B2 bradykinin receptor (B2BKR) polymorphism and change in left ventricular mass in response to antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial.
OBJECTIVE
Hypertension is associated with a number of adverse morphologic and functional changes in the cardiovascular system, including left ventricular (LV) hypertrophy. Studies have demonstrated that bradykinin, through the B2 bradykinin receptor (B2BKR), mediates important cardiovascular effects that may protect against LV hypertrophy. Recently, a +9/-9 exon 1 polymorphism of the B2BKR was shown to be strongly associated with LV growth response among normotensive males undergoing physical training. We aimed to clarify whether the processes found in exercise-induced LV growth in normotensive people also occur in pathological LV hypertrophy.


METHODS
We determined the B2BKR genotype of 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, included in a double-blind study to receive treatment for 48 weeks with either the angiotensin II type 1 (AT1) receptor antagonist irbesartan or the beta1-adrenoceptor antagonist atenolol.


RESULTS
B2BKR +9/+9 genotypes responded poorly in LV mass regression, independent of blood pressure reduction or treatment, as compared to the other genotypes (adjusted mean change in LV mass index = -10.0 +/- 4.6 versus -21.6 +/- 2.2 g/m2, P = 0.03).


CONCLUSIONS
Our results suggest an impact of the B2BKR polymorphism on LV mass regression during antihypertensive treatment.
Hallberg
Pär
P
Department of Medical Sciences, Clinical Research Department 2, Uppsala University Hospital, 75185 Uppsala, Sweden. par.hallberg@medsci.uu.se
Lind
Lars
L
Michaëlsson
Karl
K
Karlsson
Julia
J
Kurland
Lisa
L
Kahan
Thomas
T
Malmqvist
Karin
K
Ohman
K Peter
KP
Nyström
Fredrik
F
Melhus
Håkan
H
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects; D011110:Polymorphism, Genetic; D043782:Receptor, Bradykinin B2 / Q000235:genetics*; D013548:Sweden; D013777:Tetrazoles / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D043782:Receptor, Bradykinin B2; D013777:Tetrazoles; D001262:Atenolol; D000077405:Irbesartan