Fast track — ArticlesHeart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial
Introduction
Heart rate is increasingly being postulated as a modifiable risk factor for cardiovascular disease. Previous studies have shown a relation between elevated resting heart rate and the risk of cardiovascular disease in the general population1 and in patients with stable coronary artery disease with or without hypertension.2, 3 However, the threshold at which risk increases in coronary patients, and the quantitative relation between heart rate increase and outcome, are less well defined; data from the Coronary Artery Surgery Study suggested that risk increases around 83 beats per min (bpm) and above,2 whereas analysis of the International Verapamil SR/Trandolapril Study indicated increased risk above 75 bpm, well below the conventional definition of tachycardia (>90 bpm).3 There are many hypothetical mechanisms through which elevated heart rate might directly affect cardiovascular risk, mostly related to increased myocardial oxygen demand,4 energy depletion,5 accelerated atherosclerosis,6, 7, 8, 9 or increased risk of plaque rupture.10
The placebo arm of the BEAUTIFUL (morBidity-mortality EvAlUaTion of the If inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction) study11, 12 provided a large population with coronary artery disease and left-ventricular systolic dysfunction, who were well treated in terms of cardiovascular prevention. We tested the hypothesis that elevated resting heart rate at baseline is a marker for subsequent cardiovascular death and morbidity.
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Study design and participants
The design and baseline characteristics for the BEAUTIFUL trial have been described previously.11, 12 Briefly, BEAUTIFUL included men and women aged 55 years or older with coronary artery disease, left-ventricular ejection fraction of less than 40%, and end-diastolic short-axis internal dimension larger than 56 mm, identified by echocardiography. The patients were in sinus rhythm and had a resting heart rate of 60 bpm or greater. Resting heart rate was measured at baseline in the supine
Results
The baseline characteristics of the patients enrolled in the placebo group are shown in table 1. Patients with a heart rate of 70 bpm or greater were younger and had a lower left-ventricular ejection fraction and a higher systolic blood pressure than those with a heart rate of less than 70 bpm, and were more likely to have higher NYHA (New York Heart Association) heart failure class, to be smokers or diabetics, and less likely to be treated with β blockers. The mean age of the population was 65
Discussion
In this prospective study, we report an association between elevated heart rate and the risk of cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular dysfunction. Our study confirms previous reports that elevated heart rate is a predictor of mortality and heart failure in patients with coronary artery disease.2, 3 However, our results also extend these observations to coronary events such as admission to hospital for fatal and non-fatal myocardial
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