Structural and neurohormonal factors in left ventricular hypertrophy and inhibition of the renin-angiotensin-aldosterone system

Abstract

Hypertensive left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular morbidity and mortality. The aim of this thesis was to study how different neurohormonal systems relate to left ventricular mass, and to study structural and functional cardiovascular changes in hypertensive LVH. Furthermore to evaluate how inhibition of the renin- angiotensin-aldosterone system (RA-AS) influences cardiovascular changes.

Two different hypertensive populations were studied. One relatively large group of hypertensive patients with echocardiographic verified LVH, who were treated with AT1- receptor blockade or beta-receptor blockade for one year. The other group consisted of never treated non-diabetic hypertensive patients, and were treated with an ACE inhibitor or a beta-receptor blocker for one year.

Increased left ventricle mass was related to determinants of RAAS. Both AT,receptor blockade and inhibition of ACE, reduced left ventricular mass more than beta-receptor blockade did, at same level of blood pressure lowering. This suggests that RAAS plays an important role in the development and maintenance of LVH, beyond its effect on blood pressure control. In contrast, insulin, proinsulin, insulin sensitivity (assessed by euglycemic clamp technique) and leptin, were not related to left ventricular mass, when body size was accounted for. Neither were plasma and urine catecholamines related to LVH. Our results do not support that insulin, leptin or sympathetic nervous system have direct myocardial growth stimulating effects, although these neurohormonal systems may have peripheral effects that promote the development of LVH.

Prolonged QT dispersion, which indicates cardiac electric instability, related to LVH. AT, -receptor blockade, but not beta-receptor blockade, reduced QT dispersion, as well as repolarisation time, independently of changes in left ventricular mass, blood pressure, or heart rate. This suggests that inhibition of RAAS may induce structural and electrical remodeling in a direction that could decrease the risk of malignant arrhythmias in hypertensive patients.

Patients with increased relative left ventricular wall thickness (concentric LW), who are at higher risk of future cardiovascular events, displayed elevated levels of soluble cell adhesion molecules, markers of endothelium dysfunction. Thus, our results may indicate an association between more advanced hypertensive heart disease and vascular alterations. Interestingly, E-selectin was related to aldosterone.

Thus, we suggest that RAAS plays an important role for development and maintenance of structural and functional cardiovascular changes, and blockade of the AT, -receptor may improve cardiac function and possibly prognosis in hypertensive LVH.