Cardiovascular Prognosis of Subclinical Chronic Obstructive Pulmonary Disease in Patients with Suspected or Confirmed Coronary Artery Disease.

Background: Chronic obstructive pulmonary disease (COPD) worsens prognosis in patients with coronary artery disease (CAD). However, the cardiovascular prognosis in patients with stable or mildly symptomatic COPD remains unclear. Here, we sought to determine the long-term cardiovascular events in patients with subclinical or early-stage COPD with concomitant CAD. Methods: This was a longitudinal analytical study involving 117 patients with suspected or established CAD who underwent assessment of pulmonary function by spirometry and who were followed up for six years (March 2015-January 2021). The patients were divided into two groups, one comprising COPD (n=44) and the other non-COPD (n=73) patients. Cox regression was used to evaluate the association between COPD and cardiovascular events, with adjustment for the established CAD risk factors, and the effect size was measured by the Cohen test. Results: COPD patients were older (p=0.028), had a greater frequency of diabetes (p=0.026), were more likely to be smokers (p<0.001), and had higher modified Medical Research Council scores (p<0.001). There was no difference between the groups regarding gender, body mass index, hypertension, dyslipidemia, family history of CAD, and type of angina. CAD frequency and the proportion of patients with severe and multivessel CAD were significantly higher among COPD than among non-COPD patients (all p<0.001). At six-year follow-up, patients with COPD were more likely to have experienced adverse cardiovascular events than those without COPD (p<0.001; effect size, 0.720). After adjusting for established CAD risk factors, COPD occurrence remained an independent predictor for long-term adverse cardiovascular events (OR: 5.13; 95% CI: 2.29-11.50; p<0.0001). Conclusion: COPD was associated with increased severity of coronary lesions and a greater number of adverse cardiovascular events in patients with suspected or confirmed CAD. COPD remained a predictor of long-term cardiovascular events in stable patients with subclinical or early-stage of COPD, independently of the established CAD risk factors.

Evaluation of parathyroid function and mineral metabolism in psychiatric patients using lithium salts.

OBJECTIVE: To evaluate parathyroid function and mineral metabolism in psychiatric patients users of lithium salts. MATERIALS AND METHODS: We measured the serum levels of calcium, ionized calcium, inorganic phosphorus, alkaline phosphatase, albumin, parathyroid hormone (PTH), urea, creatinine, 25-hydroxy-vitamin D and lithium of 35 patients diagnosed with bipolar disorder in use of lithium carbonate (LC) for at least one year (Lithium Group - LG) and 35 healthy subjects (Control Group - CG). RESULTS: The LG and CG were matched by sex and age. There was only statistic difference in relation to the levels of PTH and ionized calcium, with p < 0.004 and p < 0.03, respectively. Secondary form of hyperparathyroidism (HPT) was found in eight (22.8%) LG patients and in none of the CG. There was no correlation between lithemia, usage time and dosage of LC. CONCLUSION: Our data demonstrate that lithium may create an imbalance in the parathyroid axis, characterized by elevated levels of PTH.

Evaluation of parathyroid function and mineral metabolism in psychiatric patients using lithium salts / Avaliação da função paratireoidiana e metabolismo mineral em pacientes psiquiátricos usuários de sais de lítio

Objective: To evaluate parathyroid function and mineral metabolism in psychiatric patients users of lithium salts. Materials and methods: We measured the serum levels of calcium, ionized calcium, inorganic phosphorus, alkaline phosphatase, albumin, parathyroid hormone (PTH), urea, creatinine, 25-hydroxy-vitamin D and lithium of 35 patients diagnosed with bipolar disorder in use of lithium carbonate (LC) for at least one year (Lithium Group – LG) and 35 healthy subjects (Control Group – CG). Results: The LG and CG were matched by sex and age. There was only statistic difference in relation to the levels of PTH and ionized calcium, with p < 0.004 and p < 0.03, respectively. Secondary form of hyperparathyroidism (HPT) was found in eight (22.8%) LG patients and in none of the CG. There was no correlation between lithemia, usage time and dosage of LC. Conclusion: Our data demonstrate that lithium may create an imbalance in the parathyroid axis, characterized by elevated levels of PTH. .

Objetivo: Avaliar a função paratireoidiana e o metabolismo mineral em pacientes psiquiátricos usuários de sais de lítio. Materiais e métodos: Foram avaliados os níveis séricos de cálcio total, cálcio iônico, fósforo inorgânico, fosfatase alcalina, albumina, paratormônio (PTH), ureia, creatinina, 25-hidroxivitamina D e lítio de 35 pacientes diagnosticados com transtorno afetivo bipolar usuários de carbonato de lítio (CL) há pelo menos um ano (Grupo Lítio – GL) e 35 indivíduos saudáveis (Grupo Controle – GC). Resultados: O GL e o GC foram pareados por sexo e idade. Somente se observou diferença estatística em relação aos níveis de PTH e cálcio iônico, com p < 0,004 e p < 0,03, respectivamente. Hiperparatireoidismo secundário foi encontrado em oito (22.8%) pacientes do GL e em nenhum do GC. No GL, não houve correlação entre litemia, tempo de uso e posologia do CL. Conclusão: Nossos dados demonstram que o lítio pode suscitar um desequilíbrio no eixo paratireoideano, caracterizado por níveis elevados de PTH. .

Função diastólica do ventrículo esquerdo em obesos graves em pré-operatório para cirurgia bariátrica / Left ventricular diastolic function in morbidly obese patients in the preoperative for bariatric surgery

FUNDAMENTO: Obesidade é uma doença crônica, multifatorial, associada a aumento do risco cardiovascular, especialmente a insuficiência cardíaca diastólica. OBJETIVO: Avaliar a função diastólica do ventrículo esquerdo em obesos graves em pré-operatório para cirurgia bariátrica, relacionando com os fatores de risco cardiovascular e a estrutura cardíaca. MÉTODOS: Trata-se de um estudo transversal, com 132 pacientes candidatos a cirurgia bariátrica, submetidos a avaliação ecocardiográfica transtorácica e dos fatores de risco cardiovascular, sendo: 97 mulheres (73,5%), idade média de 38,5 ± 10,5 anos e IMC de 43,7 ± 7,2 Kg/m². Foram divididos em três grupos: 61 com função diastólica normal, 24 com disfunção diastólica leve e 47 com disfunção diastólica moderada/grave, dos quais 41 com disfunção diastólica moderada (padrão pseudonormal) e seis com disfunção diastólica grave (padrão restritivo). RESULTADOS: Hipertensão arterial sistêmica, idade e gênero foram diferentes nos grupos com disfunção diastólica. Os grupos com disfunção tiveram maior diâmetro do átrio esquerdo, do ventrículo esquerdo, volume do átrio esquerdo em quatro e duas câmaras, índice de volume atrial esquerdo e índice de massa do ventrículo esquerdo corrigido para a superfície corpórea e para altura. CONCLUSÃO: A elevada frequência de disfunção diastólica do ventrículo esquerdo na fase pré-clínica em obesos graves justifica a necessidade de uma avaliação ecocardiográfica criteriosa, com o objetivo de identificar indivíduos de maior risco, para que medidas de intervenção precoce sejam adotadas.

BACKGROUND: Obesity is a chronic and multifactorial disease, associated with increased cardiovascular risk, especially diastolic heart failure. OBJECTIVE: To evaluate left ventricular diastolic function in morbidly obese patients in the pre-operative for bariatric surgery, correlating it with cardiovascular risk factors and heart structure. METHODS: This is a cross-sectional study with 132 patients eligible for bariatric surgery submitted to transthoracic echocardiography assessment and of cardiovascular risk factors, as follows: 97 women (73.5%), mean age 38.5 ± 10.5 years and BMI of 43.7 ± 7.2 kg / m². Patients were divided into three groups: 61 with normal diastolic function, 24 with mild diastolic dysfunction and 47 with moderate/severe diastolic dysfunction, of which 41 with moderate diastolic dysfunction (pseudonormal pattern) and six with severe diastolic dysfunction (restrictive pattern). RESULTS: Hypertension, age and gender were different in the groups with diastolic dysfunction. Groups with dysfunction had higher left atrial diameter, left ventricular diameter, left atrial volume in four and two chambers, left atrial volume index and left ventricular mass index corrected for body surface area and height. CONCLUSION: The high frequency of left ventricular diastolic dysfunction in the preclinical phase in morbidly obese patients justifies the need for careful echocardiographic assessment, aiming at identifying individuals at higher risk, so that early intervention measures can be carried out.

[Physiology of the GH-IGF axis]. / Fisiologia do eixo GH-sistema IGF.

Growth, the main characteristic of childhood and adolescence, has a similar pattern in the majority of the individuals. Genetic background and GH-IGF axis are the factors that directly influence this process. Pituitary GH acts on growth mainly through the regulation of IGF system. The IGFs (IGF-1 and IGF-2) are growth factors produced in the majority of the organs and body tissues. They have autocrine, paracrine and endocrine actions on metabolism and cell proliferation, growth and differentiation. The IGFs bind with high specificity and affinity to a family of 6 binding proteins, called IGFBPs (1 to 6) that modulate their bioactivity. Most of the known IGF actions are mediated via IGF type 1 receptor (IGF1R). In this article we are going to review the composition and regulation of the GH-IGF axis and the role of each component in the regulation of the growth process.

Fisiologia do eixo GH-sistema IGF / Physiology of the GH-IGF axis

O crescimento, principal característica da infância e da adolescência, apresenta padrão semelhante na maioria dos indivíduos. A herança genética e os componentes do eixo GH-IGF são os fatores que diretamente influenciam esse processo. O GH, produzido na hipófise, exerce sua ação sobre o crescimento mediante regulação do sistema IGF. Os IGFs (IGF-1 e IGF-2) são fatores de crescimento produzidos na maioria dos órgãos e tecidos do organismo, possuindo ações autócrinas, parácrinas e endócrinas sobre o metabolismo intermediário, proliferação, crescimento e diferenciação celular. Associam-se com elevado grau de especificidade e de afinidade à família de seis proteínas carreadoras, denominadas IGFBPs (IGFBP-1 a -6), as quais modulam suas bioati-vidades. A maioria das ações conhecidas dos IGFs é exercida mediante sua ligação com o receptor tipo 1 (IGF-1R). Neste artigo será revisada a composição e a regulação do eixo GH-sistema IGF, assim como a participação de cada um dos seus diferentes componentes no processo de regulação do crescimento humano.

Growth, the main characteristic of childhood and adolescence, has a similar pattern in the majority of the individuals. Genetic background and GH-IGF axis are the factors that directly influence this process. Pituitary GH acts on growth mainly through the regulation of IGF system. The IGFs (IGF-1 and IGF-2) are growth factors produced in the majority of the organs and body tissues. They have autocrine, paracrine and endocrine actions on metabolism and cell proliferation, growth and differentiation. The IGFs bind with high specificity and affinity to a family of 6 binding proteins, called IGFBPs (1 to 6) that modulate their bioactivity. Most of the known IGF actions are mediated via IGF type 1 receptor (IGF1R). In this article we are going to review the composition and regulation of the GH-IGF axis and the role of each component in the regulation of the growth process.

Lack of evidence of premature atherosclerosis in untreated severe isolated growth hormone (GH) deficiency due to a GH-releasing hormone receptor mutation.

BACKGROUND: GH deficiency (GHD) acquired at adult age as a result of pathological processes of the pituitary gland or the hypothalamus causes changes that are associated with worsening cardiovascular risk. They include increase in abdominal obesity, total and low- density lipoprotein cholesterol, and C-reactive protein. GHD adults also have thickening of the carotid arteries. It has been postulated that GHD is the link between hypopituitarism and the increase in cardiovascular and cerebrovascular mortality observed in hypopituitarism. However, several confounding factors exist, such as associated pituitary deficits and replacement of other hormones or surgical or radiological therapies used to treat the underlying pituitary of hypothalamic pathologies. OBJECTIVE: The aim of this study was to determine the consequences of lifetime isolated GHD (IGHD) on the metabolic and cardiovascular status of adult members of a large Brazilian cohort with severe IGHD due to a homozygous mutation in the GHRH receptor gene. DESIGN: Twenty-two GH naive adult dwarfs (10 men and 12 women; aged 44 +/- 12 yr) were compared with 22 healthy volunteers (10 men and 12 women; aged 45 +/- 12 yr) living in the same area. RESULTS: GHD subjects had increased abdominal obesity, higher total and low-density lipoprotein cholesterol, and higher C-reactive protein than controls. They did not have an increase in carotid wall thickness, and there was no evidence of premature atherosclerosis as evaluated by exercise echocardiography. CONCLUSIONS: In this homogeneous cohort residing in a rural area of Brazil, lifetime, untreated severe IGHD is not associated with evidence of premature atherosclerosis despite unfavorable cardiovascular risk profile.

Thyroid morphology and function in adults with untreated isolated growth hormone deficiency.

OBJECTIVE: GH influences thyroid function and anatomy. Although goiter is frequent in acromegalic patients, the effects of GH deficiency (GHD) are difficult to assess, because hypopituitaric subjects who lack GH often also have a partial or complete deficit of TSH. STUDY DESIGN: We studied thyroid morphology and serum levels of thyroid hormones in adult members of a large Brazilian kindred with untreated isolated GHD due to a homozygous mutation in the GHRH receptor gene (GHRHR; nine men and 15 women; GHD group) and compared them to subjects heterozygous for the same mutation (eight men and 10 women; HET group) and subjects homozygous for the wild-type allele [seven men and 11 women; control (CO) group]. RESULTS: GHD subjects had a smaller thyroid volume (TV) than HET and CO. The TV of the HET group was intermediate between those of the GHD and CO groups. When TV was corrected by body surface area, it remained smaller in the GHD and HET groups than in the CO group, but the difference between GHD and HET groups disappeared. The GHD group had lower serum T3 levels than the CO group and higher free T4 levels than HET and CO groups. CONCLUSIONS: Individuals with severe untreated GHD due to a homozygous GHRHR mutation and heterozygous carriers of the same mutation have smaller TV than normal subjects, suggesting that GH has a permissive role in the growth of the thyroid gland. In addition, GHD subjects have reduced serum total T3 and increased serum free T4, suggesting a reduction in the function of the deiodinase system.

Papel do eixo GH/IGF-1 na fisiopatologia da síndrome metabólica: resistência insulínica e lesão de órgãos-alvo / GH/IGF-1 axis and the pathogenesis of metabolic syndrome: focus on insulin resistance and target organ damage

Síndrome metabólica é definida como um agrupamento de fatores lipídicos e não-lipídicos, de origem metabólica, tendo como marcador fisiopatológico comum a resistência insulínica. É uma entidade extremamente heterogênea, apresentando-se com 16 fenótipos possíveis. A busca do conhecimento de marcadores moleculares, de novos fenótipos intermediários e o entendimento da complexa interação genética/meio-ambiente (por exemplo, interação no micro-ambiente uterino) pode promover o aparecimento de novas terapias que visem facilitar o controle dos fatores hemodinâmicos e metabólicos definidores de síndrome metabólica e, conseqüentemente, amortizar a elevada morbimortalidade dos portadores desta síndrome epidêmica. Dentre estes mecanismos, emerge o eixo GH/IGF-1 como sistema candidato para explicar parte da sua expressão fenotípica. Destacam-se, neste artigo, as evidências que apontam para: (1) associação entre síndrome metabólica e desregulação (hipofunção) do eixo GH/IGF-1; (2) associação entre deficiência de GH e expressão fenotípica da síndrome metabólica; e (3) perspectiva terapêutica da reposição de GH corrigindo as múltiplas alterações características da síndrome metabólica, quando da presença de deficiência relativa do GH

Diagnóstico clínico e laboratorial da deficiência isolada do hormônio do crescimento em crianças e adolescentes portadores da mutação no gene do receptor do hormônio liberador do hormônio de crescimento em Itabaianinha, Sergipe / Clinical and laboratorial diagnosis isolated deficiency of growth hormone in children and adolescents with mutation in receptor gene of growth hormone-releasing hormone in Itabaianinha, SE, Brazil

INTRODUÇAO: Em Itabaianinha - Sergipe é encontrado o maior grupo descrito na literatura de habitantes com o fenótipo associado à deficiência isolada do hormônio do crescimento (DIGH) em função da mutação IVS1+ 1, G->A no gene do receptor do hormônio liberador do hormônio de crescimento (GHRH). O objetivo do presente trabalho é descrever o fenótipo clínico e laboratorial dos pacientes da cidade. MATERIAIS E MÉTODOS: Foram selecionados 12 indivíduos com fenótipo clínico de DIGH e 10 voluntários controles sem deficiência de GH, ambos com idade inferior a 20 anos, para estudo de corte transversal. RESULTADOS E DISCUSSAO: Os portadores de DIGH apresentaram hiporresponsividade ao teste de clonidina e à hipoglicemia insulínica e níveis séricos abaixo dos valores de referência para o fator de crescimento insulina símile I (IGF-I) e proteína ligadora do fator de crescimento símile a insulina 3 (IGFBP-3) (6 ±4ng/ml e 510 ± 151ng/ml, respectivamente p < 0,01). O estudo mostrou não haver alterações de função tireoidiana, níveis de hormônios gonadais, cortisol e no estudo da sela túrcica nessa população. Os indivíduos de Itabaianinha apresentam maior número de características fenotípicas (baixa estatura proporcionada, facies típica, adiposidade central, etc.) quando comparados aos grupos descritos na literatura com outras mutações no GHRH-R. CONCLUSAO: Os dados demonstram que a população da cidade apresenta deficiência isolada do hormônio de crescimento do tipo IB. Além disso, a baixa estatura não está associada a alterações múltiplas de hormônios hipofisários ou outras patologias não-hormonais.

Familial isolated growth hormone deficiency is associated with increased systolic blood pressure, central obesity, and dyslipidemia.

To assess the metabolic and cardiovascular consequences of GH deficiency (GHD) on cardiovascular risk factors, we studied a homogeneous population with GHD due to a homozygous defect in the GHRH receptor gene. Anthropometric, metabolic, and cardiovascular measurements (at rest, during treadmill exercise, and during orthostatic stress) and echocardiographic data were obtained from 16 GH-naive, GH-deficient (GHD) adults and 31 age-, sex-, and body mass index-matched control (CO) subjects. The percentage of fat mass, waist to hip ratio, and total and low density lipoprotein cholesterol were higher in the GHD group. However, high density lipoprotein cholesterol, triglyceride, and fasting glucose levels were similar between groups, and fasting insulin and homeostasis model assessment of insulin resistance (HOMA(IR)) were lower in the GHD group. Systolic blood pressure (SBP) was higher in the GHD group, but no difference in diastolic blood pressure or heart rate (HR) existed. Blood pressure and HR responses to exercise did not differ between groups. During passive orthostatic stress the decrease in SBP was higher in the GHD than in the CO group, whereas an increase in diastolic blood pressure was not observed in the GHD group. Moreover, the increase in HR was blunted in the GHD compared with the CO group. Left ventricular mass and mass index were lower in the GHD group. In conclusion, this genetically homogeneous isolated GHD population presents a syndrome characterized by central obesity, dyslipidemia, and elevated SBP but reduced cardiac dimensions compared with controls.