Cláudio Córdova

Association between the -174 G/C promoter polymorphism of the interleukin-6 gene and cardiovascular disease risk factors in Brazilian older women

In worldwide studies, interleukin-6 (IL-6) is implicated in age-related disturbances. The aim of the present report was to determine the possible association of IL-6 -174 C/G promoter polymorphism with the cytokine profile as well as with the presence of selected cardiovascular risk features. This was a cross-sectional study on Brazilian women aged 60 years or older. A sample of 193 subjects was investigated for impaired glucose regulation, diabetes, hypertension, and dyslipidemia. Genotyping was done by direct sequencing of PCR products. IL-6 and C-reactive protein were quantified by high-sensitivity assays. General linear regression models or the Student t-test were used to compare continuous variables among genotypes, followed by adjustments for confounding variables. The chi-square test was used to compare categorical variables. The genotypes were consistent with Hardy-Weinberg equilibrium proportions. In a recessive model, mean waist-to-hip ratio, serum glycated hemoglobin and serum glucose were markedly lower in C homozygotes (P = 0.001, 0.028, and 0.047, respectively). In a dominant hypothesis, G homozygotes displayed a trend towards higher levels of circulating IL-6 (P = 0.092). Non-parametric analysis revealed that impaired fasting glucose and hypertension were findings approximately 2-fold more frequent among G homozygous subjects (P = 0.042 and 0.043, respectively). Taken together, our results show that the IL-6 -174 G-allele is implicated in a greater cardiovascular risk. To our knowledge, this is the first investigation of IL-6 promoter variants and age-related disturbances in the Brazilian elderly population.

Association of systemic inflammatory activity with coronary and carotid atherosclerosis in the very elderly

OBJECTIVE To verify the existence of association between plasma levels of pro- or anti-inflammatory mediators and atherosclerotic burden at coronary and carotid arteries in individuals aged of 80 or more years old. METHODS Healthy individuals aged between 80 and 102 years old (n = 178) underwent evaluation of plasma cytokines and acute phase proteins, intima-media thickness (IMT) and presence of plaques in carotid arteries by ultrasound and coronary artery calcification (CAC) by cardiac computed tomography. RESULTS There was no association between CAC and carotid plaques (p = 0.8), maximum (p = 0.06) or mean IMT (p = 0.2). No association was found between the presence of carotid plaques and CRP (p = 0.4), TNF-α (p = 0.8) or IL-10 (p = 0.2). Likewise, individuals in the first three quartiles for CRP, TNF-α or IL-10 had similar values of CAC, mean and maximum IMT. In contrast, individuals above the 75th percentile for CRP or for TNF-α had enhanced maximum IMT (p = 0.017 and p < 0.0001) and CAC (p = 0.026 and p = 0.01) and subjects with IL-10 levels above the 75th percentile had lower maximum IMT (p = 0.027) and CAC (p = 0.006) as compared with those below this percentile. There was no difference in mean IMT for individuals above or below the 75th percentile for CRP, TNF-α or IL-10. CONCLUSION In very old individuals, CAC and maximum IMT were positively associated with systemic inflammatory activity only in those above the 75th percentile. The markers of atherosclerotic burden at coronary and carotid arteries were not related to each other and were distinctly associated with pro- and anti-inflammatory mediators, suggesting that atherosclerosis development is different in these vascular beds.

The influence of intense intermittent versus moderate continuous exercise on postprandial lipemia

INTRODUCTION: Postprandial lipemia is characterized by an increased concentration of circulating lipids after fat intake and is an independent risk factor for cardiovascular disease. Exercise is known to reduce postprandial lipemia and its negative clinical outcomes. OBJECTIVE: This study investigated the effect of intense intermittent versus moderate continuous exercise using the same energy expenditure in postprandial lipemia. MATERIALS AND METHODS: Twenty healthy men (aged 21.5±3.5 years) performed a random sequence of either rest or 500 Kcal tests separated by a minimum 48 h interval as follows: (a) no exercise (control), (b) intense intermittent exercise, or (c) moderate continuous exercise. Each test series was completed 30 min before ingestion of a high-fat meal (1 g fat/kg). Venous blood was collected before and at 1, 2, 3 and 4 hours after the high-fat meal. Postprandial lipemia was assessed using the area under the curve approach as well as a kinetic profile of mean lipid variables. Statistical significance was tested at the p≤0.05 level. RESULTS: With both statistical approaches, intense intermittent and moderate continuous exercises were both effective in reducing postprandial triglycerides; however, only intense intermittent exercise reduced the levels of postprandial very low density lipoprotein. Intense intermittent and continuous exercise produced lower levels of insulinemia using the area under the curve analysis only. CONCLUSION: Intense intermittent or continuous exercise with an energy expenditure of 500 kcal completed 30 min before ingestion of high-fat meal reduced postprandial lipid levels to different levels in physically active men. Understanding these relevant differences will enable clinicians to provide the best exercise prescription for patients.

Non-alcoholic fatty liver disease and metabolic syndrome in Brazilian middle-aged and older adults

CONTEXT AND OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is a complex clinicopathological entity characterized by diffuse or focal fat accumulation in the hepatic parenchyma of patients who deny abusive alcohol consumption. This study aimed to assess idiopathic NAFLD in community-dwelling, middle-aged and older adults living in the Brazilian Federal District. Associations between NAFLD and components of metabolic syndrome and the whole syndrome were investigated. DESIGN AND SETTINGS This was a cross-sectional study on 139 subjects aged 55 years or older. METHODS NAFLD was diagnosed by means of clinical procedures, to exclude subjects with signs of liver disorders, abusive alcohol consumption and influence from hepatotoxic drugs. Phenotypes were graded based on ultrasound examination. Metabolic syndrome was defined using the NCEP ATP III criteria. Laboratory tests were performed to assist clinical examinations and define the syndrome. RESULTS NAFLD was present in 35.2% of the subjects. Taken together, the two most intense phenotypes correlated with increased serum fasting glucose, triglyceride and VLDL cholesterol levels. Metabolic syndrome was diagnosed in 25.9% of the sample. In addition to associating NAFLD with specific traits of metabolic syndrome, non-parametric analysis confirmed the existence of a relationship (p < 0.05) between the steatotic manifestation and the syndromic condition. CONCLUSION Compared with the literature, this study reveals greater frequency of idiopathic NAFLD among Brazilian middle-aged and older adults than is described elsewhere. The findings also suggest that impaired glycemic metabolism coupled with increased fat delivery and/or sustained endogenous biosynthesis is the most likely physiopathogenic mechanisms underlying the onset of NAFLD in this population.

Acute exercise performed close to the anaerobic threshold improves cognitive performance in elderly females

The objective of the present study was to compare the effect of acute exercise performed at different intensities in relation to the anaerobic threshold (AT) on abilities requiring control of executive functions or alertness in physically active elderly females. Forty-eight physically active elderly females (63.8 +/- 4.6 years old) were assigned to one of four groups by drawing lots: control group without exercise or trial groups with exercise performed at 60, 90, or 110% of AT (watts) and submitted to 5 cognitive tests before and after exercise. Following cognitive pretesting, an incremental cycle ergometer test was conducted to determine AT using a fixed blood lactate concentration of 3.5 mmol/L as cutoff. Acute exercise executed at 90% of AT resulted in significant (P < 0.05, ANOVA) improvement in the performance of executive functions when compared to control in 3 of 5 tests (verbal fluency, Tower of Hanoi test (number of movements), and Trail Making test B). Exercising at 60% of AT did not improve results of any tests for executive functions, whereas exercise executed at 110% of AT only improved the performance in one of these tests (verbal fluency) compared to control. Women from all trial groups exhibited a remarkable reduction in the Simple Response Time (alertness) test (P = 0.001). Thus, physical exercise performed close to AT is more effective to improve cognitive processing of older women even if conducted acutely, and using a customized exercise prescription based on the anaerobic threshold should optimize the beneficial effects.

Long-Term Resistance Training Is Associated with Reduced Circulating Levels of IL-6, IFN-Gamma and TNF-Alpha in Elderly Women

Objective: The increase in inflammatory activity associated with aging is a characteristic of chronic disease processes that accounts for most of the mortality in the elderly. Resistance training (RT) has been shown to promote metabolic and functional benefits in this population. The objective of this study was to investigate the association between long-term RT and circulating levels of the proinflammatory mediators IL-6, TNF-α and IFN-γ in elderly women. Methods: This cross-sectional study included 54 older outpatients divided into a group that underwent RT (n = 28) for an average of 8.6 ± 0.3 months and a sedentary group (n = 26). Measurements were taken only at the end of the intervention, and cytokine values were log-transformed. Dietary intake was controlled as a confounding factor. Results: The RT group presented reduced levels of log10IFN-γ (approx. 45%; p = 0.003), log10IL-6 (approx. 30%; p = 0.002) and log10TNF-α (approx. 22%; p = 0.036). Total caloric intake and systolic arterial blood pressure were significantly lower in the RT group (p = 0.001 and p = 0.022, respectively). Pearson’s product moment correlation test revealed a negative association between the fat-free mass (FFM) index and log-transformed IL-6 levels (p = 0.03; n = 54) and a trend towards significance for the correlation between the FFM index and log10IFN-γ (p = 0.05; n = 54). Conclusion: Long-term, moderate-intensity RT in elderly women is associated with lower circulating levels of cytokines that are potentially implicated in disorders associated with physical inactivity and aging.

Acute effects of resistance training on cytokines and osteoprotegerin in women with metabolic syndrome

Chronic inflammation has been identified as an important component of metabolic syndrome (MetS). Inhibition of the inflammatory mediator signals is a promising strategy against insulin resistance, atherosclerosis and other problems associated with MetS. Regular exercise decreases the components associated with MetS, including inflammatory cytokines. However, the relationship between an acute resistance training (RT) session, cytokine levels and MetS is unclear. Therefore, the aim was to evaluate the effects of a single bout of acute RT on tumour necrosis factor (TNF‐α), interleukins (IL) IL‐1a, IL‐1β, IL‐12, IL‐6, IL‐10 and osteoprotegerin (OPG) in women with MetS. Twenty‐four women were divided into 2 groups: metabolic syndrome (MetS) and non‐metabolic syndrome (Non‐MetS). After the familiarization and testing for 1 repetition maximum (1RM), participants completed 3 sets of 10 repetitions in the following exercises: machine leg press, leg extension, leg curl, chest press, lat front pull‐down and machine shoulder press with 60% of 1RM followed by 15 repetitions of abdominal crunches. A rest interval of 1 min was allowed between sets and exercises. Plasma TNF‐α, IL‐1a, IL‐1β, IL‐12, IL‐6, IL‐10 and OPG were measured before, immediately post and 60 min after RT. MetS group showed significantly higher concentrations of IL‐1β (P = 0·024) and IL‐6 (P = 0·049) and a trend for higher TNF‐α values (P = 0·092) compared with Non‐MetS. There was no group × time interactions after the RT session on the measured cytokines and osteoprotegerin. In conclusion, acute RT session induced no additional increase in pro‐inflammatory cytokines nor a decrease in anti‐inflammatory cytokines and OPG in women with MetS.

A common polymorphism in the renin angiotensin system is associated with differential outcome of antihypertensive pharmacotherapy prescribed to Brazilian older women

BACKGROUND Since variations on the renin angiotensin (RA) system tend to exert effects on blood pressure, we investigated the association of the common ACE and AT1R polymorphisms with response to a multivariate pharmacotherapy. METHODS This prospective study involved 169 hypertensive, community-dwelling older women. Genotypes were obtained by length analysis or direct sequencing of PCR products. Blood pressure-lowering pharmacotherapy was conducted according to current Brazilian Guidelines on Hypertension. RESULTS Genotype frequencies were in agreement to the Hardy-Weinberg equilibrium. Interventions were found to represent actual hypertension-management practices in Brazil, and accounted for a significant reduction in both systolic (P<0.001) and diastolic (P<0.001) blood pressure. Concerning the effect of polymorphisms, no influence of the ACE and AT1R genotypes were found on the magnitude of the treatment-induced blood pressure reduction (P>0.05). Nonetheless, the clinical result varied according to the ACE alleles since mean systolic pressure was roughly 10 mm Hg higher in insertion (I) homozygotes than in the deletion (D) counterparts either in baseline (P=0.001) and endpoint (P=0.010). CONCLUSION The outcome of the antihypertensive pharmacotherapy advocated by national guidelines was significantly influenced by the ACE I/D polymorphism but not by the AT1R 1166 A/C polymorphism among postmenopausal women.

Amerindian Genetic Ancestry Protects against Alzheimer's Disease

Background: Alzheimer’s disease (AD) is the most common form of dementia worldwide, and bears remarkable evidence for a differential prevalence among continental populations. In this scenario, estimating ancestry proportions in recently admixed populations is a strategy that can help increasing knowledge about the genetic structure of this complex trait. Aim/Methods: Our purpose was to assess mean ancestry estimates for the three main parental contributors to the Brazilian contingent (European, African and Amerindian) using a panel of 12 ancestry informative markers. Outpatients with the late-onset form of AD (n = 120) were compared for ancestry levels with non-cognitively impaired subjects (n = 412) in the Midwest Brazil, controlling for classic clinical, social and anthropometric risk factors. Results: Our findings show a 3-fold greater genetic Amerindian content among control subjects compared to AD patients (p < 0.001). Conclusion: Our results suggest that the allelic architecture of Native Americans can confer protection against the onset of the disease.

Beneficial effects of physical activity in an HIV-infected woman with lipodystrophy: a case report.

IntroductionLipodystrophy is common in patients infected with human immunodeficiency virus receiving highly active antiretroviral therapy, and presents with morphologic changes and metabolic alterations that are associated with depressive behavior and reduced quality of life. We examined the effects of exercise training on morphological changes, lipid profile and quality of life in a woman with human immunodeficiency virus presenting with lipodystrophy.Case presentationA 31-year-old Latin-American Caucasian woman infected with human immunodeficiency virus participated in a 12-week progressive resistance exercise training program with an aerobic component. Her weight, height, skinfold thickness, body circumferences, femur and humerus diameter, blood lipid profile, maximal oxygen uptake volume, exercise duration, strength and quality of life were assessed pre-exercise and post-exercise training. After 12 weeks, she exhibited reductions in her total subcutaneous fat (18.5%), central subcutaneous fat (21.0%), peripheral subcutaneous fat (10.7%), waist circumference (WC) (4.5%), triglycerides (9.9%), total cholesterol (12.0%) and low-density lipoprotein cholesterol (8.6%). She had increased body mass (4.6%), body mass index (4.37%), humerus and femur diameter (3.0% and 2.3%, respectively), high-density lipoprotein cholesterol (16.7%), maximal oxygen uptake volume (33.3%), exercise duration (37.5%) and strength (65.5%). Quality of life measures improved mainly for psychological and physical measures, independence and social relationships.ConclusionsThese findings suggest that supervised progressive resistance exercise training is a safe and effective treatment for evolving morphologic and metabolic disorders in adults infected with HIV receiving highly active antiretroviral therapy, and improves their quality of life.