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1.
Eur J Clin Invest ; 47(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28981140

RESUMO

BACKGROUND: Profilin-1 is a ubiquitous, actin-binding protein that plays an important role in the regulation of actin polymerization and cytoskeleton remodelling and contributes to vascular dysfunction. We conducted this study to investigate the association of serum profilin-1 levels with fatal and nonfatal CVE in a cohort of patients with stage 1-5 CKD. MATERIALS AND METHODS: Serum concentrations of profilin-1 levels were determined by enzyme-linked immunosorbent assay. Endothelium-dependent vasodilatation (flow-mediated dilatation [FMD]) and endothelium-independent vasodilatation (nitroglycerine-mediated dilatation [NMD]) of the brachial artery were assessed noninvasively, using high-resolution ultrasound. RESULTS: Both fatal and nonfatal CVE were significantly higher in patients with high profilin-1 levels. Kaplan-Meier survival curves showed that patients with profilin-1 below the median value (114 pg/mL) had higher cumulative survival compared with patients who had profilin-1 levels above the median value (log-rank test, P < .001). CONCLUSIONS: This is the first study that demonstrates the serum profilin-1 is independently associated with endothelial dysfunction, cardiovascular events and survival in patients with CKD.


Assuntos
Doenças Cardiovasculares/sangue , Profilinas/sangue , Insuficiência Renal Crônica/sangue , Adulto , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiopatologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Causas de Morte , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mortalidade , Prognóstico , Insuficiência Renal Crônica/fisiopatologia , Ultrassonografia , Vasodilatação/fisiologia
2.
Blood Press ; 24(1): 55-60, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25390761

RESUMO

Vascular inflammation plays an important role in the pathophysiology of hypertension and high levels of endocan may reflect ongoing vascular inflammation in hypertensive patients. In the present hypothesis-generating study, we aimed at investigating the comparative effects of amlodipine and valsartan on endocan levels in newly diagnosed hypertensive patients. The study population consisted of 37 untreated hypertensive patients who were randomized to the two treatment arms. After baseline assessment, each patient was randomly allocated to either 10 mg daily of amlodipine (n = 18, 7 males) or 160 mg daily of valsartan (n = 19, 3 males) and treated for a 3-month period. Sphygmomanometric blood pressure (BP) and serum endocan were measured before and every 2 weeks during drug treatment. There was no statistically significant difference between the two treatment arms as far as baseline socio-demographic and clinical characteristics are concerned. After a 3-month treatment period, systolic and diastolic BP values significantly reduced by antihypertensive treatment (p < 0.001). Furthermore, endocan levels were significantly decreased in both treatment arms (p < 0.05). However, amlodipine caused a greater percent decrease in circulating endocan levels compared with valsartan at the end of the treatment period. Both drugs reduced high sensitivity C-reactive protein values. However, the statistical significant difference vs baseline was achieved only in the group treated with amlodipine. No correlation was found between endocan plasma levels and BP reduction. The results of this hypothesis-generating study suggest that amlodipine and valsartan decrease endocan levels in newly diagnosed hypertensive patients. The effects, which are more evident with amlodipine, may contribute to the anti-inflammatory effects exerted by the two drugs on the vascular target.


Assuntos
Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Endotélio Vascular , Hipertensão , Proteínas de Neoplasias/sangue , Proteoglicanas/sangue , Tetrazóis/administração & dosagem , Valina/análogos & derivados , Adulto , Pressão Sanguínea/efeitos dos fármacos , Proteína C-Reativa , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Hipertensão Essencial , Feminino , Humanos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valina/administração & dosagem , Valsartana
3.
Kidney Int ; 86(6): 1213-20, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24988065

RESUMO

Plasma endocan levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. There are currently no data on endocan in patients with chronic kidney disease (CKD). Therefore, we measured plasma endocan in 251 patients with CKD (stage 1-5) and 60 control individuals. Plasma endocan concentrations correlated with estimated glomerular filtration rate (eGFR), different markers of inflammation (pentraxin 3 and high-sensitivity C-reactive protein), and vascular abnormalities (flow-mediated vasodilation (FMV) and carotid intima media thickness (CIMT)). All-cause mortality and cardiovascular events (CVE) were also analyzed with respect to plasma endocan. Patients with CKD showed significantly increased plasma endocan (4.7 [IQR 1.9-9.4] compared with controls [IQR 1.1-1.5] ng/ml), with values progressively higher across stages of CKD. On univariate analysis, plasma endocan concentrations correlated negatively with eGFR and FMV, but positively with both markers of inflammation and CIMT. However, on multivariate analysis only high-sensitivity C-reactive protein, FMV, and CIMT remained significantly associated with plasma endocan. On Cox survival analysis, endocan levels were associated with all-cause mortality and CVE in these patients. Thus, plasma endocan increases in the presence of decreasing eGFR and influences all-cause mortality and CVE in patients with CKD independent of traditional and nontraditional risk factors.


Assuntos
Doenças Cardiovasculares/sangue , Proteínas de Neoplasias/sangue , Proteoglicanas/sangue , Insuficiência Renal Crônica/sangue , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/etiologia , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Feminino , Taxa de Filtração Glomerular , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/mortalidade , Fatores de Risco , Componente Amiloide P Sérico/metabolismo , Vasodilatação/fisiologia
4.
Rheumatology (Oxford) ; 53(11): 2002-8, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24907154

RESUMO

OBJECTIVES: Secondary amyloidosis is the most important complication of FMF and endothelial function is more severely impaired. Elevated asymmetric dimethyl arginine (ADMA) may mediate the excess cardiovascular disease (CVD) risk of this group. We aimed to compare endothelial function characteristics, including ADMA, in patients with FMF-related amyloidosis and primary glomerulopathies and to define risk factors for a CVD event. METHODS: We undertook a cross-sectional study with prospective follow-up including consecutive patients with FMF-related amyloidosis (n = 98) or other non-diabetic glomerulopathies (n = 102). All patients had nephrotic-range proteinuria and normal glomerular filtration rate. Flow-mediated dilatation (FMD) was assessed and ADMA levels, CRP and pentraxin 3 (PTX3) were determined. Patients were followed for cardiovascular events. RESULTS: Amyloidosis patients secondary to FMF showed higher levels of ADMA, CRP and PTX3 and lower FMD as compared with patients with other glomerulopathies. Cardiovascular events (n = 54) were registered during 3 years of follow-up. Increased ADMA levels and lower FMD were observed in patients with cardiovascular risk in both groups, but especially in individuals with amyloidosis. CONCLUSION: Patients with FMF-related amyloidosis have increased CVD event risk, probably related to the high ADMA levels, elevated inflammatory markers and decreased FMD measures observed in these patients.


Assuntos
Amiloidose/complicações , Doenças Cardiovasculares/etiologia , Endotélio Vascular/fisiopatologia , Febre Familiar do Mediterrâneo/complicações , Vasodilatação/fisiologia , Adolescente , Adulto , Amiloidose/fisiopatologia , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Febre Familiar do Mediterrâneo/fisiopatologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Turquia/epidemiologia , Adulto Jovem
5.
Am J Med Sci ; 347(2): 118-24, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23928544

RESUMO

BACKGROUND: Red cell distribution width (RDW) is a measure of erythrocyte size variability and has been shown as an independent predictor of mortality. The aim of this article was to evaluate the association of RDW with endothelial dysfunction in patients with chronic kidney disease (CKD). METHODS: Patients with 1 to 5 stages of CKD were included in the study. Endothelial function was assessed with flow-mediated dilatation (FMD). Estimated glomerular filtration rate (eGFR) and carotid intima media thickness (CIMT) were determined. Clinicodemographic characteristics, biochemical values, complete blood counts, ferritin, C-reactive protein (CRP) and cholesterol levels were recorded. Spearman's correlation was used to determine correlates of RDW. Multivariate linear regression model was used to assess independent associates of FMD. RESULTS: Overall, 367 patients with CKD 1 to 5 were included in the study. RDW showed a significant increase from stage 1 to stage 5 CKD. Median RDW was 13.5. Patients with RDW values higher than median had significantly lower hemoglobin, eGFR and FMD values and higher CIMT and CRP values compared with patients who had RDW values below median. RDW showed a significant positive correlation with the presence of diabetes mellitus, CIMT and CRP, whereas a significant negative correlation with eGFR, ferritin and FMD. Multivariate analysis showed independent predictors of FMD as RDW, presence of diabetes, hemoglobin, eGFR, CRP, and serum albumin. CONCLUSIONS: Multivariate regression model revealed RDW as a significant predictor of FMD independent of major confounding factors, such as diabetes, inflammation, anemia and kidney function in CKD.


Assuntos
Endotélio Vascular/patologia , Eritrócitos/citologia , Eritrócitos/fisiologia , Insuficiência Renal Crônica/patologia , Adulto , Idoso , Espessura Intima-Media Carotídea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada
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