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Year : 2020  |  Volume : 2  |  Issue : 2  |  Page : 80-85

Visit-to-visit blood pressure variability in patients with chronic heart failure with reduced ejection fraction

1 Department of Internal Diseases with Courses of Cardiology and Functional Diagnostics, Peoples' Friendship University of Russia (RUDN University), Moscow, Russia
2 Russian Clinical and Research Center of Gerontology, Pirogov's Russian National Research Medical University), Moscow, Russia
3 MPS Hospital, Podbelskovo Street, Department of Cardiac Surgery, RUDN University, Moscow, Russia
4 Department of Cardiology, Illinois Masonic Medical Center, Chicago, IL USA, India
5 Department of Pharmacology & Clinical Pharmacy, College of Medicine & Health Sciences, Sultan Qaboos University; Gulf Health Research, Muscat, Oman

Date of Submission19-Jun-2020
Date of Decision25-Jun-2020
Date of Acceptance26-Jun-2020
Date of Web Publication21-Aug-2020

Correspondence Address:
Prof.Dr. Zhanna Kobalava
Head of the Department, Department of Internal Medicine with the Subspecialty of Cardiology and Functional Diagnostics Named after Prof. V.S. Moiseev, Institute of Medicine, RUDN University Moscow
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ACCJ.ACCJ_17_20

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Background: There is a growing evidence of the prognostic significance of visit-to-visit blood pressure variation in different groups of patients but for heart failure with reduced ejection fractions remains a matter of controversy. Objective: The objective of the study was to evaluate the impact of visit-to-visit blood pressure variability (BPV) on the prognosis in patients with stable heart failure (HF) with reduced ejection fraction (EF). Methods: The retrospective analysis included 100 pts (80 men, age 64.4 ± 9.3 years, baseline BP 127.6 ± 15.1/77.9 ± 8.3 mmHg) with chronic heart failure II-IV NYHA functional class with mean EF 32.3 ± 4.3%. All patients received optimal medical therapy for HF. BP was measured with a validated oscillometric device. Visit-to-visit BPV was calculated as standard deviation, and the coefficient of variation of average BP for seven visits during 18 months. The endpoints were death, myocardial infarction, stroke, and hospitalization for HF. Results: Visit-to-visit systolic BPV (SBPV) ranged between 2.3 and 20.0 mmHg. A total of 47 endpoints in 37 patients were recorded. The patients with endpoints had higher visit-to-visit SBPV (11.2 ± 4.0 vs. 9.5 ± 3.5 mmHg, P < 0.05). Logistic regression analysis revealed that the risk of all negative outcomes was independently associated with lower EF (adjusted odds ratio (aOR) 0.84; 95% confidence interval (CI): 0.73-0.97; P = 0.02) and SBPV > 10.9 mmHg (aOR 3.0; 95% CI: 1.27–7.06; P = 0.01). Conclusions: Visit-to-visit SBPV >10.9 mmHg as well as lower EF were independently associated with negative outcomes in patients with stable HF with reduced EF.

Keywords: Chronic heart failure, reduced ejection fraction, visit-to-visit blood pressure variability; Russia

How to cite this article:
Kobalava Z, Kotovskaya Y, Troitskaya E, Babaeva L, Parvathy UT, Brady PA, Al-Zakwani I. Visit-to-visit blood pressure variability in patients with chronic heart failure with reduced ejection fraction. Ann Clin Cardiol 2020;2:80-5

How to cite this URL:
Kobalava Z, Kotovskaya Y, Troitskaya E, Babaeva L, Parvathy UT, Brady PA, Al-Zakwani I. Visit-to-visit blood pressure variability in patients with chronic heart failure with reduced ejection fraction. Ann Clin Cardiol [serial online] 2020 [cited 2023 Jun 4];2:80-5. Available from:

  Introduction Top

Visit-to-visit systolic blood pressure variability (SBPV) has prognostic significance for negative cardiovascular (CV) outcomes in the general population and high-risk groups.[1],[2],[3],[4],[5],[6] Blood pressure variability (BPV) is a complex phenomenon whereby BP variations are observed during the different periods of time. These time periods define physiological differences between regulatory mechanisms responsible for different types of BPV.[7],[8] Prognostic significance of visit-to-visit BPV is well established in patients with arterial hypertension (AH),[2],[4],[9],[10],[11],[12],[13],[14] diabetes mellitus (DM), and chronic kidney disease.[3],[15],[16]

Recent studies have shown independent associations of visit-to-visit BPV with adverse outcomes in patients with stroke [17] and with ST-elevation myocardial infarction.[18] Chronic heart failure with reduced ejection fraction (HFr EF) is regarded as a state of “paradoxical epidemiology”: Higher blood pressure is associated with better outcome.[16],[19],[20],[21] Partially, this finding can be explained by the fact that in chronic HF (CHF) a higher BP reflects better cardiac output.[22] Previous studies of BPV in CHF focused on short-term BPV assessed with 24-h BP monitoring. In these studies, general characteristics, association with EF, and the level of NTproBNP were evaluated and correlations of low 24-h BP variability with more severe course of the disease, and its poor prognostic significance were shown.[23],[24],[25],[26] However, determinants of visit-to-visit BPV principally differ from those of the short-term one and are lacking in this population and are controversial.[27]

The aim of the study was to characterize visit-to-visit BPV and assess its possible prognostic significance in the group of patients with controlled AH and chronic HFr EF.

  Methods Top

We retrospectively analyzed the data of 100 patients with controlled AH and stable HF with EF <40% (NYHA class II-IV) and baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) >400 pmol/l.[28] Patients were followed at the clinic of internal disease and cardiology in Peoples' Friendship University of Russia (RUDN University). Only patients who had data on BP level for at least seven visits during 18 months with equal intervals between the visits were included. All patients received optimal standard therapy of chronic HFr EF.[29] The exclusion criteria included known intolerance to angiotensin-converting enzyme inhibitor (ACEi); systolic BP of < 90 mm Hg; documented or suspected significant renal artery stenosis; serum creatinine of > 220 μmol/L; serum potassium of < 3.5 mmol/L or greater than 5.7 mmol/L. Study endpoints were death from any cause, hospitalization for acute decompensated HF, myocardial infarction (MI), and stroke.

BP was measured with a validated oscillometric device. Measurements were performed in the morning between 8 a. m. and 11 a. m. before a regular dose of anti-hypertensive medications on the same arm after 5 min of rest. All the measurements were taken in the sitting position. Two-three measurements with the interval not less than 1 min were made. For patients with atrial fibrillation (AF), at least three measurements were performed. The average BP level was calculated for each visit.

Calculation of visit-to-visit blood pressure variability

BPV was only determined in circumstances where doses of anti-hypertensive therapy were unchanged for at least 2 months before 18 months after. Visit-to-visit clinical BPV was evaluated for seven sequential visits with equal intervals of 10 weeks between them for each patient. Two measures of BPV were calculated for each subject: the standard deviation (SD) and the coefficient of variation. The within-subject SD is the SD of each blood pressure measure over all follow-up visits for each subject. The coefficient of variation is the SD in blood pressure divided by the mean blood pressure over all follow-up visits.[30]

Statistical analysis

Baseline characteristics were presented as mean ± SD, median with interquartile range and number (%) as appropriate. Kolmogorov–Smirnov test for normality was used. Mann–Whitney and Chi-square tests were used for the statistical comparisons of two groups. One-factor and multi-factor correlation analysis and receiver-operating characteristic (ROC)-curves analysis were done. Spearmen's correlation coefficients were calculated to evaluate the relationships between the variables. Multiple linear regression was performed to assess the variables associated with the outcomes. ROC curves were used to assess the sensitivity and specificity of studied parameters. The results were considered statistically significant in P < 0.05. Statistical analyses were performed using Statistica version 8 (Statistica version 8, Dell, Texas, USA).

  Results Top

Baseline characteristics are presented in [Table 1]. All patients received maximum tolerated doses of ACEI and beta-blockers, 69% of patients were prescribed furosemide daily, 51% received spironolactone, 89% received aspirin, and 42% were prescribed digoxin. EF was 32.3 ± 4.3% (ranging from 19.0% to 39.0%). The median NT-proBNP was 1200 (828–3354 pmol/l). A total of 47 endpoints were registered in 37 patients: 21 deaths, 17 hospitalizations for HF, 6 MI, and 3 strokes. Those with endpoints were characterized by significantly higher frequency of DM occurrence (54.1% vs. 33.3%; P = 0.04). Average baseline BP of the cohort was 127.6 ± 15.1/77.9 ± 8.3 mmHg. Baseline HR was 72.3 ± 10.4 bpm. After 18 months of follow-up, average BP was 123.6 ± 13.6/74.8 ± 8.9 mmHg and HR was 69.3 ± 9.1 bpm. Baseline and final BP levels were similar in groups with and without adverse outcomes [Table 2].
Table 1: Baseline characteristic of the study group

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Table 2: Clinical blood pressure and heart rate stratified by the presence of outcome endpoints

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Despite relatively stable BP values, visit-to-visit variability demonstrated a wide range: SD for SBP from 2.3 to 20 mmHg (average 10.2 ± 3.8 mmHg), for diastolic BP (DBP) – from 1.5 to 13.1 mmHg (average 6.3 ± 2.2 mmHg). The average coefficient of variation for SBP was 8.2 ± 3.0%, for DBP–6.9 (5.6;9.6%). AF, present in 22 patients, could be a potential reason for BPV. Patients with AF had higher HR at baseline and at the end of follow-up, but similar BP and visit-to-visit BPV levels [Table 3]. The average level of SBPV was significantly higher in the group with CV outcomes [Table 4].
Table 3: Characteristics of the cohort stratified according to the presence of atrial fibrillation

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Table 4: Visit-to-visit blood pressure variability stratified according to the presence of outcome endpoints

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Spearmen correlation analysis revealed a significant correlation between negative outcome DM (r = 0.20), NYHA class III (r = 0.21), and visit-to-visit SBPV (r = 0.22). Multiple logistic regression analysis had shown independent associations of all negative outcomes with lower EF and higher visit-to-visit SBPV. The same associations were shown for death outcome alone [Table 5].
Table 5: Multivariate logistic regression for negative outcomes and death

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ROC analysis was performed to determine the sensitivity and specificity of visit-to-visit SBPV as a predictor of negative outcomes [Figure 1]. After the inclusion of other variables associated with negative prognostic factors in patients with HFr EF (age, EF, NT-proBNP concentration, ACEI dose, SBP, and HR), only visit-to-visit SBPV > 10.9 mmHg was highly sensitive and specific for the prediction of negative outcomes (72.7% sensitivity, 80% specificity; area under curve = 0.74, 95% confidence interval [CI]: 0.53–0.94; P = 0.02).
Figure 1: Results of receiver operating characteristic-analysis for visit-to-visit BP variability in patients with endpoints. ACEi: Angiotensin-converting enzyme inhibitor, EF: Ejection fraction, HR: Heart rate, NT-proBNP: N-terminal prohormone of brain natriuretic peptide, SBP: Systolic blood pressure, SBPV: Systolic blood pressure variability

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Groups with visit-to-visit SBPV above and below 10.9 mmHg were similar by baseline clinical and demographical characteristics, risk factors, baseline, and final BP and HR. No associations with visit-to-visit SBPV increase were found. No correlations were observed between visit-to-visit BPV and renal function, creatinine and estimated glomerular filtration rate (GFR) changes with outcomes.

  Discussion Top

The present study provides important insights into visit-to-visit BPV and its influence on outcomes in HF patients with reduced EF. We observed that visit-to-visit variability of clinical SBP may be an important parameter not only in patients with uncomplicated AH [4],[11],[12] but also in a vulnerable population of HFr EF patients. Supposing that medication intake could contribute to visit-to-visit BPV, analysis of comparison of visit-to-visit BP variability with renal function variability was undertaken, as factor of treatment (especially with ACEI and diuretics) is able to influence the levels of serum creatinine and GFR.

Our study included 100 patients with stable CHF with reduced EF <40% and increase of NT-proBNP > 400 pmol/l, with a history of controlled AH and CHD in most of the cases. The evaluation of visit-to-visit BP variability was carried out on the background of stable evidence-based therapy of CHF. The results of the analysis demonstrated for the first time that despite stable target office BP levels visit-to-visit SBPV > 10.9 mmHg was associated with adverse outcomes in this population. Our results are consistent with the findings of the HEAAL study [26] that included patients with chronic HFr EF with NYHA class II-IV (n = 3732) randomized to high and low losartan doses (150 and 50 mg). In that study, visit-to-visit BP variability was calculated as SD, coefficient of variation and average real variability for the 12 visits during 6.8 years of unchanged therapy. Average visit-to-visit SBP variability is similar to the results of our study (11.05 ± 4.28 mmHg and 10.2 ± 3.8 mmHg for SD; 8.8 ± 3.2% and 8.2 ± 3.0% for coefficient of variation, respectively).

The HEAAL analysis also showed that high visit-to-visit SBP variability was associated with increased risk of CV outcomes (HR 1.023, 95% CI 1.013–1.034, P < 0.0001), regardless of losartan dose.[27] These results are also relevant to the data received in our study. Taken together, the results confirm that short-term (24-h BP monitoring) and long-term (visit-to-visit) BPV reflect the influence of different regulatory systems. Possible unfavorable significance of higher visit-to-visit BPV may be explained by the fact that in chronic HFr EF the capability of the organism to maintain stable BP level is lost and its sensitivity to environmental influences, including drugs, is high. This suggests that patients with HFr EF may have an autonomous BPV phenotype that paralleled the progressive and sustained CV target organ damage associated with the disease.[27]

Our finding that only EF and visit-to-visit variability of clinical SBP were the significant predictors of adverse outcomes may be explained in different ways. First, the small size of the sample is an important limitation of the study. Second, as the level NT-proBNP was the criterion for patients' selection, we included patients with high NT-proBNP initially having poorer prognosis.

Prognostic significance of age, NYHA functional class, SBP, HR, EF, and NT-proBNP in patients with CHF is well known.[31] The assessment of the variability of these indexes at long-term observation in relatively stable patients with HF receiving evidence-based therapy may be important. Several studies that assessed BPV in HF were focused mostly on short-term indexes: contradictory data related to its prognostic significance were received, but the results generally confirmed the associations between low 24-h BP variability and adverse outcomes. This was explained by the impairment of neurohormonal regulation that is considered to be the main mechanism of this type of BPV and by inability of CV system to provide BP adaptation in conditions of CHF.[32]

The study limitations include retrospective design and relatively small sample. Besides, factor of the therapy (time of intake and spectrum of medications, their action duration, and doses) was not analyzed in details. Hence, larger prospective studies are needed to confirm these results. The absence of correlations of the outcomes with age, NT-proBNP, and SBP may be explained by the small size of the group.

  Conclusions Top

Heterogeneity of individual visit-to-visit BP variability is observed in patients with compensated CHF with reduced EF, despite stable BP level. Visit-to-visit SBPV >10.9 mmHg and low-ejection fraction may be the important predictors of adverse CV outcomes and death.

Data availability

The data are available upon request. Contact author is Dr. Elena Troitskaya, associate professor at the Department of Internal Diseases with Courses of Cardiology and Functional Diagnostics, Peoples' Friendship University of Russia (RUDN University). E-mail: trelen@yandex. ru, phone number + 79165140285. Mail address: 61, Vavilova street, Moscow, Russia, 117292.

Financial support and sponsorship

The publication was prepared with the financial support of the “RUDN University Program 5-100.”

Conflicts of interest

There are no conflicts of interest.

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  [Figure 1]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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