Determinants and Clinical Impact of Visit-to-visit Blood Pressure Variability in Patients with Heart Failure with Preserved Ejection Fraction

Abstract

Introduction: Blood pressure (BP) affects the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). However, the implications of its variability are poorly understood. This study aimed to explore the determinants and prognostic significance of visit-to-visit BP variability (V2V-BPV) in HFpEF.

Methods: Consecutive patients with HFpEF at the Sakakibara Heart Institute of Okayama underwent routine BP measurements. V2V-BPV, calculated as the coefficient of variation of systolic BP over one year, was assessed. The primary endpoint comprised all-cause mortality and heart failure hospitalization.

Results: Among 288 outpatients with HFpEF (average age 73 ± 10 years, 60.8% male), BP was measured 6.1 ± 1.7 times, with a median V2V-BPV of 7.3%. The high V2V-BPV group (≥7.3%) had marginally but significantly elevated B-type natriuretic peptide (BNP) levels and higher Meta-Analysis Global Group In Chronic Heart Failure risk scores (MAGGIC scores). V2V-BPV was independently associated with an increased risk of the primary endpoints (hazard ratio 1.08 per percentage point; p = 0.025), even after adjustments for systolic BP, BNP, MAGGIC score, and the number of BP measurements. A similar relationship was observed between all-cause mortality and V2V-BPV (adjusted hazard ratio 1.12, p = 0.049 with MAGGIC score). Hemoglobin level was an independent predictor of high V2V-BPV in multiple sensitivity analyses.

Conclusions: In patients with HFpEF, V2V-BPV was independently associated with adverse events, with hemoglobin level emerging as a determinant. Further research is warranted to determine whether BP stabilization can improve the prognosis of HFpEF.

Keywords: blood pressure variability; heart failure preserved ejection fraction; hypertension.

Figure 1.

The patient enrollment flowchart. Among 620 patients with heart failure who measured BP more than 4 times during the study period, 307 were excluded due to reduced LVEF, and an additional 25 were excluded based on other aforementioned criteria. As a result, 288 stable outpatients with HFpEF were included in the analysis. Patients were divided into 2 groups based on the median V2V-BPV value (7.3%). BP: blood pressure; HFpEF: heart failure with preserved ejection fraction; LVEF: left ventricular ejection fraction; V2V-BPV: visit-to-visit BP variability.

Figure 2.

The scatterplot of V2V-BPV and Mean systolic BP. There was no significant association between V2V-BPV and Mean systolic BP (r = −0.009, p = 0.89). x indicates the CV of systolic BP, and y indicates mean systolic BP. The scatterplot was created using Microsoft Excel (Microsoft Corp., Redmond, WA, USA). BP: blood pressure; CV: Coefficient of Variation; V2V-BPV: visit-to-visit BP variability.

Figure 3.

Kaplan-Meier curve analysis for the primary endpoint of a composite of all-cause mortality and heart failure hospitalization It showed that the high V2V-BPV group had a significantly higher event rate for the primary outcomes than the low V2V-BPV group (p = 0.001; Figure A). When stratified by the quartile of V2V-BPV, the curves indicated that higher V2V-BPV was associated with a higher event rate (p = 0.008, Figure B). BP: blood pressure; V2V-BPV: visit-to-visit BP variability.

Figure 4.

Kaplan-Meier curve analysis for the secondary endpoint of all-cause death The high and low V2V-BPV groups divided by the median value of V2V-BPV showed significantly different event risks. The quartile groups of V2V-BPV revealed a numerically higher risk in the higher V2V-BPV group, although the difference was not statistically significant, possibly due to the small number of events. BP: blood pressure; V2V-BPV: visit-to-visit BP variability.

Figure 5.

Seasonal distribution of BP measurements. BP measurements were evenly distributed in every season. BP: blood pressure.