Research ArticleEffect of visit-to-visit blood pressure variability on cardiovascular events in patients with coronary artery disease and well-controlled blood pressure
Introduction
Outcomes from recent post hoc analyses of major clinical end point trials and observational cohort studies have demonstrated that long-term visit-to-visit blood pressure variability (BPV) has prognostic value for detecting the development of cardiovascular events.1, 2, 3, 4, 5, 6 Although the pathogenic mechanisms underlying the relationship between visit-to-visit BPV and all-cause mortality are unclear,7 it is thought that variability may be related to inconsistent systolic blood pressure (SBP) control as well as more frequent exposure to higher maximum SBP, which were reported to be strong predictors of stroke in the United Kingdom Transient Ischaemic Attack (UK TIA) trial.1, 8
A clear relationship between visit-to-visit BPV and cardiovascular outcomes has not been observed in all analyses of clinical outcome trials.9, 10 For example, in a post hoc analysis of the European Lacidipine Study on Atherosclerosis (ELSA), visit-to-visit BPV was not associated with either end-organ damage or cardiovascular events, in patients with mild-to-moderate hypertension and at low cardiovascular risk.10 Therefore, the influence of visit-to-visit BPV on cardiovascular outcomes may differ according to the characteristics and the cardiovascular risk of the study population. The effects of visit-to-visit BPV on cardiovascular outcomes in patients with coronary artery disease (CAD) and well-controlled BP at baseline have not been specifically investigated using data from randomized clinical end point trials. Patients with CAD are at high risk for future cardiovascular events11 and as such, the association between visit-to-visit BPV and cardiovascular events may be important and should be investigated even in patients with relatively well-controlled BP. We performed a post hoc analysis to investigate the association between BPV and cardiovascular end points in patients with CAD using data extracted from two randomized, double-blind, cardiovascular end point studies (The Comparison of Amlodipine vs. Enalapril to Limit Occurrences of Thrombosis [CAMELOT] study and The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial [PREVENT]).12, 13
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Study Designs and Subjects
The study design and methodology of the CAMELOT and PREVENT studies have been described previously.12, 13 Briefly, the CAMELOT study was a randomized, double-blind, placebo-controlled, multicenter study comparing amlodipine, enalapril, or placebo in 1991 patients (aged 30–79 years) with angiographically documented CAD (≥20% stenosis diameter by visual estimation) and diastolic blood pressure (DBP) <100 mm Hg. Patients with left main CAD >50%, left ventricular ejection fraction of <40%, or
Study Population and BP Measurements
Baseline characteristics of the 1677 patients enrolled in CAMELOT, and 776 enrolled in PREVENT, and included in this post hoc study are given in Table 1, stratified by BPV quartile. The average number of BP measurements from the CAMELOT study was 8.4 for the amlodipine arm (N = 561) and 8.3 readings for both the enalapril (N = 548) and placebo (N = 568) arms, respectively. In PREVENT, the average number of readings was 9.2 for the amlodipine arm (N = 396) and 9.1 for the placebo arm (N = 380).
Discussion
The potential prognostic value of long-term visit-to-visit BPV is becoming apparent in certain populations, after post hoc analyses of long-term cardiovascular end point trials and observational studies.1, 2, 3, 4, 5, 6 Further information is still needed in certain sub-populations. Our study investigated the association between visit-to-visit BPV and major adverse cardiovascular outcomes in patients with hypertension and documented CAD, and there were several key findings. First,
Conclusion
In this post hoc analysis, BPV was significantly associated with cardiovascular events in patients with CAD and well-controlled BP. When analyzed separately by treatment, BPV was the significant and independent determinant for primary cardiovascular outcomes in the amlodipine group alone for the CAMELOT study. In addition BPV, but not mean SBP, was significantly associated with cardiovascular events with or without adjustment for other risk variables in both the CAMELOT and the PREVENT studies.
Acknowledgments
Medical writing support was provided by Karen Burrows, MPhil, CMPP, of Engage Scientific Solutions (Horsham, UK) and was funded by Pfizer.
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Grant Support: This study was sponsored by Pfizer.
Conflict of interest: S.P. acts as a paid consultant to Pfizer. P.Y., C.C., and B.W.J. are employees of Pfizer.