Elsevier

International Journal of Cardiology

Volume 168, Issue 2, 30 September 2013, Pages 1490-1495
International Journal of Cardiology

Predictive value of night-time heart rate for cardiovascular events in hypertension. The ABP-International study

https://doi.org/10.1016/j.ijcard.2012.12.103Get rights and content

Abstract

Background

Data from prospective cohort studies regarding the association between ambulatory heart rate (HR) and cardiovascular events (CVE) are conflicting.

Methods

To investigate whether ambulatory HR predicts CVE in hypertension, we performed 24-hour ambulatory blood pressure and HR monitoring in 7600 hypertensive patients aged 52 ± 16 years from Italy, U.S.A., Japan, and Australia, included in the ‘ABP-International’ registry. All were untreated at baseline examination. Standardized hazard ratios for ambulatory HRs were computed, stratifying for cohort, and adjusting for age, gender, blood pressure, smoking, diabetes, serum total cholesterol and serum creatinine.

Results

During a median follow-up of 5.0 years there were 639 fatal and nonfatal CVE. In a multivariable Cox model, night-time HR predicted fatal combined with nonfatal CVE more closely than 24 h HR (p = 0.007 and = 0.03, respectively). Daytime HR and the night:day HR ratio were not associated with CVE (p = 0.07 and = 0.18, respectively). The hazard ratio of the fatal combined with nonfatal CVE for a 10-beats/min increment of the night-time HR was 1.13 (95% CI, 1.04–1.22). This relationship remained significant when subjects taking beta-blockers during the follow-up (hazard ratio, 1.15; 95% CI, 1.05–1.25) or subjects who had an event within 5 years after enrollment (hazard ratio, 1.23; 95% CI, 1.05–1.45) were excluded from analysis.

Conclusions

At variance with previous data obtained from general populations, ambulatory HR added to the risk stratification for fatal combined with nonfatal CVE in the hypertensive patients from the ABP-International study. Night-time HR was a better predictor of CVE than daytime HR.

Introduction

Several studies have demonstrated an association between resting heart rate (HR) and cardiovascular mortality both in general populations [1], [2], [3] and in patients with hypertension [4], [5] or cardiac diseases [6], [7]. However, a few HR readings taken in a clinic environment might be poorly representative of the actual HR levels leading to an underestimation of their real predictive power. HR assessed out of the office in association with ambulatory blood pressure is more representative of a subject's usual HR and offers additional information about the HR circadian pattern, including HR during the sleep period. Several studies have specifically explored the association between ambulatory HR and fatal and nonfatal cardiovascular events (CVE) but the evidence relating outcome to ambulatory HR remains incomplete and lacks consistency [8], [9], [10], [11], [12], [13], [14]. Most investigators reported only on fatal outcomes, with night-time HR or a blunted fall in HR at night predicting all-cause mortality in some of these studies [8], [9], [12], [13]. HR nondipping predicted CVE in one study [14]. In keeping with what was observed with ambulatory blood pressure [15], these results suggest that HR during sleep, or the day–night HR dip might have better predictive power than daytime HR. The few studies that reported information on CVE failed to demonstrate an independent association between ambulatory HR and cardiovascular outcomes either in general populations [12], [13] or in hypertensive patients [8]. Establishing the predictive value of ambulatory HR for CVE in hypertension would have important therapeutic implications because antihypertensive drugs with cardiac slowing properties may exert an additional benefit in patients with high HR.

The “Ambulatory Blood Pressure in referred hypertensive subjects: an International database” (ABP-International) is an international consortium composed of normotensive and hypertensive subjects assessed with 24-hour ambulatory blood pressure and HR measurements. The aim of the current study was to explore the relationship between ambulatory HR at baseline and fatal combined with nonfatal CVE in this international database and to investigate the relationship between 24-hour, daytime, and night-time HR and CVE in the 7600 hypertensive patients from this database.

Section snippets

Study population

The ABP-International study is an international registry established in order to investigate the relationship of 24-hour ambulatory blood pressure and HR with morbidity and mortality in a large patient population recruited in different centers around the world. The database was constructed by systematically merging 8 prospective studies from 3 European, 3 Japanese, 1 North American, and 1 Australian centers. Although protocols were not standardized, studies were conducted following similar

Results

The study population consisted of 3435 women (45.2%) and 4165 men (54.8%). Of these, 6583 were Caucasians (86.6%) and 1017 were Asians (13.4%). None of the subjects considered for this analysis had atrial fibrillation or other relevant arrhythmias at baseline assessment. At enrollment, 1556 participants (20.5%) were current smokers, and 608 (8.0%) were diabetics. Mean age ± SD was 52.4 ± 15.8 years, office systolic blood pressure was 155.7 ± 16.5 mm Hg, diastolic BP was 95.0 ± 9.5 mm Hg, and body mass index

Discussion

The present analysis relating to a cohort of untreated hypertensive patients from the ABP-International database has demonstrated an independent association of ambulatory HR with fatal combined with nonfatal CVE in these patients. This relationship was linear and similar in the two genders. Among the ambulatory HRs, the model including night-time HR was more informative in predicting the outcome than models with daytime or 24-hour HR. For every 10-beats/min increment in night-time HR, the

Acknowledgments

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.

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