Javier Sobrino

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.

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.

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.

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.

Reproducibility of the circadian blood pressure pattern in 24-h versus 48-h recordings: the Spanish Ambulatory Blood Pressure Monitoring Registry.

Objectives To assess the reproducibility of the circadian blood pressure (BP) pattern over a 48-h period by comparing the first 24 h of ambulatory blood pressure monitoring (ABPM) with the following 24 h and with the mean over 48 h. Patients and methods Patients undergoing 48-h ABPM within the National ABPM Registry of the Spanish Society of Hypertension, based on 800 Spacelabs 90207 monitors distributed throughout Spain in hypertension units and primary healthcare centres, were included. Between June 2004 and September 2005, 611 valid 48-h ABPM recordings were obtained, 235 corresponded to patients without antihypertensive treatment. Results The percentages of patients classified as non-dipper for the first 24 h, the second 24 h and the 48-h average were 47, 50 and 48%, respectively. When the first and second 24-h periods were compared, 147 (24%) subjects switched from dipper (D) to non-dipper (ND) or vice-versa. When the first 24-h period was compared to the 48-h average, 66 (11%) subjects switched patterns. The proportions were similar separately for systolic blood pressure (SBP) and diastolic blood pressure (DBP) and between treated and untreated patients. In subjects with poor ABPM reproducibility, night-to-day ratios were of an intermediate value between those of subjects always classified as D or ND. Conclusion Categorization of D or ND based on a single 24-h ABPM is moderately reproducible, since one out of every five patients change profile over the following 24 h. Nevertheless, the use of 48-h ABPM in clinical practice should be assessed according to cost-effectiveness criteria. Night-to-day ratios may be helpful in identifying patients with a stable profile.

Gender Differences in Office and Ambulatory Control of Hypertension

BACKGROUND Gender differences in hypertension control have not been explored fully. METHODS We studied 15,212 white men and 13,936 white women with treated hypertension who were drawn from the Spanish Ambulatory Blood Pressure Registry. For each participant, we obtained office blood pressure (BP) (average of 2 readings) and 24-hour ambulatory BP (average of measurements performed every 20 minutes during day and night). RESULTS Only 16.4% of women and 14.7% of men had both office (<140/90 mm Hg) and ambulatory (<130/80 mm Hg) BP controlled (P<.001). Women had a lower frequency of masked hypertension (office BP<140/90 mm Hg and ambulatory BP> or =130/80 mm Hg) than men (5.9% vs 7.9%, P<.001). Women had a higher frequency of isolated office hypertension (office BP> or =140/90 mm Hg and ambulatory BP<130/80 mm Hg) (32.5% vs 24.2%, P<.001). Although office BP control (office BP<140/90 mm Hg, regardless of ambulatory values) was similar in women and men (22.3% vs 22.6%, P=.542), ambulatory BP control (ambulatory BP<130/80 mm Hg, regardless of office values) was higher in women than in men (48.9% vs 38.9%, P<.001). After adjustment for age, number of antihypertensive drugs, hypertension duration, and risk factors, gender differences in BP control remained practically unchanged. CONCLUSION Ambulatory BP control was higher in women than in men. This may be due to the higher frequency of isolated office hypertension in women, and it is not explained by gender differences in other important clinical characteristics.

Once-daily fixed-combination irbesartan 300 mg/ hydrochlorothiazide 25 mg and circadian blood pressure profile in patients with essential hypertension

BACKGROUND More than 60% of patients with hypertension included in morbidity and mortality trials needed >or=2 drugs to achieve a substantial, sustained reduction in blood pressure. Tolerable combinations using higher doses of antihypertensive drugs are frequently required to control blood pressure. OBJECTIVE The goal of this study was to assess the effect of a once-daily fixed combination of irbesartan 300 mg/hydrochlorothiazide (HCTZ) 25 mg on the circadian blood pressure profile in patients with essential hypertension that was not controlled with full-dose single therapy or low-dose combined therapy. METHODS Study patients were recruited consecutively from the outpatient hypertension clinics of 3 university hospitals in Spain. After a 1-week washout period, patients with a mean daytime blood pressure >135/85 mm Hg were treated with irbesartan 300 mg/HCTZ 25 mg once daily for 12 weeks. Twenty-four-hour ambulatory blood pressure monitoring was performed at the end of the washout period and during the last week of treatment. RESULTS Fifty-seven patients with essential hypertension (28 men, 29 women) were enrolled; their mean (SD) age was 60.4 (7.2) years (range, 45-78 years). After treatment, a significant reduction in both clinic and ambulatory mean (SD) blood pressure values was observed in the whole group of 57 patients (from 146.0 [11.0] mm Hg to 123.3 [13.3] mm Hg, P < 0.001 for 24-hour systolic blood pressure [SBP]; from 89.9 [8.2] mm Hg to 76.5 [9.4] mm Hg, P < 0.001 for 24-hour diastolic blood pressure [DBP]. The mean lowering of ambulatory SBP and DBP at peak was 25.2 (14.5) mm Hg and 14.7 (9.5) mm Hg, respectively, and at trough, 22.3 (18.3) mm Hg and 12.3 (10.9) mm Hg. The trough-to-peak ratio of the group was 0.92 for SBP (0.97 in responders) and 0.84 for DBP (0.89 in responders). The smoothness index, calculated as the mean of all individual values, was 1.7 (1.0) for SBP (1.8 [0.9] in responders) and 1.3 (0.8) for DBP (1.5 [0.6] in responders). Seven side effects in 6 patients were reported. No metabolic changes were observed, and no patient discontinued the study because of treatment-related adverse effects. CONCLUSIONS The fixed combination of irbesartan 300 mg/HCTZ 25 administered once daily produced a crude meaningful effect in reducing 24-hour blood pressure and was well tolerated. The circadian profile was preserved, as shown by trough-to-peak ratios and smoothness index values for both SBP and DBP.

Diferencias entre el control clínico y ambulatorio de la hipertensión arterial en pacientes muy ancianos. Proyecto CARDIORISC–MAPAPRES

BACKGROUND AND OBJECTIVE Hypertension is highly prevalent in the very elderly. We studied control rates of hypertension according to clinic blood pressure (BP) and ambulatory BP monitoring (ABPM) in treated hypertensives aged > or =80 years. PATIENTS AND METHOD Data came from the Spanish Society of Hypertension ABPM Registry (CARDIORISC - MAPAPRES project), which comprises a nation-wide network of more than 1,000 physicians sending standardized ABPM registries via web. Between June 2004 and April 2007 we obtained a 33.829-patient database. Control of hypertension was defined at the clinic when office BP was <140/90mmHg and at the ABPM when mean BP during the 24-h period was <130/80mmHg. RESULTS We identified 2,311 patients (6.8%) aged > or =80 years. Mean age (SD) was 83.1 (3.2) years and 63% were women. Control of clinic BP was observed in 21.5% of cases (95%CI: 19.1-23.9) and control of 24-h BP in ABPM was 42.1% (95%CI: 39.7-45.3). Prevalence of masked hypertension was 7.0% (95%CI: 6.0-8.0) and prevalence of office-resistant control (white coat) was 27.6% (95% CI: 25.7-29.4). Diabetes, kidney disease, and duration of hypertension were associated with lack of control in ABPM. CONCLUSIONS In very old hypertensives, control of clinic BP was 21.5% but ambulatory-based hypertension control was 42.1%. Physicians should be aware that the likelihood of misestimating BP control is high in these subjects. A wider use of ABPM in the elderly with hypertension should be considered.

Long-acting lacidipine versus short-acting nifedipine in the treatment of asymptomatic acute blood pressure increase

We compared antihypertensive efficacy and safety of a single administration of equipotent doses of lacidipine versus nifedipine in the hypertensive urgencies. Twenty-nine asymptomatic essential hypertensive patients (nine men, 20 women) with a mean age of 55.03+/-11.19 years and baseline diastolic blood pressure (DBP) of > or =120 mm Hg after resting 30 min, not taking antihypertensive drugs for the last 24 h, were randomized in a single-blind fashion to receive lacidipine, 4 mg (LCD, 15 patients) or short-acting nifedipine, 20 mg (NFD, 14 patients) in a single dose. Blood pressure (BP) and heart rate (HR) were taken every 30 min during the first 8 h and every 2 h until 24 h of follow-up. Baseline BP values were similar in the two groups (LCD, 222.5+/-32.8/124.6+/-8.4 mm Hg vs. NFD, 215.9+/-20.6/128+/-7.7 mm Hg; p = NS). Both drugs promoted a significant reduction of systolic blood pressure (SBP; 169.6+/-27.8 vs. 170.6+/-25.3 mm Hg) and diastolic blood pressure (DBP; 104.1+/-16 vs. 102.9+/-12.4 mm Hg) after 8 h. However, either SBP (165+/-27.3 vs. 190.6+/-18.2 mm Hg; p = 0.008) and DBP (99.9+/-12.3 vs. 117.2+/-11.4 mm Hg; p = 0.001) were significantly higher in the NFD group after 24-h dosing. Eleven patients in the LCD group had a decrease in BP >25% of the baseline value both 8 and 24 h after the dose. Although 10 patients showed the same response in the NFD group 8 h after the dose, only four patients maintained these values at 24 h. One patient treated with NFD had a transient cerebrovascular ischemic attack. No adverse effects were observed in the LCD group. We conclude that the long-acting calcium antagonist lacidipine was more effective than the short-acting nifedipine in both controlling BP and maintaining this BP reduction over 8 h in essential hypertensive patients with acute asymptomatic BP increase.