Incident atrial fibrillation and heart failure in treated hypertensive patients with left ventricular hypertrophy
Authors: Bang C , Greve A , Kober L , Muthiah A , Kjeldsen S , Julius S , Wachtell K , Devereux R B , Okin P 
Published: October 2022

Abstract

Background
Hypertension and left ventricular hypertrophy (LVH) are predictors of atrial fibrillation (AF) and heart failure (HF). The incidence rates of AF and HF and especially the combination of these two complications in hypertensive patients with LVH receiving antihypertensive treatment are unknown, and so are the association with risk levels of other cardiovascular diseases and death in hypertensive patients with LVH who develop new onset AF and HF.

Purpose
We aimed to investigate the appearance and severity of AF and HF in 8,702 hypertensive patients aged 55–80 years with LVH receiving antihypertensive treatment in a prospective and randomized clinical trial primarily designed to investigate the preventive effect on a composite endpoint of myocardial infarction, stroke and cardiovascular death.

Methods
Included were patients who had sinus rhythm in ECG and no history of AF or HF when they were randomly allocated to blinded study medication with losartan or atenolol. Additional medication was given with hydrochlorothiazide and calcium antagonist if needed to gain blood pressure control. Incident AF was detected by annual ECGs and from adverse event reports submitted by the 930 clinical investigators. Incident HF was diagnosed according to Framingham criteria. Endpoints including incident HF, myocardial infarction, stroke and cardiovascular death were reported with relevant documentation by the investigators, and adjudicated by an expert endpoint committee.

Results
Incident AF occurred in 679 patients (7.8%) and HF in 246 patients (2.8%) during 4.7±1.1 years mean follow-up. Incident AF was associated with a &gt;4-fold increased risk of developing subsequent HF (HR=4.7; 95% CIs, 3.1–7.0; P&lt;0.001) in multivariable Cox analyses adjusting for age, sex, race, randomized treatment, standard cardiovascular risk factors and incident myocardial infarction. The development of HF as a time-dependent variable was associated with a multivariable-adjusted 3-fold increase of the primary study endpoint (HR=3.11; 95% CIs, 1.52 to 6.39; P&lt;0.001) which was the composite of myocardial infarction, stroke or cardiovascular death.
Incident HF was associated with a &gt;3-fold increased risk of developing subsequent AF (HR=3.3; 95% CIs, 2.3–4.9; P&lt;0.001). This development of AF was associated with more than a 2-fold increase of the composite of myocardial infarction, stroke or cardiovascular death in multivariable Cox analysis (HR=2.26; 95% CIs, 1.09–4.67; P=0.028).

Conclusions
Incident atrial fibrillation and heart failure are associated with increased risk of the other in treated hypertensive patients with left ventricular hypertrophy. These hypertensive patients who subsequently develop both atrial fibrillation and heart failure during antihypertensive treatment have particularly high risk of an additional composite endpoint consisting of myocardial infarction, stroke or cardiovascular death.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): The study originally received support from Merck & Co., Inc.