Background
Stroke, as the leading cause of death in China, affected over 12 million Chinese residents in 2013 [
1]. It was estimated that over 2 million newly diagnosed stroke patients annually, and the incidence was projected to increase substantially [
2]. Over 70 % of patients after stroke struggle to perform activities of daily living (ADL) and require substantial household and medical care [
3]. A long-term cohort study (a mean of 13-year follow-up) described the disability trajectories and found a steep decrease in post-stroke functional ability [
4]. Many studies have reported that the recurrence rate of stroke was approximately 10 % within one year [
5], and with an increase to 12 % over five years [
6]. The disability was more serious in recurrent stroke patients, two times higher than that of their first-ever counterparts in one year [
7]. Some cost-effectiveness analyses have indicated that functional disability was one of the strong determinants of the medical costs of stroke patients independent of its subtype and severity [
8,
9], while the recovery of functional ability can effectively decrease the medical costs and improve the quality of life of stroke patients.
Epidemiological evidence has shown that aging is the strongest non-modifiable risk factor for the morbidity of stroke and disability [
10,
11]. The 2013 Global Burden of Disease study in China has shown that geriatric patients accounted for over 70 % of stroke deaths [
12]. In general, the biological aging process is embedded with the interaction of multiple chronic diseases (MCDs) to form the pathogenesis of stroke [
13]. A systematic review indicated that the prevalence of MCDs ranged from 55 to 98 % in elderly population [
14]. In elderly stroke patients, the most prevalent chronic disease was hypertension (80 %); diabetes accounted for over 23 % [
10]. Atrial fibrillation and chronic kidney disease were also associated with an increased risk of stroke [
15,
16]. Furthermore, aging itself and its resulting MCDs have been shown to accelerate the simultaneous occurrence of stroke and functional disability [
14]. Given that population aging continues to increase in China [
17], studies addressing functional disability in elderly stroke patients are warranted.
In addition to MCDs, social activity is a potential pathway linking the aging process with stroke and functional disability. Commonly, social activity reflects the participation of activities that can enable connection and communication with other persons broadly, in the social milieu [
18]. It has been found that over 40 % of the geriatric population suffers from social isolation (absence of social activity) due to the shifts in social relationships, including the geographic migration and death of family members [
19]. Emerging evidence has shown that the presence of social isolation is associated with an increase in the risk of stroke [
20] and disability [
21]. Furthermore, it was found that either pre-stroke or post-stroke social activity was a robust predictor of stroke outcomes: pre-stroke social isolation was linked to a 40 % increase in adverse outcomes (including myocardial infarction, stroke recurrence, or death) after stroke [
22], while Jansen’s study reported that 1-year post-stroke social isolation was still strongly associated with 3-year post-stroke disability [
23].
Despite the independent association of MCDs and social isolation with stroke and disability has been suggested by previous studies [
20,
21], little is known about whether the combination of these two conditions resulted from aging-related functional disability in elderly stroke patients. These two conditions reflected two aspects at the individual level: MCDs are a general indicator of physical health [
14], while social activity reflects healthy social engagement and is strongly linked with mental health [
20], but they interact with each other and cannot be treated separately. Based on a previous finding that social activity decreased the risk of MCDs in a European macro-regional study [
24], we hypothesized that the combination of MCDs and social isolation can increase functional disability more than a single condition alone in elderly stroke patients. Thus, the objective of this study was to test the hypothesis in stroke patients aged 60–90 years using data from the Departments of Rehabilitation Medicine in 103 hospitals in China.
Results
A total of 4046 elderly stroke patients aged 74.6 ± 8.5 years were included in this study, and their characteristics by age groups, are summarised in Table
1. Patients aged 60–69, 70–79, and 80–90 years accounted for about one-third, respectively. Among the total patients, 2231 (55.1 %) were male, 56 (1.4 %) were the minority, and over half were recruited from tertiary hospitals or eastern China. Patients who are currently drinking accounted for 7.2 %, and smoking accounted for 20.0 %. Approximately 75.0 % of patients suffered a stroke for the first time, and over 75.0 % of stroke were ischemic type. Over 40.0 % of patients had social isolation and suffered more than two chronic diseases. Moreover, 71.0 % of patients had a severe functional disability, 18.0 % had a moderate functional disability after stroke. Importantly, the prevalence of social isolation, MCDs ≥ 2, and severe functional disability increased with aging.
Table 1
Descriptive characteristics of 4046 elderly stroke patients according to age group
Demographic |
Gender |
Male | 862 (65.4) | 789 (57.8) | 580 (42.6) |
Female | 456 (34.6) | 576 (42.2) | 783 (57.4) |
Ethnicity |
Han | 1290 (97.9) | 1345 (98.5) | 1355 (99.4) |
Minority | 28 (2.1) | 20 (1.5) | 8 (0.6) |
Marital status |
Single (Widowed, Divorced, and Unmarried) | 90 (6.8) | 126 (9.2) | 326 (23.9) |
Married | 1228 (93.2) | 1239 (90.8) | 1037 (76.1) |
Annual Household Income (yuan) a |
<50,000 | 443 (33.6) | 453 (33.2) | 367 (26.9) |
50,000-100,000 | 521 (39.5) | 504 (36.9) | 562 (41.2) |
> 100,000 | 350 (26.6) | 407 (29.8) | 430 (31.5) |
Education Level a |
Primary school and lower | 371 (28.1) | 422 (30.9) | 520 (38.2) |
Middle school | 414 (31.4) | 408 (29.9) | 352 (25.8) |
High school | 328 (24.9) | 316 (23.2) | 265 (19.4) |
College and higher | 134 (10.2) | 161 (11.8) | 151 (11.1) |
Region |
Eastern | 769 (58.3) | 838 (61.4) | 953 (69.9) |
Central | 200 (15.2) | 144 (10.5) | 78 (5.7) |
Western | 272 (20.6) | 336 (24.6) | 315 (23.1) |
Northeast | 77 (5.8) | 47 (3.4) | 17 (1.2) |
Hospital Level a |
Primary | 65 (4.9) | 103 (7.5) | 202 (14.8) |
Secondary | 366 (27.8) | 421 (30.8) | 622 (45.6) |
Tertiary | 861 (65.3) | 816 (59.8) | 498 (36.5) |
Drinking a |
No | 1174 (89.1) | 1254 (91.9) | 1308 (96.0) |
Yes | 142 (10.8) | 104 (7.6) | 51 (3.7) |
Smokinga |
No | 987 (74.9) | 1046 (76.6) | 1175 (86.2) |
Yes | 328 (24.9) | 313 (22.9) | 183 (13.4) |
Clinical |
Fall experience a |
No | 1107 (84.0) | 1144 (83.8) | 1173 (86.1) |
Fall without hurt | 42 (3.2) | 45 (3.3) | 29 (2.1) |
Fall with light hurt | 49 (3.7) | 67 (4.9) | 50 (3.7) |
Fall with heavy hurt | 37 (2.8) | 50 (3.7) | 83 (6.1) |
Stroke Occurrence a |
First time | 1012 (76.8) | 1031 (75.5) | 985 (72.3) |
Two times | 224 (17.0) | 263 (19.3) | 267 (19.6) |
Three and more times | 80 (6.1) | 67 (4.9) | 101 (7.4) |
Stroke type |
Ischemic | 890 (67.5) | 1061 (77.7) | 1186 (87) |
Hemorrhagic | 375 (28.5) | 248 (18.2) | 139 (10.2) |
Combined | 53 (4.0) | 56 (4.1) | 38 (2.8) |
Social isolation |
Yes | 646 (49.0) | 586 (42.9) | 402 (29.5) |
No | 672 (51.0) | 779 (57.1) | 961 (70.5) |
Multiple chronic diseases b |
0 | 208 (15.8) | 167 (12.2) | 130 (9.5) |
1 | 588 (44.6) | 522 (38.2) | 468 (34.3) |
≥ 2 | 522 (39.6) | 676 (49.5) | 765 (56.1) |
Functional disability c |
No | 122 (9.3) | 100 (7.3) | 38 (2.8) |
Mild | 81 (6.1) | 67 (4.9) | 57 (4.2) |
Moderate | 307 (23.3) | 234 (17.1) | 170 (12.5) |
Severe | 808 (61.3) | 964 (70.6) | 1098 (80.6) |
We found that social isolation and MCDs were independently associated with functional disability after stroke (Table
2). After adjusting for demographic characteristics, current lifestyles, and clinical information, patients with social isolation were more likely to report severe (OR = 9.51, 95 % CI: 6.62–13.66,
P < 0.001) and moderate (OR = 2.92, 95 % CI: 1.99–2.49,
P < 0.001) disability relative to those without social isolation. Likewise, relative to patients with no MCDs, those with MCDs = 1 were more likely report severe (OR = 2.29, 95 % CI: 1.55–3.40,
P < 0.001) and moderate disability (OR = 1.78, 95 % CI: 1.17–2.71,
P = 0.008), so do the patients with MCD ≥ 2 (OR = 3.20, 95 % CI: 2.14–4.78,
P < 0.001 for severe disability; OR = 2.61, 95 % CI: 1.70-4.00,
P < 0.001 for moderate disability).
Table 2
The independent association of social isolation and multiple chronic diseases with the functional disability after stroke in elderly patients
Severe vs. no disability |
Social isolation |
No | Ref | | | Ref | | |
Yes | 9.56 | (6.87-13.30) | <0.001 | 9.51 | (6.62-13.66) | <0.001 |
Multiple chronic diseases |
0 | Ref | | | Ref | | |
1 | 2.65 | (1.84-3.81) | <0.001 | 2.29 | (1.55-3.40) | <0.001 |
≥ 2 | 3.49 | (2.41-5.06) | <0.001 | 3.20 | (2.14-4.78) | <0.001 |
Moderate vs. no disability |
Social isolation |
No | Ref | | | Ref | | |
Yes | 2.71 | (1.90-3.87) | <0.001 | 2.92 | (1.99-4.29) | <0.001 |
Multiple chronic diseases |
0 | Ref | | | Ref | | |
1 | 1.91 | (1.28-2.85) | 0.002 | 1.78 | (1.17-2.71) | 0.008 |
≥ 2 | 2.57 | (1.72-3.85) | <0.001 | 2.61 | (1.70-4.00) | <0.001 |
Mild vs. no disability |
Social isolation | | | | | | |
No | Ref | | | Ref | | |
Yes | 1.58 | (1.00-2.48) | 0.05 | 1.59 | (0.98-2.58) | 0.061 |
Multiple chronic diseases |
0 | Ref | | | Ref | | |
1 | 1.65 | (0.98-2.79) | 0.06 | 1.54 | (0.90-2.64) | 0.117 |
≥ 2 | 1.75 | (1.03-2.98) | 0.039 | 1.66 | (0.95-2.88) | 0.073 |
Table
3 displays the combined association of social isolation and MCDs with functional disability after stroke. The fully adjusted ORs of those with social isolation and MCDs ≥ 2 were 34.96 (95 % CI: 18.89–64.69,
P < 0.001) for severe disability, 8.15 (95 % CI: 4.30-15.46,
P < 0.001) for moderate disability, and 2.88 (95 % CI: 1.24–6.67,
P = 0.014) for mild disability compared with those without social isolation or any chronic disease. Patients with social isolation and MCDs = 1 were also likely to report functional disability and the magnitude increased by its severity (OR = 2.45, 95 % CI: 1.07–5.61,
P = 0.034 for mild; OR = 4.16, 95 % CI: 2.21–7.83,
P < 0.001 for moderate; OR = 20.30, 95 % CI: 11.14–36.97,
P < 0.001 for severe).
Table 3
The combined association of social isolation and multiple chronic diseases with the functional disability after stroke in elderly patients
Severe vs. no disability |
No | 0 | Ref | | | Ref | | |
1 | 2.98 | (1.98-4.48) | <0.001 | 2.78 | (1.75-4.43) | <0.001 |
≥ 2 | 4.04 | (2.67-6.11) | <0.001 | 3.68 | (2.29-5.91) | <0.001 |
Yes | 0 | 17.75 | (8.16-38.64) | <0.001 | 16.54 | (7.14-38.32) | <0.001 |
1 | 20.32 | (12.14-34.01) | <0.001 | 20.30 | (11.14-36.97) | <0.001 |
≥ 2 | 36.28 | (20.74-63.46) | <0.001 | 34.96 | (18.89-64.69) | <0.001 |
Moderate vs. no disability |
No | 0 | Ref | | | Ref | | |
1 | 2.04 | (1.31-3.17) | 0.002 | 1.94 | (1.19-3.14) | 0.008 |
≥ 2 | 2.46 | (1.57-3.85) | <0.001 | 2.53 | (1.54-4.14) | <0.001 |
Yes | 0 | 3.98 | (1.71-9.29) | 0.001 | 3.91 | (1.60-9.59) | 0.003 |
1 | 3.86 | (2.20-6.77) | <0.001 | 4.16 | (2.21-7.83) | <0.001 |
≥ 2 | 7.75 | (4.29-14.01) | <0.001 | 8.15 | (4.30-15.46) | <0.001 |
Mild vs. no disability |
No | 0 | Ref | | | Ref | | |
1 | 1.91 | (1.08-3.39) | 0.026 | 2.00 | (1.06-3.77) | 0.032 |
≥ 2 | 2.09 | (1.17-3.73) | 0.013 | 2.14 | (1.12-4.10) | 0.021 |
Yes | 0 | 3.30 | (1.19-9.18) | 0.022 | 3.88 | (1.32-11.40) | 0.014 |
1 | 2.02 | (0.96-4.24) | 0.065 | 2.45 | (1.07-5.61) | 0.034 |
≥ 2 | 3.16 | (1.48-6.73) | 0.003 | 2.88 | (1.24-6.67) | 0.014 |
The age-stratified analysis regarding their independent associations (Table
4) indicated that social isolation was not significantly associated with moderate disability (adjusted OR = 1.72, 95 % CI: 0.78–3.79,
P = 0.178), so did the association between MCDs and moderate disability. However, their association with severe disability was still significant, but the magnitude of OR for social isolation was the lowest in the 80–90 years group (OR = 5.48 in 80–90 years; 11.79 in 70–79 years; 11.61 in 60–69 years) and it for MCDs was the lowest in the 60–69 years group (OR = 1.60/1.98 for MCDs = 1/≥ 2 in 60–69 years; 3.28/5.07 in 70–79 years; 2.73/3.94 in 80–90 years).
Table 4
The independent association of social isolation and multiple chronic diseases with the functional disability after stroke in elderly patients by age groups
Severe vs. no disability |
Social isolation |
No | Ref | | | | | | | | |
Yes | 11.61 | (6.22-21.69) | <0.001 | 11.79 | (6.34-21.94) | <0.001 | 5.48 | (2.62-11.5) | <0.001 |
Multiple chronic diseases |
0 | Ref | | | | | | | | |
1 | 1.60 | (0.84-3.03) | 0.151 | 3.28 | (1.76-6.12) | <0.001 | 2.73 | (1.03-7.2) | 0.043 |
≥ 2 | 1.98 | (1.01-3.87) | 0.048 | 5.07 | (2.67-9.62) | <0.001 | 3.94 | (1.56-9.94) | 0.004 |
Moderate vs. no disability |
Social isolation |
No | Ref | | | | | | | | |
Yes | 3.81 | (2.00-7.28) | <0.001 | 3.34 | (1.73-6.45) | <0.001 | 1.72 | (0.78-3.79) | 0.178 |
Multiple chronic diseases |
0 | Ref | | | | | | | | |
1 | 1.37 | (0.71-2.67) | 0.352 | 2.21 | (1.12-4.37) | 0.022 | 2.18 | (0.75-6.37) | 0.152 |
≥ 2 | 1.94 | (0.97-3.89) | 0.061 | 3.48 | (1.74-6.93) | <0.001 | 3.03 | (1.09-8.41) | 0.033 |
Mild vs. no disability |
Social isolation |
No | Ref | | | | | | | | |
Yes | 2.31 | (1.02-5.25) | 0.045 | 1.23 | (0.51-3.00) | 0.643 | 1.01 | (0.40-2.55) | 0.987 |
Multiple chronic diseases |
0 | Ref | | | | | | | | |
1 | 0.99 | (0.44- 2.25) | 0.986 | 2.48 | (0.93-6.56) | 0.068 | 1.65 | (0.45-6.06) | 0.451 |
≥ 2 | 0.71 | (0.29-1.76) | 0.457 | 2.83 | (1.06-7.57) | 0.039 | 2.61 | (0.77-8.90) | 0.125 |
The combined association of social isolation and MCDs with the functional disability after stroke was also stratified by age (Table
5). Likewise, their combination was significantly associated with severe and moderate disability in different age groups, and the magnitude of its OR in 70–79 years group was the highest and increased from moderate to severe disability simultaneously. However, the association of their combination with mild disability was not significant anymore in different age groups.
Table 5
The combined association of social isolation and multiple chronic diseases with the functional disability after stroke in elderly patients by age groups
Severe vs. no disability |
No | 0 | Ref | | | Ref | | | Ref | | |
1 | 2.20 | (1.05-4.60) | 0.036 | 2.92 | (1.41-6.05) | 0.004 | 4.55 | (1.28-16.10) | 0.019 |
≥ 2 | 2.43 | (1.12-5.27) | 0.025 | 4.54 | (2.15-9.58) | <0.001 | 6.18 | (1.95-19.65) | 0.002 |
Yes | 0 | 29.14 | (5.54-153.38) | <0.001 | 9.98 | (3.12-31.96) | <0.001 | 23.11 | (2.49-214.24) | 0.006 |
1 | 16.42 | (6.21-43.43) | <0.001 | 33.96 | (11.87-97.16) | <0.001 | 18.10 | (5.14-63.79) | <0.001 |
≥ 2 | 32.92 | (11.32-95.77) | <0.001 | 58.05 | (19.55-172.38) | <0.001 | 26.98 | (7.92-91.87) | <0.001 |
Moderate vs. no disability |
No | 0 | Ref | | | Ref | | | Ref | | |
1 | 1.46 | (0.69-3.05) | 0.321 | 2.45 | (1.11-5.41) | 0.027 | 3.51 | (0.89-13.81) | 0.072 |
≥ 2 | 1.81 | (0.84-3.91) | 0.133 | 3.33 | (1.48-7.48) | 0.004 | 4.37 | (1.24-15.41) | 0.022 |
Yes | 0 | 5.83 | (1.05-32.41) | 0.044 | 3.51 | (0.97-12.68) | 0.056 | 6.60 | (0.61-71.11) | 0.119 |
1 | 3.81 | (1.40-10.33) | 0.009 | 6.39 | (2.05-19.92) | 0.001 | 4.18 | (1.06-16.55) | 0.042 |
≥ 2 | 8.89 | (3.02-26.18) | <0.001 | 13.57 | (4.30-42.82) | <0.001 | 6.28 | (1.66-23.77) | 0.007 |
Mild vs. no disability |
No | 0 | Ref | | | Ref | | | Ref | | |
1 | 1.21 | (0.49-3.00) | 0.687 | 3.20 | (1.00-10.26) | 0.051 | 3.73 | (0.62-22.48) | 0.151 |
≥ 2 | 0.69 | (0.25-1.93) | 0.477 | 3.97 | (1.23-12.82) | 0.021 | 6.68 | (1.28-34.78) | 0.024 |
Yes | 0 | 4.66 | (0.65-33.45) | 0.126 | 3.06 | (0.50-18.70) | 0.227 | 9.35 | (0.65-135.41) | 0.101 |
1 | 1.61 | (0.45-5.71) | 0.462 | 4.00 | (0.81-19.69) | 0.088 | 3.19 | (0.51-19.85) | 0.214 |
≥ 2 | 2.44 | (0.60-9.86) | 0.211 | 3.38 | (0.63-18.17) | 0.156 | 4.02 | (0.69-23.38) | 0.121 |
Results from the sensitivity analysis (Table
S1 and
S2) indicated that both independent and combined associations of social isolation and MCDs with the functional disability after stroke were robust after excluding patients who had a fall experience with heavy hurt.
Discussion
Results from our study indicated that both social isolation and MCDs were independent risk factors for functional disability after stroke in elderly patients. Moreover, the hypothesis that a combination of these factors was associated with a greater extent of risk for functional disability than a single factor alone, was successfully assessed. The coexistence of social isolation and MCDs ≥ 2 was associated with a nearly 35 times higher risk for severe disability, 8 times higher risk for moderate disability than no social isolation combined with no MCDs.
This study, including 4046 elderly stroke patients from 103 clinical settings of 23 cities, was a nationally representative study in some degree. To the best of our knowledge, it is the first to address the combined association of social isolation and MCDs with functional disability in elderly population of China. We believe that these findings will provide insights that future prevention and intervention strategies for functional disability may integrate the social content with combined treatments of MCDs to achieve more effectiveness. However, the interpretation of these results also needs to consider the following limitations. First, the cross-sectional design of this study was restricted to draw the causal relationships among the variables. Second, the sampling method was non-random and included hospitals that collaborated with our departments. Nonetheless, the inherent bias may have been avoided since our study covered over 100 hospitals in 23 sites to ensure its generalisability. Additionally, our study only selected stroke patients aged 60–90 years, therefore our results may not be applicable to other aged populations. Third, the majority of variables were self-reported, recall bias thereby could not be avoided. Furthermore, considering that this study covered a large sample size and many organizations, the investigation of lifestyles selected only smoking and drinking as confounders, which might miss the information on other lifestyles relating to disability, including dietary behaviors, physical activity, and ex-smoking [
33]. However, some information was investigated based on the standardized protocol to ensure study quality among different hospitals. For instance, self-reported MCDs were validated by their medical records, and functional disability was required to be evaluated by trained and experienced therapists. Fourth, our study only recorded the stroke type and occurrence and missed its severity, while the severity directly influences the functional ability [
34,
35].
BI is the most popular method to measure functional disability in stroke patients [
36]. Although the BI cut-off points for categorizing stroke patients with an unfavorable outcome were different from study to study, each study stressed the fact that the prevalence of functional disability was severe in stroke patients [
36,
37]. There is a paucity of studies that consider elderly stroke patients in China. To the best of our knowledge, only Li et al. used the same classification criterion of BI (severe disability ≤ 55) in disabled elderly stroke patients with a small sample size (
n = 158) and showed that the prevalence of severe disability was more than half [
26]. The results of our study, similar to Li’s research, found that the prevalence of mild and severe disability was nearly 90 %. Moreover, our study found the prevalence of severe disability increased with aging (from 61.3 % in 60–69 years to 80.6 % in 80–90 years). Additionally, compared with studies in other countries using the same BI cut-off, the prevalence of severe disability in our study was more than double that of a Brazilian study of 260 middle-aged and elderly stroke survivors (31.5 %) [
35], more than six times that of the Northern Manhattan Stroke Study of 340 elderly stroke patients [
38].
The identification of risk factors for functional disability after stroke is key to the formulation of prevention and treatment strategies in elderly patients. In our study, MCDs status was found to be a risk factor for functional disability. Studies focusing on elderly stroke patients were limited, and we found some similar findings in a population with a single condition (geriatric or stroke) [
39]. A recent systematic review of 3339 stroke patients from seven hospital-based cohort studies, indicated that MCDs were longitudinally associated with an 11 % increase in the risk of functional disability after stroke, irrespective of the different methods used for assessing MCDs and functional disability [
39]. Meanwhile, a large cohort study including the Chinese geriatric population also showed that MCDs significantly increased the risk of functional disability by 117 % [
40]. Another cohort study with a small sample size but with a mean age over 85 years found no significant association between them [
41]. However, the findings of this study also identified a significant association between MCDs and functional disability in 80–90 years, but the magnitude of its OR was much lower than the other two young age groups (60–69 and 70–79 years). These findings suggested that the inconsistency of their association might be attributed to age. On the one hand, based on trajectory analysis [
4], functional disability tended to be stable beyond the age of 80 years; on the other hand, the combination of MCDs and the age of over 80 years had a high probability of leading to death [
40]. In fact, MCD status was inevitable to some extent in the aging process, [
14] and nearly half of the participants in our study suffered from two and more chronic diseases, which was consistent with a recent systematic review [
14]. Many possible explanations have addressed this issue. Sharing similar risk factors, including genetic, environmental, social, physiological, and psychosocial factors, was the common one [
14,
42]. For example, chronic inflammation and oxidative stress played an important role in the initiation and progression of MCDs related to aging [
42,
43]. Besides, the shared risk factors were more likely to be the mechanisms by which MCDs synergistically increased the functional disability [
43]. Furthermore, another systematic review proposed that certain chronic disease clusters were internally and highly correlated [
28]. As for stroke, we found that hypertension (77 %), diabetes (32 %), and heart diseases (33 %) were more common in stroke patients than the other two chronic diseases. A review similarly indicated that hypertension was the most important risk factor for stroke and sustained the highest population-attributable risk (34.6 %) among obesity, several classic chronic diseases (diabetes, hyperlipidemia, coronary artery disease, and arterial fibrillation), and lifestyles (smoking and physical inactivity) [
44]. Thus, the prevention of post-stroke functional disability requires the control and management of hypertension, diabetes, and heart diseases.
Another strong risk factor for functional disability in our study was social isolation, which has been well documented in many cohort studies. [
45‐
47] Although these studies were conducted in older adults without referring to stroke, they consistently indicated that social activity could reduce or delay the decline of functional disability caused by aging [
45‐
47]. Social isolation may have a deleterious effect on neural networks and decreased musculoskeletal function, accelerating the functional disability related to aging [
21]. In addition, many other behavioral and psychosocial pathways underlined the improvement in depression and cognitive decline associations with social activity; they all are important psychological risk factors for functional disability and stroke [
22,
46]. Social networks change to smaller and close-knit ones during aging [
19] and after stroke. [
48] A clinical study has reported that baseline social isolation robustly predicted the stroke and prognosis outcome. [
48] Thus, both primary prevention and secondary therapies for stroke and functional disability should consider the promotion of social engagement among older adults.
Importantly, the novel finding of our study is that the combination of social isolation and MCDs is associated with a much higher risk for functional disability than a single condition. Although the exact mechanisms regarding the relationship of their combination with functional disability have yet to be explained sufficiently, we can understand its plausibility from several dimensions: (1) both aging and stroke are the common risk factors for them [
4,
7,
14,
20], although they represent social and biological levels, respectively; (2) social isolation may interact with MCDs through biological, behavioral, and neurological links. A previous study reported that a series of downstream biological changes, including abnormalities in cortisol secretion and a deterioration in immune and anti-oxidative stress functions, was easy to detect in people with social isolation [
49‐
51]. From a behavioral point of review, social isolation constantly leads to the development of many unhealthy lifestyles, which accordingly increases the risk for MCDs [
50]. As for the neurology aspect, a recent review synthesized the evidence and found that social isolation combined with other mental disorders (depression and anxiety) accelerated the activation of the hypothalamic-pituitary-adrenocortical axis and subsequently moderates the biological process [
51]. Patients with low socioeconomic status are more likely to experience social isolation and loneliness [
52], they also have higher risks of MCDs [
53], which has been also demonstrated by a macro-regional analysis [
24]. Furthermore, those with advanced socioeconomic status participating in more social activities and with fewer MCDs have more wiliness to absorb rehabilitation knowledge to decline the degree of functional disability [
54]. Additionally, It should be noted that the OR of social isolation in the comparison between severe and no disability was still much higher than that of the other two comparisons (moderate vs. no disability; mild vs. no disability). Given that the intervention on social isolation through encouraging the participation of social activities was much more available than MCD management, future interventions aiming to increase functional ability and quality of life of elderly stroke patients should pay more attention to social activity.
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