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1.
Sci Rep ; 14(1): 18026, 2024 08 04.
Article in English | MEDLINE | ID: mdl-39098981

ABSTRACT

Ballistic impacts on human thorax without penetration can produce severe injuries or even death of the carrier. Soft tissue finite element models must capture the non-linear elasticity and strain-rate dependence to accurately estimate the dynamic human mechanical response. The objective of this work is the calibration of a visco-hyperelastic model for soft tissue simulants. Material model parameters have been calculated by fitting experimental stress-strain relations obtained from the literature using genetic algorithms. Several parametric analyses have been carried out during the definition of the optimization algorithm. In this way, we were able to study different optimization strategies to improve the convergence and accuracy of the final result. Finally, the genetic algorithm has been applied to calibrate two different soft tissue simulants: ballistic gelatin and styrene-ethylene-butylene-styrene. The algorithm is able to calculate the constants for visco-hyperelastic constitutive equations with high accuracy. Regarding synthetic stress-strain curves, a short computational time has been shown when using the semi-free strategy, leading to high precision results in stress-strain curves. The algorithm developed in this work, whose code is included as supplementary material for the reader use, can be applied to calibrate visco-hyperelastic parameters from stress-strain relations under different strain rates. The semi-free relaxation time strategy has shown to obtain more accurate results and shorter convergence times than the other strategies studied. It has been also shown that the understanding of the constitutive models and the complexity of the stress-strain objective curves is crucial for the accuracy of the method.


Subject(s)
Algorithms , Elasticity , Finite Element Analysis , Stress, Mechanical , Humans , Viscosity , Models, Biological , Biomechanical Phenomena , Gelatin/chemistry
2.
Metabolites ; 14(8)2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39195533

ABSTRACT

The association of thyroid function with essential and non-essential amino acids is understudied, despite their common metabolic roles. Thus, our aim was to evaluate the association of thyroid function with the levels of branched-chain amino acids (BCAAs-leucine, isoleucine, and valine) and of alanine in the general population. We utilized data from the São Paulo research center of ELSA-Brasil, a longitudinal population-based cohort study. Thyroid parameters included thyroid stimulating hormone (TSH), free T4 and free T3 levels, and the FT4:FT3 ratio. BCAAs and alanine were analyzed on a fully automated NMR platform. The current analysis included euthyroid participants and participants with subclinical hyperthyroidism and hypothyroidism. We used Pearson's coefficient to quantify the correlation between thyroid-related parameters and amino acids. Linear regression models were performed to analyze whether thyroid parameters were associated with BCAAs and alanine levels. We included 4098 participants (51.3 ± 9.0 years old, 51.5% women) in this study. In the most adjusted model, higher levels of TSH were associated with higher levels of alanine, FT4 levels were inversely associated with isoleucine levels, FT3 levels were statistically significant and positively associated with valine and leucine, and the T3:T4 ratio was positively associated with all amino acids. We observed that subclinical hypothyroidism was positively associated with isoleucine and alanine levels in all models, even after full adjustment. Our findings highlight the association of subclinical hypothyroidism and thyroid-related parameters (including TSH, free T4, free T3, and FT4:FT3 ratio) with BCAAs and alanine. Further studies are needed to explore the mechanisms underlying this association. These insights contribute to our understanding of the influence of thyroid-related parameters on BCAA and alanine metabolism.

4.
Clin Biochem ; 131-132: 110812, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39197573

ABSTRACT

OBJECTIVES AND AIM: This study aimed to identify precise biomarkers and develop targeted therapeutic strategies for preventing premature atherosclerotic cardiovascular disease in patients with familial hypercholesterolemia (FH) by investigating the quantitative and qualitative abnormalities in the metabolic network of lipids in these patients using an advanced lipidomics platform. DESIGN & METHODS: The study population comprised 18 homozygous (HoFH), 18 heterozygous (HeFH) FH patients, and 20 healthy controls. Cholesterol oxidation products (oxysterol, COPs) and main lipid classes were determined using gas chromatography-mass spectrometry. Results were expressed as percentages of total fat matter for lipid classes and percentages of total COPs for oxysterols. The principal component analysis (PCA) was also carried out, to highlight the correlation between studied parameters and groups investigated. RESULTS: Patients (both HoFH and HeFH) showed lower content of free fatty acids (FFAs) and greater values of triacylglycerols (TAGs) in comparison to controls. HoFH showed lower monoacylglycerols (P<0.01) and higher free cholesterol (FC) (P<0.05) when compared to HeFH and controls. The total content of COPs ranged from 1.96 to 4.25 mg/dL, from 2.27 to 4.05 mg/dL, and from 0.79 to 4.12 mg/dL in healthy controls, HoFH and HeFH groups, respectively, with no significant differences between patients and controls. In general, the 7α-hydroxycholesterol (7α-HC) was greater than other COPs. However, no significant differences were found between the three studied groups. Moreover, an opposite trend was observed between 7α-HC and 7-ketocholesterol (7-KC). Additionally, when PCA was carried out, the first two PCs explained 92.13 % of the total variance, of which the PC1 describes 53.94 % of variance mainly correlated to TAGs, diacylglycerols (DAGs), and 7-KC. On the other hand, the PC2 was correlated primarily for FFAs, FC and esterified sterols (E-STE). CONCLUSIONS: In conclusion, abnormal levels of TAGs, DAGs and 7-KC were associated with HeFH while HoFH was associated with the abnormal amount of E-STE.


Subject(s)
Hyperlipoproteinemia Type II , Lipidomics , Oxysterols , Humans , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/metabolism , Hyperlipoproteinemia Type II/genetics , Oxysterols/metabolism , Oxysterols/blood , Male , Lipidomics/methods , Female , Adult , Middle Aged , Case-Control Studies , Triglycerides/blood , Gas Chromatography-Mass Spectrometry/methods , Biomarkers/blood
5.
Curr Atheroscler Rep ; 26(10): 589-602, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39150672

ABSTRACT

PURPOSE OF REVIEW: Although the clinical benefit of reducing low-density lipoprotein cholesterol (LDLc) in patients with coronary artery disease (CAD) is well-established, the impact on plaque composition and stability is less clear. Our narrative review aimed to assess the clinical effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on coronary plaque characteristics specifically focusing from atheroma progression to regression and stabilization. RECENT FINDINGS: The combination of statin therapy and PCSK9 inhibitors (evolocumab and alirocumab) promotes plaque stability in patients following an acute coronary syndrome. The GLAGOV study highlighted the relationship between achieved LDLc levels and changes in percentage atheroma volume. Similarly, the PACMAN-AMI study concluded that the qualitative and quantitative changes in coronary plaque were associated with the levels of LDLc. Assessing the severity of coronary artery stenosis and the extent of atherosclerotic burden by means of imaging techniques (e.g., IVUS, OCT and near-infrared spectroscopic) have significantly advanced our understanding of the benefits from promoting plaque regression and achieving to features of plaque stabilization through increasingly intensive lipid-lowering strategies.


Subject(s)
Coronary Artery Disease , PCSK9 Inhibitors , Plaque, Atherosclerotic , Proprotein Convertase 9 , Humans , Plaque, Atherosclerotic/drug therapy , Plaque, Atherosclerotic/diagnostic imaging , Coronary Artery Disease/drug therapy , Proprotein Convertase 9/metabolism , Cholesterol, LDL/blood , Cholesterol, LDL/metabolism , Cholesterol, LDL/drug effects , Anticholesteremic Agents/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
6.
Cureus ; 16(6): e62306, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39006643

ABSTRACT

Minimal change disease (MCD), typically linked with pediatric nephrotic syndrome, presents challenges in early identification and diagnosis in adult populations. This case report emphasizes the importance of tailored diagnostic and treatment approaches for adults with MCD. Our patient presented with fatigue, shortness of breath, and confusion, along with other symptoms leading to a renal biopsy which confirmed MCD. This highlights the diagnostic significance of kidney biopsy in adults. While steroids remain the standard treatment, challenges such as resistance and side effects lead to the consideration of alternatives like tacrolimus. There are nuanced differences between adult and pediatric MCD presentations, for which our study calls for increased awareness among physicians. Steroids are considered a first-line treatment for MCD, but prolonged use of steroids has significantly increased risk and alternative therapies should be considered. This study presents an example of MCD in adult populations, urging ongoing research for enhanced understanding and tailored management strategies. It emphasizes the pivotal role of physician awareness, alternative treatments, and continued investigation to improve outcomes for adults with MCD.

8.
Circ Cardiovasc Imaging ; 17(7): e016152, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39012945

ABSTRACT

BACKGROUND: Elevated levels of lipoprotein(a) (Lp(a)) are independently associated with an increased risk of atherosclerotic cardiovascular disease events. However, the mechanisms driving this association are poorly understood. We aimed to evaluate the association between Lp(a) and coronary plaque characteristics in a contemporary US cohort without clinical atherosclerotic cardiovascular disease, undergoing coronary computed tomography angiography, the noninvasive gold standard for the assessment of coronary atherosclerosis. METHODS: We used baseline data from the Miami Heart Study-a community-based, prospective cohort study-which included asymptomatic adults aged 40 to 65 years evaluated using coronary computed tomography angiography. Those taking any lipid-lowering therapies were excluded. Elevated Lp(a) was defined as ≥125 nmol/L. Outcomes included any plaque, coronary artery calcium score >0, maximal stenosis ≥50%, presence of any high-risk plaque feature (positive remodeling, spotty calcification, low-attenuation plaque, napkin ring), and the presence of ≥2 high-risk plaque features. RESULTS: Among 1795 participants (median age, 52 years; 54.3% women; 49.6% Hispanic), 291 (16.2%) had Lp(a) ≥125 nmol/L. In unadjusted analyses, individuals with Lp(a) ≥125 nmol/L had a higher prevalence of all outcomes compared with Lp(a) <125 nmol/L, although differences were only statistically significant for the presence of any coronary plaque and ≥2 high-risk features. In multivariable models, elevated Lp(a) was independently associated with the presence of any coronary plaque (odds ratio, 1.40, [95% CI, 1.05-1.86]) and with ≥2 high-risk features (odds ratio, 3.94, [95% CI, 1.82-8.52]), although only 35 participants had this finding. Among participants with a coronary artery calcium score of 0 (n=1200), those with Lp(a) ≥125 nmol/L had a significantly higher percentage of any plaque compared with those with Lp(a) <125 nmol/L (24.2% versus 14.2%; P<0.001). CONCLUSIONS: In this contemporary analysis, elevated Lp(a) was independently associated with the presence of coronary plaque. Larger studies are needed to confirm the strong association observed with the presence of multiple high-risk coronary plaque features.


Subject(s)
Asymptomatic Diseases , Biomarkers , Computed Tomography Angiography , Coronary Angiography , Coronary Artery Disease , Lipoprotein(a) , Plaque, Atherosclerotic , Humans , Middle Aged , Female , Male , Lipoprotein(a)/blood , Florida/epidemiology , Prospective Studies , Coronary Angiography/methods , Coronary Artery Disease/epidemiology , Coronary Artery Disease/blood , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/diagnosis , Adult , Biomarkers/blood , Aged , Risk Factors , Coronary Vessels/diagnostic imaging , Up-Regulation , Predictive Value of Tests , Risk Assessment , Prevalence , Vascular Calcification/diagnostic imaging , Vascular Calcification/epidemiology , Vascular Calcification/blood
9.
Rev Port Cardiol ; 2024 Jul 06.
Article in English, Portuguese | MEDLINE | ID: mdl-38972451

ABSTRACT

Atherosclerotic cardiovascular disease (ASCVD) remains the major cause of premature death and disability; effective cardiovascular (CV) risk prevention is fundamental. The World Heart Federation (WHF) Cholesterol Roadmap provides a framework for national policy development and aims to achieve ASCVD prevention. At the invitation of the WHF, a group of experts from the Portuguese Society of Cardiology (SPC), addressed the cholesterol burden at nationally and discussed possible strategies to include in a Portuguese cholesterol roadmap. The literature review showed that the cholesterol burden in Portugal is high and especially uncontrolled in those with the highest CV risk. An infographic scorecard was built to include in the WHF collection, for a clear idea about CV risk and cholesterol burden in Portugal, which would also be useful for health policy advocacy. The expert discussion and preventive strategies proposal followed the five pillars of the WHF document: awareness improvement; population-based approaches for CV risk and cholesterol; risk assessment/population screening; system-level approaches; surveillance of cholesterol and ASCVD outcomes. These strategies were debated by all the expert participants, with the goal of creating a national cholesterol roadmap to be used for advocacy and as a guide for CV prevention. Several key recommendations were outlined: include all stakeholders in a multidisciplinary national program; create a structured activities plan to increase awareness in the population; improve the quality of continuous CV health education; increase the interaction between different health professionals and non-health professionals; increment the referral of patients to cardiac rehabilitation; screen cholesterol levels in the general population, especially high-risk groups; promote patient self-care, engage with patients' associations; use specific social networks to spread information widely; create a national database of cholesterol levels with systematic registry of CV events; redefine strategies based on the evaluation of results; create and involve more patients' associations - invert the pyramid order. In conclusion, ASCVD and the cholesterol burden remain a strong global issue in Portugal, requiring the involvement of multiple stakeholders in prevention. The Portuguese cholesterol roadmap can provide some solutions to help urgently mitigate the problem. Population-based approaches to improve awareness and CV risk assessment and surveillance of cholesterol and ASCVD outcomes are key factors in this change. A call to action is clearly needed to fight hypercholesterolemia and ASCVD burden.

11.
J Clin Lipidol ; 18(4): e525-e536, 2024.
Article in English | MEDLINE | ID: mdl-38910104

ABSTRACT

BACKGROUND: The International Atherosclerosis Society (IAS) published an evidence-informed guidance for familial hypercholesterolemia (FH) that provides both clinical and implementation recommendations. We reference examples of strategies from the literature to explore how these implementation recommendations can be tailored into implementation strategies at the local-level for stakeholders guided by a framework proposed by Sarkies and Jones. METHODS: Four authors of the IAS guidance selected two published exemplar implementation recommendations for detection, management, and general implementation. Each recommendation was described as an implementation strategy using Proctor's guidance for specifying and reporting implementation strategies. It recommends reporting the actor (who), action (what), action-target (who is impacted), temporality (how often), and dose (how much) for each implementation strategy. RESULTS: Detection: A centralized cascade testing model, mobilized nurses (actor) to relative's homes, after the diagnosis of the proband (temporality), once (dose) to consent, obtain a blood sample and health information (action) on relatives (action-target). MANAGEMENT: A primary care initiative to improve FH management included an educational session (action) with clinicians (action-target), computer-based reminder message and message to patients to have their cholesterol screened once (dose) at a visit or outreach (temporality) by researchers (actor). General: A partnership between a statewide public pathology provider, local public hospital network, primary health network, government health ministry, and an academic university (actors) was established to implement a primary-tertiary shared care model (action) to improve the detection of FH (action-target). CONCLUSIONS: We demonstrate that implementation recommendations can be specified and reported for different local contexts with examples on monitoring, evaluation, and sustainability in practice.


Subject(s)
Hyperlipoproteinemia Type II , Implementation Science , Humans , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/therapy , Practice Guidelines as Topic
13.
Lipids Health Dis ; 23(1): 156, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796450

ABSTRACT

The degradation of low-density lipoprotein receptor (LDLR) is induced by proprotein convertase subtilisin/kexin type 9 (PCSK9), resulting in elevated plasma concentrations of LDL cholesterol. Therefore, inhibiting the interactions between PCSK9 and LDLR is a desirable therapeutic goal for managing hypercholesterolemia. Aptamers, which are RNA or single-stranded DNA sequences, can recognize their targets based on their secondary structure. Aptamers exhibit high selectivity and affinity for binding to target molecules. The systematic evolution of ligands by exponential enrichment (SELEX), a combination of biological approaches, is used to screen most aptamers in vitro. Due to their unique advantages, aptamers have garnered significant interest since their discovery and have found extensive applications in various fields. Aptamers have been increasingly utilized in the development of biosensors for sensitive detection of pathogens, analytes, toxins, drug residues, and malignant cells. Furthermore, similar to monoclonal antibodies, aptamers can serve as therapeutic tools. Unlike certain protein therapeutics, aptamers do not elicit antibody responses, and their modified sugars at the 2'-positions generally prevent toll-like receptor-mediated innate immune responses. The focus of this review is on aptamer-based targeting of PCSK9 and the application of aptamers both as biosensors and therapeutic agents.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Lipid Metabolism , Proprotein Convertase 9 , Proprotein Convertase 9/metabolism , Proprotein Convertase 9/genetics , Proprotein Convertase 9/blood , Humans , Biosensing Techniques/methods , Receptors, LDL/metabolism , SELEX Aptamer Technique , Hypercholesterolemia/drug therapy , Hypercholesterolemia/diagnosis , Hypercholesterolemia/blood , Animals , PCSK9 Inhibitors
14.
Am J Cardiol ; 221: 29-36, 2024 06 15.
Article in English | MEDLINE | ID: mdl-38636622

ABSTRACT

Atherosclerosis is an inflammatory disease. Coronary artery calcium (CAC) is a marker of atherosclerotic disease events and mortality risk. Increased GlycA, an emerging marker of inflammation, is associated with a higher risk for coronary artery disease (CAD). However, there is conflicting evidence on whether GlycA predicts subclinical CAD progression. We hypothesized that GlycA can predict subclinical CAC incidence/progression in healthy participants. We included 2,690 ELSA-Brasil cohort participants without cardiovascular/chronic inflammatory disease not receiving statin therapy who had GlycA levels measured and 2 interval CAC assessments between 2010 and 2018. Multivariable logistic and linear regression models were computed to evaluate GlycA as a predictor of CAC incidence and progression. CAC incidence required a baseline CAC of 0. CAC progression required a baseline CAC >0. The mean age of participants was 48.6 ± 7.7 years, 56.7% were women, and 54.6% and 16.1% (429 of 2,690) were White and Black, respectively. The mean CAC interscan period was 5.1 ± 0.9 years, the mean GlycA level was 414.7 ± 65 µmol/L, and the incidence of CAC was 13.1% (280 of 2,129). The GlycA level odds ratio for CAC incidence was 1.002 (95% confidence interval 1.0005 to 1.005, p = 0.016), adjusted for demographics, lifestyle, a family history of early CAD (≤60 years), lipids, and co-morbidities. The GlycA (≤p25 vs ≥p75) odds ratio for CAC progression (Berry definition) was 1.77 (95% confidence interval 1.07 to 2.96, p = 0.03) in a similar multivariable-adjusted model. Higher GlycA levels were associated with CAC incidence and progression in a healthy Brazilian cohort.


Subject(s)
Coronary Artery Disease , Disease Progression , Vascular Calcification , Humans , Female , Male , Middle Aged , Incidence , Coronary Artery Disease/epidemiology , Vascular Calcification/epidemiology , Vascular Calcification/diagnostic imaging , Brazil/epidemiology , Biomarkers/blood , Longitudinal Studies , Adult , Risk Factors
15.
Curr Vasc Pharmacol ; 22(4): 273-286, 2024.
Article in English | MEDLINE | ID: mdl-38639275

ABSTRACT

BACKGROUND: Identification of biomarkers to distinguish between stable and unstable plaque formation would be very useful to predict plaque vulnerability. METHODS: We downloaded microarray profiles of gene set enrichment (GSE) accession numbers including GSE71226 and GSE20680 (group A: containing healthy vs stable plaque samples) and GSE62646 and GSE34822 (group B: containing stable vs unstable plaque samples) from Gene expression omnibus (GEO) database. Differentially expressed genes were compared in both data sets of each group. RESULTS: Ten and 12 key genes were screened in groups A and B, respectively. Gene Ontology (GO) enrichment was applied by the plugin "BiNGO" (Biological networks gene ontology tool) of the Cytoscape. The key genes were mostly enriched in the biological process of positive regulation of the cellular process. The protein-protein interaction and co-expression network were analyzed by the STRING (search tool for the retrieval of interacting genes/proteins) and GeneMANIA (gene multiple association network integration algorithm) plugin of Cytoscape, respectively, which showed that Epidermal growth factor (EGF), Heparin-binding EGF like growth factor (HBEGF), and Matrix metalloproteinase 9 (MMP9) were at the core of the network. Further validation of key genes using two datasets showed that Phosphodiesterase 5A (PDE5A) and Protein S (PROS1) were decreased in unstable plaques, while Suppressor of cytokine signaling (SOCS3), HBEGF, and Leukocyte immunoglobulin-like receptor B4 (LILRB4) were increased. CONCLUSION: The present study used several datasets to identify key genes associated with stable and unstable atherosclerotic plaque.


Subject(s)
Computational Biology , Databases, Genetic , Gene Expression Profiling , Gene Regulatory Networks , Plaque, Atherosclerotic , Protein Interaction Maps , Humans , Plaque, Atherosclerotic/genetics , Genetic Markers , Transcriptome , Oligonucleotide Array Sequence Analysis , Gene Expression Regulation , Genetic Predisposition to Disease , Signal Transduction/genetics
16.
Cien Saude Colet ; 29(4): e19772023, 2024 Apr.
Article in Portuguese, English | MEDLINE | ID: mdl-38655973

ABSTRACT

The present theoretical essay is based on six reports concerning same-sex couples and gay and lesbian people in order to interconnect homoparenting and the adoption of children with disabilities, through the lenses of human and social sciences in public health. The reports were interpreted in light of studies on same-sex adoption and the adoption of children with disabilities. Feminist approaches related to care and disability were also included in the interpretative perspective, operating as expressive webs of grammars of ableism. It was found that media approaches endorse the right to family formation and the adoption of children with disabilities by homoparental families, but with little critical depth on the category of disability and without highlighting support for the adoption of all adoptee profiles. Moreover, the intersections between homophobia and ableism increase discriminatory and oppressive logics, with the union of social groups considered to be "undesirable" representing a strategy of governmentality that reveals the complexity of grammars of ableism, applied to the sexual and reproductive rights of LGBTQIA+ adopters and to the fundamental rights of children and adolescents with disabilities who are available for adoption.


O ensaio teórico parte de seis reportagens sobre casais homoafetivos e pessoas gays e lésbicas para interseccionar homoparentalidade e adoção de crianças com deficiência, pelas lentes das ciências humanas e sociais em saúde coletiva. As reportagens foram interpretadas à luz dos estudos sobre adoção homoparental e adoção de crianças com deficiência. Abordagens feministas sobre cuidado e deficiência também compuseram o olhar interpretativo, operando como teias expressivas das gramáticas do capacitismo. Verificou-se que as abordagens midiáticas endossam o direito à constituição familiar e à adoção de crianças com deficiência por famílias homoparentais, sem aprofundar criticamente a categoria deficiência e sem destacar apoio à adoção de todos os perfis de adotandos. E que as intersecções entre homofobia e capacitismo incrementam lógicas discriminatórias e de opressão, sendo a união de grupos considerados "indesejáveis" uma estratégia de governamentalidade que revela a complexidade das gramáticas do capacitismo aplicadas aos direitos sexuais e reprodutivos de adotantes LGBTQIA+ e aos direitos fundamentais de crianças e adolescentes com deficiência disponíveis para adoção.


Subject(s)
Adoption , Disabled Children , Humans , Child , Female , Male , Adolescent , Sexual and Gender Minorities/psychology , Homophobia/psychology , Human Rights , Feminism
17.
Curr Med Res Opin ; 40(sup1): 33-41, 2024.
Article in English | MEDLINE | ID: mdl-38597064

ABSTRACT

Stable angina, one manifestation of chronic coronary syndrome (CCS), is characterised by intermittent episodes of insufficient blood supply to the myocardium, provoking symptoms of myocardial ischaemia, particularly chest pain. These attacks usually occur during exercise or stress. Anti-ischaemic drugs are the mainstay of pharmacologic management of CCS with symptoms of angina. ß-blockers reduce heart rate and myocardial contractility, thus reducing myocardial oxygen consumption. These drugs have been shown to ameliorate the frequency of anginal attacks and to improve exercise capacity in these patients. Current management guidelines include ß-blockers as a first-line management option for most patients with CCS and symptoms of myocardial ischaemia, alongside dihydropyridine calcium channel blockers (CCB). The presence of comorbid angina and heart failure is a strong indication for starting with a ß-blocker. ß-blockers are also useful in the management of angina symptoms accompanied by a high heart rate, hypertension (with or without a renin-angiotensin-aldosterone-system [RAS] blocker or CCB), or microvascular angina (with a RAS blocker and a statin). A ß-blocker is not suitable for a patient with low heart rate (<50 bpm), although use of a ß-blocker may be supported by a pacemaker if the ß-blocker is strongly indicated) and should be used at a low dose only in patients with low blood pressure.


Subject(s)
Angina, Stable , Coronary Artery Disease , Myocardial Ischemia , Humans , Angina, Stable/drug therapy , Angina, Stable/chemically induced , Calcium Channel Blockers/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Adrenergic beta-Antagonists/pharmacology , Heart Rate , Coronary Artery Disease/drug therapy
18.
Arterioscler Thromb Vasc Biol ; 44(5): 1156-1164, 2024 May.
Article in English | MEDLINE | ID: mdl-38545781

ABSTRACT

BACKGROUND: Pediatric patients with homozygous familial hypercholesterolemia (HoFH) have an increased risk of atherosclerotic cardiovascular disease and difficulty meeting low-density lipoprotein cholesterol (LDL-C) goals. In this post hoc analysis, we evaluated pooled safety and efficacy data from 3 studies in pediatric patients with HoFH treated with the PCSK9 (proprotein convertase subtilisin/kexin type 9) monoclonal antibody inhibitor evolocumab. METHODS: Patients with HoFH aged 10 to 17 years received treatment with open-label evolocumab 420 mg subcutaneously monthly or biweekly in the TAUSSIG, RAMAN, or HAUSER-OLE clinical studies. All patients received background statins with or without ezetimibe. Study duration ranged from 12 to 260 weeks. The primary end point was treatment-emergent adverse events per 100 patient-years. Efficacy end points were changes from baseline to week 12 in lipids and PCSK9. RESULTS: Of the 39 patients in the pooled analysis, 69.2% were males, median age was 13.0 years, and 79.5% (31/39) had genotyped HoFH with LDLR pathogenic variants. Overall, median exposure to evolocumab was 18.2 (Q1, Q3: 3.0, 18.5) months. Treatment-emergent adverse events with an exposure-adjusted patient incidence rate of ≥5% were upper respiratory tract infection (6.6%), influenza (5.2%), and acne (5.0%) per 100 patient-years. Exposure-adjusted patient incidence of serious treatment-emergent adverse events was 13.3% per 100 patient-years. Excluding 4 patients receiving lipoprotein apheresis, week 12 median percentage change from baseline in LDL-C was -2.9% (Q1, Q3: -21.7, 1.5); however, 42.9% (15/35) of patients achieved ≥15% reduction in LDL-C from baseline. Residual LDLR (LDL receptor) activity was not associated with a reduction in LDL-C. CONCLUSIONS: In this pooled data analysis from 3 studies in pediatric patients with HoFH, evolocumab was well tolerated, with no new safety signals reported. These safety findings are consistent with findings from previous studies of evolocumab. Patients showed marked variability in LDL-C reduction. Results from this pooled analysis support guidelines suggesting a trial of PCSK9 inhibitor therapy regardless of estimated residual LDLR function. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01624142, NCT03403374, and NCT02624869.


Subject(s)
Antibodies, Monoclonal, Humanized , Anticholesteremic Agents , Cholesterol, LDL , Homozygote , Hyperlipoproteinemia Type II , PCSK9 Inhibitors , Adolescent , Child , Female , Humans , Male , Age Factors , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Anticholesteremic Agents/therapeutic use , Anticholesteremic Agents/adverse effects , Biomarkers/blood , Cholesterol, LDL/blood , Drug Therapy, Combination , Ezetimibe/therapeutic use , Ezetimibe/adverse effects , Genetic Predisposition to Disease , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/drug therapy , Hyperlipoproteinemia Type II/genetics , Hyperlipoproteinemia Type II/diagnosis , Phenotype , Proprotein Convertase 9/genetics , Serine Proteinase Inhibitors/adverse effects , Serine Proteinase Inhibitors/therapeutic use , Time Factors , Treatment Outcome , Clinical Studies as Topic
19.
J Clin Lipidol ; 18(3): e384-e393, 2024.
Article in English | MEDLINE | ID: mdl-38431498

ABSTRACT

BACKGROUND: Statins are the main strategy to reduce dyslipidemia-related cardiovascular risk. Nevertheless, there is scarce evidence on the real-world statins use in primary care settings in low-middle-income countries. OBJECTIVE: We conducted a cross-sectional retrospective study using anonymized data routinely collected by community health workers in Brazil aimed to evaluate statin use and associated factors in a primary prevention population with cardiovascular risk enhancers. METHODS: Study population consisted of adults with hypertension, diabetes, and/or dyslipidemia. The primary and secondary outcomes were the proportion of individuals self-reporting statins use on any dose and high-dose statins/high-intensity lipid-lowering therapy (LLT), respectively. RESULTS: Of the 2,133,900 adult individuals in the database, 415,766 (19.5%) were included in the study cohort. From this cohort, 89.1% had hypertension, 28.9% diabetes, and 5.5% dyslipidemia. The mean age was 61.5 (standard deviation 14.5) years, 63.4% were female, and 61.0% were of mixed-race. Only 2.6% and 0.1% of individuals self-reported the use of statins and high-dose statins/high-intensity LLT, respectively. Older age (odds ratio [OR] 1.96; 95% confidence interval [CI] 1.88, 2.05, p < 0.001), living in the South region of Brazil (OR 4.39; 95% CI 3.97, 4.85, p < 0.001), heart failure (OR 2.60; 95% CI 2.33, 2.89, p < 0.001), chronic kidney disease (OR 1.49; 95% CI 1.35, 1.64, p < 0.001), and anti-hypertensive medications use (OR 4.38; 95% CI 4.07, 4.71, p < 0.001) were independently associated with statin use. CONCLUSION: In a real-world evidence study analyzing data routinely collected in a digitized primary care setting, we observed a very low use of statins in a primary prevention population with cardiovascular risk enhancers in Brazil. Socio-demographic factors and co-morbidities were associated with higher statins use rates.


Subject(s)
Cardiovascular Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Primary Health Care , Primary Prevention , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Female , Male , Cross-Sectional Studies , Brazil/epidemiology , Middle Aged , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/epidemiology , Primary Prevention/methods , Retrospective Studies , Aged , Adult , Dyslipidemias/drug therapy , Dyslipidemias/epidemiology
20.
Cureus ; 16(2): e54380, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38505462

ABSTRACT

Guillain-Barré syndrome (GBS) in post-transplant patients is a rare clinical presentation. Although in the literature this neurological condition has been mainly associated with viral infections secondary to immunosuppression, GBS should not only be suspected in patients with an acute condition. It is essential to always rule out a viral or bacterial cause, looking for the most common sources, i.e., urinary, respiratory, and gastrointestinal. The diagnosis of GBS is clinically based, and its management is based on the use of intravenous immunoglobulin (IVIG) or plasma exchange. Its timely diagnosis allows treatment to be started early, thus improving the prognosis of these patients and reducing the time of hospitalization and complications associated with it. This report shows how an interdisciplinary approach is vital in such cases, as both the precipitant and the disease must be managed to decrease the morbidity and mortality associated with this condition. It is crucial to evaluate the benefits and risks of withdrawing immunosuppressive treatment in post-transplant patients, and being able to recognize when restarting them is indicated.

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