Fibroblast growth factor 21 in heart failure

Fibroblast growth factor 21 (FGF21) is a peptide hormone involved in energy homeostasis that protects against the development of obesity and diabetes in animal models. Its level is elevated in atherosclerotic cardiovascular diseases (CVD) in humans. However, little is known about the role of FGF21 in heart failure (HF). HF is a major global health problem with a prevalence that is predicted to rise, especially in ageing populations. Despite improved therapies, mortality due to HF remains high, and given its insidious onset, prediction of its development is challenging for physicians. The emergence of cardiac biomarkers to improve prediction, diagnosis, and prognosis of HF has received much attention over the past decade. Recent studies have suggested FGF21 is a promising biomarker candidate for HF. Preclinical research has shown that FGF21 is involved in the pathophysiology of HF through the prevention of oxidative stress, cardiac hypertrophy, and inflammation in cardiomyocytes. However, in the available clinical literature, FGF21 levels appear to be paradoxically raised in HF, potentially implying a FGF21 resistant state as occurs in obesity. Several potential confounding variables complicate the verdict on whether FGF21 is of clinical value as a biomarker. Further research is thus needed to evaluate whether FGF21 has a causal role in HF, and whether circulating FGF21 can be used as a biomarker to improve the prediction, diagnosis, and prognosis of HF. This review draws from preclinical and clinical studies to explore the role of FGF21 in HF

Association of lower total bilirubin level with statin usage: the United States National Health and Nutrition Examination Survey 1999–2008

OBJECTIVE: A low circulating level of bilirubin is associated with increased cardiovascular risk. As statins can stimulate heme oxygenase-1 (HO-1), which increases bilirubin production, we investigated whether statins in routine use increase total bilirubin levels in subjects at high cardiovascular risk. METHODS: Data from 3290 subjects with self-reported history of hypercholesterolemia, diabetes, or cardiovascular diseases in the United States National Health and Nutrition Examination Survey (NHANES) 1999-2008 were analyzed. RESULTS: Subjects taking statins (n = 1156) had lower total bilirubin levels than those not taking any lipid-lowering medication (n = 2134) after adjusting for age, sex, race/ethnicity, and survey period (adjusted mean = 0.699 vs 0.729 mg/dl respectively, P=0.001). The association remained significant after adjusting for more covariates (P = 0.002), but was attenuated after further adjusting for glycosylated hemoglobin, insulin resistance index, and low-density lipoprotein (LDL) cholesterol (P = 0.043). The use of lovastatin, rosuvastatin, and cerivastatin was associated with lower total bilirubin levels in the full adjustment model (P < 0.05). CONCLUSION: The use of statins was associated unexpectedly with lower total bilirubin levels. This could be explained at least partly by the effect of statins on glycemia and LDL cholesterol. Our results do not suggest that the anti-oxidant and anti-inflammatory effects of statins are due to HO-1 induction and increased serum bilirubin levels.postprin

Relationship of fibroblast growth factor 21 with the prevalence and progression of vascular and valvular calcification: Multi-ethnic study of atherosclerosis

Background: Elevated circulating levels of fibroblast growth factor 21 (FGF21) are associated with cardiovascular disease (CVD). Therefore, we investigated the relationship of plasma FGF21 with calcification at different vascular and valvular sites. Methods: A total of 5786 participants, free of clinically apparent CVD at baseline and with valid data on plasma FGF21 and calcification (Agatston score, volume and density) at coronary arteries, thoracic arteries, mitral and aortic valves, and aortic valve ring, were included in the analysis. Vascular calcification was measured at 2–3 follow-up visits. Results: At baseline, higher FGF21 levels were associated with prevalent descending thoracic aortic calcification (DTAC) (prevalence ratio = 1.06 [95% CI 1.01–1.11] per SD increase in log-transformed unit, P = 0.016). Among participants without prevalent calcification, higher FGF21 levels were associated with incident DTAC (relative risk [RR] = 1.13 [95% CI 1.04–1.22], P = 0.002). Among all participants, higher FGF21 levels were also associated with the progression of DTAC score and volume (RR = 1.07 [95% CI 1.03–1.12] and 1.08 [95% CI 1.03–1.12] respectively, both P < 0.01). No significant association of FGF21 was found for prevalence (prevalence ratio = 0.89–1.05), incidence (RR = 0.97–1.16) and progression of calcification (RR = 0.94–1.14) at the other sites. Conclusion: Higher FGF21 levels were associated with the presence, incidence and progression of DTAC. However, the magnitude of this association was similar to those of the non-significant associations of FGF21 levels with calcifications at other sites. Further research is needed to assess the potential of FGF21 as a biomarker for vascular calcification

Statin Prescription Patterns and Associations with Subclinical Inflammation

Background and Objectives: Statins have been extensively utilised in atherosclerotic cardiovascular disease (ASCVD) prevention and can inhibit inflammation. However, the association between statin therapy, subclinical inflammation and associated health outcomes is poorly understood in the primary care setting. Materials and Methods: Primary care electronic health record (EHR) data from the electronic Practice-Based Research Network (ePBRN) from 2012–2019 was used to assess statin usage and adherence in South-Western Sydney (SWS), Australia. Independent determinants of elevated C-reactive protein (CRP) were determined. The relationship between baseline CRP levels and hospitalisation rates at 12 months was investigated. Results: The prevalence of lipid-lowering medications was 14.0% in all adults and 44.6% in the elderly (≥65 years). The prevalence increased from 2012 to 2019 despite a drop in statin use between 2013–2015. A total of 55% of individuals had good adherence (>80%). Hydrophilic statin use and higher intensity statin therapy were associated with elevated CRP levels. However, elevated CRP levels were not associated with all-cause or ASCVD hospitalisations after adjusting for confounders. Conclusions: The prevalence and adherence patterns associated with lipid-lowering medications highlighted the elevated ASCVD-related burden in the SWS population, especially when compared with the Australian general population. Patients in SWS may benefit from enhanced screening protocols, targeted health literacy and promotion campaigns, and timely incorporation of evidence into ASCVD clinical guidelines. This study, which used EHR data, did not support the use of CRP as an independent marker of future short-term hospitalisations

Acolhimento na Atenção Básica: Navegações e Mergulhos nos Discursos e Práticas Produzidos no Cotidiano de uma Unidade de Saúde da Família.

RESUMO HOFFMANN, Catharina. Acolhimento na Atenção Básica: navegações e mergulhos nos discursos e práticas produzidos no cotidiano de uma Unidade de Saúde da Família. Orientadora: Profa. Dra. Maristela Dalbello Araújo. Vitória/ES: PPGPSI/UFES, 2009. 167f. Dissertação de Mestrado. Esta pesquisa abrange os processos de produção de saúde, tendo como objeto de estudo os discursos e práticas de saúde relacionados ao acolhimento. O contexto de análise é a Atenção Básica do município de Vitória/ES e o campo de pesquisa, o cotidiano da Unidade de Saúde da Família da Ilha do Príncipe. O estudo utilizou como referência os aportes teóricos da Análise Institucional e da Saúde Coletiva. Buscou-se analisar o modo como os trabalhadores fazem acolhimento no cotidiano do serviço, além de escutar as concepções e os discursos produzidos a respeito, na relação com suas práticas cotidianas, o que inclui os processos de trabalho e as interações com os usuários. Para isso, utilizou-se a Cartografia como estratégia metodológica. Os dados foram produzidos no período de fevereiro a setembro de 2008, por meio de observação, diário de campo e entrevistas realizadas com usuários e trabalhadores da USF. Os resultados produzidos expressam que o processo de trabalho e sua gestão são fragmentados e burocratizantes. Há intenção dos trabalhadores de rever os processos de trabalho, entretanto, isto encontra obstáculos na prática. No tocante ao acolhimento, a exigência que os trabalhadores sofrem para que atendam a uma certa produtividade é um aspecto que compromete a qualidade da relação entre as equipes e destas com o usuário, afetando o atendimento às necessidades destes e a própria oferta de ações de saúde. As necessidades que os trabalhadores esperam acolher estão circunscritas à doença ou sintoma manifesto fisicamente. Demonstrou-se que ir ao serviço para conversar constitui-se em uma demanda valorizada pelos usuários, sendo acolhida por alguns trabalhadores. Evidenciou-se que a comunicação nas equipes é restrita às discussões de questões administrativas e procedimentos. A hierarquização entre os níveis de formação contribui para entender o acolhimento como uma atividade ou procedimento que é atribuição de uma categoria específica (auxiliares de enfermagem), a qual supõe-se, tem capacidade técnica para fazê-lo no ato de recepção do usuário. Constatou-se que as ações de saúde não são pactuadas com os usuários, de modo que o PSF não garante o acolhimento. Porém, os tensionamentos nas relações cotidianas entre trabalhador e usuário favorecem a problematização do acolhimento como ação que pode ultrapassar a recepção. Fica evidente a necessidade de reorganização dos processos de trabalho e de se engendrar subjetividades por uma humanização que valorize os processos de singularização, de modo a se promover uma real democracia no acesso à saúde, na qualidade da assistência e na garantia dos princípios do SUS. Palavras-chave: acolhimento; processos de trabalho em saúde; produção de subjetividade; relação trabalhador-usuário

The imperialist claws of MetaCapitalism

The information and industrial revolutions are so different and yet similar. Both enjoyed the emergence of accounting measurement and management techniques which privileged the efficient allocation of resources as the principal imperative to a firm\u27s participation in a free market economy. MetaCapitalism is one such corporate change strategy which promised untold wealth and unprecedented growth, and under that guise a predatory Darwinistic corporate strategy was implemented. Fundamentally, it promotes extreme outsourcing and downsizing of human capital, de-capitalisation of all non-core capital assets and the diminished role of the State in the global free market economy. Yet the most disturbing aspect is its complete and total disregard for even the slightest social or public policy implications. Essentially then, its most salient danger is an unmistakable endorsement of a fundamentalist brand of value free, reckless capitalism that is ultimately detrimental not only to the long-term business interest, but human as well. One of the main findings of evaluating the Fortune 100 companies\u27 performance in implementing MetaCapitalism was the resulting monopolies. Lenin described monopolies as essential to imperialism which is the highest stage of capitalism. The parallels between the resulting monopolies under MetaCapitalism, and what Lenin described as the final stage of Capitalism are poignant. I would like to draw upon those parallels in the hope that earlier work might enlighten our understanding and inform our critique of MetaCapiatlism

Sphingomyelin phosphodiesterase-1 (SMPD1) coding variants do not contribute to low levels of high-density lipoprotein cholesterol

<p>Abstract</p> <p>Background</p> <p>Niemann-Pick disease type A and B is caused by a deficiency of acid sphingomyelinase due to mutations in the sphingomyelin phosphodiesterase-1 (<it>SMPD1</it>) gene. In Niemann-Pick patients, <it>SMPD1 </it>gene defects are reported to be associated with a severe reduction in plasma high-density lipoprotein (HDL) cholesterol.</p> <p>Methods</p> <p>Two common coding polymorphisms in the <it>SMPD1 </it>gene, the G1522A (G508R) and a hexanucleotide repeat sequence within the signal peptide region, were investigated in 118 unrelated subjects of French Canadian descent with low plasma levels of HDL-cholesterol (< 5^thpercentile for age and gender-matched subjects). Control subjects (n = 230) had an HDL-cholesterol level > the 25^thpercentile.</p> <p>Results</p> <p>For G1522A the frequency of the G and A alleles were 75.2% and 24.8% respectively in controls, compared to 78.6% and 21.4% in subjects with low HDL-cholesterol (<it>p </it>= 0.317). The frequency of 6 and 7 hexanucleotide repeats was 46.2% and 46.6% respectively in controls, compared to 45.6% and 49.1% in subjects with low HDL-cholesterol (<it>p </it>= 0.619). Ten different haplotypes were observed in cases and controls. Overall haplotype frequencies in cases and controls were not significantly different.</p> <p>Conclusion</p> <p>These results suggest that the two common coding variants at the <it>SMPD1 </it>gene locus are not associated with low HDL-cholesterol levels in the French Canadian population.</p

The relationship of neutrophil elastase and proteinase 3 with risk factors, and chronic complications in type 2 diabetes: A Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) sub-study

Introduction: Neutrophil elastase (NE) and proteinase 3 (PR3) are novel inflammation biomarkers. We investigated their associations with chronic complications, determinants of biomarker levels and effects of fenofibrate in patients with type 2 diabetes mellitus (T2DM) from Fenofibrate Intervention and Event Lowering in Diabetes study. Methods: Plasma NE and PR3 levels were quantified at baseline (n = 2000), and relationships with complications over 5-years assessed. Effects of fenofibrate on biomarker levels (n = 200) were determined at four follow-up visits. Results: Higher waist-to-hip ratio, homocysteine and C-reactive protein and lower apoA-II were determinants of higher NE and PR3 levels. Higher NE levels were associated with on-trial stroke and cardiovascular mortality, and higher PR3 levels with on-trial stroke, but associations were not significant after adjustment for confounding factors. Although higher NE and PR3 levels were associated with baseline total microvascular disease, only NE levels were associated with on-trial neuropathy or amputation. These associations were not significant after adjusting for multiple comparisons. NE and PR3 levels did not change with fenofibrate. Conclusions: In T2DM plasma NE and PR3 levels are associated with vascular risk factors, and total microvascular disease at baseline, but on rigorous analyses were not associated with on-trial complications. Levels were not changed by fenofibrate

High density lipoproteins improve insulin sensitivity in high-fat diet-fed mice by suppressing hepatic inflammation

Obesity-induced liver inflammation can drive insulin resistance. HDL has anti-inflammatory properties, so we hypothesized that low levels of HDL would perpetuate inflammatory responses in the liver and that HDL treatment would suppress liver inflammation and insulin resistance. The aim of this study was to investigate the effects of lipid-free apoAI on hepatic inflammation and insulin resistance in mice. We also investigated apoAI as a component of reconstituted HDLs (rHDLs) in hepatocytes to confirm results we observed in vivo. To test our hypothesis, C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks and administered either saline or lipid-free apoAI. Injections of lipid-free apoAI twice a week for 2 or 4 weeks with lipid-free apoAI resulted in: i) improved insulin sensitivity associated with decreased systemic and hepatic inflammation; ii) suppression of hepatic mRNA expression for key transcriptional regulators of lipogenic gene expression; and iii) suppression of nuclear factor κB (NF-κB) activation. Human hepatoma HuH-7 cells exposed to rHDLs showed suppressed TNFα-induced NF-κB activation, correlating with decreased NF-κB target gene expression. We conclude that apoAI suppresses liver inflammation in HFD mice and improves insulin resistance via a mechanism that involves a downregulation of NF-κB activation. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc