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Introduction: The main objective was to compare the mean change in augmentation index of hypertensive patients treated with nebivolol or atenolol., Methods: Multicenter, double-blind randomized study conducted in six Spanish centers. We enrolled outpatients between the ages of 40 and 65 years with mild or moderate essential hypertension (systolic blood pressure, SBP ≥ 140 mmHg to ≤ 179 mmHg and diastolic blood pressure, DBP ≥ 90 mmHg to ≤ 109 mmHg after a 2-week run-in placebo period). Patients received nebivolol 5 mg or atenolol 50 mg once daily. At week 3, atenolol could be titrated up to 100 mg qd for non-responders. Additionally, patients not achieving normal blood pressure after 6 weeks could be treated with 25 mg hydrochlorothiazide. Follow-up visits were at 3, 6 and 10 weeks., Results: The final study population of 138 patients (58% men; median age 52.6 years, range 40-67 years) was randomized into two groups of 69 patients each. Baseline characteristics of the two groups were similar. At the screening visit, 69% presented with mild hypertension. Nebivolol modified the mean augmentation index to a lesser extent than atenolol after 10 weeks (mean difference 3.1%, 95% CI 0.55-5.69; p = 0.027). A higher proportion of patients in the atenolol group required a diuretic. Reductions in central aortic pressure and peripheral arterial pressure were similar for both treatment groups., Conclusions: The study confirms that nebivolol produces a less pronounced impact on augmentation index than atenolol.

Background: Clinical inertia has been defined as mistakes by the physician in starting or intensifying treatment when indicated. Inertia, therefore, can affect other stages in the healthcare process, like diagnosis. The diagnosis of dyslipidemia requires ≥2 high lipid values, but inappropriate behavior in the diagnosis of dyslipidemia has only previously been analyzed using just total cholesterol (TC)., Objectives: To determine clinical inertia in the dyslipidemia diagnosis using both TC and high-density lipoprotein cholesterol (HDL-c) and its associated factors., Design: Cross-sectional., Setting: All health center visits in the second half of 2010 in the Valencian Community (Spain)., Patients: 11,386 nondyslipidemic individuals aged ≥20 years with ≥2 lipid determinations., Measurement Variables: Gender, atrial fibrillation, hypertension, diabetes, cardiovascular disease, age, and ESCARVAL training course. Lipid groups: normal (TC<5.17 mmol/L and normal HDL-c [≥1.03 mmol/L in men and ≥1.29 mmol/L in women], TC inertia (TC≥5.17 mmol/L and normal HDL-c), HDL-c inertia (TC<5.17 mmol/L and low HDL-c), and combined inertia (TC≥5.17 mmol/L and low HDL-c)., Results: TC inertia: 38.0% (95% CI: 37.2-38.9%); HDL-c inertia: 17.7% (95% CI: 17.0-18.4%); and combined inertia: 9.6% (95% CI: 9.1-10.2%). The profile associated with TC inertia was: female, no cardiovascular risk factors, no cardiovascular disease, middle or advanced age; for HDL-c inertia: female, cardiovascular risk factors and cardiovascular disease; and for combined inertia: female, hypertension and middle age., Limitations: Cross-sectional study, under-reporting, no analysis of some cardiovascular risk factors or other lipid parameters., Conclusions: A more proactive attitude should be adopted, focusing on the full diagnosis of dyslipidemia in clinical practice. Special emphasis should be placed on patients with low HDL-c levels and an increased cardiovascular risk.

Background: The objective was to investigate the association between BMI and single nucleotide polymorphisms previously identified of obesity-related genes in two Spanish populations. Forty SNPs in 23 obesity-related genes were evaluated in a rural population characterized by a high prevalence of obesity (869 subjects, mean age 46 yr, 62% women, 36% obese) and in an urban population (1425 subjects, mean age 54 yr, 50% women, 19% obese). Genotyping was assessed by using SNPlex and PLINK for the association analysis., Results: Polymorphisms of the FTO were significantly associated with BMI, in the rural population (beta 0.87, p-value <0.001). None of the other SNPs showed significant association after Bonferroni correction in the two populations or in the pooled analysis. A weighted genetic risk score (wGRS) was constructed using the risk alleles of the Tag-SNPs with a positive Beta parameter in both populations. From the first to the fifth quintile of the score, the BMI increased 0.45 kg/m2 in Hortega and 2.0 kg/m2 in Pizarra. Overall, the obesity predictive value was low (less than 1%)., Conclusion: The risk associated with polymorphisms is low and the overall effect on BMI or obesity prediction is minimal. A weighted genetic risk score based on genes mainly acting through central nervous system mechanisms was associated with BMI but it yields minimal clinical prediction for the obesity risk in the general population.

Background: Clinical inertia, the failure of physicians to initiate or intensify therapy when indicated, is a major problem in the management of hypertension and may be more prevalent in elderly patients. Overcoming clinical inertia requires understanding its causes and evaluating certain factors, particularly those related to physicians., Objective: The objective of our study was to determine the rate of clinical inertia and the physician-reported reasons for it., Methods: An observational, cross-sectional, multi-center study was carried out in a primary care setting. We included 512 physicians, with a consecutive sampling of 1,499 hypertensive patients with clinical inertia., Main Outcome Measure: Clinical inertia was defined when physicians did not modify treatment despite knowing that the therapeutic target had not been reached. Clinical inertia was considered to be justified (JCI) when physicians provided an explanation for not intensifying treatment and as not justified (nJCI) when no reasons were given., Results: JCI was observed in 30.1 % (95 % CI 27.8-32.4) of patients (n = 451) and nJCI in 69.9 % (95 % CI 67.6-72.2) (n = 1,058). JCI was associated with higher blood pressure (BP) values (both systolic and diastolic) and diabetes (p = 0.012) than nJCI. nJCI was associated with patients having an isolated increase of systolic or diastolic or high borderline BP values or cardiovascular disease., Conclusion: Physicians provided reasons for not intensifying treatment in poorly controlled patients in only 30 % of instances. Main reasons for not intensifying treatment were borderline BP values, co-morbidity, suspected white coat effect, or perceived difficulty achieving target. nJCI was associated with high borderline BP values and cardiovascular disease.

Introduction: There are few clinical trials that provide evidence to support the hypothesis that combined therapies offer a favorable risk-benefit ratio in the reduction of cardiovascular mortality and morbidity. Combined therapies containing an angiotensin-converting enzyme inhibitor (ACEI) with a calcium channel blocker (CCB) is one of the recommended combinations in the reappraisal of the European Society of Hypertension., Areas Covered: The authors have performed a systematic review of the available clinical evidence on the use of combined therapies containing an ACEI with a CCB versus other combinations in the management of arterial hypertension (HT) and in the reduction of cardiovascular morbidity/mortality, according to recommendations of The Cochrane Handbook for Systematic Reviews of Interventions. They identified 122 potentially relevant studies. Of these, 38 included combined therapies in one or both treatment arms. Overall, a total of 12 publications were retrieved from the search and provided data on the effects of the combined therapy with an ACEI and a CCB on cardiovascular mortality/morbidity in patients with HT. Clinical evidence corresponds to three double-blind clinical trials: ASCOT-BPLA, ACCOMPLISH and Syst-EUR., Expert Opinion: The analysis demonstrates the superiority of the combined therapy with ACEI/CCB not only in the overall population included in the studies but also in subsets of patients with a high cardiovascular risk such as diabetes and chronic kidney disease.

Dihydropyridinic calcium channel blockers are a subclass of antihypertensive drugs with growing significance in the therapeutic armamentarium. Early studies in the 1990s had aroused certain fears with regard to the safety of the first drugs from this class, since they had a fast onset of action and a short half-life, and thus they were associated with reflex adrenergic activation. New molecules with long half-lives and high lipophilia have shown safety and efficacy in the control of blood pressure, as well as in the reduction of several end points related to hypertension. Moreover, these new molecules, which block special subtypes of calcium channel receptors, provide drugs not only with an action profile that goes beyond the antihypertensive effect, but also with a lower rate of side effects. Therefore, in the light of new studies that include calcium channel blockers alone or in combination, these agents will probably be used even more extensively for the management of hypertension in the following years.

Background: Some studies have described a large number of hypertensive patients who are followed by a primary care physician without achieving adequate blood pressure (BP) control but whose treatment nevertheless is not intensified. It is not known whether physicians are aware of this clinical inertia and what factors are associated with this problem., Objective: The aim of this study was to describe the factors associated with clinical inertia in hypertensive patients., Methods: This was an observational, cross-sectional, multicentre study conducted in a network of primary care centres and hospital hypertension units in Spain. Using a consecutive sampling approach, 512 physicians selected 5077 hypertensive patients in whom they suspected poor BP control after chart review. The main variables documented were BP control and cardiovascular risk according to European Society of Hypertension guidelines, changes in treatment after visit, type of treatment, and healthcare setting. A binomial logistic regression multivariate analysis, adjusted for physician, was performed., Results: Of the selected patients, 70.9% had poor BP control according to measurements taken in the physician's office, and in 1499 (42.1%) of those poorly controlled patients, treatment was not intensified (clinical inertia). Factors associated with clinical inertia were as follows: being seen at a primary care centre (p < 0.001), not having left ventricular hypertrophy (p < 0.001) or microalbuminuria (p < 0.001), taking fixed-dose (p = 0.049) or free-dose (p = 0.001) combination therapy, BP measured in other settings (nurse's office, patient's home) than the physician's office (p = 0.034) or the pharmacy (p = 0.019), older age (p = 0.032), and lower systolic (p < 0.001) and diastolic (p < 0.001) BP. Of the hypertensive patients with clinical inertia, 90.2% (95% CI 88.7, 91.7) had high cardiovascular risk., Conclusions: Clinical inertia was associated with a profile that included older age, lack of co-morbid conditions and being seen at a primary care centre.

The SCORE table indiscriminately recommends the use of total cholesterol (SCORE-TC) or atherogenic index (SCORE-AI) for calculating cardiovascular (CV) risk. We evaluated reliability and agreement between both methods and the clinical implications for the identification of high CV risk. Observational study (n=8942) in a 40- to 65-year-old population. Spearman's Rho correlation was 0.987 (P<.001), the agreement intraclass correlation coefficient was 0.671 (IC 95% 0.413-0.796; with Bland-Altman's method, the average of the differences between models was 0.74. Kappa index was poor, 0.297 (P<.001) and positive specific agreement was 0.31. Discrepancies fitted individuals with high CV risk with SCORE-TC and not-high with SCORE-AI (4.7%) and 5.8% (n=518) of individuals were classified as high-risk according to SCORE-TC versus 1.1% (n=95) according to SCORE-AI. Poor agreement was found between SCORE-TC and SCORE-IA for identification of high cardiovascular risk individuals., (Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Introduction and Objectives: Age and arterial hypertension are two of the main factors associated with atrial fibrillation and an increased risk of embolism. The objective of this study was to determine the prevalence of atrial fibrillation and the extent of antithrombotic use in hypertensive patients aged ≥65 years in the Spanish region of Valencia., Methods: Each study investigator enrolled the first three hypertensive patients aged ≥65 years who came for a consultation on the first day of each week for 5 weeks. Each patient's risk factors, history of cardiovascular disease, CHADS(2) score and medical treatment were noted and an ECG was recorded. Data were analyzed centrally. A patient was regarded as having atrial fibrillation if it was observable on the ECG or reported in medical records., Results: The study included 1,028 hypertensive patients with a mean age of 72.8 years. Overall, 10.3% had atrial fibrillation: in 6.7%, it was observable on the ECG while 3.6% were in sinus rhythm but had a history of the condition. Factors associated with atrial fibrillation were age, alcohol intake, structural heart disease and glomerular filtration rate. In total, 76.2% of patients with ECG evidence of atrial fibrillation and a CHADS(2) score >1 were taking anticoagulants compared with 41.7% of those who had a history of the condition but were currently in sinus rhythm., Conclusions: The prevalence of atrial fibrillation in our group of hypertensives was 10.3%; in 1.7%, it was previously undiagnosed. Antithrombotic use was high in patients with current atrial fibrillation, but lower in those who had experienced an episode previously., (Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Introduction and Objectives: Age and arterial hypertension are two of the main factors associated with atrial fibrillation and an increased risk of embolism. The objective of this study was to determine the prevalence of atrial fibrillation and the extent of antithrombotic use in hypertensive patients aged >or=65 years in the Spanish region of Valencia., Methods: Each study investigator enrolled the first three hypertensive patients aged >or=65 years who came for a consultation on the first day of each week for 5 weeks. Each patient's risk factors, history of cardiovascular disease, CHADS2 score and medical treatment were noted and an ECG was recorded. Data were analyzed centrally. A patient was regarded as having atrial fibrillation if it was observable on the ECG or reported in medical records., Results: The study included 1,028 hypertensive patients with a mean age of 72.8 years. Overall, 10.3% had atrial fibrillation: in 6.7%, it was observable on the ECG while 3.6% were in sinus rhythm but had a history of the condition. Factors associated with atrial fibrillation were age, alcohol intake, structural heart disease and glomerular filtration rate. In total, 76.2% of patients with ECG evidence of atrial fibrillation and a CHADS2 score >1 were taking anticoagulants compared with 41.7% of those who had a history of the condition but were currently in sinus rhythm., Conclusions: The prevalence of atrial fibrillation in our group of hypertensives was 10.3%; in 1.7%, it was previously undiagnosed. Antithrombotic use was high in patients with current atrial fibrillation, but lower in those who had experienced an episode previously.

The Efectividad de un Programa de Intervención en el Control de la Presión Arterial de los Hipertensos en Riesgo de Desarrollar Insuficiencia Cardiaca (HEROIC) study was designed to assess whether an educational program for primary care physicians could improve blood pressure (BP) control in hypertensive patients at high risk for developing heart failure. The program contained a combination of educational training (live group sessions or online training) and information feedback. Two hundred twenty-six physicians completed the program and provided valid data in 2489 patients before and 2168 after 1 year. There was a small but significant reduction of -1.1 mm Hg (P=.009) in systolic BP and a higher proportion of patients achieved their BP target (13.6% vs 15.6%, P=.055). Thus, the authors concluded that there was a slight improvement in BP control after the educational program, but this change was not sufficient to avoid development of heart failure. More complex and intensive programs are needed for this type of prevention.

Background: The relationship between basal heart rate (HR) and the occurrence of myocardial ischemia, sudden death, cardiovascular mortality have been described. Therefore, further studies are warranted to evaluate the behaviour of heart rate in different scenarios. We sought to determine whether ambulatory heart rate is associated with the presence of target organ damage (TOD) in hypertensive patients., Patients and Methods: Crossectional study of essential hypertensive patients in whom a twenty-four hour ambulatory blood pressure monitoring (ABPM) was performed. The relationship between TOD and 24 hour ambulatory heart rate (HR) was analyzed., Results: Five hundred and sixty-six patients with arterial hypertension were included (55.8% male, mean age 59.9 +/- 14.2 years). 15% were smokers, 62.2% had dyslipidemia, 18.4% diabetes mellitus. Heart rate values were higher during activity as compared to the resting period (72.8 vs 63.3 bpm, p < 0.001). Heart rate, in both periods, was not associated with the presence of TOD. Nevertheless, the patients with nocturnal HR > or = 65 bpm have high risk and a high prevalence of TOD. This relationship was also present in multivariate analysis (HR 2.41; CI 95% 1.41-4.11; p=0.001)., Conclusion: An elevated nocturnal HR, > or = 65 bpm, obtained with ABPM registry, is associated with the presence of TOD in hypertensive patients. ABPM is a powerful tool for hypertensive patients not only to monitor BP control but also to obtain information on HR which may provide additional information about current and future cardiovascular risk.

Objectives: The objective of the present study was to quantify both diagnostic and therapeutic inertia in hypertension and to identify patient-associated variables., Patients and Methods: Cross-sectional, multicenter study of 35 424 subjects carried out in 428 health centers and/or primary care clinics in the Valencian Community, Spain, in a preventive activity conducted during 2003 and 2004. Diagnostic inertia was identified when a patient without known hypertension had high blood pressure (BP) but was labeled "normal" by the medical staff, and therapeutic inertia when treatment was not modified for a hypertensive patient on the presence of high BP values. Bivariate and multivariate statistical analyses were performed to identify patient's characteristics associated with inertia., Results: Diagnostic inertia was present in 32.5% (95% CI 31.4-33.6) and therapeutic inertia in 37.0% (95% CI 35.6-38.5) of the cases. Both were more frequent in cases of isolated systolic or diastolic high BP. In the multivariate models, the factors associated with diagnostic inertia were type-2 diabetes (p=0.041), non-smoking (p=0.004), previous coronary heart disease (p=0.001), BP values (p<0.001) and body mass index (p=0.031), whereas for therapeutic inertia they were type-2 diabetes (p=0.003), previous coronary heart disease (p=0.016) or stroke (p<0.001) and BP values (p<0.001)., Conclusions: Clinical inertia, either diagnostic or therapeutic, was present in one of every three cases of high BP. The most frequent factors associated with clinical inertia were the presence of associated conditions, which requires lower BP goals and the BP values.

Aims: To evaluate the relationship between systolic blood pressure (SBP) and long-term mortality in patients with acute heart failure (AHF) stratified by ejection fraction (LVEF): reduced (< or =40%) vs. preserved (> or =50%)., Methods and Results: We studied 1049 consecutive patients admitted with AHF. Systolic blood pressure was determined in the emergency department. Left-ventricular ejection fraction was categorized as < or =40% (n = 288), 41-49% (n = 174), or > or =50% (n = 587). Cox regression analysis was used for multivariable analysis. Mean age and SBP were 73 +/- 11 years and 150 +/- 36 mmHg, respectively. During a median follow-up of 18 months, 290 deaths (33.1%) were identified. Higher SBP was associated with lower mortality. In multivariable analysis, a differential effect of SBP across LVEF status was documented (P-value for interaction = 0.036). In linear models, SBP was shown to be inversely related with mortality in both groups (per 10 mmHg decrease): HR((LVEF > or = 50%)): 1.06, CI 95% = 1.01-1.11; P = 0.016, and HR((LVEF < or = 40%)): 1.16, 95% CI = 1.08-1.25; P < 0.001). When SBP was modelled with restrictive cubic splines, an inverse and almost linear relationship with mortality was shown in patients with LVEF < or =40% (P < 0.001), whereas in patients with LVEF > or =50%, SBP followed a J-shape curve., Conclusion: In patients with AHF, SBP showed a differential prognostic effect on mortality according to LVEF status; when LVEF was < or =40%, SBP was linearly and inversely associated with mortality. Conversely, in patients with LVEF > or =50% this relationship showed a J-shape pattern.

The impact of classic cardiovascular risk factors on oxidative stress status in a high-risk cardiovascular Mediterranean population of 527 subjects was estimated. Oxidative stress markers (malondialdehyde, 8-oxo-7'8'-dihydro-2'-deoxyguanosine, oxidized/reduced glutathione ratio) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) were analysed in circulating mononuclear blood cells. Malondialdehyde, oxidized glutathione and the ratio of oxidized to reduced glutathione were significantly higher while catalase and glutathione peroxidase activities were significantly lower in high cardiovascular risk participants than in controls. Statistically significant differences were obtained after additional multivariate control for sex, age, obesity, diabetes, lipids and medications. Among the main cardiovascular risk factors, hypertension was the strongest determinant of oxidative stress in high risk subjects studied at a primary prevention stage.

Introduction and Objectives: To determine the prevalence of a low high-density lipoprotein cholesterol (HDL-C) concentration in 11,042 hypertensive Spanish women aged >or=55 years, to identify factors associated with a low concentration, and to evaluate its relationship with cardiovascular disease (CVD)., Methods: Analysis of RIMHA cross-sectional study findings. Data on demographic, biochemical and clinical variables were obtained. Relationships between a low HDL-C concentration (<46 mg/dL) and CVD and between the HDL-C concentration (in quintiles) and CVD were studied by multivariate logistic regression modeling., Results: The prevalence of a low HDL-C concentration was 24.3% (95% confidence interval [CI], 23.5-25.1%), and was higher in women with diabetes or CVD. A low HDL-C concentration was independently associated with excess weight, smoking, diabetes and the presence of CVD, and inversely with age. The prevalence of CVD was higher in women with a low HDL-C concentration (24.7% vs. 18.4% in those with a normal concentration; P< .001). There was an independent association between a low HDL-C concentration and CVD after adjustment for other risk factors (odds ratio [OR]=1.42; 95% CI, 1.26-1.60; P< .001) and with silent target organ damage (OR=1.31; 95% CI, 1.15-1.49; P< .001). Similarly, there was an independent inverse association between the HDL-C concentration (in quintiles) and the prevalence of CVD, particularly for HDL-C concentrations <58 mg/dL., Conclusions: One in four hypertensive women aged >or=55 years had a low HDL-C concentration, which was independently associated with the presence of CVD. Moreover, there was an inverse association between the HDL-C concentration and the prevalence of CVD, even at normal HDL-C concentrations.

Background and Objective: Information about the prevalence of the metabolic syndrome (MS) in elderly population is scarce. The objectives of this study were to assess the prevalence of MS in Spanish population=60 years-old and the associated factors., Patients and Method: Epidemiological population-based cross-sectional study carried out on a randomized representative simple of subjects aged=60 years-old across the Spanish territory, stratified according to autonomous communities, census and population setting. Demographic, clinical, biochemical and electrocardiographic data were collected. MS was defined following the National Education Cholesterol Program (NCEP) criteria., Results: 7331 subjects -53.4% women; mean age (standard deviation): 71.6 (6.9) years- were included. The prevalence of MS was 39.9% (95% confidence interval [CI], 34.5-42.4) and was greater in women (45.2%; 95% CI, 43.7-46.8%) than in men (33.8%; 95% CI, 32.3-35.4%) (p<0.001), and lower in the urban setting. High blood pressure (HBP) was the most prevalent criterion, followed by abdominal obesity and hypertriglyceridemia. Subjects with MS were younger, with higher body mass index and blood pressure, and had more prevalence of organ damage and cardovascular disease (p<0,001). In the multivariate analysis, female gender, HBP, diabetes and abdominal obesity were the most strongly related factors., Conclusions: Four out of 10 subjects aged 60 years-old or more had MS, and this was related mainly to female gender, HBP, obesity and diabetes.

Background and Objective: Monotherapy with any class of antihypertensive drug effectively controls blood pressure (BP) in only about 50% of patients. Consequently, the majority of patients with hypertension require combined therapy with two or more medications. This study aimed to evaluate the effectiveness (systolic BP [SBP]/diastolic BP [DBP] control) and tolerability of the fixed-dose combination enalapril/nitrendipine 10 mg/20 mg administered as a single daily dose in hypertensive patients., Methods: This was a post-authorization, multicentre, prospective, observational study conducted in primary care with a 3-month follow-up. Patients throughout Spain with uncontrolled hypertension (> or =140/90 mmHg for patients without diabetes mellitus, or > or =130/85 mmHg for patients with diabetes) on monotherapy or with any combination other than enalapril + nitrendipine, or who were unable to tolerate their previous antihypertensive therapy, were recruited. Change from previous to study treatment was according to usual clinical practice. BP was measured once after 5 minutes of rest in the sitting position. Therapeutic response was defined as follows: 'controlled' meant controlled BP (<140/90 mmHg for nondiabetic patients, or <130/85 mmHg for diabetic patients); 'response' meant controlled BP, or a decrease in SBP of > or =20 mmHg and in DBP of > or =10 mmHg. The main laboratory test parameters were documented at baseline and after 3 months. Patients aged >65 years, with diabetes, with isolated systolic hypertension (ISH; SBP > or =140 mmHg for patients without diabetes, SBP > or =130 mmHg for patients with diabetes) and who were obese (body mass index [BMI] > or =30 kg/m2) were analysed separately., Results: Of 6537 patients included, 5010 and 6354 patients were assessed in effectiveness and tolerability analyses, respectively. In the tolerability analysis population, there were 3023 men (47.6%) and 3321 women (52.4%). The mean (+/- SD) age of the tolerability analysis group was 62.8 (+/- 10.7) years. A total of 71.1% of the patients presented at least one clinical cardiovascular risk factor other than hypertension, with the most frequent being dyslipidaemia (42.3%), obesity (29.2%) and diabetes (23.9%). After 3 months of treatment, SBP and DBP showed mean (+/- SD) decreases of 26.5 (+/- 14.4) mmHg and 14.9 (+/- 9.0) mmHg, respectively, and 73.0% of patients responded to treatment while 40.9% achieved BP control (70.8%/36.1% in 2658 patients aged >65 years; 61.7%/46.8% in 1521 patients with diabetes; 55.3%/44.2% in 731 patients with ISH; 72.0%/36.4% in 1762 obese patients). Adverse events were reported in 10.8% of patients (n = 689). During the follow-up period, ten patients died and seven patients had serious adverse events; in no case was a causal relationship attributed to the study product., Conclusions: The rate of SBP/DBP control achieved demonstrates the effectiveness of the fixed-dose enalapril/nitrendipine 10 mg/20 mg combination administered as a single daily dose in patients with essential hypertension not adequately controlled with monotherapy or with any combination other than enalapril + nitrendipine. The proportion and type of adverse events reported were as expected and have already been described for both components of the enalapril/nitrendipine 10 mg/20 mg combination. These results confirm the effectiveness of a strategy based on a fixed-dose enalapril/nitrendipine 10 mg/20 mg combination in reducing BP and achieving BP control goals.

Objective: The objective was to assess the impact of weight changes on blood pressure (BP), lipids and glucose goals in a cohort of hypertensive subjects., Design: Prospective follow-up., Setting: Hypertension clinic., Patients: 326 hypertensive non-diabetic subjects, 46% with metabolic syndrome (MS)., Interventions: Usual care treatment, which included diet, physical exercise and drugs prescribed when indicated. All patients were observed for up to 1 year., Main Outcome Measures: BP and low-density lipoprotein-cholesterol (LDL-C) goal were those in ESH/ESC and ATP III recommendations, respectively. The glucose goal was to delay progression to type 2 diabetes mellitus, or to achieve blood glucose <100 mg/dl for non-diabetics. According to body weight changes, patients were categorized using adjusted ROC curves models., Results: Overall, there was a significant weight increment of 0.5 kg (95% CI 0.1-0.9 kg); 28 patients (8.6%) lost more than 5 kg, and only four (1.2%) lost more than 10 kg. BP, LDL-C and glucose goals were achieved in 56%, 78% and 61% of patients, respectively. To lose or not gain weight was an independent prognostic factor to achieve the BP goal in all the patients and the LDL goal in the presence of MS. For glucose control, being treated with beta-blockers and/or diuretics was a negative factor., Conclusions: In hypertensive subjects, even small changes in weight may have an important impact on achieving cardiovascular goals, mainly in those with MS.

Background and Objective: Data on the prevalence of obesity in elderly population in Spain are scarce. The objective of this work was to describe the prevalence of obesity and the related factors in a random sample of Spanish population aged 60 years-old or more, stratified by autonomous communities., Subjects and Method: We analyzed the PREV-ICTUS study, a population-based study carried out between September and December 2005 in a random sample stratified by autonomous communities according to the census of inhabitants and the habitat in each community. Subjects were classified as with normal weight (body mass index [BMI] < 25 kg), overweight (BMI 25-29.9) and obesity (BMI > or = 30 kg)., Results: In 6,843 subjects -mean age (standard deviation): 71.9 (7.1) years-old; 53.3% women-, prevalence of obesity was 34.5% (95% confidence interval [CI], 33.3-35.5%), higher in women (38.4%; 95% CI, 36.8-39.9%) than in men (30.0%; 95% CI, 28.4-31.6%; p < 0.001), with a tendency to decrease in the older population. In total, 81.7% of the population showed overweight (BMI > or = 25). Prevalence differed among communities from 46.4% to 20.7% (p < 0.001). In the multivariate analysis, obesity was inversely related to age (odds ratio [OR] = 0.98 per each year increment), and directly to female gender (OR = 1.25), rural (OR = 1.50) or semi-urban habitat (OR = 1.38), sedentary lifestyle (OR = 1.86) and non-smoking history (OR = 1.19)., Conclusions: Obesity was present in one out of 3 individuals of this reasonably representative sample of the Spanish population in an age range, 60 years-old or more, which concentrates a high cardiovascular risk. Differences in the prevalence among autonomus communities were detected.

Objective: To assess the relationship between different serum lipid profiles and the prevalence of established cardiovascular disease (CVD) in an elderly population., Research Design and Methods: An analysis was undertaken of the PREV-ICTUS population-based study on Spanish subjects aged > or =60 years. The following definitions were used: abnormal LDL cholesterol (LDL-C): > or =130 mg/dl (> or =3.3 mmol/L), or > or =100 mg/dl (> or =2.5 mmol/L) in those with diabetes or CVD, or treatment with any hypolipidaemic drug; low HDL cholesterol (HDL-C): <40 mg/dl (<1 mmol/L) (men), or <50 mg/dl (<1.3 mmol/L) (women), and abnormal triglycerides (TG): > or =150 mg/dl (> or =1.7 mmol/L) or treatment with fibrates. We defined eight groups: A (normal lipid profile), B (isolated abnormal LDL-C), C (isolated abnormal TG), D (isolated low HDL-C), E (abnormal LDL-C and HDL-C), F (abnormal LDL-C and TG), G (abnormal TG and HDL-C), H (abnormal LDL-C, HDL-C and TG). A multivariate analysis was performed to assess the relationship between each lipid profile and CVD., Results: A total of 6010 subjects (mean age 71.7 years, 53.5% women, 73.2% with hypertension, 29.2% with diabetes mellitus, 24.3% with CVD), were included in the analysis. LDL-C elevation was present in 78.1%, 23.3% had low HDL-C and 35.7% abnormal TG. Combined dyslipidaemias were frequent (40.3%). Odds ratios (95% confidence intervals) for CVD, compared with those with a normal lipid profile, were 2.07 (1.24-3.46) for abnormal HDL-C (p = 0.005), 4.09 (3.10-5.39) for abnormal LDL-C; 6.41 (4.59-8.95) for abnormal LDL-C plus HDL-C, 5.33 (3.98-7.14) for abnormal LDL-C plus TG and 7.59 (5.51-10.5) for those with the three parameters altered (all p < 0.001). Compared with those with isolated LDL-C elevation, those with abnormal LDL-C plus HDL-C had 1.57 (1.30-1.97) higher odds of having CVD (p < 0.001), the figures being 1.30 (1.11-1.53) for those with abnormal LDL-C plus TG and 1.86 (1.52-2.28) for those with abnormal LDL-C, TG plus HDL-C (p < 0.001)., Conclusions: Lipid abnormalities are frequent in the elderly, and are associated with the presence of CVD. Low HDL-C and/or abnormal TG levels, when added to abnormal LDL-C, are associated with a higher prevalence of CVD, suggesting the advisability of a comprehensive lipid evaluation and treatment earlier in life.

Background and Objectives: To analyze the impact of occult renal failure (ORF) in the individual risk stratification and on the blood pressures (BP) and low-density lipoprotein (LDL) goals in an aged population, according to the ESH/ESC Hypertension Guidelines., Methods: A cross-sectional, population-based study on individuals aged 60 years or more carried out in Primary Care Centers of Spain. Kidney function was estimated from calculated creatinine clearance (eGFR), Cockroft and Gault formula. Ten-year cardiovascular risk was estimated through the ESH/ESC table including or not including the eGFR. Estimates of the modification in BP and LDL-cholesterol (cLDL) goals were calculated., Results: In 6419 subjects, 4242 subjects (66%) had normal renal function, 1971 (31%) had ORF (normal creatinine and low eGFR) and 206 (3%) had insufficient renal function (high creatinine and all of them low eGFR). Inclusion of ORF as target organ damage resulted in an increase in the estimated risk in 10.8% of the total sample, increasing the percentage of high-risk subjects. In the latter case, new BP and cLDL goals (<130/80 mmHg and <100 mg/dl) should be needed in 475 (7.4%) and 413 (6.4%) additional subjects, respectively., Conclusion: Inclusion of the ORF resulted in a significant increase in the percentage of subjects with estimated high cardiovascular risk.

Background and Objective: To assess the prevalence of low glomerular filtration rate (GFR < 60 ml/min/1.73 m2) in general population of subjects aged 60 years or older of Spain, and the related factors., Patients and Method: Analysis of PREV-ICTUS, a population-based study carried out in a sample of subjects aged 60 years or more, randomly selected and stratified by Autonomic Communities according to the census of inhabitants and the habitat in each Community. Demographic data, cardiovascular risk factors and diseases were collected. GFR was calculated using the MDRD (Modification of Diet in Renal Disease) equation., Results: In 6,799 subjects (age 71.9 years-old; 53.6% women; 72.9% with arterial hypertension [HT]; 27.0% with diabetes mellitus [DM]; 24.3% with cardiovascular disease), 25.9% had low GFR (95% confidence interval, 24.8-26.9). The prevalence increased linearly, from 16.5% in subjects aged 60-64 years to 46.5% in those aged 85 or more (p < 0.001), and was higher in women (36.1% vs 14.1% in men, p < 0.001). In the multivariate analysis, low GFR was independently related to advanced age (odds ratio [OR] between 1.30 y 4.20), female gender (OR = 5.82), HT older than 7 years (OR = 1.23), uric acid (OR = 1.52 for each increment of 1 mg/dl) and cardiovascular disease (OR = 1.68). The association with DM did not reach statistical significance. In a model without cardiovascular disease, related factors remained the same, increasing the significance of HT older than 7 years (OR = 1.31) and of DM (OR = 1.19)., Conclusion: One out or 4 subjects of this sample showed low GFR. The variables directly associated with low GFR were advanced age, female gender, HT of longer evolution, cardiovascular disease, increased uric acid, and, in one model, DM.

Introduction: The aims of this study were to evaluate the consistency between the SCORE (Systematic Coronary Risk Evaluation) and REGICOR (Registre Gironí del cor) scales in identifying high cardiovascular risk and to describe the characteristics of those individuals for whom scale results were discrepant., Methods: This cross-sectional study involved 8942 subjects aged 40-65 years who had an indication for a complete lipid profile. The agreement between SCORE (for low-risk countries) and Framingham-REGICOR (with a high risk threshold of 10%) scales in classifying patients as high risk was evaluated using the kappa statistic. Subjects for whom there was a discrepancy between classifications were identified and variables associated with this discrepancy were determined by multivariate analysis involving binary logistic regression., Results: The REGICOR scale classified 6.7% of subjects (95% confidence interval [CI], 6.2%-7.3%) as high-risk, while SCORE classified 12.5% (95% CI 11.8%-13.2%) as high-risk. Discrepant findings were observed in 10.2% of the total population (8% had a high risk on SCORE but not REGICOR, and 2.2% had a high risk on REGICOR but not SCORE; kappa=0.420; P< .001). The best agreement was observed between SCORE and REGICOR with a high-risk threshold of 8% (kappa=0.463). Multivariate analysis showed that a high risk on SCORE but not REGICOR was associated with lower age, female sex, a high fasting glucose level, and raised diastolic blood pressure, and a high risk on REGICOR but not SCORE, with male sex, smoking, and a low high-density lipoprotein (HDL) cholesterol level. These variables accounted for the extent of the discrepancy in 93.2% of cases., Conclusions: The SCORE and REGICOR (threshold 10%) scales identified different populations as being at a high risk, though the agreement between them was reasonably good. The concurrence of a number of factors (e.g., male sex, low HDL-cholesterol, and smoking) in a subject with a low risk on the SCORE scale should be regarded as increasing the cardiovascular risk.

Objective: Oxidative stress is implicated in hypertension and the NADPH oxidase systems constitute the main source of superoxide in vascular wall. We searched for new polymorphisms within the CYBA promoter, the human gene that encodes the p22phox protein, and studied their potential association with essential hypertension., Design: A case-control study in a random sample of the general population., Methods: CYBA polymorphisms were determined by restriction fragment length polymorphism and allelic discrimination. NADPH oxidase activity was quantified in phagocytic cells by chemiluminescence., Results: We identified three novel polymorphisms, at positions -852, -675 and -536 from the ATG codon. Only the -675(A/T) polymorphism associated with essential hypertension. The prevalence of the TT genotype and the T allele frequency were significantly higher (P < 0.05) in hypertensives than in normotensives. Furthermore, TT hypertensives exhibited higher (P < 0.05) systolic blood pressure values than TA/AA hypertensives. Increased phagocytic NADPH oxidase activity was observed in TT subjects compared to TA and AA individuals (P < 0.05). Enhanced carotid intima-media thickness, a surrogate marker of atherosclerosis, was found in TT subjects compared to TA and AA individuals (P < 0.05). Finally, mutagenesis experiments demonstrated a functional role of this polymorphism on the CYBA promoter activity., Conclusion: The -675 (A/T) CYBA polymorphism may be a novel genetic marker associated with essential hypertension. Furthermore, TT subjects exhibit features of NADPH oxidase-mediated oxidative stress and asymptomatic atherosclerosis.

Introduction and Objectives: The aims of this study were to determine the prevalence of atrial fibrillation in individuals aged 60 years or more in Spain using a random sample of the population and to identify associated factors., Methods: An analysis of the PREV-ICTUS study, a randomized cross-sectional population-based study of individuals aged 60 years or more, was carried out. Data on demographic variables, cardiovascular risk factors, and cardiovascular disease were obtained from medical records. The diagnosis of atrial fibrillation was based on the patient's medical history and an electrocardiogram performed during the study., Results: In the 7108 individuals studied (mean age 71.9 [7.1] years, 53.6% female), the prevalence of atrial fibrillation was 8.5% (95% confidence interval [CI] 7.9-9.2%). It was higher in males (9.3% vs 7.9% in females; P=.036) and increased from 4.2% in individuals aged 60-64 years to 16.5% in those aged 85 years or more (chi-squared test for linear trend, P< .001). Multivariate analysis showed that existing cardiovascular disease, hypertension, age, and left ventricular hypertrophy had the strongest associations with atrial fibrillation. Although there was a strong relationship between hypertension and atrial fibrillation (odds ratio 2.53, 95% CI, 1.60-4.01), no association was found between poor blood pressure control and atrial fibrillation. A weak association with diabetes mellitus was found only when arterial pressure was included in the model, but not when a diagnosis of hypertension was included., Conclusions: In this cross-sectional population-based study of elderly individuals, the prevalence of atrial fibrillation was 8.5%, and was strongly associated with existing cardiovascular disease, hypertension, age and left ventricular hypertrophy.

Antimalarial drugs are used for the control of mild manifestations of autoimmune diseases due to their low toxicity. Hydroxychloroquine (HCQ), a alpha-hydroxylated derivative of chloroquine, is usually preferred because of its higher tolerability. Mild and unspecific gastrointestinal symptoms are the main secondary effects related to HCQ use. Less than 1% of subjects show liver enzyme increase, although the percentage can be as high as 50% in subjects with chronic liver disease. A woman with mixed connective tissue disease who developed a reversible acute hepatitis shortly after the initiation of low-dose HCQ is presented. Two previous cases of patients with acute liver failure have previously been published. All three cases have been reported in the absence of previous liver disease. It seems to be a dose-dependent, idiosyncratic, and molecule-specific toxic effect and must be considered, taking into account the potential bad prognosis.

Unlabelled: The potential use of oxidative stress products as disease markers and progression is an important aspect of biomedical research. In the present study, the quantification of urine 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) concentration has been used to express the oxidation status of hypertensive subjects. 8-oxo-dG has been simultaneously isolated and assayed in nuclear (nDNA) and mitochondrial DNA (mtDNA). In addition, oxidative stress of mononuclear cells has been estimated by means of GSH and GSSG levels and GSSG/GSH ratio in hypertensive subjects before and after antihypertensive treatment. It is shown that oxidative stress decreases significantly in hypertensive patients after treatment the effect being accompanied by reduction of their blood pressure. A significant correlation is observed comparing the yield of urine 8-oxo-dG and that isolated from mitochondria DNA. Moreover, urinary excretion of 8-oxo-dG also correlates with the GSSG/GSH ratio of cells., Conclusion: urine 8-oxo-dG assay is a good marker for monitoring oxidative stress changes in hypertensives.

The objective was to assess the stroke risk and prevalence of the cardiovascular risk factors and to analyze their relationship with the specific stroke rates of mortality in each of the autonomic communities of Spain. We conducted a multicenter, cross-sectional study of population >60 years old in Spanish primary care centers. In all of the subjects, clinical, biochemical, and electrocardiographic data were obtained, and the 10-year stroke risk was calculated using the Framingham score. Mortality rates of stroke, age and sex adjusted, were obtained for each of the autonomic communities from the Ministry of Health. A total of 7343 subjects (mean age: 71.6 years, 53.4% women, 34.4% obese, and 27.1% diabetic subjects) were analyzed. A total of 73% were already diagnosed with hypertension. Among hypertensive subjects, 29.1% had blood pressure on therapeutic objective, and, of the total population, 35.7% had blood pressure under control. ECG-left ventricular hypertrophy was present in 12.9% of the subjects. The estimated stroke risk was 19.6%. Stroke mortality rates were significantly related to the estimated 10-year stroke risk (r=0.41; P<0.05) in each autonomic community. Poor hypertension control (P=-0.42; P<0.05) and prevalence of ECG-left ventricular hypertrophy (P=0.52; P<0.05) were the main factors related to the stroke mortality rates after controlling by age, sex, obesity, diabetes, and urban setting. Differences in stroke mortality throughout the autonomic communities of Spain were associated with indexes of worse blood pressure handling, low control rates, and high left-ventricular hypertrophy.

Endothelial dysfunction is the initial pathophysiological step in a progression of vascular damage that leads to overt cardiovascular and chronic kidney disease. Angiotensin II, the primary agent of the renin-angiotensin system (RAS), has a central role in endothelial dysfunction. Therefore, RAS blockade with an angiotensin receptor blocker (ARB) and/or angiotensin-converting enzyme (ACE) inhibitor provides a rational approach to reverse endothelial dysfunction, reduce microalbuminuria, and, thus, improves cardiovascular and renal prognosis. ARBs and ACE inhibitors act at different points in the RAS pathway and recent evidence suggests that there are differences regarding their effects on endothelial dysfunction. In addition to blood pressure lowering, studies have shown that ARBs reduce target-organ damage, including improvements in endothelial dysfunction, arterial stiffness, the progression of renal dysfunction in patients with type 2 diabetes, proteinuria, and left ventricular hypertrophy. The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) Programme is expected to provide the ultimate evidence of whether improved endothelial function translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartan, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade). Completion of ONTARGET is expected in 2008.

The aim of this study is to assess the relationship among metabolic syndrome (MS), target organ damage (TOD) and established cardiovascular disease (CVD) in non-diabetic hypertensive elderly patients. ERIC-HTA is cross-sectional, multicentre study carried out in primary care, on hypertensive patients aged 55 or older. MS was defined by the NCEP-ATP III criteria, using body mass index (>28.8 kg/m(2)) instead of abdominal perimeter. In 8331 non-diabetic hypertensive patients (3663 men and 4668 women, mean age 67.7 years), the prevalence of MS was 32.6% (men: 29.0%; women: 36.8%). A linear association was observed between a greater number of components of MS and a greater prevalence of left ventricle hypertrophy (LVH) on the electrocardiogram (p<0.001), impaired kidney function (p<0.001) and established CVD (p = 0.001). In a multivariate model, MS in non-diabetic hypertensive patients was related to a greater prevalence of LVH (OR 1.31 [95% CI: 1.15-1.48]), impaired kidney function (OR 1.45 [95% CI: 1.29-1.63]) and established CVD (OR 1.22 [95% CI: 1.08-1.37]). This relationship persisted after stratifying by gender. In conclusion, in this elderly non-diabetic hypertensive population, the presence of MS was independently related to a greater prevalence of hypertensive TOD and established CVD, suggesting a role of MS as a cardiovascular risk marker in hypertension.

The prevalence and significance of microalbuminuria in hypertensive patients with impaired fasting glucose (IFG) has received very little attention. A total of 10,320 hypertensive patients who attended primary care centers were enrolled in this study, and the final analysis was done in 7625 patients: 1459 without IFG (plasma glucose <100 mg/dl), 3010 with IFG (plasma glucose > or =100 mg/dl and <126 mg/dl), and 3156 with type 2 diabetes (plasma glucose >126 mg/dl). Microalbuminuria was determined using the Micro Albustix reactive strip from Bayer (high urinary albumin excretion [UAE]: Albumin/creatinine ratio > or =3.4 mg/mmol). The proportion of patients with high UAE was 39.4, 48.3, and 65.6%, respectively, in the three groups (P < 0.01 for the trend). The differences in UAE between the group with IFG and the group with normal fasting glucose persisted after adjustment for age, gender, systolic BP, fasting plasma glucose, and cardiovascular comorbidity (odds ratio 1.74; 95% confidence interval 1.08 to 2.80). Hypertensive patients with IFG and high UAE showed a higher prevalence of ischemic heart disease, cardiac insufficiency, left ventricular hypertrophy, atrial fibrillation, and renal insufficiency than the group with normal UAE. Global prevalence of cardiovascular conditions was 30.4% in the group with high UAE compared with 21.4% in the group with normal UAE (odds ratio 1.60; 95% confidence interval 1.31 to 1.95). It is concluded that almost half of hypertensive patients with IFG have high UAE and a higher prevalence of associated cardiovascular involvement and renal insufficiency.

Background and Objective: Measurement of blood pressure by using the auscultatory method coupled with mercury sphygmomanometer is rapidly being replaced for monitor using the oscillometric one. Discrepancies between the two methods and the factors related to them were analyzed in a large subset of adults., Material and Method: Blood pressure values were obtained sequentially in the same arm by using a mercury sphygmomanometer and a Spacelabs monitor devices. The relationship between both kinds of measurements was assessed by the Pearson's correlation coefficients and the concordance by using the Bland and Altman method. Differences between the two methods were calculated and the factors related to the differences were sought by multiple regression models., Results: A total of 1,742 adult subjects were analyzed. Pearson's correlation coefficients were 0.927, 0.922, 0.886, 0.962 for SBP, DBP, MBP and PR, respectively. Oscillometric method overestimate and infraestimate SBP values in the two extreme of SBP values, the lowest SBP the highest the values and vice versa. A similar trend was observed for DBP although the differences were minor. Pulse wave amplitude explains the 24% of the variance observed for SBP and arm circumference the 8% for DBP., Conclusions: Blood pressure values measured by oscillometric methods are influenced for pulse wave amplitude and by the arm circumference. These need to be taken in account when blood pressure assessment is obtained by using this method.

Introduction and Objectives: Left ventricular hypertrophy (LVH) is the earliest manifestation of cardiac damage in hypertension. Its appearance is associated with a poor cardiovascular prognosis. The objectives of this study were to determine the prevalence of electrocardiographic LVH and to assess the epidemiological characteristics of hypertensive patients receiving primary care., Patients and Method: A cross-sectional multicenter study of hypertensive patients aged 55 years or more was carried out in a primary care setting. Blood pressure was measured using the standard method. Cardiovascular history was determined from medical records and LVH was assessed electrocardiographically using Cornell's criteria., Results: In total, 15 798 patients (mean age 68.0 years, 55.3% women, and 30.4% with diabetes mellitus) were evaluated. Of these, 3207 (20.3%) had electrocardiographic signs of LVH. The prevalence was higher in males, diabetics, smokers, and patients with high blood pressure or renal or cardiovascular disease. Compared to patients without LVH, those with the condition were older, were more often male, and were more likely to have diabetes or renal or cardiovascular disease. Multivariate analysis showed that LVH was independently associated with advanced age, male gender, diabetes, smoking, poor blood pressure control, and the presence of cardiovascular or renal disease. Blood pressure control was poorer in patients with LVH than in those without it., Conclusions: The prevalence of electrocardiographic LVH is high, with affected patients being more likely to have diabetes or renal or cardiovascular disease. Moreover, blood pressure control is poor in these patients, and more aggressive pharmacological management is needed.

Stroke is the leading cause of mortality in women in Spain. RIMHA is a cross-sectional multicenter study in hypertensive women aged 55 or more in primary care to estimate the 10-year risk for a first stroke. Clinical history, cardiovascular risk factors and diseases, electrocardiogram, blood samples and blood pressure (BP) were recorded. Stroke and coronary risk were estimated using the appropriate Framingham scales; 12875 patients were included (mean age 68.0+/-8.5 years, 29.1% with diabetes, 19.7% with cardiovascular disease). Electrocardiographic left ventricular hypertrophy (LVH) was present in 19.2% BP was controlled in 42.9% of non-diabetic (BP<140/90 mmHg) and 9.7% of diabetic patients (BP<130/80 mmHg). The 10-year risk (+/- SD) for a first stroke was estimated as 15.8+/-16.3%, and the coronary risk as 12.0+/-6.3. In the multivariate analysis, the most contributing factors for stroke risk estimation were age, systolic BP, LVH and atrial fibrillation. In conclusion, the 10-year estimated stroke risk for Spanish hypertensive women aged 55 years or more was higher than the estimated coronary risk, in accordance with the high rates of morbidity and mortality due to stroke among women in Spain. The most powerful risk factors were older age, poor BP control, LVH and atrial fibrillation.

Experimental evidence and observations in humans strongly support an interactive role of mutated alpha-adducin, sodium (Na(+))/potassium (K(+))-adenosine triphosphatase (ATPase) activity and endogenous ouabain in Na(+) homeostasis and the pathogenesis of hypertension. The Ouabain and Adducin for Specific Intervention on Sodium in HyperTension (OASIS-HT) trial is an early Phase II dose-finding study, which will be conducted across 39 European centers. Following a run-in period of 4 weeks without treatment, eligible patients will be randomized to one of five oral doses of rostafuroxin consisting of 0.05, 0.15, 0.5, 1.5, or 5.0 mg/day. Each dose will be compared to a placebo in a double-blind crossover experiment with balanced randomization. Treatment will be initiated with the active drug and continued with placebo or vice versa. Each double-blind period will last 5 weeks. The primary end point is the reduction in systolic blood pressure defined as the average of three clinic readings with the patient in the sitting position. Secondary end points include the reduction in diastolic blood pressure on clinic measurement, the decrease in the 24-h blood pressure, and the incidence of end points related to safety. Secondary objectives are to investigate the dependence of the blood pressure-lowering activity on the plasma concentration of endogenous ouabain and the genetic variation of the enzymes involved in the metabolism of this hormone, and the adducin cytoskeleton proteins. Eligible patients will have Grade I or II systolic hypertension without associated conditions and no more than two additional risk factors. In conclusion, OASIS-HT is a combination of five concurrent crossover studies, one for each dose of rostafuroxin to be studied. To our knowledge, OASIS-HT is the first Phase II dose-finding study in which a genetic hypothesis is driving primary and secondary end points.

Background and Objective: Stroke is a major cause of morbidity and mortality in hypertensive population. The aim of this study is to estimate the 10-year risk of a first stroke in Spanish hypertensive population using the Framingham scale., Patients and Method: Cross-sectional multicenter study in primary care environment, on hypertensive patients aged 55 or more (10 consecutive patients each physician). Blood pressure (BP) was measured according to standardized rules. Stroke and coronary risk were estimated using the Framingham scale., Results: 16,129 patients (mean age 67.7 years; 57.1% women; 30.4% with diabetes mellitus; 26.6% with previous history of cardiovascular disease) were analyzed. 20.3% showed electrocardiographic left ventricular hypertrophy (more prevalent in males, diabetics, with systolic BP > or = 140 mmHg; p < 0.001). The goal of BP control was reached in 30.1% of non-diabetic patients and only in 5.9% of diabetics. The estimated 10-year risk of a first stroke (standard deviation) was estimated to be 19.9% (16.8), and the coronary risk 19.2% (14.0). While males had an estimated risk of coronary disease above the stroke risk, women had an estimated risk of a first stroke greater than the estimated risk of coronary disease., Conclusions: The estimated risk of stroke among Spanish hypertensive population is high, and the main risk factors (age, systolic BP, diabetes and left ventricular hypertrophy) tend to aggregate. In women estimated risk of stroke in greater than estimated coronary risk. The risk of stroke must be taken into account in the assessment and treatment of hypertensive patients.

The objective was to study factors related to the changes induced by antihypertensive treatment on oxidative status, antioxidant activities, and reactive oxygen species by-products in whole blood and mononuclear peripheral cells. Eighty-nine hypertensive patients (mean age 46 years, 46 men, average 24-h blood pressure 139/88 mm Hg, body mass index 29) were included. After 3 months of nonrandomized allocation to antihypertensive treatment (20 nonpharmacologic, 36 beta-blockers, 33 angiotensin receptor blocker), oxidized/reduced glutathione ratio and malondialdehyde were significantly reduced, and the activity of superoxide dismutase, catalase, and glutathione peroxidase was significantly increased in both whole blood and peripheral mononuclear cells. The content of damaged base 8-oxo-2'-deoxyguanosine in nuclear and mitochondrial DNA in hypertensive subjects was also significantly reduced during the antihypertensive treatment. In a group of 42 subjects, the oxidative stress was further reduced and the antioxidant enzyme activities further increased after 12 months of antihypertensive treatment. The changes were independent of the kind of antihypertensive treatment. In conclusion, antihypertensive treatment improved the increased oxidative stress and the decreased antioxidant mechanisms. It is independent of the type of treatment and the beneficial effect of treatment increases over time., (Copyright 2004 American Journal of Hypertension, Ltd.)

Background and Objective: Although renal pathologies are becoming an emergent problem in the population infected by the human immunodeficiency virus (HIV), there is very scarce information about the natural course of this problem. The objective of the present study is to describe renal lesions in an autopsy series of HIV-infected patients never treated with antiretroviral therapies., Patients and Method: Autopsy information has been retrospectively retrieved from 61 HIV-infected subjects (mean age, 36,9 [8,4] years; 58,6% drug abusers, 84% males) died in our hospital between 1984 and 1997. None of the patients received antiretroviral therapy. All autopsy and clinical reports were considered, as well as basic analytical parameters about renal function. Renal autopsy samples were specifically reviewed., Results: At the time of the last admission, 9.8% of patients had renal insufficiency, who made up 44.3% of patients having renal insufficiency anytime. Infections were the main cause of death (76%). The majority of patients (93.4%) showed histopathological renal abnormalities, which were highly heterogeneous. Renal lesions were mainly located on the tubules (96.7%) and the interstitium (60.7%). Moreover, glomeruli were affected in 55.7% of patients. Most frequent histopathological diagnosis was acute tubular necrosis (16.4%) and septic nephritic abscesses (16.4%), followed by tubulointerstitial nephritis (9%). HIV-associated nephropathy was present in two patients (3.3%). There were no significant differences when considering the existent of renal failure., Conclusions: Renal histological abnormalities are frequent in the natural evolution of HIV infection. There is an important heterogeneity of lesions, mainly involving tubules, interstitium and mesangium. The cause of renal lesions is predominantly septic, according to the chief systemic process. It does not exist any relationship between renal analytical parameters and the presence of renal damage.

The objective was to study oxidative status, antioxidant activities, and reactive oxygen species byproducts in whole blood and mononuclear peripherals cells and their relationship with blood pressure. Sixty-six hypertensive patients and 16 normotensive volunteers as a control group were studied. In both, whole blood and peripheral mononuclear cells oxidized/reduced glutathione ratio and malondialdehyde was significantly higher, and the activity of superoxide dismutase, catalase, and glutathione peroxidase was significantly lower in hypertensive patients when compared with normal subjects. The content of damaged base 8-oxo-2'-deoxyguanosine in nuclear and mitochondrial deoxyribonucleoproteins of hypertensive subjects was also significantly higher than that of the normotensive control subjects. No differences in these measurements were found among hypertensive subjects grouped in tertiles of 24-hour average mean blood pressure or between "white-coat" and established hypertensive subjects. Furthermore, no relationship was observed between the average of 24-hour mean blood pressure and oxidized/reduced glutathione ratio, reactive oxygen species byproducts, malondialdehide, or genomic 8-oxo-2'-deoxyguanosine. In whole blood and in mononuclear cells from hypertensive subjects, there was an increase in oxidative stress and a reduction in the activity of antioxidant mechanisms that appeared to be independent of the blood pressure values.

Background and Objective: We aimed to assess the blood pressure (BP) control in patients with diabetes mellitus (DM) treated in primary care (PC) and to establish the factors associated with a suboptimal control of BP., Patients and Method: This was a multicenter, transverse study. Ninety investigators included 875 patients with DM (57.8% women), with a mean (SD) age of 64 (11.8) years. BP was measured according to the Sixth Report of Joint National Committee (JNC-VI) and Word Health Organization/International Society Hypertension (WHO/ISH) recommendations, calculating the arithmetic mean of three consecutive measurements. Patients with a previous established diagnosis were considered to be hypertensive, and an optimal control was considered when BP values were lower than 130/85 mmHg., Results: 66.7% (n = 583) patients with DM were previously diagnosed of hypertension (HT); 86.3% (CI 95%: 83.0-89.1) of those with type 2 DM and 87.8% (CI95%: 70.9-96.0) of those with type 1 DM did not have an optimal control of BP at the visit (BP >= 130 and/or 85 mmHg). 56.8% (CI 95%: 50.1-63.3) of those with type 2 DM and 23.8% (CI 95%: 12.6-39.8) of those with type 1 DM with unknown HT had a BP >= 130 and/or 85 mmHg at the visit. The median of antihypertensive drugs used was 1 (1-2). In a multivariate analysis, age, higher body mass index (BMI), higher cholesterol levels and uric acid were associated with a worse BP control (p < 0.001)., Conclusions: In our study, 66.7% of patients with DM attended in PC had known HT and only 13.6% had an optimal BP control. Diabetic patients with HT were undertreated, with a median of one antihypertensive drug.

The objective of the present study was to assess central aortic pressure and wave reflection in children and adolescents at different birth weights. Two hundred nineteen healthy children (126 girls), from 7 to 18 years of age (mean, 11.3 years) and born at term after a normotensive pregnancy, were included. The subjects were divided according to birth weight: <2.5 kg, from 2.5 to 2.999 kg, from 3.0 to 3.5 kg, and >3.5 kg. Pressure waveforms were recorded from the radial artery of the wrist, and the waveform data were then processed by the SphygmoCor radial/aortic transform software module to produce the estimated aortic pressure waveform. Augmentation index, an estimate of the pulse wave reflection, was significantly higher in children with the lowest birth weights compared with the other birth weight groups. In a multiple regression analysis, short stature, low heart rate, female gender, and lower birth weight had independent significant inverse correlations to the augmentation index when adjusted for diastolic blood pressure (R2=0.21). In summary, the results showed a relatively aged phenotype of large-vessel function in the children with the lowest birth weights. These early alterations may be amplified throughout life and may contribute to the increased cardiovascular risk associated with low birth weight.

Reversible posterior leukoencephalopathy syndrome (RPLS) is an uncommon entity related to multiple and different pathologies, the most common being hypertensive crisis. It is believed to be secondary to the breakdown on the blood-brain barrier. At the beginning, it is undistinguishable from other leukoencephalopathies. However, the disappearance of brain lesions after removal of the potential cause, establish the differential diagnosis with other leukoencephalopathies. We present the case of an HIV-infected patient with a RPLS related to a hypertensive crisis short after the initiation of indinavir-containing highly active antiretroviral therapy. Once blood pressure was controlled and indinavir replaced by nelfinavir, white matter lesions at magnetic resonance imaging disappeared. The clinical and radiologic evolution excludes other diagnosis as progressive multifocal leukoencephalopathy and points indinavir as a potential hypertension-inducing agent in HIV-infected predisposed subjects.

Background: The renin-angiotensin system (RAS) is known to regulate the blood pressure (BP). Several RAS polymorphisms have been associated with essential hypertension (EH), but there is uncertainty about this association. We examined whether the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene, and the M235T polymorphism of the angiotensinogen (AGT) gene were associated with EH in a sample of Spanish hipertensive patients., Patients and Method: We studied 1,204 patients with EH (BP > 140/90 mmHg): 668 males, aged 50.8 (13.6) years with systolic BP 151.7 (19.1) and diastolic BP 94.3 (13) mmHg [mean (SD)] and 536 females, aged 52.4 (13.9) years with systolic BP 155.1 (19.8) and diastolic BP 94.5 (12.3) mmHg. As a control group, 367 men and 280 women with no family history of cardiovascular disease who had a normal blood pressure were included. Polymorphisms were determined by PCR amplification of genomic DNA, followed by enzyme digestion for the AGT gene polymorphism., Results: The genotype distribution and allele frequencies of the two RAS polymorphisms were similar in hypertensive and control subjects. Similarly, there were no differences in BP level with regard to the genotype in male or female patients. In addition, we did not find any compound effect of the I/D ACE gene and M235T AGT gene polymorphisms on BP levels in hypertensive subjects., Conclusions: This study suggests that in the population studied, the contribution of the ACE I/D polymorphism and the AGT M235T polymorphism in the development of EH is less important than previously estimated.