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In-hospital delays in permanent cardiac pacemaker (PPM) implantation are common and may result in in-hospital infection among patients waiting for PPM implantation (pre-PPM-HI). This study investigated the predictors and prognostic impact of these events.We retrospectively evaluated 905 consecutive patients (68.2 ± 16.0 years; 54% males) who underwent PPM implantation. Clinical characteristics, pre-PPM-HI and 30-day mortality were recorded and a risk score for pre-PPM-HI was generated using multivariable logistic regression coefficients.Eigthy-nine patients (10% of the sample) developed pre-PPM-HI. Multivariable logistic regression analysis identified urinary catheter use, complete atrioventricular block, implantation of temporary pacemaker and diabetes mellitus as independent predictors of pre-PPM-HI. The generated score (range 0-10.1) played a better role in predicting pre-PPM-HI than individual factors, yielding an area under the curve [95%CI] of 0.754 [0.705-0.803]. Patients with score ≥ 7.5 had 18-fold greater risk of developing pre-PPM-HI than those with score 2.5. Furthermore, multivariable Cox-regression analysis showed that patients who developed pre-PPM-HI had greater 30-day mortality after PPM implantation (hazard ratio [95%CI] = 2.90 [1.18-7.16], p = 0.021) compared with their counterparts.This study reveals that pre-PPM-HI is an independent predictor of early mortality after PPM implantation. In addition, a clinical score developed from simple clinical variables accurately identified patients at high risk of pre-PPM-HI. In scenarios where delays in PPM implantation are unavoidable, such as reference hospitals with high demand, the use of this tool can potentially help in the hierarchy of patients and in the reduction of this adverse event.

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.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.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;In T2D individuals, early referral to OCT examination should be pursued for all individuals with concurrent proteinuria.ClinicalTrials.gov Identifier: NCT04949152.

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.

There are concerns that hypertension control may decrease during the COVID-19 pandemic. This study evaluated the impact of the COVID-19 pandemic on office blood pressure (OBP) and home blood pressure monitoring (HBPM) control in a large Brazilian nationwide sample. The results of an adjusted spline analysis evaluating the trajectory of OBP and HBPM control from 01/Jan/2019 to 31/Dec/2020 among independent participants who were untreated (n = 24,227) or treated (n = 27,699) with antihypertensive medications showed a modest and transient improvement in OBP control among treated individuals, which was restricted to the early months following the COVID-19 pandemic outbreak. Furthermore, slight reductions in OBP and HBPM values were detected in the early months following the COVID-19 pandemic outbreak among treated (n = 987) participants for whom blood pressure measurements before and during the pandemic were available, but not among untreated (n = 495) participants. In conclusion, we found no major adverse influence of the COVID-19 pandemic on OBP and HBPM control in a large nationwide sample., *Adjusted prevalence of high office blood pressure (OBP) and home blood pressure monitoring (HBPM) before and during the Covid-19 pandemic among independent treated participants. **p

Purpose Patients hospitalized with COVID-19 may develop a hyperinflammatory, dysregulated cytokine “storm” that rapidly progresses to acute respiratory distress syndrome, multiple organ dysfunction, and even death. Remote ischaemic conditioning (RIC) has elicited anti-inflammatory and cytoprotective benefits by reducing cytokines following sepsis in animal studies. Therefore, we investigated whether RIC would mitigate the inflammatory cytokine cascade induced by COVID-19. Methods We conducted a prospective, multicentre, randomized, sham-controlled, single-blind trial in Brazil and South Africa. Non-critically ill adult patients with COVID-19 pneumonia were randomly allocated (1:1) to receive either RIC (intermittent ischaemia/reperfusion applied through four 5-min cycles of inflation (20 mmHg above systolic blood pressure) and deflation of an automated blood-pressure cuff) or sham for approximately 15 days. Serum was collected following RIC/sham administration and analyzed for inflammatory cytokines using flow cytometry. The endpoint was the change in serum cytokine concentrations. Participants were followed for 30 days. Results Eighty randomized participants (40 RIC and 40 sham) completed the trial. Baseline characteristics according to trial intervention were overall balanced. Despite downward trajectories of all cytokines across hospitalization, we observed no substantial changes in cytokine concentrations after successive days of RIC. Time to clinical improvement was similar in both groups (HR 1.66; 95% CI, 0.938–2.948, p 0.08). Overall RIC did not demonstrate a significant impact on the composite outcome of all-cause death or clinical deterioration (HR 1.19; 95% CI, 0.616–2.295, p = 0.61). Conclusion RIC did not reduce the hypercytokinaemia induced by COVID-19 or prevent clinical deterioration to critical care. Trial Registration ClinicalTrials.gov Identifier: NCT04699227.

A estratificação de risco cardiovascular (CV) é uma etapa fundamental na avaliação do paciente hipertenso e permite a definição de metas terapêuticas de pressão arterial mais adequadas e a identificação e manejo de agravamentos de saúde associados à hipertensão arterial sistemica (HAS). Para se obter uma estimativa de risco adequada do paciente hipertenso, a Diretriz Brasileira de HAS de 2020 (DBHA-2020) recomenda que seja feita a investigação sistemática de fatores de risco (FR), lesões em órgãos-alvo (LOA) e doença CV e/ou renal. Os principais FR são: sexo masculino, idade superior a 55 anos para homens e 65 anos para mulheres, história familiar de doença CV prematura, tabagismo, dislipidemia, diabetes e obesidade. De acordo com a DBHA-2020, são considerados de alto risco CV os pacientes com pressão arterial ≥130/85 mmHg no consultório, que tenham LOA, diabetes ou doença CV/renal; todos os hipertensos com mais de 2 FR; os hipertensos em estágio 2 com 1 ou 2 FR, e os hipertensos em estágio 3. Nos pacientes considerados de risco CV moderado, a DBHA-2020 sugere a avaliação adicional de indicadores de LOA subclínica (hipertrofia ventricular esquerda por ecocar- diografia, albuminúria, índice tornozelo-braquial e velocidade de onda de pulso) com o intuito de incrementar a acurácia do risco estimado. Entretanto, é importante ressaltar que as estimativas de risco ainda apresentam limitações quanto à acurácia, em especial por se basearem exclusivamente em medidas de pressão arterial no consultório e não considerarem a duração da exposição aos FR, à HAS e ao tratamento anti-hipertensivo.

Background The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. Results The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Background Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve endothelial dysfunction and reduce cardiovascular events in individuals with type 2 diabetes (T2D). Proprotein convertase subtilisin/kexin 9 (PCSK9i) inhibitors reduce cardiovascular events in high-risk patients. Whether the addition of PCSK9i to SGLT2i treatment adds benefits is not known. Objectives To assess the PCSK9-i effect on the endothelial function of T2D individuals under treatment with SGLT2-i. Methods Individuals with T2D were randomized in a 1:1 ratio to a 16-week treatment with either empagliflozin (E) or empagliflozin plus evolocumab (EE). The primary endpoint was post-treatment change from baseline in flow-mediated dilation (FMD) at 1-min. Secondary outcomes included changes in plasma levels of nitric oxide metabolites and isoprostane. Results A total of 110 patients were enrolled, the mean age was 58 years, and 71% were men. The median post-treatment change in FMD at 1-min was 2.7% (interquartile range [IQR]: 0.9%) and 0.4% (IQR: 0.9%) in the EE and E groups, respectively (p Conclusions In individuals with T2D, the addition of evolocumab on top of empagliflozin improves endothelial function.

Carotid intima-media thickness (cIMT) is considered a marker of subclinical atherosclerosis and is related to target-organ damage in hypertensive patients. However, increased cIMT may be due to increases in the thickness of intima (cIT) and media (cMT) layers. This study evaluated whether cIMT layers (cIT and cMT) had a greater association with carotid atherosclerotic plaques and left ventricular hypertrophy (LVH) than cIMT in hypertensive subjects. We cross-sectionally evaluated clinical, carotid, and echocardiography characteristics of 186 hypertensive patients followed at an outpatient clinic. High-resolution images of common carotid arteries were obtained by ultrasonography equipped with 10-MHz transducers, and cIT, cMT, and cIMT were manually measured using an image-processing software. Among all participants (n = 186; age = 60.8 ± 10.9 years, 43% males), there were 58% with carotid plaques and 58% with LVH. Mean cIT, cMT, and cIMT values were 0.267 ± 0.060, 0.475 ± 0.107, and 0.742 ± 0.142 mm, respectively. In logistic regression analysis adjusted for relevant covariates, carotid plaques showed stronger association with cIT than with cMT and cIMT. Furthermore, cIT showed greater area under the ROC curve (0.92; 95% CI 0.87-0.96) than cIMT (0.79; 95% CI 0.72-0.85) and cMT (0.64; 95% CI 0.56-0.72) to identify plaques. Conversely, cIT, cMT, and cIMT had modest association and accuracy to identify LVH (area under the ROC curve = 0.61, 0.57, and 0.60, respectively). In conclusion, cIT is a more accurate marker of atherosclerosis than cMT or cIMT, while cIT and cMT provide no incremental value in identifying LVH when compared with cIMT among hypertensive subjects.

Background Sodium glucose co-transporter 2 inhibitors (SGLT2is) prevent hospitalization resulting from heart failure (HHF). However, patients with type 2 diabetes mellitus use multiple antihyperglycemic drugs to achieve glycosylated hemoglobin (HbA1c) targets. In these drug combinations, the risk of HHF is unpredictable and so is the parallel effect of glucose-lowering. Purpose To examine the impact of antihyperglycemic drugs and their association on HHF. Data Sources Forty randomized controlled trials (RCTs) reporting HHF. Study Selection Published RCTs were the data source. Data Extraction Incidence rates of HHF. Data Synthesis Random additive-effects network meta-analysis showed that metformin (P = 0.55), sulfonylureas (P = 0.51), glucagon-like peptide-1 receptor-agonist (P = 0.16), and dipeptidyl peptidase 4 inhibitors (DPP4is; P = 0.54) were neutral on the risk of HHF. SGLT2is and SGLT2is + DPP4is reduced the risk of HHF with a hazard ratio (HR) of 0.68 (95% CI, 0.60-0.76; P Limitations There are no data to verify drug combinations available for clinical use and to discriminate the effect of drugs within each of the therapeutic classes. Conclusions The risk of HHF is reduced by SGLT2is as monotherapy or in combination with DPP4is and increased by TZDs as monotherapy or in combination. Glucose-lowering provides an additive effect of reducing HHF.

This study compared the ability of guideline-proposed office blood pressure (OBP) screening thresholds [European Society of Hypertension (ESH) guidelines: 130/85 mmHg for individuals with an OBP 140/90 mmHg; American College of Cardiology/American Heart Association (ACC/AHA) guidelines: 120/75 mmHg for individuals with an OBP 130/80 mmHg] and novel screening scores to identify normotensive individuals at high risk of having masked hypertension (MH) in an office setting. We cross-sectionally evaluated untreated participants with an OBP 140/90 mmHg (n = 22,266) and an OBP 130/80 mmHg (n = 10,005) who underwent home blood pressure monitoring (HBPM) (derivation cohort) from 686 Brazilian sites. MH was defined according to criteria suggested by the ESH (OBP 140/90 mmHg; HBPM ≥ 135/85 mmHg), Brazilian Society of Cardiology (BSC) (OBP 140/90 mmHg; HBPM ≥ 130/80 mmHg) and ACC/AHA (OBP 130/80 mmHg; HBPM ≥ 130/80 mmHg). Scores were generated from multivariable logistic regression coefficients between MH and clinical variables (OBP, age, sex, and BMI). Considering the ESH, BSC, and ACC/AHA criteria, 17.2%, 38.5%, and 21.2% of the participants had MH, respectively. Guideline-proposed OBP screening thresholds yielded area under curve (AUC) values of 0.640 (for ESH criteria), 0.641 (for BSC criteria), and 0.619 (for ACC/AHA criteria) for predicting MH, while scores presented as continuous variables or quartiles yielded AUC values of 0.700 and 0.688 (for ESH criteria), 0.720 and 0.709 (for BSC criteria), and 0.671 and 0.661 (for ACC/AHA criteria), respectively. Further analyses performed with alternative untreated participants (validation cohort; n = 2807 with an OBP 140/90 mmHg; n = 1269 with an OBP 130/80 mmHg) yielded similar AUC values. In conclusion, the accuracy of guideline-proposed OBP screening thresholds in identifying individuals at high risk of having MH in an office setting is limited and is inferior to that yielded by scores derived from simple clinical variables.

A avaliação de pacientes com teor muito baixo de colesterol da lipoproteína de alta densidade (HDL) permanece sendo um desafio clínico pela complexidade de sua as-sociação com o risco cardiovascular e pela multicausalidade. Em indivíduos com HDL colesterol (HDL-C) muito reduzido decorrente de doenças monogênicas como doença de Tangier, deficiência de LCAT e hipoalfalipoproteinemia familiar há risco elevado de aterosclerose prematura. Apesar de estudos observacionais também demonstrarem essa associação entre o HDL-C e a doença aterosclerótica, análises baseadas em comparações de populações com pequenas variações da HDL-C mediadas por alterações poligênicas, isto é, randomização mendeliana, não confirmam esses achados, sugerindo ser uma as-sociação indireta ou de heterogeneidade nas diversas fisiopatogenias relacionadas com o mecanismo de redução do HDL-C. Os ensaios que avaliaram algumas das funções da HDL demonstram um grau de associação mais robusto entre o sistema HDL e o risco aterosclerótico, mas como não foram primariamente delineados para modificar a funcio-nalidade dessa lipoproteína, não temos dados suficientes para estabelecer uma relação de causalidade. O que temos no presente são ensaios clínicos randomizados de terapias que aumentam a concentração de HDL-C por uma ampla gama de mecanismos e essa elevação farmacológica do HDL-C ainda não mostrou redução de eventos cardiovasculares de modo independente. Em conjunto, essas evidências tornam claro que: (i) é insuficiente dosar o HDL-C como forma de estimar a função do sistema ateroprotetor relacionado à HDL ou mesmo o risco cardiovascular e (ii) não sabemos até o presente como aumentar a proteção cardiovascular com terapias voltadas ao metabolismo da HDL. Esses dois elementos nos têm obrigado a um esforço maior na compreensão dos mecanismos de ação molecular e interação celular da HDL, abandonando completamente a visão tradicional centrada na concentração plasmática de HDL-C. Novos agentes terapêuticos direcionados para aprimorar a funcionalidade da HDL estão sendo desenvolvidos. Nesta revisão, detalharemos esse novo entendimento e o novo horizonte do uso do sistema HDL na atenuação do risco aterosclerótico residual.

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.

RATIONALE, AIMS AND OBJECTIVES Emergency short-stay unit (SSU) alleviates emergency department (ED) overcrowding, but may affect in-hospital indicators. Cardiology patients comprise a substantial part of patients admitted at SSU. This study evaluated whether SSU opening differentially modified in-hospital indicators at a whole general hospital and at its cardiology division (CARD). METHODS We retrospectively analysed indicators based on 859 686 ED visits, and 171 547 hospital admissions, including 12 110 CARD admissions, from 2007 to 2018 at a general tertiary hospital, and compared global ED indicators and in-hospital indicators at the hospital and CARD before (2007-2011) and after (2011-2018) SSU opening. RESULTS After SSU opening, monthly ED bed occupancy rate decreased (mean ± SD 200 ± 18% vs 187 ± 22%; P

Traditional risk scores improved the definition of the initial therapeutic strategy in acute coronary syndrome (ACS), but they were not designed for predicting long-term individual risks and costs. In parallel, attempts to directly predict costs from clinical variables in ACS had limited success. Thus, novel approaches to predict cardiovascular risk and health expenditure are urgently needed. Our objectives were to predict the risk of major/minor adverse cardiovascular events (MACE) and estimate assistance-related costs.We used a 2-step approach that: (1) predicted outcomes with a common pathophysiological substrate (MACE) by using machine learning (ML) or logistic regression (LR) and compared with existing risk scores; (2) derived costs associated with noncardiovascular deaths, dialysis, ambulatory-care-sensitive-hospitalizations (ACSH), strokes, and MACE. With consecutive ACS individuals (n = 1089) from 2 cohorts, we trained in 80% of the population and tested in 20% using a 4-fold cross-validation framework. The 29-variable model included socioeconomic, clinical/lab, and coronarography variables. Individual costs were estimated based on cause-specific hospitalization from the Brazilian Health Ministry perspective.After up to 12 years follow-up (mean = 3.3 ± 3.1; MACE = 169), the gradient-boosting machine model was superior to LR and reached an area under the curve (AUROC) of 0.891 [95% CI 0.846-0.921] (test set), outperforming the Syntax Score II (AUROC = 0.635 [95% CI 0.569-0.699]). Individuals classified as high risk (90th percentile) presented increased HbA1c and LDL-C both at24 hours post-ACS and 1-year follow-up. High-risk individuals required 33.5% of total costs and showed 4.96-fold (95% CI 3.71-5.48, P.00001) greater per capita costs compared with low-risk individuals, mostly owing to avoidable costs (ACSH). This 2-step approach was more successful for finding individuals incurring high costs than predicting costs directly from clinical variables.ML methods predicted long-term risks and avoidable costs after ACS.

Type 2 diabetes prevention requires the accurate identification of those at high risk. Beyond the association of fasting serum triacylglycerols with diabetes, triacylglycerol-enriched remnant lipoproteins (TRLs) more accurately reflect pathophysiological changes that underlie progression to diabetes, such as hepatic insulin resistance, pancreatic steatosis and systemic inflammation. We hypothesised that TRL-related factors could improve risk prediction for incident diabetes. We included individuals from the Brazilian Longitudinal Study of Adult Health cohort. We trained a logistic regression model for the risk of incident diabetes in 80% of the cohort using tenfold cross-validation, and tested the model in the remaining 20% of the cohort (test set). Variables included medical history and traits of the metabolic syndrome, followed by TRL-related measurements (plasma concentration, TRL particle diameter, cholesterol and triacylglycerol content). TRL features were measured using NMR spectroscopy. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). Among 4463 at-risk individuals, there were 366 new cases of diabetes after a mean (±SD) of 3.7 (±0.63) years of follow-up. We derived an 18-variable model with a global AUROC of 0.846 (95% CI: 0.829, 0.869). Overall TRL-related markers were not associated with diabetes. However, TRL particle diameter increased the AUROC, particularly in individuals with HbA1c

AimTo assess the impact of the HbA1c levels achieved with antidiabetic therapies (ADTs) on the risk of MACE.MethodsA systematic search was performed in PubMed, Cochrane, and ClinicalTrials. gov for RCTs published up to March 2022 reporting the occurrence of MACE and all-cause mortality in individuals with T2DM treated with all marketed ADTs, including a sample size ≥100 individuals in each study arm and follow-up ≥24 weeks. A systematic review and additive-effects network meta-analysis with random effects and a multivariate meta-regression were utilized to assess the impact of achieved HbA1c on incident MACE.ResultsWe included 126 RCTs with 143 treatment arms, 270,874 individuals, and 740,295 individuals-years who were randomized to an active treatment vs. control group. Among all ADTs, only therapy with SGLT2i, GLP1-RA, or pioglitazone similarly reduced the risk of MACE compared to placebo. The achievement of HbA1c ≤ 7.0% in RCTs with the 3 drug classes in the active arm was associated with an adjusted HR of 0.91 (95% CI 0.80, 0.97; p = 0.017) compared with HbA1c>7.0%, without affecting all-cause mortality. These results, however, were not maintained among all ADTs.ConclusionsAchieving lower glucose levels with SGLT2i, GLP1-RA, or pioglitazone is linearly associated with a reduced risk of MACEs, without affecting all-cause mortality.Systematic Review Registrationwww.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213127, identifier: CRD42020213127.

Disagreements in office brachial and central blood pressure (BP) have resulted in the identification of novel hypertension phenotypes, namely isolated central hypertension (ICH) and isolated brachial hypertension (IBH). This study investigated the relationship of ICH and IBH with ambulatory BP phenotypes among 753 individuals (mean age = 47.6 ± 15.2 years, 48% males) who underwent office and 24‐hours brachial and central BP measures using a Mobil‐O‐Graph PWA monitor. Thresholds for elevated office central and brachial BP were 130/90 and 140/90 mm Hg. Results of multivariable analysis adjusted for potential confounders showed that ICH (n = 25) had 3.71‐fold (95% CI 1.48‐9.32; P = .005) greater risk of masked hypertension than normal brachial/central BP (n = 362), while IBH (n = 20) had 4.65‐fold (95% CI 1.76‐12.25; P = .002) greater risk of white coat hypertension compared with combined brachial/central hypertension (n = 346). These findings suggest that the diagnosis of ICH and IBH might be useful in identifying individuals at higher risk of presenting discordant office and ambulatory BP phenotypes.

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.

OBJECTIVE The current study investigated the prevalence of white-coat hypertension (WCH) and white-coat uncontrolled hypertension (WUCH) throughout the age spectrum among individuals with office isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH) and systolic-diastolic hypertension (SDH) who were untreated or treated with antihypertensive medications, respectively. METHODS We cross-sectionally evaluated 8809 untreated (42% males, 52.1 ± 16.2 years) and 9136 treated (39% males, 59.7 ± 14.5 years) individuals from two independent Brazilian populations who underwent home blood pressure monitoring. Participants were also categorized as younger (

Background and aims Osteoporosis and coronary heart disease (CHD) are very common conditions among elderly people, and both represent a public health concern due to their prognostic consequences. Osteoporosis and CHD share many risk factors and pathophysiological mechanisms, such as calcification pathways. Clinical evidence associates lower bone mass with cardiovascular diseases and endothelial dysfunction. Hence, this study aims to investigate whether bone mass density is associated with subclinical atherosclerosis and/or endothelial dysfunction in the very elderly. Methods We performed a cross-sectional study of cohort enrolled individuals, ages 80 years or older (n = 208), who had never manifested cardiovascular diseases. Medical evaluation, blood tests, flow-mediated dilation (FMD), carotid intimal-media thickness (IMT), Dual Energy X-ray Absorptiometry (DEXA) and Coronary Calcium Score (CCS) were obtained. Odds Ratio (OR) was calculated by multivariate logistic regression models using CCS, FMD and IMT categories. Adjustments for covariates were done. Results Overall bone mass was independently and inversely associated with CCS categories [OR:1.68(1.16–8.85); p = 0.024] and IMT categories [OR:2.97(1.11–7.90); p = 0.030]. Conversely, overall bone mass was independent and directly associated with FMD categories [OR:2.73(1.36–70.39); p = 0.023]. Conclusions This study indicates that overall bone mass is independently and inversely associated with subclinical atherosclerosis, endothelial dysfunction and thickness of carotid in the very elderly.

ObjectiveThis study compared clinical, echocardiographic, and prognostic characteristics among patients with aortic dissection (AD) with (HypHist) and without (No-HypHist) hypertension history and evaluated the association of blood pressure (BP) at presentation with 1-year mortality, left ventricular (LV) remodeling and renal dysfunction.MethodsWe investigated clinical and echocardiographic characteristics and 1-year mortality among 367 patients with AD (81% HypHist, 66% Type-A) from three Brazilian centers.ResultsPatients with No-HypHist were more likely to have Marfan syndrome, bicuspid aortic valve, to undergo surgical therapy, were less likely to have LV hypertrophy and concentricity, and had similar mortality compared with HypHist patients. Adjusted restricted cubic spline analysis showed that systolic BP (SBP) and diastolic BP (DBP) at presentation had a J-curve association with mortality among patients with No-HypHist, but did not associate with death among patients with HypHist (p for interaction = 0.001 for SBP and = 0.022 for DBP). Conversely, the association between SBP at presentation and mortality was influenced by previous use of antihypertensive medications in the HypHist group (p for interaction = 0.002). Results of multivariable logistic regression analysis comprising the whole sample showed direct associations of SBP and DBP at presentation with LV hypertrophy (p = 0.009) and LV concentricity (p = 0.015), respectively, and an inverse association between pulse pressure at presentation and estimated glomerular filtration rate (eGFR) 2 (p = 0.008).ConclusionCombined information on BP at presentation, previous diagnosis of hypertension, and use of antihypertensive medications might be useful to predict mortality risk and to estimate extra-aortic end-organ damage among patients with AD.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entrance, and studies have suggested that upon viral binding, ACE2 catalytic activity could be inhibited; therefore, impacting the regulation of the renin-angiotensin-aldosterone system (RAAS). To date, only few studies have evaluated the impact of SARS-CoV-2 infection on the blood levels of the components of the RAAS. The objective of this study was to determine the blood levels of ACE, ACE2, angiotensin-II, angiotensin (1–7), and angiotensin (1–9) at hospital admission and discharge in a group of patients presenting with severe or critical evolution of coronavirus disease 2019 (COVID-19). We showed that ACE, ACE2, angiotensin (1–7), and angiotensin (1–9) were similar in patients with critical and severe COVID-19. However, at admission, angiotensin-II levels were significantly higher in patients presenting as critical, compared to patients presenting with severe COVID-19. We conclude that blood levels of angiotensin-II are increased in hospitalized patients with COVID-19 presenting the critical outcome of the disease. We propose that early measurement of Ang-II could be a useful biomarker for identifying patients at higher risk for extremely severe progression of the disease.

Background: Among individuals with type 2 diabetes mellitus (T2DM), RCTs designed to investigate the cardiovascular effects of achieving HbA1c ≤7.0% by using insulin and sulfonylureas were unable to prevent the incidence of major adverse cardiovascular events (MACE) defined as CV death, non-fatal myocardial infarction, and non-fatal stroke. Intense glucose-lowering with newer antidiabetic therapies (ADTs) including SGLT2i, GLP1-RA, pioglitazone and DPP4i show lower risk of hypoglycemia and could lead to additive effect in preventing MACE. In this context, this study was designed to assess the impact of the HbA1c levels achieved with newer ADTs on the risk of MACE. Methods. We searched MEDLINE/PubMed, Cochrane and ClinicalTrials.gov. RCTs published up to January/2021 reporting the occurrence of MACE and all-cause mortality in individuals with T2DM, including a sample size ≥100 individuals in each study arm and follow-up ≥24 weeks, were selected. Data was extracted by four independent observers following PRISMA guidelines. We performed a systematic review and additive-effects network meta-analysis with random effects and a multivariate meta-regression to assess the impact of achieved HbA1c on incident MACE. Results. A total of 122 RCTs were included with 139 treatment arms, 256,990 individuals, and 689,346 individuals-years who were randomized to an active treatment vs. control group. Therapy with SGLT2i, GLP1-RA, or pioglitazone similarly reduced the risk of MACE compared to placebo (HR 0.88 [95%CI 0.83, 0.94, p7.0%. All-cause mortality was not influenced by HbA1c thresholds.Conclusions: Achieving lower glucose levels with newer ADTs is linearly associated with a reduced risk of MACEs, without affecting all-cause mortality. Targeting HbA1c between 6.5 and 7% with SGLT2i, GLP1A, pioglitazone or DPP4i brings cardiovascular benefits considering the available RCT evidence.Study registration: PROSPERO CRD42020200649

Background. Optimal control of traditional risk factors only partially attenuates the exceeding cardiovascular mortality of individuals with diabetes. Employment of machine learning (ML) techniques aimed at identification of novel features of risk prediction is a compelling target to tackle residual cardiovascular risk. Objective. To identify clinical phenotypes of T2D which are more prone for developing cardiovascular disease. Methods. The Brazilian Diabetes Study is a single-center, ongoing, prospective registry of T2D individuals. Eligible patients are 30 years-old or older, with a confirmed T2D diagnosis. After an initial visit for signature of informed consent form and medical history registration, all volunteers undergo biochemical analysis, echocardiography, carotid ultrasound, ophthalmologist visit, dual x-ray absorptiometry, coronary artery calcium score, polyneuropathy assessment, advanced glycation end-products reader, and ambulatory blood pressure monitoring. A 5-year follow-up will be conducted by yearly phone interviews for endpoints disclosure. The primary endpoint is the difference between ML-based clinical phenotypes in the incidence of a composite of death, myocardial infarction, revascularization, and stroke. Since June/2016, 1030 patients (mean age: 57 years, diabetes duration of 9.7 years, 58% male) were enrolled in our study. Mean follow-up time was 3.7 years in October/2021. Conclusions. The BDS will be the first large population-based cohort dedicated to the identification of clinical phenotypes of T2D at higher risk of cardiovascular events. Data derived from this study will provide valuable information on risk estimation and prevention of cardiovascular and other diabetes-related events. ClinicalTrials.gov Identifier: NCT04949152

ObjectiveLeft ventricular hypertrophy (LVH) is a common complication of hypertension and microRNAs (miRNAs) are considered to play an important role in cardiac hypertrophy development. This study evaluated the relationship between circulating miRNAs and LVH in hypertensive patients.MethodsTwo cohorts [exploratory (n = 42) and validation (n = 297)] of hypertensive patients were evaluated by clinical, laboratory and echocardiography analysis. The serum expression of 754 miRNAs in the exploratory cohort and 6 miRNAs in the validation cohort was evaluated by the TaqMan OpenArray® system and quantitative polymerase chain reaction, respectively.ResultsAmong the 754 analyzed miRNAs, ten miRNAs (miR-30a-5p, miR-let7c, miR-92a, miR-451, miR-145-5p, miR-185, miR-338, miR-296, miR-375, and miR-10) had differential expression between individuals with and without LVH in the exploratory cohort. Results of multivariable regression analysis adjusted for confounding variables showed that three miRNAs (miR-145-5p, miR-451, and miR-let7c) were independently associated with LVH and left ventricular mass index in the validation cohort. Functional enrichment analysis demonstrated that these three miRNAs can regulate various genes and pathways related to cardiac remodeling. Furthermore, in vitro experiments using cardiac myocytes demonstrated that miR-145-5p mimic transfection up-regulated the expression of brain and atrial natriuretic peptide genes, which are markers of cardiac hypertrophy, while anti-miR-145-5p transfection abrogated the expression of these genes in response to norepinephrine stimulus.ConclusionsOur data demonstrated that circulating levels of several miRNAs, in particular miR-145-5p, miR-451, and let7c, were associated with LVH in hypertensive patients, indicating that these miRNAS may be potential circulating biomarkers or involved in hypertension-induced LV remodeling.

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.To evaluate the relationship between HDL-C and oxLDL-Ab levels.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 values0.05 were considered statistically significant.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.HDL-C and oxLDL-Ab are independently related.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.Avaliar a relação entre os níveis de HDL-C e oxLDL-Ab.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 p0,05 foram considerados estatisticamente significativos.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.HDL-C e oxLDL-Ab estão independentemente relacionados.

BackgroundThe unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear.Methods and FindingsWe develop a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care to explore the potential public-health impact of a range of different potential therapeutics, under a range of different scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) drug efficacy in the absence of supportive care. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. We find the impact of drugs like dexamethasone (which are delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics.ConclusionsThere is a global asymmetry in who is likely to benefit from advances in the treatment of COVID-19 to date, which have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

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 2 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 P

BACKGROUND Low socioeconomic status has for long been considered an important modifiable risk factor for developing cardiovascular disease, plausibly by lower access to healthcare, lower therapeutic adhesion, and overlapping of other known risk factors. Nevertheless, whether family income and social isolation of poor communities seen in Brazil impact outcomes following ST-segment elevation myocardial infarction (STEMI) remain scarcely understood. METHODS STEMI diagnosed patients were consecutively enrolled from the Brazilian Heart Study (ClinicalTrials.gov Identifier: NCT02062554) and categorized according to median family income (US$350), address-based human development index (HDI), and distance between communities and a tertiary hospital (DCTH). Incidence of death after 48 months was compared by using adjusted Cox regressions. p-alues

Atherogenic dyslipidemia is a risk factor for cardiovascular diseases. The present study aimed to evaluate the association between triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and the triglycerides to high-density lipoprotein (TG/HDL-C) ratio with carotid-femoral pulse wave velocity (cf-PWV), a marker of vascular stiffness. Anthropometric, biochemical, and clinical data from 13,732 adults were used to assess this association. Individuals within the third TG/HDL-C tertile presented worse anthropometric, biochemical, and clinical profiles as compared with the participants in the lower TG/HDL-C tertile. There was a linear association between TG, HDL-C, and TG/HDL-C ratio and cf-PWV in both men and women (stronger in women). After adjustment for confounders, lower levels of HDL-C were associated with increased cf-PWV in men (9.63 ± .02 m/s) and women (8.90 ± .03 m/s). However, TG was not significantly associated with cf-PWV after adjustment, regardless of sex. An increased TG/HDL-C ratio is associated with higher cf-PWV only in women (9.01 ± .03 m/s), but after adjustment for HDL-C levels, the association was non-significant (8.99 ± .03 m/s). These results highlight the stronger association of HDL-C with arterial stiffness, and that the association of TG/HDL-C with cf-PWV is dependent on HDL-C.

Data on the association of blood pressure (BP) phenotypes with office and out-of-office markers of vascular stiffness and pressure wave reflection are sparse. This study investigated office and 24-h measures of brachial BP, pulse wave velocity (PWV), and central augmentation index (AIx) across hypertension phenotypes among individuals not using BP-lowering medications [normotension (NT), white-coat hypertension (WH), masked hypertension (MH) and sustained hypertension (SH)] and those using BP-lowering medications [controlled hypertension (CH), white-coat uncontrolled hypertension (WUCH), masked uncontrolled hypertension (MUCH) and sustained uncontrolled hypertension (SUCH)]. We evaluated 454 untreated (age = 45 ± 15 years, 50% males) and 238 treated (age = 52 ± 15 years, 45% males) individuals who underwent office and 24-h brachial BP, PWV, and AIx measures using a Mobil-O-Graph PWA monitor. In the analysis adjusted for age and sex, WH had higher (p < 0.05) office PWV (7.53 ± 0.09 vs 6.89 ± 0.05), office AIx (27.9 ± 1.3 vs 23.8 ± 0.8), and daytime AIx (24.6 ± 0.7 vs 22.7 ± 0.4) compared with those of NT, while WUCH had higher (p < 0.05) office PWV (8.28 ± 0.11 vs 7.43 ± 0.08) and 24-h PWV (7.54 ± 0.09 vs 7.21 ± 0.07) than those of CH. MH had higher (p < 0.05) 24-h PWV (7.00 ± 0.09 vs 6.69 ± 0.04) and 24-h AIx (24.3 ± 0.9 vs 21.9 ± 0.4) than those of NT, whereas MUCH had higher (p < 0.05) 24-h PWV (7.64 ± 0.13 vs 7.21 ± 0.07) than that of CH. Lastly, SH or SUCH had significantly higher office and 24-h PWV and AIx than those of NT and CH, respectively. In conclusion, these results suggest that individuals with masked BP phenotypes are more predisposed to have adverse out-of-office vascular characteristics, while individuals with white-coat phenotypes have adverse office and out-of-office vascular characteristics compared with those of individuals with normal BP levels.

Background: Age, smoking, hypercholesterolemia, and hypertension are major risk factors for atherosclerotic cardiovascular disease. Objective: We examined whether the effects of alirocumab on low-density lipoprotein cholesterol (LDL-C) differed according to age, hypertension, or smoking status. Methods: Data were pooled from 10 Phase 3 ODYSSEY randomized trials (24–104 weeks’ duration) in 4983 people with heterozygous familial hypercholesterolemia (FH) or non–familial hypercholesterolemia (3188 on alirocumab, 1795 on control [620 on ezetimibe and 1175 on placebo]). Most participants received concomitant maximum tolerated statin therapy. In 8 trials, the alirocumab dose was increased from 75 mg every 2 weeks (Q2W) to 150 mg Q2W at Week 12 if predefined risk-based LDL-C goals were not achieved at Week 8 (≥70 mg/dL in very high cardiovascular risk; ≥100 mg/dL in moderate or high cardiovascular risk). Two trials compared alirocumab 150 mg Q2W vs placebo. The efficacy and safety of alirocumab were assessed post hoc in subgroups stratified by age (

Despite decades of therapeutic advances, myocardial infarction remains a leading cause of death worldwide. Recent studies have identified HDLs (high-density lipoproteins) as a potential candidate for mitigating coronary ischemia/reperfusion injury via a broad spectrum of signaling pathways. HDL ligands, such as S1P (sphingosine-1-phosphate), Apo (apolipoprotein) A-I, clusterin, and miRNA, may influence the opening of the mitochondrial channel, insulin sensitivity, and production of vascular autacoids, such as NO, prostacyclin, and endothelin-1. In parallel, antioxidant activity and sequestration of oxidized molecules provided by HDL can attenuate the oxidative stress that triggers ischemia/reperfusion. Nevertheless, during myocardial infarction, oxidation and the capture of oxidized and proinflammatory molecules generate large phenotypic and functional changes in HDL, potentially limiting its beneficial properties. In this review, new findings from cellular and animal models, as well as from clinical studies, will be discussed to describe the cardioprotective benefits of HDL on myocardial infarction. Furthermore, mechanisms by which HDL modulates cardiac function and potential strategies to mitigate postmyocardial infarction risk damage by HDL will be detailed throughout the review.

The values used to define the presence of white-coat or masked blood pressure (BP) effects are arbitrary. The aim of this study was to investigate the accuracy of several cutoff points based on the difference between office and home BP (ΔBP) values to detect white-coat uncontrolled (WUCH) and masked uncontrolled (MUCH) hypertension, which are phenotypes with adverse prognoses, in a large cohort of treated hypertensive patients. This multicenter cross-sectional study included 6,049 treated hypertensive patients (40% males, mean age 59.1 ± 14.4 years) who underwent office and home BP monitoring. We compared the sensitivity, specificity, area under curve (AUC), and positive (PPV) and negative (NPV) predictive values of several ΔBP cutoffs to detect WUCH and MUCH. The 15/9 mmHg cutoff, which reflects a 1.0 standard deviation of the ΔBP, showed the best AUC (0.783, 95% CI = 0.772-0.794) for the detection of WUCH, particularly in individuals with office grade 1 hypertension (AUC = 0.811, 95% CI = 0.793-0.829). The -1/-1 mmHg cutoff, which considers all individuals who had lower systolic or diastolic BP levels in the office than at home, had the highest AUC (0.822, 95% CI = 0.808-0.836) for the detection of MUCH. Both cutoff values also had the best performances for identifying all patients with higher and lower office-than-home BP grades. In conclusion, the 15/9 and -1/-1 mmHg cutoffs showed the best performance for the detection of treated hypertensive patients with WUCH and MUCH, respectively, and therefore might be markers of significant white-coat and masked effects and could be useful for identifying preferential targets for more routine home BP measures.

Coronary reperfusion with HDL from healthy volunteers attenuates ischemia and reperfusion injury in animal models. In myocardial infarction (MI) patients, such an interaction is unclear. Hence, our first objective was to verify if there is interaction between HDL-C and MI mass in patients and the role of coronary reperfusion in the interaction. Furthermore, we investigated whether the effect in MI size of reperfusion with HDL obtained from healthy participants or MI patients could differ.HDL-C was measured the first day after MI and MI mass was quantified by cardiac magnetic resonance (n = 94) and peak CKMB (n = 393). In an ex vivo rat heart model, we compared MI area and dP/dt max after coronary reperfusion with HDL from MI patients or healthy volunteers.HDL-C above the median (35 mg/dL) was associated with higher peak CKMB [255 (145-415) vs. 136 (84-287) UI/L; p = 0.02], higher MI mass [17 (9-21) vs. 10 (6-14) g; p0.01] and lower left ventricular ejection fraction [47 (34-53) vs. 51 (43-59); p = 0.02] than their counterparts. In restricted cubic spline and multivariate linear regression, HDL-C was directly associated with peak CKMB (p0.01) and MI mass (p0.01) only in reperfused patients with time to reperfusion4 h. Reperfusion with healthy HDL, but not from MI patients, reduced MI mass (p0.01) and improved dP/dt max (p = 0.02).In MI patients undergoing early coronary reperfusion, HDL-C levels at admission are directly associated with MI size. In contrast to healthy HDL, reperfusion with HDL from MI patients do not reduce MI area in an ex vivo animal model.

Background and aims Macrophages derived from monocytes play an important role in atherosclerosis progression. Subpopulations of circulating classical, intermediate, and non-classical monocytes possess distinct functions and phenotypes, and participate in the pathogenesis of disease. The aim of this study was to compare the quantity and phenotypes of circulating monocyte subpopulations in patients with established atherosclerosis and healthy control individuals. Additionally, the study aimed to provide insight into the functional activity of monocytes against a heat shock protein (HSP60). Methods Chemokine and pattern recognition receptors in monocyte subsets obtained from peripheral blood of acute and chronic coronary artery disease patients and controls were quantified by flow cytometry. Furthermore, monocytes from healthy controls were stimulated in vitro with HSP60, and the cytokines produced by them were evaluated by flow cytometry. Results Eighteen controls (C), 34 individuals with risk factors for cardiovascular disease (RF), 32 patients with stable angina (SA), and 16 patients with unstable angina (UA) were enrolled in the study. The absolute count of intermediate monocytes was found to be increased in patients of the UA group; high frequencies of the chemokine receptors CCR2, CCR5, and CX3CR1 were also observed in this subpopulation. Moreover, the pattern recognition receptors TLR2 and TLR4 were more frequent in intermediate monocytes from the UA group. Furthermore, the intermediate monocytes from healthy individuals produced IL-12p70 after stimulation with HSP60. Conclusions Our results show that intermediate monocytes of UA patients exhibited an enhanced expression of the receptors involved in the recognition of damage-associated molecular patterns (DAMPs) and enhancement of the migratory function. Hence, they might contribute to the propagation and progression of inflammation observed in atherosclerosis, especially in the acute setting.

SUMMARY Although long ago described, there is no established consensus regarding the real existence of Diabetic Cardiomyopathy (CMPDM). Due to its complex pathophysiology, it has been difficult for clinical and experimental research to establish clear connections between diabetes mellitus (DM) and heart failure (HF), as well as to solve the mechanisms of the underlying myocardial disease. However, the epidemiological evidence of the relationship of these conditions is undisputed. The interest in understanding this disease has intensified due to the recent results of clinical trials evaluating new glucose-lowering drugs, such as sodium-glucose transporter inhibitors 2, which demonstrated favorable responses considering the prevention and treatment of HF in patients with DM. In this review we cover aspects of the epidemiology of CMPDM and its possible pathogenic mechanisms, as well as, present the main cardiac phenotypes of CMPDM (HF with preserved and reduced ejection fraction) and implications of the therapeutic management of this disease. RESUMO Apesar de há muito tempo descrita, não existe consenso estabelecido quanto à real existência da cardiomiopatia diabética (CMPDM). Devido à sua complexa fisiopatologia, tem sido árduo à pesquisa clínica e experimental estabelecer conexões claras entre diabetes mellitus (DM) e insuficiência cardíaca (IC), assim como solucionar os mecanismos da doença subjacente do miocárdio. No entanto, as evidências epidemiológicas da relação dessas condições são incontestáveis. O interesse em compreender melhor essa doença tem recrudescido devido aos recentes resultados de ensaios clínicos avaliando novos fármacos hipoglicemiantes, como os inibidores do transportador de sódio-glicose 2, que demonstraram respostas favoráveis, considerando-se a prevenção e tratamento da IC em pacientes portadores de DM. Nesta revisão, percorremos aspectos da epidemiologia da CMPDM e de seus possíveis mecanismos patogênicos, além de apresentarmos os principais fenótipos cardíacos da CMPDM (IC com fração de ejeção preservada e reduzida) e implicações do manejo terapêutico desta doença.

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.

OBJECTIVE Smoking increases the risk of peripheral artery disease, but the mechanisms are not well established. This study evaluated the association of local circumferential wall tension (CWT), markers of vascular remodeling and stiffness, and traditional risk factors with popliteal and carotid plaques among smokers and nonsmokers. METHODS Two hundred fifty-two individuals (126 smokers and 126 nonsmokers) underwent clinical, laboratory, and popliteal and carotid ultrasound analysis. Popliteal and carotid CWT measures were calculated in supine and orthostatic positions, and supine position, respectively. RESULTS Popliteal plaques were more common in smokers than nonsmokers (39 vs. 19%; P

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, Brasilia, 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

This study investigated the impact of changing abnormal home blood pressure monitoring (HBPM) cutoff from 135/85 to 130/80 mmHg on the prevalence of hypertension phenotypes, considering an abnormal office blood pressure cutoff of 140/90 mmHg. We evaluated 57 768 individuals (26 876 untreated and 30 892 treated with antihypertensive medications) from 719 Brazilian centers who performed HBPM. Changing the HBPM cutoff was associated with increases in masked (from 10% to 22%) and sustained (from 27% to 35%) hypertension, and decreases in white‐coat hypertension (from 16% to 7%) and normotension (from 47% to 36%) among untreated participants, and increases in masked (from 11% to 22%) and sustained (from 29% to 36%) uncontrolled hypertension, and decreases in white‐coat uncontrolled hypertension (from 15% to 8%) and controlled hypertension (from 45% to 34%) among treated participants. In conclusion, adoption of an abnormal HBPM cutoff of 130/80 mmHg markedly increased the prevalence of out‐of‐office hypertension and uncontrolled hypertension phenotypes., Several studies published in last decade have suggested that abnormal home blood pressure monitoring (HBPM) levels should be considered when ≥130/80 mmHg rather than ≥135/85 mmHg. Shifting the HBPM cutoff from 135/85 to 130/80 mmHg and keeping the office abnormal cutoff at 140/90 mmHg led to a twofold increase in the prevalence of masked hypertension phenotypes, an approximate 50% decrease in the prevalence of white‐coat hypertension phenotypes, and increased the detection of sustained hypertension phenotypes and decreased the detection of normotension and controlled hypertension.

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.