Brain structural variability due to aging and gender in cognitively healthy Elders: results from the Sao Paulo Ageing and Health study.

BACKGROUND AND PURPOSE: Several morphometric MR imaging studies have investigated age- and sex-related cerebral volume changes in healthy human brains, most often by using samples spanning several decades of life and linear correlation methods. This study aimed to map the normal pattern of regional age-related volumetric reductions specifically in the elderly population. MATERIALS AND METHODS: One hundred thirty-two eligible individuals (67-75 years of age) were selected from a community-based sample recruited for the São Paulo Ageing and Health (SPAH) study, and a cross-sectional MR imaging investigation was performed concurrently with the second SPAH wave. We used voxel-based morphometry (VBM) to conduct a voxelwise search for significant linear correlations between gray matter (GM) volumes and age. In addition, region-of-interest masks were used to investigate whether the relationship between regional GM (rGM) volumes and age would be best predicted by a nonlinear model. RESULTS: VBM and region-of-interest analyses revealed selective foci of accelerated rGM loss exclusively in men, involving the temporal neocortex, prefrontal cortex, and medial temporal region. The only structure in which GM volumetric changes were best predicted by a nonlinear model was the left parahippocampal gyrus. CONCLUSIONS: The variable patterns of age-related GM loss across separate neocortical and temporolimbic regions highlight the complexity of degenerative processes that affect the healthy human brain across the life span. The detection of age-related limbic GM decrease in men supports the view that atrophy in such regions should be seen as compatible with normal aging.

Conjugated equine estrogen, raloxifene and arterial stiffness in postmenopausal women.

METHODS: We analyzed the influence of conjugated equine estrogen (CEE) and raloxifene on arterial stiffness. Sixty-seven healthy, normotensive women 1-10 years into menopause were assigned to receive oral placebo, conjugated equine estrogen 0.625 mg, or raloxifene 60 mg. Arterial stiffness was evaluated by measuring the carotid-femoral and femoral-dorsalis pedis pulse wave velocity (CF PWV, FP PWV). Systolic pressure augmentation index (AI) at the carotid artery was obtained with applanation tonometry. RESULTS: Arterial stiffness was not affected by any treatment regimen: placebo (CF PWV before vs. after: 644 vs. 626 cm/s, p = 0.09; FP PWV before vs. after: 1006 vs. 1012 cm/s,p = 0.77; AI before vs. after = 30 vs. 29%, p = 0.55), CEE (CF PWV before vs. after: 642 vs. 600 cm/s, p = 0.11; FP PWV before vs. after: 952 vs. 971 cm/s, p = 0.66; AI before vs. after: 25 vs. 32%, p = 0.82), and raloxifene (CF PWV before vs. after: 636 vs. 601 cm/s, p = 0.12; FP PWV before vs. after: 964 vs. 941 cm/s, p = 0.62; AI before vs. after: 25 vs. 25%, p = 0.65). A correlation occurred between basal stiffness and the degree of reduction in indexes measured, indicating that the higher the basal stiffness, the greater the degree of reduction, particularly in the CEE group: CF PWV (r = - 0.602, p = 0.001); FP PWV (r = - 0.455, p = 0.022); AI (r = - 0.410, p = 0.042). CONCLUSIONS: Conjugated equine estrogen and raloxifene do not seem to affect arterial stiffness of healthy normotensive women less than 10 years since menopause. Reduction in arterial stiffness seems related to its basal level.

Relationship between soluble thrombomodulin in patients with intermittent claudication and critical ischemia.

INTRODUCTION: Thrombomodulin (TM) has been described as a marker of endothelial injury in atherosclerosis. The role of TM as a predictor of PAD severity is to be proven. The goal of the present study is to compare the level of plasmatic (TMp) in patients with intermittent claudication with patients with critical ischemia in the lower limbs. MATERIALS AND METHODS: TMp was measured using ELISA in the plasma of 41 patients with intermittent claudication degree 1 and in 40 patients presenting critical ischemia in the lower limbs degrees 2 and 3, according to TASC. The hypotheses of normality and homogeneity of the variance had been proven via Shapiro-Wilk and Levene tests, respectively. The comparison of the TMp between the groups was done using the t-Student test. RESULTS: No statistically significant difference was observed. The average levels of TMp for intermittent claudication were 5.2 ng/ml (0.78-13.61 ng/ml) and TMp for critical ischemia in the lower limbs were 6.34 (0.82-18.22 ng/ml) where p=0.265. CONCLUSION: TMp does not seem to be an appropriate marker for PAD severity.

Suppression of inflammatory and fibrotic responses in allergic inflammation by the amniotic membrane stromal matrix.

BACKGROUND: The amniotic membrane (AM), which is the innermost layer of the placenta, was shown to possess anti-inflammatory and anti-fibrotic properties in various in vitro and clinical studies. PURPOSE: To evaluate the anti-fibrotic and anti-inflammatory effects of the AM matrix (AMM) on human conjunctival and lung fibroblasts in an in vitro system that tests fibrotic and inflammatory responses at the effector stages of allergic inflammation. METHODS: Human conjunctival or lung fibroblasts were seeded on plastic or on the stromal aspect of the AM, which was mounted on plastic inserts. Sonicates of human peripheral blood eosinophils activated with lipopolysaccharide (LPS), or human mast cell (HMC-1) leukaemia cell sonicates, were added to sub-confluent fibroblast monolayers. Proliferation of the sub-confluent fibroblasts was assessed using the [3H]-thymidine incorporation assay. The production of transforming growth factor (TGF)-beta1, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-8 in conjunctival or lung fibroblasts was measured in conditioned media from these cultures by ELISA. RESULTS: After 4 days in culture, the [3H]-thymidine incorporation assay indicated a reduced proliferation of activated conjunctival and lung fibroblasts when cultured directly on the AMM. The production of both TGF-beta1 and IL-8 was significantly suppressed in activated conjunctival fibroblasts cultured on the AMM compared with those cultured on plastic, while the production of both TGF-beta1 and GM-CSF was decreased in human lung fibroblast cultured on the AMM. CONCLUSIONS: The AMM is capable of suppressing fibrotic responses in an in vitro system of effector stages of ocular allergic inflammation. These data may provide a basis for exploring matrix components in the AM for the treatment of allergic eye disease.

Late-life depression, heart failure and frontal white matter hyperintensity: a structural magnetic resonance imaging study.

The relevance of the relationship between cardiac disease and depressive symptoms is well established. White matter hyperintensity, a bright signal area in the brain on T2-weighted magnetic resonance imaging scans, has been separately associated with cardiovascular risk factors, cardiac disease and late-life depression. However, no study has directly investigated the association between heart failure, major depressive symptoms and the presence of hyperintensities. Using a visual assessment scale, we have investigated the frequency and severity of white matter hyperintensities identified by magnetic resonance imaging in eight patients with late-life depression and heart failure, ten patients with heart failure without depression, and fourteen healthy elderly volunteers. Since the frontal lobe has been the proposed site for the preferential location of white matter hyperintensities in patients with late-life depression, we focused our investigation specifically on this brain region. Although there were no significant group differences in white matter hyperintensities in the frontal region, a significant direct correlation emerged between the severity of frontal periventricular white matter hyperintensity and scores on the Hamilton scale for depression in the group with heart failure and depression (P = 0.016, controlled for the confounding influence of age). There were no significant findings in any other areas of the brain. This pattern of results adds support to a relationship between cardiovascular risk factors and depressive symptoms, and provides preliminary evidence that the presence of white matter hyperintensities specifically in frontal regions may contribute to the severity of depressive symptoms in cardiac disease.

Late-life depression, heart failure and frontal white matter hyperintensity: a structural magnetic resonance imaging study

The relevance of the relationship between cardiac disease and depressive symptoms is well established. White matter hyperintensity, a bright signal area in the brain on T2-weighted magnetic resonance imaging scans, has been separately associated with cardiovascular risk factors, cardiac disease and late-life depression. However, no study has directly investigated the association between heart failure, major depressive symptoms and the presence of hyperintensities. Using a visual assessment scale, we have investigated the frequency and severity of white matter hyperintensities identified by magnetic resonance imaging in eight patients with late-life depression and heart failure, ten patients with heart failure without depression, and fourteen healthy elderly volunteers. Since the frontal lobe has been the proposed site for the preferential location of white matter hyperintensities in patients with late-life depression, we focused our investigation specifically on this brain region. Although there were no significant group differences in white matter hyperintensities in the frontal region, a significant direct correlation emerged between the severity of frontal periventricular white matter hyperintensity and scores on the Hamilton scale for depression in the group with heart failure and depression (P = 0.016, controlled for the confounding influence of age). There were no significant findings in any other areas of the brain. This pattern of results adds support to a relationship between cardiovascular risk factors and depressive symptoms, and provides preliminary evidence that the presence of white matter hyperintensities specifically in frontal regions may contribute to the severity of depressive symptoms in cardiac disease.

Hormone replacement therapy increases levels of antibodies against heat shock protein 65 and certain species of oxidized low density lipoprotein.

Hormone replacement therapy (HRT) reduces cardiovascular risks, although the initiation of therapy may be associated with transient adverse ischemic and thrombotic events. Antibodies against heat shock protein (Hsp) and oxidized low density lipoprotein (LDL) have been found in atherosclerotic lesions and plasma of patients with coronary artery disease and may play an important role in the pathogenesis of atherosclerosis. The aim of the present study was to assess the effects of HRT on the immune response by measuring plasma levels of antibodies against Hsp 65 and LDL with a low and high degree of copper-mediated oxidative modification of 20 postmenopausal women before and 90 days after receiving orally 0.625 mg equine conjugate estrogen plus 2.5 mg medroxyprogesterone acetate per day. HRT significantly increased antibodies against Hsp 65 (0.316 +/- 0.03 vs 0.558 +/- 0.11) and against LDL with a low degree of oxidative modification (0.100 +/- 0.01 vs 0.217 +/- 0.02) (P<0.05 and P<0.001, respectively, ANOVA). The hormone-mediated immune response may trigger an inflammatory response within the vessel wall and potentially increase plaque burden. Whether or not this immune response is temporary or sustained and deleterious requires further investigation.

Hormone replacement therapy increases levels of antibodies against heat shock protein 65 and certain species of oxidized low density lipoprotein

Hormone replacement therapy (HRT) reduces cardiovascular risks, although the initiation of therapy may be associated with transient adverse ischemic and thrombotic events. Antibodies against heat shock protein (Hsp) and oxidized low density lipoprotein (LDL) have been found in atherosclerotic lesions and plasma of patients with coronary artery disease and may play an important role in the pathogenesis of atherosclerosis. The aim of the present study was to assess the effects of HRT on the immune response by measuring plasma levels of antibodies against Hsp 65 and LDL with a low and high degree of copper-mediated oxidative modification of 20 postmenopausal women before and 90 days after receiving orally 0.625 mg equine conjugate estrogen plus 2.5 mg medroxyprogesterone acetate per day. HRT significantly increased antibodies against Hsp 65 (0.316 ± 0.03 vs 0.558 ± 0.11) and against LDL with a low degree of oxidative modification (0.100 ± 0.01 vs 0.217 ± 0.02) (P<0.05 and P<0.001, respectively, ANOVA). The hormone-mediated immune response may trigger an inflammatory response within the vessel wall and potentially increase plaque burden. Whether or not this immune response is temporary or sustained and deleterious requires further investigation

Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly patients with hypertension and coronary artery disease.

OBJECTIVE: Antihypertensive therapy with thiazides decreases coronary events in elderly patients. However, the influence of diuretics on myocardial ischemia has not been fully investigated. The aim of this study was to compare the effect of chlorthalidone and diltiazem on myocardial ischemia. METHODS: Following a randomized, double-blind, crossover protocol, we studied 15 elderly hypertensive patients aged 73.6+/-4.6 years with myocardial ischemia. All patients had angiographically documented coronary artery disease. We measured patients using 48- hour ambulatory electrocardiogram monitoring and exercise testing. After a 2-week period using placebo, patients received chlorthalidone or diltiazem for 4 weeks. RESULTS: Both treatments lowered systolic and diastolic blood pressures. The number of ischemic episodes on ambulatory electrocardiogram recordings was reduced with the use of chlorthalidone (2.5+/-3.8) and diltiazem (3.2+/-4.2) when compared with placebo (7.9+/-8.8; p<0.05). The total duration of ischemic episodes was reduced in both treatments when compared with placebo (chlorthalidone: 19.2+/-31.9min; diltiazem: 19.3+/-29.6min; placebo: 46.1+/-55.3min; p<0.05). CONCLUSION: In elderly hypertensive patients with coronary artery disease, chlorthalidone reduced myocardial ischemia similarly to diltiazem. This result is consistent with epidemiological studies and suggests that reduction of arterial blood pressure with thiazide therapy plays an important role in decreasing myocardial ischemia.

Plasma kinetics of a cholesterol-rich emulsion in young, middle-aged, and elderly subjects.

Low density lipoprotein (LDL) plasma concentration is increased in the elderly. In this group, the incidence of coronary artery disease (CAD) is greater and LDL remains an important risk factor for CAD development. In this study, the plasma kinetics of a cholesterol-rich emulsion that binds to LDL receptors was studied in 10-subject groups of the elderly (70 +/- 4 yr), middle-aged (42 +/- 5 yr) and young (23 +/- 2 yr). All were normolipidemic, nonobese, nondiabetic subjects who did not have CAD. The emulsion was labeled with 14C-cholesteryl oleate and injected intravenously into the subjects. Blood samples were drawn at regular intervals over 24 h to determine the plasma decay curve of the emulsion radioactive label and to estimate its plasma fractional clearance rate (FCR, in h(-1)). FCR of the emulsion label was smaller in elderly compared to young subjects (0.032 +/- 0.035 and 0.071 +/- 0.049 h(-1), respectively; mean +/- SD, P< 0.05). FCR of the middle-aged subjects (0.050 +/- 0.071 h(-1)) was intermediate between the values of the elderly and young subjects, although not statistically different from them. A negative correlation was found betweeen the emulsion FCR and subjects' age (r = -0.47, P = 0.008). We conclude that aging is accompanied by progressively diminished clearance of the emulsion cholesterol esters and, by analogy, of the native LDL.

Depression with irritability in patients undergoing coronary artery bypass graft surgery: the cardiologist's role.

The purpose of this study was to investigate the determinants and maintenance factors of depression in patients undergoing coronary artery bypass graft (CABG) surgery. Fifty CABG candidates were selected randomly for evaluation before and after surgery. Depressive disorders occurred in 22.0% of the patients preoperatively and 21% postoperatively. Irritability as a symptom was more prevalent in depressed than nondepressed patients preoperatively (P=.04) and postoperatively (P=.006). Although depression was the most prevalent diagnosis in the patients' psychiatric histories and evaluations, benzodiazepines were prescribed more frequently than antidepressants (70% vs 3%). Cardiologists should consider that the irritability in some patients undergoing CABG may obscure the diagnosis of depression. The correct recognition of depression is essential to reduce inappropriate benzodiazepine prescription and to apply appropriate treatment.

Clinical predictors of prognosis in severe aortic stenosis in unoperated patients > or = 75 years of age.

In elderly patients with severe aortic stenosis, clinical evaluation can dictate decision making. Asymptomatic patients in normal sinus rhythm, without left atrial enlargement and without bundle branch block, can be safely followed clinically, regardless of echocardiographic findings.

Comparison of risk of orthostatic hypotension in elderly depressed hypertensive women treated with nortriptyline and thiazides versus elderly depressed normotensive women treated with nortriptyline.

This is a nonblind, case-controlled study comparing the risk of orthostatic hypotension (OH) in 2 groups of elderly depressed women: 22 normotensive and 21 hypertensive patients receiving thiazides. Blood pressure measurements and tilt-table tests produced similar results: increased drop in systolic blood pressure (SBP) after standing (p <0.001), with no significant differences between the groups (p = 0.523). There were no changes on diastolic blood pressure (DBP) after standing, or in SBP or DBP at rest. Dizziness was reported by 23 subjects (53.5%) before treatment, and by 16 subjects (38.1%) at week 8. Complaints of dizziness were not associated with OH (Kappa = 0.07).

Exercise and heart failure. Relation of the severity of the disease to the anaerobic threshold and the respiratory compensation point.

OBJECTIVE - To identify, the anaerobic threshold and respiratory compensation point in patients with heart failure. METHODS - The study comprised 42 Men,divided according to the functional class (FC) as follows: group I (GI) - 15 patients in FC I; group II (GII) - 15 patients in FC II; and group III (GIII) - 12 patients in FC III. Patients underwent a treadmill cardiopulmonary exercise test, where the expired gases were analyzed. RESULTS - The values for the heart rate (in bpm) at the anaerobic threshold were the following: GI, 122+/-27; GII, 117+/-17; GIII, 114+/-22. At the respiratory compensation point, the heart rates (in bpm) were as follows: GI, 145+/-33; GII, 133+/-14; GIII 123+/-22. The values for the heart rates at the respiratory compensation point in GI and GIII showed statistical difference. The values of oxygen consumption (VO2) at the anaerobic threshold were the following (in ml/kg/min): GI, 13. 6+/-3.25; GII, 10.77+/-1.89; GIII, 8.7+/-1.44 and, at the respiratory compensation point, they were as follows: GI, 19.1+/-2. 2; GII, 14.22+/-2.63; GIII, 10.27+/-1.85. CONCLUSION - Patients with stable functional class I, II, and III heart failure reached the anaerobic threshold and the respiratory compensation point at different levels of oxygen consumption and heart rate. The role played by these thresholds in physical activity for this group of patients needs to be better clarified.

[Heart failure at a large tertiary hospital of São Paulo]. / Insuficiência cardíaca em grande hospital terciário de São Paulo.

PURPOSE: To study the incidence, main causes, aggravating factors and secondary diagnoses of heart failure (HF) during 1995 at the Instituto do Coração of São Paulo. METHODS: Data from hospitalized patients according to the PRODESP data base were analyzed. The following data were studied; age, sex, principal and secondary diagnoses, surgical procedures and mortality. To analyze the data, tables according to sex, age and main cause were built. Analysis of variance and t test were employed to verify differences between groups. RESULTS: In 1995, 903 out of 9620 patients were hospitalized due to HF. The majority were male (60.4%) and the patients' age was between two days and 98 years old (mean 52.6). Ischemic (32.6), dilated (25.8%) and valvar heart disease (22%) were the main causes of HF. 32.1% were submitted to correction of the HF main cause, specially those with valvar heart disease (62.3%). There was greater incidence of multiple diagnoses in aged patients. The mortality was greater in patients younger than 20 and in those older than 80 years old. CONCLUSION: The incidence of HF at INCOR during 1995 was 9.38%. Ischemic myocardiopathy was the most frequent HF cause. The mortality was greater among children, probably because of heart disease complexity and, in the above-80 group due to the greater comorbidity.

[Effect of myocardial revascularization on asymptomatic ischemic episodes]. / Efeito da cirurgia de revascularização miocárdica sobre os episódios isquêmicos assintomáticos.

PURPOSE: To evaluate the effect of coronary artery bypass graft surgery (CABG) on ischemic asymptomatic episodes (IAE). METHODS: Twenty eight males (means age 57.3 +/- 9.6 years) with stable angina and no microcirculation abnormalities, who presented with IAE after medication withdrawal, were studied using ambulatory electrocardiography monitoring. Presence of IEA was analyzed before and 4 months after CABG according to its frequency and heart rate (HR) response. CAGB was considered complete in 75% of the cases. RESULTS: The number or IAE was reduced from 162 (9 symptomatic) in the preoperative period to 4 after surgery (p < 0.05). In two patients with IAE in the postoperative period, coronariography confirmed obstruction of aortocoronary grafts. Analysis of HR at the beginning and peak of IAE suggested as mechanisms both reduced blood flow and increased oxygen consumption by the myocardium. CONCLUSION: CABC eliminated IAE regardless of HR. When IAE is present after surgery, graft occlusion should be suspected.

Insuficiência cardíaca em grande hospital terciário de São Paulo / Heart failure in a large tertiary hospital of São Paulo

OBJETIVO - Verificar a incidência, principais causas, fatores desencadeantes ou de piora da insuficiência cardíaca (IC) no ano de 1995, no Instituto do Coração de São Paulo. MÉTODOS - Foram analisados os registros referentes a pacientes internados, obtidos do banco de dados da PRODESP. Analisaram-se nos pacientes co IC os dados: idade, sexo, diagnóstico principal e secundários, procedimentos executados e óbitos. Para fim de análise, construiram-se tabelas de distribuição conforme o sexo, idade e diagnóstico principal. Análise de variância e teste do qui-quadrado foram empregados para verificar diferença entre os grupos estudados. RESULTADOS - Dos pacientes internados (903 de 9620) 9,38 'por cento' apresentaram IC. As idades variaram de 2 dias a 98 (média 52,6) anos e a maioria era do sexo masculino (60,4 'por cento'). Miocardiopatia isquêmica (32,6 'por cento'), miocardiopatia dilatada (25,8 'por cento') e valvopatias (22,0 'por cento') foram as principais causas de IC. Foram submetidos à cirurgia, angioplastia, ou implante de marcapasso, 32,1 'por cento' dos pacientes, sendo os valvopatas na maioria submetidos à correção de sua cardiopatia de base (63,3 'por cento'). Houve maior incidência de múltiplos diagnósticos secundários com o aumento da idade. A mortalidade foi maior nos com idade <20 anos e nos >80anos. CONCLUSÄO - A incidência de IC foi de 9,38 'por cento', sendo miocardiopatia isquêmica a causa mais freqüente. Foi possível corrigir a causa da IC em 32,1 'por cento'. A mortalidade foi maior nas crianças provavelmente pela maior complexidade de sua cardiopatia e nos mais idosos devido à maior associação de diagnósticos secundários ou fatores agravantes.

Efeito da cirurgia de revascularizaçäo miocárdica sobre os episódios isquêmicos assintomáticos / Effect of coronary artery bypass graft surgery on ischemic asymptomatic episodes

OBJETIVO - Avaliar o efeito da cirurgia de revascularizaçäo miocárdica (CRM) sobre episódios isquêmicos assintomáticos (EIA). MÉTODOS - Foram estudados 28 homens, com angina estável (idade média 57,3ñ9,6) anos sem condiçöes relacionadas a alteraçöes de microcirculaçäo e que, após retirada da medicaçäo, apresentaram EIA à eletrocardiografia ambulatorial (ECGA). No pré-operatório e 4 meses após a cirurgia foram analisados os comportamentos dos EIA, segundo sua freqüência, e o de suas freqüências cardíacas (FC). A revascularizaçäo miocárdica foi completa em 75 'por cento' dos casos. RESULTADOS - O número dos EIA foi reduzido de 162 (9 sintomáticos) no pré-operatório para, apenas, 4 no pós-operatório (p<0,05). Nos dois pacientes com EIA no operatório, estudo cinecoronariográfico confirmou obstruçäo de enxertos aortocoronários. A análise das FC no início e pico dos EIA sugeriram envolvimento de mecanismo de reduçÝo de oferta e aumento de consumo de oxigênio pelo miocárdio. CONCLUSÄO - A CRM eliminou os episódio isquêmicos relacionados ou näo ao aumento da FC. Quando os EIA encontram-se presentes após CRM, devemos considerar a possibilidade de oclusäo de enxerto.