Suplementação de Vitamina D Induz Remodelação Cardíaca em Ratos: Associação com a Proteína de Interação com a Tiorredoxina e a Tiorredoxina / Vitamin D Supplementation Induces Cardiac Remodeling in Rats: Association with Thioredoxin-Interacting Protein and Thioredoxin

Resumo Fundamento: A vitamina D (VD) tem um importante papel na função cardíaca. No entanto, a vitamina exerce uma curva "dose-resposta" bifásica na fisiopatologia cardiovascular e pode causar efeitos deletérios, mesmo em doses não tóxicas. A VD exerce suas funções celulares ligando-se ao seu receptor. Ainda, a expressão da proteína de interação com a tiorredoxina (TXNIP) é positivamente regulada pela VD. A TXNIP modula diferentes visa de sinalização celular que podem ser importantes para a remodelação cardíaca. Objetivos: Avaliar se a suplementação com VD leva à remodelação cardíaca, e se a TXNIP e a tiorredoxina (Trx) estão associadas com esse processo. Métodos: Duzentos e cinquenta ratos Wistar machos foram alocados em três grupos: controle (C, n=21), sem suplementação com VD; VD3 (n = 22) e VD10 (n=21), suplementados com 3,000 e 10,000 UI de VD/ kg de ração, respectivamente, por dois meses. Os grupos foram comparados por análise de variância (ANOVA) com um fator e teste post hoc de Holm-Sidak (variáveis com distribuição normal), ou pelo teste de Kruskal-Wallis e análise post-hoc de Dunn. O nível de significância para todos os testes foi de 5%. Resultados: A expressão de TXNIP foi mais alta e a atividade do Trx foi mais baixa no grupo VD10. Os animais que receberam suplementação com VD apresentaram aumento de hidroperóxido lipídico e diminuição de superóxido dismutase e glutationa peroxidase. A proteína Bcl-2 foi mais baixa no grupo VD10. Observou-se uma diminuição na β-oxidação de ácidos graxos, no ciclo do ácido tricarboxílico, na cadeia transportadora de elétrons, e um aumento na via glicolítica. Conclusão: A suplementação com VD levou à remodelação cardíaca e esse processo pode ser modulado por TXNIP e Trx, e consequentemente por estresse oxidativo.

Abstract Background: Vitamin D (VD) has been shown to play an important role in cardiac function. However, this vitamin exerts a biphasic "dose response" curve in cardiovascular pathophysiology and may cause deleterious effects, even in non-toxic doses. VD exerts its cellular functions by binding to VD receptor. Additionally, it was identified that the thioredoxin-interacting protein (TXNIP) expression is positively regulated by VD. TXNIP modulate different cell signaling pathways that may be important for cardiac remodeling. Objective: To evaluate whether VD supplementation lead to cardiac remodeling and if TXNIP and thioredoxin (Trx) proteins are associated with the process. Methods: A total of 250 Male Wistar rats were allocated into three groups: control (C, n=21), with no VD supplementation; VD3 (n = 22) and VD10 (n=21), supplemented with 3,000 and 10,000 IU of VD/ kg of chow respectively, for two months. The groups were compared by one-way analysis of variance (ANOVA) and Holm-Sidak post hoc analysis, (variables with normal distribution), or by Kruskal-Wallis test and Dunn's test post hoc analysis. The significance level for all tests was 5%. Results: TXNIP protein expression was higher and Trx activity was lower in VD10. The animals supplemented with VD showed increased lipid hydroperoxide and decreased superoxide dismutase and glutathione peroxidase. The protein Bcl-2 was lower in VD10. There was a decrease in fatty acid β-oxidation, tricarboxylic acid cycle and electron transport chain with shift to increase in glycolytic pathway. Conclusion: VD supplementation led to cardiac remodeling and this process may be modulated by TXNIP and Trx proteins and consequently oxidative stress.

Vitamin D Supplementation Induces Cardiac Remodeling in Rats: Association with Thioredoxin-Interacting Protein and Thioredoxin. / Suplementação de Vitamina D Induz Remodelação Cardíaca em Ratos: Associação com a Proteína de Interação com a Tiorredoxina e a Tiorredoxina.

BACKGROUND: Vitamin D (VD) has been shown to play an important role in cardiac function. However, this vitamin exerts a biphasic "dose response" curve in cardiovascular pathophysiology and may cause deleterious effects, even in non-toxic doses. VD exerts its cellular functions by binding to VD receptor. Additionally, it was identified that the thioredoxin-interacting protein (TXNIP) expression is positively regulated by VD. TXNIP modulate different cell signaling pathways that may be important for cardiac remodeling. OBJECTIVE: To evaluate whether VD supplementation lead to cardiac remodeling and if TXNIP and thioredoxin (Trx) proteins are associated with the process. METHODS: A total of 250 Male Wistar rats were allocated into three groups: control (C, n=21), with no VD supplementation; VD3 (n = 22) and VD10 (n=21), supplemented with 3,000 and 10,000 IU of VD/ kg of chow respectively, for two months. The groups were compared by one-way analysis of variance (ANOVA) and Holm-Sidak post hoc analysis, (variables with normal distribution), or by Kruskal-Wallis test and Dunn's test post hoc analysis. The significance level for all tests was 5%. RESULTS: TXNIP protein expression was higher and Trx activity was lower in VD10. The animals supplemented with VD showed increased lipid hydroperoxide and decreased superoxide dismutase and glutathione peroxidase. The protein Bcl-2 was lower in VD10. There was a decrease in fatty acid ß-oxidation, tricarboxylic acid cycle and electron transport chain with shift to increase in glycolytic pathway. CONCLUSION: VD supplementation led to cardiac remodeling and this process may be modulated by TXNIP and Trx proteins and consequently oxidative stress.

FUNDAMENTO: A vitamina D (VD) tem um importante papel na função cardíaca. No entanto, a vitamina exerce uma curva "dose-resposta" bifásica na fisiopatologia cardiovascular e pode causar efeitos deletérios, mesmo em doses não tóxicas. A VD exerce suas funções celulares ligando-se ao seu receptor. Ainda, a expressão da proteína de interação com a tiorredoxina (TXNIP) é positivamente regulada pela VD. A TXNIP modula diferentes visa de sinalização celular que podem ser importantes para a remodelação cardíaca. OBJETIVOS: Avaliar se a suplementação com VD leva à remodelação cardíaca, e se a TXNIP e a tiorredoxina (Trx) estão associadas com esse processo. MÉTODOS: Duzentos e cinquenta ratos Wistar machos foram alocados em três grupos: controle (C, n=21), sem suplementação com VD; VD3 (n = 22) e VD10 (n=21), suplementados com 3,000 e 10,000 UI de VD/ kg de ração, respectivamente, por dois meses. Os grupos foram comparados por análise de variância (ANOVA) com um fator e teste post hoc de Holm-Sidak (variáveis com distribuição normal), ou pelo teste de Kruskal-Wallis e análise post-hoc de Dunn. O nível de significância para todos os testes foi de 5%. RESULTADOS: A expressão de TXNIP foi mais alta e a atividade do Trx foi mais baixa no grupo VD10. Os animais que receberam suplementação com VD apresentaram aumento de hidroperóxido lipídico e diminuição de superóxido dismutase e glutationa peroxidase. A proteína Bcl-2 foi mais baixa no grupo VD10. Observou-se uma diminuição na ß-oxidação de ácidos graxos, no ciclo do ácido tricarboxílico, na cadeia transportadora de elétrons, e um aumento na via glicolítica. CONCLUSÃO: A suplementação com VD levou à remodelação cardíaca e esse processo pode ser modulado por TXNIP e Trx, e consequentemente por estresse oxidativo.

Zinc Supplementation Attenuates Cardiac Remodeling After Experimental Myocardial Infarction.

BACKGROUND/AIMS: The objective of our study was to evaluate the effects of zinc supplementation on cardiac remodeling following acute myocardial infarction in rats. METHODS: Animals were subdivided into 4 groups and observed for 3 months: 1) Sham Control; 2) Sham Zinc: Sham animals receiving zinc supplementation; 3) Infarction Control; 4) Infarction Zinc. After the followup period, we studied hypertrophy and ventricular geometry, functional alterations in vivo and in vitro, changes related to collagen, oxidative stress, and inflammation, assessed by echocardiogram, isolated heart study, western blot, flow cytometer, morphometry, and spectrophotometry. RESULTS: Infarction induced a significant worsening of the functional variables. On the other hand, zinc attenuated both systolic and diastolic cardiac dysfunction induced by infarction. Considering the infarct size, there was no difference between the groups. Catalase and superoxide dismutase decreased in infarcted animals, and zinc increased its activity. We found higher expression of collagens I and III in infarcted animals, but there was no effect of zinc supplementation. Likewise, infarcted animals had higher levels of IL-10, but without zinc interference. Nrf-2 values were not different among the groups. Infarction increased the amount of Treg cells in the spleen as well as the amount of total lymphocytes. Zinc increased the amount of CD4+ in infarcted animals, but we did not observe effects in relation to Treg cells. CONCLUSION: zinc attenuates cardiac remodeling after infarction in rats; this effect is associated with modulation of antioxidant enzymes, but without the involvement of collagens I and III, Nrf-2, IL-10, and Treg cells.

Cardiac Remodeling Induced by All-Trans Retinoic Acid is Detrimental in Normal Rats.

BACKGROUND/AIMS: This study aimed to discern whether the cardiac alterations caused by retinoic acid (RA) in normal adult rats are physiologic or pathologic. METHODS AND RESULTS: Wistar rats were assigned into four groups: control animals (C, n = 20) received a standard rat chow; animals fed a diet supplemented with 0.3 mg/kg/day all-trans-RA (AR1, n = 20); animals fed a diet supplemented with 5 mg/kg/day all-trans-RA (AR2, n = 20); and animals fed a diet supplemented with 10 mg/kg/day all-trans-RA (AR3, n = 20). After 2 months, the animals were submitted to echocardiogram, isolated heart study, histology, energy metabolism status, oxidative stress condition, and the signaling pathway involved in the cardiac remodeling induced by RA. RA increased myocyte cross-sectional area in a dose-dependent manner. The treatment did not change the morphological and functional variables, assessed by echocardiogram and isolated heart study. In contrast, RA changed catalases, superoxide dismutase, and glutathione peroxidases and was associated with increased values of lipid hydroperoxide, suggesting oxidative stress. RA also reduced citrate synthase, enzymatic mitochondrial complex II, ATP synthase, and enzymes of fatty acid metabolism and was associated with increased enzymes involved in glucose use. In addition, RA increased JNK 1/2 expression, without changes in TGF-ß, PI3K, AKT, NFκB, S6K, and ERK. CONCLUSION: In normal rats, RA induces cardiac hypertrophy in a dose-dependent manner. The non-participation of the PI3K/Akt pathway, associated with the participation of the JNK pathway, oxidative stress, and changes in energy metabolism, suggests that cardiac remodeling induced by RA supplementation is deleterious.

Association between Functional Variables and Heart Failure after Myocardial Infarction in Rats / Associação entre Variáveis Funcionais e Insuficiência Cardíaca após o Infarto do Miocárdio em Ratos

Background: Heart failure prediction after acute myocardial infarction may have important clinical implications. Objective: To analyze the functional echocardiographic variables associated with heart failure in an infarction model in rats. Methods: The animals were divided into two groups: control and infarction. Subsequently, the infarcted animals were divided into groups: with and without heart failure. The predictive values were assessed by logistic regression. The cutoff values predictive of heart failure were determined using ROC curves. Results: Six months after surgery, 88 infarcted animals and 43 control animals were included in the study. Myocardial infarction increased left cavity diameters and the mass and wall thickness of the left ventricle. Additionally, myocardial infarction resulted in systolic and diastolic dysfunction, characterized by lower area variation fraction values, posterior wall shortening velocity, E-wave deceleration time, associated with higher values of E / A ratio and isovolumic relaxation time adjusted by heart rate. Among the infarcted animals, 54 (61%) developed heart failure. Rats with heart failure have higher left cavity mass index and diameter, associated with worsening of functional variables. The area variation fraction, the E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate were functional variables predictors of heart failure. The cutoff values of functional variables associated with heart failure were: area variation fraction < 31.18%; E / A > 3.077; E-wave deceleration time < 42.11 and isovolumic relaxation time adjusted by heart rate < 69.08. Conclusion: In rats followed for 6 months after myocardial infarction, the area variation fraction, E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate are predictors of heart failure onset.

Fundamento: A predição de insuficiência cardíaca após o infarto agudo do miocárdio pode ter importantes implicações clínicas. Objetivo: Analisar as variáveis funcionais ecocardiográficas associadas com insuficiência cardíaca no modelo do infarto em ratos. Métodos: Os animais foram divididos em dois grupos: infarto e controle. Após, os animais infartados foram divididos em grupos com e sem insuficiência cardíaca. Os valores preditivos foram avaliados por regressão logística. Os valores de corte preditivos de insuficiência cardíaca foram determinados por meio de curvas ROC. Resultados: Após 6 meses da cirurgia, 88 animais com infarto e 43 animais controle foram incluídos no estudo. O infarto aumentou os diâmetros das cavidades esquerdas, a massa e a espessura da parede do ventrículo esquerdo. Adicionalmente, o infarto resultou em disfunção sistólica e diastólica, caracterizada por menores valores da fração de variação de área, velocidade de encurtamento da parede posterior, tempo de desaceleração da onda E, associada com maiores valores da relação E/A e tempo de relaxamento isovolumétrico ajustado pela frequência cardíaca. Dentre os animais infartados, 54 (61%) desenvolveram insuficiência cardíaca. Ratos com insuficiência cardíaca apresentaram maiores índices de massa e diâmetros das cavidades esquerdas, associadas com piora das variáveis funcionais. A fração de variação de área, relação E/A, tempo de desaceleração da onda E e tempo de relaxamento isovolumétrico ajustado pela frequência cardíaca foram variáveis funcionais preditoras de insuficiência cardíaca. Os valores de corte das variáveis funcionais associados com insuficiência cardíaca foram: fração de variação de área < 31,18%; E/A > 3,077; tempo de desaceleração da onda E < 42,11 e tempo de relaxamento isovolumétrico ajustado pela frequência cardíaca < 69,08. Conclusão: Em ratos acompanhados por 6 meses após o infarto, a fração de variação de área, relação E/A, tempo de desaceleração da onda E e tempo de relaxamento isovolumétrico ajustado pela frequência cardíaca são preditores do aparecimento de insuficiência cardíaca.

Association between Functional Variables and Heart Failure after Myocardial Infarction in Rats.

BACKGROUND: Heart failure prediction after acute myocardial infarction may have important clinical implications. OBJECTIVE: To analyze the functional echocardiographic variables associated with heart failure in an infarction model in rats. METHODS: The animals were divided into two groups: control and infarction. Subsequently, the infarcted animals were divided into groups: with and without heart failure. The predictive values were assessed by logistic regression. The cutoff values predictive of heart failure were determined using ROC curves. RESULTS: Six months after surgery, 88 infarcted animals and 43 control animals were included in the study. Myocardial infarction increased left cavity diameters and the mass and wall thickness of the left ventricle. Additionally, myocardial infarction resulted in systolic and diastolic dysfunction, characterized by lower area variation fraction values, posterior wall shortening velocity, E-wave deceleration time, associated with higher values of E / A ratio and isovolumic relaxation time adjusted by heart rate. Among the infarcted animals, 54 (61%) developed heart failure. Rats with heart failure have higher left cavity mass index and diameter, associated with worsening of functional variables. The area variation fraction, the E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate were functional variables predictors of heart failure. The cutoff values of functional variables associated with heart failure were: area variation fraction < 31.18%; E / A > 3.077; E-wave deceleration time < 42.11 and isovolumic relaxation time adjusted by heart rate < 69.08. CONCLUSION: In rats followed for 6 months after myocardial infarction, the area variation fraction, E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate are predictors of heart failure onset.

Tomato (Lycopersicon esculentum) Supplementation Induces Changes in Cardiac miRNA Expression, Reduces Oxidative Stress and Left Ventricular Mass, and Improves Diastolic Function.

The aim of this study was to evaluate the effects of tomato supplementation on the normal rat heart and the role of oxidative stress in this scenario. Male Wistar rats were assigned to two groups: a control group (C; n = 16), in which animals received a control diet + 0.5 mL of corn oil/kg body weight/day, and a tomato group (T; n = 16), in which animals received a control diet supplemented with tomato +0.5 mL of corn oil/kg body weight/day. After three months, morphological, functional, and biochemical analyses were performed. Animals supplemented with tomato had a smaller left atrium diameter and myocyte cross-sectional area (CSA) compared to the control group (C group: 474 (415-539); T group: 273 (258-297) µm²; p = 0.004). Diastolic function was improved in rats supplemented with tomato. In addition, lipid hydroperoxide was lower (C group: 267 ± 46.7; T group: 219 ± 23.0 nmol/g; p = 0.039) in the myocardium of rats supplemented with tomato. Tomato intake was also associated with up-regulation of miR-107 and miR-486 and down-regulation of miR-350 and miR-872. In conclusion, tomato supplementation induces changes in miRNA expression and reduces oxidative stress. In addition, these alterations may be responsible for CSA reduction and diastolic function improvement.

Pamidronate attenuates diastolic dysfunction induced by myocardial infarction associated with changes in geometric patterning.

BACKGROUND/AIMS: The aim of this study was to evaluate the influence of pamidronate on ventricular remodeling after myocardial infarction. METHODS: Male Wistar rats were assigned to four groups: a sham group, in which animals were submitted to simulated surgery and received weekly subcutaneous injection of saline (S group; n=14); a group in which animals received weekly subcutaneous injection of pamidronate (3 mg/kg of body weight) and were submitted to simulated surgery (SP group, n=14); a myocardial infarction group, in which animals were submitted to coronary artery ligation and received weekly subcutaneous injection of saline (MI group, n=13); and a myocardial infarction group with pamidronate treatment (MIP group, n=14). The rats were observed for three months. RESULTS: Animals submitted to MI had left chamber enlargement and worse diastolic and systolic function compared with SHAM groups. E/A ratio, LV posterior and relative wall thickness were lower in the MIP compared with the MI group. There was no interaction between pamidronate administration and MI on systolic function, myocyte hypertrophy, collagen content, and calcium handling proteins. CONCLUSION: Pamidronate attenuates diastolic dysfunction following MI.

Periostin as a modulator of chronic cardiac remodeling after myocardial infarction.

OBJECTIVE: After acute myocardial infarction, during the cardiac repair phase, periostin is released into the infarct and activates signaling pathways that are essential for the reparative process. However, the role of periostin in chronic cardiac remodeling after myocardial infarction remains to be elucidated. Therefore, the objective of this study was to investigate the relationship between tissue periostin and cardiac variables in the chronic cardiac remodeling induced by myocardial infarction. METHODS: Male Wistar rats were assigned to 2 groups: a simulated surgery group (SHAM; n = 8) and a myocardial infarction group (myocardial infarction; n = 13). After 3 months, morphological, functional and biochemical analyses were performed. The data are expressed as means±SD or medians (including the lower and upper quartiles). RESULTS: Myocardial infarctions induced increased left ventricular diastolic and systolic areas associated with a decreased fractional area change and a posterior wall shortening velocity. With regard to the extracellular matrix variables, the myocardial infarction group presented with higher values of periostin and types I and III collagen and higher interstitial collagen volume fractions and myocardial hydroxyproline concentrations. In addition, periostin was positively correlated with type III collagen levels (r = 0.673, p = 0.029) and diastolic (r = 0.678, p = 0.036) and systolic (r = 0.795, p = 0.006) left ventricular areas. Considering the relationship between periostin and the cardiac function variables, periostin was inversely correlated with both the fractional area change (r = -0.783, p = 0.008) and the posterior wall shortening velocity (r = -0.767, p = 0.012). CONCLUSIONS: Periostin might be a modulator of deleterious cardiac remodeling in the chronic phase after myocardial infarction in rats.

Mechanisms involved in the beneficial effects of spironolactone after myocardial infarction.

INTRODUCTION: Our objective was to analyze the effect of spironolactone on cardiac remodeling after experimental myocardial infarction (MI), assessed by matricellular proteins levels, cardiac collagen amount and distribution, myocardial tissue metalloproteinase inhibitor-1 (TIMP-1) concentration, myocyte hypertrophy, left ventricular architecture, and in vitro and in vivo cardiac function. METHODS: Wistar rats were assigned to 4 groups: control group, in which animals were submitted to simulated surgery (SHAM group; n=9); group that received spironolactone and in which animals were submitted to simulated surgery (SHAM-S group, n=9); myocardial infarction group, in which animals were submitted to coronary artery ligation (MI group, n=15); and myocardial infarction group with spironolactone supplementation (MI-S group, n=15). The rats were observed for 3 months. RESULTS: The MI group had higher values of left cardiac chambers and mass index and lower relative wall thicknesses compared with the SHAM group. In addition, diastolic and systolic functions were worse in the MI groups. However, spironolactone did not influence any of these variables. The MI-S group had a lower myocardial hydroxyproline concentration and myocyte cross-sectional area compared with the MI group. Myocardial periostin and collagen type III were lower in the MI-S group compared with the MI-group. In addition, TIMP-1 concentration in myocardium was higher in the MI-S group compared with the MI group. CONCLUSIONS: The predominant consequence of spironolactone supplementation after MI is related to reductions in collagens, with discrete attenuation of other remodeling variables. Importantly, this effect may be modulated by periostin and TIMP-1 levels.

Periostin as a modulator of chronic cardiac remodeling after myocardial infarction

OBJECTIVE: After acute myocardial infarction, during the cardiac repair phase, periostin is released into the infarct and activates signaling pathways that are essential for the reparative process. However, the role of periostin in chronic cardiac remodeling after myocardial infarction remains to be elucidated. Therefore, the objective of this study was to investigate the relationship between tissue periostin and cardiac variables in the chronic cardiac remodeling induced by myocardial infarction. METHODS: Male Wistar rats were assigned to 2 groups: a simulated surgery group (SHAM; n = 8) and a myocardial infarction group (myocardial infarction; n = 13). After 3 months, morphological, functional and biochemical analyses were performed. The data are expressed as means±SD or medians (including the lower and upper quartiles). RESULTS: Myocardial infarctions induced increased left ventricular diastolic and systolic areas associated with a decreased fractional area change and a posterior wall shortening velocity. With regard to the extracellular matrix variables, the myocardial infarction group presented with higher values of periostin and types I and III collagen and higher interstitial collagen volume fractions and myocardial hydroxyproline concentrations. In addition, periostin was positively correlated with type III collagen levels (r = 0.673, p = 0.029) and diastolic (r = 0.678, p = 0.036) and systolic (r = 0.795, p = 0.006) left ventricular areas. Considering the relationship between periostin and the cardiac function variables, periostin was inversely correlated with both the fractional area change (r = -0.783, p = 0.008) and the posterior wall shortening velocity (r = -0.767, p = 0.012). CONCLUSIONS: Periostin might be a modulator of deleterious cardiac remodeling in the chronic phase after myocardial infarction in rats. .

Serum metalloproteinases 2 and 9 as predictors of gait status, pressure ulcer and mortality after hip fracture.

INTRODUCTION: The aim of this study is to evaluate the serum activity of metalloproteinases (MMPs) -2 and -9 as predictors of pressure ulcer (PU), gait status and mortality 6 months after hip fracture. METHODS: Eighty-seven patients over the age of 65 admitted to the orthopedic unit from January to December 2010 with hip fracture were prospectively evaluated. Upon admission, patient demographic information, including age, gender and concomitant diseases, was recorded. Blood samples were taken for analysis of MMP -2 and -9 activity by gel zymography and for biochemical examination within the first 72 hours of the patient's admission, after clinical stabilization. The fracture pattern (neck, trochanteric or subtrochanteric), time from admission to surgery, surgery duration and length of hospital stay were also recorded. RESULTS: Two patients were excluded due to the presence of pathological fractures (related to cancer), and three patients were excluded due to the presence of PU before admission. Eighty-two patients, with a mean age of 80.4 ± 7.3 years, were included in the analysis. Among these patients, 75.6% were female, 59.8% had PU, and 13.4% died 6 months after hip fracture. All patients underwent hip fracture repair. In a univariate analysis, there were no differences in serum MMP activity between hip fracture patients with or without PU. In addition, the multiple logistic regression analysis models, which were adjusted by age, gender, length of hospital stay and C-reactive protein, showed that the pro-MMP-9 complexed with neutrophil gelatinase-associated lipocalin form (130 kDa) was associated with gait status recovery 6 months after hip fracture. CONCLUSIONS: In conclusion, serum pro-MMP-9 is a predictor of gait status recovery 6 months after hip fracture.

Mini Nutritional Assessment predicts gait status and mortality 6 months after hip fracture.

The aim of the present study was to evaluate the Mini Nutritional Assessment (MNA), the Nutritional Risk Screening (NRS) 2002 and the American Society of Anesthesiologists Physical Status Score (ASA) as predictors of gait status and mortality 6 months after hip fracture. A total of eighty-eight consecutive patients over the age of 65 years with hip fracture admitted to an orthopaedic unit were prospectively evaluated. Within the first 72 h of admission, each patient's characteristics were recorded, and the MNA, the NRS 2002 and the ASA were performed. Gait status and mortality were evaluated 6 months after hip fracture. Of the total patients, two were excluded because of pathological fractures. The remaining eighty-six patients (aged 80·2 (sd 7·3) years) were studied. Among these patients 76·7 % were female, 69·8 % walked with or without support and 12·8 % died 6 months after the fracture. In a multivariate analysis, only the MNA was associated with gait status 6 months after hip fracture (OR 0·773, 95 % CI 0·663, 0·901; P= 0·001). In the Cox regression model, only the MNA was associated with mortality 6 months after hip fracture (hazard ratio 0·869, 95 % CI 0·757, 0·998; P= 0·04). In conclusion, the MNA best predicts gait status and mortality 6 months after hip fracture. These results suggest that the MNA should be included in the clinical stratification of patients with hip fracture to identify and treat malnutrition in order to improve the outcomes.