Dallas, TX - 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."