[Special recommendations for lipid-lowering treatment: efficacy and safety]. / Periodicidade e escolha de exames laboratoriais na terapia hipolipemiante.

Pharmacologic lipid-lowering interventions should be monitored periodically to assess efficacy and safety parameters. Statins are usually well-tolerated drugs and major side effects include increased serum liver and muscle enzymes (AST, ALT, CK). Treatment should be stopped or diminished in case of significant increase of AST or ALT (> 3x ULN), or CK (> 10x ULN). Other lipid lowering agents may also produce hepatotoxicity or myositis, especially in association with statins (fibrates and nicotinic acid) or in presence of metabolic abnormalities (thyroid, liver or renal disorders). Nicotinic acid can also increase glucose and uric acid plasma levels. Laboratory tests might be performed prior to hypolipidemic drug treatment and should be repeated every three months during the first year and then at 6-mo intervals. Shorter intervals should be recommended in individual cases.

[Intracoronary inflammatory markers after percutaneous coronary interventions]. / Marcadores inflamatórios intracoronarianos após intervenções coronarianas percutâneas.

OBJECTIVE: To analyze intracoronary release of inflammatory markers (IM) after percutaneous coronary interventions (PCI) and compare their concentrations concerning the type of PCI used (rotablator vs. balloon angioplasty). METHODS: Twenty-two patients with average age of 60 +/- 11.9 years old, 12 of male sex, with stable coronary disease, submitted to elective treatment of a single coronary lesion, using rotablator (N = 11) or balloon pre-dilatation (N = 11) for stent implant were randomized. Samples were collected at aorta root and coronary sinus, immediately before and 15 minutes after intervention. All dosages were made before stent implant, and the cytokines TNF-a, IL-6 and IL-1 and the soluble adhesion molecules ICAM-1, E-selectin and P-selectin were analyzed by using ELISA method. RESULTS: TNF-a and IL-6 concentrations increased after PCI, respectively from 9.5 +/- 1.5 pg/ml to 9.9 +/- 1.8 pg/ml (p = 0.017) and from 6.0 +/- 2.4 pg/ml to 6.9 +/- 3.0 pg/ml (p < 0.001). There was no significant changes in IL-1, ICAM-1 and P-selectin, and a decrease in E-selectin concentrations after the procedures (52.0 +/- 17.5 ng/ml to 49.3 +/- 18.7 ng/ml; p = 0.009) was observed. There were no significant differences between IM concentrations after PCI, concerning the type of procedure used. CONCLUSION: At the early period, post-percutaneous coronary interventions, an increase of intracoronary concentrations of TNF-a and IL-6, and absence of significant difference between concentrations of inflammatory markers released in coronary flow through rotablator and balloon angioplasty were observed.

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.

Comparison of the lipid profile, blood pressure, and dietary habits of adolescents and children descended from hypertensive and normotensive individuals.

OBJECTIVE: To compare blood pressure, lipid profile, food intake, and anthropometric data of adolescents with or without a familial history of hypertension. METHODS: Forty-three adolescents from both sexes were assessed, with ages ranging from 11 to 18 years old. Twenty had hypertensive parents, and 23 had normotensive parents. The following variables were examined: blood pressure, food intake, anthropometric data, lipid profile, and the results of following dietary guidelines (American Heart Association). RESULTS: The offspring of hypertensive parents had greater baseline systolic blood pressure (109 +/- 3 vs. 99 +/- 2 mm Hg, P=0.01), diastolic blood pressure (68 +/- 2 vs. 62 +/- 2 mm Hg, p=0.04), greater TC/HDL-C ratio (4.1 +/- 0.3 vs. 3.2 +/- 0.2, P<0.01), and greater LDL/HDL-C (2.7 +/- 0.2 vs. 1.9 +/- 0.1, P<0.01), and smaller values of HDL-C (43 +/- 2 vs.53 +/- 2 mg/dL, P<0.005). Dietary intake and anthropometric measures assessed did not differ between the groups. Even though dietary intervention resulted in reductions in body mass index (21.0+/- 1.2 vs. 20.1 +/- 1.1 kg/m(2), P<0.01), it did not change dyslipidemia present in the offspring of hypertensive individuals. CONCLUSION: Increased blood pressure levels and less favorable lipid profiles are found among offspring of hypertensive parents, where low levels of HDL-C were the most relevant finding regardless of anthropometric or nutritional variables.

Periodicidade e escolha de exames laboratoriais na terapia hipolipemiante / Special recommendations for lipid-lowering treatment: efficacy and safety

Intervenções farmacológicas com hipolipemiantes devem ser monitoradas periodicamente para avaliar eficácia e parâmetros de segurança. As estatinas são drogas normalmente bem toleradas e os seus principais efeitos colaterais incluem aumento das enzimas hepáticas (AST e ALT) e muscular (CK). O tratamento deve ser interrompido ou diminuído no caso de um aumento significativo das AST ou ALT (> 3x LSN), ou CK (> 10x LSN). Outros agentes hipolipemiantes também podem produzir hepatotoxicidade ou miosite, fibratos e ácido nicotínico, especialmente em associação com as estatinas ou na presença de anormalidades metabólicas (tireoidite, hepatopatia e nefropatia). Acido nicotínico pode também aumentar os níveis plasmáticos de glicose e ácido úrico. Testes laboratoriais podem ser utilizados no seguimento da terapia hipolipemiante e devem ser repetidos a cada três meses durante o primeiro ano e então em intervalos de seis meses. Intervalos menores são recomendados para casos especiais.

Marcadores inflamatórios intracoronarianos após intervenções coronarianas percutâneas / Intracoronary inflammatory markers after percutaneous coronary interventions

OBJETIVO: Analisar a liberação intracoronariana de marcadores inflamatórios (MI) após intervenções coronarianas percutâneas (ICP) e comparar suas concentrações com relação ao tipo de ICP utilizada (rotablator vs angioplastia por balão). MÉTODOS: Foram randomizados 22 pacientes com média de idade de 60±11,9 anos, 12 do sexo masculino, portadores de síndromes coronarianas estáveis, submetidos ao tratamento eletivo de uma única lesão coronariana utilizando rotablator (N=11) ou pré-dilatação por balão (N=11) para implante de stents. As amostras foram colhidas na raiz da aorta e no seio coronariano, imediatamente antes e 15 minutos após as intervenções. Todas as dosagens foram feitas antes do implante do stent, sendo analisadas as citocinas TNF-a, IL-6 e IL-1 e as moléculas de adesão solúveis ICAM-1, E-selectina e P-selectina, utilizando o método ELISA. RESULTADOS: As concentrações de TNF-a e IL-6 aumentaram após as ICP, passando respectivamente de 9,5±1,5 pg/ml para 9,9±1,8 pg/ml (p=0,017) e de 6,0±2,4 pg/ml para 6,9±3,0 pg/ml (p<0,001). Não houve mudança significativa na expressão de IL-1, ICAM-1 e P-selectina, observando-se diminuição nas concentrações de E-selectina após os procedimentos (52,0±17,5 ng/ml para 49,3±18,7 ng/ml; p=0,009). Não houve diferença significativa entre as concentrações dos MI após as ICP, com relação ao tipo de procedimento utilizado. CONCLUSAO: No período precoce, pós-intervenções coronarianas percutâneas, observou-se aumento das concentrações intracoronárias de TNF-a e IL-6 e ausência de diferença significativa entre as concentrações dos marcadores inflamatórios liberados na circulação coronariana por rotablator e pela angioplastia com balão.

Efeitos da lipoproteína LDL-oxidada sobre a proliferação e a motilidade espontânea in vitro de células endoteliais de artérias coronárias humanas / Effects of oxidized LDL on in vitro proliferation and spontaneous motility of human coronary artery endothelial cells

OBJETIVO: Investigar os efeitos de baixas concentrações de LDL oxidada (LDL-ox) sobre a proliferação e a motilidade espontânea de células endoteliais de artérias coronárias humanas (CEACH) em cultura. MÉTODOS: Culturas de CEACH foram tratadas com baixas concentrações de LDL nativa (LDLn), isolada de plasma humano, e com LDL minimamente oxidada por diferentes métodos químicos, e os efeitos, comparados entre si. RESULTADOS: LDLn não apresentou efeitos deletérios sobre o endotélio em proliferação e na motilidade in vitro de CEACH, porém na mais alta concentração e por tempo mais prolongado inibiu a proliferação celular. As LDL-ox, quimicamente, pela espermina nonoato (ENO) e 3-morfolinosidnonimina (SIN-1) expressaram efeitos inibitórios significativos sobre a proliferação e a motilidade in vitro de CEACH proporcionais às maiores concentrações e graus de oxidação das LDL. CONCLUSÃO: LDL-ox apresenta efeito citotóxico, inibindo a proliferação e a motilidade espontânea de células endoteliais de artérias coronárias humanas em cultura, proporcionalmente à concentração e ao grau de oxidação da LDL, enquanto, LDL nativa é relativamente inócua.

Efeitos da pravastatina nas lipoproteínas, Lp(a), apo B e apo A-I em pacientes com hipercolesterolemia primária / Effects of Pravastatin on Lipoproteins, Lp(a), apo B and apo A-I in Patients with Primary Hypercholesterolemia

PURPOSE--To evaluate the effects of pravastatin on lipoproteins, Lp (a), apo B and apo A-I and its tolerability in primary hypercholesterolemic patients in our outpatient lipid clinic. METHODS--Twenty-two primary hypercholesterolemic patients were evaluated. They had all been treated previously with other hypocholesterolemic drugs, including the statins, forming a specific and homogeneous group with hypercholesterolemia and definite coronary risk. After 7 weeks with American Heart Association phase I diet and placebo drug, pravastatin was administered during 12 weeks. All patients received an initial daily dose of 10 mg for six weeks. After this period, this dose was increased to 20 mg. The levels of cholesterol, triglycerides, high-density lipoprotein, lipoprotein (a) and apolipoproteins A-1 and B were determined. RESULTS--No changes occurred with diet and placebo, but pravastatin at a daily dose of 10 mg, reduced significantly cholesterol level (7.22 per cent) LDL-cholesterol (13.08 per cent) and increased HDL-cholesterol (7.8 per cent). The results were better with 20 mg, achieving a reduction of (28.21 per cent) in cholesterol, (36.88 per cent) in LDL-cholesterol, (17.06 per cent) in apo B level and an increase of (10.06 per cent) in HDL-cholesterol. The smaller effect observed with the more commonly used dosage (10 mg/day) was most probably due to the characteristics of the sample with already established hypercholesterolemia, being thus dependent of higher concentrations of medications, as observed in previous treatments in our outpatient clinic. Side affects with this drug were rare. No biochemical changes were observed that would interrupt the continuation of therapy. CONCLUSION--Pravastatin was well tolerated and promoted favorable changes in the total cholesterol, LDL, apo B and cholesterol/HDL and LDL/HDL ratios of primary hypercholesterolemic patients

Avaliação da eficácia e segurança do etofibrato em pacientes dislipidêmicos. Estudo multicêntrico / Evaluation of efficacy and safety of etofibrate in primary hyperlipidemia. A multicenter study

PURPOSE: To evaluate the clinical efficacy of etofibrate in primary hyperlipidemia in patients from clinical centers representative of all main Brazilian cities. METHODS: One thousand, nine hundred and fourty three hyperlipidemic patients were submitted to diet and drug treatment with etofibrate (500 mg/day) for eight weeks. The data b WAS analyzed as to changes in the lipoprotein profile, as well as the side effects. RESULTS: There was an important reduction in total cholesterol (19.88), triglycerides (29.59), LDL-c (14.89) and VLDL-c (14.54) concentration. There was a significant increase in HDL-c (18.14). Adverse effects were observed in 8.5 of the patients, without major clinical relevance, however, in 1.44 the treatment had to be interrupted. CONCLUSION: Administration of etofibrate promoted positive changes in all parameters of the lipid and lipoprotein profile, thus reducing the risk of atherosclerotic disease, without significant side effects in the great majority of sample studied.