Augmentation index, a predictor of cardiovascular events, is increased in children and adolescents with primary nephrotic syndrome.

BACKGROUND: Arterial stiffness is associated with an increased risk of cardiovascular diseases. Augmentation index (AIx@75), a measure of arterial stiffness and wave reflection, has not been evaluated in patients with primary nephrotic syndrome (PNS). We investigated whether central and peripheral vascular profiles, hemodynamic parameters, and biochemical tests are associated with AIx@75 in PNS patients. METHODS: This observational study involved 38 children and adolescents with PNS (12.14 ± 3.65 years) and 37 healthy controls (13.28 ± 2.80 years). Arterial stiffness and vascular and hemodynamic parameters were measured noninvasively using the Mobil-O-Graph® (IEM, Stolberg, Germany). In the PNS group, biochemical tests and corticosteroid dosage/treatment time were analyzed. RESULTS: Peripheral and central systolic blood pressure (SBPp, SBPc) Z-scores were significantly higher in the PNS patients. AIx@75 was significantly higher in the PNS patients (25.14 ± 9.93%) than in controls (20.84 ± 7.18%). In the control group, AIx@75 negatively correlated with weight (r = - 0.369; p = 0.025), height (r = - 0.370; p = 0.024), and systolic volume/body surface (r = - 0.448; p = 0.006). In the PNS group, a univariate linear correlation showed that AIx@75 negatively correlated with weight (r = - 0.360; p = 0.027), height (r = 0.381; p = 0.18), and systolic volume/body surface (r = - 0.447; p < 0.002) and positively with the Z-score of SBPp (r = 0.407; p = 0.011), peripheral diastolic blood pressure (DBPp, r = 0.452; p = 0.004), SBPc (r = 0.416; p = 0.009), DBPc (r = 0.407; p = 0.011), triglycerides (r = 0.525; p = 0.001), and cholesterol [total (r = 0.539; p < 0.001), LDLc (r = 0.420; p = 0.010), and non-HDLc (r = 0.511; p = 0.001)]. CONCLUSIONS: Early abnormalities of AIx@75 and vascular parameters suggest that patients with PNS, even in stable condition, present subclinical indicators for the development of cardiovascular disease.

Vascular function in asthmatic children and adolescents.

BACKGROUND: Epidemiological studies have demonstrated an increased incidence of cardiovascular events in patients with bronchial asthma, but little is known about the relationship between asthma and vascular function. The purpose of this study was to evaluate endothelial function and arterial stiffness in children and adolescents with asthma. METHODS: A cross-sectional controlled study was designed. Measurements of endothelial function and arterial stiffness in asthmatic (13.6 ± 0.6 years) and control groups (14.9 ± 0.7 years) were taken by the non-invasive peripheral arterial tonometry (EndoPAT2000) determined by using the natural logarithm of the reactive hyperemia index (LnRHI) and the augmentation index (AIx@75%), respectively. Patients with asthma were also administered two questionnaires to evaluate asthma control and quality of life. Exercise functional capacity was evaluated using the Shuttle Walking Test (SWT). Only male participants were included in the present study. RESULTS: LnRHI and the walked distance during the SWT were similar between groups (p = 0.23 and p = 0.50, respectively). AIx@75% was significantly higher in the asthmatic group (-7.75 ± 1.7) compared to the control group (-15.25 ± 1.8), p < 0.04. In the control group, the LnRHI correlated positively with baseline systolic blood pressure (r = 0.53, p = 0.02) and mean arterial pressure (r = 0.50, p = 0.03), age (r = 0.61, p = 0.007), weight (r = 0.63, p = 0.004) and height (r = 0.56, p = 0.015). Besides that LnRHI correlated with FVC (r = 0.69, p = 0.002), FEV1, (r = 0.53, p = 0.03) and negatively with Tiffeneau index (FEV1/FVC%, r = -0.49 p = 0.04). The LnRHI of the asthmatic group did not correlate with the different variables evaluated. CONCLUSION: The increased AIx@75% without changes in LnRHI in asthmatic patients could mean that an early detection of vascular impairment may precede endothelial dysfunction, and that different mechanisms may contribute to the pathogenesis and progression of cardiovascular events in this population. A large prospective and randomized controlled study should be done to evaluate the physiopathological mechanisms underlying the association between arterial stiffness and asthma.

Blocking the L-type Ca2+ channel (Cav 1.2) is the key mechanism for the vascular relaxing effect of Pterodon spp. and its isolated diterpene methyl-6α-acetoxy-7ß-hydroxyvouacapan-17ß-oate.

Pterodon spp. Vogel (Fabaceae), popularly known as "sucupira", has ethnopharmacological application which is described as having antispasmodic and relaxant effects. Hence, it was hypothesized that sucupira oil-resin (SOR) could induce smooth muscle relaxation. So, this study investigated the mechanisms involved in the vasorelaxant effect of SOR and its isolated diterpene (methyl-6α-acetoxy-7ß-hydroxyvouacapan-17ß-oate). Vascular reactivity experiments were performed using rat aortic rings (n=5-8) with (E+) or without endothelium (E-) in an isolated bath organ. The SOR (0-56 µg/mL) relaxed phenylephrine (E+: 86.7±7.1%; E-: 92.3±4.7%) and KCl contracted rings (E-: 97.1±2.8%). In the same way, diterpene (0-48 µg/mL) also relaxed phenylephrine (E+: 94.5±3.6%; E-: 92.2±3.4%) and KCl contracted rings (E-: 99.7±0.2%). The pre-incubation of arterial rings with cyclopiazonic acid (reticular Ca2+-ATPase inhibitor), tetraethylammonium (K+ channels blocker) or MDL-12,330A (adenylyl cyclesinhibitor) did not modify either SOR- or diterpeneinduced vasorelaxation. However, ODQ (guanylyl cyclase inhibitor) impaired only diterpene-induced vasorelaxation. SOR and diterpene significantly reduced CaCl2-induced contraction stimulated by Bay K8644 (1 µM), phenylephrine (0.1 µM) or KCl solution (40 mM). Computational molecular docking studies demonstrated that the vasodilator effect of diterpene relies on blocking the Cav 1.2 channel, and patch clamp results showed that diterpene substantially decreased the ionic current through Cav 1.2 in freshly dissociated vascular smooth muscle cells. These findings suggest that SOR and its isolated diterpene induce endothelium-independent vascular relaxation by blocking the L-type Ca2+ channel (Cav 1.2).

Predictors and reference equations for augmentation index, an arterial stiffness marker, in healthy children and adolescents.

OBJECTIVES: To investigate predictors and propose reference equations for the augmentation index normalized to 75 bpm heart rate (AIx@75) in healthy children and adolescents. METHODS: This was a cross-sectional, observational study involving 134 healthy children and adolescents aged 9 to 19 years old. Participants were categorized into child (n=53) and adolescent (n=81) groups, as well as into male (n=69) and female (n=65) groups. We evaluated AIx@75, vascular and hemodynamic parameters, anthropometric data, physical activity profile, and quality of life (Peds-QL4.0; physical, emotional, social and school domains). RESULTS: The predictors of AIx@75 in the whole sample were age, peripheral diastolic blood pressure (pDBP), mean arterial pressure, pulse pressure amplification (PPA), systolic volume (SV), cardiac index (CI), and pulse wave velocity (PWV; R2=80.47%). In the male group, the predictors of AIx@75 were SV, CI, total vascular resistence (TVR), and PWV (R2=78.56%), while in the female group, they were pDBP, PPA, SV, and PWV (R2=82.45%). In the children, they were pDBP, PPA, SV, and PWV (R2=79.17%), while in the adolescents, they were body mass index, pDBP, PPA, SV, TVR, and PWV (R2=81.57%). CONCLUSION: In the present study, we used a representative sample from Belo Horizonte to establish normality values of AIx@75. We also identified, for the first time, independent predictors of AIx@75 in healthy children and adolescents categorized by sex and age. Determining AIx@75 reference equations may facilitate the early diagnosis of preclinical atherosclerosis and allow an objective measure of the vascular effects of therapeutic interventions aimed at modifying cardiovascular risk factors.

Positive end-expiratory pressure attenuates hemodynamic effects induced by an overload of inspiratory muscles in patients with COPD.

BACKGROUND: Inspiratory muscle training (IMT) using a Threshold® device is commonly used to improve the strength and endurance of inspiratory muscles. However, the effect of IMT, alone or with positive end-expiratory pressure (PEEP), on hemodynamic parameters in patients with chronic obstructive pulmonary disease (COPD) remains unknown. OBJECTIVE: To assess the effects of an overload of inspiratory muscles using IMT fixed at 30% of the maximal inspiratory pressure (MIP), and IMT associated with 5 cmH2O of PEEP (IMT + PEEP), on the echocardiographic parameters in healthy subjects and patients with COPD. METHODS: Twenty patients with COPD (forced expiratory volume in 1 second 53.19±24.71 pred%) and 15 age-matched healthy volunteers were evaluated using spirometry, MIP, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) dyspnea scale. The E- (fast-filling phase) and A- (atrial contraction phase) waves were evaluated at the tricuspid and mitral valves during inspiration and expiration in the following sequence: at basal conditions, using IMT, and using IMT + PEEP. RESULTS: Patients with COPD had reduced MIPs versus the control group. Ten patients had CAT scores <10 and 12 patients had mMRC scores <2. E-wave values at the mitral valve were significantly decreased with IMT during the inspiratory phase in both groups. These effects were normalized with IMT + PEEP. During the expiratory phase, use of IMT + PEEP normalized the reduction in E-wave values in the COPD group. During inspiration at the tricuspid valve, reduction in E-wave values during IMT was normalized by IMT + PEEP in COPD group. During the expiratory phase, the value of the E-waves was significantly reduced with overload of the inspiratory muscles in both groups, and these effects were normalized with IMT + PEEP. A-waves did not change under any conditions. CONCLUSION: Acute hemodynamic effects induced by overloading of the inspiratory muscles were attenuated and/or reversed by the addition of PEEP in COPD patients.

Depression diagnosed by the mini international neuropsychiatric interview plus (MINI) in patients with chronic obstructive pulmonary disease: relationship with functional capacity and quality of life.

BACKGROUND: The prevalence of depression in patients with chronic obstructive pulmonary disease (COPD) is associated with a worsening of prognosis. Most studies classify COPD patients as depressive or non-depressive based on symptoms, rather than on a diagnosis using specific tools. Thus, the aim of this study was to determine the impact of depression, as diagnosed by the Mini International Neuropsychiatric Interview Plus (MINI), on functional capacity estimated by the 6-minute walk test (6MWT) and unsupported upper-limb exercise test, and quality of life estimated by Saint George's Respiratory Questionnaire (SGRQ), among patients with COPD. RESULTS: Using the MINI as a diagnostic tool, 22.2 % of all patients (6.6 % of all men and 41.6 % of all women) were diagnosed with depression. No significant differences were found between depressive and non-depressive patients with regard to anthropometric measurements, lung function, functional capacity, or quality of life variables. The best models for the dependent variables representing functional capacity and quality of life revealed that the covariates SGRQTOTAL and gender (R(2) = 16.7 %) were significant in explaining the response variable for functional capacity of the upper limbs. Results also showed that age, monthly income, insomnia, and the results of a 6MWT were significant in explaining overall quality of life (R(2) = 46 %), and that the percentage of the predicted forced expiratory volume in the first second post-bronchodilator and gender were significant in explaining walking distance (R(2) = 22 %). Depression, as diagnosed by the MINI, was not significant in explaining any of the dependent variables. CONCLUSIONS: Despite a high prevalence of depression in COPD patients, especially in women, depression, as diagnosed by the MINI, was not correlated with functional capacity tests or quality of life in patients with moderate to very severe COPD in the present study. This suggests that depression identified by this diagnostic test may be more accurate than depression diagnosed by tests that evaluate symptoms, as they may be influenced by the perceptions of the patient in relation to their health.

Predictors and reference equations for augmentation index, an arterial stiffness marker, in healthy children and adolescents

OBJECTIVES: To investigate predictors and propose reference equations for the augmentation index normalized to 75 bpm heart rate (AIx@75) in healthy children and adolescents. METHODS: This was a cross-sectional, observational study involving 134 healthy children and adolescents aged 9 to 19 years old. Participants were categorized into child (n=53) and adolescent (n=81) groups, as well as into male (n=69) and female (n=65) groups. We evaluated AIx@75, vascular and hemodynamic parameters, anthropometric data, physical activity profile, and quality of life (Peds-QL4.0; physical, emotional, social and school domains). RESULTS: The predictors of AIx@75 in the whole sample were age, peripheral diastolic blood pressure (pDBP), mean arterial pressure, pulse pressure amplification (PPA), systolic volume (SV), cardiac index (CI), and pulse wave velocity (PWV; R2=80.47%). In the male group, the predictors of AIx@75 were SV, CI, total vascular resistence (TVR), and PWV (R2=78.56%), while in the female group, they were pDBP, PPA, SV, and PWV (R2=82.45%). In the children, they were pDBP, PPA, SV, and PWV (R2=79.17%), while in the adolescents, they were body mass index, pDBP, PPA, SV, TVR, and PWV (R2=81.57%). CONCLUSION: In the present study, we used a representative sample from Belo Horizonte to establish normality values of AIx@75. We also identified, for the first time, independent predictors of AIx@75 in healthy children and adolescents categorized by sex and age. Determining AIx@75 reference equations may facilitate the early diagnosis of preclinical atherosclerosis and allow an objective measure of the vascular effects of therapeutic interventions aimed at modifying cardiovascular risk factors.