Left Ventricular Hypertrophy With Exercise and ACE Gene Insertion/Deletion Polymorphism

Background —Local cardiac renin-angiotensin systems may regulate left ventricular (LV) hypertrophic responses. The absence (deletion D) of a 287-bp marker 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 growth factor angiotensin II on the angiotensin type 1 (AT 1 ) receptor or increased degradation of growth-inhibiting kinins. We sought to confirm ACE genotype–associated exertional LV growth and to clarify the role of the AT 1 receptor 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 1 receptors) or placebo throughout 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 growth was similar in the losartan arm: 11.0 versus 3.7 g for DD versus II genotypes ( P =0.034). When indexed to lean body mass, LV growth in the II subjects 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 confirmed. Additionally, LV growth in DD (unlike II) subjects is in excess of the increase in lean body mass. These effects are not influenced by AT 1 receptor 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 receptors (eg, angiotensin type 4) or lower degradation of growth-inhibitory kinins.