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1.
Int J Mol Sci ; 25(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38791535

RESUMO

Hypercholesterolemia-associated oxidative stress increases the formation of oxidized low-density lipoprotein (oxLDL), which can affect endothelial cell function and potentially contribute to renal dysfunction, as reflected by changes in urinary protein excretion. This study aimed to investigate the impact of exogenous oxLDL on urinary excretion of albumin and nephrin. LDL was isolated from a patient with familial hypercholesterolemia (FH) undergoing lipoprotein apheresis (LA) and was oxidized in vitro with Cu (II) ions. Biochemical markers of LDL oxidation, such as TBARS, conjugated dienes, and free ε-amino groups, were measured. Wistar rats were treated with a single intraperitoneal injection of PBS, LDL, or oxLDL (4 mg of protein/kg b.w.). Urine was collected one day before and two days after the injection. We measured blood lipid profiles, urinary protein excretion (specifically albumin and nephrin), and markers of systemic oxidative stress (8-OHdG and 8-iso-PGF2α). The results showed that injection of oxLDL increased urinary albumin excretion by approximately 28% (310 ± 27 µg/24 h vs. 396 ± 26 µg/24 h, p = 0.0003) but had no effect on nephrin excretion. Neither PBS nor LDL had any effect on urinary albumin or nephrin excretion. Additionally, oxLDL did not affect systemic oxidative stress. In conclusion, hypercholesterolemia may adversely affect renal function through oxidatively modified LDL, which interferes with the renal handling of albumin and leads to the development of albuminuria.


Assuntos
Albuminúria , Lipoproteínas LDL , Estresse Oxidativo , Ratos Wistar , Lipoproteínas LDL/sangue , Lipoproteínas LDL/metabolismo , Animais , Humanos , Ratos , Albuminúria/urina , Masculino , Oxirredução , Proteínas de Membrana/metabolismo , Hiperlipoproteinemia Tipo II/metabolismo , Hiperlipoproteinemia Tipo II/urina
2.
Clin Chem Lab Med ; 59(5): 857-867, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33554544

RESUMO

OBJECTIVES: Low-density lipoprotein cholesterol (LDL-C) is the main laboratory parameter used for the management of cardiovascular disease. The aim of this study was to compare measured LDL-C with LDL-C as calculated by the Friedewald, Martin/Hopkins, Vujovic, and Sampson formulas with regard to triglyceride (TG), LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C)/TG ratio. METHODS: The 1,209 calculated LDL-C results were compared with LDL-C measured using ultracentrifugation-precipitation (first study) and direct (second study) methods. The Passing-Bablok regression was applied to compare the methods. The percentage difference between calculated and measured LDL-C (total error) and the number of results exceeding the total error goal of 12% were established. RESULTS: There was good correlation between the measurement and calculation methods (r 0.962-0.985). The median total error ranged from -2.7%/+1.4% (first/second study) for Vujovic formula to -6.7%/-4.3% for Friedewald formula. The numbers of underestimated results exceeding the total error goal of 12% were 67 (Vujovic), 134 (Martin/Hopkins), 157 (Samspon), and 239 (Friedewald). Less than 7% of those results were obtained for samples with TG >4.5 mmol/L. From 57% (Martin/Hopkins) to 81% (Vujovic) of underestimated results were obtained for samples with a non-HDL-C/TG ratio of <2.4. CONCLUSIONS: The Martin/Hopkins, Vujovic and Sampson formulas appear to be more accurate than the Friedewald formula. To minimize the number of significantly underestimated LDL-C results, we propose the implementation of risk categories according to non-HDL-C/TG ratio and suggest that for samples with a non-HDL-C/TG ratio of <1.2, the LDL-C level should not be calculated but measured independently from TG level.


Assuntos
Doenças Cardiovasculares , LDL-Colesterol , Humanos , Reprodutibilidade dos Testes , Triglicerídeos , Ultracentrifugação
3.
J Clin Apher ; 36(3): 370-378, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33386762

RESUMO

BACKGROUND: Lipoprotein apheresis (LA) is a safe method of reducing atherogenic lipoproteins and improving cardiovascular (CV) outcomes. We aimed to assess the reductions in low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] levels in patients undergoing regular LA therapy and to evaluate its influence on the incidence rate of adverse cardiac and vascular events (ACVE) and major adverse cardiac events (MACE). METHODS: A longitudinal study in Poland evaluated the prospective and retrospective observational data of 23 patients with hyperlipoproteinaemia (a) [hyper-Lp(a)] and familial hypercholesterolemia (FH), undergoing 1014 LA sessions between 2013 and 2020. Their pre- and post-apheresis LDL-C and Lp(a) levels were assessed to calculate the acute percent reductions. The time period used to evaluate annual rates of ACVE and MACE before and after initiation of LA was matched in each patient. RESULTS: The pre-apheresis LDL-C and Lp(a) concentrations were 155 (107-228) (mg/dL) (median and interquartile range) and 0.56 (0.14-1.37) (g/L), respectively. LA therapy resulted in a reduction of LDL-C to 50 (30-73.5) (mg/dL) and of Lp(a) to 0.13 (0.05-0.34) (g/L), representing a percent reduction of 70.0% and 72.7% for LDL-C and Lp(a), respectively. We found a significant reduction in the annual rate of ACVE (0.365[0.0-0.585] vs (0.0[0.0-0.265]; P = .047) and MACE (0.365[0.0-0.585] vs 0.0[0.0-0.265]; P = .031). CONCLUSIONS: The findings of our study indicate that LA treatment in patients with hyperlipoproteinaemia (a) and FH on maximally tolerated lipid lowering therapies leads to a substantial reduction in LDL-C and Lp(a) concentrations and lowers CV event rates in Polish patients.


Assuntos
Remoção de Componentes Sanguíneos/métodos , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/terapia , Hiperlipoproteinemias/terapia , Lipoproteína(a)/sangue , Adulto , Idoso , Doenças Cardiovasculares/sangue , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/complicações , Estudos Longitudinais , Pessoa de Meia-Idade
4.
Microvasc Res ; 129: 103974, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31923388

RESUMO

OBJECTIVE: The aim of the study was to test the hypothesis that alterations in large arteries are associated with microvascular remodelling and decreased retinal capillary blood flow. METHODS: The study group comprised of 88 patients with essential hypertension and 32 healthy controls. Retinal microcirculation was evaluated by scanning laser Doppler flowmetry. Macrovascular changes were assessed on the basis of arterial stiffness measurement (carotid-femoral pulse wave velocity), its hemodynamic consequences (central pulse pressure, augmentation pressure, augmentation index) and intima media thickness of common carotid artery. RESULTS: Pulse wave velocity was inversely correlated to mean retinal capillary blood flow in hypertensive patients (R = -0.32, p < 0.01). This relationship remained significant in multivariate regression analysis after adjustment for age, sex, central systolic blood pressure (BP) and body mass index (ß = -31.27, p < 0.001). Lumen diameter (LD) of retinal arterioles was significantly smaller in hypertensive then normotensive subjects (79.4 vs. 83.8, p = 0.03). Central and brachial systolic, diastolic and mean BPs were significantly correlated with LD and outer diameter of retinal arterioles. The relationship between LD and central BPs remained significant in multivariate analysis (ß = -0.15, p = 0.03 for cSBP; ß = -0.22, p = 0.04 for cDBP; ß = -0.21, p = 0.03 for cMBP). Moreover, in a subgroup with cardiac damage central and brachial pulse pressure were positively associated with retinal wall thickness, wall cross sectional area, and wall to lumen ratio. CONCLUSION: In conclusion, the study provides a strong evidence that microcirculation is coupled with macrocirculation not only in terms of structural but also functional parameters.


Assuntos
Hipertensão Essencial/fisiopatologia , Retinopatia Hipertensiva/fisiopatologia , Microcirculação , Microvasos/fisiopatologia , Vasos Retinianos/fisiopatologia , Rigidez Vascular , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Progressão da Doença , Hipertensão Essencial/complicações , Hipertensão Essencial/diagnóstico , Feminino , Humanos , Retinopatia Hipertensiva/diagnóstico , Retinopatia Hipertensiva/etiologia , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Remodelação Vascular
5.
J Sports Sci ; 38(22): 2597-2602, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32684111

RESUMO

Exertional heat stroke (EHS) is a potentially life-threatening condition with a variety of symptoms and abnormal laboratory findings. Nevertheless, data evaluating the course of making an EHS diagnosis in real-life practice, as well as the role of predisposing psychological components are limited. Thus, the aim of our study was to present a multi-faceted differentiation process and show the role of unhealthy competition in the development of EHS. We describe a case of a young amateur runner, admitted to the hospital due to loss of consciousness, further mental confusion, and increased body temperature above 40°C. Head scans excluded brain haemorrhage and stroke. Elevated troponin I levels suggested an acute coronary syndrome (ACS) or myocarditis. An increase of procalcitonin levels, signs of rhabdomyolysis and severe liver injury resulted in evaluation for infection and acute hepatic damage. Subsequently, the patient's negative results pointed us to a diagnosis of EHS. In-depth anamnesis revealed that the patient's excessive effort during the race was linked to the male-female competition. EHS can present diagnostic challenges, as it mimics various diseases, such as stroke, myocarditis, ACS, infection, or liver dysfunction. In addition, the role of psychological components, such as unhealthy competition, in the development of EHS should be considered.


Assuntos
Comportamento Competitivo/fisiologia , Golpe de Calor/diagnóstico , Corrida/fisiologia , Corrida/psicologia , Alanina Transaminase/sangue , Biomarcadores/sangue , Confusão/etiologia , Creatina Quinase/sangue , Diagnóstico Diferencial , Feminino , Golpe de Calor/complicações , Golpe de Calor/diagnóstico por imagem , Humanos , Fígado/diagnóstico por imagem , Fígado/enzimologia , Fígado/lesões , Motivação , Pró-Calcitonina/sangue , Rabdomiólise/diagnóstico , Troponina I/sangue , Inconsciência/etiologia , Adulto Jovem
6.
Am Heart J ; 218: 32-45, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31706143

RESUMO

BACKGROUND: There is a paucity of data on the distribution of cardiovascular risk factors in patients with familial hypercholesterolemia (FH) as compared to the general population. The aim of the study was to compare cardiovascular risk factors in a cohort of FH patients to the representative sample of adults in Poland who represent a high-cardiovascular risk European region. METHODS: We compared the distribution of risk factors in 1,382 individuals with FH phenotype referred for genetic testing between 2006 and 2014 to the National Centre of Familial Hypercholesterolemia in Gdansk, Poland. The cohort was comprised of 637 positive FH(+) and 745 negative FH(-) patients who were compared to a nationally representative sample of 2,413 adults age 18-79, standardized by age and sex, from the NATPOL 2011 study (NATPOL). We analyzed patients' distribution of history of atherosclerotic cardiovascular disease (ASCVD) and standard risk factors including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure (SBP, DBP), body mass index, smoking, and diabetes. RESULTS: FH(+) patients (mean age 45.6 years) had the highest LDL-C of 241.7 mg/dL (95% CI 234.8-248.5) compared to 206.1 mg/dL (200.5-211.7) in FH(-) patients (mean age 48.2) and 126.2 mg/dL (124.8-127.6) in NATPOL. Mean SBP was the lowest in FH(+) patients at 128.7 mm Hg (126.7-130.7) compared to 133.4 mm Hg (132.6-134.3) in NATPOL and 134.4 mm Hg (132.3-136.5) in FH(-). No differences were found in the prevalence of diabetes and body mass index. Smoking was less common in FH(+) at 12.4% (9.4-15.4) compared to both FH(-) and NATPOL: 20.4% (16.6-24.1) and 28.4% (26.6-30.2), respectively. The prevalence of individuals with a history of ASCVD in both FH(+) and FH(-) was nearly 3-fold higher compared to NATPOL: 26% (21.8-30.1) and 26.6% (22.2-30.9) versus 9.5% (8.3-10.7), respectively. CONCLUSIONS: The FH(+) patients had significantly higher mean LDL-C, but the levels of nonlipid factors were lower or similar compared to the other groups. Both FH(+) and FH(-) were characterized by a heavy burden of ASCVD. This suggests that cholesterol, and no other risk factors, is a key contributor to cardiovascular risk in patients with FH, especially those with genetic mutation.


Assuntos
Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/genética , Mutação , Adulto , Idoso , Aterosclerose/epidemiologia , Determinação da Pressão Arterial , Índice de Massa Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus/epidemiologia , Feminino , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Prevalência , Fatores de Risco , Fumar/epidemiologia , Triglicerídeos/sangue
7.
Catheter Cardiovasc Interv ; 93(4): 574-582, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30311397

RESUMO

BACKGROUND: There is a paucity of data on left main (LM) percutaneous coronary intervention (PCI) therapy with dedicated DES platforms. The LM-STENTYS is a multicenter registry aimed at evaluating clinical outcome after PCI of LM performed with a self-apposing Stentys DES implantation. METHODS: The registry consists of 175 consecutive patients treated with Stentys DES implanted to LM. The primary endpoint was the composite of major adverse cardiac and cerebral events (MACCE) defined as cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), and stroke assessed after 1 year. The secondary endpoint was stent thrombosis (ST) at 1 year. RESULTS: The median age was 69 years (IQR, 62-78 years). Acute coronary syndrome (ACS) was the presenting diagnosis in 117 (66.9%) patients [74 (63.2%) unstable angina, 31 (26.5%) NSTEMI, 12 (10.3%) STEMI] and stable angina (SA) was present in 58 (33.1%) patients. The median SYNTAX score was 23.0 (IQR, 18.7-32.2) in the SA group and 25.0 (IQR, 20.0-30.7) in the ACS group. During 1-year follow-up in the SA group two (3.4%) MACCE occurred, both of them were cardiac deaths. In ACS patients there were 19 (16.2%) MACCE [9 (7.7%) cardiac deaths, 11 (9.4%) MIs, 11(9.4%) TLR, 1(0.9%) stroke]. Altogether, three (1.7%) cases of acute ST were noted, all of them in ACS subset. CONCLUSION: LM PCI using self-apposing Stentys DES showed favorable clinical outcomes at 1-year in patients with SA. Events of ST in the ACS group warrant further research.


Assuntos
Síndrome Coronariana Aguda/terapia , Angina Estável/terapia , Angioplastia Coronária com Balão/instrumentação , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/mortalidade , Idoso , Angina Estável/diagnóstico por imagem , Angina Estável/mortalidade , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/mortalidade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Trombose Coronária/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Recidiva , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Resultado do Tratamento
8.
Blood Press ; : 1-10, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32228237

RESUMO

Purpose: In the course of hypertension, left ventricular hypertrophy and diastolic dysfunction develop very often and may progress toward heart failure. The aim of the study was to analyze the relationship between abnormalities of retinal microcirculation and cardiac damage defined as left ventricular hypertrophy and/or diastolic dysfunction.Materials and methods: The study comprised 88 patients with essential hypertension. The group was divided into two subgroups: hypertensives without cardiac damage (n = 55) and with cardiac damage (n = 33). Control group comprised 32 normotensive subjects. Scanning laser Doppler flowmetry was used to evaluate retinal microcirculation. Echocardiography was used to assess cardiac damage.Results: Lumen diameter of retinal arterioles was significantly smaller in patients with cardiac damage vs. controls (77 vs. 84 µm, p = 0.02). Additionally, there was an evident trend with respect to lumen diameter (LD) across all three studied subgroups; i.e.: the smallest dimeters were present in cardiac damage patients, moderate size in hypertensives' without cardiac damage, and the largest diameters in healthy controls (pfor trend < 0.01). Lumen diameter was inversely correlated with cardiac intraventricular septum diameter (R = -0.25, p = 0.02), left ventricular mass (R = -0.24, p = 0.02), and left atrial volume (R = -0.22, p = 0.04). Wall to lumen ratio was associated with intraventricular septum diameter (R = 0.21, p = 0.044) and left atrial volume (R = 0.21, p = 0.045). In multivariable regression analysis, lumen diameter was independently associated with intraventricular septum diameter (ß = -0.05, p = 0.03), left ventricular mass (ß = -1.15, p = 0.04), and left atrial volume (ß = -0.42, p = 0.047); wall to lumen ratio was independently associated with intraventricular septum diameter (ß = 3.67, p = 0.02) and left atrial volume (ß = 30.0, p = 0.04).Conclusions: In conclusion, retinal arterioles lumen diameter and wall to lumen ratio were independent biomarkers of cardiac damage. Retinal examination performed by means of scanning laser Doppler flowmetry might be a valuable tool to improve cardiovascular risk stratification of hypertensive patients.

9.
Echocardiography ; 35(11): 1772-1781, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30255609

RESUMO

BACKGROUND: Hereditary haemochromatosis (HH) is a common inherited disease. Abnormally increased intestinal iron absorption and accelerated recycling of iron by macrophages lead to progressive body iron accumulation and the generation of oxidative stress. In the late stages, iron overload can lead to dysfunction of the left ventricle (LV). It is believed that two-dimensional speckle tracking echocardiography (2D STE) can evaluate LV dysfunction more accurately than conventional echocardiography. This accurate evaluation seems to be clinically important in the early stages of HH before substantial damage of the LV. Evaluation of this assessment was the purpose of this paper. METHODS: We prospectively enrolled 24 patients with early diagnosed HH and without any history of cardiovascular diseases; 23 healthy age- and sex-matched volunteers constituted the control group. Standard echocardiographic parameters and LV rotation and strain parameters were assessed and compared between the groups. RESULTS: All echocardiographic parameters were within normal ranges, and there were no differences between the groups. 2D STE revealed significantly worse basal and apical rotation, twist and torsion values in HH patients. The peak systolic longitudinal strain was decreased in HH patients, even though the LV ejection fraction (LVEF) was normal. There were weak correlations between the iron turnover and 2D STE parameters. CONCLUSIONS: 2D STE seems to be more sensitive than traditional echocardiography for detecting LV abnormalities in HH patients who are diagnosed early. The results of this study may be clinically useful, but their relevance and therapeutic implications remain to be confirmed by further studies.


Assuntos
Ecocardiografia/métodos , Hemocromatose/complicações , Hemocromatose/fisiopatologia , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
Eur Heart J ; 38(9): 648-660, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28025189

RESUMO

AIMS: Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. METHODS AND RESULTS: This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein-Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann-Whitney estimator 0.54, 95% confidence interval [CI] 0.47-0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200-370 mL (60% of patients) (Mann-Whitney estimator 0.61, 95% CI 0.52-0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. CONCLUSION: The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.


Assuntos
Insuficiência Cardíaca/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Isquemia Miocárdica/terapia , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
11.
Neurol Neurochir Pol ; 52(5): 593-598, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30170703

RESUMO

BACKGROUND: Heart failure (HF) is common among patients with ischemic stroke (IS), however its impact on outcome after iv-thrombolysis has not been fully determined. Moreover, definition of HF has been recently modified, but majority of stroke studies classified patients regarding an old HF criteria. Thus, the aim of our study was to evaluate the relationship between both, newly and formerly defined HF and the long-term outcome, mortality and the presence of hemorrhagic complications in patients with acute IS treated with iv-thrombolysis. METHODS: We retrospectively evaluated data from 328 Caucasian patients with IS consecutively treated with iv-thrombolysis. HF was defined according to old and new definition; long-term outcome was assessed with modified Rankin Scale (mRS) score and mortality rate on 90th days after IS. RESULTS: The incidence of HF did not differ between patients with favorable (mRS 0-2) and unfavorable (mRS 3-6) functional outcome respectively for the old and for the new definition (10.4% vs. 15.5, p = 0.17; 17.4% vs. 18.1%, p = 0.88) and between those who survived and died within 90 days after IS (11.7% vs. 20.0%, p = 0.27; 17.2% vs. 25.0%, p = 0.38, respectively). Multivariate analysis showed no impact of HF diagnosis on outcome (p = 0.94) or mortality (p = 0.64). CONCLUSION: The presence of systolic HF, defined according to an old and a new definition, does not determine safety and efficacy of cerebral iv-thrombolysis in patients with IS.


Assuntos
Isquemia Encefálica , Insuficiência Cardíaca , Acidente Vascular Cerebral , Fibrinolíticos , Humanos , Estudos Retrospectivos , Terapia Trombolítica , Ativador de Plasminogênio Tecidual , Resultado do Tratamento
12.
Cell Immunol ; 322: 26-33, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28939130

RESUMO

Lung cancer cells harboring multiple mutations as a consequence of long-term damage by different etiologic factors are responsible for high immunogenicity. Immune checkpoint inhibitors significantly improve treatment results in non-small cell lung cancer (NSCLC). Unfortunately, the role of T-lymphocytes in early NSCLC has not been sufficiently elucidated. The aim of this study was to characterize peripheral blood T cells expressing several selected surface antigens (CD4, CD8, CD25, CD28, PD-1, CTLA-4) and transcription factors (T-bet, ROR-yt, Fox-P3, GATA-3) in this patient population. The study group (LC) consisted of 80 treatment-naïve patients with T1/2aN0M0 NSCLC and was compared with 40 cancer-free patients matched for non-oncological diseases and demographic parameters (CG). Significantly higher counts of CTLA-4+cells (in both CD4+and CD8+subtypes), a lower proportion of PD-1 expressing cells and a significantly higher percentage of Fox-P3+CD4+cells were found in the LC group. The high proportion of CD4+PD-1+cells significantly correlated with poor outcomes in LC group, while low CD4/CD8 ratio predicted a better prognosis. Based on our results it seems that NSCLC even at early stages of development initiate changes in the proportions of T cells that may have a significant impact on the clinical outcome.


Assuntos
Antígenos CD/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Neoplasias Pulmonares/imunologia , Ativação Linfocitária/imunologia , Idoso , Antígeno CTLA-4/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Feminino , Fatores de Transcrição Forkhead/imunologia , Humanos , Neoplasias Pulmonares/terapia , Contagem de Linfócitos , Masculino , Receptor de Morte Celular Programada 1/imunologia , Estudos Prospectivos , Resultado do Tratamento
13.
Blood Press ; 26(2): 81-86, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27435119

RESUMO

The aim of this study was to assess the relationship between 24 h blood pressure (BP) profile, extent of significant coronary artery stenosis, confirmed by coronary angiography, and cardiovascular events in patients with coronary artery disease. Coronary angiographies were performed for all included subjects and significant coronary artery stenosis was considered as ≥ 50% stenosis by atherosclerotic plaque. Twenty-four-hour ambulatory BP monitoring was performed. Major advanced cardiovascular events (MACE) included revascularization, cardiovascular mortality, total mortality, acute coronary syndromes and stroke. BP analysis revealed higher night-time systolic blood pressure (SBP) values in patients with three or more significant coronary artery stenoses than in those without significant stenosis (120.7 ± 16.4 vs 116.7 ± 14.3 mmHg, p < 0.001), lower night-time SBP dip in patients with three or more significant coronary artery stenoses than in those without significant stenosis (5.7 ± 3.2 vs 7.4 ± 6.8 mmHg, p < 0.001) and lower night-time diastolic blood pressure dip in patients with three or more significant stenoses than in patients without significant stenosis (9.4 ± 7.4 vs 11.9 ± 7.4 mmHg, p < 0.001). Night-time SBP values, night-time/daytime SBP dip and extent of significant coronary artery stenosis were risk factors for MACE, revascularization and cardiovascular mortality. In conclusion, the study shows that advanced coronary artery disease is related to blunted night-time BP dipping and cardiovascular complications.


Assuntos
Pressão Sanguínea , Angiografia Coronária , Doença da Artéria Coronariana , Estenose Coronária , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade
14.
Blood Press ; 26(3): 174-180, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28092973

RESUMO

OBJECTIVES: Ambulatory systolic-diastolic pressure regression index (ASDPRI) as a composite marker of cardiovascular (CV) properties is related to CV complications. However, genetic determinants of ASDPRI are not known. The aim of this study is to report the relationship between certain single nucleotide polymorphisms (SNP) and ASDPRI in hypertensive patients with CAD confirmed by coronary angiography. METHODS: A total of 1345 hypertensive subjects with CAD were included. SNPs were selected from genome-wide association studies. SNPs were reported to be associated with coronary artery disease risk. There were significant differences in 24 h and daytime and nighttime ASDPRIs for PHCTR1, LPA and ADAMTS7 polymorphisms. Genetic risk score (GRS18) was constructed to evaluate additive effect of 18 SNPs for ASDPRI. RESULTS: Analysis of covariance revealed a significant relationship between the PPAB2B (ß - 0.85; 95 CI -1.85--0.16, p < 0.02), WDR12 (ß - 1.31; 95 CI -2.19--0.43, p < 0.01) polymorphisms and nighttime ASDPRI dipping. Analysis of covariance revealed a significant relationship between GRS 18 and 24-h ASDPRI (ß 0.34; 95 CI 0.16-0.31, p < 0.01). CONCLUSIONS: In conclusion, ADAMTS7 and LPA polymorphisms are related to 24-h ASDPRI but PPAB2B and WDR12 gene polymorphisms are associated with nighttime ASDPRI dipping. A total of 24-h ASDPRI is determined by GRS18.


Assuntos
Pressão Sanguínea , Doença das Coronárias/genética , Hipertensão/genética , Polimorfismo de Nucleotídeo Único , Receptores de Ácidos Lisofosfatídicos/genética , Proteína ADAMTS7/genética , Idoso , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano , Doença das Coronárias/complicações , Doença das Coronárias/fisiopatologia , Diástole , Feminino , Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Estudos Retrospectivos , Risco , Sístole
15.
Dev Period Med ; 21(1): 43-50, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28551692

RESUMO

INTRODUCTION: Familial hypercholesterolemia (FH) is one of the most common autosomal dominant disorders. It is characterized by elevated LDL cholesterol levels occurring already by early childhood. Awareness of health risks in FH patients should incite health professionals to actively seek and treat children with lipid disorders to reduce their risk of myocardial infarction and stroke. OBJECTIVE: The aim of the study was to evaluate the suitability of taking into account the following parameters: ApoB/ApoA index, IMT and e-tracking examination, when initiating statin therapy in FH patients. Materials and methods The study included 57 male and female patients aged 9.57±3.2 years (ranging from 1 year to 17 years), diagnosed with familial hypercholesterolemia confirmed by molecular testing. All the participants had their lipid profile, ApoA and ApoB levels determined. Carotid intima-media thickness (IMT) was measured by carotid ultrasound and arterial stiffness was assessed by e-tracking. The dietary treatment efficacy was monitored in 40 patients and the 12-month combination treatment efficacy in 27 patients. The study was conducted prospectively and retrospectively. Statistical analysis was performed with the EPIINFO Ver. 7.1.1.14 statistical software package. RESULTS: Patients with familial hypercholesterolemia had high mean levels of total cholesterol and LDL cholesterol (287±67 mg/dL and 213±73 mg/dL respectively). 34.37% of the study subjects had a markedly increased ApoB/ApoA index. On IMT or e-tracking examination all the subjects (100%) had vascular abnormalities. After 6 months of a low-cholesterol diet, the mean total and LDL cholesterol levels in the serum had been reduced by 7.2% and 6.2%, respectively. Statins in an average dose of 10.42±2.49 mg daily were prescribed to 36 patients. After one year of the statin therapy, the average serum total and LDL cholesterol levels were 203.5±34.8 mg/dL and 139.1±32.1 mg/dL, respectively, and were still above the target values. Moreover, side effects of the statin therapy were monitored. An increase in AST levels seen in the study group was not statistically significant. The mean creatine kinase level was within the range of normal. Moreover, in our study material we estimated the risk of cardiovascular events in relation to the ApoB/ApoA index. Higher cardiovascular risk was found in 34.37% participants. CONCLUSIONS: Increased risk of cardiovascular events based on ApoB/ApoA index and carotid e-tracking or IMT examination in paediatric patients with FH is an indication for statin therapy initiation.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Colesterol/sangue , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hiperlipoproteinemia Tipo II/sangue , Masculino , Resultado do Tratamento
16.
Curr Hypertens Rep ; 18(7): 51, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27193773

RESUMO

Heart failure (HF) is a major and growing public health problem. This condition is associated with poor prognosis, a high rate of mortality, frequent hospitalization and increasing costs to health care systems. Pharmacological approaches aimed at reducing morbidity and mortality in HF have primarily focused on inhibition of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS), both of which have been associated with disease development, progression and adverse cardiovascular (CV) outcomes. The increasing number of hospitalizations for HF decompensation suggests the failure of available treatment options, indicating the necessity for alternative therapeutic approaches. Alongside pharmacological and cardiac resynchronization therapies in selected patients with arrhythmia, recent advancements in the management of HF have been directed at inhibiting relevant neurogenic pathways underlying disease development and progression. Initial evidence regarding the safety and effectiveness of interventional procedures suggests that HF patients may benefit from novel adjunctive therapies. Here we review the critical role of sympathetic activation in HF and the rationale for therapeutic interventions including device-based and interventional approaches aimed at restoring autonomic neural balance in this condition.


Assuntos
Insuficiência Cardíaca/terapia , Animais , Doença Crônica , Insuficiência Cardíaca/etiologia , Humanos , Hipertensão/complicações , Sistema Renina-Angiotensina , Fatores de Risco
17.
Catheter Cardiovasc Interv ; 86(2): E49-57, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25599675

RESUMO

AIMS: The effectiveness of revascularization of chronic total occlusion (CTO) remains intriguing. Thus, we sought to investigate whether a successful PCI for single CTO improves outcomes in a setting of stable angina and chronic occlusion of single coronary artery. METHODS AND RESULTS: Of 11 957 consecutive patients referred for nonurgent PCI between 2003 and 2010, 1110 displayed single CTO and were enrolled to the central CTO-registry database. The primary end-point included all-cause mortality, the secondary end-point a composite of safety outcome measure of all-cause death, nonfatal-MI, the need for urgent revascularization and stroke. The major adverse cardiovascular event (MACE) records were extracted from the national administrative database and all patients were linked to the long-term follow-up. Since the patient assignment was not random, we performed the propensity scoring to minimize selection bias; 734 patients (66%) had a successful PCI-CTO. Compared with successful procedures, unsuccessful procedures had similar rates of all-cause death both in crude (HR, 0.78; 95%CI, 0.49-1.25; P = 0.30) and adjusted analysis (HR, 0.80; 95%CI, 0.50-1.28; P = 0.34). A similar, significant reduction in overall MACE was noted with successful PCI-CTO compared with unsuccessful procedure in unadjusted (HR, 0.74; 95%CI, 0.56-0.96; P = 0.020) and adjusted calculation (HR, 0.73; 95%CI, 0.56-0.96; P = 0.019). Patients after successful PCI-CTO as compared with failed recanalization less frequently underwent surgical revascularization. The benefit was sustained at 3 years follow-up. CONCLUSIONS: Successful PCI for single CTO does not improve long-term survival, nonetheless, is associated with reduced overall MACE and the need for surgical revascularization.


Assuntos
Angina Estável/terapia , Oclusão Coronária/terapia , Intervenção Coronária Percutânea , Idoso , Angina Estável/diagnóstico , Angina Estável/fisiopatologia , Distribuição de Qui-Quadrado , Doença Crônica , Oclusão Coronária/diagnóstico , Oclusão Coronária/mortalidade , Oclusão Coronária/fisiopatologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/etiologia , Razão de Chances , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Pontuação de Propensão , Sistema de Registros , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento
18.
Blood Press ; 24(2): 90-5, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25668594

RESUMO

INTRODUCTION: It has been reported in coronary heart disease (CHD) patients that mortality is inversely associated with body mass index (BMI), and directly associated with waist circumference (WC). The purpose of this study was to examine the association of the general obesity parameter (BMI) and the adipose tissue discriminator (WC) with cardiovascular (CV) risk in patients with CHD established by coronary angiography. OBJECTIVES: 1345 subjects with CHD were included in the PROGNOSIS (Prognostic Value of Ambulatory Blood Pressure Monitoring in Patients with Coronary Artery Disease Confirmed by Angiography) study. PATIENTS AND METHODS: A multivariate Cox proportional regression model adjusted for potential confounders was used to assess the relative risk of total and CV mortality according to the parameters of general obesity (BMI) and adipose tissue distribution (WC).The mean age of subjects was 63.2 ± 9.2 years, and 57% were men. Results. There was direct relationship between WC and both total mortality [hazard ratio, HR = 1.03 (95% CI 1.01-1.10), p < 0.01] and CV mortality [HR = 1.03 (95% CI 1.01-1.07), p < 0.03], but an inverse relationship between BMI and both total mortality [HR = 0.91 (95% CI 0.86-0.98), p < 0.03] and CV mortality [HR = 0.97 (95% CI 0.87-0.99), p < 0.05]. After combining WC with BMI, the group of subjects with BMI < 25 kg/m(2) and WC ≥ 104 cm had the highest rates of both total and CV mortality of all CHD patients. CONCLUSIONS: Assessment based on a combination of WC and BMI is superior to assessment based on a separate estimation of these parameters in both total and CV mortality risk evaluation.


Assuntos
Doenças Cardiovasculares/complicações , Hipertensão/complicações , Obesidade/complicações , Circunferência da Cintura/fisiologia , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco
19.
Blood Press ; 23(2): 96-101, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23899114

RESUMO

OBJECTIVES: The goal of our study was to estimate the impact of abnormal night-time blood pressure (BP) on cardiovascular (CV) mortality in hypertensive patients with significant atherosclerosis established in coronary angiography. METHOD: We enrolled 891 patients, 63.7 ± 9.4 years of age. They were divided into patients with normal daytime BP values, and patients with abnormal daytime BP values. During a follow-up period of 4.7 years in total, all-cause mortality and both CV and non-CV mortality were assessed. RESULTS: In the group with normal daytime BP, a clinic BP value ≥ 140/90 mmHg was observed in 25.7% (n = 161) of patients, and a night-time BP value ≥ 120/70 mmHg was observed in 37.8% (n = 236) of patients. In the group of patients with normal daytime BP in comparison with those with abnormal daytime BP, there was lower CV mortality (5.6% vs 9.8%, p < 0.02). Abnormal daytime BP was associated with a hazard ratio of CV mortality of 1.80 (95% CI 1.08-3.00, p < 0.02), and abnormal night-time BP with a hazard ratio of 1.63 (95% CI 1.03-2.66, p < 0.04). CONCLUSION: Assessment of both daytime and night-time BP is essential and superior over clinic BP in CV risk evaluation in patients with coronary artery disease confirmed in coronary angiography.


Assuntos
Pressão Sanguínea/fisiologia , Doença da Artéria Coronariana/diagnóstico , Hipertensão/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Determinação da Pressão Arterial , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano/fisiologia , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Feminino , Humanos , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Prognóstico , Medição de Risco , Fatores de Risco , Taxa de Sobrevida
20.
Sci Rep ; 14(1): 2762, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307884

RESUMO

Lipoprotein apheresis (LA) is a therapeutic option for hyperlipoproteinemia(a) (hyper-Lp(a)) and atherosclerotic cardiovascular disease (ASCVD). LA improves blood rheology, reduces oxidative stress parameters and improves endothelial function. The underlying molecular mechanisms of LA beneficial effects are unknown, but it has been suggested that LA exhibits multiple activities beyond simply removing lipoproteins. We hypothesized that LA removes not only lipoproteins, but also extracellular vesicles (EVs). To test this hypothesis, we performed a prospective study in 22 patients undergoing LA for hyper-Lp(a) and ASCVD. Different EVs subtypes were measured before and directly after LA, and after 7 days. We used calibrated flow cytometry to detect total particle concentration (diameter > ~ 100 nm), total lipoproteins concentration (diameter > 200 nm, RI > 1.51), total EV concentration (diameter > 200 nm, RI < 1.41), concentrations of EVs derived from erythrocytes (CD235a+; diameter > 200 nm, RI < 1.41), leukocytes (CD45+; diameter > 200 nm, RI < 1.41) and platelets (CD61+, PEVs; diameter > 200 nm, RI < 1.41). LA reduced the concentrations of all investigated EVs subtypes and lipoproteins. Lp(a) concentration was lowered by 64.5% [(58% - 71%); p < 0.001]. Plasma concentrations of EVs > 200 nm in diameter derived from platelets (CD61 +), leukocytes (CD45+) and erythrocytes (CD235a+) decreased after single LA procedure by 42.7% [(12.8-54.7); p = 0.005], 42.6% [(29.7-54.1); p = 0.030] and 26.7% [(1.0-62.7); p = 0.018], respectively, compared to baseline. All EV subtypes returned to the baseline concentrations in blood plasma after 7 days. To conclude, LA removes not only Lp(a), but also cell-derived EVs, which may contribute to LA beneficial effects.


Assuntos
Aterosclerose , Remoção de Componentes Sanguíneos , Vesículas Extracelulares , Hiperlipoproteinemias , Humanos , Estudos Prospectivos , Lipoproteína(a) , Remoção de Componentes Sanguíneos/métodos , Aterosclerose/terapia
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