This study aims to test the hypothesis that in some hypertensive subjects the blood pressure (BP) response to angiotensin-converting enzyme inhibition differs from that to angiotensin receptor blockade (ARB); a responder to angiotensin-converting enzyme inhibition may not respond to ARB or the opposite. A randomized, open-label, crossover, comparative trial of lisinopril 20 mg compared with telmisartan 80 mg (5 weeks per treatment period) was conducted in 32 untreated hypertensives using 24-hour ambulatory BP monitoring. Subjects were classified as "responders" and "nonresponders" using an arbitrary threshold of ambulatory BP response (> or =10 mm Hg systolic or > or =5 diastolic) or the median response achieved by each drug. No difference was detected between the drugs in their effect on ambulatory BP (mean difference 1.2+/-7.1/0.7+/-5.1 mm Hg, systolic/diastolic). Significant correlations were found between the antihypertensive responses to the two drugs (r=0.77, p<0.001). Using the arbitrary response criterion, there was a difference between the drugs in the responses in 28%/13% of subjects (9/4 patients) for systolic/diastolic BP (19%/25% using the median response criterion). These data suggest that in some hypertensive patients the BP response to angiotensin-converting enzyme inhibition may fail to predict the response to ARB. It appears that there are differences in the antihypertensive action of angiotensin-converting enzyme inhibitors and ARBs that may be clinically important.

Office and out-of-office blood pressure measurements are being used for the diagnosis of hypertension in children and adolescents. The US National Heart, Lung, and Blood Institute have recently presented a new classification of blood pressure. On the basis of office measurements the 90th, 95th and 99th percentile for gender, age and height are used to classify children and adolescents as normotensive, pre-hypertensive and stage-1 or stage-2 hypertensive. Although auscultation using a standard mercury sphygmomanometer remains the recommended method, accumulating evidence suggests that ambulatory blood pressure monitoring is useful for the detection of white-coat hypertension and the prediction of target organ damage in children and adolescents. Studies have shown ambulatory blood pressure to be more reproducible than office measurements and normative tables for ambulatory measurements have been developed from cross-sectional studies in children and adolescents. In regard to home measurements in children, there are limited data from small trials showing lower blood pressure levels than daytime ambulatory blood pressure. In conclusion, ambulatory blood pressure monitoring is already finding a role as a supplementary source of information in children and adolescents, whereas at present home measurements should not be used for decision making in this population.

Is an important adjunct to clinic measurements

Systolic blood pressure is a major cardiovascular risk factor which is often associated with arterial stiffness. Markers of arterial stiffness, such as pulse pressure and carotid-femoral pulse wave velocity, have been proved independent predictors of cardiovascular risk. Recent evidence suggests that the renin-angiotensin system is involved in the pathogenesis of systolic hypertension and arterial stiffness. Outcome trials have shown impressive cardiovascular protection by reducing systolic blood pressure (BP) with drug treatment. However, in clinical practice systolic hypertension remains largely uncontrolled, first, because systolic BP goal is more difficult to be reached than diastolic and, second, because physicians are often reluctant to intensify treatment in patients with systolic BP close to 150 mmHg. Recent trials have focused on the effects of antihypertensive drugs not only on blood pressure, but also on pulse pressure and pulse-wave velocity. Blockade of the renin-angiotensin-aldosterone system, using angiotensin-converting enzyme inhibitors and more recently angiotensin receptor blockers, has been shown to provide beneficial effects on arterial stiffness that appear to be independent of their antihypertensive effects. Recent outcome trials have shown significant cardiovascular protection with angiotensin receptor blockers. These drugs have an excellent placebolike profile of adverse effects which is maintained when these drugs are combined with low-dose diuretics. Therefore, an angiotensin receptor blocker-based treatment strategy appears to be an attractive and evidence-based approach for the management of systolic hypertension, the reduction of arterial stiffness and the prevention of cardiovascular disease.

Hypertension is a leading cause of morbidity and mortality worldwide and its control rates remain poor. In 2003, several official organizations presented new guidelines for hypertension management. These guidelines were developed using an evidence-based interpretation of the available information. Recommendations on hypertension prevention, diagnosis, patients' evaluation, decision to treat, antihypertensive drug selection and goals of treatment are included. There is considerable agreement among the new guidelines and only a few points of disagreement, that are of minor significance. Emphasis has been placed on the simplicity of recommendations in order for them to be easily applied by primary care physicians. This review focuses on the key messages of the 2003 guidelines and the areas of agreement and disagreement among them.

The development of drugs which block the renin-angiotensin system (RAS) has been proven a major advance in cardiovascular medicine. Angiotensin converting enzyme (ACE) inhibitors, which block the formation of angiotensin II from the inactive angiotensin I, are widely used as first line treatment in hypertension, heart failure and diabetic nephropathy. More recently, selective antagonists of the angiotensin type-1 receptor (AT1R) have become available for clinical use. Accumulating evidence suggests that AT1R antagonists have similar effects to ACE inhibitors in hypertension, heart failure and diabetic nephropathy. Although ACE inhibitors and AT1R antagonists block the same system, experimental evidence suggest that their mechanisms of action differ in several respects, such as increased bradykinin and angiotensin 1-7 levels with ACE inhibitors and AT2R activation with AT1R antagonists. Nevertheless, the clinical significance of these differences remains largely unknown and, in practice, the only clear advantage of AT1R antagonists over ACE inhibitors is the absence of cough as a side effect. Recent clinical data suggest that combined ACE inhibition and AT1R antagonism offer additive effects in reducing blood pressure in hypertension, in reducing proteinuria in nephropathy and in improving prognosis in heart failure. Further evidence suggests that some hypertensive patients may have a good antihypertensive response with ACE inhibition but not with AT1R antagonism, or the reverse. These data suggest that these two drug classes have important similarities, because they act on the same system, but they also appear to have important differences, which are not only of theoretical but also of clinical importance.

An algorithm has been proposed for the detection of white coat hypertension among subjects with elevated blood pressure (BP) on at least three clinic visits using home BP monitoring (screening test) and, if this is low, ambulatory BP monitoring (diagnostic test). This study aims to test this strategy in practice. The proposed algorithm was applied in 133 untreated subjects with elevated BP assessed in a previous prospective study using repeated clinic, home and ambulatory BP measurements. The proportions of detected and missed cases of white coat hypertension and the diagnostic value of the algorithm were calculated. By applying the algorithm, 99 subjects (74%) were found eligible for home measurements and 35 (26%) for ambulatory monitoring. There were 38 subjects with white coat hypertension (38%), of whom 15 (39%) were not detected by the proposed strategy. The sensitivity, specificity, and the positive and negative predictive value of the algorithm to diagnose white coat hypertension were 61, 81, 66 and 77%, respectively. Of the 34 subjects with normal BP on the third clinic visit, 15 (42%) had elevated home and/or ambulatory BP. These data suggest that, using the proposed strategy, many white coat hypertensives may remain undetected and may receive unnecessary long-term drug treatment. Therefore, more research is needed on the optimal strategy for detecting white coat hypertension in clinical practice.

Based on outcome trials, guidelines for hypertension management recommend lower blood pressure (BP) goals using an individualized treatment strategy (IND) and referral to a specialist of patients uncontrolled after 6 months of treatment. This study aimed to evaluate the performance of General Practitioners (GPs) in reaching the recommended BP goals using the IND, or a stepwise treatment strategy (STEP) as used in the outcome trials. Trained GPs were randomized to reach the BP goals within 6 months using the IND or a STEP strategy in untreated or treated uncontrolled hypertensives. In all, 24 GPs recruited 528 patients of whom 443 were analysed (mean age 65+/-9 years, 42% men, 70% treated, STEP/IND 12/12 GPs, 231/211 patients). After 6 months, 83% of the patients had reached the diastolic BP goal, whereas only 51% the systolic (P<0.0001 for difference). Factors associated with uncontrolled systolic BP were diabetes, age >60 years and triple antihypertensive therapy at baseline. A faster BP reduction was achieved during the first 3 months using the STEP strategy, but at the cost of using more drugs (combination therapy in 68/59% for STEP/IND, P=0.06). At 6 months similar rates of control were achieved with the two strategies. In conclusion, in primary care the diastolic BP goal can be reached within 6 months in the majority of patients, whereas systolic BP remains uncontrolled in 50% of the cases. The IND should be the recommended treatment strategy, but further investigation is required on the reasons for treatment failure and the optimal strategy for its improvement.

The terms 'self-blood pressure' and 'home blood pressure' are being used to describe measurements of blood pressure taken by the patients at home. However, home measurements are not always self-measurements, because these are often taken by the patients' relatives. There is little evidence on the effect of self-measurement on the level of blood pressure taken using automated electronic devices. In regard to clinic blood pressure, two studies using automated devices found no difference between measurements taken by physicians or patients themselves, irrespective of whether self-measurements were taken in the presence or the absence of the physician. In regard to home blood pressure, one randomized crossover trial showed no difference between home measurements taken by the patients themselves or their relatives using fully automated devices. On the other hand, many studies have consistently shown home blood pressure to be lower than clinic pressure. Taken together these data suggest that self-measurement has no effect on the level of blood pressure, either in the clinic, or at home. The lower level of home in comparison to clinic blood pressure seems to be exclusively attributed to the effect of the different setting, rather than the person who is taking measurements. Therefore the term 'self blood pressure' seems to be a misnomer, whereas the term 'home blood pressure' represents a more appropriate term for home measurements taken by patients or their relatives.

The Ty1- copia-like retrotransposon is one of the commonest class of transposable elements in the plant kingdom, often comprising several percent of the total DNA content. We aimed to study the evolutionary relationships of Olea retroelements, using part of the reverse transcriptase domain, as well as the genomic and chromosomal organization of these sequences in Olea europaea chromosomes and their transcription activity and copy number. Fourteen clones, that were isolated from four different species, were sequenced and a phylogenetic tree was constructed based on their predicted amino acids. Five clones derived from O. europaea were clustered together with a 87% nucleotide sequence homology and two Olea oleaster clones showed 98% sequence homology. The rest of the clones showed heterogeneity among them, leading to a common ancestral transposon that existed before the genus arose. The Ty1- copia-like sequences have a dispersed genomic organization, physically distributed on all chromosomes, showing minor clustering in some cases and low copy numbers in the smallest chromosome pair. The total copy number in the O. europaea genome was estimated by dot blotting to be 40,000 in a haploid nucleus, but a number of these are non-functional since the sequenced clones contained stop codons and frame-shifts. Some Ty1- copia-like copies, present in O. europaea, were found to be methylated, while no differences in methylation were observed between DNA isolated from young leaves and callus-suspension cultures.