Coronary artery disease (CAD) and hypertension (HT) are two highly prevalent cardiovascular diseases,
while atrial fibrillation (AF) is the most common cardiac arrhythmia. [1,2] According to the  Report on Cardiovascular Health and Diseases in China 2021, approximately 11 million adults suffered from CAD, and 245 million adults suffered from HT. A nationwide survey of Chinese adults showed that the weighted  prevalence of AF was 1.8% in participants aged ≥45 years in China and increased with age from 0.6% in the population aged between 45 and 54 years to 5.0% of those aged >75 years. Approximately 7.9 million adults are estimated to have AF.  CAD, HT, and AF share common risk factors, such as age, obesity, diabetes, and sleep apnea.  Therefore, these three diseases frequently coexist. When patients complicated by CAD and HT develop AF, the risks of myocardial infarction, ischemic stroke (IS), and hemorrhagic stroke (HS) greatly increase. [6-8] [9-12]
Previous studies have reported that the
prevalence of CAD in patients with AF ranges from 17.0% to 46.5%. Data from the Chinese subgroup of the Global Anticoagulant Registry study in the FIELD (GARFIELD) showed that the  prevalence of CAD was 32.4% among hospitalized patients with AF. The difference in this  prevalence was derived from restricted populations of varying sample sizes. Similarly, the prevalence of AF in patients with coronary heart disease greatly varies in different studies and different populations. The incidence of AF was 0.2% to 5.0% and 2.0% to 23.0% in patients with CAD and acute coronary syndrome (ACS), respectively. Acute myocardial infarction (AMI) is a risk factor for AF, and 6.0% to 21.0% of patients with AMI have AF. [13,15] Therefore, the 2020 ESC Guidelines for the Diagnosis and Management of Atrial Fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS) suggest that novel oral anticoagulants (NOACs) combined with antiplatelet therapy is recommended as class IA to prevent IS/systemic embolism in patients with AF and ACS, chronic coronary syndrome, or receiving percutaneous coronary intervention (PCI).  However, observational studies have shown that appropriate anticoagulant therapy is underused in patients with AF and ACS.  Generally, the comorbidity of hypertension and coronary artery disease (HT-CAD) with AF is common in clinical practice and contributes to a poor prognosis. However, there have been few studies on the  prevalence and treatment status of hospitalized patients with both HT-CAD and AF. Therefore, we aimed to investigate the prevalence of AF in patients with HT-CAD, clinical characteristics of hospitalized patients with the comorbidities of HT-CAD and AF, and current application of anticoagulant/antiplatelet therapy, providing a basis for strategies on interventions targeting comprehensive underlying conditions. Methods
Design and study population
This cross-sectional study was conducted using data from the coronary angiography register and electronic medical record database of inpatients in the Department of Cardiology, Chinese People's Liberation Army General Hospital from August 5, 2008 to July 22, 2018. Except for pregnant women, hospitalized patients who were diagnosed with CAD (International Classification of Diseases [ICD]-10 codes: I20–I22, I24–I25) and HT (ICD-10 code: I10), with or without AF (ICD-10 code: I48), were included in this study. With regard to patients with multiple hospitalizations, we only used their data from the first hospitalization with the diagnosis of HT-CAD. We eventually included 20,747 patients for analyses. They were from 31 Chinese provinces/autonomous regions, mainly including Beijing (30.59%), Hebei (19.21%), Henan (9.82%), and Shandong (8.71%). This study protocol was approved by the Ethics Committee of Chinese People's Liberation Army General Hospital (No. S2020-172-01) which exempted the informed consent.
Data collection and definitions
The data of clinical characteristics were collected from the electronic medical record database of inpatients, such as demographic characteristics, lifestyle (drinking and smoking), anthropometric measurements, laboratory tests, echocardiographic examination, medical history and comorbidities, treatment patterns, and in-hospital outcomes. For patients who had repeated clinical examinations during hospitalization, only the examination results of the first time were included in our analyses. We also recorded the use of medications (antiplatelet agents, anticoagulants, antihypertensive drugs, and lipid-lowering agents) and cardiac revascularization procedures (PCI and coronary artery bypass grafting [CABG]).
All patients underwent coronary angiography. CAD was defined as at least one coronary artery obstruction/stenosis with a diameter of >50% or a history of PCI and CABG, or old myocardial infarction.
HT was defined as systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg, taking antihypertensive drugs, or having a history of HT diagnosed by a physician.  The definition of AF was based on the medical history reported by the participant himself/herself or an electrocardiogram (ECG) or an ambulatory ECG (Holter). Cardiovascular-related comorbidities, such as diabetes mellitus (DM), heart failure (HF), chronic kidney disease (CKD), IS, HS, and chronic obstructive pulmonary disease (COPD), were ascertained based on the medical records while discharged.  Statistical analysis
All analyses were performed using SAS (Version 9.4; SAS Institute, Cary, NC, USA). The Kolmogorov–Smirnov test was used to identify whether the data were normally distributed. One-way analysis of variance was used to estimate the difference among continuous variables that were normally distributed, and the values were expressed as mean ± standard deviation. The Kruskal–Wallis test was used to estimate the differences among continuous variables that were not normally distributed, and the values were expressed as median (interquartile range). The chi-squared test was used to estimate differences among categorical variables which were shown as frequencies and percentages. The relevant clinical characteristics were described and stratified according to gender, age, BP level, and the CHA
2DS 2-VASc score. The study period was divided into the following: 2008 to 2011, 2012 to 2014, and 2015 to 2018. Temporal trends of antiplatelet and anticoagulation medication in these three periods were analyzed using the Mantel–Haenszel test. Multivariate logistic regression models were used to analyze the effect of cardiovascular-related risk factors (age, gender, body mass index [BMI], triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], smoking status, drinking status, HF, DM, CKD, and COPD) on the prevalence of AF in inpatients with HT-CAD. A two-sided P < 0.05 was considered statistically significant. Results
Prevalence of AF in patients with HT-CAD
We included 20,747 patients with HT-CAD in the study. A total of 1011 (4.87%) patients were complicated by AF (44.71% of paroxysmal AF, 13.85% of persistent AF, and 41.44% of undefined AF). The
prevalence of AF in HT-CAD patients increased with age in both women and men: 0.78% (2/255) and 1.02% (26/2561), 1.97% (26/1319) and 2.88% (131/4555), 3.66% (96/2625) and 5.53% (239/4322), and 8.73% (193/2210) and 10.28% (298/2900), respectively at the ages of <50 years, 50 to 59 years, 60 to 69 years, and ≥70 years [ Figure 1]. Figure 1:
prevalence of AF in patients with HT-CAD stratified by age and gender. P values indicate the statistical significance of comparison. AF: Atrial fibrillation; HT-CAD: Comorbidity of hypertension and coronary artery disease. Clinical characteristics of HT-CAD patients with or without AF
As shown in
Table 1, patients with AF (68.8 ± 9.4 years old) were older than those without AF (61.8 ± 10.6 years old, P < 0.01), and they had lower rates of current smoking and current drinking, but higher rates of past smoking, and a history of PCI and CABG than those without AF. They had lower SBP ( P = 0.02) and higher DBP ( P = 0.01), lower estimated glomerular filtration rate ( P < 0.01), and higher uric acid (UA) concentration ( P < 0.01) than those without AF. With regard to blood lipid control, HT-CAD patients with AF had lower total cholesterol (TC) and TG (both P < 0.01), and LDL-C concentration ( P = 0.01), but higher HDL-C concentration ( P < 0.01) than those without AF. There was no statistically significant difference in the control rate of BP between HT-CAD patients with and without AF (BP < 130/80 mmHg: 26.61% [269/1011] vs. 27.05% [5338/19,736], P = 0.76; BP <140/90 mmHg: 52.23% [528/1011] vs. 52.40% [10,340/19,736], P = 0.92). In addition, according to echocardiographic data, we found that HT-CAD patients with AF had a lower ejection fraction (EF; P < 0.01) and higher left atrial diameter (LAD; P < 0.01), left ventricular mass index (LVMI; P < 0.01), and left atrial volume index (LAVI; P < 0.01) than those without AF.
Table 1 -
Clinical characteristics of HT-CAD patients with or without AF.
n = 19,736) AF (
n = 1011)
61.8 ± 10.6
68.8 ± 9.4
26.22 ± 3.35
26.01 ± 3.42
137.93 ± 19.88
136.47 ± 20.02
77.36 ± 11.99
78.36 ± 13.41
BP <140/90 mmHg
BP <130/80 mmHg
SBP ≥160 mmHg
74.47 ± 11.46
77.35 ± 15.22
5.54 (4.87, 7.04)
5.43 (4.81, 6.75)
4.11 ± 1.07
3.95 ± 0.97
1.42 (1.04, 1.97)
1.20 (0.92, 1.69)
2.38 (1.85, 3.02)
2.33 (1.82, 2.89)
1.05 ± 0.28
1.08 ± 0.29
5.51 (4.55, 6.75)
6.09 (4.88, 7.74)
84.57 ± 19.82
73.61 ± 20.64
341.45 ± 94.27
364.24 ± 111.54
58.29 ± 8.12
55.68 ± 9.61
46.26 ± 5.30
47.60 ± 5.92
35.77 ± 4.36
40.63 ± 6.31
11.14 ± 1.44
11.20 ± 1.55
10.27 ± 1.15
10.30 ± 1.14
44.94 ± 10.82
47.03 ± 12.33
8.60 (7.21, 10.46)
12.47 (9.19, 16.23)
SAPT + OAC
DAPT + OAC
Number of antihypertensive drugs used
Length of hospitalization (days)
7.0 (5.0, 10.0)
9.0 (6.0, 14.0)
Death in hospital
Data are expressed as
n (%), mean ± standard deviation, or median (Q 1, Q 3). F value is the statistic of one-way analysis of variance. H value is the statistic of Kruskal–Wallis test. χ value is the statistic of chi-squared test. 2 ∗Number of missing values: Blood pressure measurements: Two in non-AF group; BMI: A total of 195 in non-AF group and 16 in AF group; BUN: A total of 423 in non-AF group and 11 in AF group; Drinking status: A total of 1147 in non-AF group and 58 in AF group; EF: A total of 4408 in non-AF group and 231 in AF group; eGFR: A total of 383 in non-AF group and 10 in AF group; FBG: A total of 2524 in non-AF group and 70 in AF group; HDL-C: A total of 1860 in non-AF group and 79 in AF group; HR: One in non-AF group; IVS: A total of 4625 in non-AF group and 241 in AF group; LAD: A total of 4633 in non-AF group and 239 in AF group; LAVI: A total of 4712 in non-AF group and 243 in AF group; LDL-C: A total of 1870 in non-AF group and 77 in AF group; Length of hospitalization: A total of 30 in non-AF group and two in AF group; LVD: A total of 4636 in non-AF group and 240 in AF group; LVMI: A total of 4719 in non-AF group and 247 in AF group; LVPW: A total of 4655 in non-AF group and 241 in AF group; Medication data: A total of 11 in non-AF group; Smoking status: A total of 1046 in non-AF group and 53 in AF group; TC: A total of 1822 in non-AF group and 76 in AF group; TG: A total of 1823 in non-AF group and 76 in AF group; Treatment: A total of 195 in non-AF group and 21 in AF group; UA: A total of 502 in non-AF group and 16 in AF group.ACEI: Angiotensin-converting enzyme inhibitor; AF: Atrial fibrillation; ARB: Angiotensin receptor antagonist; BMI: Body mass index; BP: Blood pressure; BUN: Blood urea nitrogen; CABG: Coronary artery bypass grafting; CCB: Calcium channel blockers; DAPT: Double antiplatelet therapy; DBP: Diastolic blood pressure; EF: Ejection function; eGFR: Estimated glomerular filtration rate; FBG: Fasting blood glucose; HT-CAD: Comorbidity of hypertension and coronary artery disease; HDL-C: High-density lipoprotein cholesterol; HR: Heart rate; IVS: Interventricular septum thickness; LAD: Left atrial diameter; LAVI: Left atrial volume index; LDL-C: Low-density lipoprotein cholesterol; LVD: Left ventricular diameter; LVMI: Left ventricular mass index; LVPW: Left ventricular posterior wall thickness; NOACs: Novel oral anticoagulants; OAC: Oral anticoagulation; PCI: Percutaneous coronary intervention; SAPT: Single antiplatelet therapy; SBP: Systolic blood pressure; TC: Total cholesterol; TG: Triglyceride; UA: Uric acid.
In terms of medication, there was no statistically significant difference in the use of single antiplatelet therapy (SAPT) between HT-CAD patients with and without AF (
P = 0.61). HT-CAD patients with AF had a lower rate of using double antiplatelet therapy (DAPT, P < 0.01), but higher rates of only orally taking anticoagulation (OAC) and using SAPT + OAC therapy or DAPT + OAC therapy than those without AF (all P < 0.01). With regard to antihypertensive drugs, HT-CAD patients with AF took more diuretics and less calcium channel blockers than those without AF (both P < 0.01). HT-CAD patients with AF were more likely to use three or more antihypertensive drugs than those without AF ( P < 0.01). The length of hospitalization and the hospital mortality rate were statistically significantly longer and higher among HT-CAD patients with AF.
For HT-CAD patients with AF, the incidence rates of HF, CKD, IS, and COPD were 32.34% (327/1011), 23.15% (234/1011), 20.97% (212/1011), and 5.24% (53/1011) respectively, which were significantly higher than those of HT-CAD patients without AF (12.34% [2435/19,736], 12.08% [2384/19,736], 15.12% [2984/19,736], and 2.36% [466/19,736] respectively, all
P < 0.01) [ Figure 2]. Figure 2:
Comorbidities comparison between HT-CAD patients with and without AF.
P values indicate the statistical significance of comparison. AF: Atrial fibrillation; CKD: Chronic kidney disease; COPD: Chronic obstructive pulmonary disease; DM: Diabetes mellitus; HF: Heart failure; HS: Hemorrhagic stroke; HT-CAD: Comorbidity of hypertension and coronary artery disease; IS: Ischemic stroke. Associations between cardiovascular disease-related risk factors and AF
We further analyzed the associations between traditional cardiovascular disease-related risk factors and AF in patients with HT-CAD using multivariate logistic regression [
Table 2]. We found that HF was associated with a 2.93-fold risk of AF (adjusted odds ratio: 2.93, 95% confidence interval: 2.53–3.39) in patients with HT-CAD after adjusting for other potential confounders. In addition, age, gender (male), BMI, and CKD were independently associated with an increased risk of AF in patients with HT-CAD; however, LDL-C and HDL-C concentrations, diabetes, and COPD were not associated risk factors.
Table 2 -
Associated risk factors for AF in patients with HT-CAD.
Crude OR (95% CI)
P value Adjusted OR (95% CI)
Age (per 1-year increase)
BMI (per 1-kg/m
2 increase) 0.98 (0.96–1.00)
TG (per 1-mmol increase)
LDL-C (per 1-mmol increase)
HDL-C (per 1-mmol increase)
AF: Atrial fibrillation; BMI: Body mass index; CI: Confidence intervals; CKD: Chronic kidney disease; COPD: Chronic obstructive pulmonary disease; DM: Diabetes mellitus; HDL-C: High-density lipoprotein cholesterol; HF: Heart failure; HT-CAD: Comorbidity of hypertension and coronary artery disease; LDL-C: Low-density lipoprotein cholesterol; OR: Odds ratio; TC: Total cholesterol; TG: Triglyceride.
Temporal trends in antithrombotic therapy among patients with HT-CAD and AF
We analyzed the temporal changes in antithrombotic therapy among patients with both HT-CAD and AF from 2008 to 2018 [
Figure 3]. All the patients with HT-CAD complicated by AF had a CHA 2DS 2-VASc score of ≥2, which indicated a high risk of thromboembolic events. Therefore, OAC treatment needs to be considered in these patients. According to the study period divided into three parts (2008–2011, 2012–2014, and 2015–2018), the proportion of patients who received OAC therapy (including OAC only, DAPT + warfarin/NOACs, and SAPT + warfarin/NOACs) increased from 2008 to 2018, however, only 30.06% (159/529) of patients received anticoagulant therapy between 2015 and 2018. Because a considerable number of patients with both HT-CAD and AF did not receive standard antithrombotic therapy, the current situation of antithrombotic therapy in these patients with a high risk of thromboembolism urgently needs to be improved in China. Figure 3:
Temporal changes of the anticoagulants use in patients with HT-CAD and AF in 2008–2011, 2012–2014, and 2015–2018.
P values indicate the statistical significance of changing trend. AF: Atrial fibrillation; DAPT: Double antiplatelet therapy; HT-CAD: Comorbidity of hypertension and coronary artery disease; NOACs: Novel oral anticoagulants; OAC: Oral anticoagulation; SAPT: Single antiplatelet therapy. Distribution of the CHA
2DS 2-VASc score and the control of BP in patients with both HT-CAD and AF
As shown in
Figure 4, a total of 73.49% patients (743/1011) with both HT-CAD and AF had a CHA 2DS 2-VASc score ≥4, and 17.80% (180/1011) and 8.70% (88/1011) of them had a CHA 2DS 2-VASc score of 3 and 2, respectively. For men, almost two-thirds of patients had a CHA 2DS 2-VASc score ≥4, and 22.33% (155/694) and 12.68% (88/694) of them had a CHA 2DS 2-VASc score of 3 and 2, respectively. In women, 92.11% (292/317) patients with HT-CAD and AF had a CHA 2DS 2-VASc score ≥4, and only 7.89% (25/317) had a CHA 2DS 2-VASc score of 3. Moreover, we further evaluated the BP control of patients with different scores. We found that the rate of BP controlled at <140/90 mmHg was 52.23% (528/1011) in patients with HT-CAD and AF, while that controlled at <130/80 mmHg was only 26.61% (269/1011). In addition, 12.27% of patients (124/1011) with HT-CAD and AF had a SBP ≥160 mmHg [ Table 1]. The status of poor BP control in patients with HT-CAD and AF showed similar trends in different genders. However, there was no statistically significant difference in BP control among patients with different CHA 2DS 2-VASc scores. Figure 4:
BP control in patients with both HT-CAD and AF based on different CHA
2DS 2-VASc scores. The BP control based on different CHA 2DS 2-VASc scores in (A) all patients with HT-CAD and AF, (B) men with HT-CAD and AF, and (C) women with HT-CAD and AF. P values indicate the statistical significance of changing trend. AF: Atrial fibrillation; BP: Blood pressure; HT-CAD: Comorbidity of hypertension and coronary artery disease; SBP: Systolic blood pressure. Discussion
In this large hospitalization-based survey, we investigated the
prevalence and clinical characteristics of AF in patients with HT-CAD. Overall, the prevalence of AF in patients with HT-CAD was 4.87% (1011/20,747) and it increased with age. Patients with HT-CAD and AF had a higher incidence of cardiovascular-related comorbidities, such as HF (32.34%), CKD (23.15%), IS (20.97%), and COPD (5.24%) than those with HT-CAD and without AF. Moreover, age, gender (male), BMI, HF, and CKD were associated with an increased risk of AF in patients with HT-CAD. In addition, 73.49% of the patients with HT-CAD and AF had a high risk of IS (CHA 2DS 2-VASc score ≥4), but only one-fifth of patients with HT-CAD and AF received OAC therapy.
HT, CAD, and AF are three important public health problems. These three conditions share similar risk factors and often coexist in the same patient.
However, few studies have reported the  prevalence and characteristics of these three comorbidities. In the present study, we found that the prevalence of AF in patients with HT-CAD (4.87%) was higher than that in the general population (0.4%–2.3%). We further found that age, gender (male), obesity, HF, and CKD were related to an increased risk of AF in patients with HT-CAD. Our findings are consistent with those from the Framingham Heart Study, which showed that HF, aging, valvular heart disease, and HT were the top four risk factors for AF. [21-24] DM is one of the most important risk factors for AF, and it can increase the risk of AF by twofold.  However, we did not observe that DM was associated with a risk of AF in patients with HT-CAD. Two reasons might explain the conflicting results between studies. First, the  prevalence and clinical characteristics of AF in patients with simple DM were different from those with HT-CAD combined significantly different with DM. Second, the cardiovascular and metabolism disorder in patients with HT-CAD may mask the contribution of DM to AF development. In addition, the present study showed that patients with both HT-CAD and AF had a higher incidence of cardiovascular-related comorbidities than those with HT-CAD but without AF. This finding suggests that the coexistence of HT, CAD, and AF may play an important role in the incidence of cardiovascular-related comorbidities.
The combination of anticoagulation with antiplatelet therapy is recommended by 2020 ESC Guidelines for the Diagnosis and Management of Atrial Fibrillation developed in collaboration with the EACTS to prevent thromboembolism in patients with AF and ACS, PCI, or chronic coronary syndrome.
However, we found a low use of OAC in patients with both HT-CAD and AF. The current status of OAC treatment was significantly improved according to our study compared with the previously reported rate of 2.5% to 2.7% for OAC treatment in the Chinese population.  The proportion of patients with both HT-CAD and AF who have received anticoagulant treatment has increased during the recent decade. In our study, we found that approximately 80.00% to 90.00% of patients with the comorbidities of HT, CAD, and AF received antiplatelet therapy. However, only 30.06% received anticoagulant therapy between 2015 and 2018. The treatment patterns of patients with both HT-CAD and AF suggest that antiplatelet therapy is encouraged, but anticoagulant therapy is insufficiently used. The combination of antiplatelet and anticoagulation therapies should be considered as an essential treatment to prevent thrombotic events and AF-related thromboembolic events. Moreover, combined antithrombotic therapies may contribute to reduced cardiovascular adverse events in patients with both HT-CAD and AF. 
BP control also plays an important role in preventing cardiovascular events in patients with HT-CAD and AF. This study showed that the rate of diuretic use in HT-CAD patients with AF was statistically significantly higher than that in patients without AF. Additionally, the rate of using the combination of three antihypertensive drugs was also significantly higher in HT-CAD patients with AF. This finding indicates that BP in patients with HT-CAD and AF may be difficult to control. Therefore, they are more likely to suffer from HF, CKD, IS, and HS.
In fact, we also found that BP control was unsatisfactory in patients with HT-CAD and AF. In particular, only 26.61% of them had a BP <130/80 mmHg, and 12.27% still had a SBP ≥160 mmHg. The management of cardiovascular risk factors and concomitant diseases for patients with the comorbidities of HT-CAD and AF needs to be improved to reduce the incidence of cardiovascular events. [27-29]
One of the strengths of the present study is the large sample size of hospitalized patients with a broad spectrum of characteristics. Additionally, we put great emphasis on data quality. All patients also underwent a standard coronary angiography examination. However, some limitations to this study should be considered. First, the patients included in our study were from a large-scale tertiary hospital in 31 provinces/autonomous regions in China. But two-thirds of them were residents of Beijing, Hebei, Henan, and Shandong. The location limitation may have restricted the generalizability of our findings to some extent. Second, it was a cross-sectional study, which could not clarify the effect of AF on the prognosis of patients with HT-CAD. Third, although the diagnosis of AF was based on a medical history, ECG, or 24-hour Holter, the
prevalence of AF may have been underestimated because of possible omission of some patients with paroxysmal AF.
In conclusion, our large-sample survey showed that the
prevalence of AF in patients with HT-CAD was higher than that in the general population. Patients with the comorbidities of HT-CAD and AF had more cardiovascular-related comorbidities, and a lower rate of use of anticoagulant and a low BP control rate. The use of anticoagulant therapy and the management of cardiovascular-related comorbidities and risk factors are urgently required to reduce the recurrence of cardiovascular events. Acknowledgments
We thank all the participants who contributed their data and all the staff in Department of Cardiology, Chinese People's Liberation Army General Hospital.
This work was supported by the grants from the Capital Health Research and Development of Special, Beijing Health Commission (No. 2020-2-5013), and the National Natural Science Foundation of China (No. 82070433).
Conflicts of interest
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