[Study of the prevalence and multiplicity of cardiovascular risk factors in hypertensive individuals from the city of Brusque, SC, Brazil]. / Estudo de prevalência e multiplicidade de fatores de risco cardiovascular em hipertensos do Município de Brusque, SC.

OBJECTIVE: To investigate the prevalence and multiplicity of additional risk factors (RF) in a population sample of hypertensive smokers, diagnosed and enrolled at the Hiperdia Program of the Ministry of Health, in the city of Brusque, SC, Brazil. METHODS: Determination of the anthropometrical parameters and laboratory variables recognized as cardiovascular risk factors. RESULTS: Elevated prevalence of RF in addition to systemic arterial hypertension (SAH) and smoking, configuring the multiplicity that concurs with a marked elevation of the risk of cardiovascular events in this population sample. CONCLUSION: In hypertensive populations, the prevention, identification and RF control measures must be implemented; computerized programs such as the Hiperdia/MS can help in patients follow-up, allowing a more stringent multidisciplinary approach, especially regarding the analysis of the attainment of treatment goals and the subsequent decrease of cardiovascular risk.

[Pharmacology of fibrates]. / Farmacologia do fibratos.

Fibrates are drugs commonly used in hypertriglyceridemias. After their absorption, fibrates are metabolized by the liver, using P450 isoenzymes not shared by statins. However, for some fibrates, such as genfibrozil, an interaction with statins can occur during their liver glucuronidation, or by displacement of free fraction of statins linked to proteins in plasma. Plasma half-life is variable among fibrates (2-80 h). Recently it has been shown that fibrates produce plasma lipid changes mainly by stimulating peroxisome-proliferation activation receptors alpha. Through this action, there is an increase in the transcription of some genes related to lipid metabolism, such as LLP, APOAI, APOAII, ABCA-1, as well as decrease in the expression of APOCIII, and many other actions.

[Drug combinations: statins and fibrates]. / Associação de medicamentos: estatinas e fibratos.

Monotherapy for the treatment of dyslipidemias is commonly insufficient to achieve all lipid targets recommended by current guidelines. Therefore, the use of combined treatment has emerged as a new option in many cases in the last few years. A review of 36 studies in which the combination of statins with fibrates was used revealed 29 cases of rhabdomyolysis with a prevalence of 0.12% in the risk of myopathy. Combination of a statin with genfibrozil appeared to cause more rhabdomyolysis than with newest fibrates (especially when compared with fenofibrate or bezafibrate). Advanced age, diabetes, females, concomitant medications, renal insufficiency, excess in alcohol intake, exercises, trauma and surgery were all associated with higher rates of adverse effects.

[Hypolipidemic therapy in special situations: hypothyroidism and liver disease]. / Terapia hipolipemiante em situações especiais--hipotireoidismo e hepatopatias.

Hypothyroidism is common in the elderly, especially among women. It should be suspected in the presence of classic signals and symptoms, and can be detected by an elevation of serum thyroid stimulating hormone (TSH). Lipid abnormalities in the presence of subclinical hypothyroidism are of minor importance. However, the importance of specific treatment (hormone replacement) increases with the magnitude of thyroid disturbance. Some hypolipidemic agents can aggravate prior liver disease, however, recent studies have shown that statins might be useful in the presence of steatohepatitis. Some associations of hypolipidemic drugs can increase liver enzymes, and careful monitoring is recommended.

Predictive Potential of Twenty-Two Biochemical Biomarkers for Coronary Artery Disease in Type 2 Diabetes Mellitus.

We investigated the potential of a panel of 22 biomarkers to predict the presence of coronary artery disease (CAD) in type 2 diabetes mellitus (DM2) patients. The study enrolled 96 DM2 patients with (n = 75) and without (n = 21) evidence of CAD. We assessed a biochemical profile that included 22 biomarkers: total cholesterol, LDL, HDL, LDL/HDL, triglycerides, glucose, glycated hemoglobin, fructosamine, homocysteine, cysteine, methionine, reduced glutathione, oxidized glutathione, reduced glutathione/oxidized glutathione, L-arginine, asymmetric dimethyl-L-arginine, symmetric dimethyl-L-arginine, asymmetric dimethyl-L-arginine/L-arginine, nitrate plus nitrite, S-nitrosothiols, nitrotyrosine, and n-acetyl-ß-glucosaminidase. Prediction models were built using logistic regression models. We found that eight biomarkers (methionine, nitratate plus nitrite, n-acetyl-ß-glucosaminidase, BMI, LDL, HDL, reduced glutathione, and L-arginine/asymmetric dimethyl-L-arginine) along with gender and BMI were significantly associated with the odds of CAD in DM2. These preliminary findings support the notion that emerging biochemical markers might be used for CAD prediction in patients with DM2. Our findings warrant further investigation with large, well-designed studies.

Effects of oxidized LDL on in vitro proliferation and spontaneous motility of human coronary artery endothelial cells.

OBJECTIVE: To investigate the effects of low concentrations of oxidized LDL (oxLDL) on the proliferation and spontaneous motility of human coronary artery endothelial cells (HCAEC) in culture. METHODS: Cultures of HCAEC were treated with low concentrations of native LDL (nLDL) isolated from human plasma and with LDL minimally oxidized through different chemical methods; the effects were compared. RESULTS: Native LDL had no deleterious effects on in vitro proliferation and motility of HCAEC; however, at its highest concentration and for a longer exposure, nLDL inhibited cell proliferation. The LDL chemically oxidized by spermine nonoate (SNO) and 3-morpholinylsydnonimine (SYN-1) had significant inhibiting effects on in vitro proliferation and motility of HCAEC, which were proportional to the greatest concentrations and degrees of oxidation of LDL. CONCLUSION: OxLDL has a cytotoxic effect, inhibiting the proliferation and spontaneous motility of HCAEC in culture. This effect is proportional to the concentration and degree of oxidation of LDL; native LDL is relatively innocuous.

Relevance of target-organ lesions as predictors of mortality in patients with diabetes mellitus.

BACKGROUND: Patients with diabetes are in extract higher risk for fatal cardiovascular events. OBJECTIVE: To evaluate major predictors of mortality in subjects with type 2 diabetes. METHODS: A cohort of 323 individuals with type 2 diabetes from several regions of Brazil was followed for a long period. Baseline electrocardiograms, clinical and laboratory data obtained were used to determine hazard ratios (HR) and confidence interval (CI) related to cardiovascular and total mortality. RESULTS: After 9.2 years of follow-up (median), 33 subjects died (17 from cardiovascular causes). Cardiovascular mortality was associated with male gender; smoking; prior myocardial infarction; long QTc interval; left ventricular hypertrophy; and eGFR <60 mL/min. These factors, in addition to obesity, were predictors of total mortality. Cardiovascular mortality was adjusted for age and gender, but remained associated with: smoking (HR = 3.8; 95% CI 1.3-11.8; p = 0.019); prior myocardial infarction (HR = 8.5; 95% CI 1.8-39.9; p = 0.007); eGFR < 60 mL/min (HR = 9.5; 95% CI 2.7-33.7; p = 0.001); long QTc interval (HR = 5.1; 95% CI 1.7-15.2; p = 0.004); and left ventricular hypertrophy (HR = 3.5; 95% CI 1.3-9.7; p = 0.002). Total mortality was associated with obesity (HR = 2.3; 95% CI 1.1-5.1; p = 0.030); smoking (HR = 2.5; 95% CI 1.0-6.1; p = 0.046); prior myocardial infarction (HR = 3.1; 95% CI 1.4-6.1; p = 0.005), and long QTc interval (HR = 3.1; 95% CI 1.4-6.1; p = 0.017). CONCLUSIONS: Biomarkers of simple measurement, particularly those related to target-organ lesions, were predictors of mortality in subjects with type 2 diabetes.

Importância do diabetes mellitus na estratificação do risco de doença arterial coronária e risco cardiovascular global / Importance of diabetes mellitus in the risk stratification of coronary arterial disease and global cardiovascular risk

O diabetes mellitus é uma doença epidêmica. Os adultos portadores de diabetes têm taxas de doenças cardiovasculares duas a três vezes maiores do que aquelas observadas em adultos não diabéticos. O reconhecimento de que o diabetes é uma doença heterogênea em relação ao risco cardiovascular foi fundamental para a identificação correta dos indivíduos sob maior risco, os quais necessitam de tratamento farmacológico mais intensivo, e daqueles cujo risco é menor, em que o uso de medidas não farmacológicas isoladamente em uma fase inicial é opcional. Ferramentas para estratificação de risco mais precisas, uso apropriado de métodos de rastreamento de isquemia no paciente assintomático e indicação dos métodos de imagem são brevemente revisados neste capítulo. O tratamento de todos os fatores de risco inclui a moderna abordagem do paciente com diabetes, visando a redução de eventos macro e microvasculares. Descritores: Diabetes mellitus; Doença da artéria coronariana; Infarto do miocárdio; Acidente vascular cerebral.

Diabetes mellitus can be considered an epidemic disease. Adults with diabetes have two to three times higher rates of cardiovascular disease than those observed in non-diabetic adults. The recognition that diabetes is a heterogeneous disease in relation to cardiovascular risk was fundamental for the correct identification of individuals at higher risk, who require more intensive pharmacological intervention, and those at lower risk, where the use of non-pharmacological strategies alone in an initial phase is optional. More precise risk stratification tools, the appropriate use of screening methods for tracking ischemia in the asymptomatic patient, and the indication of imaging tests will be summarized in this review. Treatment based on global risk factor control includes the modern approach for the patient with diabetes, aiming at reducing both macro- and microvascular events.

Relevance of Target-Organ Lesions as Predictors of Mortality in Patients with Diabetes Mellitus / Relevância de Lesões em Órgãos-Alvo como Preditores de Mortalidade em Pacientes com Diabetes

Background: Patients with diabetes are in extract higher risk for fatal cardiovascular events. Objective: To evaluate major predictors of mortality in subjects with type 2 diabetes. Methods: A cohort of 323 individuals with type 2 diabetes from several regions of Brazil was followed for a long period. Baseline electrocardiograms, clinical and laboratory data obtained were used to determine hazard ratios (HR) and confidence interval (CI) related to cardiovascular and total mortality. Results: After 9.2 years of follow-up (median), 33 subjects died (17 from cardiovascular causes). Cardiovascular mortality was associated with male gender; smoking; prior myocardial infarction; long QTc interval; left ventricular hypertrophy; and eGFR <60 mL/min. These factors, in addition to obesity, were predictors of total mortality. Cardiovascular mortality was adjusted for age and gender, but remained associated with: smoking (HR = 3.8; 95% CI 1.3-11.8; p = 0.019); prior myocardial infarction (HR = 8.5; 95% CI 1.8-39.9; p = 0.007); eGFR < 60 mL/min (HR = 9.5; 95% CI 2.7-33.7; p = 0.001); long QTc interval (HR = 5.1; 95% CI 1.7-15.2; p = 0.004); and left ventricular hypertrophy (HR = 3.5; 95% CI 1.3-9.7; p = 0.002). Total mortality was associated with obesity (HR = 2.3; 95% CI 1.1-5.1; p = 0.030); smoking (HR = 2.5; 95% CI 1.0-6.1; p = 0.046); prior myocardial infarction (HR = 3.1; 95% CI 1.4-6.1; p = 0.005), and long QTc interval (HR = 3.1; 95% CI 1.4-6.1; p = 0.017). Conclusions: Biomarkers of simple measurement, particularly those related to target-organ lesions, were predictors of mortality in subjects with type 2 diabetes. .

Fundamento: Pacientes com diabetes apresentam-se em extrato de maior risco para eventos cardiovasculares fatais. Objetivo: Avaliar os principais preditores associados às taxas de mortalidade em pacientes com diabetes tipo 2. Métodos: Estudo de coorte composto por 323 indivíduos com diabetes mellitus do tipo 2, de várias regiões do Brasil, acompanhados em longo prazo. Dados clínicos, laboratoriais e eletrocardiográficos foram obtidos no período basal e aplicados no modelo Cox de regressão, para examinar a associação dessas variáveis com as taxas de mortalidade e determinação de hazard ratio (HR) e intervalo de confiança (IC). Resultados: Após 9,2 anos (mediana) de seguimento, 33 pacientes morreram (sendo 17 por causas cardiovasculares). A mortalidade cardiovascular foi associada a gênero masculino, tabagismo, infarto do miocárdio prévio, intervalo QTc longo, hipertrofia ventricular esquerda e taxa de filtração glomerular (TFG) <60 mL/min. Esses biomarcadores, além da obesidade, também foram preditores para mortalidade total. Após ajustes para idade e gênero, a mortalidade cardiovascular, manteve-se associada a tabagismo (HR = 3,8; IC 95% 1,3-11,8; p = 0,019), infarto prévio do miocárdio (HR = 8,5; IC 95% 1,8-39,9; p = 0,007), TFG < 60 mL/min (HR = 9,5; IC 95% 2,7-33,7; p = 0,001), intervalo QTc longo (HR = 5,1; IC 95% 1,7-15,2; p = 0,004), hipertrofia ventricular esquerda (HR = 3,5; IC 95% 1,3-9,7; p = 0,002). A mortalidade total foi associada com obesidade (HR = 2,3; IC 95% 1,1-5,1; p = 0,030), tabagismo (HR = 2,5; IC 95% 1,0-6,1; p = 0,046), infarto prévio do miocárdio (HR = 3,1; 95% CI 1,4-6,1; p = 0,005) e intervalo QTc longo (HR = 3,1; 95% CI 1,4-6,1; p = 0,017). Conclusões: Biomarcadores de simples mensuração, particularmente os que traduzem lesões de ...

Biomarkers of oxidative stress and endothelial dysfunction in glucose intolerance and diabetes mellitus.

OBJECTIVES: To evaluate biomarkers of endothelial dysfunction and oxidative stress in glucose intolerance (GI) compared to overt diabetes (DM2). DESIGN AND METHODS: 140 volunteers including 96 with DM2, 32 with GI and 12 controls (C) were studied. (*)NO metabolites, (*)NO synthase inhibitors, thiols and N-acetyl-beta-glucosaminidase (NAGase) activity were analyzed by chemiluminescence, capillary electrophoresis, ELISA and colorimetric assay, respectively. RESULTS: (*)NO metabolites were higher in GI (NOx: p=0.03; S-nitrosothiols: p=0.001) and DM2 (p=0.006; p=0.0006) groups in relation to group C, while nitrotyrosine was higher only in the DM2 group in comparison to the other groups. NAGase activity was elevated in GI (p=0.003) and DM2 (p=0.0004) groups in relation to group C, as well as, ADMA (p=0.01; p=0.003) and GSSG (p=0.01; p=0.002). CONCLUSIONS: (*)NO metabolites, (*)NO synthase inhibitors, thiols and NAGase are biomarkers suitable to indicate endothelial dysfunction and oxidative stress in the early stages of impaired response to insulin.

Estudo de prevalência e multiplicidade de fatores de risco cardiovascular em hipertensos do Município de Brusque, SC / Study of the prevalence and multiplicity of cardiovascular risk factors in hypertensive individuals from the city of Brusque, SC, Brazil

OBJETIVO: Investigar a prevalência e a multiplicidade de fatores de risco (FR) adicionais em uma amostra populacional de indivíduos hipertensos e tabagistas, diagnosticados e inscritos no Programa Hipertensos e Diabéticos do MS (HIPERDIA/Ministério da Saúde), no Município de Brusque, SC, Brasil. MÉTODOS: Determinação de parâmetros antropométricos e variáveis laboratoriais reconhecidas como fatores de risco cardiovascular. RESULTADO: Elevada prevalência de FR adicionais à hipertensão arterial (HAS) e ao tabagismo, configurando a multiplicidade que concorre com uma elevação acentuada do risco de eventos cardiovasculares nessa amostra populacional. CONCLUSÃO: Em populações de hipertensos, medidas de prevenção, identificação e controle de FR devem ser implementadas e programas informatizados, como o Hiperdia/MS, podem auxiliar no seguimento dos pacientes, possibilitando uma abordagem multidisciplinar mais criteriosa, sobretudo na análise do alcance das metas de tratamento e conseqüente redução de risco cardiovascular.

Farmacologia do fibratos / Pharmacology of fibrates

Os fibratos são as drogas de escolha nas hipertrigliceridemias. Após sua absorção, os fibratos são metabolizados pelo fígado, utilizando isoenzimas P450 não compartilhadas pelas estatinas. Entretanto, para alguns fibratos, como o genfibrozil, uma interação com estatinas pode ocorrer durante a sua glucuronidação, ou pelo deslocamento de frações livres de estatina ligadas às proteínas plasmáticas. A vida-média plasmática é variável entre os fibratos (2-80 h). Recentemente, foi demonstrado que os fibratos promovem suas ações lipídicas pelo estímulo dos PPAR-alfa. Através dessa ação, existe um incremento na transcrição de alguns genes relacionados com o metabolismo lipídico, como a LLP, APOAI, APOAII, ABCA-1, bem como uma diminuição na expressão da APOCIII, e muitas outras ações.

Associação de medicamentos: estatinas e fibratos / Combination of drugs: statins and fibrates

Monoterapia para o tratamento das dislipidemias é frequentemente insuficiente para o alcance das metas recomendadas pelas diretrizes. Entretanto, nos últimos anos, o uso de terapia combinada tem se apresentado como uma nova opção em muitos casos. Uma revisão de 36 estudos envolvendo a combinação de estatinas com fibratos apresentou 29 casos de rabdomiólise e uma prevalência geral de miopatia de 0,12 por cento. A combinação de estatinas com o genfibrozil parece causar mais rabdomiólise que com os fibratos de nova geração (especialmente quando comparado com fenofibrato ou bezafibrato). Idade avançada, diabetes, mulheres, medicações concomitantes, disfunção renal, consumo excessivo de álcool, exercícios, traumatismos e cirurgias estão também associados com maior risco de efeitos adversos.

Terapia hipolipemiante em situações especiais: hipotireoidismo e hepatopatias / Hypolipidemic therapy in special situations: hypothyroidism and liver disease

O hipotireoidismo é comum entre pessoas idosas, especialmente entre as mulheres. A suspeita diagnóstica deve se basear na presença de sinais e sintomas clássicos e a detecção pode ser feita pela elevação dos níveis do hormônio tireo-estimulante (TSH). Anormalidades lipídicas na presença de hipotireoidismo sub-clínico são de menor impacto. Entretanto, a reposição específica de hormônio tireoideano é tão mais importante quanto a magnitude do distúrbio glandular. Na vigência de doença hepática, alguns agentes hipolipemiantes podem levar a um agravamento do quadro, entretanto, estudos recentes têm mostrado que as estatinas podem ser utilizadas na presença de esteatose hepática. Terapia hipolipemiante combinada pode induzir aumentos de enzimas hepáticas e o monitoramento cuidadoso é recomendado nestes pacientes.