Irbesartan in hypertensive patients with LVH and the angiotensinogen 174 TM genotype led to a greater reduction in left ventricular mass than the TT genotype (-23 vs +0.5 g/m2; P=0.005).
RCT (n=84)
Double-blind
Do specific RAAS gene polymorphisms affect the reduction in left ventricular mass in patients with essential hypertension and LVH treated with irbesartan versus atenolol?
Specific RAAS gene polymorphisms, particularly angiotensinogen T174M, predict the degree of left ventricular mass reduction in hypertensive patients treated with the AT1-receptor antagonist irbesartan.
BACKGROUND: Our aim was to determine if gene polymorphisms in the renin-angiotensin-aldosterone system (RAAS) were related to the degree of change in left ventricular hypertrophy (LVH) during antihypertensive treatment. METHODS AND RESULTS: Patients with essential hypertension and echocardiographically diagnosed LVH were included in a double-blind study to receive treatment with either the angiotensin II type 1 receptor (AT1-receptor) antagonist irbesartan (n = 41), or the beta-1 adrenergic receptor blocker atenolol (n = 43) as monotherapy for 3 months. The angiotensinogen T174M and M235T, the angiotensin-converting enzyme I/D, the AT1-receptor A1166C and the aldosterone synthase (CYP11B2) -344 C/T polymorphisms were analysed and related to the change in left ventricular mass (LVM). Patients with the angiotensinogen 174 TM genotype treated with irbesartan responded with the greatest reduction in LVM (-23 +/- 31SD g/m2 for TM and +0.5 +/- 18 g/m2 for TT, P = 0.005), independent of blood pressure reduction. Both the angiotensinogen 235 T-allele (P = 0.02) and the AT1-receptor 1166 AC genotype responded with the greatest reduction in LVM when treated with irbesartan (-0.1 +/- 19 g/m2 for AA and -18 +/- 30 g/m2 for AC, P = 0.02), independent of blood pressure reduction. These polymorphisms were not associated with the change in LVM during treatment with atenolol. DISCUSSION: The angiotensinogen T174M and M235T and the AT1-receptor A1166C polymorphisms were related to the change in LVH during antihypertensive treatment with an AT1-receptor antagonist; of these angiotensinogen T174M was the most powerful. This highlights the role of the RAAS for left ventricular hypertrophy and the potential of pharmacogenetics as a tool for guidance of antihypertensive therapy.
Kurland et al. (Mon,) conducted a rct in Essential hypertension and left ventricular hypertrophy (n=84). Irbesartan vs. Atenolol was evaluated on Change in left ventricular mass (LVM). Irbesartan in hypertensive patients with LVH and the angiotensinogen 174 TM genotype led to a greater reduction in left ventricular mass than the TT genotype (-23 vs +0.5 g/m2; P=0.005).