Introduction
Atrial fibrillation (AF), the most common arrhythmia, imposes a huge global public health burden.[1,2] [3] [4] [5,6] [7,8] systolic blood pressure (SBP) level should not exceed 140 mmHg.[5]
Methods
Ethical approval
The study protocol was approved by the ethics committee of each center (Fuwai Hospital [2012-143]) and drafted in accordance with the Declaration of Helsinki . All participants provided signed informed consent.
Study design and population
This Chinese AF registry study conducted from 2008 to 2011 enrolled 2016 consecutive AF patients from 20 emergency centers (which were shown in supplementary materials, https://links.lww.com/CM9/B505 Figure 1 , 26 patients without detailed data were excluded, and 1990 subjects were included in the statistical analysis. Specific reasons for these patients visiting the emergency department was presented in Supplementary Table 1 (https://links.lww.com/CM9/B505
Figure 1: Flowchart of the study assessing the effect of the baseline BP on all-cause death in patients with AF. AF: Atrial fibrillation; BP: Blood pressure; DBP: Diastolic blood pressure; SBP: Systolic blood pressure .
Patients with AF were grouped based on SBP critical values as follows: ≤110 mmHg, >110 to ≤120 mmHg, >120 to ≤140 mmHg, >140 to ≤160 mmHg, and >160 mmHg. Cut-offs for the diastolic blood pressure (DBP) subgroups were as follows: <70 mmHg, ≥70 to <80 mmHg, ≥80 to <90 mmHg, and ≥90 mmHg.
Data collection
Demographics, BP on admission, heart rate on admission, and medications were all documented by electronic health records or by outpatient interviews of AF patients. Comorbidities on admission were also recorded, including hypertension, heart failure (HF), valvular heart disease, diabetes, coronary artery disease (CAD), myocardial infarction (MI), and stroke or transient ischemic attack (TIA). The CHADS2 score was calculated based on clinical guidelines.[9]
Follow-up and endpoints
All participants in this study were followed up for 1 year ± 1 month by physicians who were unaware of the protocol, either by telephone or in an outpatient interview. The primary endpoint of the study was all-cause death, which was defined as death from any causes. All participant deaths were confirmed by relatives, medical records, or physicians.
Statistical analysis
IBM SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA) and R version 4.0.4 (R Foundation for Statistical Computing, Vienna, Austria) were used to conduct the statistical analyses. Continuous variables are described as mean ± standard deviation, or median with interquartile range, according to their distributions. Categorical variables are presented as number and percentage. The differences in continuous variables were compared using the one-way Analysis of Variance or Kruskal–Wallis tests when appropriate; categorical variables were compared by Pearson's chi-squared tests. Kaplan–Meier survival curves for all-cause death based on SBP or DBP subgroups were created and checked using log-rank tests. We checked the proportional hazards assumption for SBP and DBP subgroups by using the Schoenfeld residuals method. SBP and DBP subgroups were compliant with proportional hazards assumption. Then, we conducted multivariable Cox regression analyses to calculate hazard ratio (HR) and 95% confidence interval (CI) for all-cause death. Risk predictors, including age, body mass index (BMI), type of AF, HF, CAD, diabetes mellitus, aspirin, oral anticoagulants, digoxin, statins, diuretics, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and beta-blockers were adjusted in the multivariable Cox regression models. A restricted cubic spline was also conducted for the adjusted HRs, using the baseline SBP and DBP as continuous variables. Furthermore, subgroup analyses were conducted to evaluate the interactions and associations between the baseline BP and all-cause mortality in different subgroups, including age (<70 years or ≥70 years), gender, BMI (<25 kg/m2 or ≥25 kg/m2 ), prior hypertension history (with or without hypertension), CAD (with or without CAD), HF (with and without HF) and CHADS2 score (≤1 or ≥2) subgroups. All statistical analyses were two-tailed, and P values <0.05 were regarded statistically significant.
Results
Baseline characteristics
Baseline characteristics of the study subjects according to baseline SBP groups are presented in Table 1 . Among the 1990 subjects, the median age was 71.0 years (60.0–78.0 years), and 45.0% (n = 896) were men. Patients with a higher baseline SBP were older and more likely to have a higher BMI and increased proportion of permanent AF. In addition, patients with a higher SBP tended to have comorbidities. In contrast, patients with the lowest SBP tended to have HF, and used more digoxin than other patients. Table 2 presents the clinical characteristics of patients with AF based on the baseline DBP groups. Those with a higher baseline DBP had a higher BMI. However, the distribution of AF types according to the baseline DBP stratification was not significantly different. Notably, the highest DBP group (DBP ≥90 mmHg) and the lowest DBP group (DBP <70 mmHg) tended to have more comorbidities, including HF, CAD, and MI.
Table 1 -
Clinical characteristics of patients with AF divided by baseline SBP.
Items
SBP ≤110 mmHg (n = 410)
110 < SBP ≤ 120 mmHg (n = 350)
120 < SBP ≤ 140 mmHg (n = 648)
140 < SBP ≤ 160 mmHg (n = 393)
SBP > 160 mmHg (n = 189)
χ
2 value
P- values
Age (years)
62.8 ± 15.0
67.0 ± 13.9
69.1 ± 12.4
72.0 ± 10.6
73.8 ± 11.0
–
<0.001
Male
175 (42.7)
171 (48.9)
284 (43.8)
181 (46.1)
85 (45.0)
3.569
0.467
BMI (kg/m2 )
23.0 ± 3.7
23.2 ± 3.7
23.8 ± 3.6
23.8 ± 3.3
23.8 ± 3.5
–
<0.001
HR (beat/min)
103 ± 31
102 ± 29
100 ± 29
102 ± 29
103 ± 29
–
0.652
AF type
17.447
0.026
Paroxysmal
88 (21.5)
93 (26.6)
147 (22.7)
83 (21.1)
38 (20.1)
Persistent
147 (35.9)
108 (30.9)
192 (29.6)
116 (29.5)
45 (23.8)
Permanent
175 (42.7)
149 (42.6)
309 (47.7)
194 (49.4)
106 (56.1)
CHADS2 score
185.228
<0.001
0
109 (26.6)
87 (24.9)
86 (13.3)
31 (7.9)
7 (3.7)
1
161 (39.3)
110 (31.4)
212 (32.7)
106 (27.0)
35 (18.5)
2
68 (16.6)
82 (23.4)
152 (23.5)
102 (26.0)
62 (32.8)
3
43 (10.5)
40 (11.4)
109 (16.8)
77 (19.6)
47 (24.9)
4
18 (4.4)
19 (5.4)
61 (9.4)
50 (12.7)
23 (12.2)
5
9 (2.2)
12 (3.4)
22 (3.4)
24 (6.1)
12 (6.3)
6
2 (0.5)
0 (0)
6 (0.9)
3 (0.8)
3 (1.6)
Medical history
Hypertension
114 (27.8)
141 (40.3)
391 (60.3)
309 (78.6)
155 (82.0)
305.492
<0.001
HF
185 (45.1)
121 (34.6)
229 (35.3)
125 (31.8)
84 (44.4)
22.074
<0.001
CAD
126 (30.7)
108 (30.9)
278 (42.9)
225 (57.3)
98 (51.9)
84.507
<0.001
MI
30 (7.3)
16 (4.6)
51 (7.9)
30 (7.6)
20 (10.6)
7.135
0.129
Diabetes mellitus
47 (11.5)
38 (10.9)
99 (15.3)
81 (20.6)
44 (23.3)
27.546
<0.01
Valvular heart disease
76 (18.5)
121 (34.6)
85 (13.1)
29 (7.4)
22 (11.6)
88.366
<0.001
Stroke/TIA
53 (12.9)
54 (15.4)
133 (20.5)
91 (23.2)
43 (22.8)
19.954
0.001
Medications
Oral anticoagulants
96 (23.4)
65 (18.6)
94 (14.5)
59 (15.0)
21 (11.1)
21.297
<0.001
Aspirin
199 (48.5)
185 (52.9)
369 (56.9)
232 (59.0)
107 (56.6)
11.323
0.023
Digoxin
155 (37.8)
124 (35.4)
182 (28.1)
94 (23.9)
54 (28.6)
24.419
<0.001
Amiodarone
38 (9.3)
38 (10.9)
49 (7.6)
45 (11.5)
21 (11.1)
5.840
0.211
Statin
67 (16.3)
58 (16.6)
159 (24.5)
135 (34.4)
57 (30.2)
51.002
<0.001
ACEI
68 (16.6)
78 (22.3)
152 (23.5)
107 (27.2)
53 (28.0)
16.373
0.003
ARB
39 (9.5)
45 (12.9)
114 (17.6)
85 (21.6)
35 (18.5)
26.818
<0.001
Beta-blockers
164 (40.0)
149 (42.6)
299 (46.1)
186 (47.3)
76 (40.2)
7.024
0.135
CCB
47 (11.5)
54 (15.4)
164 (25.3)
128 (32.6)
68 (36.0)
81.948
<0.001
Diuretics
182 (44.4)
133 (38.0)
244 (37.7)
134 (34.1)
74 (39.2)
9.487
0.050
Data are expressed as n (%) or mean ± standard deviation. ACEI: Angiotensin-converting enzyme inhibitor; AF: Atrial fibrillation; ARB: Angiotensin II receptor blocker; BMI: Body mass index values; CAD: Coronary artery disease; CCB: Calcium channel blocker; DBP: Diastolic blood pressure; HF: Heart failure; HR: Heart rate; MI: Myocardial infarction; SBP: Systolic blood pressure ; TIA: Transient ischemic attack; –: Not available.
Table 2 -
Clinical characteristics of patients with AF divided by baseline DBP.
Items
DBP <70 mmHg (n = 364)
70 ≤ DBP <80 mmHg (n = 507)
80 ≤ DBP <90 mmHg (n = 595)
DBP ≥ 90 mmHg (n = 524)
χ
2 value
P values
Age (years)
68.6 ± 15.2
67.0 ± 13.9
68.9 ± 12.8
69.3 ± 11.6
–
0.022
Male
148 (40.7)
234 (46.2)
272 (45.7)
242 (46.2)
3.312
0.346
BMI (kg/m2 )
22.6 ± 3.6
23.4 ± 3.4
23.6 ± 3.7
24.2 ± 3.6
–
<0.001
HR (beat/min)
99 ± 31
99 ± 30
100 ± 27
108 ± 28
–
<0.001
AF type
8.841
0.183
Paroxysmal
77 (21.2)
128 (25.2)
129 (21.7)
115 (21.9)
Persistent
118 (32.4)
154 (30.4)
195 (32.8)
141 (26.9)
Permanent
169 (46.4)
225 (44.4)
271 (45.5)
268 (51.1)
CHADS2 score
56.633
<0.001
0
66 (18.1)
106 (20.9)
99 (16.6)
49 (9.4)
1
108 (29.7)
171 (33.7)
198 (33.3)
147 (28.1)
2
86 (23.6)
106 (20.9)
133 (22.4)
141 (26.9)
3
50 (13.74)
66 (13.02)
89 (15.0)
111 (21.2)
4
39 (10.7)
36 (7.1)
47 (7.9)
49 (9.4)
5
14 (3.8)
21 (4.1)
25 (4.2)
19 (3.6)
6
1 (0.3)
1 (0.2)
4 (0.7)
8 (1.5)
Medical history
Hypertension
157 (43.1)
229 (45.2)
339 (57.0)
385 (73.5)
113.605
<0.001
HF
153 (42.0)
189 (37.3)
191 (32.1)
211 (40.3)
12.318
0.006
CAD
153 (42.0)
195 (38.5)
232 (39.0)
255 (48.7)
14.372
0.002
MI
35 (9.6)
37 (7.3)
28 (4.7)
47 (9.0)
10.818
0.013
Diabetes mellitus
54 (14.8)
66 (13.0)
89 (15.0)
100 (19.1)
7.710
0.052
Valvular heart disease
78 (21.4)
96 (18.9)
98 (16.5)
61 (11.6)
17.353
0.001
Stroke/TIA
70 (19.2)
89 (17.6)
112 (18.8)
103 (19.7)
0.812
0.847
Medications
Oral anticoagulants
61 (16.8)
90 (17.8)
112 (18.8)
72 (13.7)
5.570
0.134
Aspirin
185 (50.8)
273 (53.8)
320 (53.8)
314 (59.9)
8.310
0.040
Digoxin
112 (30.8)
161 (31.8)
180 (30.3)
156 (29.8)
0.527
0.913
Amiodarone
29 (8.0)
45 (8.9)
54 (9.1)
63 (12.0)
5.159
0.161
Statin
78 (21.4)
108 (21.3)
134 (22.5)
156 (29.8)
13.649
0.003
ACEI
56 (15.4)
115 (22.7)
131 (22.0)
156 (29.8)
25.826
<0.001
ARB
55 (15.1)
63 (12.4)
101 (17.0)
99 (18.9)
8.725
0.033
Beta-blockers
147 (40.4)
221 (43.6)
261 (43.9)
245 (46.8)
3.581
0.310
CCB
80 (22.0)
102 (20.1)
135 (22.7)
144 (27.5)
8.492
0.037
Diuretics
140 (38.5)
204 (40.2)
207 (34.8)
216 (41.2)
5.740
0.125
Data are expressed as n (%) or mean ± standard deviation. ACEI: Angiotensin-converting enzyme inhibitor; AF: Atrial fibrillation; ARB: Angiotensin II receptor blocker; BMI: Body mass index values; CAD: Coronary artery disease; CCB: Calcium channel blocker; DBP: Diastolic blood pressure; HF: Heart failure; HR: Heart rate; MI: Myocardial infarction; SBP: Systolic blood pressure ; TIA: Transient ischemic attack; –: Not available.
Clinical outcomes
During the 1-year follow-up period, 24 (1.1%) patients were lost to follow-up, and 276 (13.9%) all-cause deaths occurred. In Figure 2 , Kaplan–Meier curves compared by the log-rank test illustrate the all-cause mortality based on the baseline SBP [Figure 2 A] and DBP [Figure 2 B] groups. The SBP group with an SBP between 110 mmHg and 120 mmHg had the lowest risk of all-cause death. In contrast, an SBP ≤110 mmHg or >160 mmHg was associated with an elevated risk of all-cause death (P = 0.014). On the other hand, the groups with a baseline DBP of 70 to 80 mmHg or 80 to 90 mmHg were associated with a lower risk of all-cause death, while the group with DBP <70 mmHg was associated with the highest risk of all-cause death (P = 0.002).
Figure 2: Kaplan–Meier analysis according to baseline (A) SBP and (B) DBP groups for all-cause death. DBP: Diastolic blood pressure; SBP: Systolic blood pressure .
The multivariable Cox regression model was performed for all-cause death [Figure 3 ], which was adjusted for confounders, including gender, age, BMI, type of AF, HF, CAD, diabetes mellitus, prior stroke/TIA, aspirin, oral anticoagulants, digoxin, statin, diuretics, beta-blockers, ACEIs, ARBs, and CCBs. An SBP group of >110 mmHg to ≤120 mmHg was defined as the reference [Figure 3 A]. Compared with the reference, the risk of all-cause death was increased in groups with an SBP ≤110 mmHg (HR, 1.963; 95% CI, 1.306–2.951), >120 mmHg to ≤140 mmHg (HR, 1.098; 95% CI, 0.736–1.639), >140 mmHg to ≤160 mmHg (HR, 1.417; 95% CI, 0.934–2.150), and >160 mmHg (HR, 1.187; 95% CI, 0.731–1.927). For DBP [Figure 3 B], the group with a baseline DBP of 80 to 90 mmHg was used as a reference. The risk of all-cause mortality was higher in groups with DBP <70 mmHg (HR, 1.628; 95% CI, 1.163–2.281), ≥70 mmHg to <80 mmHg (HR, 1.255; 95% CI, 0.894–1.762), and ≥90 mmHg (HR, 1.194; 95% CI, 0.851–1.677).
Figure 3: Multivariable Cox regression for all-cause death and baseline (A) SBP and (B) DBP. The analyses were adjusted for age, gender, BMI, type of AF, HF, CAD, diabetes mellitus, prior stroke/TIA, aspirin, oral anticoagulants, digoxin, statins, diuretics, beta-blockers, ACEIs, ARBs, and CCBs. ACEIs: Angiotensin-converting enzyme inhibitor; AF: Atrial fibrillation; ARBs: Angiotensin receptor blockers; BMI: Body mass index; CAD: Coronary artery disease; CCBs: Calcium channel blockers; CI: Confidence interval; DBP: Diastolic blood pressure; HF: Heart failure; HR: Hazard ratio; SBP: Systolic blood pressure ; TIA: Transient ischemic attack.
According to the restricted cubic splines for the adjusted HR of all-cause death [Figure 4 ], the associations between the baseline SBP [Figure 4 A] or DBP [Figure 4 B] and all-cause death showed J-shaped associations (non-linear P < 0.001 and non-linear P = 0.010, respectively). The risk of all-cause death notably increased at a lower baseline SBP and DBP. The baseline SBP and DBP values associated with the lowest risk of all-cause mortality were 120 mmHg and 80 mmHg, respectively.
Figure 4: Restricted cubic splines for adjusted HRs for all-cause death and baseline (A) SBP and (B) DBP. The shaded areas indicate 95% Cis. The analyses were adjusted for age, gender, BMI, type of AF, HF, prior stroke/TIA, CAD, diabetes mellitus, aspirin, oral anticoagulants, digoxin, statins, diuretics, beta-blockers, ACEIs, ARBs, and CCBs. ACEIs: Angiotensin-converting enzyme inhibitor; AF: Atrial fibrillation; ARBs: Angiotensin receptor blockers; BMI: Body mass index; CAD: Coronary artery disease; CCBs: Calcium channel blockers; Cis: Confidence intervals; DBP: Diastolic blood pressure; HF: Heart failure; HRs: Hazard ratios; SBP: Systolic blood pressure ; TIA: Transient ischemic attack.
Subgroup analyses [Supplementary Figures 1 and 2, https://links.lww.com/CM9/B505 2 score (all P for interaction >0.05). DBP <80 mmHg was associated with a higher risk of all-cause death, especially among those with HF (P for interaction = 0.038).
Discussion
This study showed that the Chinese cohort of AF had a high prevalence of hypertension. A J-shaped association was observed between the BP (SBP and DBP) and all-cause death in AF patients. Additionally, our results demonstrated a significantly higher risk of all-cause death in those with SBP ≤110 mmHg and DBP <70 mmHg. These findings imply that an excessively low SBP and DBP might be associated with a higher risk of all-cause death in patients with AF. This relationship was consistent in important clinical subgroups, including those considering age, gender, BMI, hypertension history, CAD, and CHADS2 score.
Hypertension is considered a major risk factor for all-cause death in the general population[10,11] [12] [13] [14,15] [16-18] [6] [19] [20] Systolic Blood Pressure Intervention Trial research group[21] [22]
Our study indicated that AF patients with a baseline SBP ≤ 110 mmHg had a 1.9-fold higher risk of all-cause mortality than those with a baseline SBP of 110 to 120 mmHg. Consistent with our study, previous studies also suggested that a lower SBP was related to a higher risk of all-cause mortality in AF patients.[7,23-25] [26] [23] post hoc analysis of patients enrolled in the AF Follow-up Investigation of Rhythm Management (AFFIRM) trial suggested that the incidence of all-cause mortality was lowest when the DBP was 78 mmHg, and pharmacologic therapy to treat AF such as medications for rate or rhythm control, may be associated with the risk of all-cause mortality when DBP is reduced to <60 mmHg.[7]
The relationship between low BPs and a high risk of death seems complex. Low BPs often represent frail conditions and tissue hypoperfusion, which are more likely to be associated with a worse prognosis.[27] [23,28,29] [27] [30] [31,32] [33,34] [27,35] [36,37]
It should be mentioned that this study had some limitations. First, although this study was a multicenter registry study, it only included the Chinese population, which was comprised mainly of elderly patients from the emergency department. In addition, only one BP measurement on admission was recorded in the emergency department, which may not accurately reflect the BP during the follow-up. Therefore, our results should be carefully interpreted. In addition, this was an observational study without randomization, and systematic bias might have influenced the results. We cannot infer a causal relationship between low BP and the risk of mortality. Large-scale randomized clinical trials are needed to verify the findings. Moreover, the rate of oral anticoagulants’ use was not ideal in this study because the database used in this study was completed in 2011, and the 20 sub-centers included in this study possessed different medical healthcare levels, from rural to urban, across China. However, this study, based on real-world data, might provide new evidence for ideal BP management in the AF population.
In conclusion, according to our results, SBP ≤10 mmHg or DBP <70 mmHg in patients with AF was associated with a significantly elevated risk of all-cause mortality. An excessively low BP may be a risk for patients with AF.
Funding
This work was supported by Capital's Funds for Research and Application of Clinical Diagnosis and Treatment Technology (Z191100006619121), and High-level Hospital Clinical Research Funds (2022-GSP-GG-26).
Conflicts of interest
None.
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