The effect of lifestyle interventions on depressive symptom severity in individuals with type-2 diabetes: A meta-analysis of randomized controlled trials.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a severe metabolic condition which is commonly comorbid with depression. Lifestyle factors are involved in the pathophysiology of both conditions; however, the role of lifestyle interventions remains unclear. OBJECTIVE: The objective of this study is to systematically review the literature on randomized controlled trials evaluating the effect of lifestyle interventions on depressive scores in patients with T2DM. METHODS: A systematic search was conducted in computerized databases before October 2022. A random-effects model was used to investigate the effect of lifestyle interventions on depression scores and meta-regression was conducted to assess the influence of age and disease onset. RESULTS: Six trials met the eligibility criteria for inclusion. A statistically significant reduction in depression scores was found for groups receiving lifestyle interventions compared to controls (SMD = -0.49 [95%CI -0.89 to -0.08]; p = 0.0269]). Interventions increased in efficacy with the age of the participants but no significant correlation was found with years since disease onset. Participants in a control group receiving a less intense lifestyle intervention demonstrated improved depression scores when compared to those who received standard care or no intervention at all. Trial design and outcome measurement tools were heterogeneous between studies and limited data on antidepressant use was available which may introduce bias into the results. CONCLUSION: Lifestyle interventions were effective at improving depressive symptom severity in patients with T2DM.

Association between adiposity and emergent depressive symptoms in a 10-years prospective cohort of older adults: The EpiFloripa Aging study.

BACKGROUND: The association between obesity and depressive symptoms has been described in the literature, but there is a scarcity of longitudinal data. This study aimed to verify the association between body mass index (BMI) and waist circumference and the incidence of depressive symptoms over a 10-year follow-up in a cohort of older adults. METHODS: Data from the first (2009-2010), second (2013-2014), and third (2017-2019) waves of the EpiFloripa Aging Cohort Study were used. Depressive symptoms were assessed by the 15-item Geriatric Depression Scale (GDS-15) and classified in significant depressive symptoms for those with ≥6 points. The Generalized Estimating Equations model was used to estimate the longitudinal association between BMI and waist circumference and depressive symptoms across a 10-year follow-up. RESULTS: The incidence of depressive symptoms (N = 580) was 9.9 %. The relationship between BMI and the incidence of depressive symptoms in older adults followed a U-shaped curve. Older adults with obesity had an incidence relative ratio of 76 % (IRR = 1.24, p = 0.035) for increasing the score of depressive symptoms after 10 years, compared to those with overweight. The higher category of waist circumference (Male: ≥102; Female: ≥88 cm) was associated with depressive symptoms (IRR = 1.09, p = 0.033), only in a non-adjusted analysis. LIMITATIONS: Relatively high follow-up dropout rate; Few individuals in the underweight BMI category; BMI must be considered with caution because it does not measure only fat mass. CONCLUSIONS: Obesity was associated with the incidence of depressive symptoms when compared with overweight in older adults.

Psychometric properties of the Smartphone Addiction Inventory - Short Form (SPAI-SF) in Brazilian adolescents.

The Smartphone Addiction Inventory - Short Form (SPAI-SF) is shorter version (10 items) of the original version of SPAI (26 items). In this study, we aimed to: (i) adapt and test the internal structure of the SPAI-SF, using confirmatory factor analysis (CFA), multigroup confirmatory factor analysis (MGCFA), and network analysis; (ii) analyze the internal consistency, temporal stability, criterion, predictive and construct validities of the SPAI-SF. A total of 392 adolescents (M = 12.76; SD = 1.00) completed the following measures: demographic questionnaire, SPAI-SF, Smartphone Addiction Scale - Short Version (SAS-SV), and the Internet Addiction Test (IAT). The CFA showed good fit indices with the original four factors, and MGCFA indicated measurement invariance for gender. Network analysis provided an understanding of the core symptoms of problematic smartphone use (PSU) for both boys and girls. The intraclass correlation coefficient (ICC) was 0.865 (95% CI: 0.841 - 0.887) and indicated a robust temporal stability. The instrument demonstrated acceptable overall reliability measured by Cronbach's alpha and McDonald's Omega criteria (α = 0.722; ω = 0.725) and did not show floor and ceiling effects. The scale's significant correlations demonstrated convergent and criterion validities of the SPAI-SF with SAS-SV, IAT, and Smartphone usage data. The SPAI-SF is a reliable instrument to detect PSU in adolescents.

Effects of the ketogenic diet on cognition: a systematic review.

INTRODUCTION: Ketogenic diet (KD) therapy has been used as a dietary intervention in drug-resistant epilepsy for several years. Research currently suggests that KD therapy may carry neuroprotective and cognition enhancing effects for individuals with non-epileptic conditions as well as for healthy individuals. Therefore, KD may have potential as a non-invasive, nutritional treatment approach for difficult to manage conditions such as neurodegenerative illnesses or mood disorders. The aim of this review is to summarize the available evidence on ketogenic interventions and the resulting cognitive outcomes. MATERIALS AND METHODS: The paper was based on PRISMA 2020 guidelines. The search was conducted in June 2021 on the following databases: CENTRAL, PubMed, EMBASE, PsycInfo, Web of Science. The search yielded 2014 studies, of which 49 were included. RESULTS: There were 22 animal studies assessing murine models and 27 studies on humans. The primary indications in these studies were epileptic conditions, neurodegenerative disorders, cognitive impairment, and healthy populations. DISCUSSION: Administration of KD seems to confer cognitive-enhancing effects in areas such as working memory, reference memory and attention. Studies found that KD treatment in animals has the potential to alleviate age-related cognitive decline. Over 80% of the 27 human studies reported a favourable effect of intervention, and none reported a detrimental effect of KD. While these findings suggest that KD may improve the functioning of certain cognitive domains, definitive conclusions were limited by studies with small sample sizes, the absence of controls and randomization, and the lack of objective measures of cognition.

The course of attention-deficit/hyperactivity disorder through midlife.

The course of ADHD from childhood up to young adulthood has been characterized in several studies. However, little is known about the course of symptoms into middle age and beyond. This study aims to evaluate predictors of ADHD trajectories in midlife based on three assessments. The follow-up sample comprised 323 adults with ADHD, evaluated at baseline and seven and thirteen years later, from the average ages of 34 up to 47 years old. ADHD status at reassessments was used to characterize trajectories. Demographics, ADHD features, comorbidities, and polygenic scores for ADHD and genetically correlated psychiatric disorders were evaluated to predict ADHD trajectories. Study retention rate was 67% at T2 (n = 216) and 62% at T3 (n = 199). Data from patients evaluated three times showed that 68.8% coursed stable, 25.5% unstable, and 5.7% remission trajectory of ADHD. Women, individuals with more severe syndromes, higher frequency of comorbidities at reassessments, and genetic liability to depression present a higher probability of a stable trajectory. Our findings shed light on midlife ADHD trajectories and their gender, genomic and clinical correlates.

Is there a place for dietetic interventions in adult ADHD?

Current treatments for Attention-Deficit/Hyperactivity Disorder (ADHD) in adults are limited by lack of response and side effects in about one third of the individuals. Changes towards a healthier lifestyle could have a positive impact beyond the relief of specific symptoms. However, it is not clear if nutritional interventions influence mental health and cognition. The objective of this study was to summarize the available literature addressing the impact of different diets in ADHD. The most promising dietetic approaches in ADHD are diets considered to be healthy (Mediterranean-type; DASH) and the Few-Foods Diet for children. Studies should take into account the presence of multiple confounders, biases associated with difficulties in blinding participants and researchers, and search for possible mechanisms of action, so we can have better evidence to guide clinical mental care of adults with ADHD.

A Possible Antidepressive Effect of Dietary Interventions: Emergent Findings and Research Challenges.

Purpose: Despite recent advancements in the treatment of depression, the prevalence of affected individuals continues to grow. The development of new strategies has been required and emerging evidence has linked a possible antidepressant effect with dietary interventions. In this review, we discuss recent findings about the possible antidepressant effect of dietary interventions with an emphasis on the results of randomized controlled trials. Recent findings: A high consumption of refined sugars and saturated fat and a low dietary content of fruits and vegetables has been associated with the development of depression. There is evidence supporting a small to moderate beneficial effect of a Mediterranean-type diet in depression. In addition, new dietary protocols are being studied for their use as possible interventions, such as the ketogenic diet, Nordic diet, and plant-based diet. Summary: Lifestyle interventions surrounding diet and nutrition are a relatively affordable way to enhance response to treatment and to be employed as an adjunct in mental health care. Most studies, however, are limited by the difficulty in controlling for the placebo effect. Mediterranean-style diets seem to be the most promising as an adjunctive treatment for mood disorders. Larger randomized controlled trials that could assess predictors of response to dietary interventions are needed to establish a clear positive effect of diet and guide clinical care and nutritional recommendations concerning mental health care.

ADHD in childhood predicts BMI and body composition measurements over time in a population-based birth cohort.

BACKGROUND/OBJECTIVES: Obesity has been reported as an attention-deficit hyperactivity disorder (ADHD) comorbidity. So far, few studies have aimed to explore the potential causal relationship between ADHD and obesity, as well as used other measures of body composition like fat-free mass (FFM) and fat mass (FM) as measures of obesity. This study aimed to test the association between ADHD and body composition (body mass index [BMI] and others) and to evaluate the potential causal relationship with obesity. SUBJECTS/METHODS: Data from the 1993 Pelotas (Brazil) birth cohort at age 11-, 15-, 18-, and 22-year follow-up was used. We performed a cross-lagged panel model (CLPM) analysis between ADHD symptoms and BMI to explore the causal relationship between both traits. Finally, we tested whether ADHD, inattention, and hyperactivity symptom scales were associated with BMI, FM, and FFM at 22 years. RESULTS: In the CLPM, higher ADHD scores at age 11 predicted higher BMI at age 15 (ß = 0.055, 95% CI [0.037; 0.073]). ADHD symptoms at age 11 was also associated with a decrease in the FFM (ß = -0.16, 95% CI [-0.28; -0.05]), and an increase in the BMI (ß = 0.17, 95% CI [0.10; 0.23]) and FM (ß = 0.17, 95% CI [0.06; 0.29]) at 22 years. At 22 years of age, ADHD was associated with FFM and FM. Moreover, an increase in BMI was observed with an increase in several symptoms of ADHD in general (ß = 0.06, 95% CI [0.004; 0.12]), and hyperactivity symptoms (ß = 0.15, 95% CI [0.05; 0.25]). CONCLUSION: ADHD at 11 years predicted a higher BMI at 15 years, and body fat composition in adulthood, suggesting higher scores on ADHD symptoms in early life may be a critical point for body composition in early adulthood. The hyperactivity symptoms may play an important role in the BMI increase.

The neurodevelopmental nature of attention-deficit hyperactivity disorder in adults.

BACKGROUND: Population studies have suggested that most adults with attention-deficit hyperactivity disorder (ADHD) did not have the disorder in childhood, challenging the neurodevelopmental conceptualisation of ADHD. Arbitrary definitions of age at onset and lack of defined trajectories were accounted for the findings. AIMS: The objective of this study was to assess the proportion of individuals presenting with either a neurodevelopmental trajectory or late-onset disorder, and to assess risk factors associated with them. METHOD: Data of 4676 individuals from the 1993 Pelotas birth cohort at 11, 15, 18 and 22 years of age were used. Polythetic and latent class mixed model analyses were performed to define ADHD trajectories from childhood to adulthood, and characterise the neurodevelopmental or late-onset courses. Regression models were applied to assess factors associated with different trajectories. RESULTS: Classical polythetic analyses showed that 67% of those with ADHD at 22 years of age had a neurodevelopmental course of the disorder. Latent class mixed model analysis indicated that 78% of adults with ADHD had a trajectory of persistent symptoms, more common in males. The remaining adults with ADHD had an ascending symptom trajectory that occurred after puberty, with late-onset ADHD associated with female gender and higher IQ. CONCLUSIONS: Both polythetic and latent trajectories analyses provided empirical evidence supporting that the large majority of adults with ADHD had a neurodevelopmental disorder.

Reduced fronto-striatal volume in attention-deficit/hyperactivity disorder in two cohorts across the lifespan.

Attention-Deficit/Hyperactivity Disorder (ADHD) has been associated with altered brain anatomy in neuroimaging studies. However, small and heterogeneous study samples, and the use of region-of-interest and tissue-specific analyses have limited the consistency and replicability of these effects. We used a data-driven multivariate approach to investigate neuroanatomical features associated with ADHD in two independent cohorts: the Dutch NeuroIMAGE cohort (n = 890, 17.2 years) and the Brazilian IMpACT cohort (n = 180, 44.2 years). Using independent component analysis of whole-brain morphometry images, 375 neuroanatomical components were assessed for association with ADHD. In both discovery (corrected-p = 0.0085) and replication (p = 0.032) cohorts, ADHD was associated with reduced volume in frontal lobes, striatum, and their interconnecting white-matter. Current results provide further evidence for the role of the fronto-striatal circuit in ADHD in children, and for the first time show its relevance to ADHD in adults. The fact that the cohorts are from different continents and comprise different age ranges highlights the robustness of the findings.

Methylphenidate Alters Functional Connectivity of Default Mode Network in Drug-Naive Male Adults With ADHD.

Objective: This study evaluated the hypothesis that methylphenidate immediate release (MPH-IR) treatment would improve Default Mode Network (DMN) within-connectivity. Method: Resting-state functional connectivity of the main nodes of DMN was evaluated in a highly homogeneous sample of 18 drug-naive male adult participants with ADHD. Results: Comparing resting-state functional connectivity functional magnetic resonance imaging (R-fMRI) scans before and after MPH treatment focusing exclusively on within-DMN connectivity, we evidenced the strengthening of functional connectivity between two nodes of the DMN: posterior cingulate cortex (PCC) and left lateral parietal cortex (LLP). Conclusion: Our results contribute to the further understanding on how MPH affects functional connectivity within DMN of male adults with ADHD and corroborate the hypothesis of ADHD being a delayed neurodevelopmental disorder.

ADGRL3 rs6551665 as a Common Vulnerability Factor Underlying Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder.

Neurodevelopmental disorders are prevalent, frequently occur in comorbidity and share substantial genetic correlation. Previous evidence has suggested a role for the ADGRL3 gene in Attention-Deficit/Hyperactivity Disorder (ADHD) susceptibility in several samples. Considering ADGRL3 functionality in central nervous system development and its previous association with neurodevelopmental disorders, we aimed to assess ADGRL3 influence in early-onset ADHD (before 7 years of age) and Autism Spectrum Disorder (ASD). The sample comprises 187 men diagnosed with early-onset ADHD, 135 boys diagnosed with ASD and 468 male blood donors. We tested the association of an ADGRL3 variant (rs6551665) with both early-onset ADHD and ASD susceptibility. We observed significant associations between ADGRL3-rs6551665 on ADHD and ASD susceptibilities; we found that G-carriers were at increased risk of ADHD and ASD, in accordance with previous studies. The overall evidence from the literature, corroborated by our results, suggests that ADGRL3 might be involved in brain development, and genetic modifications related to it might be part of a shared vulnerability factor associated with the underlying neurobiology of neurodevelopmental disorders such as ADHD and ASD.

Does collateral retrospective information about childhood attention-deficit/hyperactivity disorder symptoms assist in the diagnosis of attention-deficit/hyperactivity disorder in adults? Findings from a large clinical sample.

OBJECTIVES: In accordance with consolidated clinical practice, Diagnostic and Statistical Manual of Mental Disorders, 5th edition suggests a key role of collateral information in the evaluation of retrospective childhood attention-deficit/hyperactivity disorder symptoms in adults despite poor evidence supporting its use. This study aims to assess the incremental value of collateral information on the presence of childhood attention-deficit/hyperactivity disorder symptoms when evaluating adults with attention-deficit/hyperactivity disorder. METHODS: Adult patients with attention-deficit/hyperactivity disorder (n = 449) and non-attention-deficit/hyperactivity disorder subjects (n = 143) underwent an extensive clinical assessment based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. For patients, retrospective collateral information regarding childhood attention-deficit/hyperactivity disorder was obtained and used to sort them into two groups: agreement (n = 277) and disagreement (n = 172) between self- and collateral reports. We compared demographic, clinical and response to treatment profiles among groups to test the relevance of collateral information on the specific issue of childhood attention-deficit/hyperactivity disorder symptoms. RESULTS: Both attention-deficit/hyperactivity disorder groups had higher rates of several comorbidities (oppositional defiant, conduct, substance use and bipolar disorders; all p < 0.001) and impairments than controls. Disagreement between self- and collateral reports on childhood attention-deficit/hyperactivity disorder symptoms occurred in 38% of patients. Overall, attention-deficit/hyperactivity disorder disagreement and agreement groups had similar profiles in response to treatment and comorbidity, and the few differences detected in impairment measures were of small magnitude (Eta(2) < 0.05). CONCLUSION: Although collateral report has an important role for diagnosing attention-deficit/hyperactivity disorder in children, it has no incremental value in the evaluation of childhood attention-deficit/hyperactivity disorder symptoms in adults with a self-reported history of attention-deficit/hyperactivity disorder assessed in clinical settings.

Precisamos falar sobre tecnologia: caracterizando clinicamente os subtipos de dependência de tecnologia / We need to talk about technology: clinical characterization of the technology addiction subtypes

Os desenvolvimentos tecnológicos na área das telecomunicações e tecnologia da informação modificaram não só como as pessoas se comunicam, mas também como elas se relacionam com a própria tecnologia. A forma extrema desse comportamento, conhecida como dependência de tecnologia, é um transtorno caracterizado pela inabilidade de controlar o uso de tecnologia (internet, jogos eletrônicos, smartphones) mesmo que esse uso já esteja causando impacto negativo nas principais áreas da vida do indivíduo (relacionamentos interpessoais, saúde física, desempenho acadêmico, desempenho no trabalho). O objetivo deste artigo é revisar os subtipos de dependência de tecnologia (jogos eletrônico, redes sociais, pornografia e smartphones) que apresentam maior relevância em nossa prática clínica, apresentando suas definições e características, e ilustrando-os através de vinhetas clínicas. Além disso, discutiremos como a avaliação da relação de nossos pacientes com as tecnologias pode ser útil do ponto de vista clínico mesmo para aqueles que não apresentem um transtorno decorrente desse uso nem o tenham como motivo da busca de atendimento.(AU)

Technological developments in telecommunications and information technology have changed not only how people communicate but also how they relate to the technology itself. The extreme form of this behavior, known as technology addiction, is a disorder characterized by the inability to control the use of technology (internet, video games, smartphones) even if such use is already causing a negative impact on major areas of one's life (interpersonal relationships, physical health, academic achievement, job performance). The aim of this paper is to review the technology addiction subtypes (electronic games, social networking, pornography and smartphones) that have greater relevance in clinical practice, with its definitions and characteristics, and illustrating them through clinical vignettes. In addition, we discuss how the evaluation of the relationship of our patients with the technologies can be useful from a clinical point of view even for those who do not present a disorder resulting from this use and not seeking care due to a technology addiction.(AU)

Redes sociais e adolescência: conexões / Social networks and adolescence: connections

Este artigo tem por objetivo fazer um estudo das conexões existentes entre o período da adolescência e o uso das redes sociais. A partir da compreensão dos motivos que levam as pessoas a utilizar as redes sociais e de uma revisão do desenvolvimento normal adolescente, tentou-se entender o que motivaria os jovens para o uso dessas ferramentas. Foi concluído que conflitivas típicas dessa etapa, como a reconstrução da identidade, a importância do grupo e o confronto de gerações, fazem com que esses ambientes virtuais tenham intensa atração nessa fase da vida. Dessa forma, pais e profissionais da saúde devem estar atentos ao envolvimento dos seus filhos adolescentes com essas mídias sociais

This article aims to study the links between the period of adolescence and the use of social networks. From understanding the reasons that lead people to use social networks and a revision of the normal adolescent development, was tried to understand what would motivate young people to use social networks. It was concluded that the typicals psychodynamics conflicts of generations, make these virtual environments have an intense attraction during this time of life. For this reasons, it is important for parents and health professionals to be aware about the relationship between adolescents and social medias

Dependência de jogos eletrônicos em crianças e adolescentes / Video game addiction

Com o incrível avanço tecnológico das últimas décadas, os jogos eletrônicos se tornaram uma das principais atividades de lazer de crianças e adolescentes. Os problemas relacionados ao uso excessivo dos games despertam cada vez mais a atenção de profissionais da saúde, e o número de artigos sobre o tema tem aumentado progressivamente. MÉTODOS: Foi realizada uma revisão não sistemática da literatura utilizandose os bancos de dados PubMed, SciELO e LILACS. RESULTADOS: São descritas as características dos jogos e dos jogadores que parecem estar envolvidos nesse comportamento de dependência, assim como as características clínicas, as bases neurobiológicas, o perfil de comorbidades e as opções de tratamento. A inclusão da categoria Internet Gaming Disorder no DSM-5 demonstra a importância que a comunidade científica tem dado ao assunto e estimula o desenvolvimento de mais pesquisas nessa área. Estudos epidemiológicos, clínicos e de neuroimagem observam que trata-se de um transtorno prevalente principalmente entre os jovens, que acarreta prejuízo significativo na vida dos indivíduos acometidos e que apresenta grandes semelhanças com outros comportamentos de dependência. Discute-se também a influência e os potenciais mecanismos pelos quais os jogos violentos podem estimular a agressividade, principalmente entre os jogadores que já apresentam outros fatores de risco para esse comportamento. CONCLUSÃO: Apesar do crescente corpo de evidências científicas disponíveis na literatura, muitas dúvidas ainda necessitam de esclarecimento e mais pesquisas sobre o tema devem ser estimuladas para que se tenha um maior êxito no reconhecimento e tratamento desse transtorno.(AU)

Along with the amazing technological development seen in the last decades, video games have become one of the main entertainment activities of children and adolescents. The problems due to the overuse of video games have increasingly drawn more attention from health professionals, and the number of publications is growing steadily. METHODS: A non-systematic literature review using the PubMed database, SciELO and LILACS databases was performed. RESULTS: The characteristics of games and players that seem to be involved in addictive behavior, as well as clinical characteristics, neurobiology, comorbidity profile and treatment options are described. The inclusion of Internet Gaming Disorder in DSM-5 demonstrates the importance that the scientific community has given to the subject, and stimulates the development of further research. Epidemiological, clinical and neuroimaging studies show that it is a prevalent disorder particularly among youth, which causes significant impairment in the life of affected individuals, and that presents strong similarities with other addictive behaviors. The influence and potential mechanisms by which violent games can stimulate aggression, especially among players who already have other risk factors for this behavior is also discussed. CONCLUSION: Despite the growing body of scientific evidence available in the literature, many questions still need clarification, and further research on the topic should be encouraged in order to improve the recognition and treatment of this disorder.(AU)

Relationship between endogenous testosterone and cardiovascular risk in early postmenopausal women.

Cardiovascular disease (CVD) is the leading cause of death among postmenopausal women. Changes in endothelial function play an important role in the pathophysiology of atherosclerosis, and evidence suggests that interventions to improve endothelial function could modify the rates of progression and the risk of cardiovascular events. In addition, a positive association between markers of endothelial dysfunction and androgenicity has been described in women with polycystic ovary syndrome, suggesting a correlation with the early-onset endothelial dysfunction found in these patients. We performed a cross-sectional study to verify whether endogenous testosterone levels are correlated with markers of inflammation and endothelial function and with anthropometric and metabolic profile in 53 postmenopausal women. Serum testosterone, sex hormone-binding globulin, C-reactive protein (CRP), fibrinogen, and plasma endothelin-1 (ET-1) were determined. Patients were stratified into 2 groups (higher or lower than the mean testosterone levels of the studied sample). Mean age was 55 years (+/-5), and median time since menopause was 5.5 years (interquartile range, 3-8 years). Body mass index and waist circumference were significantly higher in the group with testosterone levels >or=0.49 ng/mL. Median CRP levels were greater in the group with higher testosterone levels (1.17 [0.17-2.36] vs 0.17 [0.17-0.61] mg/L, P = .039). Median ET-1 levels were also higher in women with greater testosterone levels (0.84 [0.81-0.97] vs 0.81 [0.74-0.84] pg/mL, P = .023). An association of testosterone with CRP (r = 0.416, P = .004) and ET-1 (r = 0.323, P = .031) was observed. This association was dependent on homeostasis model assessment index for ET-1 but not CRP. Testosterone was also associated with waist circumference and blood pressure (P = .001). These data suggest that endogenous testosterone levels in recently postmenopausal women may be part of a proatherogenic profile. Longitudinal studies are needed to assess if androgenicity represents a risk factor for cardiovascular disease and the clinical relevance of its association with ET-1 and CRP in this population.