Left ventricular hypertrophy with exercise and ACE gene insertion/deletionpolymorphism - A randomized controlled trial with losartan

Background-Local cardiac renin-angiotensin systems may regulate left ventri cular (LV) hypertrophic responses. The absence (deletion [D]) of a 287-bp m arker in the ACE gene is associated with greater myocardial ACE levels and exercise-related LV growth than is its presence (insertion [I]), an effect potentially mediated through either increased activity of the cellular grow th factor angiotensin II on the angiotensin type 1 (AT(I)) receptor or incr eased degradation of growth-inhibiting kinins, We sought to confirm ACE gen otype-associated exertional LV growth and to clarify the role of the AT, re ceptor in this association. Methods and Results-One hundred forty-one British Army recruits homozygous for the ACE gene (79 DD and 62 II) were randomized to receive losartan (25 mg/d, a subhypotensive dose inhibiting tissue AT, receptors) or placebo thr oughout a 10-week physical training program. LV mass, determined by cardiac magnetic resonance, increased with training (8.4 g, P<0.0001 overall; 12.1 versus 4.8 g for DD versus II genotype in the placebo limb, P=0.022), LV g rowth was similar in the losartan arm: 11.0 versus 3.7 g for DD versus II g enotypes (P=0.034), When indexed to lean body mass, LV growth in the II sub jects was abolished, whereas it remained in the DD subjects (-0.022 versus 0.131 g/kg, respectively; P=0.0009). Conclusions-ACE genotype dependence of exercise-induced LV hypertrophy is c onfirmed. Additionally, LV growth in DD (unlike II) subjects is in excess o f the increase in lean body mass. These effects are not influenced by AT, r eceptor antagonism with the use of losartan (25 mg/d), The 2.4-fold greater LV growth in DD men may be due to the effects of angiotensin II on other r eceptors leg, angiotensin type 4) or lower degradation of growth-inhibitory kinins.