An elevated resting heart rate is associated with an increased risk of cardiac events in high-risk hypertension, according to a secondary analysis of a large randomized trial.
Among patients randomized to two different antihypertensives, each 10 beats per minute increase in baseline heart rate was associated with a relative 16% greater risk of cardiovascular mortality and morbidity (P<0.0001), according to Stevo Julius, MD, ScD, of the University of Michigan in Ann Arbor.
The relationship remained significant (P<0.0001) even among those patients who had their blood pressure controlled to less than 140/90 mm Hg (average 130/77 mm Hg), Julius reported at the American Society of Hypertension meeting here.
“In all diseases of civilization it has been shown that lowering of cardiovascular risk components - glucose, lipids, blood pressure - decreases cardiovascular events,” he said. “So we are saying that we see no reason why lowering the heart rate should not also be beneficial.”
Julius said hypertension guidelines should recognize tachycardia as a potent and clinically relevant cardiovascular risk factor.
Agreeing was Franz Messerli, MD, director of the hypertension program at St. Luke’s-Roosevelt Hospital Center in New York City.
“We have known for quite some time that heart rate is a neglected risk factor for cardiovascular disease,” said Messerli, an officer of ASH.
He pointed out, however, that lowering heart rate has not always improved outcomes.
“So we are in a kind of paradoxical situation where we clearly know a high heart rate is no good, but lowering heart rate by pharmacologic therapy is not always beneficial.”
Julius said there was an increasing interest in the relationship between heart rate and mortality, as reflected in a greater number of research papers addressing the issue.
To explore the impact of heart rate on outcomes, he and his colleagues conducted an analysis of data from the VALUE trial, which included 15,245 patients with high-risk hypertension from 30 countries.
The trial compared the rate of composite cardiovascular mortality and morbidity, the primary endpoint, between an amlodipine- or valsartan (Diovan)-based treatment. As reported in 2004, there was no significant difference between the two groups.
For the purposes of the current analysis, all of the patients were pooled together.
An increase in heart rate of 10 bpm from baseline was not only associated with the composite cardiovascular endpoint, but with the individual components of heart failure (HR 1.25), sudden cardiac death (HR 1.20), myocardial infarction (HR 1.09), and stroke (HR 1.12). All were significant at P<0.05.
Adjusting for baseline blood pressure and other cardiovascular risk factors did not substantially change the results.
When the patients were divided into quintiles of baseline heart rate, an apparent threshold developed at 79 bpm, the floor of the fifth quintile, above which the risk of a cardiovascular event jumped significantly.
Patients in the highest quintile had a significantly increased risk of the primary composite endpoint and of heart failure for each of the five years of the trial (P<0.05 for all), showing that baseline heart rate predicted events in both the early and late phases of the trial.
"This is important because if, for example, tachycardia were a marker of subclinical heart failure or of some morbidity or mortality, you would expect a lot of events in the first two years and then to taper off, but this is a permanent trend," Julius said.
The findings were similar for in-trial heart rate measured after the first year of the trial. Patients in the highest quintile had significantly elevated risks of the primary endpoint, sudden cardiac death, MI, stroke, and heart failure (P≤0.023 for all).
After adjusting for several factors, including in-trial and baseline blood pressure and baseline heart rate, patients in the highest quintile of in-trial heart rate were more likely to have the primary endpoint (HR 1.46), heart failure (HR 1.88), and sudden cardiac death (HR 1.52) (P<0.05 for all), but not MI and stroke.
By Todd Neale, Staff Writer, MedPage Today
Primary source: American Society of Hypertension
Julius S, et al “Tachycardia predicts cardiovascular events in the VALUE trial” ASH 2010; Abstract LB-OR-01.