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Obesity and overweight are nowadays very prevalent worldwide. They are known to be linked with an increased risk of developing cardiovascular comorbidities and mortality. Abdominal obesity is frequently associated with a collection of metabolic disorders that include elevated blood pressure, characteristic lipid abnormalities (low high-density lipoprotein cholesterol and high triglycerides) and increased fasting glucose, with an underlying situation of insulin resistance, which has been defined as metabolic syndrome, conferring a high cardiovascular risk profile to these subjects. A multidisciplinary approach is required, including lifestyle changes and pharmacological and surgical approaches. Intensive management of all the risk factors of the metabolic syndrome is also needed to reduce body weight and waist circumference, lessen insulin resistance and avoid the development of new-onset diabetes and cardiovascular disease associated with this entity. This article will review the recently published literature and guideline updates on this topic, although it is not yet included in the highlights.

The evaluation of patients with resistant hypertension should be directed toward confirming true treatment resistance, identifying the causes contributing to treatment resistance (including secondary causes of hypertension), and documenting target-organ damage. Treatment of resistant hypertension is aimed at reversing lifestyle factors contributing to treatment resistance, accurately diagnosing and appropriately treating secondary causes of hypertension, and effectively using multidrug regimens. Lifestyle changes, pharmacologic therapies, and nonpharmacologic therapies have all shown benefits in patients with resistant hypertension, but much additional knowledge is needed to better identify and treat these patients.

Chronic kidney disease is a leading global health problem with an increasing prevalence. Hypertension is present in most patients with chronic kidney disease, and hypertension-related nephrosclerosis is a top cause of progressive renal damage and end-stage renal disease. Systolic blood pressure (BP) and pulse pressure, together with nocturnal BP, are the most important factors favoring the progression of renal failure. Consequently, strict control of BP and other cardiovascular risk factors is required, including an adequate degree of suppression of the renin-angiotensin system in every patient.

Resistant hypertension, commonly described as the failure to achieve goal blood pressure (BP) despite an appropriate regimen of three antihypertensive drugs at the maximal tolerated doses, one of which is diuretic, is increasingly recognized as an important problem of public health. Large population studies with office measurements suggest that the prevalence of resistance hypertension is approximately at 6-12 % of the general hypertensive population and 8-28 % of treated hypertensives. However, these estimations do not take into account factors of pseudo-resistance, most importantly, the white-coat effect that can be effectively ruled out with ambulatory blood pressure monitoring (ABPM). Recent studies have clearly shown that when ABPM is used, at least 30-35 % of patients labeled as "resistant hypertensives" turn out to have well-controlled BP on ambulatory basis, a finding changing entirely the estimates of prevalence of resistance hypertension and actual patient handling. Furthermore, current evidence suggests that ABPM is a much more accurate predictor of cardiovascular events in resistant hypertension compared to office BP and thus can offer a better risk stratification for these high-risk individuals. Finally, ABPM offers the potential of a better evaluation of the effect of pharmacologic and non-pharmacologic therapeutic interventions. This review attempts to summarize recent evidence on the advantages of ABPM in the diagnosis, prognosis, and management of resistant hypertension.

Indices of altered renal function (eg, microalbuminuria, increased serum creatinine concentration, or decrease in estimated creatinine clearance, particularly overt proteinuria) are independent predictors of cardiovascular morbidity and mortality. These parameters should be routinely evaluated in the elderly and in high cardiovascular risk populations, particularly when hypertension is present. Hypertensive kidney damage should be prevented by early aggressive treatment of hypertensive patients with microalbuminuria. To avoid further aggravation of high cardiovascular risk, antihypertensive agents devoid of unwanted metabolic side effects should be used. Epidemiologic information suggests that renal and cardiovascular outcome run parallel in this segment of the population.

The attainment of adequate renal protection requires strict blood pressure control and a diminution of proteinuria or microalbuminuria to values as near from normalcy as possible. It has been considered that by getting the first, the second could be attained at the same price. Recent data have confirmed that renal protection in hypertensive patients, diabetics or not, requires combination therapy that has to include an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker. A calcium channel blocker can be added to this without renal compromise. A diuretic will also be needed in most cases. Proteinuria will diminish with this combination in particular if up-titration of the drug blocking the effects of angiotensin II is performed. The control of other associated risk factors is also required, in particular smoking and lipids.

Increased serum urate concentration is commonly seen in clinical practice. It does not represent a specific disease, nor is it an indication for therapy. Hyperuricemia can be the consequence of increased uric acid production and/or decreased renal capacity to excrete uric acid. In essential hypertension, it has been described in up to one third of patients and is directly related to an increase in renal vascular resistance and inversely correlated with renal plasma flow. In other words, abnormal renal hemodynamics, commonly seen in the initial stages of the disease, account for the increased serum urate concentration. This can be maintained if a decrease in glomerular filtration rate takes place. The increase in uric acid has been shown to be a potent predictor of the development of cardiovascular events and death. In addition, uric acid, particularly when elevated, could represent an independent risk factor. On the other hand, an altered renal function predicts in an independent manner a higher cardiovascular risk. For this reason, the predictive capacity of uric acid could be partly dependent on the fact that hyperuricemia runs in parallel with a deranged renal function.

Chronic renal failure, proteinuria, and arterial hypertension run in parallel in the presence of diabetic nephropathy. New goal blood pressure levels have been established in diabetic patients: 130/85 mm Hg and 125/75 mm Hg depending on the level of proteinuria being below or above 1 g/d. New and lower threshold blood pressure (> 130/85 mm Hg) to initiate pharmacologic therapy is required in the presence of diabetes mellitus in order to facilitate the strict blood pressure control that is required. It must be considered that both renal and cardiovascular protection are obtained with strict blood pressure control, which otherwise seems to require blockade of angiotensin II effects when proteinuria above 1 g/d is present. While awaiting the publication of long-term follow-up studies looking at renal and cardiovascular outcome in diabetic and other nephropathies in which calcium channel blockers are compared with other antihypertensive drugs, calcium channel blockers will remain the drugs needed to attain the expected goal blood pressure in diabetics, both alone (in the absence of microalbuminuria or macroalbuminuria) or in combination, particularly with angiotensin converting enzyme inhibitors.

Lowering blood pressure by pharmacologic intervention reduces the incidence of cardiovascular events. Nevertheless, despite the widespread availability of effective antihypertensive medications, the vast majority of hypertensive patients worldwide continue to have inadequate blood pressure control. The development of new antihypertensive drugs could contribute to improving the hypertension control rate, and the blockade of new pathophysiologic pathways involved in blood pressure regulation would offer additional benefits. The dual inhibition of the angiotensin II receptor and neprilysin could provide clinical benefits in a range of cardiovascular diseases, including hypertension and heart failure.

Introduction In June 2007, the European Society of Hypertension and the European Society of Cardiology published the new joint edition of the European Guidelines for the Management of Arterial Hypertension [ 1 , 2 ]. New editions of guidelines must be well received, considering that application of their recommendations will improve our clinical practice. This article briefl y reviews some aspects of the new guidelines: why they were needed, revisions since the previous version, and how their recommendations can help improve blood pressure control.

Recent data suggest that patients at risk for development of type 2 diabetes can be identified in clinical practice. Physicians should take notice of the presence of several characteristics related to the development of diabetes when they select long-term medications devoted to CV protection for these patients. An adequate drug selection can avoid metabolic complications that lead to the development of diabetes during the long-term follow-up of high-risk patients. In grade 1 or recent-onset hypertension, it could be useful to search for the metabolic syndrome, using the newer drugs to reduce the blood pressure and to prevent the development of diabetes. Large-scale clinical trials specifically designed to assess the benefits of pharmacologic therapies in individuals who are at risk for developing type 2 diabetes, such as the DREAM study, the NAVIGATOR trial, or the SCOUT study, should contribute to highlighting the role of pharmacologic strategies in preventing the development of diabetes in prediabetic patients.

The inhibition of the effects of angiotensin II is necessary to ensure the best degree of renal protection by the simultaneous control of blood pressure (BP) and the achievement of the maximal antiproteinuric capacity. The inhibition can be attained through the administration of either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB). Uptitration of antihypertensive therapy is frequently required to achieve the desired BP goal in patients presenting with renal disease, with or without proteinuria. Control of BP is good for both cardiovascular and renal protection. Sometimes, in particular when BP levels are high in the absence of therapy, the simple control of BP without inhibiting the renin- angiotensin system can be accompanied by a significant drop in proteinuria. On the other hand, the possibility that an ACE inhibitor or an ARB diminishes protein excretion in urine in the absence of changes in BP has been considered after the known evidence that these classes of drugs are renoprotective independently of their effect on BP control. The aim of this paper is to briefly review the evidence in favor of uptitration of either class of inhibitors of the renin-angiotensin system as compared with the combination of the two for the control of either BP or proteinuria.

There is incontrovertible evidence that association of type 2 diabetes with hypertension markedly increases the risk of cardiovascular events, death, and nephropathy. In type 2 diabetes, even blood pressure values usually considered below the threshold for hypertension (ie, 140/90 mm Hg) in nondiabetic subjects represent an additional risk of clinical relevance. Evidence that more intensive blood pressure lowering is beneficial in type 2 diabetes over less intensive lowering is also overwhelming. However, most published trials show the need for combination therapy in the great majority of patients, and even with combination therapy it is difficult to attain the expected goal blood pressure, in particular goal systolic blood pressure. It should be recognized that the systolic blood pressure goal of less than 130 mm Hg is a very difficult one to achieve in diabetics. Evidence of the superiority or inferiority of different drug classes is vague and contradictory. Recent evidence concerning angiotensin II receptor antagonists has shown a significant reduction of cardiovascular events, cardiovascular death, and total mortality when losartan was compared with atenolol, but not when irbesartan was compared with amlodipine. If renal endpoints are considered, evidence of the benefit of angiotensin II receptor antagonists in type 2 diabetes is more robust than that available with angiotensin-converting enzyme inhibitors. Primary prevention of development of microalbuminuria seems to be greatly facilitated by strict blood pressure control. However, by attaining normal blood pressure levels (< 130/80 mm Hg), better preservation of glomerular filtration rate does not seem to be insured.

In this article we emphasize the need for prompt intervention in diabetic patients with high blood pressure in order to protect the heart, brain, kidney, and the vascular tree against arteriosclerotic damage, which is the main cause of mortality in type 1, and particularly type 2 diabetes mellitus. Recent placebo-controlled, randomized trials indicate that compared with the nondiabetic population, a lower blood pressure threshold for intervention and a lower target blood pressure are adequate in terms of target organ protection. Although all major classes of antihypertensive drugs have demonstrated a potential benefit in treating diabetic hypertensive patients, blocking the renin-angiotensin system with angiotensin converting enzyme (ACE) inhibitors is especially useful in patients at high risk for myocardial infarction and/or renal damage. The new class of antihypertensive agents that block the angiotensin II receptor have renal effects very close to those observed with ACE inhibitors. The potential role of this new class in the treatment of hypertension in diabetes will depend on the results of ongoing trials.