Very low HDL levels: clinical assessment and management

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

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

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

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

Hipertensão mascarada: qual a importância da mrpa neste contexto? / Masked hypertension: how important is hbpm in this context?

A hipertensão arterial (HA) é o principal fator contributivo para as doenças cardiovasculares, as quais constituem a mais importante causa de morte prevenível no mundo. A falta de conhecimento da população acerca da doença, e consequentemente de um diagnóstico adequado, torna baixo o número de pessoas que se tratam. O aspecto silencioso da HA, e a má adesão ao tratamento proposto, dentre outros fatores, contribuem para o elevado risco de complicações. A medida da pressão arterial (PA) neste contexto apresenta grande importância não apenas no diagnóstico, mas também no acompanhamento de portadores de HA, podendo ser realizada de forma casual, em consultório, ou fora do mesmo com a utilização de outros métodos para tal. Dentre as medidas de PA, a monitorização residencial da PA (MRPA) se destaca. É um método destinado a fazer registro da PA fora do ambiente de consultório, obedecendo a um protocolo previamente estabelecido e normatizado. Além disto, a MRPA apresenta custos menores do que a monitorização ambulatorial da PA (MAPA). De acordo com a atual Diretriz Brasileira de HA, são considerados anormais valores de PA consultório ≥ 140/90 mmHg e de MRPA ≥ 130/80 mmHg. Sob esta perspectiva, a MRPA é um exame que permite que se faça o diagnóstico de HA verdadeira (PA elevada no consultório e na MRPA), normotensão verdadeira (PA normal no consultório e na MRPA), HA do avental branco (HAB) (PA elevada no consultório e normal na MRPA) e HA mascarada (HM) (PA normal no consultório e elevada na MRPA). O diagnóstico de HM é bastante relevante na prática clínica, pois em termos prognósticos, a HM apresenta um risco cardiovascular maior que a HAB e a normotensão verdadeira. Além disto, a incidência de eventos cardiovasculares na HM é similar ou até superior à da HA verdadeira.

Hypertension is the main contributing factor to cardiovascular diseases, which are the most important cause of death in the world. The lack of proper diagnosis, mainly due to the silent aspect of hypertension, makes the rate of people undergoing treatment low, contributing to the high risk of complications. The measurement of blood pressure (BP) in this context is important not only in the diagnosis, but also in the follow-up of patients with hypertension, and it can be performed casually, in the office, or outside the office, using other methods for this purpose. Home blood pressure monitoring (HBPM) is a method designed to record BP outside the office environment, following a previously established and standardized protocol and has a lower cost than ambulatory blood pressure monitoring (ABPM) According to the current Brazilian hypertension guideline, office BP values ≥ 140/90 mmHg and HBPM values ≥ 130/80 mmHg are considered abnormal. From this perspective, HBPM is a test that allows the diagnosis of true hypertension (high BP in the office and in HMBP), true normotension (normal BP in the office and in the HBPM), white coat hypertension (high BP in the office and normal BP in HBPM) and masked hypertension (normal BP in the office and high in HBPM). The diagnosis of masked hypertension is quite relevant in clinical practice, because this phenotype has greater cardiovascular risk than true normotension and white coat hypertension. On the other hand, the incidence of cardiovascular events is similar or even greater in masked hypertension in comparison with true hypertension.

Espironolactona ou clonidina como quarto fármaco na hipertensão resistente? / Spironolactone or clonidine as the fourth drug to treat resistant hypertension?

A hipertensão arterial resistente (HAR) é definida como a ausência de controle pressórico nas medidas de pressão arterial (PA) de consultório a despeito do uso de três ou mais anti-hipertensivos em doses adequadas, incluindo-se preferencialmente um diurético, ou o controle pressórico atingido às custas do uso de quatro ou mais medicamentos. O uso de espironolactona, um antagonista dos receptores de aldosterona, como quarto fármaco no tratamento da HAR é indicado pelas principais diretrizes sobre o assunto, e tem a sua eficácia comprovada em ensaios clínicos e meta análises. Um estudo comparou o uso de clonidina, um agonista adrenérgico alfa-2, como quarto fármaco para tratamento da HAR em comparação com a espironolactona. Embora o desfecho primário (taxa de controle da PA no consultório ou na medida ambulatorial da PA) tenha sido similar com as duas medicações, a espironolactona mostrou maior redução na PA de 24h quando comparada à clonidina. Neste contexto, a clonidina pode ser uma alternativa à espironolactona, particularmente em grupos específicos de pacientes que tenham contraindicação ao uso de espironolactona, como os que apresentam hipercalemia ou doença renal crônica pré dialítica.

Resistant Hypertension (RH) is defined as the absence of blood pressure (BP) control despite the use of three antihypertensive drugs in adequate doses, or the achievement of BP control with the use of four or more medications. The use of spironolactone, an antagonist of aldosterone receptors, as the fourth medication in the treatment of RH is recommended by current Management of Hypertension Guidelines, and its efficacy has been proved in clinical trials and meta-analysis. One clinical trial compared the use of clonidine, an adrenergic alpha-2 agonist, versus spironolactone as an option as the fourth drug in the treatment of RH. The results showed similar rates of the primary outcome (BP control at the office and at ambulatory monitoring) with both drugs, although spironolactone promoted greater reduction in 24h BP when compared with clonidine. In this context, clonidine can be used as an alternative to spironolactone, particularly among specific groups of patients that have contraindications to the use of spironolactone, such as patients with hyperkalemia or end stage renal disease.

Intensive treatment of hyperglycemia in the acute phase of myocardial infarction: the tenuous balance between effectiveness and safety - a systematic review and meta-analysis of randomized clinical trials

SUMMARY INTRODUCTION In acute myocardial infarction (AMI), each 18 mg/dl (1 mmol/L) increment is associated with a 3% increase in mortality rates. All strategies applied for reducing blood glucose to this date, however, have not presented encouraging results. METHODOLOGY We searched the Medline (PubMed) and Cochrane Library databases for randomized clinical trials (RCTs) from 1995 to 2017 that used the intensive strategy or GIK therapy for blood glucose control during the acute stage of the AMI. We included eight studies. In order to identify the effects of GIK or insulin therapy, we calculated a overall risk ratio (RR) with meta-analysis of fixed and random effects models. A two-tail p-value of < 0.05 was considered statistically significant. RESULTS A total of 28,151 patients were included: 1,379 intensively treated with insulin, 13,031 in GIK group, and 13,741 in the control group. The total mortality was 10.5% (n=2,961) and the RR of 1.03 [95%CI 0.96-1.10]; I2 = 31%; p = 0.41 for the combined intensive insulin plus GIK groups in comparison with the control group. In meta-regression analyses, intense reductions in blood glucose (> 36 mg/dL) in relation to the estimated average blood glucose (estimated by HbA1c) were associated with higher mortality, whereas lower reductions in blood glucose (< 36 mg/dL) were not associated with mortality. The lowering of blood glucose in the acute phase of MI compared with the average blood glucose was more effective around 18 mg/dL. CONCLUSION This meta-analysis suggests that there may be a tenuous line between the effectiveness and safety of reducing blood glucose in the acute phase of MI. The targets must not exceed a reduction greater than 36 mg/dL in relation to estimated average blood glucose.

RESUMO INTRODUÇÃO No infarto agudo do miocárdio (IAM), cada incremento de 18 mg/dl (1 mmol/L) se associa a um aumento de 3% na mortalidade. As estratégias de redução da glicemia tentadas até o momento, entretanto, não trouxeram resultados animadores. METODOLOGIA Foram pesquisadas nas bases de dados Medline (PubMed) e Cochrane Library os ensaios clínicos randomizados (ECRs) de 1995 a 2017 que utilizaram estratégia intensiva ou a terapia GIK no controle glicêmico durante a fase aguda do IAM. Foram incluídos oito estudos. Para identificar os efeitos da insulinoterapia ou da terapia GIK, calculamos um risco relativo geral (RR) com meta-análises de modelos de efeitos fixos e aleatórios. Um valor de p-bicaudal < 0,05 foi considerado estatisticamente significativo. RESULTADOS Foram incluídos 28.151 pacientes, sendo 1.379 no grupo de tratamento intensivo da glicemia, 13.031 no GIK e 13.741 no controle. A mortalidade total foi de 2.961 (10,5%), computando um risco relativo de 1,03 [95%CI 0,96-1,10]; I 2 = 31%; p = 0,41 para o grupo intensivo ou GIK contra o grupo conservador. Reduções intensas (> 36 mg/dL) em relação à glicemia estimada média se associaram à maior mortalidade, enquanto reduções menores não se associaram com seu incremento ou redução. A redução glicêmica na fase aguda em relação à glicemia estimada média foi mais efetiva e segura na faixa em torno de 18 mg/dL. CONCLUSÃO Esta meta-análise levanta a hipótese de haver um limite tênue entre efetividade e segurança para a redução glicêmica na fase aguda, sendo que os alvos não devem exceder uma redução maior do que 36 mg/dL de glicemia.

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.

Incidence of preoperative high blood pressure in cataract surgery among hypertensive and normotensive patients.

Incidence of preoperative rise in blood pressure (BP) in cataract surgery among hypertensive and normotensive patients. Objective: To study the incidence of preoperative rise in BP in cataract surgery among normotensive individuals and hypertensive patients with historic good BP control in a population without other major chronic diseases. Settings: Ophthalmology Service of a University Hospital. Materials and Methods: A prospective study with 822 patients older than 40 years of age, with cataract surgery indication, and without major chronic diseases other than hypertension. The patients were divided in two groups: hypertensive and normotensive. Preoperative data, physical exams and medical adverse events were recorded in an evaluation questionnaire. Results: The sample included 427 normotensive (52%) and 395 hypertensive patients (48%). The two groups had similar proportions of operations that were cancelled and not subsequently rescheduled, 2% (eight patients) in each group. The incidence of preoperative rise in BP was 3.7% in the normotensive group and 10.9% in the hypertensive group (P < 0.001). Conclusion: Hypertensive patients with historic good BP control and without other major co-morbidities present a larger incidence of preoperative rise in BP than normotensive individuals in cataract surgery.

Competência clínica de alunos de Medicina em estágio clínico: comparação entre métodos de avaliação / Clinical competence of medical students during clinical clerkship: a comparison of evaluation methods

OBJETIVO: Comparar quatro métodos de avaliação com base nas notas obtidas por alunos do quarto ano de Medicina em estágio clínico. MÉTODO: Ao final do estágio clínico em Ginecologia e Obstetrícia, Clínica Médica e Pediatria, em unidades de atenção primária, 106 alunos do quarto ano foram avaliados com base em quatro métodos: Prova Teórica (Pt), Portfólio (Pf), Avaliação Estruturada do Atendimento Clínico (AE) e Conceito Global Itemizado (CGI), (escala 0-10). A análise estatística utilizou coeficiente alfa de Cronbach, teste de Wilcoxon para dados pareados, coeficiente de correlação de Pearson, análise de componentes principais e distância euclidiana. RESULTADOS: As medianas mais baixas foram de PT, e as mais altas, de AE. Houve diferença significativa nas distribuições das notas entre todos os pares de métodos (P < 0,001). A correlação mais forte e a maior concordância ocorreram entre as notas de AE e CGI. A análise de componentes principais contrastou as notas de Pt e Pf com as de AE e CGI. CONCLUSÃO: Cada método parece enfocar diferentes aspectos da competência clínica. AE e CGI parecem avaliar competências semelhantes, em oposição a Pf e Pt. Portanto, nenhum método deve ser utilizado isoladamente para avaliar os alunos em estágio clínico.

OBJECTIVE: The objective was to compare four evaluation methods based on the grades received by fourth-year medical students in their clinical clerkship. METHOD: At the completion of the clinical clerkship in Obstetrics and Gynecology, Internal Medicine, and Pediatrics in primary care clinics, 106 fourth-year students were evaluated based on four methods, on a scale from 1 to 10: multiple-choice questions (MCQs), portfolio (P), real-case structured clinical assessment (RC-SCA), and global itemized rating (GIR). Statistical analysis used Cronbach alpha, Wilcoxon paired test, Pearson correlation coefficient, principal components analysis, and Euclidian distance. RESULTS: The lowest median scores were for MCQs and the highest for RC-SCA. The distribution of scores for all pairs of methods showed significant differences (P < 0,001). Agreement was strongest and highest between RC-SCA and GIR. Principal components analysis contrasted MCQs and P scores with those for RC-SCA and GIR. CONCLUSION: The various methods focused on different aspects of the expected clinical skills. RC-SCA and GIR appear to evaluate different skills as compared to P and MCQs. Thus, no method should be used alone to evaluate medical students in clinical clerkships.