Correlação entre a cistatina C sérica e marcadores de aterosclerose subclínica em pacientes hipertensos

FUNDAMENTO: A cistatina C sérica (s-CC), um marcador endógeno da função renal, tem sido proposta também como um marcador de risco cardiovascular. No entanto, ainda não está estabelecido se se trata de um marcador direto de aterosclerose, independentemente da função renal. OBJETIVO: O objetivo deste estudo foi correlacionar a s-CC com dois marcadores substitutos de aterosclerose subclínica. MÉTODOS: Trata-se de um estudo transversal envolvendo 103 pacientes hipertensos ambulatoriais, de meia idade (57,49 ± 11,7 anos), sendo 60 do sexo feminino (58,25%) e a maioria com função renal preservada. A s-CC foi correlacionada com a espessura mediointimal carotídea (EMIc) e a dilatação mediada por fluxo de artéria braquial (DMF), ambas avaliadas por ultrassonografia, bem como com o clearance de creatinina medido e fatores de risco cardiovascular estabelecidos. RESULTADOS: A s-CC não se correlacionou significativamente nem com a EMIc (r = -0,024, p = 0,84) nem com a DMF (r = -0,050 e p = 0,687), e não foi observada também associação significativa com fatores de risco convencionais nem marcadores inflamatórios. Na análise univariada, a s-CC se correlacionou com o clearance de creatinina medido (r = - 0,498, p < 0,001), idade (r = 0,408, p < 0,001), microalbuminúria (r = 0,291, p = 0,014), ácido úrico (r = 0,391, p < 0,001), relação E/e' (r = 0,242, p = 0,049) e escore de Framingham (r = 0,359, p = 0,001). No entanto, após análise de regressão múltipla, apenas a associação com o clearance de creatinina medido permaneceu significativa (r = -0,491, p <0,001). CONCLUSÃO: Em pacientes hipertensos ambulatoriais de meia idade, a s-CC se correlacionou com o clearance de creatinina medido,como esperado, mas não foi observada associação com marcadores de aterosclerose nem com fatores de risco cardiovascular estabelecidos.

Adesão ao tratamento e controle da pressão arterial por meio da monitoração ambulatorial de 24 horas

FUNDAMENTO: A hipertensão arterial sistêmica (HAS) é um importante fator de risco cardiovascular, no entanto os níveis de controle pressórico persistem inadequados. A avaliação da adesão ao tratamento anti-hipertensivo com a utilização da monitoração ambulatorial da pressão arterial (MAPA) de 24 horas pode representar um importante auxílio na busca de metas de controle da HAS. OBJETIVO: Avaliar a adesão ao tratamento anti-hipertensivo e a sua relação com os valores de PA obtidos pela MAPA de 24 horas entre pacientes hipertensos de centros de atenção primária à saúde (APS). MÉTODOS: Estudo transversal com 143 pacientes hipertensos de amostra representativa de serviço de APS do município de Antônio Prado, RS. Foi realizada aplicação do teste de Morisky e Green para avaliar a aderência ao tratamento e a verificação do número de medicamentos utilizados, seguida pela aplicação da MAPA de 24 horas. RESULTADOS: Observou-se que 65,7% da amostra foram considerados aderentes ao tratamento proposto, 20,3% eram moderadamente aderentes, enquanto somente 14% foram classificados como não aderentes. Do total de 143 pacientes avaliados, 79 (55,2%) foram identificados como HAS controlada (<130/80 mmHg) pelas medidas da MAPA de 24 horas, 64 (44,8%) não estavam controlados (>130/80 mmHg), 103 (72%) apresentaram ausência de descenso noturno da PA e 60 (41,9%) não estavam controlados durante o período de vigília. CONCLUSÃO: Verificamos, no presente estudo, que não há um controle adequado da HAS, com consequente perda de oportunidade dos profissionais envolvidos na APS de ajuste adequado das metas de PA preconizados. Esse fato ocorre a despeito de apropriada adesão ao tratamento anti-hipertensivo dos pacientes vinculados ao ambulatório de APS.

As manifestações de ECG do maior surto da doença de Chagas devido a infecção oral na América Latina

FUNDAMENTO: A doença de Chagas afeta mais de 15 milhões de pessoas em todo o mundo. Embora a transmissão vetorial tenha diminuído, a transmissão oral tornou-se relevante. Recentemente, nosso grupo publicou as características clínicas e epidemiológicas do maior surto relatado até hoje da doença de Chagas transmitida oralmente. OBJETIVO: Descrever alterações eletrocardiográficas que ocorrem na população de estudo durante o surto causado pela ingestão de suco de goiaba contaminado. MÉTODOS: Avaliamos 103 casos positivos, dos quais 76 (74%) tinham <18 anos de idade (média das idades: 9,1 ± 3,1 anos) e 27 (26%) tinham >18 anos (média das idades: 46 ± 11,8 anos). Todos os pacientes foram submetidos a avaliações clínicas e ECG. Caso os pacientes apresentassem palpitações ou alterações evidentes do ritmo na linha basal, o monitoramento de ECG ambulatorial seria realizado. RESULTADOS: Um total de 68 casos(66%;53 crianças e15 adultos) apresentaram anormalidades no ECG. Além disso, 69,7% (53/76) daqueles com idade < 18anos e 56% (15/27) daqueles com idade >18 anos apresentaram alguma alteração no ECG(p = ns). Anormalidades de ST-T foram observadas em 37,86% casos (39/103) e arritmias foram evidente sem 28,16% casos(29/103). Alterações de ST ocorreram em 72% daqueles com idade < 18 anos em comparação aos de > 18 anos (p < 0,0001). CONCLUSÃO: Este estudo relata o maior número de casos no mesmo surto de doença de Chagas causada por contaminação oral, com ECGs relatados. As alterações no ECG que sugerem miocardite aguda e arritmias foram as anormalidades encontradas com maior frequência.

Effect of Pitavastatin on Vascular Reactivity in Hypercholesterolemic Rabbits

Background: Pitavastatin is the newest statin available in Brazil and likely the one with fewer side effects. Thus, pitavastatin was evaluated in hypercholesterolemic rabbits in relation to its action on vascular reactivity. Objective: To assess the lowest dose of pitavastatin necessary to reduce plasma lipids, cholesterol and tissue lipid peroxidation, as well as endothelial function in hypercholesterolemic rabbits. Methods: Thirty rabbits divided into six groups (n = 5): G1 - standard chow diet; G2 - hypercholesterolemic diet for 30 days; G3 - hypercholesterolemic diet and after the 16th day, diet supplemented with pitavastatin (0.1 mg); G4 - hypercholesterolemic diet supplemented with pitavastatin (0.25 mg); G5 - hypercholesterolemic diet supplemented with pitavastatin (0.5 mg); G6 - hypercholesterolemic diet supplemented with pitavastatin (1.0 mg). After 30 days, total cholesterol, HDL, triglycerides, glucose, creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) were measured and LDL was calculated. In-depth anesthesia was performed with sodium thiopental and aortic segments were removed to study endothelial function, cholesterol and tissue lipid peroxidation. The significance level for statistical tests was 5%. Results: Total cholesterol and LDL were significantly elevated in relation to G1. HDL was significantly reduced in G4, G5 and G6 when compared to G2. Triglycerides, CK, AST, ALT, cholesterol and tissue lipid peroxidation showed no statistical difference between G2 and G3-G6. Significantly endothelial dysfunction reversion was observed in G5 and G6 when compared to G2. Conclusion: Pitavastatin starting at a 0.5 mg dose was effective in reverting endothelial dysfunction in hypercholesterolemic rabbits.

Mortality and Embolic Potential of Cardiac Tumors

Background: Cardiac tumors are rare, mostly benign with high embolic potential. Objectives: To correlate the histological type of cardiac masses with their embolic potential, implantation site and long term follow up in patients undergoing surgery. Methods: Between January 1986 and December 2011, we retrospectively analyzed 185 consecutive patients who underwent excision of intracardiac mass (119 females, mean age 48±20 years). In 145 patients, the left atrium was the origin site. 72% were asymptomatic and prior embolization was often observed (19.8%). The diagnosis was established by echocardiography, magnetic resonance and histological examination. Results: Most tumors were located in the left side of the heart. Myxoma was the most common (72.6%), followed by fibromas (6.9%), thrombi (6.4%) and sarcomas (6.4%). Ranging from 0.6cm to 15cm (mean 4.6 ± 2.5cm) 37 (19.8%) patients had prior embolization, stroke 10.2%, coronary 4.8%, peripheral 4.3% 5.4% of hospital death, with a predominance of malignant tumors (40% p < 0.0001). The histological type was a predictor of mortality (rhabdomyomas and sarcomas p = 0.002) and embolic event (sarcoma, lipoma and fibroelastoma p = 0.006), but not recurrence. Tumor size, atrial fibrillation, cavity and valve impairment were not associated with the embolic event. During follow-up (mean 80±63 months), there were 2 deaths (1.1%) and two recurrences 1 and 11 years after the operation, to the same cavity. Conclusion: Most tumors were located in the left side of the heart. The histological type was predictor of death and preoperative embolic event, while the implantation site carries no relation with mortality or to embolic event.

Impact of Different Obesity Assessment Methods after Acute Coronary Syndromes

Background: Abdominal obesity is an important cardiovascular risk factor. Therefore, identifying the best method for measuring waist circumference (WC) is a priority. Objective: To evaluate the eight methods of measuring WC in patients with acute coronary syndrome (ACS) as a predictor of cardiovascular complications during hospitalization. Methods: Prospective study of patients with ACS. The measurement of WC was performed by eight known methods: midpoint between the last rib and the iliac crest (1), point of minimum circumference (2); immediately above the iliac crest (3), umbilicus (4), one inch above the umbilicus (5), one centimeter above the umbilicus (6), smallest rib and (7) the point of greatest circumference around the waist (8). Complications included: angina, arrhythmia, heart failure, cardiogenic shock, hypotension, pericarditis and death. Logistic regression tests were used for predictive factors. Results: A total of 55 patients were evaluated. During the hospitalization period, which corresponded on average to seven days, 37 (67%) patients had complications, with the exception of death, which was not observed in any of the cases. Of these complications, the only one that was associated with WC was angina, and with every cm of WC increase, the risk for angina increased from 7.5 to 9.9%, depending on the measurement site. It is noteworthy the fact that there was no difference between the different methods of measuring WC as a predictor of angina. Conclusion: The eight methods of measuring WC are also predictors of recurrent angina after acute coronary syndromes.

Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

Background: Resistance exercise effects on cardiovascular parameters are not consistent. Objectives: The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Methods: Wistar rats were divided into three groups: control group (n = 8); sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. Results: A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2%) and an increase in the trained diabetic group (95 ± 3%) without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05) in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg) as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05) in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg) as compared to the sedentary diabetic group. Conclusions: Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats.

Evaluation of Sexual Dimorphism in the Efficacy and Safety of Simvastatin/Atorvastatin Therapy in a Southern Brazilian Cohort

Background: Dyslipidemia is the primary risk factor for cardiovascular disease, and statins have been effective in controlling lipid levels. Sex differences in the pharmacokinetics and pharmacodynamics of statins contribute to interindividual variations in drug efficacy and toxicity. Objective: To evaluate the presence of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin treatment. Methods: Lipid levels of 495 patients (331 women and 164 men) were measured at baseline and after 6 ± 3 months of simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of both drugs. Results: Women had higher baseline levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women exhibited a greater decrease in plasma TC and LDL-C levels compared with men. After adjustment for covariates, baseline levels of TC and LDL-C influenced more than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels] occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017). Conclusions: Our results show that baseline TC and LDL-C levels are the main predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In addition, they suggest the presence of sexual dimorphism in the safety of simvastatin/atorvastatin. The effect of sex differences on receptors, transporter proteins, and gene expression pathways needs to be better evaluated and characterized to confirm these observations.

Obesity does not Lead to Imbalance Between Myocardial Phospholamban Phosphorylation and Dephosphorylation

Background: The activation of the beta-adrenergic system promotes G protein stimulation that, via cyclic adenosine monophosphate (cAMP), alters the structure of protein kinase A (PKA) and leads to phospholamban (PLB) phosphorylation. This protein participates in the system that controls intracellular calcium in muscle cells, and it is the primary regulator of sarcoplasmic reticulum calcium pump activity. In obesity, the beta-adrenergic system is activated by the influence of increased leptin, therefore, resulting in higher myocardial phospholamban phosphorylation via cAMP-PKA. Objective: To investigate the involvement of proteins which regulate the degree of PLB phosphorylation due to beta-adrenergic activation in obesity. In the present study, we hypothesized that there is an imbalance between phospholamban phosphorylation and dephosphorylation, with prevalence of protein phosphorylation. Methods: Male Wistar rats were randomly distributed into two groups: control (n = 14), fed with normocaloric diet; and obese (n = 13), fed with a cycle of four unsaturated high-fat diets. Obesity was determined by the adiposity index, and protein expressions of phosphatase 1 (PP-1), PKA, PLB, phosphorylated phospholamban at serine16 (PPLB-Ser16) were assessed by Western blot. Results: Obesity caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia and did not alter the protein expression of PKA, PP-1, PLB, PPLB-Ser16. Conclusion: Obesity does not promote an imbalance between myocardial PLB phosphorylation and dephosphorylation via beta-adrenergic system.

Functional Vascular Study in Hypertensive Subjects with Type 2 Diabetes Using Losartan or Amlodipine

Background: Antihypertensive drugs are used to control blood pressure (BP) and reduce macro- and microvascular complications in hypertensive patients with diabetes. Objectives: The present study aimed to compare the functional vascular changes in hypertensive patients with type 2 diabetes mellitus after 6 weeks of treatment with amlodipine or losartan. Methods: Patients with a previous diagnosis of hypertension and type 2 diabetes mellitus were randomly divided into 2 groups and evaluated after 6 weeks of treatment with amlodipine (5 mg/day) or losartan (100 mg/day). Patient evaluation included BP measurement, ambulatory BP monitoring, and assessment of vascular parameters using applanation tonometry, pulse wave velocity (PWV), and flow-mediated dilation (FMD) of the brachial artery. Results: A total of 42 patients were evaluated (21 in each group), with a predominance of women (71%) in both groups. The mean age of the patients in both groups was similar (amlodipine group: 54.9 ± 4.5 years; losartan group: 54.0 ± 6.9 years), with no significant difference in the mean BP [amlodipine group: 145 ± 14 mmHg (systolic) and 84 ± 8 mmHg (diastolic); losartan group: 153 ± 19 mmHg (systolic) and 90 ± 9 mmHg (diastolic)]. The augmentation index (30% ± 9% and 36% ± 8%, p = 0.025) and augmentation pressure (16 ± 6 mmHg and 20 ± 8 mmHg, p = 0.045) were lower in the amlodipine group when compared with the losartan group. PWV and FMD were similar in both groups. Conclusions: Hypertensive patients with type 2 diabetes mellitus treated with amlodipine exhibited an improved pattern of pulse wave reflection in comparison with those treated with losartan. However, the use of losartan may be associated with independent vascular reactivity to the pressor effect.

Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

Background: Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective: To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods: Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results: The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion: Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

High-Sensitivity C-Reactive Protein as a Predictor of Cardiovascular Events after ST-Elevation Myocardial Infarction

Background: The association between high-sensitivity C-reactive protein and recurrent major adverse cardiovascular events (MACE) in patients with ST-elevation myocardial infarction who undergo primary percutaneous coronary intervention remains controversial. Objective: To investigate the potential association between high-sensitivity C-reactive protein and an increased risk of MACE such as death, heart failure, reinfarction, and new revascularization in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods: This prospective cohort study included 300 individuals aged >18 years who were diagnosed with ST-elevation myocardial infarction and underwent primary percutaneous coronary intervention at a tertiary health center. An instrument evaluating clinical variables and the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) risk scores was used. High-sensitivity C-reactive protein was determined by nephelometry. The patients were followed-up during hospitalization and up to 30 days after infarction for the occurrence of MACE. Student's t, Mann-Whitney, chi-square, and logistic regression tests were used for statistical analyses. P values of ≤0.05 were considered statistically significant. Results: The mean age was 59.76 years, and 69.3% of patients were male. No statistically significant association was observed between high-sensitivity C-reactive protein and recurrent MACE (p = 0.11). However, high-sensitivity C-reactive protein was independently associated with 30-day mortality when adjusted for TIMI [odds ratio (OR), 1.27; 95% confidence interval (CI), 1.07-1.51; p = 0.005] and GRACE (OR, 1.26; 95% CI, 1.06-1.49; p = 0.007) risk scores. Conclusion: Although high-sensitivity C-reactive protein was not predictive of combined major cardiovascular events within 30 days after ST-elevation myocardial infarction in patients who underwent primary angioplasty and stent implantation, it was an independent predictor of 30-day mortality.

Lipoprotein (a): Structure, Pathophysiology and Clinical Implications

The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.