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Background: Cardiovascular diseases (CVD) remain the leading cause of mortality worldwide. Medication adherence is an important issue in managing chronic CVD, directly influencing outcomes and healthcare costs. Objectives: This systematic review, supported by the Brazilian Society of Cardiology, evaluates the impact of poor adherence to cardiovascular medications on critical clinical outcomes such as death and cardiovascular events. Methods: A comprehensive search was conducted across four databases, including Medline, Embase, Lilacs, and the Cochrane Library. The review included systematic reviews with meta-analyses that reported risk estimates for adherence to cardiovascular medications. Four systematic reviews, each incorporating observational studies, were selected. Results: The principal findings indicate that an increase in adherence to medications significantly reduces the risk of cardiovascular events, stroke, and all-cause death. Specifically, a 20% improvement in adherence to antihypertensive, lipid-lowering, and other cardiovascular medications correlated with reductions in cardiovascular events by 7%, 10%, and 9%, respectively; stroke by 17%, 13%, and 18%; and death by 12%, 9%, and 10%. The certainty of the evidence was moderate, suggesting that these effects are likely present. These findings emphasize the importance of enhancing medication adherence to improve clinical outcomes in CVD management. Conclusions: Evidence has demonstrated reductions in hard endpoints in both primary and secondary prevention through the control of conditions such as hypertension and elevated LDL cholesterol concentrations, as well as the benefits of antiplatelet therapy in atherosclerotic disease. However, additional studies are needed to better elucidate the relationship between adherence to cardiovascular medications and the improvement of critical clinical outcomes.
Introdução: As doenças cardiovasculares (DCV) continuam a ser a principal causa de mortalidade em todo o mundo. A adesão ao tratamento medicamentoso é uma questão importante no manejo das DCV crônicas, influenciando diretamente os resultados e os custos com saúde. Objetivos: Esta revisão sistemática, apoiada pela Sociedade Brasileira de Cardiologia, avalia o impacto da baixa adesão aos medicamentos cardiovasculares em desfechos clínicos críticos, como morte e eventos cardiovasculares. Métodos: Foi realizada uma busca abrangente em quatro bases de dados, incluindo Medline, Embase, Lilacs e Cochrane Library. A revisão incluiu revisões sistemáticas com meta-análises que relataram estimativas de risco para a adesão aos medicamentos cardiovasculares. Foram selecionadas quatro revisões sistemáticas, cada uma incorporando estudos observacionais. Resultados: Os principais achados indicam que um aumento na adesão aos medicamentos reduz significativamente o risco de eventos cardiovasculares, acidente vascular cerebral (AVC) e morte por todas as causas. Especificamente, uma melhoria de 20% na adesão a medicamentos antihipertensivos, hipolipemiantes e outros medicamentos cardiovasculares correlacionou-se com reduções nos eventos cardiovasculares de 7%, 10% e 9%, respectivamente; AVC de 17%, 13% e 18%; e morte de 12%, 9% e 10%. A certeza das evidências foi moderada, sugerindo que esses efeitos provavelmente estão presentes. Esses achados enfatizam a importância de melhorar a adesão ao tratamento medicamentoso para aprimorar os resultados clínicos no manejo das DCV. Conclusões: As evidências demonstraram reduções em desfechos duros tanto na prevenção primária quanto secundária através do controle de condições como hipertensão e concentrações elevadas de colesterol LDL, bem como os benefícios da terapia antiplaquetária em doenças ateroscleróticas. No entanto, são necessários estudos adicionais para elucidar melhor a relação entre a adesão aos medicamentos cardiovasculares e a melhoria dos desfechos clínicos críticos.
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Despite the noteworthy advancements and the introduction of new technologies in diagnostic tools for cardiovascular disorders, the electrocardiogram (ECG) remains a reliable, easily accessible, and affordable tool to use. In addition to its crucial role in cardiac emergencies, ECG can be considered a very useful ancillary tool for the diagnosis of many non-cardiac diseases as well. In this narrative review, we aimed to explore the potential contributions of ECG for the diagnosis of non-cardiac diseases such as stroke, migraine, pancreatitis, Kounis syndrome, hypothermia, esophageal disorders, pulmonary embolism, pulmonary diseases, electrolyte disturbances, anemia, coronavirus disease 2019, different intoxications and pregnancy.
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Optimal risk assessment for primary prevention remains highly challenging. Recent registries have highlighted major discrepancies between guidelines and daily practice. Although guidelines have improved over time and provide updated risk scores, they still fail to identify a significant proportion of at-risk individuals, who then miss out on effective prevention measures until their initial ischemic events. Cardiovascular imaging is progressively assuming an increasingly pivotal role, playing a crucial part in enhancing the meticulous categorization of individuals according to their risk profiles, thus enabling the customization of precise therapeutic strategies for patients with increased cardiovascular risks. For the most part, the current approach to patients with atherosclerotic cardiovascular disease (ASCVD) is homogeneous. However, data from registries (e.g., REACH, CORONOR) and randomized clinical trials (e.g., COMPASS, FOURIER, and ODYSSEY outcomes) highlight heterogeneity in the risks of recurrent ischemic events, which are especially higher in patients with poly-vascular disease and/or multivessel coronary disease. This indicates the need for a more individualized strategy and further research to improve definitions of individual residual risk, with a view of intensifying treatments in the subgroups with very high residual risk. In this narrative review, we discuss advances in cardiovascular imaging, its current place in the guidelines, the gaps in evidence, and perspectives for primary and secondary prevention to improve risk assessment and therapeutic strategies using cardiovascular imaging.
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BACKGROUND AND OBJECTIVES: This study aimed to identify CSF proteomic signatures characteristic of Parkinson disease (PD) and evaluate their clinical utility. METHODS: This observational study used data from the Parkinson's Progression Markers Initiative (PPMI), which enrolled patients with PD, healthy controls (HCs), and non-PD participants carrying GBA1, LRRK2, and/or SNCA pathogenic variants (genetic prodromals) at international sites. Study participants were chosen from PPMI enrollees based on the availability of aptamer-based CSF proteomic data, quantifying 4,071 proteins, and classified as patients with PD without GBA1, LRRK2, and/or SNCA pathogenic variants (nongenetic PD), HCs, patients with PD carrying the aforementioned pathogenic variants (genetic PD), or genetic prodromals. Differentially expressed protein (DEP) analysis and the least absolute shrinkage and selection operator (LASSO) were applied to the data from nongenetic PD and HCs. Signatures characteristics of nongenetic PD were quantified as a PD proteomic score (PD-ProS), validated internally and then externally using data of 1,556 CSF proteins from the LRRK2 Cohort Consortium (LCC). We further tested the PD-ProS in genetic PD and genetic prodromals and examined associations with clinical progression. RESULTS: Data from 279 patients with nongenetic PD (mean ± SD, age 62.0 ± 9.6 years; male 67.7%) and 141 HCs (age 60.5 ± 11.9 years; male 64.5%) were used for PD-ProS derivation. From 23 DEPs, LASSO determined weights of 14 DEPs for the PD-ProS (area under the curve [AUC] 0.83, 95% CI 0.78-0.87), validated in an independent internal validation cohort of 71 patients with nongenetic PD and 35 HCs (AUC 0.81, 95% CI 0.73-0.90). In the LCC, only 5 of the 14 DEPs were also measured. Notably, these 5 DEPs still distinguished 34 patients with nongenetic PD from 31 HCs with the same weights (AUC 0.75, 95% CI 0.63-0.87). Furthermore, the PD-ProS distinguished 258 patients with genetic PD from 365 genetic prodromals. Finally, regardless of genetic status, the PD-ProS independently predicted both cognitive and motor decline in PD (dementia, adjusted hazard ratio in the highest quintile [aHR-Q5] 2.8 [95% CI 1.6-5.0]; Hoehn and Yahr stage IV, aHR-Q5 2.1 [95% CI 1.1-4.0]). DISCUSSION: By integrating high-throughput proteomics with machine learning, we identified PD-associated CSF proteomic signatures crucial for PD development and progression. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT01176565). A link to the trial registry page is clinicaltrials.gov/ct2/show/NCT01141023. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the CSF proteome contains clinically important information regarding the development and progression of Parkinson disease that can be deciphered by a combination of high-throughput proteomics and machine learning.
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Enfermedad de Parkinson , Humanos , Masculino , Persona de Mediana Edad , Anciano , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/complicaciones , Proteómica , Modelos de Riesgos Proporcionales , Aprendizaje Automático , Progresión de la EnfermedadRESUMEN
The pathogenesis and clinical heterogeneity of Parkinson's disease (PD) have been evaluated from molecular, pathophysiological, and clinical perspectives. High-throughput proteomic analysis of cerebrospinal fluid (CSF) opened new opportunities for scrutinizing this heterogeneity. To date, this is the most comprehensive CSF-based proteomics profiling study in PD with 569 patients (350 idiopathic patients, 65 GBA + mutation carriers and 154 LRRK2 + mutation carriers), 534 controls, and 4135 proteins analyzed. Combining CSF aptamer-based proteomics with genetics we determined protein quantitative trait loci (pQTLs). Analyses of pQTLs together with summary statistics from the largest PD genome wide association study (GWAS) identified 68 potential causal proteins by Mendelian randomization. The top causal protein, GPNMB, was previously reported to be upregulated in the substantia nigra of PD patients. We also compared the CSF proteomes of patients and controls. Proteome differences between GBA + patients and unaffected GBA + controls suggest degeneration of dopaminergic neurons, altered dopamine metabolism and increased brain inflammation. In the LRRK2 + subcohort we found dysregulated lysosomal degradation, altered alpha-synuclein processing, and neurotransmission. Proteome differences between idiopathic patients and controls suggest increased neuroinflammation, mitochondrial dysfunction/oxidative stress, altered iron metabolism and potential neuroprotection mediated by vasoactive substances. Finally, we used proteomic data to stratify idiopathic patients into "endotypes". The identified endotypes show differences in cognitive and motor disease progression based on previously reported protein-based risk scores.Our findings not only contribute to the identification of new therapeutic targets but also to shape personalized medicine in CNS neurodegeneration.
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Humanos , Masculino , Femenino , Niño , Adolescente , Lipoproteína(a)/sangre , Factores de Riesgo de Enfermedad Cardiaca , Estenosis de la Válvula Aórtica/prevención & control , Enfermedad de la Arteria Coronaria/prevención & control , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Accidente Cerebrovascular/prevención & controlRESUMEN
OBJECTIVES: This observational, cross-sectional study based aimed to test whether heart failure (HF)-disease management program (DMP) components are influencing care and clinical decision-making in Brazil. METHODS: The survey respondents were cardiologists recommended by experts in the field and invited to participate in the survey via printed form or email. The survey consisted of 29 questions addressing site demographics, public versus private infrastructure, HF baseline data of patients, clinical management of HF, performance indicators, and perceptions about HF treatment. RESULTS: Data were obtained from 98 centers (58% public and 42% private practice) distributed across Brazil. Public HF-DMPs compared to private HF-DMP were associated with a higher percentage of HF-DMP-dedicated services (79% vs 24%; OR: 12, 95% CI: 94-34), multidisciplinary HF (MHF)-DMP [84% vs 65%; OR: 3; 95% CI: 1-8), HF educational programs (49% vs 18%; OR: 4; 95% CI: 1-2), written instructions before hospital discharge (83% vs 76%; OR: 1; 95% CI: 0-5), rehabilitation (69% vs 39%; OR: 3; 95% CI: 1-9), monitoring (44% vs 29%; OR: 2; 95% CI: 1-5), guideline-directed medical therapy-HF use (94% vs 85%; OR: 3; 95% CI: 0-15), and less B-type natriuretic peptide (BNP) dosage (73% vs 88%; OR: 3; 95% CI: 1-9), and key performance indicators (37% vs 60%; OR: 3; 95% CI: 1-7). In comparison to non- MHF-DMP, MHF-DMP was associated with more educational initiatives (42% vs 6%; OR: 12; 95% CI: 1-97), written instructions (83% vs 68%; OR: 2: 95% CI: 1-7), rehabilitation (69% vs 17%; OR: 11; 95% CI: 3-44), monitoring (47% vs 6%; OR: 14; 95% CI: 2-115), GDMT-HF (92% vs 83%; OR: 3; 95% CI: 0-15). In addition, there were less use of BNP as a biomarker (70% vs 84%; OR: 2; 95% CI: 1-8) and key performance indicators (35% vs 51%; OR: 2; 95% CI: 91,6) in the non-MHF group. Physicians considered changing or introducing new medications mostly when patients were hospitalized or when observing worsening disease and/or symptoms. Adherence to drug treatment and non-drug treatment factors were the greatest medical problems associated with HF treatment. CONCLUSION: HF-DMPs are highly heterogeneous. New strategies for HF care should consider the present study highlights and clinical decision-making processes to improve HF patient care.
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Humanos , Manejo de la Enfermedad , Insuficiencia Cardíaca/terapia , Brasil , Estudios Transversales , Encuestas y CuestionariosRESUMEN
Entende-se como hipertensão mascarada (HM) a existência de níveis pressóricos aumentados fora do consultório em pessoas supostamente normotensas e não tratadas. A hipertensos medicados, aplica-se a denominação de "hipertensão mascarada não controlada" (HMNC). Estas condições expõem expressivo contingente de indivíduos a um risco não identificado para eventos cardiovasculares. O presente trabalho teve como objetivo realizar uma revisão sistemática da literatura a fim de identificar os principais estudos de associação entre HM, HMNC e o risco de eventos cardiovasculares. De um total de 566 estudos, 19 foram incluídos na revisão. Dentre estes, apenas 4 não documentaram associação entre HM/HMNC e maior risco cardiovascular. Um estudo observou apenas associação com risco de infarto agudo do miocárdio (IAM) e outro apenas com o risco de acidente cerebrovascular (AVC). Os demais 13 estudos mostraram relação entre presença de HM e/ou HMNC e maior risco de eventos cardiovasculares como AVC, IAM e/ou morte. Em conclusão, existe associação entre a presença de hipertensão mascarada e o aumento no risco de eventos cardiovasculares. Alguns fenótipos especialmente vulneráveis e possíveis estratégias diagnósticas são também objeto de discussão.
Masked hypertension (MH) is defined as a normal ambulatory blood pressure, though elevated in the outpatient setting, in supposedly normotensive patients. For hypertensive patients, the term "uncontrolled masked hypertension" (MUCH) applies. Previous data suggest that subjects who present either MH or MUCH may be exposed to higher cardiovascular risk. The authors sought to carry out a systematic review of the literature regarding the association between MH, MUCH and risk of cardiovascular events. Among 566 studies retrieved,19 were included in the review. Only 4 studies did not document an association between MH/MUCH and risk of cardiovascular events. One study found an association only with the risk of acute myocardial infarction (AMI) and another with the risk of cerebrovascular events. The remaining 13 studies revealed a relationship between the presence of MH/MUCH and a higher risk of cardiovascular events such as stroke, AMI and/or death. In conclusion, there is an association between the presence of MH/MUCH and an increased risk of cardiovascular events. Some especially vulnerable phenotypes as well as possible diagnostic strategies are also discussed.
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Humanos , Monitoreo Ambulatorio de la Presión Arterial , Factores de Riesgo de Enfermedad Cardiaca , Hipertensión/diagnóstico , Hipertensión/prevención & controlRESUMEN
BACKGROUND: Omalizumab, a humanized recombinant monoclonal anti-IgE antibody, proved to be effective in patients with chronic spontaneous urticaria (CSU), including severe and treatment-refractory CSU. Here, we report omalizumab's effect on gene expression in skin biopsies from CSU patients enrolled in a double-blind, placebo-controlled study. METHODS: Chronic spontaneous urticaria patients (18-75 years) were randomized to either 300 mg omalizumab (n = 20) or placebo (n = 10) administered s.c. every 4 weeks for 12 weeks (NCT01599637). Lesional and nonlesional skin biopsies were collected from the same area of consenting patients and assessed at baseline and on Day 85 compared with skin biopsies from the same area of 10 untreated healthy volunteers (HVs). Gene expression data were generated using Affymetrix HG-U133Plus2.0 microarrays. Statistical analyses were performed using R packages. RESULTS: At baseline, 63 transcripts were differentially expressed between lesional and nonlesional skin. Two-thirds of these lesional signatures were also differentially expressed between lesional and HV skin. Upon treatment with omalizumab, >75% of lesional signatures changed to reflect nonlesional skin expression levels (different vs placebo, P < 0.01). Transcripts upregulated in lesional skin (vs nonlesional and/or HV skin) suggested increased mast cell/leukocyte infiltration (FCER1G, C3AR1, CD93, S100A8, and S100A9), increased oxidative stress, vascularization (CYR61), and skin repair events (KRT6A, KRT16). Lesional signatures were not modulated by treatment in nonresponders (defined based on UAS7 longitudinal changes ≥16). CONCLUSION: Omalizumab, in treatment responders, reverted transcriptional signatures associated with CSU lesion phenotype to reflect nonlesional/HV expression levels; this is consistent with observed omalizumab-mediated clinical improvement observed in patients with CSU.