Alejandro de la Sierra

Clinical Features of 8295 Patients With Resistant Hypertension Classified on the Basis of Ambulatory Blood Pressure Monitoring

We aimed to estimate the prevalence of resistant hypertension through both office and ambulatory blood pressure monitoring in a large cohort of treated hypertensive patients from the Spanish Ambulatory Blood Pressure Monitoring Registry. In addition, we also compared clinical features of patients with true or white-coat–resistant hypertension. In December 2009, we identified 68 045 treated patients with complete information for this analysis. Among them, 8295 (12.2% of the database) had resistant hypertension (office blood pressure ≥140 and/or 90 mm Hg while being treated with ≥3 antihypertensive drugs, 1 of them being a diuretic). After ambulatory blood pressure monitoring, 62.5% of patients were classified as true resistant hypertensives, the remaining 37.5% having white-coat resistance. The former group was younger, more frequently men, with a longer duration of hypertension and a worse cardiovascular risk profile. The group included larger proportions of smokers, diabetics, target organ damage (including left ventricular hypertrophy, impaired renal function, and microalbuminuria), and documented cardiovascular disease. Moreover, true resistant hypertensives exhibited in a greater proportion a riser pattern (22% versus 18%; P<0.001). In conclusion, this study first reports the prevalence of resistant hypertension in a large cohort of patients in usual daily practice. Resistant hypertension is present in 12% of the treated hypertensive population, but among them more than one third have normal ambulatory blood pressure. A worse risk profile is associated with true resistant hypertension, but this association is weak, thus making it necessary to assess ambulatory blood pressure monitoring for a correct diagnosis and management.

Prevalence and Factors Associated With Circadian Blood Pressure Patterns in Hypertensive Patients

Ambulatory blood pressure (BP) monitoring has become useful in the diagnosis and management of hypertensive individuals. In addition to 24-hour values, the circadian variation of BP adds prognostic significance in predicting cardiovascular outcome. However, the magnitude of circadian BP patterns in large studies has hardly been noticed. Our aims were to determine the prevalence of circadian BP patterns and to assess clinical conditions associated with the nondipping status in groups of both treated and untreated hypertensive subjects, studied separately. Clinical data and 24-hour ambulatory BP monitoring were obtained from 42 947 hypertensive patients included in the Spanish Society of Hypertension Ambulatory Blood Pressure Monitoring Registry. They were 8384 previously untreated and 34 563 treated hypertensives. Twenty-four-hour ambulatory BP monitoring was performed with an oscillometric device (SpaceLabs 90207). A nondipping pattern was defined when nocturnal systolic BP dip was <10% of daytime systolic BP. The prevalence of nondipping was 41% in the untreated group and 53% in treated patients. In both groups, advanced age, obesity, diabetes mellitus, and overt cardiovascular or renal disease were associated with a blunted nocturnal BP decline (P<0.001). In treated patients, nondipping was associated with the use of a higher number of antihypertensive drugs but not with the time of the day at which antihypertensive drugs were administered. In conclusion, a blunted nocturnal BP dip (the nondipping pattern) is common in hypertensive patients. A clinical pattern of high cardiovascular risk is associated with nondipping, suggesting that the blunted nocturnal BP dip may be merely a marker of high cardiovascular risk.

Effectiveness of Blood Pressure Control Outside the Medical Setting

We studied the effectiveness of blood pressure (BP) control outside the clinic by using ambulatory BP monitoring (ABPM) among a large number of hypertensive subjects treated in primary care centers across Spain. The sample consisted of 12 897 treated hypertensive subjects who had indications for ABPM. Office-based BP was calculated as the average of 2 readings. Twenty-four–hour ABPM was then performed using a SpaceLabs 90207 monitor under standardized conditions. A total of 3047 patients (23.6%) had their office BP controlled, and 6657 (51.6%) were controlled according to daytime ABPM. The proportion of office resistance or underestimation of patients’ BP control by physicians in the office (office BP ≥140/90 mm Hg and average daytime ambulatory BP <135/85 mm Hg) was 33.4%, and the proportion of isolated office control or overestimation of control (office BP <140/90 mm Hg and average daytime ambulatory BP ≥135/85 mm Hg) was 5.4%. BP control was more frequently underestimated in patients who were older, female, obese, or with morning BP determination than in their counterparts. BP control was more frequently overestimated in those who were younger, male, nonobese, smokers, or with evening BP determination. Ambulatory-based hypertension control was far better than office-based hypertension control. This conveys an encouraging message to clinicians, namely that they are actually doing better than is evidenced by office-based data. However, the burden of underestimation and overestimation of BP control at the office is still remarkable. Physicians should be aware that the likelihood of misestimating BP control is higher in some hypertensive subjects.

Clinical differences between resistant hypertensives and patients treated and controlled with three or less drugs.

Background and aim: Clinical characteristics of resistant hypertensive patients in comparison to controlled patients have not been fully investigated in large cohorts. The aim of the study was to evaluate clinical differences, target organ damage and ambulatory blood pressure monitoring in resistant hypertensive patients and patients controlled on three or less drugs. Methods: In December 2010, from the Spanish Ambulatory Blood Pressure Monitoring Registry, we identified 14 461 patients fulfilling criteria of resistant hypertension and 13 436 hypertensive patients controlled on three or less drugs. Clinical characteristics were compared between these two groups. Results: Compared to controlled patients, those having resistant hypertension were older, more obese and had longer hypertension duration. They also had more frequently diabetes, dyslipidemia, reduced renal function, microalbuminuria, left-ventricular hypertrophy and previous history of cardiovascular events. In multivariate analyses, hypertension duration, obesity, abdominal obesity, left-ventricular hypertrophy, reduced estimated glomerular filtration rate, and microalbuminuria were independently associated with resistant hypertension. Resistant hypertensive patients had higher ambulatory blood pressures, but differences between office and ambulatory blood pressure (white-coat effect) were also more pronounced in this group, revealing a proportion of 40% of patients with normal 24-h blood pressure. On the contrary, values of 24-h blood pressure above 130 and/or 80 mmHg (masked hypertension) were present in 31% of apparently controlled patients. Conclusion: Resistant hypertension is associated with obesity, longer hypertension duration and kidney and cardiac damage. Ambulatory blood pressure monitoring reveals that white-coat hypertension is common among resistant hypertensive patients, as well as is masked hypertension among apparently controlled 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.

Evolution of functional link networks

This paper addresses the genetic design of functional link networks (FLN). FLN are high-order perceptrons (HOP) without hidden units. Despite their linear nature, FLN can capture nonlinear input-output relationships, provided that they are fed with an adequate set of polynomial inputs, which are constructed out of the original input attributes. Given this set, it turns out to be very simple to train the network, as compared with a multilayer perceptron (MLP). However finding the optimal subset of units is a difficult problem because of its nongradient nature and the large number of available units, especially for high degrees. Some constructive growing methods have been proposed to address this issue, Here, we rely on the global search capabilities of a genetic algorithm to scan the space of subsets of polynomial units, which is plagued by a host of local minima. By contrast, the quadratic error function of each individual FLN has only one minimum, which makes fitness evaluation practically noiseless. We find that surprisingly simple FLN compare favorably with other more complex architectures derived by means of constructive and evolutionary algorithms on some UCI benchmark data sets. Moreover, our models are especially amenable to interpretation, due to an incremental approach that penalizes complex architectures and starts with a pool of single-attribute FLN.

Salt Intake, Endothelial Dysfunction, and Salt‐Sensitive Hypertension

Numerous epidemiologic and clinical studies have demonstrated a clear relationship between high salt intake and blood pressure. However, the mechanisms of a salt‐induced increase in blood pressure—a phenomenon known as salt sensitivity—and the heterogeneity of this effect are far from being completely understood. Endothelial dysfunction, and especially the nitric oxide system, is implicated in both experimental and clinical hypertension. Animal studies indicate that endogenous nitric oxide plays an important role in renal hemodynamics and sodium homeostasis, inducing renal vasodilation and natriuresis. Studies of essential hypertensive patients have also suggested that both high salt intake and salt sensitivity are associated with impaired endothelial function. Although there are many hypotheses concerning the nature of salt sensitivity, clinical data indicate that salt‐sensitive patients may be unable to up‐regulate the production of nitric oxide in response to salt intake. This endothelial dysfunction, which is more frequent in salt‐sensitive than in salt‐resistant essential hypertensive patients, may partially explain the blood pressure increase in response to salt intake and may underlie the more pronounced target organ damage and cardiovascular risk in salt‐sensitive patients.

Clinical characteristics of isolated clinic hypertension.

Objective To analyze the clinical characteristics of patients with isolated clinic hypertension (ICH) compared with other hypertensive patients, and to evaluate the capacity of physicians to predict a diagnosis of ICH. Methods A cross-sectional, comparative multicenter descriptive study was made of 6176 hypertensive individuals without pharmacological treatment, subjected to ambulatory blood pressure monitoring (ABPM). In 2611 cases, ABPM was prescribed due to suspected ICH. The participants were consecutively selected in primary care centers and hospital hypertension units in all Spanish Autonomous Communities. ICH was defined by clinical blood pressure (BP) ≥ 140 mmHg (systolic) or ≥ 90 mmHg (diastolic), with diurnal ambulatory BP < 135 and < 85 mmHg (ICH1) or BP < 130 and < 80 mmHg (ICH2) or 24-h BP < 125 and < 80 mmHg (ICH3). Results ICH1, ICH2 and ICH3 criteria were met by 1807 (29.2%), 960 (15.5%) or 1133 (18.3%) subjects, respectively. Total sample mean age (SD) was 51.8 (14.1) years, and clinical BP 145.7 ± 17.3/89.3 ± 11.3 mmHg. Compared with the rest of the hypertensive individuals, the patients with ICH were predominantly female, of older age, with fewer smokers, and increased frequency of obesity. Moreover, they were more frequently nondippers, and with greater systolic BP in the office (P < 0.05), except when we used ICH3 criteria. The sensitivity and specificity of the physician predictions in relation to suspected ICH1, ICH2 and ICH3 were 48.7 and 60.4%, 52.9 and 59.7%, and 52.3 and 60.0%, respectively. Conclusions The prevalence of ICH is between 15 and 29%, depending on the defining criterion used. The 24-h ICH criteria are not affected by awake/sleep biases, and should be preferred. Clinical capacity for predicting ICH is low.

Urinary Albumin Excretion Is Associated With Nocturnal Systolic Blood Pressure in Resistant Hypertensives

Microalbuminuria is a known marker of subclinical organ damage. Its prevalence is higher in patients with resistant hypertension than in subjects with blood pressure at goal. On the other hand, some patients with apparently well-controlled hypertension still have microalbuminuria. The current study aimed to determine the relationship between microalbuminuria and both office and 24-hour ambulatory blood pressure. A cohort of 356 patients (mean age 64±11 years; 40.2% females) with resistant hypertension (blood pressure ≥140 and/or 90 mm Hg despite treatment with ≥3 drugs, diuretic included) were selected from Spanish hypertension units. Patients with estimated glomerular filtration rate <30 mL/min/1.73 m2 were excluded. All patients underwent clinical and demographic evaluation, complete laboratory analyses, and good technical-quality 24-hour ambulatory blood pressure monitoring. Urinary albumin/creatinine ratio was averaged from 3 first-morning void urine samples. Microalbuminuria (urinary albumin/creatinine ratio ≥2.5 mg/mmol in males or ≥3.5 mg/mmol in females) was detected in 46.6%, and impaired renal function (estimated glomerular filtration rate <60 mL/min/1.73 m2) was detected in 26.8%. Bivariate analyses showed significant associations of microalbuminuria with older age, reduced estimated glomerular filtration rate, increased nighttime systolic blood pressure, and elevated daytime, nighttime, and 24-hour diastolic blood pressure. In a logistic regression analysis, after age and sex adjustment, elevated nighttime systolic blood pressure (multivariate odds ratio, 1.014 [95% CI, 1.001 to 1.026]; P=0.029) and reduced estimated glomerular filtration rate (multivariate odds ratio, 2.79 [95% CI, 1.57 to 4.96]; P=0.0005) were independently associated with the presence of microalbuminuria. We conclude that microalbuminuria is better associated with increased nighttime systolic blood pressure than with any other office and 24-hour ambulatory blood pressure monitoring parameters.

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.