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1.
Nat Commun ; 12(1): 1041, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589633

RESUMO

Growing evidence supports that pharmacological application of growth differentiation factor 15 (GDF15) suppresses appetite but also promotes sickness-like behaviors in rodents via GDNF family receptor α-like (GFRAL)-dependent mechanisms. Conversely, the endogenous regulation of GDF15 and its physiological effects on energy homeostasis and behavior remain elusive. Here we show, in four independent human studies that prolonged endurance exercise increases circulating GDF15 to levels otherwise only observed in pathophysiological conditions. This exercise-induced increase can be recapitulated in mice and is accompanied by increased Gdf15 expression in the liver, skeletal muscle, and heart muscle. However, whereas pharmacological GDF15 inhibits appetite and suppresses voluntary running activity via GFRAL, the physiological induction of GDF15 by exercise does not. In summary, exercise-induced circulating GDF15 correlates with the duration of endurance exercise. Yet, higher GDF15 levels after exercise are not sufficient to evoke canonical pharmacological GDF15 effects on appetite or responsible for diminishing exercise motivation.


Assuntos
Regulação do Apetite/fisiologia , Exercício Físico/fisiologia , Comportamento Alimentar/fisiologia , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator 15 de Diferenciação de Crescimento/genética , Resistência Física/fisiologia , Adulto , Animais , Creatina Quinase/sangue , Creatina Quinase/genética , Regulação da Expressão Gênica , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/deficiência , Fator 15 de Diferenciação de Crescimento/sangue , Fator 15 de Diferenciação de Crescimento/metabolismo , Humanos , Interleucina-10/sangue , Interleucina-10/genética , Interleucina-6/administração & dosagem , Leptina/sangue , Leptina/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , Motivação/fisiologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Condicionamento Físico Animal , Fatores de Tempo
2.
Am Heart J ; 234: 81-89, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33421373

RESUMO

BACKGROUND: Previous studies have proposed growth differentiation factor-15 (GDF-15) as a predictor of adverse cardiovascular outcomes and mortality. The present study aimed to determine if such associations remain after accounting for death as a competing risk, and if GDF-15 provides superior prediction performance than other biomarkers. METHODS: Plasma GDF-15 levels and cardiovascular risk factors were measured in individuals without cardiovascular diseases (n = 4,143, aged 57.4 ± 5.96 years, 38.6 % men) from Malmö Diet and Cancer-Cardiovascular Cohort and were followed up for more than 20 years. Incidence of coronary events, ischemic stroke, cardiovascular mortality, and all-cause mortality was studied in relation to GDF-15 using Cox proportional hazards regression, with adjustment for potential confounders. Confounding from death as competing risk was carefully checked using the Fine and Gray subdistribution hazard model. Predictive capabilities were further evaluated using C-statistics, continuous net reclassification improvement, and integrated discrimination improvement. RESULTS: During follow-up, 424 coronary events, 327 ischemic stroke, 368 cardiovascular deaths, and 1,308 all-cause deaths occurred. After controlling for death from other causes as competing events, only all-cause mortality remained significantly related to GDF-15. The addition of GDF-15 significantly improved prediction for all-cause mortality in addition to the traditional risk factors, high-sensitive C-reactive protein and N-terminal prohormone of brain natriuretic peptide. Only N-terminal prohormone of brain natriuretic peptide improved prediction for CVD mortality. CONCLUSIONS: GDF-15 is a robust biomarker for all-cause mortality but less reliable for coronary event, ischemic stroke or cardiovascular mortality. Competing risk from death is an important consideration when interpreting the results.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Fator 15 de Diferenciação de Crescimento/sangue , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Feminino , Produtos do Gene env/sangue , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Suécia/epidemiologia
3.
Medicine (Baltimore) ; 99(50): e23253, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327246

RESUMO

BACKGROUND: To evaluate the effect of anaesthesia and ICU sedation with sevoflurane to protect the myocardium against ischemia-reperfusion injury associated to cardiac surgery assessed by troponin release. METHODS: We performed a prospective, open-label, randomized study in cardiac surgery with cardiopulmonary bypass. Patients were randomized to an algorithm-based intervention group and a control group. The main outcome was the perioperative kinetic of cardiac troponin I (cTnI). The secondary outcomes included composite endpoint, GDF-15 (macrophage inhibitory cytokine-1) value, arterial lactate levels, and the length of stay (LOS) in the ICU. RESULTS: Of 82 included patients, 81 were analyzed on an intention-to-treat basis (intervention group: n = 42; control group: n = 39). On inclusion, the intervention and control groups did not differ significantly in terms of demographic and surgical data. The postoperative kinetics of cTnI did not differ significantly between groups: the mean difference was 0.44 ±â€Š1.09 µg/ml, P = .69. Incidence of composite endpoint and GDF-15 values were higher in the sevoflurane group than in propofol group. The intervention and control groups did not differ significantly in terms of ICU stay and hospital stay. CONCLUSION: The use of an anaesthesia and ICU sedation with sevoflurane was not associated with a lower incidence of myocardial injury assessed by cTnI. Sevoflurane administration was associated with higher prevalence of acute renal failure and higher GDF-15 values.


Assuntos
Anestesia por Inalação , Anestésicos Inalatórios , Ponte Cardiopulmonar , Sedação Profunda , Sevoflurano , Troponina I/sangue , Idoso , Anestesia por Inalação/métodos , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Cuidados Críticos/métodos , Sedação Profunda/métodos , Feminino , Fator 15 de Diferenciação de Crescimento/sangue , Humanos , Tempo de Internação , Masculino , Estudos Prospectivos
4.
Kardiologiia ; 60(9): 22-29, 2020 Oct 14.
Artigo em Russo | MEDLINE | ID: mdl-33131471

RESUMO

Aim To study the relationship between the serum level of growth differentiation factor 15 (GDF-15) and clinical and functional characteristics and severity of left atrial (LA) fibrosis in patients with nonvalvular atrial fibrillation (AF).Material and methods The study included 87 patients with nonvalvular AF (62 patients with paroxysmal AF and 25 patients with persistent AF) aged 27 to 72 years (mean age, 56.9±9.2 years, 32 women). 85 % of these patients had arterial hypertension (AH), 33 % had AH and ischemic heart disease, and 12.6 % had isolated AF and were hospitalized for primary catheter ablation. General clinical evaluation, echocardiography, laboratory tests including measurement of GDF-15 and NT-proBNP concentrations in blood were performed. As a surrogate substrate of LA fibrosis during the electroanatomical voltage mapping, the area of low-voltage (<0.5 mV) zones in LA was calculated, including the total LA fibrosis area (Sf, cm2) and a percentage of fibrosis of the total LA area (Sf%).Results Median concentration of GDF-15 was 767.5 [590.0; 951.0] pg /ml. The GDF-15 level positively correlated with age, presence and severity of AH and chronic heart failure, body mass index, and degree of obesity, CHA2DS2 VASc score, level of NT-proBNP, and LA fibrosis area (Sf and Sf%) and negatively correlated with the indexes of left ventricular diastolic function, e' septal and e' lateral. The area of fibrosis increased with increasing GDF-15 concentrations divided into quartiles; Sf% exceeded 20 % at GDF-15 levels higher than median. After a comparative analysis of patients with Sf% ≤20 % and >20 %, statistically significantly different variables were included into a stepwise logistic regression analysis. Two independent predictors of LA fibrosis >20% were identified: a concentration of GDF-15 higher than median (odd ratio (OR), 3.318, 95 % confidence interval (CI): 1.184-9.298) and LA volume index (OR, 1.079, 95 % CI: 1.014-1.147). According to results of the ROC analysis, the area under the curve (AUC) was 0.762 (p=0.000), the model specificity was 72.3 %, sensitivity was 72.4 %, and the prediction accuracy was 72.4 %.Conclusion Blood levels of GDF-15 were associated with the presence and severity of major risk factors for AF and the area of LA fibrosis. In this study, a level of GDF-15 above the median and the LA volume index were independent predictors of LA fibrosis > 20% of the LA area.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Fator 15 de Diferenciação de Crescimento , Adulto , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/patologia , Feminino , Fibrose , Fator 15 de Diferenciação de Crescimento/sangue , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Humanos , Pessoa de Meia-Idade
5.
Front Immunol ; 11: 581338, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123167

RESUMO

Objectives: The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS). Methods: This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14th and May 28th 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed. Results: All patients suffered from severe ARDS, 30.8% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and naïve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment. Conclusions: Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/patologia , Pneumonia Viral/patologia , Síndrome Respiratória Aguda Grave/patologia , Idoso , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Feminino , Fator 15 de Diferenciação de Crescimento/sangue , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Unidades de Terapia Intensiva , Interleucina-10/sangue , Interleucina-6/sangue , Estudos Longitudinais , Linfopenia , Masculino , Pessoa de Meia-Idade , Pandemias , Projetos Piloto , Pneumonia Viral/imunologia , Estudos Retrospectivos , Síndrome Respiratória Aguda Grave/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia
6.
Geriatr Gerontol Int ; 20(10): 980-987, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32886834

RESUMO

AIMS: Sarcopenia is a serious problem because of its poor prognosis. Growth differentiation factor 15 (GDF15) is associated with mitochondrial dysfunction, inflammation, insulin resistance and oxidative stress, which may play crucial roles for the development of sarcopenia. We aimed to examine whether serum GDF15 level is associated with muscle mass, strength and lower extremity function in older patients with cardiometabolic disease. METHODS: Serum GDF15 levels were measured in 257 patients with cardiometabolic diseases (including 133 patients with diabetes) who had visited the frailty clinic, using a latex turbidimetric immunoassay. Appendicular skeletal muscle index, handgrip strength, timed-up-and-go test and gait speed were evaluated. Power, speed, balance and total scores based on the sit-to-stand test were calculated to assess lower extremity function. RESULTS: The highest tertile of serum GDF15 was independently associated with low handgrip strength, low gait speed, long timed-up-and-go time and scores of lower extremity function but not an appendicular skeletal muscle index in multiple logistic regression analyses after adjustment for covariates. Patients in the highest tertile of GDF15 were at the risk of having three to nine times lower grip strength, three times lower gait speed, five to six times lower mobility and five to 11 times reduction in lower extremity function as compared with those in the lowest GDF15 tertile dependent on the models. CONCLUSIONS: Elevated serum GDF15 level was independently associated with low muscle strength and lower extremity function in older patients with cardiometabolic disease. Serum GDF15 could be one of the biomarkers for muscle weakness and low physical performance. Geriatr Gerontol Int 2020; 20: 980-987.


Assuntos
Doenças Cardiovasculares/sangue , Diabetes Mellitus/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Extremidade Inferior/fisiopatologia , Força Muscular/fisiologia , Sarcopenia/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus/fisiopatologia , Feminino , Fragilidade , Força da Mão , Humanos , Masculino , Músculo Esquelético/fisiopatologia , Sarcopenia/fisiopatologia , Estudos de Tempo e Movimento , Velocidade de Caminhada/fisiologia
7.
PLoS One ; 15(8): e0237059, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764826

RESUMO

Mortality disparities are influenced by race and poverty. There is limited information about whether poverty influences biologic markers of mortality risk. Emerging data suggests that growth differentiation factor 15 (GDF15) is associated with mortality; however, the interplay between GDF15, sociodemographic factors and mortality is not known. We sought to evaluate the interactions between GDF15 and sex, race and poverty status on mortality. Serum GDF15 was measured in 1036 African American and white middle-aged men and women above and below 125% of the Federal poverty status from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Multivariable adjusted Cox regression models were used to assess the association between log-transformed GDF15 (logGDF15) and 12-year mortality outcomes (all-cause, cardiovascular- and cancer-specific outcomes) and interactions with sex, race and poverty status. Likelihood ratio tests were used to assess significance of the interaction terms. Median GDF15 was 655.2 pg/mL (IQR = 575.1). During 12.2 years of follow-up, 331 died of which 94 cardiovascular- and 87 were cancer-specific deaths. One unit of increase in logGDF15 was associated with a hazard ratio for all-cause mortality, cardiovascular- and cancer-specific mortality of 2.26 (95% confidence interval [CI], 1.94-2.64), 2.74 (95%CI, 2.06-3.63) and 1.41 (95%CI, 1.00-2.00), respectively. There was an interaction between logGDF15 and poverty status on all-cause mortality (p<0.05). The GDF15×poverty status interaction term improved model calibration for all-cause mortality. Our study provides the first evidence that the effect of elevated GDF15 on all-cause mortality is modified by poverty status.


Assuntos
Fator 15 de Diferenciação de Crescimento/sangue , Mortalidade , Pobreza , Saúde da População Urbana , Adulto , Afro-Americanos , Biomarcadores/sangue , Grupo com Ancestrais do Continente Europeu , Feminino , Envelhecimento Saudável/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estados Unidos/epidemiologia , População Urbana
8.
J Stroke Cerebrovasc Dis ; 29(8): 104973, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689596

RESUMO

BACKGROUND AND PURPOSE: As intraarterial thrombectomy (IAT) has been actively practiced, blood biomarkers that can predict outcomes after IAT have drawn attention. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine and the levels are increased during inflammation or other pathological conditions of various tissues, including the brain. However, GDF-15 levels have not been reported as a biomarker for IAT outcomes. This study was performed to evaluate whether GDF-15 was related to the extent of brain damage and whether it could predict patient prognosis after IAT. METHODS: Patients who showed large arterial occlusion and significant diffusion-perfusion mismatch on imaging underwent IAT. A total of 62 patients who underwent IAT and had blood samples for GDF-15 measurements were enrolled from July 2013 to May 2015. We assessed the infarct severity by consecutive changes on the National Institutes of Health Stroke Scale (NIHSS) during admission and the size of the infarction on brain imaging. Modified Rankin Scale scores (mRS) from 0 to 2 were considered good outcomes, representing functional independence at discharge and three months later. RESULTS: The levels of GDF-15 at the time of admission were significantly correlated with the NIHSS scored at 24 hours (r = 0.306, p = 0.016), three days after IAT (r = 0.261, p = 0.041), and at discharge (r = 0.266, p = 0.037), as well as the infarct size on diffusion-weighted image taken 24 h after IAT (r = 0.452, p = 0.001), but the levels were not correlated with the initial NIHSS or the infarct size before IAT. Multiple logistic regression showed that GDF-15 levels were an independent predictor of functional independence (mRS 0 - 2) at discharge (p = 0.028) and three months after IAT (p = 0.019). Other factors that could predict prognosis were good collateral status on the initial brain angiography and rapid recanalization within six hours from symptom onset. CONCLUSION: The GDF-15 level at the time of admission showed a significant positive correlation with the severity of cerebral damage and clinical outcome after IAT. This suggests that GDF-15 can provide useful prognostic information for patients who successfully underwent IAT in an emergency setting.


Assuntos
Isquemia Encefálica/terapia , Fator 15 de Diferenciação de Crescimento/sangue , Acidente Vascular Cerebral/terapia , Trombectomia , Idoso , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Angiografia Cerebral , Imagem de Difusão por Ressonância Magnética , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Trombectomia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
9.
Ecotoxicol Environ Saf ; 199: 110697, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32416368

RESUMO

OBJECTIVES: Based on a prospective birth cohort, we aimed to investigate the associations between maternal circulating metals exposure and gestational weight gain (GWG) across pregnancy, and explore whether maternal inflammatory cytokines could contribute to the GWG changes associated with metals exposure. METHODS: A total of 234 pregnant women from the Shanghai Maternal-Child Pairs cohort were enrolled in this panel study. 547 blood and serum samples were collected from pregnant women during three follow-up visits, and the circulating concentrations of 27 metals were determined by using the ICP-MS method. Five inflammatory cytokines in serum samples were measured through multiplexed immunoassays. The linear mixed models were used to estimate the association between each ln-transformed metal concentration and GWG across pregnancy. Robust generalized linear regression models were used to estimate the associations among circulating metals, GWG, and inflammatory cytokines. RESULTS: The GWG during pregnancy was 13.76 ± 1.40 kg. The concentrations Co, Zn, Mo, B, Ag and Te in second or third trimesters were significantly higher than those in early second trimester. The concentration of Mg decreased with the increase of pregnant weeks and no significant statistical differences were found in the concentrations of other metals in different trimesters. Among the detected 26 metals, Li and Sr concentrations were positively associated with GWG in the third trimester. The GWG increased by 0.100 kg (95% CI 0.005, 0.195) and 0.120 kg (95% CI 0.009, 0.232) with each one ln-concentration increase in circulating Li and Sr concentrations, respectively. Concentrations of Li and Sr in the third trimester were positively associated with tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6, but negatively associated with growth differentiation factor-15 (GDF-15) significantly. Besides, IL-6 and GDF-15 levels were associated with the increase or decrease of overall pregnancy GWG, respectively. CONCLUSIONS: Results showed that maternal exposure to Li and Sr were associated with increased GWG, in which maternal IL-6 and GDF-15 could contribute to the associations between metal exposures and GWG in pregnant women.


Assuntos
Poluentes Ambientais/sangue , Ganho de Peso na Gestação/efeitos dos fármacos , Fator 15 de Diferenciação de Crescimento/sangue , Interleucina-6/sangue , Lítio/sangue , Exposição Materna/efeitos adversos , Estrôncio/sangue , Adulto , China , Estudos de Coortes , Feminino , Humanos , Gravidez , Trimestres da Gravidez , Estudos Prospectivos
10.
Nutr Metab Cardiovasc Dis ; 30(6): 925-931, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32278609

RESUMO

BACKGROUND AND AIMS: Growth differentiating factor-15 (GDF-15) is a stress-induced and cardio-protective cytokine, reported to be influenced by a number of cardiovascular risk factors. In older adults, GDF-15 associated with age, black ethnicity and smoking. It is important to determine if GDF-15 could potentially be used as an early marker of cardiovascular disease, especially in young populations. We investigated whether GDF-15 associated with traditional cardiovascular risk factors (age, sex, ethnicity, blood pressure (BP), socio-economic status, waist-to-hip ratio, cholesterol, physical inactivity, smoking and alcohol use) in young apparently healthy adults. METHODS AND RESULTS: We included 1189 black and white participants (aged between 20 and 30 years). Questionnaires were used to collect demographic and physical activity data. We measured serum GDF-15, and performed 24-h ambulatory BP and pulse wave analysis. The following risk factors increased with increasing GDF-15 quartiles: age, black ethnicity, central systolic BP, 24-h diastolic BP, tumour necrosis factor-alpha, lipids, cotinine, smoking and alcohol use (all p trend ≤ 0.013). Socio-economic status and physical activity (p trend ≤ 0.014) were the lowest in the highest quartile. In multi-variable adjusted regression analyses GDF-15 associated with central systolic BP (ß = 0.076; p = 0.027), age (ß = 0.096; p = 0.006), low socio-economic status (ß = -0.12; p = 0.003), physical inactivity (ß = -0.18; p < 0.0001), tumour necrosis factor-alpha (ß = 0.28; p < 0.0001) and cotinine (ß = 0.12; p < 0.0001). CONCLUSION: In young adults, GDF-15 associated independently with multiple traditional cardiovascular risk factors including higher central systolic blood pressure, older age, lower socio-economic status, physical inactivity, inflammation and smoking. These results suggest that GDF-15 is a promising biomarker for early identification of cardiovascular risk.


Assuntos
Doenças Cardiovasculares/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Adulto , Grupo com Ancestrais do Continente Africano , Fatores Etários , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etnologia , Grupo com Ancestrais do Continente Europeu , Feminino , Nível de Saúde , Humanos , Estilo de Vida , Estudos Longitudinais , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Determinantes Sociais da Saúde , Fatores Socioeconômicos , África do Sul/epidemiologia , Regulação para Cima , Adulto Jovem
11.
Cardiovasc Diabetol ; 19(1): 40, 2020 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-32222153

RESUMO

BACKGROUND: Clinical and basic investigations have indicated a significant association between circulating growth differentiation factor 15 (GDF15) and cardiovascular disease; however, the relationship between GDF15 and lower extremity atherosclerotic disease (LEAD) has been less studied. The present study aimed to explore the association between GDF15 and LEAD in Chinese patients with type 2 diabetes mellitus (T2DM). Considering that obesity is an important factor associated with circulating GDF15 levels, whether the relationship between serum GDF15 levels and LEAD is affected by body mass index (BMI) was also analysed. METHODS: A total of 376 hospitalized T2DM patients were enrolled (161 with LEAD and 215 without LEAD). A sandwich enzyme-linked immunosorbent assay was used to detect the serum GDF15 levels. The femoral intima-media thickness (F-IMT) and LEAD were assessed by ultrasonography. RESULTS: Patients with LEAD had significantly higher serum GDF15 levels than those without LEAD, regardless of whether their BMI was < 25 kg/m2 or ≥ 25 kg/m2 (both P < 0.05). Serum GDF15 levels were independently positively related to the F-IMT (standardized ß = 0.162, P = 0.002). After adjusting for confounding factors, per 1-standard deviation (SD) increase in the serum GDF15 levels was significantly related to an approximately 1.4-fold increased risk of LEAD in the total population (P < 0.05). Regardless of whether the BMI was < 25 kg/m2 or ≥ 25 kg/m2, this association remained significant, with approximately 1.6- and 1.4-fold increased risks of LEAD, respectively (both P < 0.05). CONCLUSIONS: High serum GDF15 levels were significantly correlated with an increased risk of LEAD in T2DM patients, and this relationship was independent of BMI.


Assuntos
Aterosclerose/sangue , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Extremidade Inferior/irrigação sanguínea , Obesidade/sangue , Adulto , Aterosclerose/diagnóstico por imagem , Aterosclerose/epidemiologia , Biomarcadores/sangue , Espessura Intima-Media Carotídea , China/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/epidemiologia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Regulação para Cima
12.
Dis Markers ; 2020: 6162892, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32089755

RESUMO

Growth differentiation factor 15 (GDF-15) is strongly associated with cardiovascular disease (CVD). The aim of our study was to evaluate plasma and urinary levels of GDF-15 after pediatric renal transplantation (Rtx) and in children with chronic kidney disease (CKD) and its associations to cardiovascular risk factors. In this cross-sectional study, GDF-15 was measured in plasma and urine from 53 children with a renal transplant and 83 children with CKD and related to cardiovascular risk factors (hypertension, obesity, and cholesterol) and kidney function. Forty healthy children served as a control group. Plasma levels of GDF-15 (median and range) for a Tx (transplantation) cohort, CKD cohort, and healthy controls were, respectively, 865 ng/L (463-3039 ng/L), 508 ng/L (183-3279 ng/L), and 390 ng/L (306-657 ng/L). The CKD and Tx cohorts both had significantly higher GDF-15 levels than the control group (p < 0.001). Univariate associations between GDF-15 and hyperuricemia (p < 0.001), elevated triglycerides (p = 0.028), low HDL (p = 0.038), and obesity (p = 0.028) were found. However, mGFR (p < 0.001) and hemoglobin (p < 0.001) were the only significant predictors of GDF-15 in an adjusted analysis. Urinary GDF-15/creatinine ratios were 448 ng/mmol (74-5013 ng/mmol) and 540 ng/mmol (5-14960 ng/mmol) in the Tx cohort and CKD cohort, respectively. In the CKD cohort, it was weakly correlated to mGFR (r = -0.343, p = 0.002). Plasma levels of GDF-15 are elevated in children with CKD and after Rtx. The levels were not associated with traditional cardiovascular risk factors but strongly associated with renal function.


Assuntos
Fator 15 de Diferenciação de Crescimento/sangue , Transplante de Rim/efeitos adversos , Insuficiência Renal Crônica/metabolismo , Regulação para Cima , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Fator 15 de Diferenciação de Crescimento/urina , Humanos , Rim/fisiopatologia , Testes de Função Renal , Masculino , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco
13.
Am J Surg ; 220(3): 725-730, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32014297

RESUMO

BACKGROUND: Sleeve gastrostomy (SG) induces significant weight loss primarily as a result of increased satiety and reduced food intake. Growth differentiation factor-15 (GDF15) is a satiety hormone which induces a dramatic reduction of food intake and body weight. OBJECTIVE: To assess the effect of sleeve gastrectomy on plasma GDF 15 level and the association with the weight loss and diabetes control after SG. METHOD: We assessed plasma GDF15 level in 21 patients (15 with obesity and 6 with obesity and diabetes) before and then at 1, 3 and 12 months after SG. RESULTS: GDF15 was significantly increased at 1 month after SG compared to before surgery level (301.9 ± 135.2 pg/ml vs 215.1 ± 119.9 pg/ml, respectively p<0.05) and increased even further at 3 months (338.86 ± 131.14 pg/ml, p<0.01) and remain elevated at 12 months (329.39 ± 152.1 pg/ml p<0.05) after SG. At 3 months after surgery, the increased GDF15 level was correlated with the magnitude of BMI loss (r2 = 0.204, p<0.05). CONCLUSION: SG induces a significant increase in GDF15 level which is correlated with the magnitude of BMI loss.


Assuntos
Gastrectomia/métodos , Fator 15 de Diferenciação de Crescimento/sangue , Perda de Peso , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
14.
Cerebrovasc Dis Extra ; 10(1): 11-20, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32028277

RESUMO

BACKGROUND AND PURPOSE: Cardioembolic stroke due to paroxysmal atrial fibrillation (AF) may account for 1 out of 4 cryptogenic strokes (CS) and transient ischemic attacks (TIAs). The purpose of this pilot study was to search for biomarkers potentially predicting incident AF in patients with ischemic stroke or TIA. METHODS: Plasma samples were collected from patients aged 18 years and older with ischemic stroke or TIA due to AF (n = 9) and large artery atherosclerosis (LAA) with ipsilateral carotid stenosis (n = 8) and age- and sex-matched controls (n = 10). Analyses were performed with the Olink technology simultaneously measuring 184 biomarkers of cardiovascular disease. For bioinformatics, acquired data were analyzed using gene set enrichment analysis (GSEA). Selected proteins were validated using ELISA. Individual receiver operating characteristic (ROC) curves and odds ratios from logistic regression were calculated. A randomForest (RF) model with out-of-bag estimate was applied for predictive modeling. RESULTS: GSEA indicated enrichment of proteins related to inflammatory response in the AF group. Interleukin (IL)-6, growth differentiation factor (GDF)-15, and pentraxin-related protein PTX3 were the top biomarkers on the ranked list for the AF group compared to the LAA group and the control group. ELISA validated increased expression of all tested proteins (GDF-15, PTX3, and urokinase plasminogen activator surface receptor [U-PAR]), except for IL-6. 19 proteins had the area under the ROC curve (AUC) over 0.85 including all of the proteins with significant evolution in the logistic regression. AUCs were very discriminant in distinguishing patients with and without AF (LAA and control group together). GDF-15 alone reached AUC of 0.95. Based on RF model, all selected participants in the tested group were classified correctly, and the most important protein in the model was GDF-15. CONCLUSIONS: Our results demonstrate an association between inflammation and AF and that multiple proteins alone and in combination may potentially be used as indicators of AF in CS and TIA patients. However, further studies including larger samples sizes are needed to support these findings. In the ongoing NOR-FIB study, we plan further biomarker assessments in patients with CS and TIA undergoing long-term cardiac rhythm monitoring with insertable cardiac monitors.


Assuntos
Fibrilação Atrial/sangue , Isquemia Encefálica/sangue , Mediadores da Inflamação/sangue , Ataque Isquêmico Transitório/sangue , Acidente Vascular Cerebral/sangue , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Biomarcadores/sangue , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Proteína C-Reativa/análise , Estudos de Casos e Controles , Feminino , Fator 15 de Diferenciação de Crescimento/sangue , Humanos , Incidência , Interleucina-6/sangue , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/epidemiologia , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Projetos Piloto , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Componente Amiloide P Sérico/análise , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia
15.
Biomed Res Int ; 2020: 3630568, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104689

RESUMO

Objective: To identify the clinical correlations between plasma growth differentiation factor-15 (GDF-15), skeletal muscle function, and acute muscle wasting in ICU patients with mechanical ventilation. In addition, to investigate its diagnostic value for ICU-acquired weakness (ICU-AW) and its predictive value for 90-day survival in mechanically ventilated patients. Methods: 95 patients with acute respiratory failure, who required mechanical ventilation therapy, were randomly selected among hospitalized patients from June 2017 to January 2019. The plasma GDF-15 level was detected by ELISA, the rectus femoris cross-sectional area (RFcsa) was measured by ultrasound, and the patient's muscle strength was assessed using the British Medical Research Council (MRC) muscle strength score on day 1, day 4, and day 7. Patients were divided into an ICU-AW group and a non-ICU-AW group according to their MRC-score on the 7th day. The differences in plasma GDF-15 level, MRC-score, and RFcsa between the two groups were compared on the 1st, 4th, and 7th day after being admitted to the ICU. Then, the correlations between plasma GDF-15 level, RFcsa loss, and MRC-score on day 7 were investigated. The receiver operating characteristic curve (ROC) was used to analyze the plasma GDF-15 level, RFcsa loss, and % decrease in RFcsa on the 7th day to the diagnosis of ICU-AW in mechanically ventilated patients. Moreover, the predictive value of GDF-15 on the 90-day survival status of patients was assessed using patient survival curves. Results: Based on whether the 7th day MRC-score was <48, 50 cases were included in the ICU-AW group and 45 cases in the non-ICU-AW group. The length of mechanical ventilation, ICU length of stay, and hospital length of stay were significantly longer in the ICU-AW group than in the non-ICU-AW group (all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all. Conclusion: The plasma GDF-15 concentration level was significantly associated with skeletal muscle function and muscle wasting on day 7 in ICU patients with mechanical ventilation. Therefore, it can be concluded that the plasma GDF-15 level on the 7th day has a high diagnostic yield for ICU-acquired muscle weakness, and it can predict the 90-day survival status of ICU mechanically ventilated patients.


Assuntos
Fator 15 de Diferenciação de Crescimento/sangue , Unidades de Terapia Intensiva , Debilidade Muscular , Respiração Artificial , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/sangue , Debilidade Muscular/mortalidade , Debilidade Muscular/terapia , /mortalidade , Taxa de Sobrevida
16.
Am Heart J ; 220: 97-107, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31805424

RESUMO

BACKGROUND: Cardiorespiratory fitness (CRF) is closely linked to health status and clinical outcomes in heart failure (HF) patients. We aimed to test whether biomarkers can reflect CRF and its change over time. METHODS: This post hoc analysis used data from ambulatory cohorts of heart failure with reduced ejection fraction (HFrEF) (IRONOUT) and heart failure with preserved ejection fraction (HFpEF) (RELAX). Cardiopulmonary exercise testing, 6-minute walk distance (6MWD), and serum biomarkers were measured at baseline and 16- or 24-week follow-up (for IRONOUT and RELAX respectively). Biomarkers included N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST2, growth differentiation factor-15, and Galectin-3. RESULTS: Analysis included 225 patients with HFrEF and 216 with HFpEF. Baseline peak VO2, VE/VCO2 slope, and 6MWD showed a mild correlation with the doubling of all 4 tested biomarkers in HFrEF and HFpEF. Following multivariable adjustment (including all biomarkers), the only significant association between change in biomarker and functional parameter in HFrEF was change in NT-proBNP and change in VE/VCO2 slope (3.596% increase per doubling, 95% CI 0.779-6.492, P = .012). In HFpEF, a decrease in peak VO2 was associated with an increase in NT-proBNP (-0.726 mL/min/kg per doubling, 95% CI -1.100 to -0.353, P < .001), and a decrease in 6MWD was associated with an increase in growth differentiation factor-15 (-31.606 m per doubling, 95% CI -61.404 to -1.809, P = .038). CONCLUSIONS: In these ambulatory trial cohorts, NT-proBNP was associated with baseline and change in CRF in HFrEF and HFpEF. In contrast, novel biomarkers do not appear suitable as a reliable surrogate for serial assessment of exercise capacity in HF patients given lack of consistent independent association with CRF beyond traditional risk factors and NT-proBNP.


Assuntos
Aptidão Cardiorrespiratória , Galectina 3/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Insuficiência Cardíaca/sangue , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Biomarcadores/sangue , Doença Crônica , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico/fisiologia , Fatores de Tempo , Teste de Caminhada
17.
Crit Care Clin ; 36(1): 141-153, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31733676

RESUMO

Right ventricular failure is common in critically ill patients, as it frequently results from pulmonary embolism or pulmonary hypertension, and can complicate sepsis and the acute respiratory distress syndrome. Right ventricular dysfunction can be challenging to manage and is associated with poor outcomes in this wide array of disease. Laboratory biomarkers are rapid, noninvasive, accurate, and widely available and thus are useful in the diagnosis and management of right ventricular dysfunction in the critically ill patient. This article discusses the pathophysiology of right ventricular failure and reviews the applications of commonly used biomarkers in right ventricular dysfunction in critical care.


Assuntos
Biomarcadores/sangue , Cuidados Críticos/métodos , Proteína 3 Ligante de Ácido Graxo/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Lipocalina-2/sangue , Disfunção Ventricular Direita/sangue , Disfunção Ventricular Direita/diagnóstico , Humanos , Valor Preditivo dos Testes , Disfunção Ventricular Direita/fisiopatologia , Disfunção Ventricular Direita/terapia
18.
Endocr J ; 67(1): 91-94, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31534059

RESUMO

Uterine sarcomas are rare and aggressive gynecologic tumors with poor prognosis; therefore, early diagnosis is crucial for therapy. However, it is very difficult to distinguish uterine sarcomas from leiomyomas which are common benign uterine tumors. Therefore, the development of a diagnostic method that utilizes reliable biomarkers to distinguish uterine sarcomas from leiomyomas is important so as to identify the rare tumors. The candidate factors as novel biomarkers were searched for in public databases and a pilot study was performed for confirmation. Growth differentiation factor-15 (GDF15), progranulin, and osteopontin were identified as candidate biomarkers for diagnosing uterine sarcoma. Thus, developing a rapid and easy method to measure these factors could help establish a screening system for uterine sarcomas. In this study, we developed a novel measurement system for these factors using a compact chemical luminescence immunological automatic analyzer POCubeTM. This assay system, which is based on the flow-through membrane immunoassay, completes the whole process and generates results within 15 min. Serum concentrations of these factors measured via POCubeTM correlated well with those measured using enzyme-linked immunosorbent assay (r = 0.994 for GDF15, r = 0.992 for progranulin, and r = 0.976 for osteopontin). The POCubeTM system provides rapid and easy measurement of these factors, thereby facilitating uterine sarcoma diagnosis.


Assuntos
Fator 15 de Diferenciação de Crescimento/sangue , Leiomioma/sangue , Osteopontina/sangue , Progranulinas/sangue , Sarcoma/sangue , Neoplasias Uterinas/sangue , Diagnóstico Diferencial , Feminino , Humanos , Imunoensaio , Leiomioma/diagnóstico , Projetos Piloto , Curva ROC , Sarcoma/diagnóstico , Sensibilidade e Especificidade , Fatores de Tempo , Neoplasias Uterinas/diagnóstico
19.
Heart ; 106(6): 467-473, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31492701

RESUMO

OBJECTIVE: Despite its predictive value for mortality in various diseases, the relevance of growth differentiation factor-15 (GDF-15) as prognostic biomarker in pulmonary hypertension (PH) remains unclear. This study investigated the association between GDF-15 and outcomes in adults with PH. METHODS: This is a single-centre prospective observational cohort study. All adults with PH were included at the day of their diagnostic right heart catheterisation between 2012 and 2016. PH due to left heart disease was excluded. Venous blood sampling was performed and included GDF-15 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements. Kaplan-Meier curves and Cox regression analysis were used to investigate the association between GDF-15 and a composite endpoint of death or lung transplantation. We adjusted for age and NT-proBNP in multivariable analysis. Reference values were established by GDF-15 measurements in healthy controls. RESULTS: GDF-15 was measured in 103 patients (median age 59.2 years, 65% women, 51% pulmonary arterial hypertension). GDF-15 was elevated in 76 patients (74%). After a median follow-up of 3.4 (IQR 2.3-4.6) years, 32 patients (31.1%) reached the primary endpoint. Event-free survival 2 years after diagnosis was 100% in patients with normal GDF-15 versus 72.4% in patients with elevated GDF-15 (p=0.007). A significant association was found between GDF-15 and the primary endpoint (HR per twofold higher value 1.77, 95% CI 1.39 to 2.27, p<0.001), also after adjustment for age and NT-proBNP (HR 1.41, 95% CI 1.02 to 1.94, p=0.038). CONCLUSIONS: High GDF-15 levels are associated with an increased risk of death or transplant in adults with PH, independent of age and NT-proBNP. As non-specific biomarker, GDF-15 could particularly be useful to detect low-risk patients.


Assuntos
Fator 15 de Diferenciação de Crescimento/sangue , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/mortalidade , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos
20.
J Gerontol A Biol Sci Med Sci ; 75(1): 175-180, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30874790

RESUMO

BACKGROUND: Growth and differentiation factor 15 (GDF-15) has been associated with obesity, muscle wasting, and cachexia. The receptor for GDF-15 was recently identified in the brainstem and regulates food intake and metabolism. The relationship of plasma GDF-15 with the age-associated decline of muscle mass and strength, gait speed, and physical performance in adults has not been well characterized. METHODS: Plasma GDF-15, grip strength, 6-m gait speed, 400-m walking test time, lower extremity physical performance score, appendicular lean mass, and fat mass were measured in 194 healthy adult participants, aged 22-93 years, of the Baltimore Longitudinal Study of Aging. RESULTS: Plasma GDF-15 concentrations increased with age (p < .001) and were higher in whites compared with blacks and Asians (p = .04). Adults with higher plasma GDF-15 had slower 6-m gait speed, longer 400-m walking time, and lower physical performance score in multivariable analyses adjusting for age and race. Plasma GDF-15 was not associated with grip strength, appendicular lean mass, or fat mass. CONCLUSIONS: Elevated plasma GDF-15 is associated with slower gait speed, higher 400-m walking time, and lower physical performance in very healthy community-dwelling adults. The relationship between plasma GDF-15 and sarcopenia-related outcomes may be stronger in the population not selected to be healthy, and this hypothesis should be tested in a representative population.


Assuntos
Envelhecimento/fisiologia , Marcha/fisiologia , Avaliação Geriátrica/métodos , Fator 15 de Diferenciação de Crescimento/sangue , Vida Independente , Sarcopenia/sangue , Velocidade de Caminhada/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Seguimentos , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Desempenho Físico Funcional , Estudos Prospectivos , Sarcopenia/epidemiologia , Sarcopenia/fisiopatologia , Adulto Jovem
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