RESUMO
BACKGROUND: Elevated levels of triglyceride (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) are regarded as a residual lipid risk in low-density lipoprotein cholesterol (LDL-C)-lowering therapy. This study investigated the association between lipid risk stratified by TG and non-HDL-C and the prognosis of patients with coronary artery disease (CAD), and the association between stratified lipid risk and flow-mediated dilatation (FMD) index.MethodsâandâResults: The 624 CAD patients enrolled in flow-mediated dilation (FMD)-J study A were divided into 4 groups: low-risk group (n=413) with TG <150 mg/dL and non-HDL-C <170 mg/dL; hyper-TG group (n=180) with TG ≥150 mg/dL and non-HDL-C <170 mg/dL; hyper-non-HDL group (n=12) with TG <150 mg/dL and non-HDL-C ≥170 mg/dL; and high-risk group (n=19) with TG ≥150 mg/dL and non-HDL-C ≥170 mg/dL. Comparison of the groups showed the cumulative incidence of a 3-point major adverse cardiovascular event (MACE) was different and highest in the high-risk group in all the patients (P=0.009), and in patients with a FMD index ≥7.0% (P=0.021), but not in those with a FMD index <7.0%. Multivariable regression analysis showed that high lipid risk (P=0.019) and FMD <7.0% (P=0.040) were independently correlated with the incidence of a 3-point MACE. CONCLUSIONS: Novel stratification of lipid risk, simply using TG and non-HDL-C levels, combined with FMD measurement, is useful for predicting cardiovascular outcomes in patients with CAD.
Assuntos
Doença da Artéria Coronariana , Colesterol , HDL-Colesterol , LDL-Colesterol , Doença da Artéria Coronariana/diagnóstico por imagem , Dilatação , Humanos , Lipoproteínas , Prognóstico , Fatores de Risco , TriglicerídeosRESUMO
BACKGROUND: Circulating triglyceride (TG) levels are a current focus as a residual risk for cardiovascular (CV) events. We evaluated the relationship between circulating TG levels and future CV events in patients with coronary artery disease (CAD) who were treated with conventional therapy. MethodsâandâResults: We analyzed data for 652 patients who were enrolled in the FMD-J Study A. We investigated the associations between serum TG levels and first major CV events (death from CV cause, nonfatal acute coronary syndrome (ACS), nonfatal stroke, and CAD) for a 3-year follow-up period. Patients were divided into 4 groups based on serum TG level: low-normal (<100 mg/dL), high-normal (100-149 mg/dL), borderline hypertriglyceridemia (150-199 mg/dL), and moderate hypertriglyceridemia (≥200 mg/dL). During a median follow-up period of 46.6 months, 14 patients died (9 from CV causes), 16 had nonfatal ACS, 6 had nonfatal stroke, and 54 had CAD. The Kaplan-Meier curves for first major CV event among the 4 groups were significantly different (P=0.04). After adjustment for various confounders, serum TG level ≥100 mg/dL were significantly associated with an increased risk of first major CV events compared with serum TG level <100 mg/dL. CONCLUSIONS: Serum TG level may be a surrogate marker for predicting CV events in patients with CAD.
Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Acidente Vascular Cerebral , Triglicerídeos/sangue , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/etiologia , Síndrome Coronariana Aguda/mortalidade , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Taxa de SobrevidaRESUMO
BACKGROUND: Waist circumference (WC), waist-to-height ratio (WHtR) and body mass index (BMI) are known as easy anthropometric markers of abnormal obesity and screening tools for predicting cardiovascular outcomes, but which indices are best is unclear. We therefore investigated the superiority and association between each index and low flow-mediated dilatation (FMD) as a surrogate marker for cardiovascular outcomes in patients with morbidity in a large Japanese prospective cohort.MethodsâandâResults:A total of 1,645 Japanese patients who had coronary artery disease and hypertension or diabetes mellitus were enrolled, and 1,087 of them were analyzed. The high-WHtR group (≥0.5) showed greater morbidity and increased inflammation in association with atherosclerosis compared with the low-WHtR group. High WHtR and advanced age were identified as predictors of low FMD (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.02-1.88, P=0.037 and OR 1.55, 95% CI 1.19-2.01, P=0.001, respectively). However, WC was not associated with that risk in either sex (male: OR 1.37, 95% CI 0.97-1.93, P=0.076; female: OR 1.08, 95% CI 0.68-1.73, P=0.74), and no association was evident between high BMI and low FMD (OR 0.92, 95% CI 0.71-1.19, P=0.54). CONCLUSIONS: WHtR offers a superior predictor of decreased FMD than other anthropometric indices, and progression of arteriosclerosis might be detected more sensitively. Further study is needed to investigate the relationship between cardiovascular mortality and WHtR.
Assuntos
Endotélio/fisiopatologia , Razão Cintura-Estatura , Idoso , Povo Asiático , Aterosclerose/diagnóstico , Dilatação , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Estudos ProspectivosRESUMO
Stimulation of µ1-opioid receptors (M1ORs) in the medial nucleus solitarius (mNTS) by endomorphin-2 (EM2) elicits decreases in mean arterial pressure (MAP), heart rate (HR) and greater splanchnic nerve activity (GSNA) in Wistar rats. We tested the hypothesis that EM2-induced responses in the mNTS may be attenuated in the spontaneously hypertensive rat (SHR). Experiments were carried out in urethane-anesthetized, artificially ventilated, adult male SHR and Wistar-Kyoto rats (WKY). Alterations in responses to chemical stimulation of the hypothalamic arcuate nucleus (ARCN) after bilateral blockade of M1ORs in the mNTS were also studied. In SHR, microinjections of EM2 into the mNTS elicited smaller decreases in MAP, HR and GSNA compared to those elicited in WKY; smaller cardiovascular responses in SHR can be explained by lower expression of M1OR mRNA in the NTS of SHR compared to WKY. Decreases in MAP and GSNA and increases in HR were elicited by microinjections of N-methyl-D-aspartic acid (NMDA) into the ARCN of WKY. Bilateral blockade of M1ORs in the mNTS attenuated the decreases in MAP and GSNA and exaggerated the increases in HR elicited by the ARCN stimulation in WKY but not in SHR. Tonic inhibitory activity of neuropeptide Y/gamma-aminobutyric acid (NPY/GABA) neurons in the ARCN is attenuated in SHR; this observation may explain increases in MAP, GSNA and HR elicited by microinjections of NMDA into the ARCN of SHR. These results demonstrate that attenuation of EM2-induced responses in the mNTS of SHR may contribute to the excitatory responses elicited by ARCN stimulation in SHR.
Assuntos
Sistema Cardiovascular , Hipertensão , Oligopeptídeos , Receptores Opioides mu , Núcleo Solitário , Nervos Esplâncnicos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/metabolismo , Analgésicos Opioides/farmacocinética , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Núcleo Arqueado do Hipotálamo/fisiopatologia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Hipertensão/genética , Hipertensão/fisiopatologia , Masculino , Microinjeções , Oligopeptídeos/administração & dosagem , Oligopeptídeos/metabolismo , Oligopeptídeos/farmacocinética , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptores Opioides mu/antagonistas & inibidores , Receptores Opioides mu/genética , Núcleo Solitário/metabolismo , Núcleo Solitário/fisiopatologia , Nervos Esplâncnicos/metabolismo , Nervos Esplâncnicos/fisiopatologiaRESUMO
Pupillometry was used to evaluate the effects of the calcium channel blockers cilnidipine (CL) and amlodipine (AM) on changes in autonomic nervous activity induced by isometric exercise in patients with hypertension. After handgrip exercise, the velocity of miosis increased in both the CL and AM groups. However, the velocity of mydriasis increased in only the AM group. Velocity slopes of miosis and mydriasis were smaller in the CL group than in the AM group. The low-to-high frequency ratio obtained from pulse wave analysis increased in only the AM group. Sympathetic activation elicited by isometric exercise was suppressed more effectively by CL than by AM.
Assuntos
Anlodipino/farmacologia , Sistema Nervoso Autônomo/efeitos dos fármacos , Di-Hidropiridinas/farmacologia , Hipertensão , Miose/fisiopatologia , Midríase/fisiopatologia , Pupila , Idoso , Bloqueadores dos Canais de Cálcio/farmacologia , Exercício Físico/fisiologia , Feminino , Força da Mão/fisiologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Miose/diagnóstico , Midríase/diagnóstico , Pupila/efeitos dos fármacos , Pupila/fisiologia , Reprodutibilidade dos TestesRESUMO
AIM: There is little information on the relationships of serum small dense low-density lipoprotein cholesterol (sdLDL-C) levels and serum triglyceride (TG) levels with cardiovascular events in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM) who are receiving statins. The aim of this study was to evaluate the relationships of serum TG levels and sdLDL-C levels as residual risks for cardiovascular events in patients with CAD and type 2 DM who were being treated with statins. METHODS: The subjects were divided into four groups based on TG levels and sdLDL-C levels: sdLDL-C of ï¼40.0 mg/dL and TG of ï¼150 mg/dL, sdLDL-C of ≥ 40.0 mg/dL and TG of ï¼150 mg/dL, sdLDL-C of ï¼40.0 mg/dL and TG of ≥ 150 mg/dL, and sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL. During a median follow-up period of 1419 days, cardiovascular events occurred in 34 patients. RESULTS: The incidences of cardiovascular events were significantly higher in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ï¼150 mg/dL and in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL, but not in patients with sdLDL-C of ï¼40.0 mg/dL and TG of ≥ 150 mg/dL, than in patients with sdLDL-C of ï¼40.0 mg/dL and TG of ï¼150 mg/dL. CONCLUSIONS: Under the condition of treatment with statins, patients with CAD and type 2 DM who had sdLDL-C levels of ≥ 40.0 mg/dL had a high risk for cardiovascular events even though serum TG levels were controlled at ï¼150 mg/dL.
Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Doença da Artéria Coronariana/tratamento farmacológico , LDL-Colesterol , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fatores de Risco , TriglicerídeosRESUMO
Type 2 diabetes mellitus (T2DM) is a major cause of microvascular dysfunction. However, its effect on blood flow patterns during ischemic demand has not been adequately elucidated. In this study, we investigated the hypothesis that microvascular dysfunction in patients with T2DM manifests as brachial reactive hyperemia (BRH), defined as the ratio of peak blood flow velocities in a brachial artery before and after forearm cuff occlusion. The study enrolled 943 subjects (men, n = 152 [T2DM] and n = 371 [non-T2DM]; women, n = 107 [T2DM] and n = 313 [non-T2DM], respectively) with no history of cardiovascular disease. Semiautomatic measurements were obtained three times at 1.5-year intervals to confirm the reproducibility of factors involved in BRH for each sex. An age-adjusted mixed model demonstrated attenuated BRH in the presence of T2DM in both men (p = 0.022) and women (p = 0.031) throughout the study period. Post hoc analysis showed that the estimated BRH was significantly attenuated in patients with T2DM regardless of sex, except at baseline in women. In multivariate regression analysis, T2DM was a negative predictor of BRH at every measurement in men. For women, BRH was more strongly associated with alcohol consumption. Repeated measurements analysis revealed that T2DM was associated with attenuated postocclusion reactive hyperemia.
Assuntos
Diabetes Mellitus Tipo 2 , Hiperemia , Masculino , Humanos , Feminino , Artéria Braquial , Diabetes Mellitus Tipo 2/complicações , Reprodutibilidade dos Testes , AntebraçoRESUMO
Flow-mediated vasodilatation of the brachial artery (FMD) is a marker which is related to endothelial nitric oxide bioavailability. Commercially available ultrasound machines equipped with online computer-assisted semi-automatic analysis software to measure FMD have recently become available in Japan. These devices enable more convenient examination, enhanced reproducibility of FMD measurement, and a shortened examination time. Using such devices, in the present multicenter prospective study we propose to: 1) establish standardized FMD values and determine the annual rates of FMD change in healthy subjects; 2) confirm the predictive value of FMD for future cardiovascular events in Japanese subjects; 3) evaluate the potential usefulness of a multimarker strategy, including measurements of FMD, pulse-wave velocity (PWV), ankle-brachial pressure index, biochemical markers, and proteomic biomarkers obtained by mass spectroscopic analysis to assess the prognosis of subjects with coronary artery disease; and 4) clarify the usefulness of FMD measurement to predict the rate of progression of carotid atherosclerosis, arterial stiffness and microalbuminuria in subjects with hypertension or diabetes mellitus. In total, we estimate that approximately 4000 Japanese subjects in 3 different study groups will eventually be enrolled in this prospective observational investigation. We anticipate that the present study will provide important evidence for the usefulness of FMD measurement in the risk stratification for cardiovascular disease.
Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Artéria Braquial/fisiologia , Estenose das Carótidas/fisiopatologia , Doença da Artéria Coronariana/fisiopatologia , Processamento de Imagem Assistida por Computador , Óxido Nítrico/sangue , Software , Ultrassonografia , Vasodilatação/fisiologia , Adulto , Idoso , Índice Tornozelo-Braço , Biomarcadores/sangue , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/mortalidade , Causas de Morte , Estudos de Coortes , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Angiopatias Diabéticas/diagnóstico por imagem , Angiopatias Diabéticas/mortalidade , Angiopatias Diabéticas/fisiopatologia , Progressão da Doença , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Estudos Prospectivos , Proteômica , Fatores de RiscoRESUMO
We investigated cardiac and vascular gene profiles in response to immobilization stress (IMO) in rats, an animal model of emotional stress-induced takotsubo cardiomyopathy using microarray analysis, followed by re-confirmation with real-time reverse transcription-polymerase chain reaction. Expression levels of the identified genes were further estimated by pretreatment with an α1-adrenoceptor blocker and/or a ß1-adrenoceptor blocker. In response to IMO, expression of 46 genes was significantly altered in the heart and that of 49 genes was significantly altered in the aorta. Pathway analysis with DAVID Bioinformatics Resources indicated that regulation of transcription and response to endogenous stimulation were the top two scoring pathways. Altered expression of cardiac genes was blunted by pretreatment with a ß1-adrenoceptor blocker or α1 + ß1-adrenoceptor blockers. In contrast, that of aortic genes was blunted by pretreatment with an α1-adrenoceptor blocker or α1 + ß1-adrenoceptor blockers. Activation of α1-adrenoceptor in the blood vessels or activation of ß1-adrenoceptors in the heart were mainly responsible for emotional stress-induced alteration of cardiac and vascular gene profiles.
Assuntos
Aorta/metabolismo , Perfilação da Expressão Gênica , Miocárdio/metabolismo , Estresse Psicológico/complicações , Cardiomiopatia de Takotsubo/genética , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Análise de Variância , Animais , Aorta/efeitos dos fármacos , Biologia Computacional , Modelos Animais de Doenças , Emoções , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Ratos , Ratos Wistar , Restrição Física/psicologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estresse Psicológico/genética , Cardiomiopatia de Takotsubo/psicologia , Fatores de Tempo , Transcrição GênicaRESUMO
Blood pressure control rates remain poor in the majority of patients with hypertension. One cause of suboptimal treatment of hypertension is poor medication adherence. Medication non-adherence was 29.7% in Japanese hypertensive patients and poor adherence group showed high blood pressure levels compared with good adherence group. Many factors, race, sex, age, cognitive function, side effect, and cost benefit contribute to the medication adherence. Young male subjects showed poor adherence and new visit and no comorbidity were also main factors of antihypertensive drug discontinuation. Pharmacy care and active health promotion improved medication adherence. Fixed-dose combination therapy also improved adherence and blood pressure control.
Assuntos
Hipertensão/tratamento farmacológico , Cooperação do Paciente , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Background Diagnostic criteria of flow-mediated vasodilation (FMD), an index of endothelial function, and nitroglycerin-induced vasodilation (NID), an index of vascular smooth muscle function, of the brachial artery have not been established. The purpose of this study was to propose diagnostic criteria of FMD and NID for normal endothelial function and normal vascular smooth muscle function. Methods and Results We investigated the cutoff values of FMD and NID in subjects with (risk group) and those without cardiovascular risk factors or cardiovascular diseases (no-risk group) in 7277 Japanese subjects (mean age 51.4±10.8 years) from the Flow-Mediated Dilation Japan study and the Flow-Mediated Dilatation Japan Registry study for analysis of the cutoff value of FMD and in 1764 Japanese subjects (62.2±16.1 years) from the registry of Hiroshima University Hospital for analysis of the cutoff value of NID. Receiver-operator characteristic curve analysis of FMD to discriminate subjects in the no-risk group from patients in the risk group showed that the optimal cutoff value of FMD to diagnose subjects in the no-risk group was 7.1%. Receiver-operator characteristic curve analysis of NID to discriminate subjects in the no-risk group from patients in the risk group showed that the optimal cutoff value of NID to diagnose subjects in the no-risk group was 15.6%. Conclusions We propose that the cutoff value for normal endothelial function assessed by FMD of the brachial artery is 7.1% and that the cutoff value for normal vascular smooth muscle function assessed by NID of the brachial artery is 15.6% in Japanese subjects. Clinical Trial Registration www.umin.ac.jp Unique identifiers: UMIN000012950, UMIN000012951, UMIN000012952, and UMIN000003409.
Assuntos
Artéria Braquial/diagnóstico por imagem , Doenças Cardiovasculares/diagnóstico por imagem , Endotélio Vascular/diagnóstico por imagem , Músculo Liso Vascular/diagnóstico por imagem , Nitroglicerina/administração & dosagem , Ultrassonografia , Vasodilatação , Vasodilatadores/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artéria Braquial/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Endotélio Vascular/fisiopatologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Hiperemia/fisiopatologia , Japão , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/fisiopatologia , Valor Preditivo dos Testes , Estudos Prospectivos , Valores de Referência , Sistema de Registros , Adulto JovemRESUMO
The score based on the office systolic blood pressure, age, fasting blood glucose level, and estimated glomerular filtration rate (SAGE score) has been proposed as a useful marker to identify elevated values of carotid-femoral pulse wave velocity (PWV). The present cross-sectional study was conducted to examine whether the SAGE score is also a useful marker to identify subjects with elevated brachial-ankle PWV values in Japanese subjects with hypertension. We measured the brachial-ankle PWV and calculated the SAGE score in a total of 1019 employees of a Japanese company with hypertension and 817 subjects with hypertension derived from a multicenter study cohort. The analyses in this study were based on data from these two study groups as well as on a composite population of the two (n = 1836). The receiver operating characteristic curve analysis showed that the area under the curve to identify subjects with brachial-ankle PWV values of ≥1800 cm/s was over 0.70 in each of the three study groups. Even after adjustments, a SAGE score ≥7 had a significant odds ratio for identifying subjects with brachial-ankle PWV values ≥1800 cm/s in the 1836 study subjects from the composite occupational and multicenter study cohort (odds ratio = 2.1, 95% confidence interval = 1.4-3.0, P < 0.01). Thus, in Japanese subjects with hypertension, the SAGE score may be a useful marker for identifying subjects with elevated brachial-ankle PWV values.
Assuntos
Indicadores Básicos de Saúde , Hipertensão/epidemiologia , Análise de Onda de Pulso , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Hipertensão/fisiopatologia , Japão/epidemiologia , Masculino , Pessoa de Meia-IdadeRESUMO
The usefulness of brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, is not fully known for the management of treated hypertensive patients with a history of coronary artery disease (CAD) who have blood pressure less than 130/80 mmHg, a recommended blood pressure target in the updated major hypertension guidelines. We analyzed data for 447 treated hypertensive patients with CAD enrolled in FMD-J Study A for assessment of the predictive value of baPWV for future cardiovascular events. The primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow-up period of 47.6 months, the primary outcome occurred in 64 patients. Blood pressure less than 130/80 mmHg was significantly associated with a lower risk of the composite outcome independent of other cardiovascular risk factors in treated hypertensive patients with CAD (hazard ratio, 0.59; 95% confidence interval (CI), 0.35-0.99; P = 0.04). In treated hypertensive patients with CAD who had blood pressure less than 130/80 mmHg, baPWV above the cutoff value of 1731 cm/s, derived from receiver-operator characteristic curve analysis for the composite outcome was significantly associated with a higher risk of the composite outcome independent of conventional risk factors (hazard ratio, 2.83; 95% CI, 1.02-7.91; P = 0.04). baPWV was an independent predictor of cardiovascular events in treated hypertensive patients with CAD who had blood pressure less than 130/80 mmHg, for whom measurement of baPWV is recommended for cardiovascular risk assessment.
Assuntos
Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/fisiopatologia , Doença da Artéria Coronariana/fisiopatologia , Hipertensão/fisiopatologia , Rigidez Vascular/fisiologia , Idoso , Índice Tornozelo-Braço , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Medição de Risco , Vasodilatação/fisiologiaRESUMO
To investigate the effect of taurine on the sympathetic nervous system, I observed pressor responses of perfused mesenteric arteries by electrical stimulation and baro-reflex sensitivity of spontaneously hypertensive rats (SHR/Izm) and control Wistar-Kyoto rats (WKY/Izm) treated with taurine. Taurine added to the perfusate suppressed norepinephrine (NE) overflow and the pressor response mediated by electrical stimulation of isolated perfused mesenteric arteries. Taurine showed a greater suppressive effect on NE overflow and the pressor response mediated by electrical stimulation in SHR/Izm rats than in WKY/Izm rats. Increment of renal sympathetic nerve activity induced by jet-air stress was suppressed in SHR/Izm rats treated with 3% taurine. The arterial baro-reflex sensitivity was more sensitive in SHR/Izm rats treated with taurine than in those exposed to no taurine. These data suggest that taurine lowers blood pressure directly via the suppression of NE release from the peripheral sympathetic nerve and the improvement of impaired baro-reflex sensitivity.
Assuntos
Barorreflexo/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Taurina/farmacologia , Animais , Pressão Sanguínea , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
Background The difference in the predictive ability of the brachial-ankle pulse wave velocity (baPWV) and its stiffness index ß-transformed value (ß-baPWV, ie, baPWV adjusted for the pulse pressure) for the development of pathophysiological abnormalities related to cardiovascular disease or future occurrence of cardiovascular disease was examined. Methods and Results In study 1, a 7-year prospective observational study in cohorts of 3274 men and 3490 men, the area under the curve in the receiver operator characteristic curve analysis was higher for baPWV than for ß-baPWV for predicting the development of hypertension (0.73, 95% CI=0.70 to 0.75 versus 0.59, 95% CI=0.56 to 0.62; P<0.01) and/or the development of retinopathy (0.78, 95% CI=0.73 to 0.82 versus 0.66, 95% CI=0.60 to 0.71; P<0.01) by the end of the study period. During study 2, a 3-year observation period on 511 patients with coronary artery disease, 72 cardiovascular events were confirmed. The C statistics of both markers for predicting the development of cardiovascular events were similar. Conclusions Stiffness index ß transformation of the baPWV may attenuate the significance of the baPWV as a risk marker for development of pathophysiological abnormalities related to cardiovascular disease in male subjects.
Assuntos
Índice Tornozelo-Braço , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Análise de Onda de Pulso , Rigidez Vascular/fisiologia , Adulto , Idoso , Pressão Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de RiscoRESUMO
OBJECTIVES: The endothelial dysfunction-arterial stiffness-atherosclerosis continuum plays an important pathophysiological role in hypertension. The aim of this study was to investigate the cross-sectional association between serum uric acid (SUA) and vascular markers related to this continuum, and to assess the longitudinal association between SUA and endothelial function that represents the initial step of the continuum. METHODS: We evaluated the baseline associations between SUA levels and vascular markers that included flow-mediated vasodilatation (FMD), brachial-ankle pulse wave velocity (baPWV), and common carotid artery intima-media thickness (CCA-IMT) in 648 subjects receiving antihypertensive treatment. The longitudinal association between baseline SUA levels and FMD measured at 1.5 and 3â¯yr of follow-up was also investigated. RESULTS: At baseline, modest, but significant correlations were observed between SUA and FMD in females (râ¯=â¯-0.171), baPWV in males with SUA >368.78⯵mol/L (râ¯=â¯-0.122) and in females with a SUA levelâ¯≤â¯362.83⯵mol/L (râ¯=â¯0.217), mean CCA-IMT in females with a SUA levelâ¯≤â¯333.09⯵mol/L (râ¯=â¯0.139), and max CCA-IMT in females with SUA levelâ¯≤â¯333.09⯵mol/L (râ¯=â¯0.138). A longitudinal association between SUA and FMD was less observed in males. In females, the baseline SUA was associated significantly with FMD values at 1.5â¯yr (râ¯=â¯-0.211), and SUA levels >237.92⯵mol/L were associated significantly and independently with FMD values at 3â¯yr (râ¯=â¯-0.166). CONCLUSIONS: Lower SUA levels were associated with better vascular markers of the continuum, especially in females. Furthermore, we observed a longitudinal association between SUA and endothelial function, suggesting SUA level may be a potential marker of the continuum in hypertension.
Assuntos
Endotélio Vascular/fisiologia , Hipertensão/sangue , Ácido Úrico/sangue , Vasodilatação/fisiologia , Idoso , Biomarcadores/sangue , Espessura Intima-Media Carotídea/tendências , Estudos Transversais , Feminino , Seguimentos , Humanos , Hipertensão/diagnóstico , Hipertensão/terapia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso/métodos , Análise de Onda de Pulso/tendências , Resultado do TratamentoRESUMO
OBJECTIVES: To examine the longitudinal mutual association between endothelial dysfunction and arterial stiffness, and also to determine which of the two variables was more closely associated with the progression of subclinical organ damage. METHODS: The brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness (CIMT), estimated glomerular filtration rate, microalbuminuria and flow-mediated vasodilatation of the brachial artery (FMD) were measured three times at 1.5-year intervals in 674 Japanese patients receiving antihypertensive treatment. RESULTS: The change of the baPWV during the study period was larger in the subjects with baseline FMD values in the lowest tertile as compared to those with baseline FMD values in the highest tertile. The change of the CIMT was smaller in the subjects with baseline baPWV values in the lowest tertile than in those with baseline baPWV values in the highest tertile. After the adjustment, the FMD value at the baseline was inversely associated with the baPWV at the end of the study period (beta=-0.07, p=0.01), although, the reverse association was not significant. The baPWV, but not the FMD value, at the baseline was associated with the CIMT (beta=0.06, p=0.04) measured at the end of the study period. CONCLUSIONS: In hypertension, endothelial dysfunction was associated with the progression of arterial stiffness, although the reverse association was not confirmed. The increased arterial stiffness rather than endothelial dysfunction may be more closely associated with the progression of atherosclerotic vascular damage, and the endothelial dysfunction-arterial stiffness-atherosclerosis continuum may be important in hypertension.
Assuntos
Espessura Intima-Media Carotídea/tendências , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/fisiologia , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Rigidez Vascular/fisiologia , Idoso , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Onda de Pulso/tendênciasRESUMO
BACKGROUND: The usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known. METHODS AND RESULTS: We measured flow-mediated vasodilation (FMD) and brachial-ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow-up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver-operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06-0.74; P=0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09-0.79; P=0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01-3.44; P=0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23-3.90; P=0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed. CONCLUSIONS: In patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification. CLINICAL TRIAL REGISTRATION: URL: www.umin.ac.jp. Unique identifier: UMIN000012950.
Assuntos
Doença da Artéria Coronariana/fisiopatologia , Morte Súbita Cardíaca/epidemiologia , Insuficiência Cardíaca/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Rigidez Vascular/fisiologia , Idoso , Artéria Braquial/diagnóstico por imagem , Doenças Cardiovasculares , Doença da Artéria Coronariana/epidemiologia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Onda de Pulso , Medição de Risco , VasodilataçãoRESUMO
BACKGROUND AND AIMS: Baseline brachial artery (BBA) diameter has been reported to be a potential confounding factor of flow-mediated vasodilation (FMD). The purpose of this study was to evaluate the relationships between BBA diameter and cardiovascular risk factors and compare the diagnostic accuracy of BBA diameter in subjects without cardiovascular risk factors and patients with cardiovascular disease (CVD) with that of FMD. METHODS: We measured BBA diameter and FMD in 5695 male subjects. In addition, we retrospectively investigated the incidence of cardiovascular events using another population sample consisting of 440 male subjects, to compare the accuracy of BBA diameter with that of FMD in predicting cardiovascular events. RESULTS: BBA diameter and FMD significantly correlated with age, body mass index, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, and glucose as well as Framingham risk score. The prevalence of cardiovascular risk factors and CVD increased with the increase in BBA diameter and FMD. Area under the curve (AUC) value of the receiver operating characteristic (ROC) curve for BBA diameter to diagnose subjects without cardiovascular risk factors (0.59 vs. 0.62, p = 0.001) or patients with CVD (0.58 vs. 0.64, p < 0.001) was significantly lower than that for FMD. In the retrospective study, the AUC value of the ROC curve for BBA diameter to predict first major cardiovascular events was significantly lower than that of FMD (0.50 vs. 0.62, p = 0.03). CONCLUSIONS: In men, BBA diameter was inferior to FMD for assessment of cardiovascular risk.
Assuntos
Artéria Braquial/fisiopatologia , Doenças Cardiovasculares/epidemiologia , Vasodilatação , Adulto , Idoso , Artéria Braquial/diagnóstico por imagem , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , UltrassonografiaRESUMO
Hypertension is associated with endothelial dysfunction. Blood pressure significantly correlates with endothelial function in antihypertensive drug-naive subjects. The purpose of this study was to determine whether treatment status affects the relationship between blood pressure and endothelial function. We measured flow-mediated vasodilation (FMD) in 2297 subjects, including 1822 antihypertensive drug-naive subjects and 475 treated hypertensive patients. FMD significantly decreased in relation to increase in systolic blood pressure (8.2±3.1% in subjects with systolic blood pressure of <120 mm Hg, 7.5±2.8% for 120-129 mm Hg, 7.1±2.8% for 130-139 mm Hg, and 6.7±2.6% for ≥140 mm Hg; P<0.001). Systolic blood pressure was independently associated with FMD in untreated subjects. In contrast, there was no significant relationship between systolic blood pressure and FMD in treated hypertensive patients (4.6±3.1% in treated hypertensives with systolic blood pressure of <120 mm Hg, 4.8±2.7% for 120-129 mm Hg, 4.9±2.8% for 130-139 mm Hg, and 4.5±2.3% for ≥140 mm Hg; P=0.77). Propensity score matching analysis revealed that the prevalence of endothelial dysfunction defined as FMD of less than the division point for the lowest tertile, and the middle tertile of FMD was significantly higher in treated hypertensive patients than in untreated subjects in all systolic blood pressure categories. Endothelial function assessed by FMD was impaired regardless of the level of blood pressure achieved by antihypertensive drug treatment in hypertensive patients.