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Research Article | Open Access

Nocturnal hypertension and riser pattern are associated with heart failure rehospitalization in patients with heart failure with preserved ejection fraction

Gang HUANG1,2,3,4(), Xiao-Han LIU3, Yue ZHANG3, Yu-Xin ZHU3, Yun HE1,2,3,4, Tian-Bo WANG3, Zhen ZHANG1,2,3,4, Jun-Bo XU1,2,3,4()
Department of Cardiology, the Third People’s Hospital of Chengdu, Sichuan, China
Cardiovascular Disease Research Institute of Chengdu, Sichuan, China
Affiliated Hospital of Southwest Jiaotong University, Sichuan, China
The Second Affiliated Chengdu Clinical College of Chongqing Medical University, Sichuan, China
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Abstract

BACKGROUND

Nocturnal hypertension is reported as a risk factor for cardiovascular disease. This study aimed to explore the potential association between nocturnal hypertension and heart failure (HF) rehospitalization in patients with HF with preserved ejection fraction (HFpEF).

METHODS

A total of 538 patients with HFpEF from May 2018 to December 2021 were consequently recruited in this study and followed up until they were readmitted for HF or the end of this study. Cox regression analysis was used to reveal the potential association between nighttime blood pressure (BP) levels, nocturnal hypertension and nocturnal BP patterns and HF rehospitalization. Kaplan-Meier curve was used to assess the cumulative event-free survival rate between groups.

RESULTS

There were 537 patients with HFpEF were included in the final analysis. The mean age of the study population was 77.14 ± 8.68 years, and 41.2% of patients were men. After a median follow-up duration of 10.93 (4.19–21.13) months, 176 patients (32.7%) with HFpEF were readmitted for HF. Cox regression analysis had revealed that nighttime systolic BP level [hazards ratio (HR) = 1.018, 95% CI: 1.008–1.028, P = 0.001], nighttime diastolic BP level (HR = 1.024, 95% CI: 1.007–1.042, P = 0.007), nocturnal hypertension (HR = 1.688, 95% CI: 1.229–2.317, P = 0.001) were associated with HF rehospitalization. Kaplan-Meier analysis had demonstrated that patients with nocturnal hypertension had significantly lower event-free survival rate (log-rank P < 0.001). Furthermore, patients with a riser pattern had a higher risk of HF rehospitalization (HR = 1.828, 95% CI: 1.055–3.166, P = 0.031) and lower event-free survival rate (log-rank P = 0.003) than those with a dipper pattern. These findings were also confirmed in patients with HFpEF and hyperuricemia.

CONCLUSIONS

Nighttime BP levels, nocturnal hypertension and a riser pattern are independently associated with HF rehospitalization in patients with HFpEF, and prominently in patients with HFpEF and hyperuricemia. Well controlled nighttime BP levels should be emphasized and considered in patients with HFpEF.

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Journal of Geriatric Cardiology
Volume 20 Issue 6,
June 2023
Pages 448-458
DOI: 10.26599/1671-5411.2023.06.003
Cite this article:
HUANG G, LIU X-H, ZHANG Y, et al. Nocturnal hypertension and riser pattern are associated with heart failure rehospitalization in patients with heart failure with preserved ejection fraction. Journal of Geriatric Cardiology, 2023, 20(6): 448-458. https://doi.org/10.26599/1671-5411.2023.06.003
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Baseline characteristics of patients with heart failure with preserved ejection fraction by nocturnal hypertension.

CharacteristicsAll (n = 537)Nocturnal hypertension (n = 201)Non-nocturnal hypertension (n = 336)P-value
Data are presented as means ± SD or n (%).
Age, yrs 　　77.14 ± 8.68 　　77.71 ± 8.88 　　76.79 ± 8.55 0.208
Male 221 (41.2%) 96 (47.8%) 125 (37.2%) 0.016
Current smoking 53 (9.9%) 21 (10.4%) 32 (9.5%) 0.728
Current drinking 27 (5.0%) 13 (6.5%) 14 (4.2%) 0.238
Medical history
　Hypertension 414 (77.1%) 171 (85.1%) 243 (72.3%) 0.001
　Coronary artery disease 225 (41.9%) 88 (43.8%) 137 (40.8%) 0.494
　Diabetes mellitus 188 (35.0%) 76 (37.8%) 112 (33.3%) 0.292
　Chronic kidney disease 140 (26.1%) 59 (29.4%) 81 (24.1%) 0.180
Medication
　Angiotensin-converting enzyme inhibitors/Angiotensin II receptor blockers/Angiotensin receptor-neprilysin inhibitors 235 (43.8%) 100 (49.8%) 135 (40.2%) 0.030
　Beta-blocker 310 (57.7%) 114 (56.7%) 196 (58.3%) 0.714
　Spironolactone 239 (44.5%) 85 (42.3%) 154 (45.8%) 0.424
　Calcium channel blocker 231 (43.0%) 111 (55.2%) 120 (35.7%) < 0.001
　Diuretics 375 (69.8%) 141 (70.1%) 234 (69.6%) 0.902
　Antiplatelet 154 (28.7%) 65 (32.3%) 89 (26.5%) 0.147
　Anticoagulation 234 (43.6%) 74 (36.8%) 160 (47.6%) 0.015
　Anti-diabetic 119 (22.2%) 44 (21.9%) 75 (22.3%) 0.907
　Statin 299 (55.7%) 119 (59.2%) 180 (53.6%) 0.204
Body mass index, kg/m2 24.22 ± 3.97 24.77 ± 3.78 23.90 ± 4.06 0.014
Heart rates, beat/min 82.11 ± 19.61 80.40 ± 19.41 83.14 ± 19.68 0.074
NYHA class III or IV 416 (77.5%) 153 (76.1%) 263 (78.3%) 0.563
Left ventricular ejection fraction, % 59.30 ± 4.09 58.92 ± 4.09 59.52 ± 4.08 0.144
Office blood pressure
　Systolic blood pressure, mmHg 134.93 ± 23.06 141.88 ± 22.70 130.78 ± 22.29 < 0.001
　Diastolic blood pressure, mmHg 75.07 ± 13.30 76.58 ± 13.16 74.17 ± 13.32 0.065
24-hour ambulatory blood pressure
　Systolic blood pressure, mmHg 124.03 ± 15.29 137.09 ± 11.08 116.21 ± 11.70 < 0.001
　Diastolic blood pressure, mmHg 73.08 ± 8.59 79.19 ± 7.67 69.43 ± 6.87 < 0.001
Daytime ambulatory blood pressure
　Systolic blood pressure, mmHg 124.29 ± 14.97 136.69 ± 11.33 116.88 ± 11.61 < 0.001
　Diastolic blood pressure, mmHg 73.55 ± 10.24 79.61 ± 12.02 69.92 ± 6.879 < 0.001
Nighttime ambulatory blood pressure
　Systolic blood pressure, mmHg 122.99 ± 16.68 139.12 ± 10.18 113.34 ± 11.55 < 0.001
　Diastolic blood pressure, mmHg 72.45 ± 9.61 80.56 ± 6.98 67.59 ± 7.45 < 0.001
Laboratory parameter
　Hemoglobin, g/L 120.21 ± 21.63 118.37 ± 22.65 121.31 ± 20.95 0.103
　Fasting plasma glucose, mmol/L 6.65 ± 2.87 6.96 ± 3.33 6.47 ± 2.54 0.284
　Total cholesterol, mmol/L 3.84 ± 1.07 3.94 ± 1.18 3.78 ± 0.99 0.213
　Low-density lipoprotein cholesterol, mmol/L 2.21 ± 0.80 2.28 ± 0.81 2.17 ± 0.79 0.162
　Na+, mmol/L 140.73 ± 4.31 140.62 ± 3.44 140.79 ± 4.76 0.225
　K+, mmol/L 4.02 ± 0.60 4.10 ± 0.62 3.97 ± 0.57 0.042
　Serum uric acid, µmol/L 429.49 ± 136.25 423.14 ± 130.02 433.29 ± 139.90 0.567
　Blood urea nitrogen, mmol/L 8.54 ± 5.35 9.39 ± 6.96 8.04 ± 4.03 0.197
　Creatinine, μmol/L 113.20 ± 102.96 126.89 ± 115.92 105.00 ± 93.58 0.089
　Estimated glomerular filtration rate, mL/min per 1.73 m2 73.75 ± 27.15 70.53 ± 28.88 75.67 ± 25.90 0.081
　Brain natriuretic peptide, pg/mL 581.26 ± 653.27 649.00 ± 726.20 540.74 ± 602.96 0.024

Baseline characteristics of patients with heart failure with preserved ejection fraction by nocturnal blood pressure pattern.

CharacteristicsDipper pattern (n = 67)Non-dipper pattern (n = 249)Riser pattern (n = 221)P-value
Data are presented as means ± SD or n (%).
Age, yrs 76.54 ± 8.50 76.09 ± 9.34 78.49 ± 7.78 0.020
Male 31 (46.3%) 91 (36.7%) 99 (44.6%) 0.146
Current smoking 8 (11.9%) 25 (10.1%) 20 (9.0%) 0.771
Current drinking 5 (7.5%) 15 (6.0%) 7 (3.2%) 0.197
Medical history
　Hypertension 47 (70.1%) 190 (76.6%) 177 (79.7%) 0.255
　Coronary artery disease 26 (38.8%) 109 (44.0%) 90 (40.5%) 0.650
　Diabetes mellitus 20 (29.9%) 94 (37.9%) 74 (33.3%) 0.373
　Chronic kidney disease 15 (22.4%) 64 (25.8%) 61 (27.5%) 0.702
Medication
　Angiotensin-converting enzyme inhibitors/Angiotensin II receptor blockers/Angiotensin receptor-neprilysin inhibitors 31 (46.3%) 108 (43.5%) 96 (43.2%) 0.905
　Beta-blocker 38 (56.7%) 151 (60.9%) 121 (54.5%) 0.370
　Spironolactone 36 (53.7%) 110 (44.4%) 93 (41.9%) 0.232
　Calcium channel blocker 17 (25.4%) 102 (41.1%) 112 (50.5%) 0.001
　Diuretics 51 (76.1%) 173 (69.8%) 151 (68.0%) 0.448
　Antiplatelet 17 (25.4%) 70 (28.2%) 67 (30.2%) 0.731
　Anticoagulation 31 (46.3%) 120 (48.4%) 83 (37.4%) 0.050
　Anti-diabetic 9 (13.4%) 60 (24.2%) 50 (22.5%) 0.168
　Statin 29 (43.3%) 151 (60.9%) 119 (53.6%) 0.026
Body mass index, kg/m2 23.92 ± 3.89 24.30 ± 3.98 24.23 ± 4.01 0.945
Heart rates, beat/min 80.40 ± 19.34 82.25 ± 19.75 82.48 ± 19.59 0.777
NYHA class III or IV 53 (79.1%) 185 (74.3%) 178 (80.5%) 0.255
Left ventricular ejection fraction, % 58.57 ± 3.47 59.31 ± 4.21 59.50 ± 4.13 0.143
Office blood pressure
　Systolic blood pressure, mmHg 131.79 ± 23.34 133.89 ± 23.45 137.05 ± 22.44 0.110
　Diastolic blood pressure, mmHg 77.55 ± 14.08 74.67 ± 13.34 74.77 ± 12.98 0.472
24-hour ambulatory blood pressure
　Systolic blood pressure, mmHg 128.06 ± 17.02 123.19 ± 15.40 123.74 ± 14.47 0.085
　Diastolic blood pressure, mmHg 75.39 ± 9.04 72.52 ± 8.94 73.00 ± 7.97 0.058
Daytime ambulatory blood pressure
　Systolic blood pressure, mmHg 130.39 ± 16.56 124.10 ± 15.23 122.68 ± 13.74 0.004
　Diastolic blood pressure, mmHg 77.63 ± 11.77 73.50 ± 11.54 72.37 ± 7.59 0.002
Nighttime ambulatory blood pressure
　Systolic blood pressure, mmHg 111.73 ± 16.54 118.97 ± 14.92 130.87 ± 15.00 < 0.001
　Diastolic blood pressure, mmHg 67.09 ± 10.65 70.47 ± 8.93 76.27 ± 8.56 < 0.001
Laboratory parameter
　Hemoglobin, g/L 122.48 ± 21.70 120.46 ± 21.49 119.24 ± 21.80 0.504
　Fasting plasma glucose, mmol/L 6.24 ± 2.14 6.68 ± 2.67 6.75 ± 3.24 0.562
　Total cholesterol, mmol/L 3.84 ± 0.93 3.86 ± 1.08 3.82 ± 1.10 0.922
　Low-density lipoprotein cholesterol, mmol/L 2.20 ± 0.63 2.23 ± 0.77 2.20 ± 0.88 0.820
　Na+, mmol/L 140.75 ± 3.72 140.67 ± 3.71 140.79 ± 5.06 0.851
　K+, mmol/L 4.03 ± 0.54 4.04 ± 0.62 4.00 ± 0.59 0.581
　Serum uric acid, µmol/L 422.07 ± 130.59 433.16 ± 141.03 427.64 ± 132.92 0.797
　Blood urea nitrogen, mmol/L 8.05 ± 3.78 8.21 ± 5.20 9.06 ± 5.88 0.119
　Creatinine, μmol/L 110.71 ± 116.92 106.83 ± 76.15 121.05 ± 122.62 0.404
　Estimated glomerular filtration rate, mL/min per 1.73 m2 74.01 ± 25.75 76.37 ± 27.13 70.74 ± 27.39 0.094
　Brain natriuretic peptide, pg/mL 613.63 ± 787.42 502.58 ± 579.32 659.39 ± 679.24 0.002

Cox regression analysis of nocturnal blood pressure in patients with heart failure with preserved ejection fraction.

Nighttime systolic blood pressure levelNighttime diastolic blood pressure levelNocturnal hypertension
HR (95% CI)P-valueHR (95% CI)P-valueHR (95% CI)P-value
Model 1: not adjusted. Model 2: adjusted for age, history of hypertension, and body mass index. Model 3: adjusted for variables in Model 2 plus history of diabetes mellitus, blood urea nitrogen, estimated glomerular filtration rate, and hemoglobin.
Model 1 1.016 (1.007–1.026) 0.001 1.018 (1.002–1.035) 0.031 1.620 (1.203–2.180) 0.001
Model 2 1.020 (1.010–1.030) < 0.001 1.025 (1.008–1.043) 0.005 1.782 (1.301–2.439) < 0.001
Model 3 1.018 (1.008–1.028) 0.001 1.024 (1.007–1.042) 0.007 1.688 (1.229–2.317) 0.001

Cox analysis of nocturnal blood pressure pattern in patients with heart failure with preserved ejection fraction.

Nocturnal blood pressure patternRiser pattern vs. Dipper patternNon-dipper pattern vs. Dipper pattern
HR (95% CI)P-valueHR (95% CI)P-valueHR (95% CI)P-value
Model 1: not adjusted. Model 2: adjusted for age, history of hypertension, and body mass index. Model 3: adjusted for variables in Model 2 plus history of diabetes mellitus, blood urea nitrogen, estimated glomerular filtration rate, and hemoglobin.
Model 1 1.278 (1.121–1.457) < 0.001 2.253 (1.305–3.891) 0.004 1.429 (0.817–2.500) 0.211
Model 2 1.236 (1.077–1.419) 0.003 1.886 (1.086–3.276) 0.024 1.233 (0.701–2.168) 0.467
Model 3 1.168 (1.017–1.342) 0.028 1.828 (1.055–3.166) 0.031 1.390 (0.793–2.437) 0.250

Cox regression analysis of nocturnal blood pressure in patients with heart failure with preserved ejection fraction and hyperuricemia.

Nighttime systolic blood pressure levelNighttime diastolic blood pressure levelNocturnal hypertension
HR (95% CI)P-valueHR (95% CI)P-valueHR (95% CI)P-value
Model 1: not adjusted. Model 2: adjusted for age, history of hypertension, and body mass index. Model 3: adjusted for variables in Model 2 plus history of diabetes mellitus, blood urea nitrogen, estimated glomerular filtration rate, and hemoglobin.
Model 1 1.018 (1.006–1.030) 0.003 1.027 (1.006–1.048) 0.010 1.594 (1.001–2.539) 0.050
Model 2 1.024 (1.011–1.037) < 0.001 1.033 (1.011–1.055) 0.003 1.778 (1.266–2.620) 0.004
Model 3 1.019 (1.006–1.032) 0.003 1.024 (1.003–1.046) 0.028 1.805 (1.211–2.691) 0.004

Cox analysis of nocturnal blood pressure pattern in patients with heart failure with preserved ejection fraction and hyperuricemia.

Nocturnal blood pressure patternRiser pattern vs. Dipper patternNon-dipper pattern vs. Dipper pattern
HR (95% CI)P-valueHR (95% CI)P-valueHR (95% CI)P-value
Model 1: not adjusted. Model 2: adjusted for age, history of hypertension, and body mass index. Model 3: adjusted for variables in Model 2 plus history of diabetes mellitus, blood urea nitrogen, estimated glomerular filtration rate, and hemoglobin.
Model 1 1.322 (1.128–1.549) 0.001 2.501 (1.282–4.882) 0.007 1.484 (0.751–2.933) 0.256
Model 2 1.317 (1.118–1.552) 0.001 2.307 (1.177–4.521) 0.015 1.337 (0.673–2.656) 0.408
Model 3 1.236 (1.045–1.462) 0.013 2.038 (1.038–4.000) 0.039 1.323 (0.665–2.632) 0.426