Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomized controlled...

Area of Science:

• Cardiovascular Physiology
• Human Genetics
• Exercise Physiology

Background:

• Local cardiac renin-angiotensin systems influence left ventricular (LV) hypertrophy.
• The ACE gene deletion (D) genotype is associated with higher myocardial ACE levels and greater exercise-induced LV growth compared to the insertion (I) genotype.
• This association may involve angiotensin II signaling via the angiotensin type 1 (AT(1)) receptor or kinin degradation.

Purpose of the Study:

• To confirm the association between ACE genotype and exercise-induced LV growth.
• To investigate the role of the AT(1) receptor in this ACE genotype-dependent LV remodeling.

Main Methods:

• 141 British Army recruits (79 DD, 62 II ACE genotypes) were randomized to receive losartan (AT(1) receptor antagonist) or placebo.
• Participants underwent a 10-week physical training program.
• Left ventricular mass was assessed using cardiac magnetic resonance imaging.

Main Results:

• Exercise training increased LV mass overall (P<0.0001).
• LV growth was significantly greater in DD versus II genotypes in the placebo group (12.1g vs 4.8g, P=0.022).
• Losartan treatment did not alter LV growth differences between genotypes (11.0g vs 3.7g, P=0.034).
• Indexed to lean body mass, LV growth persisted in DD subjects but was abolished in II subjects (P=0.0009).

Conclusions:

• The ACE genotype influences exercise-induced LV hypertrophy, with the DD genotype showing greater growth.
• LV growth in DD subjects exceeded lean body mass increases and was independent of AT(1) receptor blockade with losartan.
• Alternative pathways, such as angiotensin II acting on other receptors or altered kinin metabolism, may mediate the enhanced LV growth in DD individuals.