RESUMO
An association between atherosclerosis and osteoporosis has been reported in several studies. This association could result from local intraosseous atherosclerosis and ischemia, which is shown by limb osteoporosis in patients with peripheral artery disease (PAD), but also could result from bidirectional communication between the skeleton and blood vessels. Systemic bone disorders and PAD are frequent in ESRD. Here, we investigated the possible interaction of these disorders. For 65 prevalent nondiabetic patients on hemodialysis, we measured ankle-brachial pressure index (ABix) and evaluated mineral and bone disorders with bone histomorphometry. In prevalent patients on hemodialysis, PAD (ABix<0.9 or >1.4/incompressible) was associated with low bone turnover and pronounced osteoblast resistance to parathyroid hormone (PTH), which is indicated by decreased double-labeled surface and osteoblast surface (P<0.001). Higher osteoblast resistance to PTH in patients with PAD was characterized by weaker correlation coefficients (slopes) between serum PTH and double-labeled surface (P=0.02) or osteoblast surface (P=0.03). The correlations between osteoclast number or eroded surface and serum mineral parameters, including PTH, did not differ for subjects with normal ABix and PAD. Common vascular risk factors (dyslipidemia, smoking, and sex) were similar for normal, low, and incompressible ABix. Patients with PAD were older and had high C-reactive protein levels and longer hemodialysis vintage. These results indicate that, in prevalent nondiabetic patients with ESRD, PAD associates with low bone turnover and pronounced osteoblast resistance to PTH.
Assuntos
Índice Tornozelo-Braço , Osso e Ossos/metabolismo , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Osteoporose/fisiopatologia , Doença Arterial Periférica/fisiopatologia , Diálise Renal , Adulto , Fatores Etários , Idoso , Biópsia , Densidade Óssea/fisiologia , Osso e Ossos/patologia , Proteína C-Reativa/metabolismo , Comorbidade , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/metabolismo , Hormônio Paratireóideo/sangue , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/metabolismo , Análise de Regressão , Estudos RetrospectivosRESUMO
BACKGROUND: Endothelial dysfunction in cardiovascular (CV) diseases is closely associated with increases in plasma level of shed membrane microparticles (MPs) of endothelial origin. As arterial damage is a major contributor to CV mortality, we examined whether or not increases in endothelial microparticles (EMPs) circulating levels could predict outcome in patients with end-stage renal disease (ESRD). METHODS: This prospective pilot study conducted in a community hospital (median follow-up: 50.5 months), included 81 stable haemodialysed ESRD patients (59 ± 14 years; 63% male). Platelet-free plasma obtained 72 h after last dialysis was analysed by flow cytometry, and MPs cellular origin identified as endothelial (CD31+CD41-MPs; EMPs), platelets (CD31+CD41+MPs) or erythrocyte (CD235a+MPs). The main outcome measures were global and CV mortality (fatal myocardial infarction, stroke, acute pulmonary oedema and sudden cardiac death). RESULTS: Non-survivors (n = 24) were older (P < 0.001) and characterized by higher levels of EMPs (P < 0.01) and high-sensitivity C-reactive protein (P < 0.05) and lower diastolic blood pressure (P < 0.001). Kaplan-Meier analysis demonstrated significantly higher probability of all-cause (P < 0.001) and CV mortality (P < 0.0001) between the lower and upper EMPs tertiles. Multivariate Cox regression analysis demonstrated that baseline EMP levels independently predicted all-cause [hazard ratio (HR) = 21.7, 95% confidence interval (CI): 4.23-111.18 per log EMPs/µL; P = 0.0002] and CV mortality (HR = 20.0, 95% CI: 3.86-103.5) per log EMPs/µL; P < 0.0004) after adjustment for confounding factors. EMPs baseline level was a stronger predictor of poor outcome than classical risk factors. CONCLUSION: This study demonstrates that increased plasma levels of EMPs is a robust independent predictor of severe CV outcome in end-stage renal failure patients.
Assuntos
Doenças Cardiovasculares/mortalidade , Micropartículas Derivadas de Células/metabolismo , Endotélio Vascular/patologia , Falência Renal Crônica/mortalidade , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Análise de Regressão , Diálise Renal , Fatores de Risco , Taxa de SobrevidaRESUMO
An inverse relationship between arterial calcifications and bone activity has been documented in patients with ESRD. Calcium overload is associated with arterial calcification, which is associated with arterial stiffening. Whether bone activity interacts with calcium load, aortic stiffness, or arterial calcification is unknown. This study assessed the impact of bone activity on the relationships between the dosage of calcium-containing phosphate binders and aortic stiffness (measured by pulse wave velocity) or abdominal aorta calcification score. Aortic stiffness and calcification were both positively associated with calcium load and negatively associated with bone activity. A significant interaction was found between dosage of calcium-containing phosphate binders and bone activity such that calcium load had a significantly greater influence on aortic calcifications and stiffening in the presence of adynamic bone disease. Independent of any other factor, including dosage of calcium-containing phosphate binders, adynamic bone was associated with greater aortic stiffening, suggesting cross-talk between the bone and arterial walls.
Assuntos
Aorta Abdominal/metabolismo , Osso e Ossos/metabolismo , Calcinose/metabolismo , Cálcio/metabolismo , Falência Renal Crônica/metabolismo , Adulto , Aorta Abdominal/fisiopatologia , Osso e Ossos/anatomia & histologia , Cálcio/administração & dosagem , Elasticidade , Feminino , Humanos , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Pulso Arterial , Diálise RenalRESUMO
Cardiovascular disease is a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Macrovascular disease develops rapidly in ESRD patients and is responsible for the high incidence of left ventricular hypertrophy, ischemic heart disease, cerebrovascular accidents, and peripheral artery diseases. Occlusive lesions due to atheromatous plaques frequently cause these complications; however, atherosclerosis represents only one form of structural response to metabolic and hemodynamic alterations interfering with the "natural" process of aging. The spectrum of arterial alterations in ESRD is broader, including large artery remodeling, changes in viscoelastic properties, and stiffening of arterial walls. Nonatheromatous remodeling principally changes the dampening function of arteries, characterized by stiffening of arterial walls and with deleterious effects on the left ventricle and coronary perfusion. The origin of arterial stiffening in ESRD patients is multifactorial, with extensive arterial calcifications as an important covariate.
Assuntos
Artérias/patologia , Artérias/fisiopatologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Falência Renal Crônica/complicações , Arteriosclerose/patologia , Arteriosclerose/fisiopatologia , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Doenças Cardiovasculares/etiologia , Progressão da Doença , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Humanos , Falência Renal Crônica/patologia , Falência Renal Crônica/fisiopatologiaRESUMO
BACKGROUND: Increased common carotid artery intima-media thickness (CCA-IMT) is a marker of early atherosclerosis. Low-grade inflammation is associated with the pathogenesis of atherosclerosis. Low-grade inflammation and increased CCA-IMT are observed in end-stage renal disease (ESRD). Oxidative stress is involved in uremia-related inflammation. Advanced oxidation protein products (AOPP) are markers of oxidant-mediated protein damage in ESRD. Intravenous iron given to patients on hemodialysis (HD) might induce oxidative stress. We investigated the relationships between AOPP, iron therapy, and CCA-IMT in stable HD patients. METHODS AND RESULTS: Plasma AOPP and blood chemistry, including iron status, were analyzed in a cohort of 79 ESRD patients on HD. Measurements of CCA-IMT and CCA diameter, as assessed by B-mode ultrasonography, were obtained in 60 patients. AOPP levels were elevated in ESRD patients, and in univariate (r=0.42, P<0.0001) and multivariate analyses (r=0.38, P<0.001), they correlated with serum ferritin and with the intravenous iron dose received during the 12 months preceding the study (ferritin, P<0001; AOPP, P<0.01). Univariate and multivariate analyses identified the AOPP concentration as being significantly associated with CCA-IMT (P=0.0197) and CCA wall-to-lumen ratio (r=0.560, P<0.0001). Independently of AOPP concentration, cumulative iron dose was positively related to CCA-IMT (P=0.015) in patients <60 years. CONCLUSION: In ESRD patients, CCA-IMT and CCA wall-to-lumen ratio were associated with plasma AOPP, serum ferritin, and the annual intravenous iron dose administered. These findings support the concept of a role of oxidative stress in the early atherosclerosis of ESRD patients, which may be increased by the usually recommended doses of intravenous iron.
Assuntos
Doenças das Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Primitiva/diagnóstico por imagem , Ferro/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Estresse Oxidativo , Biomarcadores/sangue , Doenças das Artérias Carótidas/etiologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Ferritinas/sangue , Humanos , Ferro/efeitos adversos , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteínas/análise , Diálise Renal , Fatores de Risco , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , UltrassonografiaRESUMO
BACKGROUND: Aortic stiffness and left ventricular hypertrophy (LVH) are predictors of mortality in hemodialysis (HD) patients. Attenuation of arterial stiffness and regression of LVH had a favorable effect on survival in these patients, but this favorable effect was observed in less than 50% of patients, the rest being resistant to therapeutical interventions. The aim of this study was to analyze the factors associated with this resistance to treatment. METHODS: 138 patients on HD were studied during a follow-up survey. From entry until the end of follow up, the changes of aortic pulse wave velocity (PWV) and of LV mass were measured in response to treatment with antihypertensive drugs and erythropoietin, together with measurements of blood chemistry, including high-sensitive C-reactive protein (CRP). Patients with decreased aortic PWV were considered to be responders (N = 68), the others to be nonresponders (N = 70). RESULTS: Nonresponders were older (P < 0.05) and had persistently higher systolic blood pressure (BP) and pulse pressure. Responders were treated more frequently with an ACE inhibitor (P < 0.001), and had lower serum CRP (P < 0.01). The baseline PWV, as well as the changes of PWV and LV mass during the follow-up were significantly and independently correlated with serum CRP level (P < 0.001). According to logistic regression after adjustment for age, gender, diabetes, history of CVD, and the nonspecific cardiovascular risk factors, the improvement of aortic stiffness and LV hypertrophy was positively associated with prescription of ACE inhibitor (P < 0.0001), and negatively with the serum CRP level (P < 0.01). CONCLUSION: These results indicate that in HD patients, the presence of low-grade inflammation decreases the efficiency of cardiovascular therapeutic interventions and participates in the persistence of cardiovascular hemodynamic overload.
Assuntos
Anti-Hipertensivos/uso terapêutico , Arteriosclerose/imunologia , Atenolol/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/imunologia , Falência Renal Crônica/terapia , Diálise Renal , Adulto , Doenças da Aorta/complicações , Doenças da Aorta/imunologia , Doenças da Aorta/patologia , Arteriosclerose/complicações , Pressão Sanguínea/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Feminino , Humanos , Hipertensão/etiologia , Hipertrofia Ventricular Esquerda/complicações , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Nitrendipino/uso terapêutico , Análise de Regressão , Vasculite/complicações , Vasculite/imunologiaRESUMO
Cardiovascular disease is a major cause of mortality in patients with end-stage renal disease, with damage to arteries as a major contributing factor. Arterial stiffness is a factor associated with high systolic and pulse pressure in these patients and is a strong independent factor associated with morbidity and mortality. Arterial stiffness is one of the principal factors opposing left ventricular ejection. The appropriate term to define the arterial factor(s) opposing left ventricular ejection is aortic input impedance. Aortic input impedance depends on TPR, arterial distensibility, and wave reflections. Distensibility defines the capacitive properties of arterial stiffness, whose role it is to dampen pressure and flow oscillations and to transform pulsatile flow and pressure in arteries into a steady flow and pressure in peripheral tissues. Stiffness is the reciprocal value of distensibility. These parameters are blood pressure dependent; arteries become stiffer at high pressure. While distensibility provides information about the elasticity of the artery as a hollow structure, the elastic incremental modulus characterizes the properties of the arterial wall biomaterials independent of vessel geometry. Alternatively, arterial distensibility can be evaluated by measuring pulse wave velocity, which increases with the stiffening of arteries. Arterial stiffening increases left ventricular afterload and alters the coronary perfusion. With increased pulse wave velocity, the wave reflections affects the aorta during systole, which increases systolic pressures and myocardial oxygen consumption and decreases diastolic blood pressure and coronary flow. The arterial stiffness is altered primarily in association with increased collagen content and alterations of extracellular matrix and calcification of the arterial wall. The arterial stiffening estimated by changes in aortic pulse wave velocity and intensity of wave reflections are independent predictors of survival in end-stage renal disease and in the general population. Improvement of arterial stiffening could be obtained by antihypertensive treatments as observed with calcium-channel blockers and angiotensin-converting enzyme inhibitors. Angiotensin-converting enzymes inhibitors increase AC and reduce wave reflections. It has been shown that reversibility of aortic stiffening and use of angiotensin-converting enzyme inhibitors had a favorable independent effect on survival in hypertensive patients with advanced renal disease.
Assuntos
Artérias/fisiopatologia , Hemodinâmica , Falência Renal Crônica/fisiopatologia , Aorta/fisiopatologia , Pressão Sanguínea , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Elasticidade , Humanos , Falência Renal Crônica/complicações , Volume SistólicoRESUMO
BACKGROUND AND OBJECTIVES: An intact endothelium is essential for adaptations between arterial vasomotor tone and shear stress (SS), i.e., flow-mediated vasodilation (FMD). Endothelial dysfunction occurs in hypertension, cardiac insufficiency, diabetes, atherosclerosis, and in end-stage renal disease (ESRD) patients, whose renal failure is associated with many of those cardiovascular diseases (CVD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using a progressive hand-warming protocol and repeated measures ANOVA, we analyzed SS-mediated increase of brachial artery diameter (ΔBA) in 22 healthy controls, 18 CVD-negative ESRD patients (ESRD-CVD(-)), and 17 CVD-positive ESRD patients (ESRD-CVD(+)) to analyze the role of uremia versus CVD on FMD. RESULTS: Hand-warming increased SS (P < 0.001) and ΔBA (P < 0.001). Negative interactions were observed between ΔBA and ESRD (P < 0.001), and between ΔBA and CVD(+) (P < 0.02), but there was no interaction between ESRD and CVD(+) (P = 0.69). For low and mild SS increases, ESRD-CVD(-) patients were characterized by similar ΔBA as controls, but it was lower than controls at higher SS (P < 0.01). In ESRD-CVD(+) patients, brachial artery diameter did not respond to mild and moderate SS increases, and showed "paradoxical" vasoconstriction at higher SS (P < 0.05). In ESRD, a positive and independent interaction was observed between ΔBA and 25(OH) vitamin D(3) insufficiency (≤15 µg/L; P < 0.02). CONCLUSIONS: These observations indicate that, independently of each other, ESRD and CVD(+) history are associated with endothelial dysfunction. They also suggest the importance of considering the relationships between SS and endothelial function in different clinical conditions.
Assuntos
Artéria Braquial/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Endotélio Vascular/fisiopatologia , Falência Renal Crônica/fisiopatologia , Vasodilatação , Adulto , Idoso , Análise de Variância , Estudos de Casos e Controles , Feminino , Temperatura Alta , Humanos , Imersão , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional , Diálise Renal , Medição de Risco , Fatores de Risco , Uremia/fisiopatologiaRESUMO
BACKGROUND: There is increasing evidence that, in addition to the well-known effects on musculoskeletal health, vitamin D status may be related to a number of non-skeletal diseases. An international expert panel formulated recommendations on vitamin D for clinical practice, taking into consideration the best evidence available based on published literature today. In addition, where data were limited to smaller clinical trials or epidemiologic studies, the panel made expert-opinion based recommendations. METHODS: Twenty-five experts from various disciplines (classical clinical applications, cardiology, autoimmunity, and cancer) established draft recommendations during a 2-day meeting. Thereafter, representatives of all disciplines refined the recommendations and related texts, subsequently reviewed by all panelists. For all recommendations, panelists expressed the extent of agreement using a 5-point scale. RESULTS AND CONCLUSION: Recommendations were restricted to clinical practice and concern adult patients with or at risk for fractures, falls, cardiovascular or autoimmune diseases, and cancer. The panel reached substantial agreement about the need for vitamin D supplementation in specific groups of patients in these clinical areas and the need for assessing their 25-hydroxyvitamin D (25(OH)D) serum levels for optimal clinical care. A target range of at least 30 to 40 ng/mL was recommended. As response to treatment varies by environmental factors and starting levels of 25(OH)D, testing may be warranted after at least 3 months of supplementation. An assay measuring both 25(OH)D(2) and 25(OH)D(3) is recommended. Dark-skinned or veiled individuals not exposed much to the sun, elderly and institutionalized individuals may be supplemented (800 IU/day) without baseline testing.
Assuntos
Vitamina D/análogos & derivados , Vitamina D/administração & dosagem , Adulto , Idoso , Autoimunidade , Osso e Ossos/fisiologia , Cálcio/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Fraturas Ósseas/etiologia , Fraturas Ósseas/prevenção & controle , Humanos , Sistema Imunitário/fisiologia , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/etiologia , Doenças Musculoesqueléticas/prevenção & controle , Neoplasias/etiologia , Neoplasias/prevenção & controle , Vitamina D/sangue , Vitamina D/farmacologia , Deficiência de Vitamina D/complicações , Adulto JovemRESUMO
PURPOSE OF REVIEW: To review the most recent publications concerning the pathophysiology and clinical impact of arterial stiffening in patients with chronic kidney disease and those with end-stage renal disease. RECENT FINDINGS: The results of recent studies confirmed that arterial stiffening is independently associated with decreased glomerular filtration rate and increased decline in parallel kidney function, and is predictive of kidney disease progression and the patient's cardiovascular outcome. Arterial stiffening is of multifactorial origin, including arterial calcifications, systemic inflammation, malnutrition, vitamin deficiencies, endothelial dysfunction, and bone activity. SUMMARY: Arterial stiffness and intensity of wave reflections are considered the principal determinants of systolic blood and pulse pressures, and their measurements are increasingly used to assess cardiovascular risk. Aortic stiffness has independent predictive value for all-cause and cardiovascular mortality in general populations and in patients with end-stage renal disease. Arterial stiffening in patients with chronic kidney disease and those with end-stage renal disease is of multifactorial origin with extensive arterial calcifications representing a major covariate. Carotid-femoral pulse wave velocity is a direct measure of aortic stiffness and is the 'gold standard' for its evaluation in clinical and epidemiological studies.
Assuntos
Artérias/fisiopatologia , Doenças Cardiovasculares/etiologia , Nefropatias/complicações , Falência Renal Crônica/complicações , Fatores Etários , Pressão Sanguínea , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Complacência (Medida de Distensibilidade) , Humanos , Nefropatias/fisiopatologia , Falência Renal Crônica/fisiopatologia , Fluxo Pulsátil , Fatores de RiscoRESUMO
Physiologic laminar shear stress (SS) is crucial for normal vascular structure and function. As a result of anemia-related lower whole-blood viscosity (WBV), SS could be reduced in patients with ESRD and might be associated with arterial functional alterations. In 44 patients with ESRD and 25 control subjects, brachial artery (BA) compliance and BA diameter changes (flow-mediated dilation [FMD[) were evaluated in response to local shear rate and SS changes during hand warming-induced hyperemia. Patients with ESRD and control subjects had similar BA blood flow, but SS was lower in patients with ESRD (P < 0.001), with lower shear rate (P < 0.01) and lower WBV (P < 0.0001). In control subjects, SS was positively (and physiologically) correlated with arterial diameter (P < 0.001). In contrast, in patients with ESRD, larger arterial diameter was associated with low SS (P < 0.05) and increased arterial wall elastic modulus (P < 0.001). Anemia-associated low WBV aggravates low shear rate, further contributing to SS reduction. These abnormalities were associated with decreased vasodilating response to endothelial mechanical stimulation. Compared with control subjects, BA compliance and FMD increases in response to hand warming-induced increased SS were lower in ESRD patients (P < 0.01), whereas their BA diameter response to glyceryl trinitrate did not differ. The long-term WBV and SS increases after anemia correction improved FMD (P < 0.01) and BA compliance (P < 0.05) and heightened arterial wall sensitivity to mechanical stimulation. Maintenance low SS as a result of anemia could play an indirect role in arterial dysfunction in patients with ESRD.
Assuntos
Artéria Braquial/fisiopatologia , Falência Renal Crônica/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Artéria Braquial/crescimento & desenvolvimento , Artéria Braquial/fisiologia , Feminino , Temperatura Alta , Humanos , Nefropatias/classificação , Nefropatias/fisiopatologia , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Pulso Arterial , Valores de Referência , Diálise Renal , Estresse MecânicoRESUMO
Shear stress is a major determinant of endothelial apoptosis, but its role in the in vivo release of shed membrane microparticles by endothelial cells remains unknown. Thus, we sought to evaluate the possible relationship between circulating endothelial microparticle levels and laminar shear stress in end-stage renal disease patients with high cardiovascular risk, whose levels of endothelial microparticles are elevated. In 34 hemodialyzed patients, we analyzed the relationships between brachial artery and aortic shear stress and circulating microparticles levels. Only endothelial microparticles were inversely correlated with laminar shear stress values (P<0.0001) or its components shear rate and whole blood viscosity, independent of age or arterial blood pressure. Changes in hematocrit resulting from hemodialysis-induced hemoconcentration or erythropoietin anemia improvement induced a significant increase in whole blood viscosity and shear stress and were associated with a significant decrease in endothelial microparticles with a significant and inverse correlation with changes in hematocrit/hemoglobin or laminar shear stress. These results demonstrate that, in end-stage renal disease patients, laminar shear stress is an important determinant of plasma levels of endothelial microparticles. Anemia as an important determinant of whole blood viscosity and shear stress, contributes to endothelial apoptosis, and could play an indirect role in the pathogenesis of accelerated arteriosclerosis in this high-risk population.
Assuntos
Membrana Celular/ultraestrutura , Células Endoteliais/ultraestrutura , Falência Renal Crônica/sangue , Falência Renal Crônica/patologia , Aorta/fisiopatologia , Apoptose , Viscosidade Sanguínea , Artéria Braquial/fisiopatologia , Endotélio Vascular/fisiopatologia , Hematócrito , Hemoglobinas/análise , Humanos , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Tamanho da Partícula , Diálise Renal , Estresse MecânicoRESUMO
In ESRD, arterial function is abnormal, characterized by decreased capacitive function (arterial stiffening) and reduced conduit function, shown by diminished flow-mediated dilation (FMD). The pathophysiology of these abnormalities is not clear, and this cross-sectional study analyzed possible relationships among arterial alterations and cardiovascular risk factors, including mineral metabolism parameters, such as serum parathormone, and vitamin D "nutritional" and "hormonal" status by measuring serum 25-hydroxyvitamin D [25(OH)D(3)] and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] levels. Aortic stiffness (pulse wave velocity), brachial artery (BA) distensibility (echotracking; n = 42), BA FMD (hand-warming; n = 37), and arterial calcification scores (echography and plain x-rays) were measured in 52 stable and uncomplicated patients who were on hemodialysis. 25(OH)D(3) and 1,25(OH)(2)D(3) serum levels were low and weakly correlated (r = 0.365, P < 0.05). After adjustment for BP and age, multivariate analyses indicated that 25(OH)D(3) and 1,25(OH)(2)D(3) were negatively correlated with aortic pulse wave velocity (P < 0.001) and positively correlated with BA distensibility (P < 0.01) and FMD (P < 0.001). Arterial calcification scores were not independently associated with 25(OH)D(3) and 1,25(OH)(2)D(3) serum concentrations. These results suggest that nutritional vitamin D deficiency and low 1,25(OH)(2)D(3) could be associated with arteriosclerosis and endothelial dysfunction in patients who have ESRD and are on hemodialysis.
Assuntos
Valva Aórtica/fisiopatologia , Artérias/fisiopatologia , Pressão Sanguínea , Falência Renal Crônica/fisiopatologia , Minerais/metabolismo , Deficiência de Vitamina D/fisiopatologia , Vitamina D/análogos & derivados , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Nefropatias/complicações , Diálise Renal , Deficiência de Vitamina D/etiologiaRESUMO
PURPOSE OF REVIEW: Cardiovascular disease is a major factor in the high mortality of patients with end-stage renal disease, and this population is particularly appropriate to analyse the impact of cardiovascular risk markers on outcome. RECENT FINDINGS: Cardiovascular risk markers in end-stage renal disease include age, left ventricular mass, carotid intima-media thickness, blood pressure and aortic stiffness (pulse wave velocity). Aortic pulse wave velocity has been shown to be an independent predictor of cardiovascular mortality in patients with end-stage renal disease and the general population. Aortic pulse wave velocity has the highest sensitivity and specificity as a predictor of cardiovascular death in end-stage renal disease patients. Pulse wave velocity is an integrated index of vascular function and structure, and is a major determinant of systolic hypertension, thereby increasing left ventricular afterload, left ventricular hypertrophy and left ventricular oxygen consumption. Decreased diastolic blood pressure, another consequence of arterial stiffening, is associated with decreased coronary perfusion contributing to ischaemic heart disease and evolution of adaptive into maladaptive left ventricular hypertrophy. SUMMARY: Aortic stiffness measurements could serve as an important tool in identifying end-stage renal disease patients at higher risk of cardiovascular disease. The ability to identify these patients would lead to better risk stratification and earlier and more cost-effective preventive therapy.
Assuntos
Arteriosclerose/etiologia , Calcinose/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diálise Renal/efeitos adversos , Adulto , Distribuição por Idade , Idoso , Arteriosclerose/epidemiologia , Biomarcadores/sangue , Calcinose/epidemiologia , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Diálise Renal/métodos , Medição de Risco , Distribuição por Sexo , Taxa de SobrevidaRESUMO
The aorta is the principal capacitive element of the arterial tree and its increased stiffness, determined by measurement of aortic pulse wave velocity (PWV), is a strong independent predictor of cardiovascular mortality in the general population and end-stage renal disease (ESRD) patients. Whether stiffness of ESRD patients' peripheral arteries has the same prognostic value has never been investigated. A cohort of 305 ESRD patients was followed for 70+/-49 months (mean+/-SD). Ninety-six deaths of cardiovascular origin occurred. At entry into the study, together with standard clinical and biochemical analyses, patients' aortic, brachial artery, and femorotibial PWV were determined. Based on Kaplan-Meier survival curve analyses and Cox proportional hazards analyses, adjusted for age, pulse pressure, and clinical data, aortic PWV was a significant and independent predictor of outcome. Neither brachial artery nor femotibial artery stiffness was able to predict cardiovascular outcome. Receiver operating characteristic curve analysis of aortic PWV indicated the cutoff value of 10.75 m/s, with 84% sensitivity, 73% specificity, 87% negative predictive value, and 72% positive predictive value. These results provide evidence that, in ESRD, increased stiffness of capacitive arteries, like the aorta, is an independent strong predictor of cardiovascular mortality, whereas stiffness of peripheral conduit arteries had no prognostic value.
Assuntos
Aorta/fisiopatologia , Artéria Braquial/fisiopatologia , Artéria Femoral/fisiopatologia , Falência Renal Crônica/fisiopatologia , Artérias da Tíbia/fisiopatologia , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Elasticidade , Feminino , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fluxo Pulsátil , Curva ROCRESUMO
PURPOSE OF REVIEW: Arterial calcification in chronic kidney disease (CKD) is associated with increased cardiovascular risk. The mechanisms responsible for arterial calcification include alterations of mineral metabolism and expression of mineral-regulating proteins. RECENT FINDINGS: Arterial calcification is similar to bone formation, involving differentiation of vascular smooth muscle cells (VSMCs) into phenotypically distinct osteoblast-like cells. Elevated phosphate and/or calcium trigger a concentration-dependent increase of calcium precipitates in VSMC in vitro. The calcification is initiated by VSMC release of membrane-bound matrix vesicles and formation of apoptotic bodies. The presence of serum prevents these changes, indicating the presence of calcification inhibitors. Arterial calcification occurs in two sites: the tunica intima and tunica media. Intimal calcification is a marker of atherosclerotic disease and is associated with arterial stenotic lesions. Medial calcification influences outcome by promoting arterial stiffening whose principal consequences are left-ventricular hypertrophy and altered coronary perfusion. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in CKD patients. Age, duration of dialysis, smoking and diabetes are risk factors for the development of arterial calcification in end-stage renal disease. Oversuppression of parathyroid hormone and low bone turnover potentiate the development of arterial calcification. SUMMARY: Arterial disease in CKD patients is characterized by extensive calcification. Evidence has accumulated pointing to the active and regulated nature of the calcification process. Elevated phosphate and calcium may stimulate sodium-dependent phosphate cotransport involving osteoblast-like changes in cellular gene expression. Arterial calcification is responsible for stiffening of the arteries with increased left-ventricular afterload and abnormal coronary perfusion as the principal clinical consequences.
Assuntos
Arteriosclerose/etiologia , Calcinose/etiologia , Uremia/complicações , Doenças Vasculares/etiologia , Animais , Artérias/patologia , Humanos , Falência Renal Crônica/complicaçõesRESUMO
Endothelial dysfunction and arterial stiffness are major determinants of cardiovascular risk in patients with end-stage renal failure (ESRF). Microparticles are membrane fragments shed from damaged or activated cells. Because microparticles can affect endothelial cells, this study investigated the relationship between circulating microparticles and arterial dysfunction in patients with ESRF and identified the cellular origin of microparticles associated with these alterations. Flow cytometry analysis of platelet-free plasma from 44 patients with ESRF indicated that circulating levels of Annexin V+ microparticles were increased compared with 32 healthy subjects, as were levels of microparticles derived from endothelial cells (three-fold), platelets (16.5-fold), and erythrocytes (1.6-fold). However, when arterial function was evaluated noninvasively in patients with ESRF, only endothelial microparticle levels correlated highly with loss of flow-mediated dilation (r = -0.543; P = 0.004), increased aortic pulse wave velocity (r = 0.642, P < 0.0001), and increased common carotid artery augmentation index (r = 0.463, P = 0.0017), whereas platelet-derived, erythrocyte-derived, and Annexin V+ microparticle levels did not. In vitro, microparticles from patients with ESRF impaired endothelium-dependent relaxations and cyclic guanosine monophosphate generation, whereas microparticles from healthy subjects did not. Moreover, in vitro endothelial dysfunction correlated with endothelial-derived (r = 0.891; P = 0.003) but not platelet-derived microparticle concentrations. In fact, endothelial microparticles alone decreased endothelial nitric oxide release by 59 +/- 7% (P = 0.025). This study suggests that circulating microparticles of endothelial origin are tightly associated with endothelial dysfunction and arterial dysfunction in ESRF.
Assuntos
Endotélio Vascular/patologia , Falência Renal Crônica/patologia , Doenças Vasculares/patologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Proteína C-Reativa/metabolismo , Membrana Celular/patologia , Estruturas da Membrana Celular/patologia , Feminino , Hemodinâmica , Hemoglobinas/análise , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Valores de Referência , Doenças Vasculares/sangueRESUMO
Epidemiological and clinical studies have shown that damage to large arteries contributes to the high cardiovascular mortality in patients with end-stage renal disease (ESRD). Atherosclerosis is the most frequent cause of arterial damage. Occlusive lesions from atherosclerotic plaques (calcification) decrease the conduit function of arteries and reduce the elasticity of capacitance arteries (stiffening), affecting their dampening function. Arterial calcification and aortic stiffness are independent predictors of cardiovascular risk in the general population, and independent predictors of all-cause and cardiovascular mortality in ESRD patients. Successful treatment to reduce blood pressure (BP) and reverse aortic stiffness has a significant, BP-independent effect on survival in ESRD patients. However, response to such treatment may be limited in patients with microinflammation and raised levels of C-reactive protein.
Assuntos
Artérias/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Arteriosclerose/epidemiologia , Arteriosclerose/etiologia , Arteriosclerose/fisiopatologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doença Crônica , Humanos , PrognósticoRESUMO
The ill effects of hypertension are usually attributed to a reduction in the caliber or the number of arterioles, resulting in an increase in total peripheral resistance (TPR). This definition does not take into account the fact that BP is a cyclic phenomenon with systolic and diastolic BP being the limits of these oscillations. The appropriate term to define the arterial factor(s) opposing LV ejection is aortic input impedance which depends on TPR, arterial distensibility (D), and wave reflections (WR). D defines the capacitive properties of arterial stiffness, whose role is to dampen pressure and flow oscillations and to transform pulsatile flow and pressure in arteries into a steady flow and pressure in peripheral tissues. Stiffness is the reciprocal value of D. These parameters are BP dependent, and arteries become stiffer at high pressure. In to D which provides information about the <
Assuntos
Artérias/fisiopatologia , Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Fluxo Pulsátil/fisiologia , HumanosRESUMO
PURPOSE OF REVIEW: As epidemiological and clinical studies have shown that damage of large arteries is a major contributory factor to the high cardiovascular morbidity of patients with end-stage renal disease, such a population is particularly appropriate for analysis the impact of arterial stiffness on cardiovascular risk assessment and reduction strategies. RECENT FINDINGS: Aortic pulse wave velocity, a marker of aortic stiffness, has been shown to be a strong independent predictor of cardiovascular and all-cause mortality in patients with end-stage renal disease on hemodialysis. Local arterial stiffness assessment, namely carotid distensibility was also shown to predict cardiovascular risk, both in end-stage renal disease patients and in renal transplant recipients. Furthermore, it was shown in a therapeutic trial that the lack of aortic pulse wave velocity attenuation, despite significant drug-induced reduction in mean blood pressure, was a significant predictor of cardiovascular death in subjects with end-stage renal disease. These results support the hypothesis that measurement of aortic pulse wave velocity could help, not only in risk assessment strategies, but also in risk reduction strategies by monitoring arterial stiffness under different pharmacological regimens. The drug-related reduction of aortic pulse wave velocity could then give prognostic information, in addition to blood pressure reduction. SUMMARY: Aortic stiffness measurements could serve as an important tool in identifying end-stage renal disease patients at higher risk of cardiovascular disease. The ability to identify these patients would lead to better risk stratification and earlier and more cost-effective preventive therapy.