High doses of lercanidipine are better tolerated than other dihydropyridines in hypertensive patients with metabolic syndrome: results from the TOLERANCE study.

AIMS/INTRODUCTION: The TOlerabilidad de LERcanidipino 20 mg frente a Amlodipino y Nifedipino en CondicionEs normales de uso study was aimed to compare the tolerability of high doses of lercanidipine with amlodipine and nifedipine gastro-intestinal therapeutic system (GITS) in the treatment of hypertension in daily clinical practice. PATIENTS/METHODS: Essential hypertensives >or= 18 years, treated during at least 1 month with lercanidipine 20 mg, amlodipine 10 mg or nifedipine GITS 60 mg, after a previous treatment course of at least 1 month with half the dose of the corresponding drugs were included. We present the data of the subgroup of patients with metabolic syndrome (MetS). RESULTS: Three hundred and thirty-seven of the 650 study population fulfilled criteria of MetS, 233 (69.1%) on lercanidipine and 104 (30.9%) on amlodipine/nifedipine GITS. Overall, a significantly lower proportion of lercanidipine-treated patients showed adverse reactions (ARs) when compared with patients receiving other-dihydropyridines (DHPs) (60.1% vs. 73.1%, p = 0.003). Similarly, the most common vasodilation-related ARs (oedema, swelling, flushing and headache) were significantly less frequent in lercanidipine group (all p < 0.01). CONCLUSION: In conclusion, lercanidipine appears to exhibit a better tolerability profile and less vasodilation-related ARs compared with other DHPs in hypertensive patients with MetS.

[Differences in the management of patients with atrial fibrillation according to whether primary care or the specialist initiates treatment with direct oral anticoagulants. The SILVER-AP and BRONCE-AP studies]. / Diferencias en el manejo de los pacientes con fibrilación auricular según inicie el tratamiento con anticoagulantes orales de acción directa el médico de atención primaria o el especialista. Estudios SILVER-AP y BRONCE-AP.

OBJECTIVES: To determine the clinical characteristics and management of patients with non-valvular atrial fibrillation (NVAF) treated with direct oral anticoagulants (DOAC) according to who initiates their prescription, the Primary Care (PC) physician or referring the patient to a specialist. MATERIAL AND METHODS: Two observational, cross-sectional and multicentre studies were compared for this purpose. The SILVER-AP study was performed in those autonomous communities in which the PC physician can prescribe DOAC directly, and the BRONCE-AP study in those autonomous communities in which the PC physician has to refer the patient to the specialist to start treatment with DOAC. Patients on chronic treatment with anticoagulants, in whom therapy was changed, and those that were on current treatment with DOAC for at least 3months, were included. RESULTS: A total of 1,036 patients (790 from SILVER-AP study and 246 from BRONCE-AP study) were included. Compared with the BRONCE-AP study, those patients included in SILVER-AP were older and had more comorbidities, as well as a higher thromboembolic and haemorrhagic risk (CHA2DS2-VASc 4.3±1.6 vs. 3.8±1.8; P<.001; HAS-BLED 2.1±0.8 vs. 1.8±1.0; P<.001). Therapeutic adherence and satisfaction with treatment were high. Low doses of DOAC were frequently prescribed, particularly with dabigatran. CONCLUSIONS: Those patients in whom the PC physician can prescribe DOAC directly have a worse clinical profile, as well as a higher thromboembolic and haemorrhagic risk than those patients in whom the PC physician has to refer to the specialist.

Clinical characteristics and management of patients with atrial fibrillation treated with direct oral anticoagulants according to blood pressure control.

OBJECTIVE: To determine the clinical characteristics and management of hypertensive patients with nonvalvular atrial fibrillation (AF) treated with direct oral anticoagulants (DOACs) according to blood pressure (BP) control. METHODS: For this purpose, data from two observational, cross-sectional and multicenter studies were combined. In both studies, patients on chronic treatment with anticoagulants and that were on current treatment with DOACs at least for 3 months were included. Adequate BP was defined as a systolic BP<140mmHg and a diastolic BP<90mmHg (<140/85mmHg if diabetes). RESULTS: Overall, 1036 patients were included. Of these, 881 (85%) had hypertension that were finally analyzed. The presence of other risk factors and cardiovascular disease was common. Mean BP was 132.6±14.3/75.2±9.2mmHg and 70.5% of patients achieved BP goals. Those patients with a poor BP control had more frequently diabetes, and a history of prior labile INR. Patients had a high thromboembolic risk, but without significant differences according to BP control. By contrast, more patients with a poor BP control had a higher bleeding risk (HAS-BLED ≥3: 24.0% vs 35.4%; P<0.001). HAS-BLED score was an independent predictor of poor BP control (odds ratio 1.435; 95% confidence interval 1.216-1.693; P<0.001). Satisfaction with anticoagulant treatment was independent of BP control. CONCLUSIONS: More than two thirds of our patients with hypertension and AF anticoagulated with DOACs achieve BP targets, what is clearly superior to that reported in the general hypertensive population.

[Prevalence of kidney insufficiency in primary care population in Spain: EROCAP study]. / Prevalencia de insuficiencia renal en Centros de Atención Primaria en España: Estudio EROCAP.

This cross-sectional, multicenter study investigated the prevalence of chronic kidney disease and associated disorders, in an adult population sample (> 18 years old) attending Primary Care services in Spain. Estimated glomerular filtration rate (Modification Diet in Renal Disease equation) was used for analysis of kidney disease prevalence according to NFK-KDOQI (The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) stages. Data were collected on serum creatinine, other laboratory parameters blood pressure, and medical history of cardiovascular risk factors or disease (hypertension, dislypidemia, diabetes, congestive heart failure, coronary artery disease, stroke or peripheral arteriopathy) in 7,202 patients attending Primary Care Centers. 47.3% were males, mean age 60,6 +/- 14,3 years, BMI 28.2 +/- 5.3, with 27,6% overweight (27-30 kg/m2) and 32,1% obese (BMI>or=30 kg/m2), The prevalence of cardiovascular risks factors were: absence in 17.3%, one factor 26.9% two 31.2%, and 23.6% presented three or more The frequency of CV risk factors was: hypertension (66.7%), dyslipidemia (48%) and diabetes (31.5%). Congestive heart failure, coronary artery disease, stroke or peripheral vascular disease frequency was lower than 10% The prevalence of eGFR < 60 ml/min x 1.73 m2 was: stage 3 (30-59 ml/min/1.73 m2) 19.7%; stage 4 (15-29 ml/min/1.73 m2) 1.2%; stage 5 no dialysis (GFR < 15 ml/min) 0.4%. This prevalence increased with age in both sexes and 33,7% of patients attending Primary Care services over 70 years presented a eGFR < 60 ml/min. Of the total patients with eGFR < 60 ml/min 37.3% had normal serum creatinine levels. This study documents the substantial prevalence of significantly abnormal renal function among patients at Primary Care level. Early identification and appropriate nephrological management of these patients with renal disease is an important opportunity for an adequate prescription of drugs that interfere with renal function, to delay the progression of renal disease and modify CV risk factors.

The impact of different echocardiographic diagnostic criteria on the prevalence of left ventricular hypertrophy in essential hypertension: the VITAE study. Ventriculo Izquierdo Tension Arterial España.

BACKGROUND: The prevalence of echocardiographic left ventricular hypertrophy in essential hypertension ranges from 12 to 96% depending on the threshold values used to define it, and on the selection bias. OBJECTIVE: To estimate the prevalence of echocardiographic left ventricular hypertrophy by different criteria in essential hypertensives seen in primary care centres. METHODS: Cross-sectional study in a population-based sample of 946 essential hypertensives randomly selected in 39 primary care centres across Spain. Echocardiographic studies were performed in reference hospitals by trained observers (concordance Cohen kappa index > 0.7) and analysed by a single observer. RESULTS: Prevalence of left ventricular hypertrophy ranged from 59.2% [95% confidence interval (CI) 56.1 -62.3] by Framingham criteria to 72.7% (95% CI 69.9-75.6) using the criteria of De Simone et al. (J Am Coll Cardiol 1995; 25: 1056-1062). Prevalence was higher in males by the Cornell-Penn criteria, but higher in females when using Framingham or De Simone et al. criteria. Eccentric hypertrophy was more frequent (51.3-54.1%) independently of the criteria used, particularly when adjusting wall-thickness-ratio for age (56.2-58.9%). Concentric remodelling was present in 6.5-11.4% and only 20.8-29.7% of patients had no evidence of left ventricular structural alterations. Factors independently associated with left ventricular hypertrophy in the logistic regression analysis were age, gender, systolic blood pressure, pulse pressure and body mass index. CONCLUSION: Prevalence of echo left ventricular structural alterations among essential hypertensives seen in primary care centres in Spain ranged from 70.3 to 79.2% depending on the threshold values used. Left ventricular hypertrophy ranged from 59.2 to 72.7% and age-adjusted concentric remodelling ranged from 6.5 to 11.4% depending on the criteria used. Only one-quarter of hypertensive patients were free from morphological alterations.

Prospective comparison of therapeutical attitudes in hypertensive type 2 diabetic patients uncontrolled on monotherapy. A randomized trial: the EDICTA study.

OBJECTIVE: To compare the anti-hypertensive effect of combination therapy versus a single drug regimen schedule (dose-titration or switching to a different drug class) in type 2 diabetic hypertensive patients with inadequate blood pressure (BP) control on monotherapy. DESIGN: Prospective, randomized, open-fashion, parallel study of two therapeutic strategies during an 8-week period. SETTING: Primary care centers in Spain. PARTICIPANTS: A total of 898 men and women with type 2 diabetes mellitus and hypertension, receiving antihypertensive treatment with one single drug and whose BP was > 140 and/or 90 mmHg. INTERVENTION: Patients were randomized to a fixed combination therapy (verapamil 180 mg plus trandolapril 2 mg; Knoll AG, Ludwigshafen, Germany) or continued on a single drug regimen, either increasing the dose of the current drug or switching to a different drug class. MAIN OUTCOME MEASURE: Absolute BP reduction in the two groups of treatment, and the percentage of normalized patients (< 140/90 mmHg) in each group. RESULTS: The diastolic BP (DBP) decrease (5.6 mmHg) was significantly greater in patients treated with combination therapy, compared to patients on monotherapy (2.9 mmHg). The decrease in systolic BP (SBP) was not significantly different (11.1 versus 10.0 mmHg). In addition, a significantly higher number of patients treated with combination therapy (82% versus 74%) reached diastolic BP normalization (< 90 mmHg). CONCLUSIONS: In type 2 hypertensive patients with uncontrolled BP despite anti-hypertensive monotherapy, the change to combination therapy was more effective in attaining DBP control than any monotherapy schedule (either increasing the dose or switching to another different drug class).

Blood pressure measurement in an ambulatory setting: concordance between physician and patient self-measurement.

The aim of this study was to determine concordance between physician and patient blood pressure (BP) measurements in an ambulatory setting. A diagnostic intervention cross-sectional study using a convenience sample was employed. A total of 106 hypertensive patients were included in the study. Patients who were unable to perform their self-measurement or those with cardiac arrhythmia were excluded. BP was determined nine times in each subject in the medical office in a randomised order: BP was taken three times by the physician using a mercury sphygmomanometer (SPH-Hg), three times by the physician using a validated, automated oscillometer (Omron HEM 705 CP), and three times by the patient himself with the same device. The intraclass correlation coefficient was calculated. In all, 59 women and 47 men aged 65.7 (10) years were analysed. Mean BP measurements for the physician using the mercury sphygmomanometer, the physician using the Omron, and the patient using the same device were: 136 (15.8)/80 (11), 137 (17.9)/80 (10), and 139* (17.6)/80 (10) mmHg, respectively. BP control was 48.1, 48.1, and 36.8*% (*P < 0.05), respectively. Intraclass correlation coefficients for systolic/diastolic pressures were: 0.77/0.65 (physician-sphygmomanometer Hg, physician-Omron; P < 0.001), 0.75/0.64 (physician-sphygmomanometer Hg, patient-Omron, P < 0.001), and 0.83/0.83 (physician-Omron, patient-Omron; P < 0.001). In conclusion, the three types of measurement in the medical office were significantly concordant. Patient office self-measurement showed a tendency to increase systolic BP and worsen BP control.

Do changes in dietary salt influence blood pressure of hypertensive patients pharmacologically controlled with verapamil? The Salt-Switching-Study (SSS).

To study how changes in dietary salt influence the blood pressure (BP) of pharmacologically controlled hypertensive patients, we have selected from a large multicenter trial two subgroups of 14 and 16 patients who attained BP control (office DBP < 90 mm Hg) after a 4-week treatment with verapamil SR 240 mg once daily, either under an unrestricted salt diet (high-salt; 14 patients) or under a moderately restricted salt diet (low-salt; 16 patients). All of them were switched to the opposite dietary salt regimen and continued on verapamil for 4 more weeks (Salt-Switching-Period). Office BP and ambulatory blood pressure monitoring (ABPM) were registered before and after the Salt-Switching-Period. Salt intake was checked by urinary sodium excretion (UNa). Patients switching from high- to low-salt reduced UNa from 180.9 +/- 22.9 to 89 +/- 28 mM Na/24h (P < 0.001) and patients switching from low- to high-salt increased UNa from 85 +/- 38.4 to 175.8 +/- 57.5 mM Na/24h (P < 0.001). No significant changes in BP were found by ABPM either in the group switching from high- to low-salt or in the group switching from low- to high-salt. In the latter group, a significant increase was observed in office DPB but not in SBP. Short-term changes in salt intake seem to have little influence on the BP of patients pharmacologically controlled with verapamil.

Effect of verapamil on home self-measurement of blood pressure and heart rate by hypertensive patients. Verapamil-Frequency Research Group.

BACKGROUND: Achievement of a controlled blood pressure and improvement of cardiovascular risk profile are the mainstays of therapy for hypertension. OBJECTIVE: To assess the responses of heart rate and blood pressure in hypertensive patients to 240 mg/day sustained release verapamil. METHODS: We assessed the effect of 240 mg/day sustained released verapamil on blood pressure and heart rate, measured in the office and at home, in 1395 hypertensive outpatients with mild-to-moderate hypertension, who were using an Omron HEM 705 CP automatic device for self-measurement. The period of observation was 3 months. RESULTS: Blood pressure decreased both in the medical office and at the patient's home, the measurements obtained at home being lower than those found in the office. Heart rate decreased in a significant and particular way. The decrease was greatest among those patients with histories of myocardial infarction and among relatively young patients, who exhibit a tendency towards higher than normal baseline heart rates. Overall, there was a shift of the heart-rate curve towards more controlled levels clustered around heart rates between 65 and 75 beats/min. Home self-measurement showed that the data gathered by the patients at home are reliable and that, when cut-off values of 140/90 mm Hg for blood pressure are used, the percentage of patients with controlled blood pressures is 62%, whereas the percentage obtained in the medical office by the physician is 56%. If cut-off values of 135/85 mm Hg are considered for self-measurements at home, according to the VI JNC recommendations, the percentage of patients with controlled blood pressures is 25.4%.

[Clinical characteristics of the white coat hypertension]. / Características clínicas del hipertenso de bata blanca.

BACKGROUND: White coat hypertension (WCH) is a relatively prevalent clinical situation (around 20% of the hypertense population). The aim of this study was to analyze the clinical characteristics of these patients. METHODS: A descriptive transversal study was carried out in general medicine consultations in a unrandomized sample of hypertensive patients receiving pharmacologic treatment. Twenty-four hour ambulatory blood pressure monitorization (ABPM) (SpaceLabs 90202-90207) was performed following three resting blood pressure (BP) determinations carried out during the visit at 5-minute intervals by mercury sphigmomanometer. WCH was defined as: BP during the consultation > 140 mmHg (systolic) or > 90 mmHg (diastolic) with a mean daily blood pressure by ABPM < 140/< 90 mmHg. RESULTS: One hundred sixty-four patients (53% males) with a mean age of 48 years (SD 15.8) and a mean time of high blood pressure of 36 months (SD 51.4) were studied. Seventy-one patients (43%) fulfilled WCH criteria. WCH was significantly associated with females (p < 0.01), hypercholesterolemia (p < 0.05), lower involvement of target organs (p < 0.05), greater nocturnal tolerance to ABPM (p < 0.05) and lower mean nocturnal blood pressure (p < 0.001). CONCLUSIONS: The prevalence of white coat hypertension is elevated. Most of these patients are females, have fewer target organ lesions that the remaining hypertensive patients although dyslipemia is more frequently observed in these cases.

[Heart rate and isolated clinical tachycardia in hypertensive patients]. / Frecuencia cardíaca y taquicardia clínica aislada en pacientes con hipertensión arterial.

BACKGROUND: There is poor information for isolated clinical tachycardia (ICT), that is to say, office tachycardia but normal ambulatory heart rate (HR). Our objective was to describe it and to know differences between hypertensive subjects with and without ICT. PATIENTS AND METHOD: Comparative study after a diagnostic intervention (ambulatory blood pressure monitoring, ABPM, SpaceLabs 90202-90207), with convenience sampling of non-treated hypertensive patients attended in primary care. We excluded subjects with heart, thyroid or lung disease. ICT were defined on the basis of office and daytime HR percentile 90 of the whole sample. RESULTS: A total of 256 subjects were included, 128 (50%) women, age 49.1 (16.1) years, with mean office blood pressure (BP) 151 (17.1)/92 (11.9) mmHg. The prevalence of ICT was 7.03% (CI 95%, 4.03-11.07) (n = 18). We didn't find any association between isolated clinical hypertension and ICT (p = 0.87). Patients with ICT have lower office and systolic night time BP, lower night time variability, higher night time BP fall, although higher 24 hours-HR and daytime-HR in comparison with non ICT hypertensive patients. In the multivariate analysis only office diastolic BP (OR, 0.93 [CI 95%, 0.87-0.98], for each mmHg increment) and office HR (OR, 1.2 [CI 95%, 1.11-1.28], for each beat for minute increment) were predictive of ICT. CONCLUSIONS: In this study 7.03% of non treated hypertensive patients present ICT, which suggest a profile of more favorable cardiovascular risk than that without ICT. Only office diastolic BP and office HR were predictive variables of ICT.

Economic evaluation of Cardio inCode®, a clinical-genetic function for coronary heart disease risk assessment.

BACKGROUND: A clinical­genetic function (Cardio inCode®) was generated using genetic variants associated with coronary heart disease (CHD), but not with classical CHD risk factors, to achieve a more precise estimation of the CHD risk of individuals by incorporating genetics into risk equations [Framingham and REGICOR (Registre Gironí del Cor)]. OBJECTIVE: The objective of this study was to conduct an economic analysis of the CHD risk assessment with Cardio inCode®, which incorporates the patient's genetic risk into the functions of REGICOR and Framingham, compared with the standard method (using only the functions). METHODS: A Markov model was developed with seven states of health (low CHD risk, moderate CHD risk, high CHD risk, CHD event, recurrent CHD, chronic CHD, and death). The reclassification of CHD risk derived from genetic information and transition probabilities between states was obtained from a validation study conducted in cohorts of REGICOR (Spain) and Framingham (USA). It was assumed that patients classified as at moderate risk by the standard method were the best candidates to test the risk reclassification with Cardio inCode®. The utilities and costs (€; year 2011 values) of Markov states were obtained from the literature and Spanish sources. The analysis was performed from the perspective of the Spanish National Health System, for a life expectancy of 82 years in Spain. An annual discount rate of 3.5 % for costs and benefits was applied. RESULTS: For a Cardio inCode® price of €400, the cost per QALY gained compared with the standard method [incremental cost-effectiveness ratio (ICER)] would be €12,969 and €21,385 in REGICOR and Framingham cohorts, respectively. The threshold price of Cardio inCode® to reach the ICER threshold generally accepted in Spain (€30,000/QALY) would range between €668 and €836. The greatest benefit occurred in the subgroup of patients with moderate­high risk, with a high-risk reclassification of 22.8 % and 12 % of patients and an ICER of €1,652/QALY and €5,884/QALY in the REGICOR and Framingham cohorts, respectively. Sensitivity analyses confirmed the stability of the study results. CONCLUSIONS: Cardio inCode® is a cost-effective risk score option in CHD risk assessment compared with the standard method.