Jose Maria Pascual

Prognostic Value of Ambulatory Blood Pressure Monitoring in Refractory Hypertension: A Prospective Study

The objective of this study was to establish whether ambulatory blood pressure offers a better estimate of cardiovascular risk than does its clinical blood pressure counterpart in refractory hypertension. This prospective study assessed the incidence of cardiovascular events over time during an average follow-up of 49 months (range, 6 to 96). Patients were referred to specialized hypertension clinics (86 essential hypertension patients who had diastolic blood pressure > 100 mm Hg during antihypertensive treatment that included three or more antihypertensive drugs, one being a diuretic). Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was performed at the time of entrance. End-organ damage was monitored yearly, and the incidence of cardiovascular events was recorded. Patients were divided into tertiles of average diastolic blood pressure during activity according to the ABPM, with the lowest tertile <88 mm Hg (LT, n=29), the middle tertile 88 to 97 mm Hg (MT, n=29), and the highest tertile >97 mm Hg (HT, n=28). While significant differences in systolic and diastolic ambulatory blood pressures were observed among groups, no differences were observed at either the beginning or at the time of the last evaluation for office blood pressure. During the last evaluation, a progression in the end-organ damage score was observed for the HT group but not for the two other groups. Twenty-one of the patients had a new cardiovascular event; the incidence of events was significantly lower for the LT group (2.2 per 100 patient-years) than it was for the MT group (9.5 per 100 patient-years) or for the HT group (13.6 per 100 patient-years). The probability of event-free survival was also significantly different when comparing the LT group with the other two groups (LT versus MT log-rank, P<.04; LT versus HT log-rank, P<.006). The HT group was an independent risk factor for the incidence of cardiovascular events (relative risk, 6.20; 95% confidence interval, 1.38 to 28.1, P<.02). Higher values of ambulatory blood pressure result in a worse prognosis in patients with refractory hypertension, supporting the recommendation that ABPM is useful in stratifying the cardiovascular risk in patients with refractory hypertension.

Ambulatory blood pressure and microalbuminuria in essential hypertension : role of circadian variability

Objective To assess the relationship of subclinical urinary albumin excretion with ambulatory and circadian variability of blood pressure. Design and methods Patients with essential hypertension (82 males and 59 females, mean + SD age 38.9 ±7.3 years) who had never been previously treated for hypertension were included in the study. Patients with nephropathy or diabetes mellitus, hyperglycemia >120mg/dl, glomerular filtration rate <80ml/min per 1.73 m2, urinary tract infection and positive dipstick for albumin or glucose were excluded. Twenty-four-hour ambulatory blood pressure monitoring on a regular working day using an oscillometric device was performed. Twenty-four-hour urinary albumin excretion was measured on two separate days using an immunonephelometric assay. Results Microalbuminuric patients (urinary albumin excretion 30–300 mg/24 h, n = 31) had significantly higher mean ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) than those with normoalbuminuria (urinary albumin excretion <30 mg/24 h, n = 96) during the 24-h, daytime (0800–2200 h) and night (2400–0600 h) periods, whereas for office blood pressure only DBP was significantly higher. Urinary albumin excretion was positively correlated with the means of SBP and DBP. Multiple regression analysis similarly confirmed that DBP during daytime was positively and day: night ratio of DBP inversely associated with urinary albumin excretion independent of age, sex and other parameters of ambulatory blood pressure. Conclusions In conclusion, the present study indicates that, in middle-aged essential hypertensive patients, the presence of microalbuminuria is a marker for the presence of higher values of blood pressure throughout a 24-h period.

Altered blood pressure during sleep in normotensive subjects with type I diabetes.

This study was designed to examine the circadian pattern of blood pressure in children and young adults with type I diabetes who were completely normotensive by standard criteria. Forty-five patients and the same number of age- and sex-matched control subjects were studied. In diabetic children of 10-14 years of age, the nocturnal fall in systolic and diastolic blood pressures was intact. In diabetics of 15-20 years of age, the fall in systolic blood pressure was blunted; in diabetics of 21-37 years of age, the fall in both systolic and diastolic blood pressures during sleep was blunted. When data from all diabetic subjects were pooled and analyzed in a multiple linear regression model, mean blood pressure during sleep correlated best with urinary albumin excretion (r = 0.60). On the basis of this finding, we subdivided our patients into two groups: a microalbuminuric group (urinary albumin excretion > 30 mg per 24 hours; mean, 160.3 +/- 29.7; n = 11) and a normoalbuminuric group (urinary albumin excretion < 30 mg per 24 hours; mean, 6.6 +/- 6.5; n = 34). Both systolic and diastolic blood pressures during sleep were higher in microalbuminuric (121.1 +/- 3.3 and 69.3 +/- 2.5 mm Hg, respectively) than in normoalbuminuric diabetics (114.2 +/- 1.8 and 60.1 +/- 1.2 mm Hg, p < 0.05) or control subjects (113.3 +/- 1.2 and 60.1 +/- 1.2 mm Hg, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Added Impact of Obesity and Insulin Resistance in Nocturnal Blood Pressure Elevation in Children and Adolescents

The aim of the present study was to analyze the relationship between insulin resistance and the ambulatory blood pressure components in obese children and adolescents. Eighty-seven overweight and obese white children and adolescents of both sexes, of European origin from 6 to 18 years of age (mean age: 10.9±2.7 years), were selected. Obesity was defined on the basis of a threshold body mass index z score >2 (Coles least mean square method) and overweight with a body mass index from the 85th to 97th percentile. A validated oscillometric method was used to measure ambulatory BP (Spacelabs 90207) during 24 hours. Fasting glucose and insulin were measured, and the homeostasis model assessment index was calculated. Subjects were grouped into tertiles of homeostasis model assessment index. No significant differences in terms of age, sex, and body mass index z score distribution were observed among groups. When adjusted by age, sex, and height, nocturnal systolic blood pressure and heart rate were significantly higher in subjects in the highest homeostasis model assessment index tertile (>4.7) as compared with those of the other groups, whereas no differences were observed for awake systolic blood pressure or heart rate. Whereas body mass index z score was more closely related with blood pressure and heart rate values, waist circumference was strongly related with insulin resistance. Moreover, both waist circumference and insulin resistance were mainly associated with higher nocturnal but not with awake blood pressure. The early increment of nocturnal blood pressure and heart rate associated with hyperinsulinemia may be a harbinger of hypertension-related insulin resistance and may contribute to heightened cardiovascular risk associated with this condition.

The spectrum of circadian blood pressure changes in type I diabetic patients

Background The objective of the present study was to characterize the spectrum of circadian blood pressure changes in type I diabetes at different stages of nephropathy by using two monitorings in each patient in order to avoid intra-individual variability. Patients and methods A total of 80 type I diabetic subjects and the same number of age, sex and awake mean blood pressure (BP)-matched controls were included. According to urinary albumin excretion, there were 57 normoalbuminurics, 15 persistent microalbuminurics and eight proteinurics. Two 24 h ambulatory blood pressure monitorings were performed at the same urinary albumin excretion stage in absence of antihypertensive treatment for each diabetic subject and for their respective control. Blood pressure and heart rate averages during 24 h, awake, sleep, and day : night ratio were calculated. Results Seven of the eight proteinuric subjects were hypertensives, whereas hypertension was absent in the normoalbuminuric and microalbuminuric groups. The intra-individual reproducibility in diabetics showed repeatability coefficients for the 24 h systolic and diastolic pressure of 33 and 42%, respectively. This reproducibility for the day : night ratio was generally worse, 57% for systolic and 59% for diastolic . A progressive increment in the mean ambulatory BP was observed across the three groups of diabetics and the differences in BP observed were most evident during the night-time period. Though no differences in the 24 h circadian pattern were present between the normoalbuminurics and their controls, nocturnal differences were observed, not only in microalbuminurics for systolic BP (P < 0.05), but also in proteinurics for both systolic BP (P < 0.01) as well as diastolic BP (P < 0.05). No differences were observed in heart rate among the diabetic groups. The non-dipping pattern in the two monitorings was observed in 80, 58, 18 and 10% of the proteinurics, microalbuminurics, normoalbuminurics and control groups , respectively. Conclusions Persistent abnormal circadian variability seems to be an early and frequent characteristic of type I diabetics with an increased urinary albumin excretion. Although present in some normalbuminuric subjects, the frequency of this abnormality increases as the incipient nephropathy progresses. By the time proteinuria is established, nearly all subjects present the abnormal pattern.

Hyperinsulinemia as a determinant of microalbuminuria in essential hypertension.

Objective To analyze the relationship between insulinemia and urinary albumin excretion in a group of nonobese, young adult hypertensive patients, who had never been treated with antihypertensive drugs. Patients and methods Forty-nine patients who fulfilled the inclusion criteria were included. Twenty-four-hour ambulatory blood pressure monitorings, urinary albumin excretion (UAE) measurements, and an oral glucose- tolerance test measuring glucose and insulin, were performed, and left ventricular mass was measured by echocardiography. Hypertensive patients were classified as normoalbuminuric when their UAE was < 30 mg/24 h (40 patients; mean UAE 13.4 ± 7.0 mg/24 h), and as microalbuminuric when their UAE was 30–300 mg/24 h (nine patients; mean UAE 90.5 ± 86.6 mg/24 h). Results In comparison with that of the normoalbuminuric group, the fasting plasma glucose concentration for the microalbuminuric group was only slightly higher (100 ± 9 versus 95 ± 8 mg/dl, NS). In contrast, the fasting insulin concentration in the microalbuminuric group was significantly higher than that observed in the normoalbuminuric group (25.2 ± 6.7 versus 16.6 ± 5.2 µU/ml, P < 0.0001). During the oral glucose-tolerance test, the area under the curve (AUC) for glucose (317 ± 41 versus 253 ± 53 mg/dl x 2/h, P < 0.001) and the AUC for insulin (253 ± 171 versus 124 ± 43 µU/ml x 2/h, P < 0.001) were significantly higher in the microalbuminuric group than were those AUC observed in the normoalbuminuric group. After adjustments for age, sex, body mass index and average 24 h ambulatory mean blood pressure were made, the fasting insulin level was associated independently with an increase in UAE in a multiple regression model with base 10 logarithm of the UAE as the dependent variable. Variations in fasting insulin level alone accounted for 33% of the UAE variance. In contrast, the 24 h ambulatory mean blood pressure, rather than the insulin level, was the strongest predictor of the left ventricular mass index. Conclusions Mild hypertensive patients with microalbuminuria were hyperinsulinemic in the absence of obesity, and their insulin level was the main determinant of microalbuminuria in these patients. Microalbuminuria in essential hypertension seems to identify patients with a cluster of cardiovascular risk factors and a bad risk profile. Thus, assessment of microalbuminuria may be useful in the stratification of risk in essential hypertension.

Importancia del síndrome metabólico en el control de la presión arterial y de la dislipemia

Fundamento y objetivo: Valorar la importancia del sindrome metabolico (SM) en el tratamiento y control de la hipertension y dislipemia. Pacientes y metodo: Estudio transversal de 1.320 pacientes hipertensos no diabeticos (634 mujeres y 686 varones) con una edad media (DE) de 58,1 (13,3) anos y con un indice de masa corporal de 29,8 (4,7) (kg/m2). El diagnostico de SM se establecio segun los criterios del NCEP-ATP III. Se considero con buen control de la presion arterial los que presentaban valores inferiores a 140/90 mmHg. Se calculo el riesgo coronario segun los criterios de Framingham y se clasifico en 3 grupos (bajo: inferior al 10%; intermedio: 10-20%; alto: superior al 20%). Se consideraron objetivos del tratamiento hipolipemiante los del ATP III, segun su grupo de riesgo. Resultados: Tenian SM 461 pacientes (35%), 246 varones (36%) y 215 mujeres (34%). Los pacientes con SM requerian mayor numero de farmacos que los pacientes sin SM para el tratamiento de la presion arterial (2,1 [1,3] frente a 1,7 [1,3]; p < 0,001), pero el grado de control de la hipertension fue similar en ambos grupos (el 53 frente al 52%; p = ns). Los pacientes con SM tenian mayor riesgo coronario global que los pacientes hipertensos sin SM (10,7 [8,3] frente a 7,9 [6,8]; p < 0,001) y cumplian menos los objetivos terapeuticos del colesterol ligado a lipoproteinas de baja densidad (el 57 frente al 74%; p < 0,001). En un analisis de regresion logistica, la presencia de SM se asocio de forma independiente, y controlando por la edad, a un 26% menos probabilidades de cumplir el doble objetivo (p < 0,001). Conclusiones: La existencia de un SM se asocia a mayor riesgo coronario, requerir mas farmacos antihipertensivos para el control de la presion arterial, menor control de los valores de colesterol ligado a lipoproteinas de baja densidad y un 26% menos posibilidades de cumplir ambos objetivos. Los pacientes con SM constituyen un objetivo prioritario en la prevencion cardiovascular.

Angiotensin II AT1 receptor gene polymorphism and microalbuminuria in essential hypertension

The objective of this study was to analyze the relationship of polymorphisms of the angiotensin II AT1 receptor gene with microalbuminuria in a group of young adults with essential hypertension. Essential hypertensives, less than 50 years old, never previously treated with antihypertensive drugs, and in absence of diabetes mellitus were included. Office blood pressure (BP), 24-h ambulatory BP monitoring, urinary albumin excretion (UAE) measurements, and DNA analysis were performed. Polymorphisms of the angiotensin II AT1-receptor gene (A1166C and C573T) were studied by polymerase chain reaction and single-strand conformation polymorphism techniques. One hundred eighty-three patients, 49 (27%) microalbuminurics, were included. Office and ambulatory BP values were significantly higher in the microalbuminuria group. No differences in the presence of microalbuminuria were observed among the genotypes of either A1166C or C573T polymorphisms of the angiotensin II receptor AT1 gene, or in the allele frequency of the A1166C or the C573T polymorphism. LogUAE was significantly different among genotypes of the C573T polymorphism [CC 1.30(1.15-1.45), CT 1.14(1.00-1.28), and TT 0.94(0.68-1.20), P < .05]. Both office and ambulatory blood pressure and the TT/C573T genotype were independently related to logUAE, and, at the same BP values, UAE was lower in subjects with this genotype. We have found that the C573T polymorphism is on linkage disequilibrium with A1166C, as the 573T allele is closely linked to the presence of the 1166A allele, but not vice versa. Haplotype analysis among subjects with the AA genotype for the A1166C polymorphism confirms the influence of the TT genotype of the C573T polymorphism on the UAE in hypertensives. The C573T polymorphism of the angiotensin II receptor AT1 gene seems to be a genetic protective factor for UAE in a population of essential hypertensives.

Comparación entre el algoritmo de Framingham y el de SCORE en el cálculo del riesgo cardiovascular en sujetos de 40-65 años

Fundamento y objetivo En el presente trabajo se analizan las implicaciones terapeuticas que en la practica clinica habitual tiene el uso de los 2 modelos de calculo del riesgo cardiovascular, y se estudian las diferencias entre los individuos clasificados como de riesgo alto por cada sistema en una poblacion de hipertensos de 40 a 65 anos. Pacientes y metodo : Se incluyo a 929 pacientes sin diabetes ni antecedentes de enfermedad cardiovascular, con al menos un ano de seguimiento en nuestra Unidad de Hipertension y Riesgo Vascular. Se estimaron el riesgo de muerte cardiovascular a los 10 anos segun la funcion Systematic Coronary Risk Evaluation (SCORE) de la guia europea y el riesgo coronario a los 10 anos segun la funcion de Framingham, modificada por el tercer informe del National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (NCEP-ATP-III). Se clasifico a los pacientes como de alto riesgo si su riesgo cardiovascular era del 5% o mayor y su riesgo coronario superior al 20%. Resultados El SCORE clasifico como de alto riesgo a un 4,1% de los pacientes, frente a un 2,5% segun Framingham. Solo un 0,2% de las mujeres fueron clasificadas como de alto riesgo por un sistema u otro, mientras que un 8,2% de los varones lo fueron por SCORE y un 4,8% por Framingham. Existia una baja concordancia entre los 2 sistemas. Solo un 1,5% de los varones se catalogo como de alto riesgo con los 2 sistemas, y ninguna mujer. Los pacientes clasificados como de alto riesgo por SCORE, pero no por Framingham, presentaban una edad superior, menos frecuencia de tabaquismo y mejor perfil lipidico que el grupo de pacientes clasificados de alto riesgo solo por Framingham. Segun las recomendaciones de NCEP-ATP-III, el tratamiento hipolipemiante estaria indicado en un 43% de los varones y un 28% de las mujeres, frente a un 28 y un 23%, respectivamente, segun la guia europea. Conclusiones A pesar de que la funcion SCORE, en comparacion con el algoritmo de Framingham, casi duplica el numero de pacientes de riesgo alto, el tratamiento hipolipemiante farmacologico estaria indicado en una menor proporcion de pacientes segun la guia europea que segun las recomendaciones del NCEP-ATP-III. Las diferencias son mas acusadas en varones.

Prognostic Value of Microalbuminuria During Antihypertensive Treatment in Essential Hypertension

Whether changes over time of urinary albumin excretion have prognostic value is a matter of discussion. The objective was to assess the prognostic value of changes in urinary albumin excretion over time in cardiovascular risk during antihypertensive treatment. Follow-up study of 2835 hypertensives in the absence of previous cardiovascular disease (mean age 55 years, 47% men, BP 138/80 mm Hg, 19.1% diabetics, and calibrated systemic coronary risk estimation 5 or >10.6%). Usual-care of antihypertensive treatment was implemented to maintain blood pressure <140/90 mm Hg. Urinary albumin excretion was assessed yearly, and the values were expressed as the creatinine ratio. Incidence of cardiovascular events, fatal and nonfatal, was recorded during the follow-up. During a median follow-up of 4.7 years (17 028 patients-year), 294 fatal and first nonfatal cardiovascular events were recorded (1.73 CVD per 100 patients/year). Independently of blood pressure, estimated glomerular filtration rate, level of cardiovascular risk, and antihypertensive treatment, microalbuminuria at baseline and at any time during the follow-up resulted in higher risk for events, hazard ratio (HR) 1.35 (95% confidence interval [CI], 1.08–1.79) and HR 1.49 (95% CI, 1.14–1.94), respectively. Likewise, development of microalbuminuria (HR 1.60; 95% CI, 1.04–2.46) or persistence from the beginning (1.53; 95% CI, 1.13–2.06) had a significantly higher rate of events than if remained normoalbuminuric (HR 1) or regress to normoalbuminuria (HR 1.37; 95% CI, 0.92–2.06) with an 18%, 18%, 8%, and 11% events, respectively, P<0.001. The study supports the value of urinary albumin excretion assessment as a prognostic factor for cardiovascular risk, but also opens the way to consider it as an intermediate objective in hypertension.