Juan J. de la Cruz

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.

Efficacy of Sequential High-Dose Doxorubicin and Ifosfamide Compared With Standard-Dose Doxorubicin in Patients With Advanced Soft Tissue Sarcoma: An Open-Label Randomized Phase II Study of the Spanish Group for Research on Sarcomas

PURPOSE To assess the progression-free survival (PFS) and antitumor response to standard-dose doxorubicin compared with sequential dose-dense doxorubicin and ifosfamide in first-line treatment of advanced soft tissue sarcoma. PATIENTS AND METHODS Patients with measurable advanced soft tissue sarcoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2, between the ages 18 and 65 years, and with adequate bone marrow, liver, and renal function were entered in the study. The stratifications were: ECOG PS (0 v 1), location of metastases, and potentially resectable disease. Patients were randomly assigned to either doxorubicin 75 mg/m(2) given as a bolus injection every 3 weeks for 6 cycles (arm A) or doxorubicin at 30 mg/m(2) per day for 3 consecutive days once every 2 weeks for 3 cycles followed by ifosfamide at 12.5 g/m(2) delivered by continuous infusion over 5 days once every 3 weeks for 3 cycles with filgastrim or pegfilgastrim support (arm B). RESULTS Between December 2003 and September 2007, 132 patients were entered onto the study. Febrile neutropenia, asthenia, and mucositis were more frequent in the arm B. The interim preplanned analysis for futility allowed the premature closure. Objective responses were observed in 23.4% of assessable patients in arm A and 24.1% in arm B. PFS was 26 weeks in the arm A and 24 weeks in arm B (P = .88). Overall survival did not differ between the two therapeutic arms (P = .14). CONCLUSION Single-agent doxorubicin remains the standard treatment in fit patients with advanced soft tissue sarcoma.

Mortalidad cardiovascular atribuible a la presión arterial elevada en la población española de 50 años o más

Fundamento y objetivo: No se dispone de informacion actual sobre la mortalidad cardiovascular atribuible a la presion arterial elevada en Espana. Pacientes y metodo: Se han estimado, mediante formulas convencionales, los riesgos atribuibles poblacionales y el numero de muertes cardiovasculares relacionadas con cifras elevadas de presion arterial sistolica (

Nocturnal Hypertension or Nondipping: Which Is Better Associated With the Cardiovascular Risk Profile?

120 mmHg) en la poblacion de 50-89 anos de Espana. Los datos sobre riesgos relativos proceden del Prospective Studies Collaboration, metaanalisis de 61 estudios de presion arterial y mortalidad, con datos de un millon de personas (30.000 del sur de Europa) sin antecedentes de enfermedad vascular. Las prevalencias de la presion arterial proceden de 2 estudios representativos de la poblacion espanola para personas de 50-59 y 60-89 anos de edad, respectivamente. El numero de muertes de causa cardiovascular ocurridas se ha tomado del Instituto Nacional de Estadistica (ano 2004). Resultados: Anualmente un total de 44.401 muertes de causa cardiovascular son atribuibles a la presion arterial elevada, lo que representa el 54% de la mortalidad cardiovascular en mayores de 50 anos: 17.312 por cardiopatia isquemica, 15.599 por enfermedad cerebrovascular y 11.490 por otras enfermedades cardiovasculares. El mayor numero de muertes atribuibles corresponde a las categorias de hipertension grados 1 y 2 (32.638) y a los mayores de 70 anos (36.345), y las presiones normal y normal-alta explican un 6% de todas las muertes atribuibles. Conclusiones: Una de cada 2 muertes de causa cardiovascular ocurridas anualmente a los individuos mayores de 50 anos son atribuibles a la presion arterial elevada, y el 90% de ellas son atribuibles a la hipertension.

Diurnal blood pressure variation, risk categories and antihypertensive treatment

BACKGROUND Both increased night blood pressure (BP) and nondipping are associated with worse cardiovascular risk and prognosis. However, as they are often related features, their relative importance has been difficult to assess separately. In this study we address separate associations of nocturnal hypertension and nondipping with cardiovascular risk profile in treated and untreated hypertensive patients. METHODS A total of 37,096 untreated patients and 62,788 patients receiving antihypertensive treatment from the Spanish Ambulatory Blood Pressure Monitoring Registry were included. Each cohort was separated into 4 groups: group 1, night systolic blood pressure (SBP) <120 mm Hg and normal dipping (>10%); group 2, night SBP <120 mm Hg and nondipping (≤10%); group 3, nocturnal hypertension (SBP ≥120 mm Hg) and normal dipping; and group 4, nocturnal hypertension and nondipping. RESULTS The smallest proportion of patients with additional cardiovascular risk factors, organ damage, and history of previous events was observed in the group with both normal night SBP and dipping, whereas those with both nocturnal hypertension and nondipping showed the largest proportion of cardiovascular risk factors and diseases. When groups showing only 1 abnormality were compared, nondipping was associated with female sex, reduced renal function, and previous cardiovascular events, whereas nocturnal hypertension was associated with male sex, smoking, and increased urinary albumin excretion. In treated patients, it was also associated with the presence of diabetes. CONCLUSION Nondipping is related to more advanced disease (reduced renal function and clinical evidence of cardiovascular disease), whereas nocturnal hypertension is associated with albuminuria. The worst cardiovascular risk profile is present in patients exhibiting both nocturnal hypertension and nondipping.

Hipercolesterolemia familiar heterocigota en España. Estudio descriptivo de 819 casos no relacionados

Ambulatory blood pressure (BP) monitoring is a useful tool aiding diagnostic and management decisions in patients with hypertension. Diurnal BP variation or circadian rhythm adds prognostic value to the absolute BP elevation. The Spanish ABPM Registry has collected information from >30 000 treated hypertensive patients attended by either primary care physicians or referral specialists. The analysis of BP diurnal variation has allowed the conclusion that nocturnal BP decline is related to the level of risk. Patients with blunted nocturnal dip frequently belong to high- or very high-risk categories and specifically are often older, obese, diabetics or with overt cardiovascular or renal disease. With respect to treatment, the non-dipper profile is more often observed in patients receiving several antihypertensive drug agents, but it does not correlate with the time of drug administration. Among patients receiving only one drug, non-dihydropyridine calcium channel blockers and α-blockers are associated with less nocturnal BP decline than other antihypertensive drug classes, even after adjusting for the level of risk.

Gender Differences in Office and Ambulatory Control of Hypertension

Fundamento La hipercolesterolemia familiar heterocigota (HFh) es un trastorno frecuente en lapoblacion general y la cardiopatia isquemica prematura, su complicacion mas importante. Elobjetivo de este estudio es describir las manifestaciones clinicas y las caracteristicas de la enfermedadcardiovascular en la HFh en Espana. Pacientes y metodo Analisis de una cohorte de 819 sujetos no relacionados entre si (449 mujeresy 370 varones), con diagnostico clinico de hipercolesterolemia familiar, procedentes de 69clinicas de lipidos. Se registraron los datos clinicos y analiticos, ademas de los antecedentespersonales y familiares de enfermedad cardiovascular. Resultados La concentracion de colesterol total (DE) en el momento del diagnostico fue de412 (87) mg/dl en las mujeres y de 400 (78) mg/dl en los varones (p Conclusion Las caracteristicas clinicas y la presencia de enfermedad cardiovascular en la HFhen Espana son similares a las descritas en otros paises. El cLDL, la edad, el sexo, el tabaquismo,la hipertension arterial y el indice de masa corporal son importantes predictores de la enfermedadcardiovascular.