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.

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.

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.

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.

Coarctation of The Aorta: A Case-Series from a Tertiary Care Hospital

Abstract Background: Coarctation of the aorta is a congenital segmental narrowing of the aortic arch with severe hemodynamic repercussions and increased cardiovascular mortality. Early surgical correction and life-time echocardiographic follow-up must be performed to improve prognosis. However, this goal has been challenged by high rates of underdiagnosis, which delay surgical correction, and by recoarctation in up to one third of operated patients. Objectives: The objectives of this study were: (i) to register the frequency of common clinical signs at diagnosis of coarctation of the aorta; (ii) to describe the course of echocardiographic parameters before and during the follow-up of coartectomized subjects; (iii) to analyze the clinical prognosis of patients according to baseline characteristics, occurrence of recoarctation and associated malformations. Methods: Case-series of 72 patients coarctectomized between June 1996 and November 2016 in a tertiary care hospital. Clinical, echocardiographic and surgical variables were considered. All patients were submitted to coarctectomy by posterolateral thoracotomy and end-to-end anastomosis. Data were classified as parametric or non-parametric by Kolmogorov-Smirnov test. Parametric data were expressed as mean and standard deviation, and non-parametric data as median and interquartile range. Continuous variables were analyzed using paired t-tests, and categorical variables were compared by chi-square test. For all analysis, a p-value of less than 0.05 was considered statistically significant. Statistical analysis was performed using SPSS, version 20.0 (IBM, Chicago, IL, USA). Results: The mean follow-up time was 5.8 years (range: 0-20 years). At diagnosis, most patients had heart murmur (88%), non-palpable pulse in the lower limbs (50%), left ventricular hypertrophy (78%), and bicuspid aortic valve (33%), with a mean aortic peak gradient of 55 mmHg. After surgical correction, those without recoarctation were less symptomatic (60 vs 4.5%; p < 0.001), had lower aortic peak gradient (54 ± 3.8 vs 13 ± 0.8; p = 0.01) and left ventricle mass (95 ± 9.2 vs. 63 ± 11; p = 0.01), and the most common complications were late hypertension (39.2%), and recoarctation (27.6%). Recoarcted patients did not show improvement of neither clinical nor echocardiographic variables. Age at repair and bicuspid aortic valve groups had comparable results with controls. Surgical procedure was safe; mean time of hospitalization was 10 days and mean surgery time 2.3 hours. Conclusions: Coarctectomy improves cardiac symptoms and left ventricular hypertrophy, with a slight effect on the incidence of hypertension. Recoarctation occurs in one-third of patients and draws attention for the need of lifelong surveillance by echocardiography.

Prevalence, treatment, and control of dyslipidemia in diabetic participants of two brazilian cohorts: a place far from heaven.

OBJECTIVE: Diabetes is one of the leading causes of cardiovascular mortality. Over the last years, mortality has decreased significantly, more in individuals with diabetes than in healthy ones. That is mostly due to the control of other cardiovascular risk factors. The objective of our study was to analyze the dyslipidemia control in two diabetes cohorts. METHODS: Patients from two distinct cohorts were studied, 173 patients from the BHS (Brasília Heart Study) and 222 patients from the BDS (Brazilian Diabetes Study). The data on dyslipidemia control were studied in both different populations. All patients had diabetes. RESULTS: There are significant differences concerning comorbidities between the LDL-C and BDS groups. The average glycated hemoglobin is of 8.2 in the LDL-C > 100 group in comparison with 7.7 and 7.5 in the 70-100 and < 70 groups, respectively (p = 0.024). There is a higher percentage of hypertensive patients with LDL between 70-100 (63.9%), when comparing the < 70 and > 100 groups (54.3% and 54.9%, respectively; p = 0.005). Diastolic pressure is higher in the group with LDL > 100, with an average of 87 mmHg, in comparison with 82.6 mmHg and 81.9 mmHg in the 70-100 and < 70 groups, respectively (p = 0.019). The group with LDL > 100 has the greatest percentage of smokers (8.7%) in comparison with the groups with LDL between 70-100 and < 70 (5.6% and 4.3%, respectively; p = 0.015). There is also a difference in the previous incidence of coronaropathy. In the group with LDL < 70, 28.3% of patients had already experienced a previous infarction, compared with 11.1% and 10.6% in the 70-100 and > 100 groups, respectively (p < 0.001). CONCLUSIONS: The data in our study have shown that the dyslipidemia control in diabetic patients is inadequate and there is a tendency of direct association between lack of blood glucose control and lack of dyslipidemia control, in addition to the association with other cardiovascular risk factors, such as diastolic hypertension and smoking. This worsened control might be related to the plateau in the descending curve of mortality, and investments in this regard can improve the cardiovascular health in diabetic patients.

HDL-Targeted Therapies During Myocardial Infarction.

It is now apparent that a variety of deleterious mechanisms intrinsic to myocardial infarction (MI) exists and underlies its high residual lethality. Indeed, despite effective coronary patency therapies, ischemia and reperfusion (I/R) injury accounts for about 50% of the infarcted mass. In this context, recent studies in animal models have demonstrated that coronary reperfusion with high-density lipoproteins (HDL) may reduce MI size in up to 30%. A spectrum of mechanisms mediated by either HDL-related apolipoproteins or phospholipids attenuates myocardial cell death. Hence, promising therapeutic approaches such as infusion of reconstituted HDL particles, new HDL by genomic therapy, or the infusion of apoA-I mimetic peptides have been sought as a way of ensuring protection against I/R injury. In this review, we will explore the limitations and potential therapeutic effects of HDL therapies during the acute phase of MI.

Prevalence, treatment, and control of dyslipidemia in diabetic participants of two brazilian cohorts: a place far from heaven

SUMMARY OBJECTIVE Diabetes is one of the leading causes of cardiovascular mortality. Over the last years, mortality has decreased significantly, more in individuals with diabetes than in healthy ones. That is mostly due to the control of other cardiovascular risk factors. The objective of our study was to analyze the dyslipidemia control in two diabetes cohorts. METHODS Patients from two distinct cohorts were studied, 173 patients from the BHS (Brasília Heart Study) and 222 patients from the BDS (Brazilian Diabetes Study). The data on dyslipidemia control were studied in both different populations. All patients had diabetes. RESULTS There are significant differences concerning comorbidities between the LDL-C and BDS groups. The average glycated hemoglobin is of 8.2 in the LDL-C > 100 group in comparison with 7.7 and 7.5 in the 70-100 and < 70 groups, respectively (p = 0.024). There is a higher percentage of hypertensive patients with LDL between 70-100 (63.9%), when comparing the < 70 and > 100 groups (54.3% and 54.9%, respectively; p = 0.005). Diastolic pressure is higher in the group with LDL > 100, with an average of 87 mmHg, in comparison with 82.6 mmHg and 81.9 mmHg in the 70-100 and < 70 groups, respectively (p = 0.019). The group with LDL > 100 has the greatest percentage of smokers (8.7%) in comparison with the groups with LDL between 70-100 and < 70 (5.6% and 4.3%, respectively; p = 0.015). There is also a difference in the previous incidence of coronaropathy. In the group with LDL < 70, 28.3% of patients had already experienced a previous infarction, compared with 11.1% and 10.6% in the 70-100 and > 100 groups, respectively (p < 0.001). CONCLUSIONS The data in our study have shown that the dyslipidemia control in diabetic patients is inadequate and there is a tendency of direct association between lack of blood glucose control and lack of dyslipidemia control, in addition to the association with other cardiovascular risk factors, such as diastolic hypertension and smoking. This worsened control might be related to the plateau in the descending curve of mortality, and investments in this regard can improve the cardiovascular health in diabetic patients.

RESUMO OBJETIVO O diabetes é importante causa de mortalidade cardiovascular. Nos últimos anos, a mortalidade diminuiu substancialmente, mais em diabéticos do que em não diabéticos, em grande parte devido ao controle de outros fatores de risco cardiovasculares. Nosso estudo tem como objetivo analisar o controle de dislipidemia em duas coortes de diabéticos. MÉTODOS Foram estudados pacientes de duas coortes distintas, sendo 173 pacientes do BHS (Brasília Heart Study) e 222 pacientes do BDS (Brazilian Diabetes Study). Os dados sobre controle de dislipidemia foram estudados nas duas populações diferentes. Todos os pacientes eram diabéticos. RESULTADOS Há diferenças significativas em relação às comorbidades entre os grupos de LDL-C no BDS. A média de hemoglobina glicada é de 8,2 no grupo com LDL-C > 100, comparado com 7,7 e 7,5 nos grupos 70-100 e < 70, respectivamente (p = 0,024). Há maior porcentagem de pacientes hipertensos com LDL entre 70-100 (63,9%), quando comparado aos grupos < 70 e > 100 (54,3% e 54,9%, respectivamente; p = 0,005). A pressão diastólica é mais elevada no grupo com LDL > 100, com média de 87 mmHg, comparado com 82,6 mmHg e 81,9 mmHg nos grupos 70-100 e < 70, respectivamente (p = 0,019). O grupo com LDL > 100 tem maior porcentagem de tabagistas (8,7%) quando comparado aos grupos com LDL entre 70-100 e < 70 (5,6% e 4,3%, respectivamente; p = 0,015). Há, também, diferença na incidência prévia de coronariopatia. No grupo com LDL < 70, 28,3% dos pacientes já apresentaram infarto prévio, comparados com 11,1% e 10,6% nos grupos 70-100 e > 100, respectivamente (p < 0,001). CONCLUSÃO Os dados do nosso estudo mostram que o controle de dislipidemia em diabéticos é inadequado, e há uma tendência de associação direta entre descontrole glicêmico e descontrole de dislipidemia, além de associação com outros fatores de risco cardiovascular, como hipertensão diastólica e tabagismo. Esse pior controle pode estar relacionado ao platô no descenso da curva de mortalidade, e o investimento nesse quesito pode melhorar a saúde cardiovascular dos diabéticos.

Inhibition of the sodium-glucose co-transporter 2 in the elderly: clinical and mechanistic insights into safety and efficacy

SUMMARY The prevalence of type 2 diabetes mellitus (T2DM) in the elderly grew sharply over the last decade. Reduced insulin sensitivity and secretory capacity, weight gain, sarcopenia, and elevated adiposity are all common metabolic and body changes in the aging population that favor an increased risk of hypoglycemia, frailty syndrome, falls, and cognitive dysfunction. First line antidiabetic therapy is frequently not safe in older individuals because of its high risk of hypoglycemia and prevalent co-morbid diseases, such as chronic kidney disease, osteoporosis, cardiovascular disease, and obesity. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a new class of antidiabetic therapy that inhibits glucose and sodium reabsorption on renal proximal convoluted tubule. Its effect is well demonstrated in various clinical scenarios in the younger population. This review and metanalysis describe particularities of the SGLT2i on the elderly, with mechanistic insights of the potential benefit and remaining challenges about the use of these drugs in this important age group. Further, we will present a meta-analysis of the main effects of SGLT2i reported in post-hoc studies in which the median age of the subgroups analyzed was over 60 years. Despite the absence of specific clinical trials for this population, our findings suggest that SGLT2i therapy on older individuals is effective to lower glucose and maintain its effect on systolic blood pressure and body weight.

RESUMO A prevalência da diabetes mellitus tipo 2 em idosos cresceu muito na última década. A redução na sensibilidade à insulina e na capacidade secretora, ganho de peso, sarcopenia e adiposidade elevada são todas alterações metabólicas e corporais comuns entre a população idosa. Essas mudanças críticas favorecem o aumento no risco de hipoglicemia, síndrome de fragilidade, quedas e disfunções cognitivas. A primeira linha de tratamento contra a diabete muitas vezes não é segura para indivíduos mais velhos devido ao alto risco de hipoglicemia e a prevalência de comorbidades patogênicas, como doença renal crônica, osteoporose, doença cardiovascular e obesidade. Os inibidores do cotransportador sódio-glicose 2 (SGLT2) são uma nova classe de tratamento contra a diabete que inibe reabsorção de glicose e sódio na parte convoluta do túbulo proximal. Seu efeito é claramente demonstrado em diversos cenários clínicos em populações mais jovens. Esta revisão e meta-análise descreve as particularidades dos SGLT2 na população idosa, abordando os mecanismos dos potenciais benefícios e desafios ainda presentes do uso destes medicamentos nesse grupo etário tão importante. Além disso, apresentaremos uma meta-análise dos principais efeitos dos SGLT2 encontrados em estudos post-hoc nos quais a idade média dos subgrupos analisados foi acima de 60 anos. Apesar da ausência de ensaios clínicos que incluem essa população, os dados encontrados sugerem que o tratamento com SGLT2 em idosos é eficaz para diminuir os níveis de glicose e tem efeitos na pressão arterial sistólica e no peso corporal.