The clinical requirements of antihypertensive therapy have remarkably and progressively changed over the last two decades, moving from the single major objective of blood pressure reduction to much more complex, integrated clinical objectives. Beside the key priority of lowering blood pressure, what we ask of any modern antihypertensive strategy is high tolerability, protection of organ damage, neutral metabolic profile, and prevention of major cardiometabolic–renal events, including myocardial infarction, stroke, congestive heart failure, vascular disease, chronic kidney disease, renal failure, and diabetes. Thus, the evaluation of any new molecular compound or combination strategy in hypertension has mandatorily considered all these aspects, and clinical developments have been adapted accordingly.
One of the major concerns raised with respect to antihypertensive therapy has been linked to the possible onset of dysmetabolic conditions, such as diabetes or lipid disorders. This is of particular relevance for long-term treatment of a chronic disease such as hypertension and may represent a potential drawback for the treatment. The common association of metabolic disorders, such as glucose intolerance, metabolic syndrome, obesity, diabetes, and dyslipidemia, to hypertension enhances this problem. Finally, the observation that some pharmacological interventions in hypertension may prompt the manifestation of metabolic disorders has generated a major focus of the scientific community toward this issue.
In particular, beta blockers, sympatholytic agents, and diuretics at high dosages and their combinations have been identified as potentially unfavorable interventions from the point of view of the metabolic balance. For this reason, in recent years, more and more consideration has been given to using thiazide diuretics at low doses, especially in combination with drugs blocking the renin-angiotensin system. This combination may affect and counteract some of the side effects linked to their chronic use in hypertension, particularly limiting hyperuricemia and hyperkalcemia, which may contribute to unbalanced cellular glucose metabolism and increased insulin resistance, finally leading to metabolic syndrome and diabetes. Indeed, given the growing prevalence of diabetes, this is considered today a major aspect of treatment strategies. Clinical development of angiotensin receptors blockers (ARBs) and their classical combination with low-dose hydrochlorothiazide (12.5 to 25 mg) has demonstrated not only that this therapeutic strategy is neutral, but that it may even be associated with reduction of new-onset diabetes, as has recently been shown in a vast meta-analysis published this year (Tocci G, et al; Am J Hypertens 2011;24(5):582-590).
This is the rationale behind this monograph in the Hot Topics in Hypertension series, which has contributions from two major experts in diabetes and hypertension, Antonio Ceriello and Roland G. Asmar, respectively. I have the privilege of introducing readers to this unique work that combines these two integrated approaches in a modern and practical way.
The first chapter by Ceriello on the clinical management of hypertension and type 2 diabetes covers pathophysiology to clinical aspects, with a special focus on high-risk patients and evidence derived from large studies conducted with the ARB telmisartan. Intriguing “metabolic” properties of this compound are featured. Asmar analyzes the history and rationale of low-dose hydrochlorothiazide and its rational and synergistic combination with RAS blockers, particularly ARBs, featuring landmark clinical trials with telmisartan.
This monograph is easy to read, full of information with enlightening illustrations, and extensively referenced. I believe it will be appreciated by physicians and specialists and will represent a starting point to further investigate and illustrate this important aspect in the management of hypertension and diabetes.