Mauricio Wajngarten

Increased Levels of C-Reactive Protein After Oral Hormone Replacement Therapy May Not Be Related to an Increased Inflammatory Response

Background—It has been suggested that hormone replacement therapy (HRT) in postmenopausal women is associated with an increased inflammatory response that may trigger acute cardiovascular events. This suggestion is mainly based on the finding of elevated C-reactive protein (CRP) levels after HRT. The aim of the present study was to evaluate a broad spectrum of vascular inflammation markers in 389 postmenopausal women with increased cardiovascular risk at baseline and after either 6 months of HRT (126 women) or no HRT (263 women). Methods and Results—Compared with baseline, CRP levels significantly increased after HRT (0.9±0.2 versus 1.6±0.4 mg/L, P <0.01); on the contrary, soluble intracellular adhesion molecule-1 decreased from 208±57 to 168±37 ng/mL (P <0.01) after HRT. Similarly, vascular cell adhesion molecule-1 decreased from 298±73 to 258±47 ng/mL (P <0.01), plasma E-selectin levels were reduced from 17.8±5.6 to 14.8±3.9 ng/mL (P <0.01), interleukin-6 levels decreased from 1.51±0.22 to 1.29±0.28 pg/mL, and s-thrombomodulin plasma levels decreased from 4.8±0.7 to 4.3±0.9 ng/mL (P <0.01). No significant changes in either CRP or vascular inflammatory marker were detected in women not taking HRT. Conclusions—The discrepancy between increased plasma levels of CRP and reduced plasma levels of all other markers of inflammation suggests that the increased CRP levels after oral HRT may be related to metabolic hepatic activation and not to an acute-phase response. HRT seems to be associated with an overall decrease in vascular inflammation.

Localized cerebral blood flow reductions in patients with heart failure: a study using 99mTc-HMPAO SPECT.

Background and Purpose. Reduced resting global cerebral blood flow has been previously detected in association with heart failure (HF), but it is not clear whether there are brain regions that could be specifically affected by those brain perfusion deficits. The authors used a fully automated, voxel‐based image analysis method to investigate, across the entire cerebral volume, the presence of resting regional cerebral blood flow (rCBF) abnormalities in HF patients compared to healthy controls. Methods. rCBF was evaluated with 99m Tc‐single‐photon emission computed tomography in 17 HF patients (New York Heart Association functional class II or III) and 18 elderly healthy volunteers. Voxel‐based analyses of rCBF data were conducted using the statistical parametric mapping software. Results. Significant rCBF reductions in HF patients relative to controls (P < .05, corrected for multiple comparisons) were detected in 2 foci, encompassing, respectively, the left and right precuneus and cuneus and the right lateral temporoparietal cortex and posterior cingulated gyrus. In the HF group, there was also a significant direct correlation between the degree of cognitive impairment as assessed using the Cambridge Mental Disorders of the Elderly Examination and rCBF on a voxel cluster involving the right posterior cingulate cortex and precuneus, located closely to the site where between‐group rCBF differences had been identified. Conclusions. These preliminary findings indicate that posterior cortical areas of the brain may be particularly vulnerable to brain perfusion reductions associated with HF and sug est that functional deficits in these regions might be relevant to the pathophysiology of the cognitive impairments presented by HF patients.

Estudo multicêntrico de idosos atendidos em ambulatórios de cardiologia e geriatria de instituições brasileiras

PURPOSE To evaluate epidemiological, clinical and therapeutic aspects of elderly patients with cardiovascular disease in Brazil. METHODS Elderly patients with cardiovascular disease treated in 36 centers of cardiology and geriatrics were investigated through a questionnaire applied to those who had an appointment during the analyzed period. RESULTS 2196 elderly patients ranging from 65 to 96 years of age were analyzed, 60% of which were females. The main risk factors were: sedentarism (74%); high blood pressure (53%), high LDL-cholesterol (33%), high total cholesterol (30%), obesity (30%), low HDL-cholesterol (15%), diabetes (13%) and smoking (6%). A higher prevalence of females existed among those with > or = 3 risk factors. The main reason for the medical appointment was high blood pressure (48%). Stress test and coronariography were requested more often in males. The most common diagnoses were hypertension (67%), and coronary disease (29%). The most often used medications were diuretics (42%). CONCLUSION There was high prevalence of risk factors (93%), mainly in females; sedentarism was the most common risk factor and prevalence increased with age; hypertension was the most common reason for a medical appointment. Diuretics were the most used drugs; congestive heart failure was the main disease associated to hospitalization (31%) and emergencies (10%).Objetivo - Avaliar aspectos epidemiologicos, clinicos e terapeuticos de idosos com doencas cardiovasculares (DCV), no Brasil. Metodos - Idosos com DCV, atendidos em 36 servicos de Cardiologia e Geriatria do Brasil, foram investigados atraves de questionario aplicado aos que tinham consulta marcada para o periodo analisado (um mes). Resultados - Estudados 2196 idosos de 65 a 96 anos, sendo 60% mulheres e analisados os fatores de risco: sedentarismo (74%), pressao arterial (PA) elevada (53%), LDL colesterol aumentado (33%), colesterol total aumentado (30%), obesidade (30%), HDL-colesterol diminuido (15%), diabetes (13%) e tabagismo (6%). Observou-se maior prevalencia nas mulheres, com tres ou mais fatores de risco. O principal motivo de consulta foi a PA elevada (48%). Teste ergometrico e cinecoronariografia, foram mais solicitados para os homens. Os diagnosticos mais comuns foram hipertensao arterial sistemica (HAS) (67%) e insuficiencia coronaria (ICo) (29%). Os medicamentos mais utilizados foram diureticos (42%). Conclusao - Foi observada alta prevalencia de fatores de risco (93%), principalmente nas mulheres; sedentarismo, como fator de risco mais frequente, aumentando de prevalencia com a idade; HAS, como principal motivo de consulta e diagnostico; menor investigacao e diagnostico de ICo em mulheres; diureticos, como os farmacos mais frequentemente prescritos; insuficiencia cardiaca como principal doenca associada a internacao (31%) e atendimento de emergencia (10%).

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.

Relationship between body mass index, waist circumference, and waist-to-hip ratio and mortality in elderly women: a 5-year follow-up study

This study examines the association between body mass index (BMI), waist-to-hip ratio (WHR), and waist circumference (WC) and all-cause and cardiovascular mortality in elderly women in a 5-year longitudinal study of 575 female outpatients 60 years and over. The highest BMI, WHR, and WC quartiles and predefined BMI categories were analyzed as predictive variables. Death occurred in 88 (15.4%). Underweight (BMI < 18.5 kg/m2) was associated with all-cause mortality in uni- and multivariate analyses, regardless of age bracket. The survival curves and univariate analysis showed that the highest WHR quartile (> or = 0.97) was associated with all-cause mortality. However, after adjustment for age, smoking, and previous cardiovascular diseases, the increase in WHR was positively associated only in women from 60 to 80 years of age. None of the anthropometric measurements was associated with cardiovascular mortality. The results indicate that underweight and increased waist-to-hip ratio were predictors of all-cause mortality in elderly women, mainly among those under 80 years.

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.

Muscle sympathetic nervous activity in depressed patients before and after treatment with sertraline

Background Sympathetic hyperactivity is one of the mechanisms involved in the increased cardiovascular risk associated with depression, and there is evidence that antidepressants decrease sympathetic activity. Objectives We tested the following two hypotheses: patients with major depressive disorder with high scores of depressive symptoms (HMDD) have augmented muscle sympathetic nervous system activity (MSNA) at rest and during mental stress compared with patients with major depressive disorder with low scores of depressive symptoms (LMDD) and controls; sertraline decreases MSNA in depressed patients. Methods Ten HMDD, nine LMDD and 11 body weight-matched controls were studied. MSNA was directly measured from the peroneal nerve using microneurography for 3 min at rest and 4 min during the Stroop color word test. For the LMDD and HMDD groups, the tests were repeated after treatment with sertraline (103.3 ± 40 mg). Results Resting MSNA was significantly higher in the HMDD [29.1 bursts/min (SE 2.9)] compared with LMDD [19.9 (1.6)] and controls [22.2 (2.0)] groups (P = 0.026 and 0.046, respectively). There was a significant positive correlation between resting MSNA and severity of depression. MSNA increased significantly and similarly during stress in all the studied groups. Sertraline significantly decreased resting MSNA in the LMDD group and MSNA during mental stress in LMDD and HMDD groups. Sertraline significantly decreased resting heart rate and heart rate response to mental stress in the HMDD group. Conclusion Moderate-to-severe depression is associated with increased MSNA. Sertraline treatment reduces MSNA at rest and during mental challenge in depressed patients, which may have prognostic implications in this group.

Ambulatory blood pressure monitoring of patients with heart failure: a new prognosis marker

OBJECTIVE To evaluate the relationship between 24-hour ambulatory arterial blood pressure monitoring and the prognosis of patients with advanced congestive heart failure. METHODS We studied 38 patients with NYHA functional class IV congestive heart failure, and analyzed left ventricular ejection fraction, diastolic diameter, and ambulatory blood pressure monitoring data. RESULTS Twelve deaths occurred. Left ventricular ejection fraction (35.2 +/-7.3%) and diastolic diameter (72.2 +/- 7.8mm) were not correlated with the survival. The mean 24-hour (SBP24), waking (SBPw), and sleeping (SBPs) systolic pressures of the living patients were higher than those of the deceased patients and were significant for predicting survival. Patients with mean SBP24, SBPv, and SBPs >/=105mmHg had longer survival (p=0.002, p=0.01 and p=0.0007, respectively). Patients with diastolic blood pressure sleep decrements (dip) and patients with mean blood pressure dip </= 6mmHg had longer survival (p=0.04 and p=0.01, respectively). In the multivariate analysis, SBPs was the only variable with an odds ratio of 7.61 (CI: 1.56; 3704) (p=0.01). Patients with mean SBP<105mmHg were 7.6 times more likely to die than those with SBP >/= 105 mmHg CONCLUSION Ambulatory blood pressure monitoring appears to be a useful method for evaluating patients with congestive heart failure.

A double-blind, placebo-controlled treatment trial of citalopram for major depressive disorder in older patients with heart failure: The relevance of the placebo effect and psychological symptoms

BACKGROUND Little is known about the treatment of depression in older patients with heart failure. This study was developed to investigate the effectiveness of antidepressant treatment for major depressive disorder (MDD) in the elderly with heart failure. METHODS We enrolled 72 older outpatients with ejection fraction <50 and diagnosed with MDD by the structured clinical interview for DSM-IV. Thirty-seven patients, 19 on citalopram and 18 on placebo, initiated an 8-week double-blind treatment phase. Measurements were performed with the 31-item Hamilton Rating Scale for Depression (Ham-D-31), the Montgomery-Asberg rating scale (MADRS) and the Systematic Assessment for Treatment Emergent Effects (SAFTEE). A psychiatrist followed up the patients weekly, performing a consultation for about 20 min to field complaints after the measurements. RESULTS A trend toward superiority of citalopram over placebo in reducing depression was observed in MADRS scores (15.05+9.74 vs 9.44+9.25, P=.082) but not on HAM-D scores. The depressive symptomatology significantly decreased in both groups (P < .001). The high rate of placebo response during the double-blind phase (56.3%) led us to conclude the study at the interim analysis with 37 patients. CONCLUSION Citalopram treatment of MDD in older patients with heart failure is well-tolerated with low rates of side effects, but was not significantly more effective than placebo in the treatment of depression. Weekly psychiatric follow-up including counseling may contribute to the improvement of depression in this population. Scales weighted on psychological symptoms such as the MADRS are possibly better suited to measure depression severity and improvement in patients with heart failure.

Frequency and significance of cardiac rhythm disturbances in healthy elderly individuals

The authors examined the prevalence and significance of cardiac rhythm disturbances in healthy elderly individuals. They selected 26 men with active lifestyles, aged 70-81 years, after clinical, routine blood tests, chest radiographs, echocardiography, resting and exercise electrocardiography, and Gated cardiac blood imaging evaluations. The men were submitted to continuous electrocardiographic monitoring during their daily routine. The recording time ranged from 838 to 1,432 min (average = 1,307 +/- 153 min). Clinical follow-up was done every six months. Sinus rhythm predominated in all subjects. The maximal, minimal, and average heart rate ranges (beats/min) were, respectively: during sleeping periods, 60-115 (85.8 +/- 13.2), 42-80 (56.6 +/- 8.7), 51-85 (64.0 +/- 8.8); and during awake periods, 85-150 (118.4 +/- 16.4), 50-85 (64.1 +/- 9.1), 61-90 (75.3 +/- 8.3). The longest sinus pauses were observed during sleep and ranged from 0.8 to 2.5 sec (1.25 +/- 0.34 sec). Atrial ectopic beats were observed in 20 individuals (76.9%). They were frequent in four (15.4%) and repetitive in nine (34.6%) of them. Short-lasting episodes of paroxysmal atrial tachycardia and paroxysmal atrial flutter were observed in one case each. Ventricular ectopic beats were recorded in 20 individuals (76.9%). They were frequent in 6 (23%) and multiform in 13 (50%) of them. Couplets were observed in 5 cases (19.2%) and episodes of nonsustained ventricular tachycardia were present in 3 individuals (11.5%). No symptoms were referred by any individual during recording. No clinical signs of heart disease or symptoms were noticed during the average 40 +/- 7.2 months of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)