The purpose of this study was to compare several diltiazem-based antihypertensive drug combinations and assess the usefulness of home blood pressure monitoring in the evaluation of the efficacy of combination pharmacotherapy. Sixteen general practitioners recruited hypertensive subjects uncontrolled on diltiazem monotherapy, who were randomized to receive eight weeks of add-on therapy with a diuretic (chlorthalidone), a dihydropyridine calcium antagonist (felodipine), an ACE inhibitor (lisinopril), or an angiotensin blocker (valsartan). Sitting office and home blood pressure was measured using electronic devices A&D 767. A total of 211 patients were randomized, and 185 completed the study. Of 52 subjects randomized to felodipine, 15 were withdrawn due to ankle edema. The additional antihypertensive effect of the second drug was smaller in 18 subjects with a white coat effect (p < 0.01). All combinations produced a significant decline in office (21.2 +/- 14.8 / 7.7 +/- 9.7 mmHg) and home (17.1 +/- 11.9 / 6.0 +/- 7.0) blood pressure (systolic / diastolic, p < 0.001). There were no differences in the efficacy of the four combinations assessed using office or home blood pressure monitoring. These data suggest that diuretics, dihydropyridines, ACE inhibitors, and angiotensin receptor blockers provide significant additional antihypertensive effects in hypertensive patients uncontrolled on diltiazem monotherapy. The diltiazem-dihydropyridine combination is often intolerable because of ankle edema. Home blood pressure monitoring is useful in the assessment of the efficacy of combination pharmacotherapy and also allows for the detection of subjects who do not require treatment intensification.

The use of ambulatory blood pressure monitoring in addition to the conventional office measurements makes possible the detection of individuals with white-coat hypertension and masked hypertension. In children referred for elevated blood pressure, both these phenomena appear to be common (10-15% for each). In a population of healthy children, white-coat hypertension appears to be as common as hypertension, whereas masked hypertension appears to be more common than white-coat hypertension or hypertension. In children with persistent white-coat or masked hypertension, assessment of target organ damage by echocardiography is required. Preliminary evidence suggests that, in contrast to white-coat hypertension, which is not associated with target organ damage, masked hypertension in children is associated with increased left ventricular mass. Children with masked hypertension should be followed up and possibly treated for hypertension if the phenomenon persists or there is evidence of target organ damage.

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.