Renal osteodystrophy and clinical outcomes: a prospective cohort study / Osteodistrofia renal e desfechos clínicos: um estudo de coorte prospectivo

Abstract Introduction: Renal osteodystrophy (ROD) refers to a group of bone morphological patterns that derive from distinct pathophysiological mechanisms. Whether the ROD subtypes influence long-term outcomes is unknown. Our objective was to explore the relationship between ROD and clinical outcomes. Methods: This study is a subanalysis of the Brazilian Registry of Bone Biopsies (REBRABO). Samples from individual patients were classified as having osteitis fibrosa (OF), mixed uremic osteodystrophy (MUO), adynamic bone disease (ABD), osteomalacia (OM), normal/minor alterations, and according to turnover/mineralization/volume (TMV) system. Patients were followed for 3.4 yrs. Clinical outcomes were: bone fractures, hospitalization, major adverse cardiovascular events (MACE), and death. Results: We enrolled 275 participants, of which 248 (90%) were on dialysis. At follow-up, 28 bone fractures, 97 hospitalizations, 44 MACE, and 70 deaths were recorded. ROD subtypes were not related to outcomes. Conclusion: The incidence of clinical outcomes did not differ between the types of ROD.

Resumo Introdução: Osteodistrofia renal (OR) refere-se a um grupo de padrões morfológicos ósseos que decorrem de mecanismos fisiopatológicos distintos. É desconhecido se os subtipos de OR influenciam desfechos em longo prazo. Nosso objetivo foi explorar as relações entre OR e desfechos. Métodos: Este estudo é uma subanálise do Registro Brasileiro de Biópsias Ósseas (REBRABO). As amostras de cada paciente foram classificadas em osteíte fibrosa (OF), osteodistrofia urêmica mista (MUO), doença óssea adinâmica (ABD), osteomalácia (OM), alterações normais/menores, e pelo sistema Remodelação / Mineralização / Volume (RMV). Os pacientes foram acompanhados por 3,4 anos. Os eventos clínicos foram: fraturas ósseas, hospitalizações, eventos cardiovasculares adversos maiores (MACE), e óbito. Resultados: Analisamos 275 indivíduos, 248 (90%) deles estavam em diálise. No acompanhamento, 28 fraturas ósseas, 97 hospitalizações, 44 MACE e 70 óbitos foram registrados. Os subtipos de OR não foram relacionados aos desfechos clínicos. Conclusão: A incidência de desfechos clínicos não diferiu entre os tipos de OR.

Renal osteodystrophy and clinical outcomes: a prospective cohort study.

INTRODUCTION: Renal osteodystrophy (ROD) refers to a group of bone morphological patterns that derive from distinct pathophysiological mechanisms. Whether the ROD subtypes influence long-term outcomes is unknown. Our objective was to explore the relationship between ROD and clinical outcomes. METHODS: This study is a subanalysis of the Brazilian Registry of Bone Biopsies (REBRABO). Samples from individual patients were classified as having osteitis fibrosa (OF), mixed uremic osteodystrophy (MUO), adynamic bone disease (ABD), osteomalacia (OM), normal/minor alterations, and according to turnover/mineralization/volume (TMV) system. Patients were followed for 3.4 yrs. Clinical outcomes were: bone fractures, hospitalization, major adverse cardiovascular events (MACE), and death. RESULTS: We enrolled 275 participants, of which 248 (90%) were on dialysis. At follow-up, 28 bone fractures, 97 hospitalizations, 44 MACE, and 70 deaths were recorded. ROD subtypes were not related to outcomes. CONCLUSION: The incidence of clinical outcomes did not differ between the types of ROD.

Relationship of blood pressure measured in the calf with arm blood pressure and arterial stiffness: a general population study.

AIM: Leg blood pressure (BP) measurement is needed when arm BP evaluation is not feasible, and calf BP, especially when measured in standing position, may have greater association with cardiovascular remodeling than arm BP. This study evaluated the relationship between calf and arm BP, and investigated whether calf BP would be superior to arm BP in predicting increased arterial stiffness [pulse wave velocity (PWV) > 10 m/s]. METHODS: We evaluated clinical and laboratory characteristics, BP measurements, and PWV in 1397 individuals resident in Baependi, Brazil, between 2017 and 2019. Arm BP was measured in the seated and supine positions while calf BP was measured in supine and standing positions using digital oscillometric devices. Carotid-femoral PWV was measured using a noninvasive mechanotransducer. RESULTS: The sample had 62.7% females, age = 48.1 ±â€Š15.4 years and 8.4% with PWV >10 m/s. Results of linear regression analysis showed that BP values of 140/90 mmHg measured in the arm in supine and seated position were equivalent to calf supine BP values of 164/81 mmHg and 166/78 mmHg and calf standing BP values of 217/137 mmHg and 221/137 mmHg, respectively. Calf-arm BP differences were associated with age, glomerular filtration rate, body mass index, smoking, low-density lipoprotein-cholesterol, diabetes and height. Furthermore, stepwise logistic regression analysis revealed that arm supine systolic BP, but not calf BP measurements, was independently associated with increased arterial stiffness. CONCLUSION: Thresholds of ≈165/80 mmHg and ≈220/135 mmHg could be used for diagnosing hypertension when only calf measurements in supine and standing positions, respectively, are available. Conversely, calf BP was not superior to arm BP in predicting increased arterial stiffness.

Effect of aluminum accumulation on bone and cardiovascular risk in the current era.

BACKGROUND: The prevalence of aluminum (Al) intoxication has declined over the past 3 decades. However, different groups still report on the diagnosis of Al in bone. Prolonged and low-intensity exposures to Al may not be captured by serum Al measurements, preventing its proper diagnosis. We hypothesize that bone Al accumulation may be related to bone and cardiovascular events in the current Era. AIMS: To detect the diagnosis of bone Al accumulation; to explore bone and cardiovascular consequences of Al accumulation. METHODS: This is a sub-analysis of The Brazilian Registry of Bone Biopsy, a prospective, multicentre cohort, with a mean follow-up of 3.4 years, including patients with CKD undergoing bone biopsy; bone fracture and major cardiovascular events (MACE) were adjudicated; Al accumulation was identified by solochrome-azurine staining; history of previous Al accumulation was registered based on information provided by the nephrologist who performed the bone biopsy; bone histomorphometry parameters, clinical data, and general biochemistry were registered. RESULTS: 275 individuals were considered; 96 (35%) patients have diagnosed with bone Al accumulation and were younger [50 (41-56) vs. 55 (43-61) years; p = 0.026], had lower body mass index [23.5 (21.6-25.5) vs. 24.3 (22.1-27.8) kg/m2; p = 0.017], higher dialysis vintage [108 (48-183) vs. 71 (28-132) months; p = 0.002], presented pruritus [23 (24%) vs. 20 (11%); p = 0.005], tendon rupture [7 (7%) vs. 3 (2%); p = 0.03) and bone pain [2 (0-3) vs. 0 (0-3) units; p = 0.02]. Logistic regression reveals that prior bone Al accumulation [OR: 4.517 (CI: 1.176-17.353); p = 0.03] and dialysis vintage [OR: 1.003 (CI: 1.000-1.007); p = 0.046] as independent determinants of bone Al accumulation; minor perturbations in dynamic bone parameters and no differences in bone fractures rate were noted; MACE was more prevalent in patients with bone Al accumulation [21 (34%) vs. 23 (18%) events; p = 0.016]. Cox regression shows the actual/prior diagnosis of bone Al accumulation and diabetes mellitus as independent predictors for MACE: [HR = 3.129 (CI: 1.439-6.804; p = 0.004) and HR = 2.785 (CI: 1.120-6.928; p = 0.028]. CONCLUSIONS: An elevated proportion of patients have bone Al accumulation, associated with a greater prevalence of bone pain, tendon rupture, and pruritus; bone Al accumulation was associated with minor perturbations in renal osteodystrophy; actual/prior diagnosis of bone Al accumulation and diabetes mellitus were independent predictors for MACE.

Effectiveness of Oral Hydration in Preventing Contrast-Induced Nephropathy in Individuals Undergoing Elective Coronary Interventions. / Eficácia da Hidratação Oral na Prevenção da Nefropatia Induzida por Contraste em Indivíduos Submetidos a Intervenções Coronárias Eletivas.

BACKGROUND: Contrast-induced nephropathy (CIN) is defined as worsening renal function, represented by an increase in serum creatinine of ≥ 25% or ≥ 0.5 mg/dL up to 72 h after exposure to iodinated contrast medium (ICM). The most effective preventive measure to date is intravenous hydration (IVH). Little is known about the effectiveness of outpatient oral hydration (OH). OBJETIVE: To investigate whether outpatient OH with water is as effective as IVH with 0.9% saline solution in preventing CIN in elective coronary procedures. METHODS: In this retrospective observational study, we analyzed the medical records and laboratory data of individuals undergoing percutaneous coronary procedures with ICM. Data collected between 2012 and 2015 refer to individuals who underwent IVH and those collected between 2016 and 2020 (after implementation of an OH protocol) correspond to individuals who underwent OH at home before and after coronary procedures as instructed by the nursing team. Statistical significance was established at α = 0.05. RESULTS: In total, 116 patients were included in this study: 58 in the IVH group and 58 in the OH group. An incidence of CIN of 15% (9/58) was observed in the group that received IVH and an incidence of 12% (7/58) was seen in the group that received OH (p = 0.68). CONCLUSION: The OH protocol, performed by the patient, appears to be as effective as the in-hospital IVH protocol for the renal protection of individuals susceptible to CIN in elective coronary interventions. These findings should be put to test in larger trials.

FUNDAMENTO: A nefropatia induzida por contraste (NIC) é definida como deterioração da função renal, representada por um aumento da creatinina sérica ≥25% ou ≥0,5 mg/dL até 72 horas após a exposição ao meio de contraste iodado (MCI). A medida preventiva mais eficaz até o momento é a hidratação venosa (HV). Pouco se sabe sobre a eficácia da hidratação oral (HO) ambulatorial. OBJETIVO: Investigar se a HO ambulatorial com água é tão eficaz quanto a HV com solução salina a 0,9% na prevenção de NIC em procedimentos coronarianos eletivos. MÉTODOS: Neste estudo observacional retrospectivo, foram analisados prontuários médicos e dados laboratoriais para coletar dados de indivíduos submetidos a procedimentos coronarianos percutâneos com MCI. Os dados coletados entre 2012 e 2015 avaliaram indivíduos que foram submetidos à HV e entre 2016 e 2020 (após a implementação de um protocolo de HO), os indivíduos que foram submetidos à HO em casa antes e depois de procedimentos coronarianos, conforme orientação da equipe de enfermagem. A significância estatística adotada foi de α=0,05. RESULTADOS: No total, 116 pacientes foram incluídos neste estudo, 58 no grupo HV e 58 no grupo HO. Observou-se incidência de NIC de 15% (9/58) no grupo que recebeu HV e 12% (7/58) no grupo que recebeu HO (p=0,68). CONCLUSÃO: O protocolo de HO realizado pelo paciente parece ser tão eficaz quanto o protocolo de HV hospitalar na proteção renal de indivíduos suscetíveis a desenvolver NIC em intervenções coronarianas eletivas. Essas descobertas devem ser testadas em ensaios mais abrangentes.

Very low HDL levels: clinical assessment and management

ABSTRACT In individuals with very low high-density lipoprotein (HDL-C) cholesterol, such as Tangier disease, LCAT deficiency, and familial hypoalphalipoproteinemia, there is an increased risk of premature atherosclerosis. However, analyzes based on comparisons of populations with small variations in HDL-C mediated by polygenic alterations do not confirm these findings, suggesting that there is an indirect association or heterogeneity in the pathophysiological mechanisms related to the reduction of HDL-C. Trials that evaluated some of the HDL functions demonstrate a more robust degree of association between the HDL system and atherosclerotic risk, but as they were not designed to modify lipoprotein functionality, there is insufficient data to establish a causal relationship. We currently have randomized clinical trials of therapies that increase HDL-C concentration by various mechanisms, and this HDL-C elevation has not independently demonstrated a reduction in the risk of cardiovascular events. Therefore, this evidence shows that (a) measuring HDL-C as a way of estimating HDL-related atheroprotective system function is insufficient and (b) we still do not know how to increase cardiovascular protection with therapies aimed at modifying HDL metabolism. This leads us to a greater effort to understand the mechanisms of molecular action and cellular interaction of HDL, completely abandoning the traditional view focused on the plasma concentration of HDL-C. In this review, we will detail this new understanding and the new horizon for using the HDL system to mitigate residual atherosclerotic risk.

Eficácia da Hidratação Oral na Prevenção da Nefropatia Induzida por Contraste em Indivíduos Submetidos a Intervenções Coronárias Eletivas / Effectiveness of Oral Hydration in Preventing Contrast-Induced Nephropathy in Individuals Undergoing Elective Coronary Interventions

Resumo Fundamento A nefropatia induzida por contraste (NIC) é definida como deterioração da função renal, representada por um aumento da creatinina sérica ≥25% ou ≥0,5 mg/dL até 72 horas após a exposição ao meio de contraste iodado (MCI). A medida preventiva mais eficaz até o momento é a hidratação venosa (HV). Pouco se sabe sobre a eficácia da hidratação oral (HO) ambulatorial. Objetivo Investigar se a HO ambulatorial com água é tão eficaz quanto a HV com solução salina a 0,9% na prevenção de NIC em procedimentos coronarianos eletivos. Métodos Neste estudo observacional retrospectivo, foram analisados prontuários médicos e dados laboratoriais para coletar dados de indivíduos submetidos a procedimentos coronarianos percutâneos com MCI. Os dados coletados entre 2012 e 2015 avaliaram indivíduos que foram submetidos à HV e entre 2016 e 2020 (após a implementação de um protocolo de HO), os indivíduos que foram submetidos à HO em casa antes e depois de procedimentos coronarianos, conforme orientação da equipe de enfermagem. A significância estatística adotada foi de α=0,05. Resultados No total, 116 pacientes foram incluídos neste estudo, 58 no grupo HV e 58 no grupo HO. Observou-se incidência de NIC de 15% (9/58) no grupo que recebeu HV e 12% (7/58) no grupo que recebeu HO (p=0,68). Conclusão O protocolo de HO realizado pelo paciente parece ser tão eficaz quanto o protocolo de HV hospitalar na proteção renal de indivíduos suscetíveis a desenvolver NIC em intervenções coronarianas eletivas. Essas descobertas devem ser testadas em ensaios mais abrangentes.

Abstract Background Contrast-induced nephropathy (CIN) is defined as worsening renal function, represented by an increase in serum creatinine of ≥ 25% or ≥ 0.5 mg/dL up to 72 h after exposure to iodinated contrast medium (ICM). The most effective preventive measure to date is intravenous hydration (IVH). Little is known about the effectiveness of outpatient oral hydration (OH). Objetive To investigate whether outpatient OH with water is as effective as IVH with 0.9% saline solution in preventing CIN in elective coronary procedures. Methods In this retrospective observational study, we analyzed the medical records and laboratory data of individuals undergoing percutaneous coronary procedures with ICM. Data collected between 2012 and 2015 refer to individuals who underwent IVH and those collected between 2016 and 2020 (after implementation of an OH protocol) correspond to individuals who underwent OH at home before and after coronary procedures as instructed by the nursing team. Statistical significance was established at α = 0.05. Results In total, 116 patients were included in this study: 58 in the IVH group and 58 in the OH group. An incidence of CIN of 15% (9/58) was observed in the group that received IVH and an incidence of 12% (7/58) was seen in the group that received OH (p = 0.68). Conclusion The OH protocol, performed by the patient, appears to be as effective as the in-hospital IVH protocol for the renal protection of individuals susceptible to CIN in elective coronary interventions. These findings should be put to test in larger trials.

Associação Positiva entre Autoanticorpos contra LDL Oxidada e HDL-C: Um Novo Mecanismo para Cardioproteção de HDL? / Positive Association between Autoantibodies Against Oxidized LDL and HDL-C: A Novel Mechanism for HDL Cardioprotection?

Resumo Fundamento No microambiente da placa aterosclerótica, os fosfolipídios oxidados expressos na superfície de lipoproteína de baixa densidade oxidada (oxLDL) se ligam a receptores scavenger em macrófagos provocando a formação de células espumosas e a progressão da placa. Autoanticorpos contra oxLDL (oxLDL-Ab) interagem com epítopos oxidativos levando à formação de imunocomplexos que são incapazes de interagir com receptores de macrófagos, assim suprimindo a aterogênese. A liberação de oxLDL-Ab pelas células B envolve a resposta da interleucina 5 e Th2, que por sua vez são potencializadas pela HDL. Assim, levantamos a hipótese de que indivíduos com níveis mais altos de HDL-C podem apresentar níveis elevados de oxLDL-Ab. Objetivo Avaliar a relação entre os níveis de HDL-C e oxLDL-Ab. Métodos Indivíduos assintomáticos (n = 193) foram agrupados de acordo com sua concentração de HDL-C para uma das três categorias seguintes: baixa (< 68 mg/dL), intermediária (de 68 a 80 mg/dL) ou alta (> 80 mg/dL). Os valores p < 0,05 foram considerados estatisticamente significativos. Resultados Nossa análise incluiu 193 indivíduos (média etária: 47 anos; masculino: 26,3%). Em comparação com os indivíduos no menor tercil de HDL-C, os mais elevados foram mais velhos (36 versus 53 anos; p = 0,001) e, menos frequentemente, masculinos (42,6% versus 20,9%; p = 0,001). Os valores médios de oxLDL-Ab aumentaram à medida que o grupo HDL-C aumentou (0,31, 0,33 e 0,43 unidades, respectivamente; p = 0,001 para tendência). A regressão linear simples encontrou uma relação significativa e positiva entre a variável independente, HDL-C, e a variável dependente, oxLDL-Ab (R = 0,293; p = 0,009). Essa relação manteve-se significativa (R = 0,30; p = 0,044), após ajuste por covariáveis. Os níveis de apolipoproteína AI também estiveram relacionados a oxLDL-Ab nos modelos de regressão linear simples e ajustada. Conclusões HDL-C e oxLDL-Ab estão independentemente relacionados.

Abstract Background In the atherosclerotic plaque microenvironment, oxidized phospholipids expressed in the oxidized low-density lipoprotein (oxLDL) surface bind to scavenger receptors of macrophages eliciting foam cell formation and plaque progression. Auto-antibodies against oxLDL (oxLDL-Ab) interact with oxidative epitopes leading to the formation of immune complexes that are unable to interact with macrophage receptors, thus abrogating atherogenesis. Release of oxLDL-Ab by B cells involves interleukin 5 and Th2 response, which in turn are potentiated by HDL. Thereby, we hypothesized that individuals with higher levels of HDL-C may plausibly display elevated titers of oxLDL-Ab. Objective To evaluate the relationship between HDL-C and oxLDL-Ab levels. Methods Asymptomatic individuals (n = 193) were grouped according to their HDL-C concentration to one of three categories: low (< 68 mg/dL), intermediate (68 to 80 mg/dL) or high (> 80 mg/dL). P values < 0.05 were considered statistically significant. Results Our analysis included 193 individuals (mean age: 47 years; male: 26.3%). Compared to individuals in the lowest HDL-C tertile, those in the highest tertile were older (36 versus 53 years; p = 0.001) and less frequently male (42.6% versus 20.9%; p = 0.001). Mean values of oxLDL-Ab increased as the HDL-C group escalated (0.31, 0.33 and 0.43 units, respectively; p = 0.001 for trend). Simple linear regression found a significant, positive relationship between the independent variable, HDL-C, and the dependent variable, oxLDL-Ab (R = 0.293; p = 0.009). This relation remained significant (R = 0.30; p = 0.044), after adjustment by covariates. Apolipoprotein AI levels were also related to oxLDL-Ab in both simple and adjusted linear regression models. Conclusion HDL-C and oxLDL-Ab are independently related.

Proteinuria in early referral to spectral domain optical coherence tomography for macular edema detection in type 2 diabetes individuals: results from the Brazilian diabetes study.

BACKGROUND: Measurement of retinal thickness by optical coherence tomography (OCT) shows higher diagnostic accuracy for diabetic macular edema (DME) than fundus photography alone. The expanding gap between the rising number of type 2 diabetes (T2D) individuals and the availability of OCT devices demands a targeted selection of individuals at higher risk of DME who would benefit the most from early referral. We sought to appraise if proteinuria should be considered in a targeted referral of T2D individuals to OCT examination. METHODS: This study was a cross-sectional analysis of 576 consecutive patients enrolled in the Brazilian Diabetes Study between June/2016 and December/2021 who underwent OCT exam and urinalysis to assess ME and proteinuria status, respectively. Differences in the prevalence of DME between proteinuria groups and across a range of diabetic retinopathy (DR) stages were evaluated. RESULTS: Among 1134 eyes included in this analysis, the prevalence of proteinuria was 22% and 18.2% of eyes had DME. Proteinuria was related to an increased prevalence of DME (13.2% vs 38.7% for control vs proteinuria, respectively; p < .001), with an OR of 4.08 [95% confidence interval (CI): 2.50-6.64, p < .001), after adjustment for covariates. Proteinuria was independently related to DME also among eyes with non-apparent DR [OR: 2.82; 95%CI: 1.34-5.93; p = .003] and non-proliferative DR (OR of 5.94, 95%CI 2.13-16.62, p < .001). Fundus photography spotted only half of the DME cases detected by OCT. CONCLUSION: In T2D individuals, early referral to OCT examination should be pursued for all individuals with concurrent proteinuria. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04949152.

Reference values for the triglyceride to high-density lipoprotein ratio and its association with cardiometabolic diseases in a mixed adult population: The ELSA-Brasil study.

BACKGROUND: Among several lipid ratios available, the triglyceride/HDL-cholesterol (TG/HDL-C) may detect individuals at risk of cardiometabolic diseases. However, its reference values for different ethnicities are not well established. OBJECTIVE: To define sex- and ethnicity-specific reference values for TG/HDL-C ratio in a large sample of healthy multiethnic adults and test its association with cardiometabolic conditions. METHODS: An apparently healthy sample (n = 2,472), aged 35-74, free of major cardiovascular risk factors, was used to generate the reference values for the TG/HDL-C. Exclusion criteria were diabetes, elevated blood pressure, obesity, hypercholesterolemia, severe hypertriglyceridemia, and smoking history. Cut-offs based on the reference values were tested in the whole ELSA Brasil study (n = 13,245), stratified by sex and ethnicity, to identify cardiometabolic conditions. RESULTS: TG/HDL-C ratio was higher in men than women, and did not change significantly with age, regardless of sex and ethnicity. Also, black individuals showed lower levels of TG/HDL-C as compared to other ethnic groups. ROC curve showed that the cut-off based on the 75th percentile displayed better sensitivities and specificities for men and women, regardless of ethnicity. Also, the sex- and ethnicity-specific cut-offs based on the 75th percentile were significantly associated with all tested cardiometabolic conditions (hypertension, diabetes, obesity, metabolic syndrome, and insulin resistance). Also, we observed that the use of a single sex-specific cut-off (men: 2.6; women: 1.7) could be used for the different ethnicities with good reliability. CONCLUSION: The defined TG/HDL-C cut-offs (men: 2.6; women: 1.7) are reliable and showed good clinical applicability to detect cardiometabolic conditions in a multiethnic population.

Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy.

There are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310-517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P < 0.001). RV mass-index and RV CM decreased to 13 ± 2.8 g/m2 and 8.13 ± 2 g/m2, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (P < 0.001). The RV ECV expansion correlated with a decrease in RV mass-index (r = -0.46; P < 0.001) and the increase in CK-MB. An RV ESV index at baseline above its median predicted an increased risk of LV dysfunction post-anthracyclines. In BC patients treated with anthracyclines, RV atrophy, systolic dysfunction, and a parallel increase of diffuse interstitial fibrosis indicate a cardiotoxic response on a similar scale as previously seen in the systemic left ventricle.

O impacto da educação na mortalidade por todas as causas após infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST): resultados do brasília heart study / The impact of education on all-cause mortality following St-segment elevation myocardial infarction (STEMI): results from the brazilian Heart study

Resumo Fundamento A baixa escolaridade tem sido considerada um fator de risco modificável significativo para o desenvolvimento de doenças cardiovasculares há bastante tempo. Apesar disso, ainda não se sabe muito sobre esse fator impactar ou não os desfechos após infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). Objetivo Investigar se a escolaridade é um fator de risco independente para mortalidade em pacientes com IAMCSST. Métodos Os pacientes com diagnóstico de IAMCSST foram consecutivamente incluídos em uma coorte prospectiva (Brasília Heart Study) e categorizados de acordo com os anos dos quartis de estudo (0-3, 4-5, 6-10 e >10 anos). Os grupos foram comparados pelo teste t de Student para variáveis contínuas e qui-quadrado para categóricas. A incidência de mortalidade por todas as causas foi comparada com Kaplan-Meyer com regressão de Cox ajustada por idade, sexo e escore GRACE. Valores de p < 0,05 foram considerados significativos. SPSS21.0 foi utilizado para todas as análises. Resultados A média de escolaridade foi de 6,63±4,94 anos. Durante o período de acompanhamento (média: 21 meses; até 6,8 anos), 83 pacientes vieram à óbito (mortalidade cumulativa de 15%). A taxa de mortalidade foi maior entre o quartil inferior em comparação com aqueles do quartil superior [18,5 vs. 6,8%; RR 2,725 (IC 95%: 1,27-5,83; p=0,01)]. Na análise multivariada, a baixa escolaridade perdeu significância estatística para mortalidade por todas as causas após ajuste para idade e sexo, com RR 1,305 (IC 95%: 0,538-3,16; p=0,556), e após ajuste pelo escore GRACE com RR 1,767 (IC 95%: 0,797-3,91; p=0,161). Conclusão Investigar se a escolaridade é um fator de risco independente para mortalidade em pacientes com IAMCSST.

Abstract Background Low schooling has been considered an important modifiable risk factor for the development of cardiovascular disease for a long time. Despite that, whether this factor impacts the outcomes following ST-segment elevation myocardial infarction (STEMI) is poorly understood. Objective To investigate whether schooling stands as an independent risk factor for mortality in STEMI patients. Methods STEMI-diagnosed patients were consecutively enrolled from a prospective cohort (Brasilia Heart Study) and categorized according to years of study quartiles (0-3, 4-5, 6-10 and >10 years). Groups were compared by student's t test for continuous variables and qui-square for categorical. Incidence of all-cause mortality was compared with Kaplan-Meyer with Cox regression adjusted by age, gender, and GRACE score. Values of p < 0.05 were considered significant. SPSS21.0 was used for all analysis. Results The mean schooling duration was 6.63±4.94 years. During the follow-up period (mean: 21 months; up to 6.8 years), 83 patients died (cumulative mortality of 15%). Mortality rate was higher among the lowest quartile compared to those in the highest quartile [18.5 vs 6.8%; HR 2.725 (95% CI: 1.27-5.83; p=0.01)]. In multivariate analysis, low schooling has lost statistical significance for all-cause mortality after adjustment for age and gender, with HR of 1.305 (95% CI: 0.538-3.16; p=0.556), and after adjustment by GRACE score with an HR of 1.767 (95% CI: .797-3.91; p=0.161). Conclusion Low schooling was not an independent risk factor for mortality in STEMI patients.

Cardiovascular safety of naltrexone and bupropion therapy: Systematic review and meta-analyses.

Despite being approved for clinical use, evidence of cardiovascular safety (CV) is lacking for treatment with bupropion, naltrexone, or their combination (B-N). The purpose of the study is to determine the relationship between these treatments and the risk of major cardiovascular adverse events (MACE). Phase 3 randomized clinical trials (RCT) evaluating bupropion, naltrexone, or B-N versus control with reported incidence of MACE. The meta-analysis included 12 RCTs, 69% for weight loss and 29% for smoking cessation, with 19,176 patients and 7354 patient-years who were randomized to an active treatment (bupropion [n = 2965] or B-N [n = 6980] or naltrexone [n = 249]) versus control (placebo [n = 6968] or nicotine patch [n = 2014]). The mean age was 54 ± 8 years (55% female), and the baseline BMI was 32 ± 5 kg/m2 . The additive network meta-analysis model for random effects showed no association between bupropion, B-N, or naltrexone and MACE (odds ratio [OR] = 0.90 [95%CI 0.65-1.25], p = 0.52; OR = 0.97 [95%CI 0.75-1.24], p = 0.79; OR = 1.08 [95%CI 0.71-1.63], p = 0.73, respectively; I2 = 0%, p = 0.86). Meta-regression analyses showed no significant association between MACE and potential confounders from RCT demographic disparities (p = 0.58). The statistical power (post hoc two-tailed) for non-inferiority was 91%, giving a strong probability of validity. Naltrexone, bupropion, or B-N is not associated with the incidence of MACE as compared with placebo.

Intra-operative esmolol and pain following mastectomy: A randomised clinical trial.

BACKGROUND: Esmolol is a beta-1 selective blocker that has been shown to reduce postoperative pain. Its antinociceptive effects have not been tested following mastectomy. OBJECTIVE: To evaluate the safety, efficacy and antinociception of intra-operative esmolol infusion after mastectomy. DESIGN: Randomised, double-blinded, placebo-controlled trial. SETTING: Tertiary referral centre, Brasília, Brazil. Recruitment: July 2015 to July 2017. PATIENTS: Seventy women scheduled for mastectomy, ASA I to III, aged 18 to 75 years. Four were excluded. INTERVENTIONS: All underwent general anaesthesia. The intervention group received a bolus of 0.5 mg kg-1 of esmolol over 10 min followed by a continuous infusion of 100 µg kg-1 min-1. The placebo group received saline. MAIN OUTCOME MEASURES: The primary outcome was pain at rest 24 h after mastectomy as measured by a 0 to 10 numeric rating scale. RESULTS: Pain scores at rest 24 h after mastectomy were lower in esmolol-treated patients compared with placebo (mean difference = -1.51, 95% confidence interval (CI), -2.36 to -0.65, P = 0.001). On arrival in the postanaesthesia care unit (PACU), the occurrence of pain was also lower in the esmolol group, at rest and on effort (P = 0.009 and P = 0.013, respectively), on discharge from PACU (P = 0.009 and P = 0.015), 12 h (P = 0.01 and P = 0.007) and on effort in the 24 postoperative hours (P = 0.003). Mean morphine consumption was reduced by 77% in the esmolol group compared with the placebo group (mean difference  = -2.52 mg, 95% CI = -3.67 to -1.38, P < 0.001). The length of hospital stay was shorter for the esmolol group (mean difference = -6.9 h, 95% CI, -13.4 to -0.31, P = 0.040). CONCLUSION: Esmolol was well tolerated, allowed a notable reduction in the dose of rescue analgesics and demonstrated superior efficacy compared to placebo for pain management after mastectomy. TRIAL REGISTRATION: ClinicalTrials/NCT02466542.

O Escore Gensini e a Carga Trombótica Adicionam Valor Preditivo ao Escore SYNTAX na Detecção de No-Reflow após Infarto do Miocárdio / Gensini Score and Thrombus Burden Add Predictive Value to the SYNTAX Score in Detecting No-Reflow after Myocardial Infarction

Resumo Fundamento O fenômeno de no-reflow após a intervenção coronária percutânea está associado a um pior prognóstico em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). O escore SYNTAX é um bom preditor de no-reflow. Objetivo Nosso objetivo foi avaliar se a carga aterosclerótica (escore Gensini) e a carga trombótica na artéria coronária culpada melhorariam a capacidade do escore SYNTAX para detectar o no-reflow. Métodos Neste estudo coorte prospectivo, foram estudados pacientes com IAMCSST consecutivos que se apresentaram dentro de 12 horas a partir do início dos sintomas. O no-reflow foi definido como fluxo TIMI < 3 ou fluxo TIMI =3 mas grau de blush miocárdico (myocardial blush grade) < 2. A carga trombótica foi quantificada de acordo com o grau TIMI de trombo (0 a 5). Resultados Foram incluídos 481 pacientes no estudo, com idade média de 61±11 anos. O fenômeno de no-reflow ocorreu em 32,8% dos pacientes. O escore SYNTAX (OR=1,05, IC95% 1,01-1,08, p<0,01), a carga trombótica (OR=1,17, IC95% 1,06-1,31, p<0,01), e o escore Gensini (OR=1,37, IC95% 1,13-1,65, p<0,01) foram preditores independentes do no-reflow. Os escores combinados apresentaram uma maior área sob a curva quando comparados ao escore SYNTAX isolado (0,78 [0,73-0,82] vs 0,73 [0,68-0,78], p=0,03). A análise da melhora da reclassificação líquida (NRI) categórica (0,11 [0,01-0,22], p=0,02) e contínua (NRI>0) (0,54 [0,035-0,73], p<0.001) mostrou melhora na capacidade preditiva do no-reflow no modelo combinado, com melhora da discriminação integrada (IDI) de 0,07 (0,04-0,09, p<0,001). Conclusões Nossos achados sugerem que, em pacientes com IAMCSST submetidos à intervenção coronária percutânea, a carga aterosclerótica e a carga trombótica na artéria culpada adicionam valor preditivo ao escore SYNTAX na detecção do fenômeno no-reflow. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

Abstract Background No-reflow after percutaneous coronary intervention is associated with poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). SYNTAX score is a good predictor of no-reflow. Objective We aimed to evaluate whether atherosclerotic burden (Gensini score) and thrombus burden in the culprit coronary artery would improve the ability of the SYNTAX score to detect no-reflow. Methods In this prospective cohort study, consecutive patients with STEMI who presented within 12 h of onset of symptoms were selected for this study. No-reflow was defined as TIMI flow < 3 o r TIMI flow = 3 but myocardial blush grade <2. Thrombus burden was quantified according to the TIMI thrombus grade scale (0 to 5). Results A total of 481 patients were included (mean age 61±11 years). No-reflow occurred in 32.8%. SYNTAX score (OR=1.05, 95%CI 1.01-1.08, p<0.01), thrombus burden (OR=1.17, 95%CI 1.06-1.31, p<0.01), and Gensini score (OR=1.37, 95%CI 1.13-1.65, p<0.01) were independent predictors of no-reflow. Combined scores had a larger area under the curve than the SYNTAX score alone (0.78 [0.73-0.82] vs 0.73 [0.68-0.78], p=0.03). Analyses of both categorical (0.11 [0.01-0.22], p=0.02), and continuous net reclassification improvement (NRI>0) (0.54 [0.035-0.73], p<0.001) showed improvement in the predictive ability of no-reflow in the combined model, with integrated discrimination improvement (IDI) of 0.07 (0.04-0.09, p<0.001). Conclusions Our findings suggest that, in patients with STEMI undergoing percutaneous coronary intervention, atherosclerotic burden and thrombus burden in the culprit artery add predictive value to the SYNTAX score in detecting the no-reflow phenomenon. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)

Reference values of office central blood pressure, pulse wave velocity, and augmentation index recorded by means of the Mobil-O-Graph PWA monitor.

Assessment of central blood pressure (BP), pulse wave velocity (PWV), and augmentation index (AIx) measurements may improve cardiovascular risk stratification. This study aimed to establish reference office values for central BP, PWV, and AIx by means of a Mobil-O-Graph PWA monitor and to evaluate the impact of cardiovascular risk factors (CVRFs) on these measurements. We cross-sectionally evaluated clinical characteristics, central BP, PWV, AIx, and peripheral BP measurements among 867 apparently healthy individuals (age = 46.0 ± 15.5 years, 39% males) who were free of obesity, hypertension, active smoking, dyslipidemia, and diabetes (CVRF-No) and 5632 individuals (age = 57.0 ± 14.7 years, 44% males) with at least one of these major CVRFs (CVRF-Yes). Reference values for central BP, PWV, and AIx were provided for the CVRF-No and CVRF-Yes groups, stratified by age and sex. PWV and AIx exhibited curvilinear increases with age, and there was an interaction between age and sex for central systolic BP and PWV in both the CVRF-No and CVRF-Yes groups. The results of a multivariable analysis including the whole sample (n = 6499) showed that obesity had a direct association with central BP, while diabetes was directly related to PWV. In addition, alcohol intake was directly associated with central BP, while performance of physical activity was inversely related to AIx. In conclusion, values of office-measured central BP, PWV, and AIx obtained in an apparently healthy population and in a population with CVRFs are now available according to age and sex and may be useful to build thresholds for use in clinical practice.