Left ventricular mass and incident hypertension: Missing pieces in the puzzle

Hypertension is a complex phenotype whose pathophysiological mechanisms and clinical correlates still remain not fully understood. In particular, the association between hypertension and subclinical cardiac organ damage is the subject of a continuous debate. Since the late 1980s, some population-based studies conducted in adolescents and adults have questioned whether left ventricular hypertrophy (LVH) is exclusively the consequence of chronic blood pressure (BP) overload that occurs when arterial hypertension is not prontly diagnosed and treated or remains poorly controlled by anti-hypertensive treatment.1-3 This is because, in contrast to the traditional view that LVH represents an adaptive change aimed at counterbalancing the hemodynamic stress, evidence has been accumulated that an increase in the LV mass (LVM), as assessed by echocardiography and, more accurately, by magnetic resonance imaging, can promote “per se” or predict the subsequent development of hypertension.4, 5 It should be emphasized that human studies had taken their rational from several experimental investigations carried out more than four decades ago that examined factors, other than BP, involved in the pathogenesis of hypertensive LVH. Among the relevant information provided by experimental studies, it is worth mentioning that in spontaneously hypertensive rats, increased LVM precedes the development of hypertension and that sympathectomy in this animal model prevents the development of hypertension but does not affect the development of LVH.6 Overall, experimental data support the concept that other factors than pressure overload contribute to the initiation and evolution of cardiac hypertrophy and, that, more in general, cardiovascular remodeling to some extent may be genetically determined. In the clinical setting, the mechanistic view of LV hypertrophy as a mere consequence of pressure overload has evolved taking into account that LVMI represents an integrated marker of the adverse impact of hemodynamic with genetic, ethnic, humoral, and hormonal factors. This means that the interplay between several demographic and clinical variables (age, ethnicity, gender, pressure and volume overload, type 2 diabetes, metabolic syndrome, obesity, sleep apnea syndrome, and kidney disease) and activation of the renin-angiotensin-aldosterone system and sympathetic nervous system may simultaneously increase LVM and the risk of incident hypertension; that is, hypertension is not necessarily a prerequisite for the development of LVH. So far, the independent role of LVM in the progression from normotension to hypertension has been investigated by few studies. In addition, some of them had methodological limitations (small sample size, retrospective analysis, and adjustment for a limited number of confounders) that do not allow to provide reliable information. More importantly, most studies were conducted in population samples with office BP 75th percentile of distribution had 2.5-fold higher adjusted risk (P < .001) of incident hypertension than those below this cut-off.4 In a large sample of young/middle-age Korean employees, classified at the initial visit as normotensive (BP < 120/80 mm Hg, n = 8034) and pre-hypertensive (BP 120-139 and/or 80-89 mm Hg, n = 4528), participants belonging to highest LVM quintile exhibited a significantly 5-year adjusted risk of incident hypertension (OR:1.35 for normotensive and 1.80 for pre-hypertensive participants, respectively, P < .001 for both) than the reference group.9 The PAMELA study, assessing the relation between entry LVM and 10-year incidence of hypertension in the participants (n = 570) identified as normotensive in both in- and out-office settings according to office, home, and ambulatory BP measurement methods, showed that increased LVMI predicted the development of new hypertension, after full adjustment for confounders.10 Furthermore, taking advantage of the fact that an echocardiographic examination was obtained in all participants at baseline and 10 years later, the study documented that delta LVMI was approximately 2-fold higher in participants who became hypertensive as compared to those with persistent normotension. In conclusion, a limited body of evidence suggests that subtle alterations of LV structure may occur even in individuals with optimal BP,4, 9 independently from the possible confounding role of masked hypertension11 and may stratify the risk of new-onset hypertension. Whether pooling clinical information with the assessment of LVM by echocardiography could be an useful strategy to refine the identification of individuals at high risk of future hypertension is an unsolved issue, and future studies aimed at investigating the predictive value of LVM in normotensive subgroups (stratified by age, gender, BMI, and level of physical activity) are needed. None.