AMI is associated with polymorphisms in the NOS3 and FGB but not in PAI-1 genes in young adults.

BACKGROUND: We investigated the relationship between NOS3, FGB and PAI-1 polymorphisms and endothelial dysfunction and risk factors for acute myocardial infarction (AMI) in young adults. METHODS: Endothelial function was measured by response to flow mediated vasodilation (FMV) and induced by nitrate (FMN). Biochemical parameters were measured by standard enzymatic methods and plasma total nitrate was analyzed by the NOA system. NOS3 (T-786C, G894T and intron 4A/B STR), FGB (C-148T and G-455A) and PAI-1 (4G/5G) polymorphisms were determined by PCR-RFLP. RESULTS: Concentrations of total and LDL cholesterol, apo B, triglycerides, nitrate, PAI-1 and fibrinogen were higher and apo AI, HDL cholesterol and FMV were lower in AMI patients than in controls (p<0.001). PAI-1 (p<0.001) but not nitrate was higher in AMI patients with low response to FMV. NOS3 T-786C and FGB C-148T polymorphisms were associated with AMI (p<0.050). NOS3 T-786C was also related to hypertension (p=0.049). NOS3 intron 4A/B STR was associated with increased concentrations of total cholesterol and apo B. NOS3-786TT/894GT haplotype was associated with increased FMV (p=0.018) than the other haplotypes. CONCLUSIONS: Our data suggest NOS3 and FGB polymorphisms are associated with AMI. NOS3 is also related to hypertension, endothelial dysfunction and variation on serum cholesterol in young adults with AMI.

Influence of age and coronary artery disease on homocysteine levels in the young old compared with the old old and the oldest old.

A total of 172 elderly individuals, divided into case and control groups based on the diagnosis of coronary artery disease, underwent coronary angiography to investigate the influence of age and coronary artery disease on homocysteine levels. The subjects were divided into three age ranges: 65-74 years, 75-79 years, and 80 years and older. Continuous homocysteinemia was associated with a risk ratio for coronary artery disease of 1.07 for each micromol/L increase in homocysteine level. Hyperhomocysteinemia (values above 14 micromol/L) constituted an independent risk factor for coronary artery disease, with a risk ratio of 2.03. There was a progression of homocysteine levels between the young old and the oldest old only among the case group elderly. There was no difference among the control group elderly. There were no significant differences in vitamin levels. The rise in homocysteine levels from the young old to the oldest old may be considered not a normal pattern, but rather a pattern associated with coronary artery disease.

[Left ventricular hypertrophy of athletes: adaptative physiologic response of the heart]. / Hipertrofia ventricular esquerda do atleta: resposta adaptativa fisiológica do coração.

OBJECTIVE: To verify whether left ventricular hypertrophy (LVH) of elite competition athletes (marathoners) represents a purely physiological, adaptative process, or it may involve pathological aspects in its anatomical and functional characteristics. METHODS: From November 1999 to December 2000, consecutive samples from 30 under 50-year-old marathoners in full sportive activity, with previously documented LVH and absence of cardiopathy were selected. They were submitted to clinical exams, electrocardiogram, color Doppler echocardiogram and exercise treadmill test (ETT). Fifteen were assorted to be also submitted to ergoespirometric test and heart magnetic resonance imaging (MRI). RESULTS: In ETT, all of them showed good physical pulmonary capacity, with no evidences of ischemic response to exercise, symptoms or arrhythmias. In Doppler echocardiogram, values of diameter and diastolic thickness of LV posterior wall, interventricular septum, LV mass and left atrium diameter, were significantly higher when compared to non-athlete control group, with similar ages and anthropometric measurements. The mean of LV mass of athletes indexed to body surface (126 g/m2) was significantly greater than the one in control group (70 g/m2) (p < 0.001). Magnetic resonance imaging (MRI) showed there was not impairment of contractile strength or LV performance, and values of end diastolic volume, end systolic volume and EF within limits of normality. On the other hand, average ventricular parietal mass, 162.93 +/- 17.90 g, and LV parietal thickness, 13.67 +/- 2.13 mm, at the end of diastole in athlete group, differed significantly from control group: 110 +/- 14.2 g (p = 0.0001) and 8 +/- 0.9 mm, respectively (p = 0.0001). The same happened to the thickness at the end of systole, which was 18.87 +/- 3.40 mm (control group: 10 +/- 1.80 mm, p = 0.0001). CONCLUSION: Results allowed for concluding that LVH in marathoners in full sportive activity period, assessed by non-invasive methods, represents an adaptative response to intensive and prolonged physical training, with purely physiological characteristics.

[Hyperhomocysteinemia as a risk factor for coronary atherosclerotic diseases in the elderly]. / Hiper-homocisteinemia como fator de risco para doença aterosclerótica coronariana em idosos.

OBJECTIVE: To investigate whether hyperhomocysteinemia is an independent risk factor for atherosclerotic disease in elderly individuals. METHODS: A case-control study with 172 elderly individuals, 88 belonging to control group and 84 to case group, who showed coronary angiography requested for clinical indications. Quantitative coronary angiography was performed in 91% of the patients. Homocysteinemia was assessed in a continuous and categorized way, through univariate and multivariate analysis. RESULTS: When analyzed continuously, in univariate analysis, it was verified that case group elderly individuals showed an average homocysteinemia levels significantly higher than the control group individuals' (14.33 +/- 4.59 micromol/l against 11.99 +/- 4.59 micromol/l, p = 0.015). In multivariate analysis, continuous homocysteinemia was associated to the risk rate for coronary artery disease of 1.07 for each 1 micromol/l increase of homocysteine level. Na increase of 5 micromol/l corresponded to the risk rate of 1.40. When analyzed in categorized way, the values found over percentile 75 of control group (14 micromol/l) were defined as hyperhomocysteinemia. Hyperhomocysteinemia was found in 34% of elderly individuals, being 37.3% in control group and 62.7% in case group (p = 0.009). In multivariate analysis, hyperhomocysteinemia constituted an independent risk factor for coronary atherosclerotic disease for elderly individuals, with a risk rate for coronary artery disease of 2.03, confidence interval 95%, 1.02-4.03. CONCLUSION: Hyperhomocysteinemia was an independent risk factor for coronary artery disease in elderly individuals.

Serum ferritin levels and other indicators of organic iron as risk factors or markers in coronary artery disease.

BACKGROUND: Several international studies have discussed whether serum ferritin is a risk marker in coronary heart disease. The objective of this study was to evaluate the importance of serum ferritin levels and other indicators of organic iron as possible risk factors or markers in coronary artery disease. Secondly, the classical factors were studied in order to identify possible associations with organic iron markers. METHODS AND RESULTS: In a medical institution, 1263 patients underwent cinecoronary arteriography from December 1997 to May 1998. A sample of 400 patients was separated, at random, to establish a comparative clinical study between two groups: group A, comprising 200 individuals with coronary atherosclerosis and group B, comprising 200 patients without coronary atherosclerosis, as confirmed by cinecoronary arteriography. From group A, 182 patients (130 males) and from group B, 157 (96 females) did not show any exclusion criteria and were considered eligible. All women were in the postmenopausal period. The blood samples were collected by a biologist, between 8.30 and 9.0 a.m., after a 12-hour fast and a 36-hour non-smoking period. In order to analyze all results, univariate analysis, the logistic regression technique and the interactive forward stepwise method were used in order to optimize the model and to predict the chances of coronary atherosclerosis. The results of the logistic regression with all the variables analyzed showed that male gender, age, smoking, triglycerides/VLDL interaction, increased serum LDL-C levels and decreased serum HDL-C levels are important to predict the chances of coronary atherogenesis. CONCLUSION: Serum levels of ferritin and of other organic iron indicators--transferrin saturation, total iron-binding capacity, hemoglobin and hematocrit--were neither risk factors nor risk markers for coronary atherosclerosis. Paradoxically, serum iron levels were higher in the group without atherosclerosis. In this study, variables classically considered as risk factors were similar to those in the literature.

Increased dietary sodium is related to severity of obstructive sleep apnea in patients with resistant hypertension and hyperaldosteronism.

BACKGROUND: Obstructive sleep apnea (OSA) is a strong and independent risk factor for the development of hypertension, particularly resistant hypertension, and cardiovascular diseases. Patients with resistant hypertension have a high prevalence of OSA in association with elevated aldosterone levels, high salt intake, and salt-sensitive BP. The objective of this study was to determine whether dietary salt and aldosterone are associated with severity of OSA in patients with resistant hypertension. METHODS: Ninety-seven patients with resistant hypertension were prospectively evaluated by overnight polysomnography and 24-h urinary sodium and aldosterone levels while maintaining their usual diet. Hyperaldosteronism was defined as a plasma renin activity of < 1 ng/mL/h and urinary aldosterone level of ≥ 12 µg/24 h. RESULTS: Overall, patients' mean clinic BP was 156.3 ± 22.4/88.9 ± 13.3 mm Hg while taking an average of 4.3 ± 1.1 antihypertensive medications. Prevalence of OSA was 77.3%. Twenty-eight (28.9%) patients had hyperaldosteronism. Urinary sodium level was an independent predictor of severity of OSA only in patients with hyperaldosteronism. CONCLUSIONS: The findings suggest that dietary salt is related to the severity of OSA in patients with resistant hypertension and hyperaldosteronism. The results support dietary salt restriction as a treatment strategy for reduction of OSA severity in these patients.

Heart failure in the elderly.

The aging of the population is, currently, a major phenomenon, drawing the attention of a number of investigators. The significant increase of life expectancies over the past few decades, in addition to social and economic consequences, has lead to a major change in the morbidity and mortality profile of elders. Heart failure (HF) is a condition in which the heart can not pump enough blood to meet the body's needs. HF is predominantly a disorder of the elderly with rates increasing exponentially. The prevalence of HF approximately doubles with each decade of life. As people live longer, the occurrence of HF rises, as well as other conditions that complicate its treatment. Impaired heart function implies a reduced duration of survival. Fortunately, many factors that can prevent HF and improve outcome are known and can be applied at any stage. This review emphasizes the importance of factors inherent in aging itself, focusing on heart disease, particularly as a disease of aging, can help critically refine management of this acute and chronic disease, as well as foster preventive strategies to reduce the incidence of this common malady.

[Nonsteroidal anti-inflammatory drugs: cardiovascular, cerebrovascular and renal effects]. / Anti-inflamatórios não esteroides: Efeitos cardiovasculares, cérebro-vasculares e renais.

The nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most often prescribed drugs in the world. This heterogeneous class of drugs includes aspirin and several other selective or non-selective cyclooxygenase (COX) inhibitors. The non-selective NSAIDs are the oldest ones and are called traditional or conventional NSAIDs. The selective NSAIDs are called COX-2 inhibitors. In recent years, the safety of NSAID use in clinical practice has been questioned, especially that of the selective COX-2 inhibitors. The evidence on the increase in cardiovascular risk with the use of NSAIDs is still scarce, due to the lack of randomized and controlled studies with the capacity of evaluating relevant cardiovascular outcomes. However, the results of prospective clinical trials and meta-analyses indicate that the selective COX-2 inhibitors present important adverse cardiovascular effects, which include increased risk of myocardial infarction, cerebrovascular accident, heart failure, kidney failure and arterial hypertension. The risk of these adverse effects is higher among patients with a previous history of cardiovascular disease or those at high risk to develop it. In these patients, the use of COX-2 inhibitors must be limited to those for which there is no appropriate alternative and, even in these cases, only at low doses and for as little time as possible. Although the most frequent adverse effects have been related to the selective COX-2 inhibition, the absence of selectiveness for this isoenzyme does not completely eliminate the risk of cardiovascular events; therefore, all drugs belonging to the large spectrum of NSAIDs should only be prescribed after consideration of the risk/benefit balance.

ACE inhibitors and plasma B-type natriuretic peptide levels in elderly patients with heart failure.

BACKGROUND: Clinical trials have demonstrated the benefits of ACE inhibitors (ACEI) in the neurohormonal activity and in the functional capacity of patients with heart failure (HF), and also that these effects are dose dependent. However, since elderly individuals have been systematically excluded from the majority of these studies, the validation and incorporation of these results in the geriatric population has been questioned. OBJECTIVE: To evaluate the effects of different doses of quinapril, an ACEI with a > 24-hour biological half-life, on plasma BNP levels, on the distance walked in the 6-minute walk test (6MWT) and on the incidence of adverse reactions in elderly individuals with systolic HF. METHODS: A total of 30 patients (76.1 +/- 5.3 years; 15 women), in NYHA functional class II-III HF, with left ventricular EF < 40% (33.5 +/- 4.5%), on diuretics (30), digoxin (24) and nitrates (13) were included. The patients were assessed at baseline and every two months, with escalating doses of quinapril of 10, 20, 30 and 40 mg. RESULTS: After eight months, BNP levels were 67.4% lower and the distance walked in the 6MWT was 64.9% longer in relation to baseline. Arterial hypotension with symptoms of low cerebral blood flow and/or renal dysfunction was not observed, so that the maximum quinapril dose could be used in all patients. CONCLUSION: The results demonstrated the benefits of ACEI on the neurohormonal profile and functional capacity of elderly individuals with systolic HF, as well as the positive relationship between dose and effect of these drugs.

Anti-inflamatórios não esteroides: Efeitos cardiovasculares, cérebro-vasculares e renais / Nonsteroidal anti-inflammatory drugs: cardiovascular, cerebrovascular and renal effects

Os anti-inflamatórios não esteroides (AINEs) encontram-se entre os medicamentos mais prescritos em todo o mundo. Essa classe heterogênea de fármacos inclui a aspirina e vários outros agentes inibidores da ciclo-oxigenase (COX), seletivos ou não. Os AINEs não seletivos são os mais antigos, e designados como tradicionais ou convencionais. Os AINEs seletivos para a COX-2 são designados COXIBEs. Nos últimos anos, tem sido questionada a segurança do uso dos AINEs na prática clínica, particularmente dos inibidores seletivos da COX-2. As evidências sobre o aumento do risco cardiovascular com o uso de AINEs são ainda incompletos, pela ausência de ensaios randomizados e controlados com poder para avaliar desfechos cardiovasculares relevantes. Entretanto, os resultados de estudos clínicos prospectivos e de meta-análises indicam que os inibidores seletivos da COX-2 exercem importantes efeitos cardiovasculares adversos, que incluem aumento do risco de infarto do miocárdio, acidente vascular cerebral, insuficiência cardíaca, insuficiência renal e hipertensão arterial. O risco desses efeitos adversos é maior em pacientes com história prévia de doença cardiovascular ou com alto risco para desenvolvê-la. Nesses pacientes, o uso de inibidores da COX-2 deve ser limitado àqueles para os quais não há alternativa apropriada e, mesmo assim, somente em doses baixas e pelo menor tempo necessário. Embora os efeitos adversos mais frequentes tenham sido relacionados à inibição seletiva da COX-2, a ausência de seletividade para essa isoenzima não elimina completamente o risco de eventos cardiovasculares, de modo que todos os fármacos do largo espectro dos AINEs somente devem ser prescritos após consideração do balanço risco/benefício.

The nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most often prescribed drugs in the world. This heterogeneous class of drugs includes aspirin and several other selective or non-selective cyclooxygenase (COX) inhibitors. The non-selective NSAIDs are the oldest ones and are called traditional or conventional NSAIDs. The selective NSAIDs are called COX-2 inhibitors. In recent years, the safety of NSAID use in clinical practice has been questioned, especially that of the selective COX-2 inhibitors. The evidence on the increase in cardiovascular risk with the use of NSAIDs is still scarce, due to the lack of randomized and controlled studies with the capacity of evaluating relevant cardiovascular outcomes. However, the results of prospective clinical trials and meta-analyses indicate that the selective COX-2 inhibitors present important adverse cardiovascular effects, which include increased risk of myocardial infarction, cerebrovascular accident, heart failure, kidney failure and arterial hypertension. The risk of these adverse effects is higher among patients with a previous history of cardiovascular disease or those at high risk to develop it. In these patients, the use of COX-2 inhibitors must be limited to those for which there is no appropriate alternative and, even in these cases, only at low doses and for as little time as possible. Although the most frequent adverse effects have been related to the selective COX-2 inhibition, the absence of selectiveness for this isoenzyme does not completely eliminate the risk of cardiovascular events; therefore, all drugs belonging to the large spectrum of NSAIDs should only be prescribed after consideration of the risk/benefit balance.

Diuréticos / Diuretics

Diuréticos, especialmente tiazídicos e correlatos, têm sido utilizados no tratamento da hipertensão arterial há mais de 40 anos e permanecem como uma das cinco classes de medicamentos anti-hipertensivos de primeira linha. Diuréticos continuam sendo utilizados em monoterapia, mas sobretudo em associações fixas ou não, com os demais agentes anti-hipertensivos devido à potencialização de seus efeitos redutores da pressão arterial. São fármacos de baixo custo e boa tolerabilidade. Suas principais reações adversas relacionam-se a distúrbios eletrolíticos e metabólicos, os quais se tornaram menos frequentes e menos intensos com a utilização de doses menores do que as empregadas inicialmente. Neste artigo são discutidos os principais efeitos colaterais do uso crônico dos diuréticos, bem como as consequências de algumas interações medicamentosas com outros agentes anti-hipertensivose fármacos em geral.

Diuretics, especially tiazides and correlates, have been used in the treatment of the arterial hypertension for more than 40 years and remain as one of the five Top line antihypertensive classes. Diuretics continue being used in monotherapy, but over all in associations, fixed or not, witht he other antihypertensive agents due the potencialization of its reducing effect of the arterial pressure. They are drugs of low cost and good tolerability. Their main adverse reactions are related to electrolytic and metabolic disturbs, which have become less frequent and less intensive with the use of lower doses in comparison with the doses employed initially. In this article the main collateral effects of the chronic use of diuretics, are discussed as well as the consequences of some drugs interactions with other antihypertensive agents and drugs of general uses.

Inibidor da ECA e concentrações do peptídeo natriurético do tipo B, em idosos com insuficiência cardíaca / ACE inhibitors and plasma B-type natriuretic peptide levels in elderly patients with heart failure / Inhibidor de la enzima conversora de la angiotensina y concentraciones del péptido natriurético de tipo B, en personas adultas mayores con insuficiencia cardiaca

Fundamento: Ensaios clínicos demonstraram os benefícios dos inibidores da ECA (IECA) na atividade neuro-hormonal e na capacidade funcional de pacientes com insuficiência cardíaca (IC), com a magnitude desses efeitos sendo proporcional à dose desses agentes. Entretanto, a sistemática exclusão dos idosos, observada na maioria desses estudos, tem questionado a validação e incorporação de tais resultados na população geriátrica. Objetivo: Avaliar os efeitos de diferentes doses de quinapril, um IECA com meia vida biológica >24 horas, nas concentrações plasmáticas do PNB, nas distâncias percorridas no teste da caminhada de 6 minutos (TC-6 min) e na incidência de reações adversas, em idosos com IC sistólica. Métodos: Foram avaliados 30 pacientes (76,1 ± 5,3 anos; 15 mulheres), IC II-III (NYHA), FE ventricular esquerda < 40% (33,5 ± 4,5%), em uso de diuréticos (30), digoxina (24) e nitratos (13). As avaliações foram realizadas no momento da inclusão (basal) e a cada dois meses, com a adição de 10, 20, 30 e 40 mg de quinapril. Resultados: Completados oito meses, as concentrações do PNB foram 67,4% menores e as distâncias percorridas no TC-6 min 64,9% maiores em relação à condição basal. Hipotensão arterial com sintomas de baixo débito cerebral e/ou disfunção renal não foram observadas, possibilitando o emprego da dose máxima de quinapril em todos os pacientes. Conclusão: Os resultados demonstraram os benefícios dos IECA no perfil neuro-hormonal e na capacidade funcional de idosos com IC sistólica, bem como a relação positiva entre a dose e o efeito desses fármacos.

Background: Clinical trials have demonstrated the benefits of ACE inhibitors (ACEI) in the neurohormonal activity and in the functional capacity of patients with heart failure (HF), and also that these effects are dose dependent. However, since elderly individuals have been systematically excluded from the majority of these studies, the validation and incorporation of these results in the geriatric population has been questioned. Objective: To evaluate the effects of different doses of quinapril, an ACEI with a > 24-hour biological half-life, on plasma BNP levels, on the distance walked in the 6-minute walk test (6MWT) and on the incidence of adverse reactions in elderly individuals with systolic HF. Methods: A total of 30 patients (76.1 ± 5.3 years; 15 women), in NYHA functional class II-III HF, with left ventricular EF < 40% (33.5 ± 4.5%), on diuretics (30), digoxin (24) and nitrates (13) were included. The patients were assessed at baseline and every two months, with escalating doses of quinapril of 10, 20, 30 and 40 mg.Results: After eight months, BNP levels were 67.4% lower and the distance walked in the 6MWT was 64.9% longer in relation to baseline. Arterial hypotension with symptoms of low cerebral blood flow and/or renal dysfunction was not observed, so that the maximum quinapril dose could be used in all patients. Conclusion: The results demonstrated the benefits of ACEI on the neurohormonal profile and functional capacity of elderly individuals with systolic HF, as well as the positive relationship between dose and effect of these drugs.

Fundamento: Ensayos clínicos revelaron los beneficios de los inhibidores de la enzima conversora de la angiotensina (IECA) en la actividad neurohormonal y en la capacidad funcional de pacientes con insuficiencia cardiaca (IC). La magnitud de esos efectos fue proporcional a la dosificación de esos agentes. Sin embargo, la sistemática exclusión de las personas adultas mayores, observada en la mayoría de esos estudios, ha conllevado al cuestionamiento de la validación e incorporación de dichos resultados en la población geriátrica. Objetivo: Evaluar los efectos de diferentes dosis de quinapril, un IECA con vida media biológica >24 horas, en las concentraciones plasmáticas del péptido natriurético de tipo B (PNB), en las distancias recorridas en el test de marcha de 6 minutos (TM6m) y en la incidencia de reacciones adversas, en personas adultas mayores con IC sistólica. Métodos: Se evaluaron a 30 pacientes (76,1 ± 5,3 años; 15 mujeres), IC II-III (NYHA), fracción de eyección (FE) ventricular izquierda < 40% (33,5 ± 4,5%), en uso de diuréticos (30), digoxina (24) y nitratos (13). Las evaluaciones se realizaron a la inclusión (basal) y a cada dos meses, con la adición de 10, 20, 30 y 40 mg de quinapril. Resultados: Completados ocho meses, las concentraciones del PNB fueron de un 67,4% menor y las distancias recorridas en el TM6m de un 64,9% mayor con relación a la condición basal. No se observaron hipotensión arterial con síntomas de bajo débito cerebral y/o disfunción renal, posibilitando así el empleo de la dosificación máxima de quinapril en todos los pacientes. Conclusión: Los resultados revelaron los beneficios de los IECA en el perfil neurohormonal y en la capacidad funcional de personas adultas mayores con IC sistólica, así como la relación positiva entre la dosificación y el efecto de esos fármacos.

Peculiaridades da farmacoterapêutica cardiovascular no idoso / Peculiarities of the cardiovascular pharmacotherapeutic in the elderly

O incremento da população geriátrica representa importante alteração demográfica do final do século XX e início do XXI. Como um grupo, idosos requerem cuidados médicos e terapêuticos mais freqüentes e utilizam o serviço de saúde em maior escala que indivíduos mais jovens. Essa revolução demográfica tem importantes implicações práticas, diagnósticas e terapêuticas. A utilização apropriada de medicamentos na população geriátrica requer o conhecimento das alterações fisiológicas do envelhecimento e dos efeitos das doenças concomitantes, que podem influenciar a farmacocinética e a farmacodinâmica, assim como das respostas terapêutica e tóxica aos medicamentos, de forma clinicamente importante. A falta de atenção cuidadosa na seleção, na posologia e na monitoração dos fármacos nessa população pode induzir benefício terapêutico incompleto e alta incidência de reações adversas. Isso é particularmente significante para os medicamentos cardiovasculares, muitos dos quais têm índice tóxico/terapêutico estreito. Como as idades cronológica e biológica freqüentemente não são comparáveis, e como existem grandes variações entre os idosos nas respostas farmacocinética e farmacodinâmica, é difícil estabelecer generalizações. Fatores socioeconômicos e a não-observância adequada da prescrição são causa importante da falha terapêutica em qualquer idade, e particularmente nos idosos. Polifarmácia, esquemas terapêuticos complicados, distúrbios visuais, auditivos ou mentais, falta de compreensão, ausência de auxílio de familiares ou afins são alguns dos muitos fatores que contribuem para a não-observância ao tratamento.

The increase of the geriatric population represents a major demographic change in the end of the 20th Century and beginning of the 21st. As a group, the elderly require a closer and more frequent medical and therapeutic care and use health services in a larger scale than younger individuals. Such demographic revolution comprehends major practical, diagnostic and therapeutic implications. The appropriate use of medication in the geriatric population requires knowledge on the physiologic changing of the aging and on the effects of the collateral diseases that may impact on the pharmacokinetics and pharmacodynamics, the therapeutic and toxic response to medication, in a substantial clinical way. The lack of careful attention in the selection, posology and monitoring of the pharmaceutical drugs in this population may incite an incomplete therapeutic benefit and a high occurrence of conflicting reactions. This is particularly meaningful in the case of cardiovascular medication, many of which have a very critical toxic/therapeutic rate. Since the chronologic and biologic ages are usually not comparable, and since there are great variation among the elderly in the harmacokinetics and pharmacodynamics responses, it is difficult to establish generalization. Social and economical factors as well as the non-observance of adequate prescription are major reasons for therapeutic failure in any age, and particularly with the elderly. Polypharmacy, complicated therapeutic schemes, visual, hearing or mental impairment, lack of comprehension, absence of assistance from family members or relatives, are some of the many factors that contribute for non-observance of treatment.

Álcool e sistema cardiovascular / Alcohol and Cardiovascular System

O consumo leve a moderado de bebidas alcoólicas, isto é, uma a duas doses por dia, associa-se à diminuição darazão de risco para a incidência de Doença Arterial Coronária e Acidente Vascular Cerebral, em comparação seja com a abstinência total de álcool, seja com seu consumo excessivo. Atribui-se benefício adicional ao uso de vinho, provavelmente devido a efeitos antioxidantes e antiplaquetários. Entretanto, a ingestão de álcool reduz a contratilidade miocárdica e exerce efeitos desfavoráveis na insuficiência cardíaca. Isso posto, o consumo moderado de álcool pode ser permitidoa quem já tem esse hábito, entretanto, não se deve recomendar seu uso a indivíduos abstêmios, porque não é possível prever seu comportamento e eventuais riscos sociais.

Hipertrofia ventricular esquerda do atleta: resposta adaptativa fisiológica do coração / Left ventricular hypertrophy of athletes: adaptative physiologic response of the heart

OBJETIVO: Verificar se a hipertrofia ventricular esquerda (HVE) de atletas competitivos de resistência (maratonistas) representa processo adaptativo, puramente fisiológico, ou se pode envolver aspectos patológicos em suas características anatômicas e funcionais. MÉTODOS: De novembro de 1999 a dezembro de 2000, foram separados consecutivamente de 30 maratonistas em atividade esportiva plena, idade inferior a 50 anos, com HVE, previamente documentada, e sem cardiopatia subjacente. Foram submetidos aos exames: clínico, eletrocardiograma, ecodopplercardiograma, e teste ergométrico (TE). Quinze foram sorteados para realizar, também, teste ergoespirométrico e ressonância magnética (RM) do coração. RESULTADOS: Nos TE, todos apresentavam boa capacidade física cardiopulmonar, sem evidências de resposta isquêmica ao exercício, sintomas ou arritmias. No ecodopplercardiograma, os valores do diâmetro e espessura diastólica da parede posterior do ventrículo esquerdo (VE), do septo interventricular, massa do VE e diâmetro do átrio esquerdo, foram significativamente maiores que os do grupo de não atletas, com idades e medidas antropométricas semelhantes. A média da massa do VE dos atletas indexada à superfície corpórea (126 g/m2) foi significativamente maior que a do grupo controle (70 g/m2) (p<0,001). A RM mostrou que não havia prejuízo da força contrátil ou da performance ventricular esquerda e valores de volume diastólico final, volume sistólico final e fração de ejeção dentro dos limites da normalidade. Por outro lado, a massa do VE média, 162,93±17,90 g, e a espessura parietal ventricular, 13,67±2,13 mm, ao final da diástole no grupo atleta, diferiu significativamente do controle: 110±14,2 g (p=0,0001) e 8±0,9 mm, respectivamente (p=0,0001). O mesmo ocorreu na média da espessura ao final da sístole, que foi 18,87±3,40 mm (controle: 10± 1,80 mm, p=0,0001). CONCLUSAO: Os resultados permitiram concluir que a HVE de maratonistas em período de atividade esportiva plena, avaliada por métodos não invasivos, representa resposta adaptativa ao treinamento físico intensivo e prolongado, com características fisiológicas.

Hiper-homocisteinemia como fator de risco para doença aterosclerótica coronariana em idosos / Hyperhomocysteinemia as a risk factor for coronary atherosclerotic diseases in the elderly

OBJETIVO: Investigar se a hiper-homocisteinemia é fator de risco independente para doença aterosclerótica coronariana em idosos. MÉTODOS: Estudo caso-controle com 172 idosos, 88 pertencentes ao grupo controle e 84 ao grupo caso, que apresentavam cineangiocoronariografia solicitada por indicações clínicas. Angiografia coronariana quantitativa foi realizada em 91 por cento dos pacientes. Homocisteinemia foi avaliada sob forma contínua e categorizada, por análise univariada e multivariada. RESULTADOS: Quando analisada sob forma contínua, verificou-se que, na análise univariada, os idosos do grupo caso apresentaram média de níveis de homocisteinemia significativamente mais elevada que a dos idosos do grupo controle (14,33±4,59 æmol/l versus 11,99± 4,59 æmol/l , p=0,015). Na análise multivariada, a homocisteinemia sob forma contínua associou-se a razão de risco para doença arterial coronariana de 1,07 a cada aumento de 1 æmol/l de nível de homocisteína. Aumento de 5 æmol/l correspondeu a razão de risco de 1,40. Quando analisada sob forma categorizada, definiu-se como hiper-homocisteinemia os valores encontrados acima do percentil 75 do grupo controle (14 æmol/l ). Hiper-homocisteinemia foi encontrada em 34 por cento dos idosos, sendo 37,3 por cento no grupo controle e 62,7 por cento no grupo caso (p=0,009). Na análise multivariada, a hiperhomocisteinemia constituiu fator de risco independente para doença aterosclerótica coronariana em idosos, com razão de risco para doença arterial coronariana de 2,03, intervalo de confiança 95 por cento, 1,02-4,03. CONCLUSAO: Hiper-homocisteinemia foi fator de risco independente para doença arterial coronariana em idosos.

Bloqueadores beta-adrenérgicos na insuficiência cardíaca / Beta-adrenergic blocking agents in heart failure

Cardiac dysfunction in heart failure is widely recognized as a progressive process, regardless of the clinical signs and symptoms. An increase in cardiac sympathetic drive is one of the earliest neurohormonal responses occurring in patients with heart failure and may be one of the major causes of the progressive remodeling leading to the decline in myocardial function, and responsible for the poor prognosis of patients with heart failure. Therefore, recent data provided by several appropriately designed clinical trials clearly indicate the benefits of beta-adrenoceptor blocking agents, combined with diuretics, ACE inhibitors, and digoxin in chronic heart failure class II to IV due to systolic ventricular dysfunction. The benefits are related to symptoms, functional capacity, remodeling, and improvement in left ventricular function, reduction in cardiovascular hospitalization, a decrease in the overall and sudden cardiac death rate, and are similar in patients with ischemic or nonischemic cardiomyopathy, independent of age, gender, or functional class. In this review we describe the cardiovascular effects of the increase in sympathetic drive, the pharmacological properties of the beta-blockers most evaluated in heart failure therapy (metoprolol, bisoprolol, and carvedilol), the major clinical trials related to these agents in heart failure, the recommendations for their appropriate use in clinical practice, the precautions to be adopted, and how to handle the more common adverse reactions

Ondas T negativas gigantes associadas à hipertrofia isolada dos músculos papilares do ventrículo esquerdo, em atletas: relato de dois casos / Giant negative T waves associated with isolated hypertrophy of the papillary muscles of the lefe ventricle, in athletes: report of 2 cases

Alteraçöes da repolarizaçäo ventricular, incluindo ondas T negativas relativamente profundas, säo comumente encontradas nos eletrocardiogramas de atletas bem treinados. Os achados ecocardiográficos mais freqüentes em atletas säo o aumento da espessura do septo interventricular e/ou da parede posterior do ventrículo esquerdo, aumento dos diámetros diastólicos de ambos os ventrículos e da massa ventricular esquerda. Relatam-se, neste trabalho, os casos de dois atletas, praticantes de futebol-de-saläo e corrida de média distância. Ambos brancos, com 32 e 35 anos de idade, assintomáticos, sem anormalidades aos exames físico e radiográfico do tórax, e submetidos a treinamento intensivo desde a infância. O eletrocardiograma evidenciou ondas T negativas gigantes em precordiais associadas a hipertensäo isolada dos músculos papilares do ventrículo esquerdo (ecocardiograma bidimensional), condiçöes essas näo relatadas anteriormente na literatura médica. O teste ergométrico näo evidenciou manifestaçöes clínicas ou eletrocardiográficas indicativas de isquemia miocárdica, e a cintilografia miocárdica com tálio-201 näo revelou áreas de hipoconcentraçäo do radioisótopo. Após reduçäo do nível de atividade atlética, as alteraçöes da repolarizaçäo ventricular regrediram completamente em um caso, porém näo houve modificaçäo do padräo ecocardiográfico. Tecem-se consideraçöes sobre esses achados e seu eventual significado