Left ventricular hypertrophy regression with antihypertensive treatment: focus on Candesartan.

Left ventricular hypertrophy (LVH) in humans is a common adaptive process induced by different physiological and pathological stimuli [1, 2]. Arterial hypertension is the most frequent cause of pathological LVH, and the development of hypertensive cardiac hypertrophy is considered a compensatory mechanism to normalize the increase wall stress and to preserve myocardial function. However, this adaptive process, which may occur even in early phases of the natural history of arterial hypertension, has a negative prognostic relevance. In fact, epidemiological prospective studies have shown that LVH, diagnosed by electrocardiographic or more accurately by echocardiographic criteria, is a powerful and independent predictor of cardiovascular morbidity, cardiovascular death and all-cause mortality in different clinical settings such as in patients with previous myocardial infarction [3], in patients with or without angiographic evidence of coronary artery disease [4], in asymptomatic hypertensive subjects [5] and the general population [6]. Thus, cardiac hypertrophy cannot be considered a physiological process and seems to be associated with maladaptive changes that affect the prognosis. There is no doubt that the most important factor for the high prevalence of LVH in hypertension is the pressure overload on the heart, although several factors directly enhancing myofibrillar replication and possibly connective tissue growth (cardiac sympathetic drive, plasma catecholamines, angiotensin II, insulin and endothelin) are more active or more frequently present in hypertensive patients than in normotensive subjects [7]. A rise in left ventricular (LV) wall stress determined by high systolic intraventricular pressure represents a potent stimulus for the development of LVH, which in turn reduces the wall stress. According to the Laplace law, the stress on the LV wall is directly proportional to the intraventricular pressure and squared radius, and is inversely related to wall thickness. The increase in wall thickness, intended to normalize or attenuate the wall stress, is secondary to cardiac muscle cell hypertrophy and a significant rise in the number of sarcomeres, which are arranged in parallel when the hypertrophy is concentric and longitudinally when the hypertrophy is eccentric [8]. This compensatory change is accompanied by at least three negative consequences. First, the capillary growth in the heart does not keep place with the rise in ventricular mass; second, coronary small arteries and arterioles undergo morphological and functional changes, which lead to increased coronary resistance and reduced coronary reserve [9, 10]. Third, the pathological increase in LV mass is associated with a disproportional proliferation of extracellular collagen matrix, which combined with impaired myocardial perfusion may contribute to the development of diastolic dysfunction and arrhythmias [11, 12]. In the present short review, we would like to focus the attention on these following issues: the role of the renin–angiotensin–aldosterone system (RAAS) in the pathogenesis of LVH, the epidemiology of LVH, the impact of echocardiography in stratifying the overall cardiovascular risk in hypertension, the prognostic significance of LVH regression, the drug-induced regression of LV mass and the role of angiotensin II antagonists in the treatment of hypertensive LVH.