Regression of electrocardiographic left ventricular hypertrophy and decreased incidence of new-onset atrial fibrillation in patients with hypertension.
BACKGROUND
Atrial fibrillation (AF) is associated with increased risk of mortality and cardiovascular events, particularly stroke, making prevention of new-onset AF a clinical priority. Although the presence and severity of electrocardiographic left ventricular hypertrophy (LVH) appear to predict development of AF, whether regression of electrocardiographic LVH is associated with a decreased incidence of AF is unclear.


OBJECTIVE
To test the hypothesis that in-treatment regression or continued absence of electrocardiographic LVH during antihypertensive therapy is associated with a decreased incidence of AF, independent of blood pressure and treatment modality.


METHODS
Double-blind, randomized, parallel-group study conducted in 1995-2001 among 8831 men and women with hypertension, aged 55-80 years (median, 67 years), with electrocardiographic LVH by Cornell voltage-duration product or Sokolow-Lyon voltage, with no history of AF, without AF on the baseline electrocardiogram, and enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension Study.


METHODS
Losartan- or atenolol-based treatment regimens, with follow-up assessments at 6 months and then yearly until death or study end.


METHODS
New-onset AF in relation to electrocardiographic LVH determined at baseline and subsequently. Electrocardiographic LVH was measured using sex-adjusted Cornell product criteria ({R(aVL) + S(V3) [+ 6 mm in women]} x QRS duration).


RESULTS
After a mean (SD) follow-up of 4.7 (1.1) years, new-onset AF occurred in 290 patients with in-treatment regression or continued absence of Cornell product LVH for a rate of 14.9 per 1000 patient-years and in 411 patients with in-treatment persistence or development of LVH by Cornell product criteria for a rate of 19.0 per 1000 patient-years. In time-dependent Cox analyses adjusted for treatment effects, baseline differences in risk factors for AF, baseline and in-treatment blood pressure, and baseline severity of electrocardiographic LVH, lower in-treatment Cornell product LVH treated as a time-varying covariate was associated with a 12.4% lower rate of new-onset AF (adjusted hazard ratio [HR], 0.88; 95% CI, 0.80-0.97; P = .007) for every 1050 mm x msec (per 1-SD) lower Cornell product, with persistence of the benefit of losartan vs atenolol therapy on developing AF (HR, 0.83; 95% CI, 0.71-0.97; P = .01).


CONCLUSIONS
Lower Cornell product electrocardiographic LVH during antihypertensive therapy is associated with a lower likelihood of new-onset AF, independent of blood pressure lowering and treatment modality in essential hypertension. These findings suggest that antihypertensive therapy targeted at regression or prevention of electrocardiographic LVH may reduce the incidence of new-onset AF.
Okin
Peter M
PM
Greenberg Division of Cardiology, Weill Medical College of Cornell University, New York, NY 10021, USA. pokin@med.cornell.edu
Wachtell
Kristian
K
Devereux
Richard B
RB
Harris
Katherine E
KE
Jern
Sverker
S
Kjeldsen
Sverre E
SE
Julius
Stevo
S
Lindholm
Lars H
LH
Nieminen
Markku S
MS
Edelman
Jonathan M
JM
Hille
Darcy A
DA
Dahlöf
Björn
B
D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000453:epidemiology* / Q000517:prevention & control; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D015994:Incidence; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012074:Remission Induction; D012306:Risk
D000959:Antihypertensive Agents; D001262:Atenolol; D019808:Losartan