Cardiovascular disease is still the leading cause of morbidity and mortality worldwide, resulting in approximately 7 million deaths each year, particularly from myocardial infarction and stroke. The worldwide incidence of patients with end-stage renal disease who require dialysis is rapidly increasing and is expected to double to 2 million by 2010. Cardiovascular and renal diseases represent the end-stage of the cardiovascular and renal continuum, whereas endothelium dysfunction is the initial pathological step. If the progression of the cardiovascular and renal continuum is not halted, endothelium dysfunction can lead to both kidney failure and overt cardiovascular disease. Numerous textbooks and monographs have been written on the treatment of cardiovascular risk factors that trigger the progression of cardiovascular and renal diseases. Why then another monograph on the management of hypertension and diabetes?
All guidelines for cardiovascular and renal protection recommend blockade of the renin-angiotensin system (RAS) to stop the progression of the disease. Throughout the last 5 years, angiotensin receptor blockers (ARBs) have been extensively researched in large-scale prospective studies. It became evident that they deserve to play a dominant role in organ protective treatment of hypertensive and diabetic patients. ARBs not only have blood-pressure-lowering and organ protective properties, but also display a placebo-like side-effect profile, which is unique for a pharmacological agent. In fact, new evidence indicates higher doses of ARBs reduce proteinuria in diabetic nephropathy more than do standard doses.
This monograph is dedicated to the ARB telmisartan, which has a specific pharmacokinetic profile (ie, long-acting) and extraordinary pharmacodynamic effects (ie, peroxisomal proliferator-activated receptor [PPAR]-gamma modulating). Both of these features are not shared to the same extent by other ARBs or by other compounds that reduce or block the activity of the RAS.
The authors begin with a discussion of the worldwide "hypertension" epidemic by focusing on the RAS and its role in hypertension-related target organ damage. Interestingly, microalbuminuria, a renal parameter, has emerged as an excellent tool not only in predicting renal prognosis but also predicting cardiovascular outcome in hypertensive diabetic patients. This relationship is masterly described throughout. The text then details landmark studies in nephrology that have analyzed the reduction of proteinuria following treatment with angiotensin-converting enzyme (ACE) inhibitors or ARBs.
Next, the extensive worldwide PROTECTION program is highlighted, which focuses on various stages of the cardiovascular and renal continuum. The PROTECTION program analyzes the effect of telmisartan in comparison to other ARBs or ACE inhibitors in terms of organ protective properties in relation to, but also far beyond, its bloodpressure-lowering effects. The comparative trials of telmisartan with other RAS blockers are outlined and related to the ONTARGET trial, which ultimately will answer whether the ARBs, ACE inhibitors, or a combination of both offer the optimal organ protective treatment in hypertension and diabetes.
This review is timely, useful, comprehensive, and includes the latest information on the PROTECTION program. In addition, the pharmacology and rationale for blocking the RAS with either of the compounds will be much appreciated by the readers. The illustrations throughout the monograph deserve special attention as well, as they are precise and informative. This balanced, state-of-the-art review depicts the RAS blockers-in particular, telmisartan-as a cardiovascular cornerstone for preventing cardiovascular and renal diseases, and will be of benefit to all clinicians in their daily encounters with hypertension and renal disease.