The risk of new-onset atrial fibrillation went up sharply with
increasing resting heart rate in patients receiving drug therapy for
hypertension in the Losartan Intervention for End Point Reduction in
Hypertension (LIFE) study, report investigators in the December 2008
issue of Circulation: Arrhythmia and Electrophysiology [1].

The LIFE analysis of 8828 hypertensive patients with LV hypertrophy
(by electrocardiography) but without a history of AF tracked heart
rate at baseline, six months, and then annually over an average of
almost five years. Each 10-bpm increment in heart rate corresponded
to a 19% increased risk of incident AF. The risk of "persistence or
development" of AF was increased by 61% in patients with heart rates
in the highest quintile, that is, >84 bpm, according to Dr Peter M
Okin (Weill Medical College of Cornell University, New York, NY) and
associates.

The link between heart rate and incident AF was independent of
antihypertensive therapy group, the blood-pressure-lowering effect
of treatment, and comorbidities. It was also independent of the anti-
AF effects both losartan itself and regression of LV hypertrophy
separately demonstrated in prior LIFE subanalyses, as previously
reported by heartwire.

"People who have higher-than-normal resting heart rates are at
increased risk of developing atrial fibrillation and deserve further
investigation to determine whether there are underlying preventable
abnormalities that are worth looking into," according to Okin. Heart
rates that go up over time should also be investigated, he said to
heartwire.

In such cases, when the patient doesn't have other obvious
conditions that can raise heart rate, like infections or acute
illness, Okin said, "physicians should take a step back and ask, why
is this happening? Heart rates go up for a reason. What else is
going on that's putting the patient at risk?"

According to the LIFE trial's primary outcomes, reported in 2002 [2]
and covered at the time by heartwire, blood pressure dropped
similarly for patients randomized to antihypertensive therapy based
on either losartan or atenolol, while the losartan group showed a
significantly decreased risk of the composite primary end point
(p=0.021), consisting of death, MI, or stroke. The 12% reduced risk
was driven predominantly by a 25% reduced risk of fatal or nonfatal
stroke (p=0.001). A subsequent analysis suggested that the risk of
incident AF and the risk of stroke among patients with AF were
significantly lower among patients who received losartan.

"The relationship between heart rate and outcomes is convincing,"
notes an accompanying editorial [3] about the current study. Dr
Rakesh Gopinathannair (University of Iowa, Iowa City) and associates
acknowledge that it was conducted post hoc and so has inherent
limitations but that "use of multiple statistical tools makes the
analysis robust."

"This novel work," write the editorialists, "has the potential to
influence drug therapy in hypertensive patients as part of an effort
to prevent atrial fibrillation. The question, however, remains as to
whether heart rate is really a modifiable risk factor." Faster heart
rates may imply more comorbidities that themselves increase the risk
of AF, or it may be that hypertension, faster heart rate, and AF
share common neurohormonal underpinnings. "The mechanisms by which
hypertension leads to atrial fibrillation and the relation between
atrial pressure, stretch, and autonomic shifts in patients who
develop atrial fibrillation remain areas of active investigation."

The LIFE trial was supported by Merck. Coauthors Darcy A Hille and
Dr Jonathan M Edelman are Merck employees "and may own stock or hold
stock options" in the company. Principal editorialist Dr Brian
Olshansky (University of Iowa) reports receiving honoraria for
speaking and funding for research and having consulted for Boston
Scientific, Medtronic, St Jude Medical, Novartis, Sanofi-Aventis,
Roche, Baxter, GlaxoSmithKline, Reliant, and Biocontrol.

Sources


Okin PM, Wachtell K, Kjeldsen SE, et al. Incidence of atrial
fibrillation in relation to changing heart rate over time in
hypertensive patients: the LIFE study. Circ Arrhythmia
Electrophysiol 2008; 1:337–343.
Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity
and mortality in the Losartan Intervention for End point reduction
in hypertension study (LIFE): a randomised trial against atenolol.
Lancet 2002; 359:995-1003.
Gopinathannair R; Sullivan RM; Olshansky B. Slower heart rates for
healthy hearts. Time to redefine tachycardia? Circ Arrhythmia
Electrophysiol 2008; 1:321-323.