Introduction
Stroke is a common disease that disrupts communication between the brain and muscles.1 Owing to severe neurological impairments, patients with stroke often remain bedridden after the acute phase and cannot perform out-of-bed activities despite weeks of rehabilitation.2 This increases the incidence of various complications, such as pressure ulcers, deep vein thrombosis and urinary tract infections.3 Thus, it is necessary to pay close attention to the healthcare of bedridden patients with stroke.
Stroke can induce cardiac structural and functional dysfunction even in the absence of primary heart disease, contributing to fatality or severe heart failure (HF) or mildly recoverable damage, such as neurogenic stress cardiomyopathy.4 5 Electrocardiographic abnormalities, reduced left ventricular ejection fraction (LVEF), impaired left-ventricular (LV) diastolic function and hypertrophy, cardiovascular autonomic dysfunction, and elevated serum myocardial enzymes have been observed in patients after stroke.6 7
Brain natriuretic peptide (BNP), primarily synthesised and released by cardiomyocytes in response to volume overload and increased wall tension, plays a crucial role in the regulation of cardiovascular homeostasis and extracellular fluid volume.8 9 BNP and its precursor N-terminal pro-BNP (NT-pro-BNP) have been investigated and highlighted as important biomarkers in the diagnosis, prognosis and risk identification of cardiac disease.10 Compared with BNP, the determination of NT-pro-BNP levels in circulation has been preferentially recommended for diagnosis and prognosis in patients with LV dysfunction.11 Elevated NT-pro-BNP is associated with the incidence of HF, atrial fibrillation and coronary artery disease and has also been demonstrated in haemorrhage or ischaemic stroke with a positive correlation to the severity of stroke, stroke recurrence and mortality after stroke.12–15 However, whether a bedridden condition affects the NT-pro-BNP levels of patients after stroke is unknown.
Therefore, this study aimed to investigate any difference in NT-pro-BNP levels between bedridden and non-bedridden patients with stroke and explore the factors influencing NT-pro-BNP levels in bedridden patients with stroke.
Methods
Design, setting and participants
This was a single-centre, cross-sectional study. We enrolled hospitalised patients diagnosed with stroke in the rehabilitation department of Shenzhen Second People’s Hospital between January 2019 and December 2022. The inclusion criteria were as follows: age ≥18 years, diagnosed with stroke according to the 10th edition of the International Classification of Stroke,16 and testing NT-pro-BNP and other routine blood parameters on admission. The exclusion criteria were as follows: HF, cardiovascular disease requiring medical treatment or surgery, acute pulmonary embolism, impaired kidney and renal function, haematological malignancy and systemic infection.
Sample size
This study was designed to investigate the difference in NT-pro-BNP levels between bedridden and non-bedridden patients with stroke and explore the factors influencing the elevated NT-pro-BNP in bedridden patients with stroke. The formula of sample size calculation is based on the study reported by Hsieh et al.17 In accordance with the results of a previous study,18 the sample size of this study will need to recruit 143 participants in each group with a type I error of 0.05 and a power of 80%. After considering a 20% sample attrition rate, the required sample size in each group has been increased to 179 participants.
Assignment of the participants
Whether the participants with stroke were bedridden or non-bedridden was assessed using the Longshi scale, a pictural and convenient tool to evaluate subjects’ ability to perform activities of daily living (online supplemental figure 1). The reliability and validity of the scale have been demonstrated in previous studies.19–22 Based on their ability to transfer out of bed or go outside, participants were divided into three groups: bedridden, domestic and community (figure 1). Individuals who could not transfer out of bed independently were assigned to the bedridden group. Those who could transfer out of bed but could not go outside independently with or without assistance were assigned to the domestic group. Those who could go outdoors independently with or without assistance were assigned to the community group. Each group has three specific assessment items: bladder and bowel management, feeding, and entertainment in the bedridden group; toileting, grooming and bathing, and housework in the domestic group; and community mobility, shopping and social participation in the community group. In our study, participants were categorised into bedridden and non-bedridden patients with stroke (domestic and community groups).
Supplemental material
Flow chart for the assessment of the Longshi scale.
Data collection
The collected data included basic information (age, gender, body mass index, stroke type, duration from stroke onset to admission and comorbidities), laboratory data and echocardiographic parameters.
The laboratory data of the participants at admission, including NT-pro-BNP, high-sensitivity C reactive protein (hs-CRP), D-dimer, serum creatinine, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), albumin and haemoglobin, were collected. NT-pro-BNP was categorised into two groups: high level (≥125 pg/mL) and low level (<125 pg/mL).23 High levels of hs-CRP and D-dimer were defined as ≥5 mg/L and ≥ 0.55 mg/L, respectively.24 25 A high level of serum creatinine was defined as ≥106 µmol/L in men and ≥97 µmol/L in women.26 Low HDL-C level was determined as <1.03 mmol/L.27 High level of LDL-C was determined as ≥3.36 mmol/L.28 A low albumin level was defined as <40 g/L.29 Low level of haemoglobin is determined as <130 g/L in men or <120 g/L in women.30
Echocardiographic data at admission were collected with the use of transthoracic echocardiography. The parameters of LV systolic and diastolic functions were determined as follows: LVEF, fractional shortening (FS), LV dimension in systole, LV dimension in diastole, and the ratio between the peak velocities of the early and late diastolic filling (E/A).
Statistical analysis
Data were analysed by using SPSS V.20 (IBM). The Kolmogorov-Smirnov test was used to determine the normality of the data distribution. Continuous data were presented as means (SD) or median (IQR). Categorical data were expressed as frequencies and percentages. Differences in laboratory measurement and echocardiographic parameters in bedridden and non-bedridden groups were assessed with the independent t-tests or non-parametric Mann-Whitney U test. Binary logistic regression analysis was conducted to identify the factors associated with high levels of NT-pro-BNP. Receiver operating characteristic (ROC) curves were generated to compute the area under the curve (AUC), cut-off value, sensitivity and specificity of the factors significantly associated with high NT-pro-BNP levels in bedridden patients with stroke. A p<0.05 was considered statistically significant.
Patient and public involvement
No patients were involved in the design, conduct, reporting or dissemination of the study.
Results
Demographic characteristics of participants
A total of 465 patients with stroke were enrolled in this study, including 281 (60.4%) bedridden and 184 (39.6%) non-bedridden patients. The baseline demographic characteristics are shown in online supplemental table 1. Most participants were male, aged <60 years, diagnosed with haemorrhagic stroke and had a duration from stroke onset to admission ≥30 days. A total of 33.1% and 32.3% of the participants had a history of smoking and alcohol consumption before stroke, respectively.
Supplemental material
Biochemical indices
A comparison of clinical biochemical indices between bedridden and non-bedridden patients with stroke is presented in table 1. Bedridden patients with stroke had higher levels of NT-pro-BNP, D-dimer and hs-CRP and lower levels of serum creatinine, HDL-C, albumin and haemoglobin than non-bedridden patients.
The comparison of laboratory data between bedridden and non-bedridden groups
Echocardiographic parameters
A comparison of the echocardiographic parameters between bedridden and non-bedridden patients with stroke is presented in table 2. Bedridden patients with stroke had lower LVEF, FS and E/A than non-bedridden patients.
The results of echocardiography
Logistic regression analysis
Binary logistic regression analysis was separately used to evaluate the association between NT-pro-BNP and other variables, including demographic characteristics, stroke background and clinical blood biochemical indices in bedridden and non-bedridden patients with stroke. In bedridden patients with stroke, age ≥75 years, high hs-CRP and creatinine levels, and low albumin levels were associated with high NT-pro-BNP levels (table 3). In non-bedridden patients, age ≥75 years and high serum creatinine levels were associated with high NT-pro-BNP levels (online supplemental table 2).
The binary analysis between NT-pro-BNP and other factors in bedridden patients with stroke
ROC curve analysis
The ROC curve analysis of hs-CRP and albumin levels for the high levels of NT-pro-BNP in bedridden patients with stroke is summarised in figure 2 and online supplemental table 3). The AUC of hs-CRP was 0.700 (p<0.001, 95% CI 0.638 to 0.762) with a cut-off value of 5.12 mg/L (sensitivity, 83.5%; specificity, 53.5%). Similarly, the AUC of albumin was 0.671 (p<0.001, 95% CI 0.606 to 0.736) with a cut-off value of 37.15 g/L (sensitivity, 61.5%; specificity, 69.8%).
The ROC analysis of hs-CRP and albumin. (A) AUC of hs-CRP was 0.700 (p<0.001, 95% CI 0.638 to 0.762). (B) AUC of albumin was 0.671 (p<0.001, 95% CI 0.606 to 0.736). AUC, area under the curve; hs-CRP, high-sensitivity C reactive protein; ROC, receiver operating characteristic.
Discussion
This study is the first to investigate the cardiac function of bedridden patients with stroke. Our results revealed that the cardiac biological marker NT-pro-BNP levels were higher in bedridden patients with stroke than in non-bedridden patients. Meanwhile, LVEF and FS, which are used to evaluate LV systolic function, and E/A, which is used to evaluate LV diastolic function, were lower in bedridden than in non-bedridden patients.31 It implies that damage to myocardial tissue and cardiac function was more severe in bedridden than in non-bedridden patients. Apart from stroke-induced myocardial injury and cardiac dysfunction, bed rest can lead to several changes in cardiac structure and function, such as loss of cardiac mass, reduced ventricular diameter, prolonged isovolumetric relaxation time, decreased stroke volume and impaired aerobic capacity, which may contribute to poor outcomes and substantial mortality risk.32 33 Thus, clinicians should highly consider the cardiac function of bedridden patients with stroke.
Serum creatinine, the main metabolite of creatine and creatine phosphate in skeletal muscle, is a direct estimate of human muscle mass.34 Our findings showed that bedridden patients with stroke have lower levels of creatinine than non-bedridden patients. This observation may be attributed to the established effect of prolonged bed rest, which can lead to muscle atrophy and in turn contribute to the decrease in creatinine level.35 36
CRP is considered as one of the system inflammatory markers.37 Our study showed that hs-CRP levels were higher in bedridden patients with stroke than in non-bedridden patients. This may be due to prolonged bedridden conditions and inactivity-induced dysregulation of complex inflammatory patterns, leading to overexpression of vascular inflammatory markers.38 39
Serum albumin, the most abundant plasma protein, is important in maintaining colloidal osmotic pressure, transporting various substances and maintaining acid-base balance in the human body.40 It indicates nutritional status and disease severity particularly in chronic and critically ill patients.41 Albumin concentration tends to decrease with prolonged bed rest.42 Consistent with these, our results showed a lower serum albumin level in the bedridden than in the non-bedridden patients with stroke.
D-dimer is a degradation product of fibrin clots through the action of plasmin. Elevated D-dimer level indicates heightened systemic formation of fibrin and an increased propensity for thrombotic events.43 Our study showed that bedridden patients had higher D-dimer levels than non-bedridden patients. This emphasises the importance of closely monitoring D-dimer levels in bedridden patients with stroke to avoid venous thromboembolism, pulmonary embolism and disseminated intravascular coagulation.
Haemoglobin level has been documented to decline by 9% and 10% at 42 and 90 days, respectively, in healthy bedridden men.44 Our findings also demonstrated that the haemoglobin levels of bedridden patients were lower than those of non-bedridden patients. This may be because bed rest accelerates fat accumulation in haematopoietic bone marrow, which in turn affects haematopoiesis.44
Furthermore, our results revealed that bedridden patients had lower HDL-C levels than non-bedridden patients. This finding is in line with the observation made by Trakaki et al,45 which illustrated that prolonged bed rest negatively impacts the HDL-C levels by suppressing the HDL-C efflux capacity. However, there was no significant difference in LDL-C levels between bedridden and non-bedridden patients with stroke.
The elevation of NT-pro-BNP is related to several factors, such as demographic characteristics, chronic disease conditions, biochemical and haematological markers, and drug treatment.46 47 Consistent with previous studies, our study showed that elevated NT-pro-BNP levels were associated with older age (age ≥75 years) in both bedridden and non-bedridden patients after stroke.48 49 Furthermore, it has been demonstrated that there is a positive relationship between creatinine and NT-pro-BNP level.50 51 Our study revealed that elevated levels of NT-pro-BNP were linked to higher serum creatinine levels in both bedridden and non-bedridden patients with stroke. This highlights the importance of monitoring changes in serum creatinine levels in patients with stroke during clinical practice.
In addition, we found that high levels of NT-pro-BNP were associated with hs-CRP and albumin only in bedridden patients with stroke. It has been verified that elevated CRP is associated with the incidence of myocardial infarction, cerebrovascular disease, chronic HF and sudden cardiac arrest.52 53 The relationship between CRP and NT-pro-BNP or BNP levels has also been demonstrated, suggesting a possible interaction between natriuretic peptides and the systemic inflammatory response of the body.54 Our study revealed that elevated NT-pro-BNP levels are associated with high CRP levels in bedridden patients after stroke. This finding is consistent with Bando’s study, which reported a positive correlation between NT-pro-BNP and CRP in patients with cancer.55 However, Cui et al did not observe a significant association between NT-pro-BNP and CRP in older patients aged ≥80 years.50 These opposite results may be attributed to the different populations studied. Furthermore, our ROC curve analysis showed that hs-CRP with a cut-off value of 5.12 mg/L was a valuable factor for high levels of NT-pro-BNP in bedridden patients with stroke. Thus, CRP-based risk stratification and treatments for high levels of NT-pro-BNP should ideally be explored in bedridden patients with stroke.
Meanwhile, the declined serum albumin has been evidenced to be associated with many adverse cardiovascular or cerebrovascular events, including HF, atrial fibrillation, infective endocarditis and stroke.56 Consistent with a previous study in patients with chronic HF,57 our results demonstrated that decreased albumin was linked to elevated NT-pro-BNP in bedridden patients with stroke. ROC curve analysis showed that serum albumin with a cut-off value of 37.15 g/L may be an important factor for high levels of NT-pro-BNP in bedridden patients with stroke. This suggests that albumin, a potential marker, may serve as a predictive tool for elevated NT-pro-BNP expression in bedridden patients after stroke.
This study had some limitations. First, the duration from stroke onset to admission was not considered in the inclusion criteria during participants enrolments. NT-pro-BNP levels have been reported to significantly increase after acute stroke and decline over time, remaining higher in patients with stroke than in healthy subjects 3 months after the stroke.58 Thus, the duration from the onset of stroke to admission needs to be specified in future studies. Second, the NT-pro-BNP level is influenced by many risk factors. However, we did not consider other possible physiological parameters, such as antihypertensive medication use, which could potentially lead to bias in results interpretation. Third, this was a single-centre study, and its broad application in bedridden patients with stroke needs to be confirmed through a multicentre study. Fourth, this was a clinical study and could not explore the pathophysiological mechanisms underlying the relationship between NT-pro-BNP and other related factors. Thus, further studies, including mechanistic evaluation, are required to confirm these emerging findings.
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