Cristina Sierra

Ambulatory blood pressure monitoring in hypertensive patients with high cardiovascular risk: a cross-sectional analysis of a 20,000-patient database in Spain.

Objective To evaluate ambulatory blood pressure monitoring (ABPM) parameters in a broad sample of high-risk hypertensive patients. Methods The Spanish Society of Hypertension is developing a nationwide project in which more than 900 physicians send ABPM registries and corresponding clinical records to a central database via www.cardiorisc.com. Between June 2004 and July 2005 a 20 000-patient database was obtained; 17 219 were valid for analysis. Results We identified 6534 patients with high cardiovascular risk according to the 2003 European Society of Hypertension/European Society of Cardiology guidelines stratification score. Office blood pressure (BP) was 158.8/89.9 mmHg and 24-h BP was 135.8/77.0 mmHg. Patients with grade 3 BP in the office showed ambulatory systolic BP values less than 160 mmHg in more than 80%. A non-dipping pattern was observed in 3836 cases (58.7%), whereas this abnormality was present in 47.9% of patients with low-to-moderate risk [odds ratio (OR) 1.54; 95% confidence interval (CI) 1.45–1.64]. The prevalence of non-dippers was higher as ambulatory BP increased (≈ 70% when 24-h systolic BP > 155 mmHg) and was similar in both groups. At the lowest levels of BP (24-h systolic BP < 135 mmHg) a non-dipping pattern was more prevalent in high-risk cases (56.6 versus 45.7%; OR 1.51; 95% CI 1.40–1.64). Conclusion There was a remarkable discrepancy between office and ambulatory BP in high-risk hypertensive patients. The prevalence of a non-dipper BP pattern was almost 60%. In the lowest levels of ambulatory BP, high-risk patients showed a higher prevalence of non-dipping BP than lower-risk cases. These observations support the recommendation of a wider use of ABPM in high-risk hypertensive patients.

Silent cerebral white matter lesions in middle-aged essential hypertensive patients.

Objective Age, hypertension, diabetes mellitus and a history of cardiovascular disease are the most important factors related to the presence of cerebral white matter lesions (WML), which are a common finding in elderly people. This study investigates which factors related to hypertension per se are associated with the presence of WML in asymptomatic, middle-aged, never-treated essential hypertensive patients. Methods A total of 66 untreated essential hypertensive patients of both genders, aged 50–60 years, with neither diabetes mellitus nor evidence of cardiovascular disease, were studied. Hypertensive patients were classified into two groups according to the presence or absence of WML in brain magnetic resonance imaging (MRI). Results A total of 39 (59.1%) hypertensives showed no WML in brain MRI, and 27 (40.9%) exhibited the presence of WML. Compared with hypertensives without WML, patients with WML showed significantly higher values of both office and 24 h ambulatory blood pressure monitoring (ABPM) systolic, diastolic, mean and pulse pressure. No differences were observed in either the nocturnal fall of blood pressure, or in blood pressure variability, assessed by 24 h standard deviation, among hypertensives with WML. In contrast, the nocturnal decline of heart rate was significantly blunted in patients with WML, compared with those without WML. Conclusions Cerebral white matter lesions are a common finding in asymptomatic middle-aged essential hypertensives. The severity of blood pressure elevation seems to be the most important factor related to the presence of WML. Neither the circadian rhythm nor the long-term variability of blood pressure were related to WML.

Idebenone treatment in paediatric and adult patients with Friedreich ataxia: Long-term follow-up

BACKGROUND Antioxidant therapy is a new therapeutical approach for patients with Friedreich ataxia. AIMS To assess the effectiveness of long-term idebenone treatment in Friedreich ataxia patients. METHODS An open-labelled prospective study. Ten paediatric patients (age range 8-18 years) and 14 adults (age range 18-46 years) with genetic diagnosis of Friedreich ataxia were treated with idebenone (5-20mg/kg/day) for 3-5 years. Neurological evolution was evaluated using the International Cooperative Ataxia Rating Scale (ICARS), and cardiological outcomes using echocardiography. RESULTS In paediatric patients, no significant differences were observed in ICARS scores and echocardiographic measurements when comparing baseline status and after 5 years of follow-up. Concerning adult cases, ICARS scores showed a significant increase in neurological dysfunctions during 3 years of therapy (Wilcoxon test, p=0.005), while echocardiographic measurements remained unchanged. CONCLUSIONS Our results indicate that longer-term idebenone treatment prevented progression of cardiomyopathy in both paediatric and adult patients, whereas its stabilizing effect on neurological dysfunction was present only in the paediatric population, mainly before puberty. This suggests that the age at which idebenone treatment is initiated may be an important factor in the effectiveness of the therapy.

Antioxidant status in hyperphenylalaninemia

Abnormal oxidative stress was observed in some inborn errors of metabolism owing to the accumulation of toxic metabolites leading to excessive free radical production and to the influence of restricted diets on the antioxidant status. Erythrocyte antioxidant enzymes activities and tocopherol concentrations were measured in a group of phenylketonuric (n = 42) and mild-hyperphenylalaninemic (n = 28) patients compared with 45 age-matched controls. We also determined plasma selenium levels in these groups. We also evaluated the possible relationship between antioxidant status and neuropsychological disorders. Erythrocyte glutathione peroxidase (GSH-Px) activity was significantly lower (P < 0.001) in both phenylketonuric and mild-hyperphenylalaninemic patients compared with the control group, but no differences were observed between the two groups of patients. Neuropsychological disturbances were more frequent in the group of PKU patients with low GSH-Px activity than in PKU patients with normal GSH-Px. Low GSH-Px activity might be explained in phenylketonuria as a result of a selenium deficiency caused by a poor selenium intake or absorption, but not in mild hyperphenylalaninemic patients with free diet. Selenium levels were normal in both groups of patients, so low glutathione peroxidase activity in both phenylketonuric and hyperphenylalaninemic groups might be influenced by other factors, such as the consequences of an unbalanced amino acid profile, common to both conditions.

Assessment of salt sensitivity in essential hypertension by 24-h ambulatory blood pressure monitoring

We used ambulatory blood pressure monitoring (ABPM) in the assessment of salt sensitivity in 40 essential hypertensive patients, comparing 24-h mean blood pressure during 7 days of low salt (20 mmol NaCl/day) and high salt (260 mmol NaCl/day) intake. Salt sensitivity was diagnosed in 18 essential hypertensive patients (45%), each of them showing a significant increase in mean blood pressure (P < .05) from low to high salt diet. Salt-sensitive patients exhibited a high-salt-dependent increase in all blood pressure parameters including 24-h systolic, mean, diastolic blood pressure, blood pressure load, area under the curve, and awake and asleep blood pressure values. These patients exhibited a nondipper profile on both low-salt and high-salt diets. Salt-resistant patients (55%) showed a decrease in awake, and an increase in asleep blood pressure values after high salt intake, thus tending to flatten the circadian blood pressure profile. We conclude that ABPM is a useful method to assess salt sensitivity. In salt-resistant patients high salt intake induces a significant increase in asleep blood pressure with no significant changes in 24-h blood pressure, promoting a flattened blood pressure curve and tending to transform a dipper into a nondipper profile, which could have important implications in end-organ damage.

Oral Insulin-Mimetic Compounds That Act Independently of Insulin

The hallmarks of insulin action are the stimulation and suppression of anabolic and catabolic responses, respectively. These responses are orchestrated by the insulin pathway and are initiated by the binding of insulin to the insulin receptor, which leads to activation of the receptor’s intrinsic tyrosine kinase. Severe defects in the insulin pathway, such as in types A and B and advanced type 1 and 2 diabetes lead to severe insulin resistance, resulting in a partial or complete absence of response to exogenous insulin and other known classes of antidiabetes therapies. We have characterized a novel class of arylalkylamine vanadium salts that exert potent insulin-mimetic effects downstream of the insulin receptor in adipocytes. These compounds trigger insulin signaling, which is characterized by rapid activation of insulin receptor substrate-1, Akt, and glycogen synthase kinase-3 independent of insulin receptor phosphorylation. Administration of these compounds to animal models of diabetes lowered glycemia and normalized the plasma lipid profile. Arylalkylamine vanadium compounds also showed antidiabetic effects in severely diabetic rats with undetectable circulating insulin. These results demonstrate the feasibility of insulin-like regulation in the complete absence of insulin and downstream of the insulin receptor. This represents a novel therapeutic approach for diabetic patients with severe insulin resistance.

Vascular stiffness and endothelial dysfunction: Correlations at different levels of blood pressure

Abstract Resistant hypertensive (RHTN) patients have endothelial dysfunction and aldosterone excess, which contribute to the development of resistance to antihypertensive treatment and cardiovascular complications. Biophysical forces within the arterial wall provide functional regulation of arterial stiffness. Carotid–femoral pulse wave velocity (PWV) and flow-mediated brachial artery dilation (FMD) can be used to evaluate vascular stiffness and endothelial function. Although both techniques have been used in several studies in hypertensive patients, it is unknown whether endothelial dysfunction is also associated with vascular stiffness in RHTN patients. Methods. One hundred and ninety-three consecutive subjects were divided in three groups: 44 RHTN, 35 well-controlled hypertensive patients (HTN) and 25 normal healthy volunteers (NT). FMD was measured by high-resolution ultrasound and PWV was calculated from measurements of the pulse transit time and the distance traveled by the pulse between carotid and femoral arteries. Results. No significant differences were observed in respect to body mass index, age or other biochemical variables among the three groups. FMD (NO-dependent) values were statistically different when comparing RHTN and well controlled HTN patients (respectively, 8.3 ± 4.7% and 10.1 ± 5.9%) and 12.3 ± 6.3% in normal subjects (p < 0.05). One-way analysis of variance (ANOVA) showed a significant difference in BP-adjusted PWV between RHTN and HTN (13.9 ± 1.0 and 11.5 ± 1.1 m/s, respectively; p < 0.05). FMD (NO-dependent) and PWV-adjusted values were strongly correlated in well-controlled HTN and NT subjects (r = − 0.74 and − 0.83, respectively). Although statistically significant, this correlation was lower in RHTN patients (r = − 0.43). Conclusion. We found a close relationship among high BP levels, endothelial dysfunction and vascular rigidity in hypertensive patients, demonstrated by a significantly higher increase in carotid–femoral PWV and a decrease in brachial artery FMD in RHTN when compared with well-controlled hypertensive patients. Although this study was not designed to test the prognostic, the vascular damage differences observed between patients with controlled vs uncontrolled hypertension suggest that the latter group may have a worse cardiovascular prognosis, requiring prospective assessment tests.

Oxidative stress in Rett syndrome

The investigation of parameters that might influence the neurological evolution of Rett syndrome might also yield new information about its pathogenic mechanisms. Oxidative stress caused by oxygen free radicals is involved in the neuropathology of several neurodegenerative disorders, as well as in stroke and seizures. To evaluate the free radical metabolism in Rett syndrome, we measured red blood cell antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase) and plasma malondialdehyde, as lipid peroxidation marker in a group of patients with Rett syndrome. No significant differences were observed in erythrocyte glutathione peroxidase, glutathione reductase and catalase activities, between the Rett syndrome patients and the control group. Erythrocyte superoxide dismutase activities were significantly decreased in Rett syndrome patients (P<0.001) compared with the control group. Plasma malondialdehyde concentrations were significantly increased in Rett syndrome patients (P<0.001). An unbalanced nutritional status in Rett syndrome might explain the reduced enzyme activity found in these patients. Our results suggest that free radicals generated from oxidation reactions might contribute to the pathogenesis of Rett syndrome. The high levels of malondialdehyde reflect peroxidative damage of biomembranes that may contribute to progressive dementia, impaired motor function, behavioural changes, and seizures, in Rett syndrome. We found a probable relationship between the degree of oxidative stress and the severity of symptoms, which should be further investigated with a larger number of patients in different disease stages.

Monitorización ambulatoria de la presión arterial (MAPA): características clínicas de 31.530 pacientes

Fundamento y objetivo La monitorizacion ambulatoria de la presion arterial (MAPA) constituye una herramienta util en el diagnostico y seguimiento de los pacientes hipertensos. El presente estudio analiza las caracteristicas clinicas de una serie de 31.530 pacientes sometidos a una MAPA dentro del Registro Nacional. Pacientes y metodo Un total de 767 investigadores incluyeron en el estudio a pacientes con sospecha o diagnostico de hipertension en los que se indico la practica de una MAPA de 24 h con un monitor validado. Se registraron las medias de presion durante los periodos diurno, nocturno y de 24 h y se definieron los perfiles circadianos en funcion del descenso nocturno de presion sistolica: dipper extremo (> 20%), dipper (10-20%), no dipper ( Resultados Los valores de presion arterial de 24 h, diurna y nocturna fueron inferiores a los obtenidos en la consulta. Un 20% de los pacientes presentaba cifras elevadas en la consulta y normales en la MAPA (hipertension arterial [HTA] de «bata blanca» o seudorresistencia), y un 9%, cifras altas en la MAPA y normales en la consulta (HTA enmascarada). Los perfiles no dipper o riser estaban presentes en mas de la mitad de los pacientes (el 40,2 y el 13,4%, respectivamente) y se asociaban a grupos de mayor riesgo cardiovascular. Conclusiones Casi una tercera parte de los pacientes presenta cifras de presion arterial no concordantes entre la medida clinica y la MAPA. Mas de la mitad, especialmente los hipertensos de mayor riesgo, presentan un perfil circadiano en el que no se produce un adecuado descenso nocturno de presion.

Cerebral hemodynamics and silent cerebral white matter lesions in middle-aged essential hypertensive patients

Cerebral white matter lesions (WML) represent a subclinical form of ischemic brain damage that have been associated with risk of future stroke. Studies have shown an association between WML and impaired cerebral autoregulation in hypertensives who had previously suffered a stroke. The aim of the study was to evaluate cerebral hemodynamics in asymptomatic hypertensives according to the presence or absence of WML. Fifty never-treated essential hypertensives (32 men, 18 women), aged 50-60 years, without clinical evidence of target organ damage were studied. All patients underwent 24-h ambulatory blood pressure monitoring, and brain-magnetic resonance imaging to establish the presence or absence of WML. Baseline cerebral blood flow velocity (CBF), pulsatility index (PI; differences between systolic and diastolic velocities), and CBF after acetazolamide infusion (vasomotor reactivity of cerebral vessels), were measured by transcranial Doppler ultrasonography in both left and right middle cerebral arteries, and averaged. Twenty hypertensive patients (40%) were found to have WML on brain resonance. No differences were observed on resting and stimulating CBF between hypertensives with and without WML. In contrast, patients with WML exhibited significantly higher PI compared with hypertensives without WML (0.79 ± 0.13 vs 0.66 ± 0.12; p = 0.003). Moreover, PI correlated with 24-h pulse pressure (r = 0.361; p = 0.015). We conclude that the presence of silent WML in middle-aged hypertensives is associated with increased cerebrovascular pulsatility. This increased pulsatility is also associated with higher pulse pressure values, suggesting a pathogenetic link between pulse pressure, pulsatility and the development of WML.