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1.
J Steroid Biochem Mol Biol ; 214: 105965, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34619249

RESUMO

Vitamin D deficiency is a negative endocrine renin-angiotensin system (RAS) modulator and PCOS women are often vitamin D deficient, leading to RAS overactivation in PCOS. A cross-sectional study was performed in 99 PCOS and 68 control women who presented sequentially. Circulating plasma levels of RAS proteins (Angiotensin-converting enzyme 2 (ACE2), renin and angiotensinogen) were measured by Slow Off-rate Modified Aptamer (SOMA)-scan and 25-hydroxyvitamin D [25(OH)D] was measured by tandem mass spectroscopy. The RAS system was found to be overactivated in the PCOS women compared to non-PCOS control women with increased renin and decreased angiotensinogen (p < 0.05); 25-hydroxyvitamin D was also significantly lower in the PCOS group (p < 0.0001). In PCOS women, plasma renin was increased in vitamin D deficient and insufficient groups compared with the vitamin D sufficient group (p < 0.005), but did not differ across non-PCOS control subgroups. In non-PCOS controls, plasma ACE2 decreased from vitamin D insufficiency to deficiency (p < 0.05). Angiotensinogen was not different across the vitamin D sufficiency, insufficiency and deficiency strata for either PCOS or non-PCOS controls. These data show that RAS activation through increased plasma renin levels was seen in vitamin D insufficient and deficient PCOS subjects compared to non-PCOS control women. In addition, decreased plasma ACE2 levels were seen in vitamin D deficiency in non-PCOS controls, which may predispose these vitamin D deficient subjects to increased cardiovascular risk and susceptibility to infectious agents such as COVID-19 where this is a risk factor.


Assuntos
Enzima de Conversão de Angiotensina 2/sangue , Angiotensinogênio/sangue , Síndrome do Ovário Policístico/sangue , Renina/sangue , Deficiência de Vitamina D/sangue , Adulto , Pressão Sanguínea , Feminino , Humanos , Síndrome do Ovário Policístico/fisiopatologia , Sistema Renina-Angiotensina , Vitamina D/sangue , Deficiência de Vitamina D/fisiopatologia , Vitaminas/sangue , Adulto Jovem
2.
Eur J Endocrinol ; 185(5): 663-672, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34468397

RESUMO

Context: Primary aldosteronism (PA) causes left ventricular hypertrophy (LVH) via hemodynamic factors and directly by aldosterone effects. Specific treatment by mineralocorticoid receptor antagonists (MRA) or adrenalectomy (ADX) has been reported to improve LVH. However, the cardiovascular benefit could depend on plasma renin concentration (PRC) in patients on MRA. Patients and objective: We analyzed data from 184 patients from the Munich center of the German Conn's Registry, who underwent echocardiography at the time of diagnosis and 1 year after treatment. To assess the effect of PRC on cardiac recovery, we stratified patients on MRA according to suppression (n = 46) or non-suppression of PRC (n = 59) at follow-up and compared them to PA patients after ADX (n = 79). Results: At baseline, patients treated by ADX or MRA had comparable left ventricular mass index (LVMI, 61.7 vs 58.9 g/m2.7, P = 0.591). Likewise, patients on MRA had similar LVMI at baseline, when stratified into treatment groups with suppressed and unsuppressed PRC during follow-up (60.0 vs 58.1 g/m2.7, P = 0.576). In all three groups, we observed a significant reduction in LVMI following treatment (P < 0.001). However, patients with suppressed PRC had no decrease in pro-BNP levels, and the reduction of LVMI was less intense than in patients with unsuppressed PRC (4.1 vs 8.2 g/m2.7, P = 0.033) or after ADX (9.3 g/m2.7, P = 0.019). Similarly, in multivariate analysis, higher PRC was correlated with the regression of LVH. Conclusion: PA patients with suppressed PRC on MRA show impaired regression of LVH. Therefore, dosing of MRA according to PRC could improve their cardiovascular benefit.


Assuntos
Hiperaldosteronismo/sangue , Hiperaldosteronismo/complicações , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/etiologia , Renina/sangue , Adrenalectomia , Adulto , Biomarcadores , Estudos de Coortes , Ecocardiografia , Eletrocardiografia , Feminino , Alemanha , Humanos , Hiperaldosteronismo/terapia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Estudos Prospectivos , Sistema de Registros , Resultado do Tratamento
3.
Crit Care ; 25(1): 294, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34391450

RESUMO

BACKGROUND: Preliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes. We sought to assess in a larger, multicenter study the relationship between serum renin and Major Adverse Kidney Events (MAKE) in intensive care unit (ICU) patients. METHODS: Prospective, multicenter study at two institutions of patients with and without acute kidney injury (AKI). Blood samples were collected for renin measurement a median of 2 days into the index ICU admission and 5-7 days later. The primary outcome was MAKE at hospital discharge, a composite of mortality, kidney replacement therapy, or reduced estimated glomerular filtration rate to ≤ 75% of baseline. RESULTS: Patients in the highest renin tertile were more severely ill overall, including more AKI, vasopressor-dependence, and severity of illness. MAKE were significantly greater in the highest renin tertile compared to the first and second tertiles. In multivariable logistic regression, this initial measurement of renin remained significantly associated with both MAKE as well as the individual component of mortality. The association of renin with MAKE in survivors was not statistically significant. Renin measurements at the second time point were also higher in patients with MAKE. The trajectory of the renin measurements between time 1 and 2 was distinct when comparing death versus survival, but not when comparing MAKE versus those without. CONCLUSIONS: In a broad cohort of critically ill patients, serum renin measured early in the ICU admission is associated with MAKE at discharge, particularly mortality.


Assuntos
Nefropatias/sangue , Renina/análise , Idoso , Estudos de Coortes , Estado Terminal/epidemiologia , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Kentucky/epidemiologia , Nefropatias/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Renina/sangue , Texas/epidemiologia
4.
Am J Physiol Regul Integr Comp Physiol ; 321(3): R504-R512, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34346722

RESUMO

The high-altitude maladaptation syndrome known as chronic mountain sickness (CMS) is characterized by polycythemia and is associated with proteinuria despite unaltered glomerular filtration rate. However, it remains unclear if indigenous highlanders with CMS have altered volume regulatory hormones. We assessed NH2-terminal pro-B-type natriuretic peptide (NT pro-BNP), plasma aldosterone concentration, plasma renin activity, kidney function (urinary microalbumin, glomerular filtration rate), blood volume, and estimated pulmonary artery systolic pressure (ePASP) in Andean males without (n = 14; age = 39 ± 11 yr) and with (n = 10; age = 40 ± 12 yr) CMS at 4,330 m (Cerro de Pasco, Peru). Plasma renin activity (non-CMS: 15.8 ± 7.9 ng/mL vs. CMS: 8.7 ± 5.4 ng/mL; P = 0.025) and plasma aldosterone concentration (non-CMS: 77.5 ± 35.5 pg/mL vs. CMS: 54.2 ± 28.9 pg/mL; P = 0.018) were lower in highlanders with CMS compared with non-CMS, whereas NT pro-BNP was not different between groups (non-CMS: 1394.9 ± 214.3 pg/mL vs. CMS: 1451.1 ± 327.8 pg/mL; P = 0.15). Highlanders had similar total blood volume (non-CMS: 90 ± 15 mL·kg-1 vs. CMS: 103 ± 18 mL·kg-1; P = 0.071), but Andeans with CMS had greater total red blood cell volume (non-CMS: 46 ± 10 mL·kg-1 vs. CMS: 66 ± 14 mL·kg-1; P < 0.01) and smaller plasma volume (non-CMS: 43 ± 7 mL·kg-1 vs. CMS: 35 ± 5 mL·kg-1; P = 0.03) compared with non-CMS. There were no differences in ePASP between groups (non-CMS: 32 ± 9 mmHg vs. CMS: 31 ± 8 mmHg; P = 0.6). A negative correlation was found between plasma renin activity and glomerular filtration rate in both groups (group: r = -0.66; P < 0.01; non-CMS: r = -0.60; P = 0.022; CMS: r = -0.63; P = 0.049). A smaller plasma volume in Andeans with CMS may indicate an additional CMS maladaptation to high altitude, causing potentially greater polycythemia and clinical symptoms.


Assuntos
Aclimatação , Doença da Altitude/fisiopatologia , Altitude , Volume Sanguíneo , Policitemia/fisiopatologia , Adulto , Albuminúria/etiologia , Albuminúria/fisiopatologia , Aldosterona/sangue , Doença da Altitude/sangue , Doença da Altitude/diagnóstico , Doença da Altitude/etiologia , Pressão Arterial , Biomarcadores/sangue , Doença Crônica , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Policitemia/sangue , Policitemia/diagnóstico , Policitemia/etiologia , Artéria Pulmonar/fisiopatologia , Renina/sangue
5.
Sci Rep ; 11(1): 17156, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433879

RESUMO

Nonclassic apparent mineralocorticoid excess (NC-AME) is proposed as a novel clinical condition with a mild phenotypic spectrum that ranges from normotension to severe hypertension. This condition is mainly characterized by a high serum cortisol to cortisone ratio (F/E) and concomitant low cortisone (E), however further metabolic changes in NC-AME have not been studied. A cross-sectional study was performed in a primary-care cohort of 396 Chilean subjects, which were classified in two groups: NC-AME (n = 28) and healthy controls (n = 27). A discovery study based in untargeted metabolomics assay in serum samples from both groups was performed by UPLC-Q-TOF/MS. Global metabolomic variations were assayed by principal component analysis and further compared by orthogonal partial least-squares discriminant analysis (OPLS-DA). NC-AME subjects exhibited higher values of blood pressure, fractional excretion of potassium, and lower plasma renin activity and urinary sodium to potassium ratio. Metabolomic analyses showed 36 differentially regulated metabolites between NC-AME and control subjects. A ROC curve analyses identified eight metabolites with high discriminatory capacity between NC-AME and control subjects. Moreover, gamma-L-glutamyl-L-methionine sulfoxide and 5-sulfoxymethylfurfural, exhibited significant association with cortisone, which are potential biomarkers of NC-AME, however further assays should elucidate its biological role in setup and progression of this phenotype.


Assuntos
Doenças das Glândulas Suprarrenais/sangue , Mineralocorticoides/sangue , Adulto , Biomarcadores/sangue , Cortisona/sangue , Feminino , Humanos , Masculino , Espectrometria de Massas/métodos , Metabolômica/métodos , Pessoa de Meia-Idade , Renina/sangue
6.
J Am Heart Assoc ; 10(14): e016543, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34259014

RESUMO

Background High-fructose diet (HFr) induces hypertension and renal damage. However, it has been unknown whether the HFr-induced hypertension and renal damage are exaggerated in subjects with salt sensitivity. We tested impacts of HFr in Dahl salt-sensitive (DS) and salt-resistant (DR) rats. Methods and Results Male DS and DR rats were fed control diet or HFr (60% fructose) with normal-salt content. After 12 weeks, plasma and urinary parameters, renal histological characteristics, and renal expression of renin-angiotensin system components were examined. Furthermore, effects of renin-angiotensin system inhibitors were also examined in DS rats fed the HFr. HFr elevated blood pressure in DS rats but not in DR rats. HFr increased urinary albumin and liver type fatty acid binding protein excretions in both rats, but the excretions were exaggerated in DS rats. HFr increased plasma lipids and uric acid in both rats, whereas HFr increased creatinine clearance in DS rats but not DR rats. Although HFr decreased plasma renin activity in DS rats, HFr-induced glomerular injury, afferent arteriolar thickening, and renal interstitial fibrosis were exaggerated in DS rats. HFr increased renal expression of angiotensinogen, renin, (pro)renin receptor, angiotensin-converting enzyme, and angiotensin II type 1 receptor in DS rat, whereas HFr increased only angiotensin-converting enzyme expression and decreased renin and angiotensin II type 1 receptor expressions in DR rats. Enalapril and candesartan attenuated the HFr-induced hypertension, albuminuria, glomerular hyperfiltration, and renal damage in DS rats. Conclusion HFr-induced hypertension and renal damage are exaggerated in DS rats via renal renin-angiotensin system activation, which can be controlled by renin-angiotensin system inhibitors.


Assuntos
Frutose/administração & dosagem , Frutose/metabolismo , Hipertensão/etiologia , Glomérulos Renais/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Animais , Anti-Hipertensivos/farmacologia , Benzimidazóis/farmacologia , Compostos de Bifenilo/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Enalapril/farmacologia , Glomérulos Renais/patologia , Masculino , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Endogâmicos Dahl , Receptor Tipo 1 de Angiotensina/metabolismo , Renina/sangue , Sódio na Dieta/administração & dosagem , Tetrazóis/farmacologia
7.
BMC Cardiovasc Disord ; 21(1): 350, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294029

RESUMO

BACKGROUND: Primary aldosteronism (PA), as a cause of secondary hypertension, can cause more serious cardiovascular damage than essential hypertension. The aldosterone-to-renin ratio (ARR) is recommended as the most reliable screening method for PA, but ARR screening is often influenced by many factors. PA cannot be easily excluded when negative ARR. CASE PRESENTATION: We report the case of a 45-year-old Chinese man with resistant hypertension. Three years ago, he underwent a comprehensive screening for secondary hypertension, including the ARR, and the result was negative. After that, the patient's blood pressure was still poorly controlled with four kinds of antihypertensive drugs, the target organ damage of hypertension progressed, and hypokalaemia was difficult to correct. When the patient was hospitalized again for comprehensive examination, we found that aldosterone levels had significantly increased, although the ARR was negative. An inhibitory test with saline was further carried out, and the results suggested that aldosterone was not inhibited; therefore, PA was diagnosed. We performed a unilateral adenoma resection for this patient, and spironolactone was continued to control blood pressure. After the operation, blood pressure is well controlled, and hypokalaemia is corrected. CONCLUSION: When the ARR is negative, PA cannot be easily excluded. Comprehensive analysis and diagnosis should be based on the medication and clinical conditions of patients.


Assuntos
Adenoma/complicações , Neoplasias das Glândulas Suprarrenais/complicações , Aldosterona/sangue , Hiperaldosteronismo/sangue , Hipertensão/etiologia , Renina/sangue , Adenoma/sangue , Adenoma/diagnóstico , Adenoma/cirurgia , Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Anti-Hipertensivos/uso terapêutico , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/etiologia , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
8.
PLoS One ; 16(7): e0253807, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34242264

RESUMO

Determining values of plasma renin activity (PRA) or plasma active renin concentration (ARC), plasma aldosterone concentration (PAC), and aldosterone-to-renin ratio (ARR) is essential to diagnose primary aldosteronism (PA), but it takes several days with conventional radioimmunoassays (RIAs). Chemiluminescent enzyme immunoassays for PAC and ARC using the Accuraseed® immunoanalyzer facilitated the determination, but relations between Accuraseed® immunoanalyzer-based and RIA-based values in samples of PA confirmatory tests and adrenal venous sampling remained to be elucidated. We addressed this issue in the present study. This is a prospective, cross-sectional study. ARC and PAC values were measured by the Accuraseed® immunoanalyzer in samples, in which PRA and PAC values had been measured by the PRA-FR® RIA and SPAC®-S Aldosterone kits, respectively. The relations between Accuraseed® immunoanalyzer-based and RIA-based values were investigated with regression analyses. The optimal cutoff of Accuraseed® immunoanalyzer-based ARR for PA screening was determined by the receiver operating characteristic analysis. After log-log transformations, linear relations with high coefficients of determination were observed between Accuraseed® immunoanalyzer-based and RIA-based data of renin and aldosterone. Following the PA guidelines of Japan Endocrine Society, Accuraseed® immunoanalyzer-based cutoffs were calculated from the regression equations: the basal PAC for PA screening >12 ng/dL, PAC for the saline infusion test >8.2 ng/dL, ARC for the furosemide-upright test <15 pg/mL, and ARR for the captopril challenge test >3.09 ng/dL per pg/mL. The optimal cutoff of Accuraseed® immunoanalyzer-based ARR for PA screening was >2.43 ng/dL over pg/mL not to overlook bilateral PA patients. The present study provided conversion formulas between Accuraseed® immunoanalyzer-based and RIA-based values of renin, aldosterone, and ARR, not only in basal samples but also in samples of PA confirmatory tests and adrenal venous sampling. Although validation studies are awaited, the present study will become priming water of harmonization of renin and aldosterone immunoassays.


Assuntos
Aldosterona/sangue , Hiperaldosteronismo/diagnóstico , Programas de Rastreamento/instrumentação , Renina/sangue , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Hiperaldosteronismo/sangue , Japão , Medições Luminescentes/instrumentação , Medições Luminescentes/normas , Medições Luminescentes/estatística & dados numéricos , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Radioimunoensaio/instrumentação , Radioimunoensaio/normas , Radioimunoensaio/estatística & dados numéricos , Valores de Referência
9.
Contemp Clin Trials ; 106: 106428, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33971295

RESUMO

Sedentary behavior (SB) has recently been recognized as a strong risk factor for cardiovascular disease, with new guidelines encouraging adults to 'sit less, move more.' Yet, there are few randomized trials demonstrating that reducing SB improves cardiovascular health. The Effect of Reducing Sedentary Behavior on Blood Pressure (RESET BP) randomized clinical trial addresses this gap by testing the effect of a 3-month SB reduction intervention on resting systolic BP. Secondary outcomes include other BP measures, pulse wave velocity, plasma renin activity and aldosterone, and objectively-measured SB (via thigh-mounted activPAL) and physical activity (via waist-worn GT3X accelerometer). RESET BP has a targeted recruitment of 300 adults with desk jobs, along with elevated, non-medicated BP (systolic BP 120-159 mmHg or diastolic BP 80-99 mmHg) and physical inactivity (self-reported aerobic physical activity below recommended levels). The multi-component intervention promotes 2-4 fewer hours of SB per day by replacing sitting with standing and light-intensity movement breaks. Participants assigned to the intervention condition receive a sit-stand desk attachment, a wrist-worn activity prompter, behavioral counseling every two weeks (alternating in-person and phone), and twice-weekly automated text messages. Herein, we review the study rationale, describe and evaluate recruitment strategies based on enrollment to date, and detail the intervention and assessment protocols. We also document our mid-trial adaptations to participant recruitment, intervention deployment, and outcome assessments due to the intervening COVID-19 pandemic. Our research methods, experiences to date, and COVID-specific accommodations could inform other research studying BP and hypertension or targeting working populations, including those seeking remote methods.


Assuntos
Exercício Físico/fisiologia , Hipertensão/terapia , Comportamento Sedentário , Local de Trabalho , Acelerometria , Adulto , Idoso , Aldosterona/sangue , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , COVID-19/epidemiologia , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Renina/sangue , Projetos de Pesquisa , SARS-CoV-2 , Adulto Jovem
10.
J Clin Endocrinol Metab ; 106(8): 2423-2435, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34008000

RESUMO

CONTEXT: The aldosterone to renin ratio (ARR) is the guideline-recommended screening test for primary aldosteronism. However, there are limited data in regard to the diagnostic performance of the ARR. OBJECTIVE: To evaluate the sensitivity and specificity of the ARR as a screening test for primary aldosteronism. METHODS: We searched the MEDLINE, Embase, and Cochrane databases until February 2020. Observational studies assessing ARR diagnostic performance as a screening test for primary aldosteronism were selected. To limit verification bias, only studies where dynamic confirmatory testing was implemented as a reference standard regardless of the ARR result were included. Study-level data were extracted and risk of bias and applicability were assessed using the QUADAS-2 tool. RESULTS: Ten studies, involving a total of 4110 participants, were included. Potential risk of bias related to patient selection was common and present in half of the included studies. The population base, ARR positivity threshold, laboratory assay, and reference standard for confirmatory testing varied substantially between studies. The reported ARR sensitivity and specificity varied widely with sensitivity ranging from 10% to 100% and specificity ranging from 70% to 100%. Notably, 3 of the 10 studies reported an ARR sensitivity of <50%, suggesting a limited ability of the ARR to adequately identify patients with primary aldosteronism. CONCLUSIONS: ARR performance varied widely based on patient population and diagnostic criteria, especially with respect to sensitivity. Therefore, no single ARR threshold for interpretation could be recommended. Limitations in accuracy and reliability of the ARR must be recognized in order to appropriately inform clinical decision-making.


Assuntos
Aldosterona/sangue , Hiperaldosteronismo/diagnóstico , Renina/sangue , Tomada de Decisão Clínica , Feminino , Humanos , Hiperaldosteronismo/sangue , Masculino , Sensibilidade e Especificidade
11.
Sci Rep ; 11(1): 9954, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976254

RESUMO

Biomarkers that reflect hemodynamic stress, inflammation, extracellular matrix remodeling, angiogenesis, and endothelial dysfunction may improve risk stratification and add valuable pathobiological insight in patients with out-of-hospital cardiac arrest (OHCA). In total, 120 patients with OHCA who survived at least 48 h after return of spontaneous circulation were consecutively included in the present analysis. Concentrations of 30 biomarkers were measured simultaneously using a multi-panel biomarker assay. Cox regression models were adjusted for age, sex, estimated glomerular filtration rate, lactate concentration, bystander resuscitation, initial cardiac rhythm, and type of targeted temperature management. Overall, 57 patients (47.5%) had a favorable neurological outcome (Cerebral Performance Category ≤ 2) at 30 days, while palliative care was initiated in 49 patients (40.8%), and 52 patients (43.3%) died. After correction for multiple testing with Bonferroni-Holm, 8 biomarkers (including Angiopoietin-2, Procalcitonin, Resistin, IL-4Rα, MMP-8, TNFα, Renin, and IL-1α) were significantly associated with all-cause death. After multivariable adjustment, only angiopoietin-2 (Adjusted (Adj) hazard ratio (HR) per 1-unit increase in standardized biomarker concentrations 1.52 (95% CI 1.16-1.99)) and renin (Adj HR 1.32 (95% CI 1.06-1.65) remained independently associated with an increased risk of death. The discriminatory performance indicated good performance for angiopoietin-2 (area under the curve (AUC): 0.75 (95% CI 0.66-0.75) and was significantly higher (P = 0.011) as compared with renin (AUC: 0.60, 95% CI 0.50-0.60). In conclusion, angiopoietin-2 was significantly associated with all-cause mortality in patients with OHCA who survived the first 48 h and may prove to be useful for risk stratification of these patients.


Assuntos
Angiopoietina-2/análise , Biomarcadores/análise , Parada Cardíaca Extra-Hospitalar/mortalidade , Idoso , Angiopoietina-2/sangue , Área Sob a Curva , Biomarcadores/sangue , Reanimação Cardiopulmonar/efeitos adversos , Feminino , Parada Cardíaca/imunologia , Parada Cardíaca/mortalidade , Hemodinâmica/fisiologia , Humanos , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/imunologia , Projetos Piloto , Prognóstico , Modelos de Riscos Proporcionais , Renina/análise , Renina/sangue , Fatores de Risco
12.
J Am Coll Cardiol ; 77(23): 2909-2919, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33957242

RESUMO

BACKGROUND: The renin-angiotensin-aldosterone system plays a key role in blood pressure (BP) regulation and is the target of several antihypertensive medications. Renal denervation (RDN) is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce BP. OBJECTIVES: The purpose of this study was to evaluate plasma renin activity (PRA) and aldosterone before and after RDN and to assess whether these baseline neuroendocrine markers predict response to RDN. METHODS: Analyses were conducted in patients with confirmed absence of antihypertensive medication. Aldosterone and PRA levels were compared at baseline and 3 months post-procedure for RDN and sham control groups. Patients in the SPYRAL HTN-OFF MED Pivotal trial were separated into 2 groups, those with baseline PRA ≥0.65 ng/ml/h (n = 110) versus <0.65 ng/ml/h (n = 116). Follow-up treatment differences between RDN and sham control groups were adjusted for baseline values using multivariable linear regression models. RESULTS: Baseline PRA was similar between RDN and control groups (1.0 ± 1.1 ng/ml/h vs. 1.1 ± 1.1 ng/ml/h; p = 0.37). Change in PRA at 3 months from baseline was significantly greater for RDN compared with control subjects (-0.2 ± 1.0 ng/ml/h; p = 0.019 vs. 0.1 ± 0.9 ng/ml/h; p = 0.14), p = 0.001 for RDN versus control subjects, and similar differences were seen for aldosterone: RDN compared with control subjects (-1.2 ± 6.4 ng/dl; p = 0.04 vs. 0.4 ± 5.4 ng/dl; p = 0.40), p = 0.011. Treatment differences at 3 months in 24-h and office systolic blood pressure (SBP) for RDN versus control patients were significantly greater for patients with baseline PRA ≥0.65 ng/ml/h versus <0.65 ng/ml/h, despite similar baseline BP. Differences in office SBP changes according to baseline PRA were also observed earlier at 2 weeks post-RDN. CONCLUSIONS: Plasma renin activity and aldosterone levels for RDN patients were significantly reduced at 3 months when compared with baseline as well as when compared with sham control. Higher baseline PRA levels were associated with a significantly greater reduction in office and 24-h SBP. (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study; NCT02439749).


Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/sangue , Artéria Renal/inervação , Renina/sangue , Simpatectomia/métodos , Biomarcadores/sangue , Monitorização Ambulatorial da Pressão Arterial , Feminino , Humanos , Hipertensão/fisiopatologia , Hipertensão/cirurgia , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina/fisiologia , Método Simples-Cego , Sístole , Resultado do Tratamento
13.
J Clin Endocrinol Metab ; 106(9): e3655-e3664, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-33942084

RESUMO

CONTEXT: Although current international guidelines recommend to avoid mineralocortcoid receptor antagonists in patients undergoing screening test for primary aldosteronism, a recent report suggested that mineralocorticoid receptor antagonist treatment can be continued without significant influence on screening results. OBJECTIVE: We aimed to evaluate the effect of mineralocorticoid receptor antagonists on the aldosterone to renin ratio in patients with primary aldosteronism. METHODS: We prospectively enrolled 121 patients with confirmed primary aldosteronism who started mineralocorticoid receptor antagonist (canrenone) treatment. Eighteen patients (11 with unilateral and 7 with bilateral primary aldosteronism) constituted the short-term study cohort and underwent aldosterone, renin, and potassium measurement after 2 and 8 weeks of canrenone therapy. The long-term cohort comprised 102 patients (16 with unilateral and 67 with bilateral primary aldosteronism, and 19 with undetermined subtype) who underwent hormonal and biochemical re-assessment after 2 to 12 months of canrenone therapy. RESULTS: Renin and potassium levels showed a significant increase, and the aldosterone to renin ratio displayed a significant reduction compared with baseline after both a short- and long-term treatment. These effects were progressively more evident with higher doses of canrenone and after longer periods of treatment. We demonstrated that canrenone exerted a deep impact on the diagnostic accuracy of the screening test for primary aldosteronism: the rate of false negative tests was raised to 16.7%, 38.9%, 54.5%, and 72.5% after 2 weeks, 8 weeks, 2 to 6 months, and 7 to 12 months of mineralocorticoid receptor antagonist treatment, respectively. CONCLUSION: Mineralocorticoid receptor antagonists should be avoided in patients with hypertension before measurement of renin and aldosterone for screening of primary aldosteronism.


Assuntos
Aldosterona/sangue , Hiperaldosteronismo/sangue , Hiperaldosteronismo/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Renina/sangue , Adolescente , Adrenalectomia , Adulto , Idoso , Canrenona/uso terapêutico , Estudos de Coortes , Reações Falso-Negativas , Feminino , Guias como Assunto , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensão/complicações , Masculino , Programas de Rastreamento , Adesão à Medicação , Pessoa de Meia-Idade , Potássio/sangue , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto Jovem
14.
Nutrients ; 13(5)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946894

RESUMO

Increased marinobufagenin (MBG) synthesis has been suggested in response to high dietary salt intake. The aim of this study was to determine the effects of short-term changes in sodium intake on plasma MBG levels in patients with primary salt-sensitive and salt-insensitive hypertension. In total, 51 patients with primary hypertension were evaluated during acute sodium restriction and sodium loading. Plasma or serum concentrations of MBG, natriuretic pro-peptides, aldosterone, sodium, potassium, as well as hematocrit (Hct) value, plasma renin activity (PRA) and urinary sodium and potassium excretion were measured. Ambulatory blood pressure monitoring (ABPM) and echocardiography were performed at baseline. In salt-sensitive patients with primary hypertension plasma MBG correlated positively with diastolic blood pressure (ABPM) and serum NT-proANP concentration at baseline and with serum NT-proANP concentration after dietary sodium restriction. In this subgroup plasma MBG concentration decreased during sodium restriction, and a parallel increase of PRA was observed. Acute salt loading further decreased plasma MBG concentration in salt-sensitive subjects in contrast to salt insensitive patients. No correlation was found between plasma MBG concentration and left ventricular mass index. In conclusion, in salt-sensitive hypertensive patients plasma MBG concentration correlates with 24-h diastolic blood pressure and dietary sodium restriction reduces plasma MBG levels. Decreased MBG secretion in response to acute salt loading may play an important role in the pathogenesis of salt sensitivity.


Assuntos
Bufanolídeos/sangue , Hipertensão/induzido quimicamente , Sódio na Dieta/administração & dosagem , Adulto , Aldosterona/sangue , Fator Natriurético Atrial/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Renina/sangue , Sódio/sangue
16.
Am J Nephrol ; 52(2): 141-151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33735863

RESUMO

INTRODUCTION: Prorenin, a precursor of renin, and renin play an important role in regulation of the renin-angiotensin system. More recently, receptor-bound prorenin has been shown to activate intracellular signaling pathways that mediate fibrosis, independent of angiotensin II. Prorenin and renin may thus be of physiologic significance in CKD, but their plasma concentrations have not been well characterized in CKD. METHODS: We evaluated distribution and longitudinal changes of prorenin and renin concentrations in the plasma samples collected at follow-up years 1, 2, 3, and 5 of the Chronic Renal Insufficiency Cohort (CRIC) study, an ongoing longitudinal observational study of 3,939 adults with CKD. Descriptive statistics and multivariable regression of log-transformed values were used to describe cross-sectional and longitudinal variation and associations with participant characteristics. RESULTS: A total of 3,361 CRIC participants had plasma available for analysis at year 1. The mean age (±standard deviation, SD) was 59 ± 11 years, and the mean estimated glomerular filtration rate (eGFR, ± SD) was 43 ± 17 mL/min per 1.73 m2. Median (interquartile range) values of plasma prorenin and renin at study entry were 4.4 (2.1, 8.8) ng/mL and 2.0 (0.8, 5.9) ng/dL, respectively. Prorenin and renin were positively correlated (Spearman correlation 0.51, p < 0.001) with each other. Women and non-Hispanic blacks had lower prorenin and renin values at year 1. Diabetes, lower eGFR, and use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, and diuretics were associated with higher levels. Prorenin and renin decreased by a mean of 2 and 5% per year, respectively. Non-Hispanic black race and eGFR <30 mL/min/1.73 m2 at year 1 predicted a steeper decrease in prorenin and renin over time. In addition, each increase in urinary sodium excretion by 2 SDs at year 1 increased prorenin and renin levels by 4 and 5% per year, respectively. DISCUSSION/CONCLUSIONS: The cross-sectional clinical factors associated with prorenin and renin values were similar. Overall, both plasma prorenin and renin concentrations decreased over the years, particularly in those with severe CKD at study entry.


Assuntos
Insuficiência Renal Crônica/sangue , Renina/sangue , Adulto , Afro-Americanos , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos Transversais , Diabetes Mellitus/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores Raciais , Insuficiência Renal Crônica/fisiopatologia , Fatores Sexuais , Sódio/urina , Fatores de Tempo
19.
Medicine (Baltimore) ; 100(11): e25049, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725980

RESUMO

ABSTRACT: A recent report demonstrated that the prevalence of obstructive sleep apnea (OSA) is 67.6% among Caucasian and Chinese patients with primary aldosteronism (PA). Moreover, the report showed a significant association between plasma aldosterone concentration (PAC) and the severity of OSA in Caucasian patients. However, no studies have examined the prevalence of OSA with PA or the association of its severity with PAC in the Japanese population. We retrospectively evaluated the prevalence and severity of OSA in 71 newly diagnosed Japanese patients with PA. Thirty-nine (55%) of the 71 patients were diagnosed with OSA, and 69% of PA patients with OSA reported snoring. No correlation was found between the respiratory event index (REI), snoring index, and PAC and plasma renin activity (PRA). In contrast, REI correlated significantly with body mass index (BMI), which was significantly correlated with PRA. In conclusion, although the severity of OSA did not correlate with PAC and PRA, there was a high prevalence of OSA among Japanese patients with PA. Moreover, the severity of OSA was strongly affected by BMI. Thus, the examination of OSA in patients with PA and the proper management of OSA might be important for the Japanese population.


Assuntos
Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Hiperaldosteronismo/complicações , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/epidemiologia , Adulto , Aldosterona/sangue , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Hiperaldosteronismo/etnologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Renina/sangue , Estudos Retrospectivos , Apneia Obstrutiva do Sono/etnologia , Apneia Obstrutiva do Sono/etiologia , Ronco/epidemiologia , Ronco/etnologia , Ronco/etiologia
20.
Eur J Endocrinol ; 184(4): 543-552, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33539316

RESUMO

Objective: While evidence on the interface between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the renin-angiotensin-aldosterone-system (RAAS) is accumulating, clinical data on RAAS peptide alteration among coronavirus disease-19 (COVID-19) patients is missing. Design and methods: In this exploratory study, we prospectively included adult patients (aged ≥ 18 years) admitted between February 26 and April 30, 2020 to a tertiary care hospital in Switzerland. We assessed the association of an underlying SARS-CoV-2 infection and equilibrium serum levels of RAAS peptides in hospitalized COVID-19 patients 1:1 propensity-score matched with patients suffering from SARS-CoV-2-negative respiratory infections. Subgroup analyses involved stratification for taking RAAS inhibitors. Results: COVID-19 patients had about 50% lower equilibrium serum RAAS peptide levels as compared with matched controls (angiotensin I: 31.6 vs 66.8 pmol/L, -52.7% (95%CI: -68.5% to -36.9%); angiotensin II: 37.7 vs 92.5 pmol/L, -59.2% (95%CI: -72.1% to -46.3%); angiotensin (1-5): 3.3 vs 6.6 pmol/L, -49.7% (95%CI: -59.2% to -40.2%); angiotensin (1-7): 4.8 vs 7.6 pmol/L, -64.9% (95%CI: -84.5% to -45.3%)). While the plasma renin activity was lower in COVID-19 patients (88.6 vs 207.9 pmol/L, -58.5% (95%CI: -71.4% to -45.6%)), there was no difference of angiotensin-converting enzyme (ACE) and ACE2 plasma activity between the groups. Subgroup analyses revealed a pronounced RAAS peptide profile depression in COVID-19 patients among those not on RAAS inhibitors. Conclusions: As compared with SARS-CoV-2-negative patients, we found a downregulated RAAS in presence of a SARS-CoV-2 infection. Whether the lower levels of the protective angiotensin (1-5) and (1-7) are linked to adverse outcomes in COVID-19 warrants further investigation.


Assuntos
Angiotensina II/sangue , Angiotensina I/sangue , Enzima de Conversão de Angiotensina 2/sangue , COVID-19/sangue , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Renina/sangue , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema Renina-Angiotensina , SARS-CoV-2
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