to establish the efficacy and feasibility of a CMC to integrate comparable clinics into broader healthcare systems, and potentially enhance cardiovascular health in patients with type 2 diabetes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT06203860.

Discovery of a novel homocysteine thiolactone hydrolase and the catalytic activity of its natural variants.

Homocysteine thiolactone (HTL), a toxic metabolite of homocysteine (Hcy) in hyperhomocysteinemia (HHcy), is known to modify protein structure and function, leading to protein damage through formation of N-Hcy-protein. HTL has been highly linked to HHcy-associated cardiovascular and neurodegenerative diseases. The protective role of HTL hydrolases against HTL-associated vascular toxicity and neurotoxicity have been reported. Although several endogeneous enzymes capable of hydrolyzing HTL have been identified, the primary enzyme responsible for its metabolism remains unclear. In this study, three human carboxylesterases were screened to explore new HTL hydrolase and human carboxylesterase 1 (hCES1) demonstrates the highest catalytic activity against HTL. Given the abundance of hCES1 in the liver and the clinical significance of its single-nucleotide polymorphisms (SNPs), six common hCES1 nonsynonymous coding SNP (nsSNPs) variants were examined and characterized for their kinetic parameters. Variants E220G and G143E displayed 7.3-fold and 13.2-fold lower catalytic activities than its wild-type counterpart. In addition, the detailed catalytic mechanism of hCES1 for HTL hydrolysis was computational investigated and elucidated by Quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) method. The function of residues E220 and G143 in sustaining its hydrolytic activity of hCES1 was analyzed, and the calculated energy difference aligns well with experimental-derived results, supporting the validity of our computational insights. These findings provide insights into the potential protective role of hCES1 against HTL-associated toxicity, and warrant future studies on the possible association between specific genetic variants of hCES1 with impaired catalytic function and clinical susceptibility of HTL-associated cardiovascular and neurodegenerative diseases.

Assessing the Risk of Heart Attack: A Bayesian Kernel Machine Regression Analysis of Heavy Metal Mixtures.

Background: The assessment of heavy metals' effects on human health is frequently limited to investigating one metal or a group of related metals. The effect of heavy metals mixture on heart attack is unknown. Methods: This study applied the Bayesian kernel machine regression model (BKMR) to the 2011-2016 National Health and Nutrition Examination Survey (NHANES) data to investigate the association between heavy metal mixture exposure with heart attack. 2972 participants over the age of 20 were included in the study. Results: Results indicate that heart attack patients have higher levels of cadmium and lead in the blood and cadmium, cobalt, and tin in the urine, while having lower levels of mercury, manganese, and selenium in the blood and manganese, barium, tungsten, and strontium in the urine. The estimated risk of heart attack showed a negative association of 0.0030 units when all the metals were at their 25th percentile compared to their 50th percentile and a positive association of 0.0285 units when all the metals were at their 75th percentile compared to their 50th percentile. The results suggest that heavy metal exposure, especially cadmium and lead, may increase the risk of heart attacks. Conclusions: This study suggests a possible association between heavy metal mixture exposure and heart attack and, additionally, demonstrates how the BKMR model can be used to investigate new combinations of exposures in future studies.

The UTHealth Houston Adult Cardiovascular Genomics Certificate Program: Efficacy and Impact on Healthcare Professionals.

Background: The demand for genetic services has outpaced the availability of resources, challenging clinicians untrained in genetic integration into clinical decision-making. The UTHealth Adult Cardiovascular Genomics Certificate (CGC) program trains non-genetic healthcare professionals to recognize, assess, and refer patients with heritable cardiovascular diseases. This asynchronous online course includes 24 modules in three tiers of increasing complexity, using realistic clinical scenarios, interactive dialogues, quizzes, and tests to reinforce learning. We hypothesized that the CGC will increase genomic competencies in this underserved audience and encourage applying genomic concepts in clinical practice. Methods: Required course evaluations include pre- and post-assessments, knowledge checks in each module, and surveys for module-specific feedback. After 6 months, longitudinal feedback surveys gathered data on the long-term impact of the course on clinical practice and conducted focused interviews with learners. Results: The CGC was accredited in September 2022. Principal learners were nurses (24%), nurse practitioners (21%), physicians (16%), and physician assistants. Scores of 283 learners in paired pre- and post-assessments increased specific skills related to recognizing heritable diseases, understanding inheritance patterns, and interpreting genetic tests. Interviews highlighted the CGC's modular structure and linked resources as key strengths. Learners endorsed confidence to use genetic information in clinical practice, such as discussing genetic concepts and risks with patients and referring patients for genetic testing. Learners were highly likely to recommend the CGC to colleagues, citing its role in enhancing heritable disease awareness. Conclusions: The CGC program effectively empowers non-genetic clinicians to master genomic competencies, fostering collaboration to prevent deaths from heritable cardiovascular diseases, and potentially transforming healthcare education and clinical practice.

A Multi-Omics Approach to Defining Target Organ Injury in Youth with Primary Hypertension.

BACKGROUND: Primary hypertension in childhood tracks into adulthood and may be associated with increased cardiovascular risk. Studies conducted in children and adolescents provide an opportunity to explore the early cardiovascular target organ injury (CV-TOI) in a population free from many of the comorbid cardiovascular disease risk factors that confound studies in adults. METHODS: Youths (n=132, mean age 15.8 years) were stratified by blood pressure (BP) as low, elevated, and high-BP and by left ventricular mass index (LVMI) as low- and high-LVMI. Systemic circulating RNA, miRNA, and methylation profiles in peripheral blood mononuclear cells and deep proteome profiles in serum were determined using high-throughput sequencing techniques. RESULTS: VASH1 gene expression was elevated in youths with high-BP with and without high-LVMI. VASH1 expression levels positively correlated with systolic BP (r=0.3143, p=0.0034). The expression of hsa-miR-335-5p, one of the VASH1-predicted miRNAs, was downregulated in high-BP with high-LVMI youths and was inversely correlated with systolic BP (r=-0.1891, p=0.0489). GSE1 hypermethylation, circulating PROZ upregulation (log2FC=0.61, p=0.0049 and log2FC=0.62, p=0.0064), and SOD3 downregulation (log2FC=-0.70, p=0.0042 and log2FC=-0.64, p=0.010) were observed in youths with elevated BP and high-BP with high-LVMI. Comparing the transcriptomic and proteomic profiles revealed elevated HYAL1 levels in youths displaying high-BP and high-LVMI. CONCLUSIONS: The findings are compatible with a novel blood pressure-associated mechanism that may occur through impaired angiogenesis and extracellular matrix degradation through dysregulation of Vasohibin-1 and Hyaluronidase1 was identified as a possible mediator of CV-TOI in youth with high-BP and suggests strategies for ameliorating TOI in adult-onset primary hypertension.

Mitochondrial Structure and Function in Human Heart Failure.

Despite clinical and scientific advancements, heart failure is the major cause of morbidity and mortality worldwide. Both mitochondrial dysfunction and inflammation contribute to the development and progression of heart failure. Although inflammation is crucial to reparative healing following acute cardiomyocyte injury, chronic inflammation damages the heart, impairs function, and decreases cardiac output. Mitochondria, which comprise one third of cardiomyocyte volume, may prove a potential therapeutic target for heart failure. Known primarily for energy production, mitochondria are also involved in other processes including calcium homeostasis and the regulation of cellular apoptosis. Mitochondrial function is closely related to morphology, which alters through mitochondrial dynamics, thus ensuring that the energy needs of the cell are met. However, in heart failure, changes in substrate use lead to mitochondrial dysfunction and impaired myocyte function. This review discusses mitochondrial and cristae dynamics, including the role of the mitochondria contact site and cristae organizing system complex in mitochondrial ultrastructure changes. Additionally, this review covers the role of mitochondria-endoplasmic reticulum contact sites, mitochondrial communication via nanotunnels, and altered metabolite production during heart failure. We highlight these often-neglected factors and promising clinical mitochondrial targets for heart failure.

Relationships of Office, Ambulatory, and Self-Measured Blood Pressure with Cardiac, Renal, and Atherosclerotic Biomarkers.

BACKGROUND: Previous studies with several limitations have comparatively analyzed the relationship between ambulatory blood pressure (BP) and self-measured BP and biomarkers of organ damage. This study extends this line of research by examining the relationship between ambulatory and self-measured BP and cardiac, renal, and atherosclerotic biomarkers in outpatients at cardiovascular risk. METHODS: In 1,440 practice outpatients who underwent office, ambulatory, and self-measured BP monitoring, we assessed the relationships of each BP with organ damage biomarkers including b-type natriuretic peptide (BNP), echocardiographic left ventricular mass index (LVMI), urine-albumin-creatinine ratio (UACR), and brachial-ankle pulse wave velocity (baPWV). RESULTS: In the comparison of correlation, self-measured systolic BP (SBP) was more strongly correlated to log-transformed (Ln) BNP (n=1,435; r=0.123 vs. r = -0.093, P<0.001), LVMI (n=1,278; r=0.223 vs. r=0.094, P<0.001), Ln-UACR (n=1,435; r=0.244 vs. r=0.154, P=0.010), and baPWV (n=1,360; r=0.327 vs. r=0.115, P<0.001) than daytime ambulatory SBP. In the linear regression models including office, ambulatory, and self-measured SBP, only self-measured SBP was significantly related to Ln-BNP (P=0.016) and LVMI (P<0.001). In the logistic regression models for the top quartile of LVMI, adding self-measured SBP improved the model predictability (P=0.027), but adding daytime ambulatory SBP did not. However, adding daytime ambulatory SBP improved the model predictability in the logistic model including office and self-measured SBP. CONCLUSIONS: Our study findings suggested that self-measured BP was associated with cardiac biomarkers independent of ambulatory BP.

Advances in nucleic acid-targeted therapies for cardiovascular disease prevention.

Nucleic acid-based therapies are being rapidly developed for prevention and management of cardiovascular diseases (CVD). Remarkable advancements have been achieved in the delivery, safety, and effectiveness of these therapeutics in the past decade. These therapies can also modulate therapeutic targets that cannot be sufficiently addressed using traditional drugs or antibodies. Among the nucleic acid-targeted therapeutics under development for CVD prevention are RNA-targeted approaches, including antisense oligonucleotides (ASO), small interfering RNAs (siRNA), and novel genome editing techniques. Genetic studies have identified potential therapeutic targets that are suggested to play a causative role in development and progression of CVD. RNA- and DNA-targeted therapeutics can be particularly well delivered to the liver, where atherogenic lipoproteins and angiotensinogen are produced. Lipoproteins currently targeted include proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein A (Apo(a)), apolipoprotein C3 (APOC3), angiopoietin-like 3 (ANGPTL3). Several large-scale clinical development programs for nucleic acid-targeted therapies in cardiovascular prevention are under way, which may also be attractive from a therapy adherence point of view, given the long action of these therapeutics. In addition to genome editing, the concept of gene transfer is presently under assessment in preclinical and clinical investigations as a potential approach for addressing LDL-R deficiency. Furthermore, ongoing research is exploring the use of RNA-targeted therapies to treat arterial hypertension by reducing hepatic angiotensinogen (AGT) production. This review summarizes the rapid translation of siRNA and ASO therapeutics as well as gene editing into clinical studies to treat dyslipidemia and arterial hypertension for CVD prevention. It also outlines potential innovative therapeutic options that are likely relevant to the future of cardiovascular medicine.

Associations of dietary magnesium intake with the risk of atherosclerotic cardiovascular disease and mortality in individuals with and without type 2 diabetes: A prospective study in the UK Biobank.

BACKGROUND: The association between dietary magnesium (Mg) intake and the risk of atherosclerotic cardiovascular disease (ASCVD) remains uncertain. We aimed to examine the associations of dietary Mg intake with the risk of ASCVD events and mortality in individuals with and without type 2 diabetes. METHODS: A total of 149,929 participants (4603 with type 2 diabetes) from the UK Biobank were included in the analyses. The hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazard models. Furthermore, interactions of dietary Mg intake with type 2 diabetes status were examined on multiplicative and additive scales. RESULTS: During a median follow-up of 12.0 and 12.1 years, 7811 incident ASCVD events and 5000 deaths (including 599 ASCVD deaths) were documented, respectively. There were significantly negative associations between sufficient dietary Mg intake (equal to or greater than the recommended daily intake) and the risk of ASCVD incidence (HR 0.63 [95 % CI 0.49;0.82]), ASCVD mortality (0.45 [0.24;0.87]), and all-cause mortality (0.71 [0.52;0.97]) in participants with type 2 diabetes, whereas no significant association was observed in participants without type 2 diabetes (1.01 [0.94;1.09] for ASCVD incidence; 1.25 [0.93;1.66] for ASCVD mortality; 0.97 [0.88;1.07] for all-cause mortality). Multiplicative and additive interactions of dietary Mg intake with type 2 diabetes status were both observed. CONCLUSION: Sufficient dietary Mg intake was significantly associated with lower risks of ASCVD events and mortality in individuals with type 2 diabetes but not in those without type 2 diabetes. Our findings provide insight into the importance of dietary Mg intake for reducing modifiable cardiovascular burden in individuals with type 2 diabetes, which may inform future personalized dietary guidelines.

Therapeutic potentials of allicin in cardiovascular disease: advances and future directions.

Cardiovascular disease (CVD) remains the predominant cause of mortality and disability worldwide. Against this backdrop, finding effective drugs for the pharmacological treatment of CVD has become one of the most urgent and challenging issues in medical research. Garlic (Allium sativum L.) is one of the oldest plants and is world-renowned for its dietary and medicinal values. Allicin (diallyl thiosulfinate) is one of the primary natural active ingredients in garlic, which has been proven to have powerful cardioprotective effects and mediate various pathological processes related to CVD, such as inflammatory factor secretion, myocardial cell apoptosis, oxidative stress, and more. Therefore, allicin holds a promising application prospect in the treatment of CVD. This review summarized the biological functions of allicin and its potential mechanisms in CVD, including antioxidation, anti-inflammation, and anti-apoptosis effects. Reckoning with these, we delved into recent studies on allicin's cardioprotective effects concerning various CVDs, such as atherosclerosis, hypertension, myocardial infarction, arrhythmia, cardiac hypertrophy, heart failure, and cardiotoxicity. Further, considering the tremendous advancement in nanomedicine, nanotechnology-based drug delivery systems show promise in addressing limitations of allicin's clinical applications, including improving its solubility, stability, and bioavailability. Through this review, we hope to provide a reference for further research on allicin in cardioprotection and drug development.

Longitudinal association between maternal cardiovascular health in pregnancy and child birth outcomes.

The American Heart Association has updated its definition of cardiovascular health (CVH) with a new framework known as Life's Essential 8 (LE8). Although gestational CVH assessment has been recommended, its significance based on LE8 for birth outcomes is unknown. We thus evaluated the status of gestational CVH based on LE8 in 3036 pregnant women of the Shanghai Maternal-Child Pairs Cohort and the population of China Maternal Nutrition and Health Sciences Survey, and also examined the association between gestational CVH and child birth outcomes. We found that only a small proportion (12.84%) had high CVH, while 1.98% had low CVH in this cohort study. In adjusted models, a 10-point increase in the gestational CVH score, indicating a more favorable score, was associated with lower neonatal size such as birth weight (ß: - 37.05 [95% confidence interval: - 52.93, - 21.16]), birth length (- 0.12[- 0.22, - 0.01]), weight-for-height z-score (- 0.07[- 0.12, - 0.03]), body mass index z-score (- 0.09 [- 0.13, - 0.04]), length-for-age Z-score (- 0.03 [- 0.06, - 0.01]), and weight-for-age z-score (- 0.08 [- 0.12, - 0.05]). Also, a 10-point increase in the gestational CVH score was associated with the lower risk of large for gestational age (LGA) (0.82 [0.73, 0.92]) and macrosomia infant (0.75 [0.64, 0.88]). CVH categories showed similar results. That is, better maternal CVH status in pregnancy was associated with lower neonatal size and lower risks for LGA and macrosomia in newborns.

U-shaped association between serum Klotho and all-cause mortality in US cardiovascular patients: a prospective cohort study.

Background: Increased levels of serum Klotho have been associated with a reduced risk of several cardiovascular diseases (CVD). However, limited studies exist on the association between serum Klotho and mortality in patients with CVD. Methods: We collected data from CVD patients in the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2016. We linked NHANES data with the National Death Index to determine the survival status of participants. Univariate and multivariable Cox regression models were used to investigate the relationship between serum Klotho levels and mortality in CVD patients. The relationship between serum Klotho quartiles and mortality in CVD patients was visualized using Kaplan-Meier (KM) curves and restricted cubic spine. Finally, subgroup analyses were used to examine the association between serum Klotho and all-cause mortality in different populations. Results: 1905 patients with CVD were finally enrolled in our study with a mean follow-up of 7.1 years. The average age of the participants was 63.4 years, with 58.40% being male. KM showed that lower Klotho levels were associated with lower survival rates. After adjusting for potential confounders, patients with higher serum Klotho levels had lower all-cause mortality (Q1: 1.00, Q2: 0.58 (0.42-0.80), Q3: 0.69 (0.47-1.01), and Q4:0.64 (0.45-0.92). However, the relationship between serum Klotho levels and cardiovascular mortality was not statistically significant. Dose-response analysis shows a U-shaped relationship between serum Klotho levels and all-cause mortality in patients with CVD (P nonlinear=0.002). Subgroup analysis indicated that participants with a history of hypertension had a higher risk of all-cause mortality in serum Klotho Q4 compared to Q1 (P trend <0.05). Conclusion: The relationship between serum Klotho levels and all-cause mortality in CVD patients exhibits a U-shaped association. The underlying mechanisms of this association need further investigation.

Prevalence of hypertension, screening, awareness, and associated risk factors in teaching institution of Etawah District, Uttar Pradesh: A cross-section study.

Background: Hypertension is one of the leading causes of death worldwide, affecting over one billion people. It is responsible for roughly half of all heart disease and stroke-related deaths globally. Because hypertension does not cause any symptoms on its own, it is commonly referred to as "the silent killer." Objective: This study aimed to determine (1) the prevalence of hypertension and its associated risk factors and (2) the level of awareness of hypertension status among study participants. Material and Methods: A facility-based cross-sectional analytical study was conducted for 3 months during January-March 2023 at the teaching institution in Etawah District, Uttar Pradesh. It was conducted among 392 study participants who were ≥18 years old. Data were collected through a predesigned, pretested, semi-structured questionnaire, and anthropometric measurement was determined using standard guidelines. Results: The overall prevalence of hypertension screening was 69.4% (male: 33.8% and female: 66.2%), respectively. The majority of hypertensives were found in female participants. Tobacco and alcohol consumption, obesity, physical inactivity, stress and strain, and an unhealthy diet were also associated with hypertension. Among 392 study participants, only 67 (24.6%) were aware of their hypertension status. Conclusion: We conclude that hypertension has been described as an "Iceberg disease" as those who suffer are usually unaware and hence usually seek healthcare services at a very late stage. Preventive measures should be needed to improve hypertension screening, awareness, treatment, and control.