RESUMO
BACKGROUND: Arterial hypertrophy and interstitial fibrosis are important characteristics in kidneys of angiotensinogen-knockout (Atg -/-) mice. In these mice, which exhibit polyuria and hypotension, sympathetic nerve signaling is estimated to be compensatorily hyperactive. Furthermore, transforming growth factor (TGF)-ß1 is overexpressed in mice kidneys. To determine whether sympathetic nerve signaling and TGF-ß1 exacerbate arterial hypertrophy and interstitial fibrosis, intervention studies of such signaling are required. METHODS: We performed renal denervation and administered the α2-adrenergic receptor (AR) antagonist, atipamezole, to Atg -/- mice. A renin inhibitor, aliskiren, which was preliminarily confirmed to reduce TGF-ß1 gene expression in kidneys of the mice, was additionally administered to assess the effect on the arterial hypertrophy and interstitial fibrosis. RESULTS: Norepinephrine content in kidneys of Atg -/- mice was three times higher than in kidneys of wild-type mice. Interventions by renal denervation and atipamezole resulted in amelioration of the histological findings. Overexpression of TGF-ß1 gene in kidneys of Atg -/- mice was altered in a manner linked to the histological findings. Surprisingly, aliskiren reduced α2-AR gene expression, interstitial fibrosis, and arterial hypertrophy in kidneys of Atg -/- mice, which lack renin substrate. CONCLUSIONS: Alpha2-AR signaling is one of the causes of persistent renal arterial hypertrophy in Atg -/- mice. Aliskiren also angiotensinogen-independently reduces the extent of renal arterial hypertrophy, partly thorough downregulation of α2-ARs. Although renal arterial hypertrophy in Atg -/- mice appears to be of multifactorial origin, TGF-ß1 may play a key role in the persistence of such hypertrophy.
Assuntos
Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Amidas/farmacologia , Fumaratos/farmacologia , Artéria Renal/patologia , Angiotensinogênio/genética , Animais , Fibrose , Hipertrofia , Japão , Rim , Camundongos , Camundongos Endogâmicos ICR , Camundongos Knockout , Renina , Tóquio , Fator de Crescimento Transformador beta1RESUMO
BACKGROUND: The carotid bulb has a high density of baroreceptors that play an important role in maintaining blood pressure. We hypothesized that atherosclerosis of the carotid bulb would reflect the severity of orthostatic hypotension more accurately than would atherosclerosis of other carotid artery segments. METHODS: This cross-sectional study included 198 non-diabetic adults. We measured the cardio-vascular ankle index as an index of arterial stiffness, intima-media thickness in each carotid artery segment (internal carotid artery, carotid bulb, distal and proximal portions, respectively, of the common carotid artery) as a measure of atherosclerosis, and heart rate variability as a measure of cardiac autonomic function. The sit-to-stand test was used to assess severity of orthostatic hypotension. RESULTS: Intima-media thickness of the carotid bulb was correlated with orthostatic systolic blood pressure change (r = -0.218, p = 0.002), cardio-ankle vascular index (r = 0.365, p < 0.001) and heart rate variability parameters. Multivariate regression analysis revealed that among all of the segments, only intima-media thickness of the carotid bulb was an independent predictor of orthostatic systolic blood pressure change (p = 0.022). CONCLUSION: Atherosclerosis of the carotid bulb was associated with severity of orthostatic hypotension, arterial stiffening and cardiac autonomic dysfunction than that of other carotid artery segments.
RESUMO
Angiotensin II type 1 receptor-associated protein (ATRAP) promotes AT1R internalization along with suppression of hyperactivation of tissue AT1R signaling. Here, we provide evidence that renal ATRAP plays a critical role in suppressing hypertension in a mouse remnant kidney model of chronic kidney disease. The effect of 5/6 nephrectomy on endogenous ATRAP expression was examined in the kidney of C57BL/6 and 129/Sv mice. While 129/Sv mice with a remnant kidney showed decreased renal ATRAP expression and developed hypertension, C57BL/6 mice exhibited increased renal ATRAP expression and resistance to progressive hypertension. Consequently, we hypothesized that downregulation of renal ATRAP expression is involved in pathogenesis of hypertension in the remnant kidney model of chronic kidney disease. Interestingly, 5/6 nephrectomy in ATRAP-knockout mice on the hypertension-resistant C57BL/6 background caused hypertension with increased plasma volume. Moreover, in knockout compared to wild-type C57BL/6 mice after 5/6 nephrectomy, renal expression of the epithelial sodium channel α-subunit and tumor necrosis factor-α was significantly enhanced, concomitant with increased plasma membrane angiotensin II type 1 receptor in the kidneys. Thus, renal ATRAP downregulation is involved in the onset and progression of blood pressure elevation caused by renal mass reduction, and implicates ATRAP as a therapeutic target for hypertension in chronic kidney disease.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Hipertensão/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Insuficiência Renal Crônica/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Pressão Sanguínea , Regulação para Baixo , Canais Epiteliais de Sódio/metabolismo , Humanos , Rim/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Insuficiência Renal Crônica/complicações , Renina/sangue , Renina/metabolismo , Sistema Renina-Angiotensina , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Contrast-induced nephropathy (CIN) and chronic kidney disease (CKD) are associated with poor outcomes after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI); however, its combined prognostic significance remains unclear. We enrolled 577 patients with AMI undergoing primary PCI within 12 h after symptom onset and measured serum creatinine on admission and the next 3 days. CKD was defined as admission estimated glomerular filtration rate <60 ml/min/1.73 m2, and CIN was defined as creatinine increase ≥0.5 mg/dl or ≥25 % from baseline within the first 72 h. Patients were stratified according to the presence or absence of CKD and CIN. In patients with no CKD and no CIN (n = 244), no CKD but CIN (n = 152), CKD but no CIN (n = 127), and both CKD and CIN (n = 54), the 3-year major adverse cardiovascular events (MACE: a combination of all-cause mortality, nonfatal reinfarction, or heart failure requiring rehospitalization) were 8, 9, 13, and 35 %, respectively (p < 0.001). Multivariate analysis showed that as compared with no CKD and no CIN, hazard ratios (95 % CI) for MACE associated with no CKD but CIN, CKD but no CIN, and both CKD and CIN were 0.91 (0.44-1.84; p = 0.79), 1.11 (0.5-2.23; p = 0.77), and 2.98 (1.48-6.04; p = 0.002), respectively. In patients with AMI undergoing primary PCI, the combination of CKD and CIN is significantly associated with adverse long-term outcomes.
Assuntos
Meios de Contraste/efeitos adversos , Angiografia Coronária/efeitos adversos , Nefropatias/induzido quimicamente , Intervenção Coronária Percutânea , Insuficiência Renal Crônica/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Creatinina/sangue , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Resultado do TratamentoRESUMO
BACKGROUND: Tolvaptan, a vasopressin V2 receptor blocker, has a diuretic effect for patients with heart failure. However, there were a few data concerning the effects of tolvaptan in patients with chronic kidney disease (CKD). METHODS: We retrospectively analyzed 21 patients with chronic heart failure and CKD. Tolvaptan was co-administered with other diuretics in-use, every day. We compared clinical parameters before and after the treatments with tolvaptan. Furthermore, we examined the correlations between baseline data and the change of body weight. RESULTS: Tolvaptan decreased the body weight and increased the urine volume (p = 0.001). The urine osmolality significantly decreased throughout the study period. Urinary Na/Cr ratio and FENa changed significantly after 4 h, and more remarkable after 8 h (p = 0.003, both). Serum creatinine increased slightly after 1 week of treatment (p = 0.012). The alteration of body weight within the study period correlated negatively with the baseline urine osmolality (r = -0.479, p = 0.038), the baseline urine volume (r = -0.48, p = 0.028), and the baseline inferior vena cava diameter (IVCD) (r = -0.622, p = 0.017). Hyponatremia was improved to the normal value, and the augmentations of the sodium concentration were negatively associated with the basal sodium levels (p = 0.01, r = -0.546). CONCLUSIONS: Tolvaptan is effective in increasing diuresis and improved hyponatremia, even in patients with CKD. The baseline urine osmolality, urine volume, and IVCD may be useful predictors for diuretic effects of tolvaptan.
Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Benzazepinas/uso terapêutico , Diuréticos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Rim/efeitos dos fármacos , Insuficiência Renal Crônica/complicações , Idoso , Antagonistas dos Receptores de Hormônios Antidiuréticos/efeitos adversos , Benzazepinas/efeitos adversos , Diurese/efeitos dos fármacos , Diuréticos/efeitos adversos , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Eliminação Renal/efeitos dos fármacos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Sódio/sangue , Sódio/urina , Fatores de Tempo , Tolvaptan , Resultado do Tratamento , Urina/química , Urodinâmica/efeitos dos fármacos , Redução de Peso/efeitos dos fármacosRESUMO
As there may be an association between within-visit blood pressure (BP) variability and cardiovascular disease (CVD), we investigated the clinical significance of this BP variability in non-dialysis chronic kidney disease (CKD) patients. MATERIALS AND METHODS: According to the median of coefficient of variation (CV) of three systolic BP (SBP) readings within a single visit, we divided hypertensive patients with stage G1-4 CKD already treated with antihypertensive therapy into the high SBP-CV group and the low SBP-CV group. Univariate and multivariate linear regression analyses were also performed to explore the contributing factors to within-visit BP variability. RESULTS: In the high SBP-CV group, the clinic BP, total cholesterol level, dyslipidemia, and past history of CVD were significantly greater, while α1-blockers and renin-angiotensin system (RAS) inhibitors usage were significantly reduced compared with the lower SBP-CV group. Within-visit BP variability was significantly and positively correlated with total cholesterol (R = 0.392, P < 0.001) and low-density lipoprotein cholesterol (R = 0.284, P = 0.013). Total cholesterol (ß = 0.269, P = 0.024), α1-blockers usage (ß = -0.260, P = 0.015), and RAS inhibitors usage (ß = -0.266, P = 0.017) were shown to independently contribute to the within-visit BP variability after adjustment for age, sex, presence of diabetes, CVD history, statins usage, and clinic SBP. CONCLUSIONS: We show that within-visit BP variability may be a clinically relevant factor of CVD risk, and lipid lowering and/or anti-hypertensive therapies using RAS inhibitors and α1-blockers may be associated with the improved within-visit BP variability observed in non-dialysis CKD patients.
Assuntos
Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/etiologia , Hipertensão/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Idoso , Anti-Hipertensivos/uso terapêutico , Determinação da Pressão Arterial , Doenças Cardiovasculares/tratamento farmacológico , Feminino , Humanos , Hipertensão/complicações , Lipoproteínas LDL/metabolismo , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Sistema Renina-Angiotensina/fisiologia , Fatores de RiscoRESUMO
Activation of tissue renin-angiotensin system (RAS), mainly mediated by an angiotensin II (Ang II) type 1 receptor (AT1R), plays an important role in the development of obesity-related metabolic disorders. We have shown that AT1R-associated protein (ATRAP), a specific binding protein of AT1R, functions as an endogenous inhibitor to prevent excessive activation of tissue RAS. In the present study, we newly generated ATRAP/Agtrap-floxed (ATRAPfl/fl) mice and adipose tissue-specific ATRAP downregulated (ATRAPadipoq) mice by the Cre/loxP system using Adipoq-Cre. Using these mice, we examined the functional role of adipose ATRAP in the pathogenesis of obesity-related metabolic disorders. Compared with ATRAPfl/fl mice, ATRAPadipoq mice exhibited a decreased ATRAP expression in visceral white adipose tissue (WAT) and brown adipose tissue (BAT) by approximately 30% and 85%, respectively. When mice were fed a high-fat diet, ATRAPfl/fl mice showed decreased endogenous ATRAP expression in WAT that was equivalent to ATRAPadipoq mice, and there was no difference in the exacerbation of dietary obesity and glucose and lipid metabolism. These results indicate that ATRAP in BAT does not influence the pathogenesis of dietary obesity or metabolic disorders. Future studies that modulate ATRAP in WAT are necessary to assess its in vivo functions in the development of obesity-related metabolic disorders.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Tecido Adiposo Marrom/metabolismo , Doenças Metabólicas/metabolismo , Obesidade/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Metabolismo dos Lipídeos , Doenças Metabólicas/etiologia , Doenças Metabólicas/genética , Camundongos , Obesidade/complicações , Obesidade/etiologiaAssuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/terapia , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Comportamento de Redução do Risco , Anti-Hipertensivos/efeitos adversos , Consenso , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Japão/epidemiologia , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
Left ventricular (LV) fibrosis plays an important role in the development of heart failure with preserved ejection fraction (HFpEF). We investigated whether chronic peroxisome proliferator-activated receptor gamma agonism with pioglitazone can prevent the development of HFpEF. We also evaluated the role of Wnt-ß-catenin signaling in the development of HFpEF, and its relationship to peroxisome proliferator-activated receptor gamma signaling. Dahl salt-sensitive rats placed on an 8% NaCl diet from age 6 weeks were used as HFpEF model. Rats placed on 0.3% NaCl diet served as controls (n = 7). HFpEF model rats were randomized to no treatment (n = 7) or treatment with pioglitazone (2.5 mg/kg per day, n = 7) at age 13 weeks. Pioglitazone administration from age 13 to 21 weeks attenuated the development of LV fibrosis and stiffening (both P < 0.05), and subsequently prevented the development of HFpEF. In the untreated HFpEF model, Wnt1, 2, 10b messenger RNA and ß-catenin protein expression levels in the left ventricle increased in the heart failure stage, along with the increase in type I collagen messenger RNA expression levels. Administration of pioglitazone attenuated the activation of Wnt-ß-catenin signaling. Our results show that pioglitazone prevented the development of LV fibrosis and HFpEF in a rat model, at least partly due to attenuated Wnt-ß-catenin signaling.
Assuntos
Insuficiência Cardíaca/prevenção & controle , Ventrículos do Coração/efeitos dos fármacos , Hipertensão/tratamento farmacológico , PPAR gama/agonistas , Tiazolidinedionas/farmacologia , Disfunção Ventricular Esquerda/prevenção & controle , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Fibrose , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , PPAR gama/metabolismo , Pioglitazona , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Endogâmicos Dahl , Cloreto de Sódio na Dieta , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Disfunção Ventricular Esquerda/genética , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Proteína Wnt1/genética , Proteína Wnt1/metabolismo , Proteína Wnt2/genética , Proteína Wnt2/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMO
BACKGROUND: Target lesion calcification is known to influence percutaneous coronary intervention. We evaluated the effects of rotational atherectomy (RA) and subsequent balloon angioplasty on calcified coronary lesions using optical coherence tomography (OCT). METHODSâANDâRESULTS: Thirty-seven calcified lesions in 36 patients were treated with RA followed by balloon angioplasty and stent implantation. In all patients, serial OCT images obtained after RA, after balloon angioplasty, and after stent implantation were analyzed at 1-mm intervals. The arc and thickness of the calcium component were measured after RA. The formation of calcium cracks was assessed after balloon angioplasty. A total of 625 segments were analyzed. The formation of calcium crack after balloon angioplasty was associated with greater stent cross-sectional area (7.38±1.92 vs. 7.13±1.68 mm(2), P=0.035) as well as greater lumen gain (3.89±1.53 vs. 3.40±1.46 mm(2), P<0.001). Segments with calcium cracks after angioplasty had a larger median calcium arc (360°, IQR, 246-360° vs. 147°, IQR, 118-199°, P<0.001) and a thinner calcium thickness (0.53±0.28 vs. 1.02±0.42 mm, P<0.001) than those without. The optimal thresholds of calcium arc and calcium thickness for the prediction of cracks were 227° and 0.67 mm, respectively. CONCLUSIONS: Larger calcium arc and thinner calcium thickness were associated with formation of calcium crack. Presence of calcium crack was the important determinant of optimal stent expansion. (Circ J 2016; 80: 1413-1419).
Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Aterectomia Coronária/efeitos adversos , Placa Aterosclerótica/patologia , Tomografia de Coerência Óptica , Calcificação Vascular/patologia , Idoso , Idoso de 80 Anos ou mais , Dilatação Patológica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/terapia , Estudos ProspectivosRESUMO
BACKGROUND: We hypothesized the cardio-ankle vascular stiffness index (CAVI) could predict future cardiovascular events. METHODSâANDâRESULTS: We enrolled 288 consecutive patients with acute coronary syndrome (ACS) who underwent CAVI measurement soon after the onset of ACS. Exclusion criteria were as follows: unable to detect significant stenosis by coronary angiography, severe aortic insufficiency, peripheral artery disease, atrial fibrillation (AF), informed consent was not given. We divided the patients into 2 groups according to the cutoff value of CAVI determined by receiver-operating characteristics curve for the prediction of cardiovascular events: low CAVI group, 135 patients with CAVI ≤8.325; high CAVI group, 153 patients with CAVI >8.325. Patients were followed up for a median period of 15 months. The primary and secondary endpoints were the incidence of cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke), and nonfatal ischemic stroke. Of the 288 patients, cardiovascular events occurred in 19 patients (6.6%). The Kaplan-Meier estimate of the event-free rate revealed cardiovascular events occurred more frequently in the high CAVI group than in the low CAVI group (log-rank, P<0.001). Multiple adjusted Cox proportional hazards analysis, including age, indicated the high CAVI group was an independent predictor of cardiovascular events (hazard ratio [HR] 18.00, P=0.005), and nonfatal ischemic stroke (HR 9.371, P=0.034). CONCLUSIONS: High CAVI is an independent predictor of cardiovascular events and nonfatal ischemic stroke in patients with ACS. (Circ J 2016; 80: 1420-1426).
Assuntos
Síndrome Coronariana Aguda/complicações , Rigidez Vascular , Síndrome Coronariana Aguda/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnósticoRESUMO
BACKGROUND: The relationship between plasma glucagon-like peptide-1 (GLP-1) and coronary plaque characteristics in humans remains unclear. METHODSâANDâRESULTS: A total of 85 culprit coronary vessels excluding the 10-mm culprit segments in non-diabetic patients with acute coronary syndrome (ACS) were examined using integrated backscatter intravascular ultrasound, performed using a 40-MHz intravascular catheter before PCI. All patients underwent 75-g oral glucose tolerance test (OGTT), and the plasma GLP-1 response was evaluated on the basis of the area under the GLP-1 concentration-time curve (GLP-1 AUC) from 0 to 120 min. Patients in the low GLP-1 AUC tertile had a significantly greater percentage lipid area than did patients in the intermediate and high tertiles (low tertile vs. intermediate tertile vs. high tertile: 57.3 ± 12.1% vs. 47.2 ± 15.4% vs. 46.3 ± 12.7%, P<0.01, ANOVA) and a smaller percentage fibrosis area (38.1 ± 9.4% vs. 44.6 ± 11.5% vs. 45.7 ± 9.0%; P=0.01, ANOVA). On multiple regression analysis, low GLP-1 AUC tertile was independently associated with percentage lipid area. CONCLUSIONS: Low plasma GLP-1 during 75-g OGTT is associated with increased lipid content in non-diabetic patients with ACS, suggesting that plaque vulnerability is increased in this subgroup of patients.
Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Peptídeo 1 Semelhante ao Glucagon/sangue , Placa Aterosclerótica , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico por imagem , Idoso , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico por imagem , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: Glycemic variability (GV) is associated with coronary plaque rupture at the culprit lesion in acute myocardial infarction (AMI). The present study determined the relationship between GV and coronary plaque vulnerability in the non-culprit vessel. METHODS AND RESULTS: The present prospective study involved 46 patients with first-episode acute coronary syndrome (ACS) who underwent optical coherence tomography in the non-culprit vessel. The relationship between GV, assessed with continuous glucose monitoring system, and the presence of thin-cap fibroatheroma (TCFA) at the non-culprit plaque with mild-to-moderate stenosis in the non-culprit vessel, was assessed. GV was quantified using mean amplitude of glycemic excursion (MAGE). Patients were divided into tertiles according to MAGE. TCFA was observed in 13 (28%) of the 46 patients. Fibrous cap thickness was thinner (MAGE tertiles: high, 80±40 µm; intermediate, 152±122 µm; low, 155±102 µm; P=0.01), and TCFA was more common (MAGE tertiles: high, 50%; intermediate, 27%; low, 7%; P=0.03) in patients with high MAGE. On multivariate logistic analysis high MAGE was the only significant determinant of TCFA, independent of coronary risk factors (OR, 5.000; P=0.021), homeostasis model assessment of insulin resistance, and hemoglobin A1c(OR, 5.674; P=0.018). CONCLUSIONS: High MAGE measured early after the onset of first-episode ACS correlated with thinner fibrous cap thickness and higher prevalence of TCFA at the non-culprit plaque in the non-culprit vessel.
Assuntos
Síndrome Coronariana Aguda/patologia , Doença da Artéria Coronariana/patologia , Infarto do Miocárdio/patologia , Placa Aterosclerótica/patologia , Tomografia de Coerência Óptica , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: There is no information on differences in the effects of moderate- and low-intensity statins on coronary plaque in patients with acute coronary syndrome (ACS). The aim of this study was to compare the effects of 4 different statins in patients with ACS, using intravascular ultrasound (IVUS). METHODSâANDâRESULTS: A total of 118 patients with ACS who underwent IVUS before percutaneous coronary intervention and who were found to have mild to moderate non-culprit coronary plaques were randomly assigned to receive either 20 mg/day atorvastatin or 4 mg/day pitavastatin (moderate-intensity statin therapy), or 10 mg/day pravastatin or 30 mg/day fluvastatin (low-intensity statin therapy). IVUS at baseline and at end of 10-month treatment was available in 102 patients. Mean percentage change in plaque volume (PV) was -11.1±12.8%, -8.1±16.9%, 0.4±16.0%, and 3.1±20.0% in the atorvastatin, pitavastatin, pravastatin, and fluvastatin groups, respectively (P=0.007, ANOVA). Moderate-intensity statin therapy induced regression of PV, whereas low-intensity statin therapy produced insignificant progression (-9.6% vs. 1.8%, P<0.001). On multivariate linear regression analysis, moderate-intensity statin therapy (P=0.02) and uric acid at baseline (P=0.02) were significant determinants of large percent PV reduction. LDL-C at follow-up did not correlate with percent PV change. CONCLUSIONS: Moderate-intensity statin therapy induced regression of coronary PV, whereas low-intensity statin therapy resulted in slight progression of coronary PV in patients with ACS. (Circ J 2016; 80: 1634-1643).
Assuntos
Síndrome Coronariana Aguda/terapia , Doença da Artéria Coronariana/terapia , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Intervenção Coronária Percutânea , Placa Aterosclerótica/terapia , Síndrome Coronariana Aguda/patologia , Idoso , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/patologia , Estudos ProspectivosRESUMO
The prognostic significance of the SYNTAX (Synergy between PCI with Taxus and cardiac surgery) score has recently been demonstrated in patients with stable multivessel or left main coronary artery disease (CAD). The present study determines whether adding the SYNTAX score to Framingham risk score (FRS), left ventricular ejection fraction (LVEF) and presence of myocardial infarction (MI) by late gadolinium enhancement (LGE) magnetic resonance imaging can improve the risk stratification in patients with stable CAD. We calculated the SYNTAX score in 161 patients with stable CAD (mean age: 66 ± 10 years old). During a mean follow-up of 2.3 years, 56 (35 %) of 161 patients developed cardiovascular events defined as cardiovascular death, non-fatal MI, cerebral infarction, unstable angina pectoris, hospitalization due to heart failure and revascularization. Multivariate Cox regression analysis selected triglycerides [hazard ratio (HR): 1.005 (95 % confidence interval (CI): 1.001-1.008), p < 0.008], presence of LGE [HR: 6.329 (95 % CI: 2.662-15.05), p < 0.001] and the SYNTAX score [HR: 1.085 (95 % CI: 1.044-1.127), p < 0.001] as risk factors for future cardiovascular events. Adding the SYNTAX score to FRS, EF and LGE significantly improved the net reclassification index (NRI) [40.4 % (95 % CI: 18.1-54.8 %), p < 0.05] with an increase in C-statistics of 0.089 (from 0.707 to 0.796). An increase in C-statistics and significant improvement of NRI showed that adding the SYNTAX score to the FRS, LVEF and LGE incrementally improved risk stratification in patient with stable CAD.
Assuntos
Meios de Contraste/administração & dosagem , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Gadolínio DTPA/administração & dosagem , Imageamento por Ressonância Magnética , Idoso , Angina Instável/etiologia , Biomarcadores/sangue , Infarto Encefálico/etiologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Progressão da Doença , Feminino , Insuficiência Cardíaca/etiologia , Hospitalização , Humanos , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/etiologia , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Volume Sistólico , Fatores de Tempo , Triglicerídeos/sangue , Função Ventricular EsquerdaRESUMO
BACKGROUND: Few studies have examined how renin-angiotensin system inhibitors (RASI) delay dialysis initiation in patients with advanced chronic kidney disease (CKD). We conducted a retrospective survey to examine this subject. METHODS: We reviewed the records of patients with advanced CKD for the 60-month period before dialysis initiation between 1990 and 2015. Patients were classified based on the decade of dialysis initiation into the 1990s, 2000s, and 2010s groups. The rates of antihypertensive medications administered were assessed. The rate of decline of renal function was evaluated by the slope of reciprocal serum creatinine (SRSC). Multiple regression analyses were conducted to evaluate factors contributing to renoprotection. RESULTS: The duration of RASI administration was longer in the 2010s than in 2000s and 1990s. Both diabetic and non-diabetic patients had lower SRSC in the 2010s compared to the 2000s. In the 2010s, the rate of RASI administration during the 60-month pre-dialysis period showed an initial rise followed by a downward trend, although the rates of administration of the other classes of antihypertensives increased continuously. Multivariate regression analyses identified age, blood pressure, diuretics, α-blockers, α-methyldopa and RASI as independent predictors of SRSC in the 2010s. The rate of RASI administration correlated with serum potassium concentration. CONCLUSION: Our findings suggest that in the 2010s, RASI with other antihypertensive agents contributed to renoprotection in advanced CKD patients, but they were underused because of the concern over hyperkalemia. In real-world clinical practice, physicians may feel great hesitation in using RASI in patients with advanced CKD.
Assuntos
Anti-Hipertensivos/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/farmacologia , Creatinina/sangue , Nefropatias Diabéticas/sangue , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Análise de Regressão , Estudos Retrospectivos , Adulto JovemRESUMO
We compared the therapeutic effects of aliskiren (direct renin inhibitor (DRI) group) with angiotensin II (Ang II) type 1 receptor blockers (ARBs) (ARB group) on clinic blood pressure (BP) and ambulatory BP in 36 hypertensive chronic kidney disease (CKD) patients. The baseline clinic BP levels and the after-treatment/baseline (A/B) ratios of clinic BP levels, estimated after 24-week treatment period, were similar in DRI group (n = 18) and ARB group (n = 18). With respect to the effects on ambulatory BP, the A/B ratios of the daytime and nighttime systolic BP in DRI group were significantly higher than those in ARB group. The A/B ratio of ankle-brachial pressure index after the study was higher in the DRI group compared with the ARB group. The results of the present study suggest that DRI therapy is not superior to ARB therapy in lowering ambulatory BP in hypertensive CKD patients, in spite of comparable clinic BP-lowering effects.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/efeitos dos fármacos , Taxa de Filtração Glomerular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Renina/antagonistas & inibidores , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Hipertensão/etiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Renina/sangueRESUMO
We examined the efficacy of single-pill irbesartan/amlodipine combination-based therapy for 12 weeks in 20 hypertensive chronic kidney disease (CKD) patients, by evaluating self-measured home blood pressure (BP) profile. The single-pill irbesartan/amlodipine combination-based therapy decreased clinic BP and home BP (morning, evening, and nighttime BPs), and improved within-visit clinic BP variability, day-by-day home BP variability (morning and evening), and nighttime home BP variability. Furthermore, the single-pill combination-based therapy reduced albuminuria and exerted improved parameters of vascular function. These results indicate that this single-pill combination-based therapy may exert beneficial effects on clinic and home BP profiles as well as on renal and vascular damages, in hypertension with CKD.
Assuntos
Anlodipino/administração & dosagem , Compostos de Bifenilo/administração & dosagem , Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Tetrazóis/administração & dosagem , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Pressão Sanguínea/fisiologia , Bloqueadores dos Canais de Cálcio/administração & dosagem , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Hipertensão/etiologia , Hipertensão/fisiopatologia , Irbesartana , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis in many parts of the world. Although previous genome-wide association studies (GWAS) identified the major susceptibility loci for IgAN, the causal genes currently remain unknown. We performed a GWAS using 23 465 microsatellite (MS) markers to identify genes related to IgAN in a Japanese population. A pooled sample analysis was conducted in three-stage screenings of three independent case-control populations, and after the final step of individual typing, 11 markers survived. Of these, we focused on two regions on 6p21 and 12q21 because they (i) showed the strongest relationship with IgAN, and (ii) appeared to be highly relevant to IgAN in view of several previous studies. These regions contained the HLA, TSPAN8 and PTPRR genes. This study on GWAS, using >20 000 MS markers, provides a new approach regarding susceptible genes for IgAN for investigators seeking new tools for the prevention and treatment of IgAN.
Assuntos
Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 6/genética , Glomerulonefrite por IGA/genética , Antígenos HLA/genética , Repetições de Microssatélites , Proteínas Tirosina Fosfatases Classe 7 Semelhantes a Receptores/genética , Tetraspaninas/genética , Povo Asiático , Feminino , Estudo de Associação Genômica Ampla , Humanos , Japão , MasculinoRESUMO
BACKGROUND: Blood glucose variability is receiving considerable attention as a new risk factor for coronary artery disease. This study aimed to investigate the association between blood glucose variability and coronary plaque tissue characteristics. METHODS: In 57 patients with acute coronary syndrome, integrated backscatter intravascular ultrasound (IB-IVUS) and gray-scale IVUS were performed before balloon dilatation or stent implantation in the culprit vessels. Standard IVUS indices were evaluated for volume index (volume/length), and plaque components were measured by IB-IVUS for percent tissue volume. In addition to conventional glucose indicators, blood glucose variability in a stable state was determined by calculating the mean amplitude of glycemic excursions (MAGE) using a continuous glucose monitoring system. RESULTS: Higher MAGE values were significantly correlated with larger percent plaque volumes (r = 0.32, p = 0.015), and increased lipid (r = 0.44, p = 0.0006) and decreased fibrous (r = -0.45, p = 0.0005) plaque components. In contrast, HbA1c or fasting plasma glucose values were not significantly correlated with plaque volumes and percent plaque components. Homeostasis model assessment of insulin resistance values were positively correlated with vessel (r = 0.35, p = 0.007) and plaque (r = 0.27, p = 0.046) volumes, but not with percent plaque components. In multiple regression analysis, higher MAGE values were independently associated with increased lipid (ß = 0.80, p = 0.0035) and decreased fibrous (ß = -0.79, p = 0.0034) contents in coronary plaques. CONCLUSIONS: Among all glucose indicators studied, only higher blood glucose variability was an independent determinant of increased lipid and decreased fibrous contents with larger plaque burden, suggesting blood glucose variability as one of the important factors related to coronary plaque vulnerability.