Transforming growth factor β 1 genotype and change in left ventricular mass during antihypertensive treatment–results from the swedish irbesartan left ventricular hypertrophy investigation versus atenolol (Silvhia)

Background : Angiotensin II, via the angiotensin II type 1 (AT1) receptor, may mediate myocardial fibrosis and myocyte hypertrophy seen in hypertensive left ventricular (LV) hypertrophy through production of transforming growth factor β 1 (TGF‐β 1 ); AT1‐receptor antagonists reverse these changes. The TGF‐(β 1 G + 915C polymorphism is associated with in‐terindividual variation in TGF‐ β 1 production. No study has yet determined the impact of this polymorphism on the response to antihypertensive treatment. Hypothesis : We aimed to determine whether the TGF‐ β 1 G + 915C polymorphism was related to change in LV mass during antihypertensive treatment with either an AT 1 ‐receptor antagonists or a beta1 ‐adrenoceptor blocker. The polymorphism was hypothesized to have an impact mainly on the irbesartan group. Methods : We determined the association between the TGF‐β 1 genotype and regression of LV mass in 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, randomized in a double‐blind study to receive treatment for 48 weeks with either the AT 1 ‐receptor antagonist irbesartan or the beta1 ‐adrenoceptor blocker atenolol. Results : Irbesartan‐treated patients who were carriers of the C‐allele, which is associated with low expression of TGF‐β 1 , responded with a markedly greater decrease in LV mass index (LVMI) than subjects with the G/G genotype (adjusted mean change in LVMI –44.7 g/m 2 vs. –22.2 g/m 2 , p = 0.007), independent of blood pressure reduction. No association between genotype and change in LVMI was observed in the atenolol group. Conclusions : The TGF‐ β 1 G + 915C polymorphism is related to the change in LVMI in response to antihypertensive treatment with the AT 1 ‐receptor antagonist irbesartan.